start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=1
article-no=
start-page=12
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241105
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Dendritic cells (DCs) are crucial in cancer immunity, because they activate cytotoxic T cells by presenting tumor antigens. Recently, oncolytic virus therapy has been recognized as a systemic immune stimulator. We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. However, their effects on DCs remained unclear. In the present study, the aim was to elucidate the mechanisms of DC activation by OBP-702, focusing particularly on tumor-derived exosomes. Exosomes (Exo53, Exo301, or Exo702) were isolated from conditioned media of human or murine pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and PAN02) after treatment with Ad-p53, OBP-301, or OBP-702. Exo702 derived from Panc-1 and MiaPaCa-2 cells significantly upregulated CD86, CD80, CD83 (markers of DC maturation), and IFN-γ in DCs in vitro. Similarly, Exo702 derived from PAN02 cells upregulated CD86 and IFN-γ in bone marrow-derived DCs in a bilateral PAN02 subcutaneous tumor model. This DC maturation was inhibited by GW4869, an inhibitor of exosome release, and anti-CD63, an antibody targeting the exosome marker. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect.
en-copyright=
kn-copyright=

en-aut-name=OhtaniTomoko
en-aut-sei=Ohtani
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KumonKento
en-aut-sei=Kumon
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YagiChiaki
en-aut-sei=Yagi
en-aut-mei=Chiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SugimotoRyoma
en-aut-sei=Sugimoto
en-aut-mei=Ryoma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Oncolys BioPharma, Inc
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Oncolytic adenovirus
kn-keyword=Oncolytic adenovirus
en-keyword=p53
kn-keyword=p53
en-keyword=Dendritic cells
kn-keyword=Dendritic cells
en-keyword=Anti-tumor immunity
kn-keyword=Anti-tumor immunity
en-keyword=Exosome
kn-keyword=Exosome
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=229
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20241004
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Primary ileal myeloid sarcoma presenting with bowel obstruction: a case report
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Myeloid sarcoma (MS) is an extramedullary tumor constituted by myeloid blasts or immature myeloid cells. It frequently occurs in conjunction with acute myeloid leukemia (AML); however, it can exceptionally manifest in patients without leukemia. Here, we present a rare case of primary MS originating in the small bowel without evidence of bone marrow involvement.<br>
Case representation A 33 year-old female with no relevant medical history was admitted to our hospital with recurrent abdominal pain. Computed tomography (CT) revealed bowel obstruction due to thickening of the ileum wall, which was suspected to be an ileal tumor. Initially, ectopic endometriosis was suspected because of abdominal pain associated with the menstrual cycle and changes observed on a follow-up CT scan. The lesion could not be detected by double-balloon endoscopy. Despite conservative treatment, the obstruction persisted, and laparoscopic partial ileal resection was performed, which revealed extensive involvement of the ileum and mesentery. Additionally, the mesentery of the resected ileum was extremely thickened. Histopathological and immunohistochemical examinations of the surgical specimen indicated ileal MS. Bone marrow aspiration after discharge was negative for cytological findings of leukemia, leading to a final diagnosis of primary ileal MS. Her postoperative course was uneventful, and she is currently undergoing systemic chemotherapy tailored to AML at another hospital.<br>
Conclusions Even though MS of the small bowel is rare and may not be considered preoperatively, similar surgical treatment to that of other small bowel malignancies can ensure proper postoperative diagnosis and appropriate chemotherapy. Given the potential need for chemotherapy, ensuring surgical safety that allows for its rapid initiation is critical.
en-copyright=
kn-copyright=

en-aut-name=MinagiHitoshi
en-aut-sei=Minagi
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KondoYoshitaka
en-aut-sei=Kondo
en-aut-mei=Yoshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShojiRyohei
en-aut-sei=Shoji
en-aut-mei=Ryohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MatsumiYuki
en-aut-sei=Matsumi
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
en-keyword=Myeloid sarcoma
kn-keyword=Myeloid sarcoma
en-keyword=Chloroma
kn-keyword=Chloroma
en-keyword=Granulocytic sarcoma
kn-keyword=Granulocytic sarcoma
en-keyword=Bowel obstruction
kn-keyword=Bowel obstruction
en-keyword=Abdominal pain
kn-keyword=Abdominal pain
END

start-ver=1.4
cd-journal=joma
no-vol=44
cd-vols=
no-issue=6
article-no=
start-page=2497
end-page=2509
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240531
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8–mediated Crosstalk
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background/Aim: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. Materials and Methods: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of α–smooth muscle actin (α-SMA), senescence-associated β-galactosidase (SA-β-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. Results: IGC cells significantly induced α-SMA+ myCAFs by secreting transforming growth factor–β, whereas DGC cells induced SA-β-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. Conclusion: sCAFs promote peritoneal metastasis of DGC via IL-8–mediated crosstalk.
en-copyright=
kn-copyright=

en-aut-name=LIYUNCHENG
en-aut-sei=LI
en-aut-mei=YUNCHENG
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TAZAWAHIROSHI
en-aut-sei=TAZAWA
en-aut-mei=HIROSHI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NAGAIYASUO
en-aut-sei=NAGAI
en-aut-mei=YASUO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FUJITASHUTO
en-aut-sei=FUJITA
en-aut-mei=SHUTO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OKURATOMOHIRO
en-aut-sei=OKURA
en-aut-mei=TOMOHIRO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SHOJIRYOHEI
en-aut-sei=SHOJI
en-aut-mei=RYOHEI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YAMADAMOTOHIKO
en-aut-sei=YAMADA
en-aut-mei=MOTOHIKO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KIKUCHISATORU
en-aut-sei=KIKUCHI
en-aut-mei=SATORU
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KURODASHINJI
en-aut-sei=KURODA
en-aut-mei=SHINJI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OHARATOSHIAKI
en-aut-sei=OHARA
en-aut-mei=TOSHIAKI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NOMAKAZUHIRO
en-aut-sei=NOMA
en-aut-mei=KAZUHIRO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=NISHIZAKIMASAHIKO
en-aut-sei=NISHIZAKI
en-aut-mei=MASAHIKO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KAGAWASHUNSUKE
en-aut-sei=KAGAWA
en-aut-mei=SHUNSUKE
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FUJIWARATOSHIYOSHI
en-aut-sei=FUJIWARA
en-aut-mei=TOSHIYOSHI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Gastric cancer
kn-keyword=Gastric cancer
en-keyword=peritoneal metastasis
kn-keyword=peritoneal metastasis
en-keyword=senescent fibroblast
kn-keyword=senescent fibroblast
en-keyword=IL-8
kn-keyword=IL-8
en-keyword=CXCR1/2
kn-keyword=CXCR1/2
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240415
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Perioperative and Postoperative Continuous Nutritional Counseling Improves Quality of Life of Gastric Cancer Patient Undergoing Gastrectomy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (−7.98% vs. −12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL.
en-copyright=
kn-copyright=

en-aut-name=HanzawaShunya
en-aut-sei=Hanzawa
en-aut-mei=Shunya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ShojiRyohei
en-aut-sei=Shoji
en-aut-mei=Ryohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MatsumiYuki
en-aut-sei=Matsumi
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakahashiAyako
en-aut-sei=Takahashi
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TakagiKosei
en-aut-sei=Takagi
en-aut-mei=Kosei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TanabeShunsuke
en-aut-sei=Tanabe
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=ShikataKenichi
en-aut-sei=Shikata
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Clinical Nutrition, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Clinical Nutrition, Okayama University Hospital
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=2
article-no=
start-page=151
end-page=161
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.
en-copyright=
kn-copyright=

en-aut-name=KomatsubaraTadashi
en-aut-sei=Komatsubara
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HaseiJoe
en-aut-sei=Hasei
en-aut-mei=Joe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OmoriToshinori
en-aut-sei=Omori
en-aut-mei=Toshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SugiuKazuhisa
en-aut-sei=Sugiu
en-aut-mei=Kazuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MochizukiYusuke
en-aut-sei=Mochizuki
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=DemiyaKoji
en-aut-sei=Demiya
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YoshidaAki
en-aut-sei=Yoshida
en-aut-mei=Aki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FujiwaraTomohiro
en-aut-sei=Fujiwara
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KunisadaToshiyuki
en-aut-sei=Kunisada
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=soft-tissue sarcoma
kn-keyword=soft-tissue sarcoma
en-keyword=radiotherapy
kn-keyword=radiotherapy
en-keyword=oncolytic adenovirus
kn-keyword=oncolytic adenovirus
en-keyword=p53
kn-keyword=p53
en-keyword=BCL-xL
kn-keyword=BCL-xL
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=3
article-no=
start-page=374
end-page=382
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240222
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A multi-center, prospective, clinical study to evaluate the anti-reflux efficacy of laparoscopic double-flap technique (lD-FLAP Study)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Double-flap technique (DFT) is a reconstruction procedure after proximal gastrectomy (PG). We previously reported a multi-center, retrospective study in which the incidence of reflux esophagitis (RE) (Los Angeles Classification ≥Grade B [LA-B]) 1 year after surgery was 6.0%. There have been many reports, but all of them were retrospective. Thus, a multi-center, prospective study was conducted.<br>
Methods: Laparoscopic PG + DFT was performed for cT1N0 upper gastric cancer patients. The primary endpoint was the incidence of RE (≥LA-B) 1 year after surgery. The planned sample size was 40, based on an estimated incidence of 6.0% and an upper threshold of 20%.<br>
Results: Forty patients were recruited, and 39, excluding one with conversion to total gastrectomy, received protocol treatment. Anastomotic leakage (Clavien–Dindo ≥Grade III) was observed in one patient (2.6%). In 38 patients, excluding one case of postoperative mortality, RE (≥LA-B) was observed in two patients (5.3%) 1 year after surgery, and the upper limit of the 95% confidence interval was 17.3%, lower than the 20% threshold. Anastomotic stricture requiring dilatation was observed in two patients (5.3%). One year after surgery, body weight change was 88.9 ± 7.0%, and PNI <40 and CONUT ≥5, indicating malnutrition, were observed in only one patient (2.6%) each. In the quality of life survey using the PGSAS-45 questionnaire, the esophageal reflux subscale score was 1.4 ± 0.6, significantly better than the public data (2.0 ± 1.0; p = 0.001).<br>
Conclusion: Laparoscopic DFT showed anti-reflux efficacy. Taken together with the acceptable incidence of anastomotic stricture, DFT can be an option for reconstruction procedure after PG.
en-copyright=
kn-copyright=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IshidaMichihiro
en-aut-sei=Ishida
en-aut-mei=Michihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ChodaYasuhiro
en-aut-sei=Choda
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MuraokaAtsushi
en-aut-sei=Muraoka
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HatoShinji
en-aut-sei=Hato
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KagawaTetsuya
en-aut-sei=Kagawa
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TanakaNorimitsu
en-aut-sei=Tanaka
en-aut-mei=Norimitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MitsuhashiToshiharu
en-aut-sei=Mitsuhashi
en-aut-mei=Toshiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Surgery, Hiroshima City  Hiroshima Citizens Hospital, Hiroshima
kn-affil=

affil-num=3
en-affil=Department of Surgery, Hiroshima City  Hiroshima Citizens Hospital, Hiroshima
kn-affil=

affil-num=4
en-affil=Department of Surgery, Kagawa Rosai  Hospital
kn-affil=

affil-num=5
en-affil=Department of Surgery, Shikoku Cancer  Center
kn-affil=

affil-num=6
en-affil=Department of Surgery, Shikoku Cancer  Center
kn-affil=

affil-num=7
en-affil=Department of Surgery, Kagawa  Prefectural Central Hospital
kn-affil=

affil-num=8
en-affil=Center for Innovative Clinical Medicine,  Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Surgery, Tsuyama Chuo  Hospital
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=
en-keyword=anti-reflux surgery
kn-keyword=anti-reflux surgery
en-keyword=double-flap technique
kn-keyword=double-flap technique
en-keyword=gastric cancer
kn-keyword=gastric cancer
en-keyword=Kamikawa procedure
kn-keyword=Kamikawa procedure
en-keyword=proximal gastrectomy
kn-keyword=proximal gastrectomy
END

start-ver=1.4
cd-journal=joma
no-vol=130
cd-vols=
no-issue=7
article-no=
start-page=1187
end-page=1195
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240205
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702).<br>
Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps).<br>
Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection.<br>
Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.
en-copyright=
kn-copyright=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KadowakiDaisuke
en-aut-sei=Kadowaki
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YoshidaYusuke
en-aut-sei=Yoshida
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SakamotoMasaki
en-aut-sei=Sakamoto
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HamadaYuki
en-aut-sei=Hamada
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SugimotoRyoma
en-aut-sei=Sugimoto
en-aut-mei=Ryoma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YagiChiaki
en-aut-sei=Yagi
en-aut-mei=Chiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OhtaniTomoko
en-aut-sei=Ohtani
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KumonKento
en-aut-sei=Kumon
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=YasuiKazuya
en-aut-sei=Yasui
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=YagiTakahito
en-aut-sei=Yagi
en-aut-mei=Takahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=18
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=20
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=11
article-no=
start-page=e0294491
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231116
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis.
en-copyright=
kn-copyright=

en-aut-name=TamuraShuta
en-aut-sei=Tamura
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HoriNaoto
en-aut-sei=Hori
en-aut-mei=Naoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=LiYuncheng
en-aut-sei=Li
en-aut-mei=Yuncheng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamadaMotohiko
en-aut-sei=Yamada
en-aut-mei=Motohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=5
article-no=
start-page=2178
end-page=2185
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Prognostic risk factors for postoperative long-term outcomes in elderly stage IA gastric cancer patients
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: The number of gastric cancer (GC) patients with other diseases is increasing due to the aging of the population. In particular, in stage IA GC patients who have multiple diseases, surgical indications should be considered after identifying prognostic factors. We therefore investigated prognostic factors for stage IA GC in the elderly.<br>
Methods: Patient characteristics were collected and analyzed retrospectively for elderly patients with stage IA GC who underwent curative surgical treatment at Okayama University Hospital between 2010 and 2015, and an elderly group (EG; 75–79 years old) and very elderly group (VEG; ≥80 years old) were compared.<br>
Results: Fifty-three patient in the EG and 31 patients in the VEG were compared. No factors associated with clinicopathological characteristics or surgical or postoperative short-term outcomes differed significantly between groups. Although no factors in the EG appeared significantly associated with poor overall survival (OS), severe comorbidity [Charlson Comorbidity Index (CCI) ≥2; P=0.019], open gastrectomy (P=0.012), high volume of blood loss (≥300 mL; P=0.013) and long postoperative hospital stay (≥14 days; P=0.041) were significantly associated with poor OS. Furthermore, only CCI ≥2 [hazard ratio (HR) =9.2; 95% confidence interval (CI): 1.2–68.9; P=0.032] was an independent prognostic factor associated with poor OS. Five-year OS was 88.9% for CCI 0/1 patients and 62.3% for CCI ≥2 patients, representing very impressive results.<br>
Conclusions: CCI ≥2 is an important prognostic factor in clinical decisions in stage IA GC patients ≥2, so careful determination of surgical indications is desirable.
en-copyright=
kn-copyright=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Gastric cancer (GC)
kn-keyword=Gastric cancer (GC)
en-keyword=elderly
kn-keyword=elderly
en-keyword=stage IA
kn-keyword=stage IA
en-keyword=comorbidity
kn-keyword=comorbidity
en-keyword=Charlson comorbidity index (CCI)
kn-keyword=Charlson comorbidity index (CCI)
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=5
article-no=
start-page=e39466
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230525
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Collagenous Colitis in a Patient With Gastric Cancer Who Underwent Chemotherapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Herein, we present a case of collagenous colitis in a patient who underwent chemotherapy for gastric cancer, comprising five cycles of S-1 plus oxaliplatin and trastuzumab, followed by five cycles of paclitaxel and ramucirumab and seven cycles of nivolumab. The subsequent initiation of trastuzumab deruxtecan chemotherapy led to the development of grade 3 diarrhea after the second cycle of treatment. Collagenous colitis was diagnosed via colonoscopy and biopsy. The patient's diarrhea improved following the cessation of lansoprazole. This case highlights the importance of considering collagenous colitis as a differential diagnosis, in addition to chemotherapy-induced colitis and immune-related adverse event (irAE) colitis, in patients with similar clinical presentations.
en-copyright=
kn-copyright=

en-aut-name=IwamuroMasaya
en-aut-sei=Iwamuro
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InooShoko
en-aut-sei=Inoo
en-aut-mei=Shoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OtsukaMotoyuki
en-aut-sei=Otsuka
en-aut-mei=Motoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=chemotherapy-induced diarrhea
kn-keyword=chemotherapy-induced diarrhea
en-keyword=immune-related adverse event colitis
kn-keyword=immune-related adverse event colitis
en-keyword=colonoscopy
kn-keyword=colonoscopy
en-keyword=collagenous colitis
kn-keyword=collagenous colitis
END

start-ver=1.4
cd-journal=joma
no-vol=567
cd-vols=
no-issue=
article-no=
start-page=216260
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230728
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dual antiplatelet therapy inhibits neutrophil extracellular traps to reduce liver micrometastases of intrahepatic cholangiocarcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The involvement of neutrophil extracellular traps (NETs) in cancer metastasis is being clarified, but the relationship between intrahepatic cholangiocarcinoma (iCCA) and NETs remains unclear. The presence of NETs was verified by multiple fluorescence staining in clinically resected specimens of iCCA. Human neutrophils were co-cultured with iCCA cells to observe NET induction and changes in cellular characteristics. Binding of platelets to iCCA cells and its mechanism were also examined, and their effects on NETs were analyzed in vitro and in in vivo mouse models. NETs were present in the tumor periphery of resected iCCAs. NETs promoted the motility and migration ability of iCCA cells in vitro. Although iCCA cells alone had a weak NET-inducing ability, the binding of platelets to iCCA cells via P-selectin promoted NET induction. Based on these results, antiplatelet drugs were applied to these cocultures in vitro and inhibited the binding of platelets to iCCA cells and the induction of NETs. Fluorescently labeled iCCA cells were injected into the spleen of mice, resulting in the formation of liver micrometastases coexisting with platelets and NETs. These mice were treated with dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor, which dramatically reduced micrometastases. These results suggest that potent antiplatelet therapy prevents micrometastases of iCCA cells by inhibiting platelet activation and NET production, and it may contribute to a novel therapeutic strategy.
en-copyright=
kn-copyright=

en-aut-name=YoshimotoMasashi
en-aut-sei=Yoshimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KajiokaHiroki
en-aut-sei=Kajioka
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TaniguchiAtsuki
en-aut-sei=Taniguchi
en-aut-mei=Atsuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YagiTomohiko
en-aut-sei=Yagi
en-aut-mei=Tomohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NogiShohei
en-aut-sei=Nogi
en-aut-mei=Shohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Aspirin
kn-keyword=Aspirin
en-keyword=Ticagrelor
kn-keyword=Ticagrelor
en-keyword=P-selectin
kn-keyword=P-selectin
en-keyword=Platelet
kn-keyword=Platelet
en-keyword=Time-lapse imaging
kn-keyword=Time-lapse imaging
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=2
article-no=
start-page=209
end-page=213
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Locally Advanced Rectal Cancer Invading the Gluteus Maximus Muscle Completely Responded to Total Neoadjuvant Therapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 70-year-old male with anal pain and fever was diagnosed with rectal cancer perforation and abscess in the right gluteus maximus (GM) muscle. He underwent a transverse colon colostomy followed by preoperative capecitabine+oxaliplatin. Some local control was achieved but a residual abscess was observed in the right GM muscle. To secure circumferential resection margin by tumor reduction, he received chemoradiotherapy as total neoadjuvant therapy (TNT) and underwent laparoscopic abdominoperineal resection, D3 lymph node dissection, combined coccyx resection, and partial resection of the right GM muscle. The skin defect and pelvic dead space were filled with a right lateral vastus lateral great muscle flap. Histopathologically, the resected specimen showed no tumor cells in the primary tumor or lymph nodes, indicating a pathological complete response (pCR). This case suggests that TNT might improve the R0 resection and pCR rates and overall survival.
en-copyright=
kn-copyright=

en-aut-name=SakamotoMasaki
en-aut-sei=Sakamoto
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=ShigeyasuKunitoshi
kn-aut-sei=Shigeyasu
kn-aut-mei=Kunitoshi
aut-affil-num=3
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=locally advanced rectal cancer
kn-keyword=locally advanced rectal cancer
en-keyword=total neoadjuvant therapy
kn-keyword=total neoadjuvant therapy
en-keyword=lateral vastus lateral great muscle flap
kn-keyword=lateral vastus lateral great muscle flap
END

start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=1
article-no=
start-page=91
end-page=95
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202302
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Case Report of Non-typical Annular Pancreas Diagnosed during Laparoscopic Gastric Surgery
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=An annular pancreas is a rare anomaly of the pancreas, defined as pancreatic tissue that totally or partly encircles the duodenum, usually the descending portion. A 76-year-old man who was diagnosed with gastric cancer cT3N0M0 Stage IIB underwent laparoscopic distal gastrectomy with D2 lymph node dissection. Intraoperatively, the dorsal half of the duodenal bulb was seen to be half surrounded by the pancreas, and a non-typical annular pancreas was diagnosed. Because of the risk to the pancreas, it was considered impossible to perform anastomosis by a linear stapler as in the usual laparoscopic procedure. Therefore, we performed laparoscopically assisted distal gastrectomy and Billroth-I reconstruction using a circular stapler, and the surgery was completed without difficulties. His postoperative course was good despite the development of a pancreatic fistula, which was an International Study Group for Pancreas Fistula biochemical leak. Some APs can be diagnosed preoperatively, but the rarer subtypes such as ours are more difficult to visualize on imaging. In gastrectomy, it is both oncologically important and technically challenging to perform lymph node dissection around the pancreas. In this case with an especially proximal pancreas, a circular stapler was considered better suited for gastroduodenal anastomosis and required a broader field than that afforded by laparoscopy. A case of non-typical annular pancreas diagnosed during laparoscopic gastric surgery is described.
en-copyright=
kn-copyright=

en-aut-name=TakahashiToshiaki
en-aut-sei=Takahashi
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KikuchSatoru
en-aut-sei=Kikuch
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakedaSho
en-aut-sei=Takeda
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KondoYoshitaka
en-aut-sei=Kondo
en-aut-mei=Yoshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=annular pancreas
kn-keyword=annular pancreas
en-keyword=gastric cancer
kn-keyword=gastric cancer
en-keyword=laparoscopic distal gastrectomye
kn-keyword=laparoscopic distal gastrectomye
END

start-ver=1.4
cd-journal=joma
no-vol=20
cd-vols=
no-issue=1
article-no=
start-page=374
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221130
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Involvement in the tumor-infiltrating CD8(+) T cell expression by the initial disease of remnant gastric cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Remnant gastric cancer (RGC) has been increasing for various reasons such as a longer life span, medical progress, and others. It generally has a poor prognosis, and its mechanism of occurrence is unknown. The purpose of this study was to evaluate the clinicopathological features of and clarify the oncological features of RGC. Methods Between January 2002 and January 2017, 39 patients with RGC following distal gastrectomy underwent curative surgical resection at the Okayama University Hospital; their medical records and immunohistochemically stained extracted specimens were used for retrospective analysis. Results On univariate analysis, initial gastric disease, pathological lymph node metastasis, and pathological stage were the significant factors associated with poor overall survival (p=0.014, 0.0061, and 0.016, respectively). Multivariate analysis of these 3 factors showed that only initial gastric disease caused by malignant disease was an independent factor associated with a poor prognosis (p=0.014, hazard ratio: 4.2, 95% confidence interval: 1.3-13.0). In addition, tumor-infiltrating CD8(+) T cells expression was higher in the benign disease group than in the malignant group (p=0.046). Conclusions Initial gastrectomy caused by malignant disease was an independent poor prognostic factor of RGC, and as one of the causes, lower level of tumor-infiltrating CD8(+) T cells in RGC may involve in.
en-copyright=
kn-copyright=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate  School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Remnant gastric cancer
kn-keyword=Remnant gastric cancer
en-keyword=Prognostic factor
kn-keyword=Prognostic factor
en-keyword=Tumor-infiltrating lymphocytes
kn-keyword=Tumor-infiltrating lymphocytes
en-keyword=CD8(+) T cell
kn-keyword=CD8(+) T cell
en-keyword=Tumor immunity
kn-keyword=Tumor immunity
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=20152
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221123
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dual-targeted near-infrared photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in the tumor microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer-associated fibroblasts (CAFs) play a significant role in tumor progression within the tumor microenvironment. Previously, we used near-infrared photoimmunotherapy (NIR-PIT), a next-generation cancer cell-targeted phototherapy, to establish CAF-targeted NIR-PIT. In this study, we investigated whether dual-targeted NIR-PIT, targeting cancer cells and CAFs, could be a therapeutic strategy. A total of 132 cases of esophageal cancer were analyzed for epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and fibroblast activation protein (FAP) expression using immunohistochemistry. Human esophageal cancer cells and CAFs were co-cultured and treated with single- or dual-targeted NIR-PIT in vitro. These cells were co-inoculated into BALB/c-nu/nu mice and the tumors were treated with single-targeted NIR-PIT or dual-targeted NIR-PIT in vivo. Survival analysis showed FAP- or EGFR-high patients had worse survival than patients with low expression of FAP or EGFR (log-rank, P < 0.001 and P = 0.074, respectively), while no difference was observed in HER2 status. In vitro, dual (EGFR/FAP)-targeted NIR-PIT induced specific therapeutic effects in cancer cells and CAFs along with suppressing tumor growth in vivo, whereas single-targeted NIR-PIT did not show any significance. Moreover, these experiments demonstrated that dual-targeted NIR-PIT could treat cancer cells and CAFs simultaneously with a single NIR light irradiation. We demonstrated the relationship between EGFR/FAP expression and prognosis of patients with esophageal cancer and the stronger therapeutic effect of dual-targeted NIR-PIT than single-targeted NIR-PIT in experimental models. Thus, dual-targeted NIR-PIT might be a promising therapeutic strategy for cancer treatment.
en-copyright=
kn-copyright=

en-aut-name=SatoHiroaki
en-aut-sei=Sato
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KawasakiKento
en-aut-sei=Kawasaki
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AkaiMasaaki
en-aut-sei=Akai
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KobayashiTeruki
en-aut-sei=Kobayashi
en-aut-mei=Teruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NishiwakiNoriyuki
en-aut-sei=Nishiwaki
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NarusakaToru
en-aut-sei=Narusaka
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KomotoSatoshi
en-aut-sei=Komoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KatsuraYuki
en-aut-sei=Katsura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KobayashiHisataka
en-aut-sei=Kobayashi
en-aut-mei=Hisataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda
kn-affil=

affil-num=18
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=27
cd-vols=
no-issue=
article-no=
start-page=3
end-page=13
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221215
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) antibody, provide improved clinical outcome in certain cancers. However, pancreatic ductal adeno-carcinoma (PDAC) is refractory to PD-1 blockade therapy due to poor immune response. Oncolytic virotherapy is a novel approach for inducing immunogenic cell death (ICD). We demonstrated the therapeutic potential of p53-expressing telo-merase-specific oncolytic adenovirus OBP-702 to induce ICD and anti-tumor immune responses in human PDAC cells with different p53 status (Capan-2, PK-59, PK-45H, Capan-1, MIA PaCa-2, BxPC-3) and murine PDAC cells (PAN02). OBP-702 significantly enhanced ICD with secretion of extracel-lular adenosine triphosphate and high-mobility group box pro-tein B1 by inducing p53-mediated apoptosis and autophagy. OBP-702 significantly promoted the tumor infiltration of CD8+ T cells and the anti-tumor efficacy of PD-1 blockade in a subcutaneous PAN02 syngeneic tumor model. Our results suggest that oncolytic adenovirus-mediated p53 overexpres-sion augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade.
en-copyright=
kn-copyright=

en-aut-name=ArakiHiroyuki
en-aut-sei=Araki
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KajiwaraYoshinori
en-aut-sei=Kajiwara
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamadaMotohiko
en-aut-sei=Yamada
en-aut-mei=Motohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=13540
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220808
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=RNA editing facilitates the enhanced production of neoantigens during the simultaneous administration of oxaliplatin and radiotherapy in colorectal cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Most cases of colorectal cancers (CRCs) are microsatellite stable (MSS), which frequently demonstrate lower response rates to immune checkpoint inhibitors (ICIs). RNA editing produces neoantigens by altering amino acid sequences. In this study, RNA editing was induced artificially by chemoradiation therapy (CRT) to generate neoantigens in MSS CRCs. Altogether, 543 CRC specimens were systematically analyzed, and the expression pattern of ADAR1 was investigated. In vitro and in vivo experiments were also performed. The RNA editing enzyme ADAR1 was upregulated in microsatellite instability-high CRCs, leading to their high affinity for ICIs. Although ADAR1 expression was low in MSS CRC, CRT including oxaliplatin (OX) treatment upregulated RNA editing levels by inducing ADAR1. Immunohistochemistry analyses showed the upregulation of ADAR1 in patients with CRC treated with CAPDX (capecitabine +OX) radiation therapy relative to ADAR1 expression in patients with CRC treated only by surgery (p <0.001). Compared with other regimens, CRT with OX effectively induced RNA editing in MSS CRC cell lines (HT29 and Caco2, p <0.001) via the induction of type 1 interferon-triggered ADAR1 expression. CRT with OX promoted the RNA editing of cyclin I, a neoantigen candidate. Neoantigens can be artificially induced by RNA editing via an OX-CRT regimen. CRT can promote proteomic diversity via RNA editing.
en-copyright=
kn-copyright=

en-aut-name=KomatsuYasuhiro
en-aut-sei=Komatsu
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakedaSho
en-aut-sei=Takeda
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakahashiKazutaka
en-aut-sei=Takahashi
en-aut-mei=Kazutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HataNanako
en-aut-sei=Hata
en-aut-mei=Nanako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=UmedaHibiki
en-aut-sei=Umeda
en-aut-mei=Hibiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YoshidaKazuhiro
en-aut-sei=Yoshida
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MoriYoshiko
en-aut-sei=Mori
en-aut-mei=Yoshiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=YasuiKazuya
en-aut-sei=Yasui
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KondoYoshitaka
en-aut-sei=Kondo
en-aut-mei=Yoshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KishimotoHiroyuki
en-aut-sei=Kishimoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=MichiueHiroyuki
en-aut-sei=Michiue
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=GoelAjay
en-aut-sei=Goel
en-aut-mei=Ajay
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Neutron Therapy  Research Center, Okayama University
kn-affil=

affil-num=18
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Department of Molecular  Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Biomedical Research  Center
kn-affil=

affil-num=20
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and  Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=2022
cd-vols=
no-issue=5
article-no=
start-page=rjac101
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220501
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Anorectal leiomyoma with GLUT1 overexpression mimicking malignancy on FDG-PET/CT
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 43-year-old female underwent pelvic magnetic resonance imaging for uterine myoma that incidentally revealed a 4.6 x 2.8 cm soft tissue mass in the anorectal region. Rectal endoscopy showed a submucosal tumor just above the anal canal. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed an anorectal tumor with very high FDG uptake. Aspiration cytology and needle biopsy were inconclusive, and the patient underwent trans-perineal tumor resection. The excised tumor was a 4.6 x 3.5 x 2.7 cm gray-white bifurcated nodular tumor. Light microscopy revealed fenestrated growth of poorly dysmorphic short spindle-shaped cells with eosinophilic sporophytes. Immunohistochemical staining was positive for alpha SMA and desmin, negative for CD117 (KIT) and S100, and the patient was diagnosed with benign leiomyoma. Tumor cells were also positive for glucose transporter-1 (GLUT1) immunohistochemically. It is important to keep in mind that FDG-PET/CT may show false-positive results even in benign anal leiomyoma for various reasons, including GLUT1 overexpression.
en-copyright=
kn-copyright=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=25
cd-vols=
no-issue=
article-no=
start-page=249
end-page=261
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220616
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Modulation of p53 expression in cancer-associated fibroblasts prevents peritoneal metastasis of cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are associated with the establishment and progression of peritoneal metastasis. This study investigated the efficacy of replicative oncolytic adenovirus-mediated p53 gene therapy (OBP-702) against CAFs and peritoneal metastasis of gastric cancer (GC). Higher CAF expression in the primary tumor was associated with poor prognosis of GC, and higher CAF expression was also observed with peritoneal metastasis in immunohistochemical analysis of clinical samples. And, we found transcriptional alteration of p53 in CAFs relative to normal gastric fibroblasts (NGFs). CAFs increased the secretion of cancer-promoting cytokines, including interleukin-6, and gained resistance to chemotherapy relative to NGFs. OBP-702 showed cytotoxicity to both GC cells and CAFs but not to NGFs. Overexpression of wild-type p53 by OBP-702 infection caused apoptosis and autophagy of CAFs and decreased the secretion of cancer-promoting cytokines by CAFs. Combination therapy using intraperitoneal administration of OBP-702 and paclitaxel synergistically inhibited the tumor growth of peritoneal metastases and decreased CAFs in peritoneal metastases. OBP-702, a replicative oncolytic adenovirus-mediated p53 gene therapy, offers a promising biological therapeutic strategy for peritoneal metastasis, modulating CAFs in addition to achieving tumor lysis.
en-copyright=
kn-copyright=

en-aut-name=OgawaToshihiro
en-aut-sei=Ogawa
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TabuchiMotoyasu
en-aut-sei=Tabuchi
en-aut-mei=Motoyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MitsuiEma
en-aut-sei=Mitsui
en-aut-mei=Ema
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UneYuta
en-aut-sei=Une
en-aut-mei=Yuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Oncolys BioPharma
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220409
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Tumor-targeted fluorescence labeling systems for cancer diagnosis and treatment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Conventional imaging techniques are available for clinical identification of tumor sites. However, detecting metastatic tumor cells that are spreading from primary tumor sites using conventional imaging techniques remains difficult. In contrast, fluorescence-based labeling systems are useful tools for detecting tumor cells at the single-cell level in cancer research. The ability to detect fluorescent-labeled tumor cells enables investigations of the biodistribution of tumor cells for the diagnosis and treatment of cancer. For example, the presence of fluorescent tumor cells in the peripheral blood of cancer patients is a predictive biomarker for early diagnosis of distant metastasis. The elimination of fluorescent tumor cells without damaging normal tissues is ideal for minimally invasive treatment of cancer. To capture fluorescent tumor cells within normal tissues, however, tumor-specific activated target molecules are needed. This review focuses on recent advances in tumor-targeted fluorescence labeling systems, in which indirect reporter labeling using tumor-specific promoters is applied to fluorescence labeling of tumor cells for the diagnosis and treatment of cancer. Telomerase promoter-dependent fluorescence labeling using replication-competent viral vectors produces fluorescent proteins that can be used to detect and eliminate telomerase-positive tumor cells. Tissue-specific promoter-dependent fluorescence labeling enables identification of specific tumor cells. Vimentin promoter-dependent fluorescence labeling is a useful tool for identifying tumor cells that undergo epithelial-mesenchymal transition (EMT). The evaluation of tumor cells undergoing EMT is important for accurately assessing metastatic potential. Thus, tumor-targeted fluorescence labeling systems represent novel platforms that enable the capture of tumor cells for the diagnosis and treatment of cancer.
en-copyright=
kn-copyright=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SakuraiFuminori
en-aut-sei=Sakurai
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MizuguchiHiroyuki
en-aut-sei=Mizuguchi
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KobayashiHisataka
en-aut-sei=Kobayashi
en-aut-mei=Hisataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ImamuraTakeshi
en-aut-sei=Imamura
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences

affil-num=2
en-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Laboratory of Biochemistry and  Molecular Biology, Graduate School  of Pharmaceutical Sciences, Osaka  University
kn-affil=

affil-num=6
en-affil=Laboratory of Biochemistry and  Molecular Biology, Graduate School  of Pharmaceutical Sciences, Osaka  University
kn-affil=

affil-num=7
en-affil=Molecular Imaging Branch, Center  for Cancer Research, National Cancer  Institute, National Institutes of Health
kn-affil=

affil-num=8
en-affil=Department of Molecular Medicine for  Pathogenesis, Ehime University Graduate  School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological  Surgery, Okayama University Graduate  School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=
en-keyword=adenovirus
kn-keyword=adenovirus
en-keyword=EMT
kn-keyword=EMT
en-keyword=survivin
kn-keyword=survivin
en-keyword=telomerase
kn-keyword=telomerase
en-keyword=vimentin
kn-keyword=vimentin
END

start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=2
article-no=
start-page=203
end-page=215
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202204
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression.
en-copyright=
kn-copyright=

en-aut-name=MasudaTomoya
en-aut-sei=Masuda
en-aut-mei=Tomoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IedaTakeshi
en-aut-sei=Ieda
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Oncolys BioPharma Inc.
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=esophageal cancer
kn-keyword=esophageal cancer
en-keyword=EMT
kn-keyword=EMT
en-keyword=TGF-β
kn-keyword=TGF-β
en-keyword=oncolytic adenovirus
kn-keyword=oncolytic adenovirus
en-keyword=E1A
kn-keyword=E1A
END

start-ver=1.4
cd-journal=joma
no-vol=407
cd-vols=
no-issue=2
article-no=
start-page=871
end-page=877
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=2022112
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Surgical technique of suprapancreatic D2 lymphadenectomy focusing on the posterior hepatic plexus for advanced gastric cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose<br>
Although D2 lymphadenectomy is currently considered a standard procedure for advanced gastric cancer (GC) worldwide, there is room for discussion about the appropriate range of suprapancreatic D2 lymphadenectomy. Focusing on the posterior hepatic plexus (PHP), which is not well recognized, we developed a surgical technique of suprapancreatic D2 lymphadenectomy, which we have called PHP-D2, and its short-term and long-term efficacies were evaluated in comparison with non-PHP-D2.<br>
<br>
Methods<br>
GC patients who underwent distal gastrectomy with D2 lymphadenectomy between July 2006 and May 2013 were enrolled, from which patients who had peritoneal metastasis and/or were peritoneal cytology-positive during surgery were excluded. Their medical records were retrospectively reviewed.<br>
<br>
Results<br>
Ninety-two patients (non-PHP-D2: 48, PHP-D2: 44) were enrolled. Shorter operation time (330 min vs 275 min, p < 0.0001) and less blood loss (290 mL vs 125 mL, p < 0.0001) were observed in PHP-D2, and no pancreatic fistulas were observed in PHP-D2. More lymph nodes of #11p (1 vs 1.5, p = 0.0328) and #12a lymph nodes (0 vs 1, p = 0.0034) were retrieved in PHP-D2, with no significant differences in #8a and #9 lymph nodes. Lymphatic recurrence was significantly less in PHP-D2 (p = 0.0166), and univariate and multivariate analyses showed that non-PHP-D2 was a significant risk factor for lymphatic recurrence (p = 0.0158), although there were no significant differences between non-PHP-D2 and PHP-D2 in 5-year overall survival and 5-year relapse-free survival.<br>
<br>
Conclusion<br>
PHP-D2 was a safe and feasible procedure that had the potential to reduce lymphatic recurrence, and it can be a standard procedure of D2 lymphadenectomy for advanced GC.
en-copyright=
kn-copyright=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakedaSho
en-aut-sei=Takeda
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
en-keyword=Gastric cancer
kn-keyword=Gastric cancer
en-keyword=D2 lymphadenectomy
kn-keyword=D2 lymphadenectomy
en-keyword=Suprapancreatic lymphadenectomy
kn-keyword=Suprapancreatic lymphadenectomy
en-keyword=Posterior hepatic plexus
kn-keyword=Posterior hepatic plexus
en-keyword=Distal gastrectomy
kn-keyword=Distal gastrectomy
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=9
article-no=
start-page=e04574
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes mellitus: A report of two cases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitor-induced diabetes mellitus is a rare immune-related adverse event. This report illustrates clinical data and insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes.
en-copyright=
kn-copyright=

en-aut-name=FujiwaraNoriko
en-aut-sei=Fujiwara
en-aut-mei=Noriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NodaYohei
en-aut-sei=Noda
en-aut-mei=Yohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KataokaHitomi
en-aut-sei=Kataoka
en-aut-mei=Hitomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=2
en-affil=Department of Primary Care and Medical Education, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Diabetes Center, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Primary Care and Medical Education, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=Minimally Invasive Therapy Center, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
en-keyword=C-peptide
kn-keyword=C-peptide
en-keyword=diabetes mellitus
kn-keyword=diabetes mellitus
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=insulin secretion
kn-keyword=insulin secretion
END

start-ver=1.4
cd-journal=joma
no-vol=29
cd-vols=
no-issue=10
article-no=
start-page=2920
end-page=2930
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210521
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.
en-copyright=
kn-copyright=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KumonKento
en-aut-sei=Kumon
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TsumuraTomoko
en-aut-sei=Tsumura
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YagiChiaki
en-aut-sei=Yagi
en-aut-mei=Chiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SugimotoRyoma
en-aut-sei=Sugimoto
en-aut-mei=Ryoma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HamadaYuki
en-aut-sei=Hamada
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

affil-num=1
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Oncolys BioPharma, Inc
kn-affil=

affil-num=15
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Extracellular vesicles
kn-keyword=Extracellular vesicles
en-keyword=Exosome
kn-keyword=Exosome
en-keyword=Abscopal effect
kn-keyword=Abscopal effect
en-keyword=Oncolytic adenovirus
kn-keyword=Oncolytic adenovirus
en-keyword=Local treatment
kn-keyword=Local treatment
en-keyword=Systemic delivery
kn-keyword=Systemic delivery
en-keyword=Drug delivery system
kn-keyword=Drug delivery system
END

start-ver=1.4
cd-journal=joma
no-vol=153
cd-vols=
no-issue=
article-no=
start-page=98
end-page=108
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20218
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Phase I dose-escalation study of endoscopic intratumoral injection of OBP-301 (Telomelysin) with radiotherapy in oesophageal cancer patients unfit for standard treatments
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose: OBP-301 (Telomelysin) is an attenuated type-5 adenovirus that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 sensitises human cancer cells to ionising radiation by inhibiting DNA repair, and radiation enhances coxsackievirus and adenovirus receptor-mediated OBP-301 infection on the contrary. We assessed OBP-301 with radiotherapy in oesophageal cancer patients unfit for standard chemoradiation treatments.<br>
<br>
Methods: A phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed oesophageal cancer patients deemed unfit to undergo surgery or chemotherapy. Study treatment consisted of OBP-301 administration by intratumoural needle injection using a flexible endoscope on days 1, 18 and 32. Radiotherapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy.<br>
<br>
Results: Of the 13 patients, 7, 3 and 3 patients were treated with 10(10), 10(11) and 10(12) virus particles, respectively. Study group comprised 10 males and 3 females, with a median age of 82 years (range, 53-91 years). All patients developed a transient, self-limited lymphopenia. Distribution studies revealed transient virus shedding in the plasma. Eight patients had local complete response (CR); all of them exhibited no pathologically viable malignant cells in biopsy specimens, and 3 patients had a partial response. The objective response rate was 91.7%. The clinical CR rate was 83.3% in stage I and 60.0% in stage II/III. Histopathological examination revealed massive infiltration of CD8 thorn cells and increased PD-L1 expression.<br>
<br>
Conclusion: Multiple courses of endoscopic intratumoural OBP-301 injection with radiotherapy are feasible and provide clinical benefits in patients with oesophageal cancer unfit for standard treatments. (C) 2021 Elsevier Ltd. All rights reserved.
en-copyright=
kn-copyright=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TanabeShunsuke
en-aut-sei=Tanabe
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KoujimaTakeshi
en-aut-sei=Koujima
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KatsuiKuniaki
en-aut-sei=Katsui
en-aut-mei=Kuniaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KanazawaSusumu
en-aut-sei=Kanazawa
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Telomerase
kn-keyword=Telomerase
en-keyword=adenovirus
kn-keyword=adenovirus
en-keyword=radiotherapy
kn-keyword=radiotherapy
en-keyword=esophageal cancer
kn-keyword=esophageal cancer
en-keyword=immunotherapy
kn-keyword=immunotherapy
END

start-ver=1.4
cd-journal=joma
no-vol=88
cd-vols=
no-issue=3
article-no=
start-page=513
end-page=524
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=2021610
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background <br>Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53–expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells.<br><br>
Materials and methods <br>The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model.<br><br>
Results <br>DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model.<br><br>
Conclusion <br>Our results suggest that MDR1 is attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.
en-copyright=
kn-copyright=

en-aut-name=SugiuKazuhisa
en-aut-sei=Sugiu
en-aut-mei=Kazuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HaseiJoe
en-aut-sei=Hasei
en-aut-mei=Joe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YamakawaYasuaki
en-aut-sei=Yamakawa
en-aut-mei=Yasuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OmoriToshinori
en-aut-sei=Omori
en-aut-mei=Toshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KomatsubaraTadashi
en-aut-sei=Komatsubara
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MochizukiYusuke
en-aut-sei=Mochizuki
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KondoHiroya
en-aut-sei=Kondo
en-aut-mei=Hiroya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OsakiShuhei
en-aut-sei=Osaki
en-aut-mei=Shuhei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraTomohiro
en-aut-sei=Fujiwara
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YoshidaAki
en-aut-sei=Yoshida
en-aut-mei=Aki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KunisadaToshiyuki
en-aut-sei=Kunisada
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=UedaKoji
en-aut-sei=Ueda
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

affil-num=1
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Project for Personalized Cancer Medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research
kn-affil=

affil-num=14
en-affil=Oncolys BioPharma, Inc
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Orthopaedic Surgery, Okayama University Hospital
kn-affil=

affil-num=17
en-affil=Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Osteosarcoma
kn-keyword=Osteosarcoma
en-keyword=Chemoresistance
kn-keyword=Chemoresistance
en-keyword=MDR1
kn-keyword=MDR1
en-keyword=Oncolytic adenovirus
kn-keyword=Oncolytic adenovirus
en-keyword=p53
kn-keyword=p53
END

start-ver=1.4
cd-journal=joma
no-vol=89
cd-vols=
no-issue=
article-no=
start-page=105946
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20215
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Efficacy and safety of short-term (3 days) enoxaparin in preventing venous thromboembolism after gastric cancer surgery: A single-center, prospective cohort study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Pharmacologic prophylaxis such as enoxaparin for venous thromboembolism (VTE) is rarely used in Japan, even following abdominal cancer surgery, for which it is recommended in relevant guidelines (at least 7 days of use) along with mechanical prophylaxis with intermittent pneumatic compression. Reasons for enoxaparin’s unpopularity include concerns over postoperative bleeding and its inconvenience in clinical practice. Here, we conducted a prospective clinical study of short-term (3 days) use of enoxaparin, which is considered to minimally impact postoperative management without increasing bleeding risk.<br>
Methods: Gastric cancer patients who underwent gastrectomy received enoxaparin for 3 days from postoperative day (POD) 1 to 4. The primary endpoint was the incidence of deep vein thrombosis (DVT), which was examined primarily via Doppler ultrasonography of the lower limbs between POD 8 and 14. The planned sample size was 70, which was calculated based on an estimated incidence rate of 9% and an upper limit of incidence rate of 20%, with alpha of 0.05 and beta of 0.2.<br>
Results: A total of 70 gastric cancer patients were enrolled, and ultimately, 68 patients received the protocol intervention and DVT evaluation. Sixty-seven patients completed 6 enoxaparin injections, but 1 patient did not complete the course due to abdominal bleeding after initiation. The incidence of DVT was 4.4% (3/68), and the 95% upper confidence interval was 12.2%, lower than the 20% threshold we set as the upper limit of DVT incidence. DVT was detected only in the peripheral veins of the lower extremities in all 3 affected patients. The incidence of bleeding-related complications, which were not severe, was 1.5% (1/68).<br>
Conclusions: Short-term (3 days) use of enoxaparin was shown to be effective and safe for VTE prophylaxis, comparable to regular use (at least 7 days), in postoperative management of gastric cancer surgery.
en-copyright=
kn-copyright=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WatanabeMegumi
en-aut-sei=Watanabe
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KuwadaKazuya
en-aut-sei=Kuwada
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TsumuraTomoko
en-aut-sei=Tsumura
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HinotsuShiro
en-aut-sei=Hinotsu
en-aut-mei=Shiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Biostatistics and Data Management, Sapporo Medical University School of Medicine
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=51
cd-vols=
no-issue=
article-no=
start-page=1978
end-page=1984
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=2021529
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Accreditation as a qualified surgeon improves surgical outcomes in laparoscopic distal gastrectomy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose: The Endoscopic Surgical Skill Quantification System for qualified surgeons (QSs) was introduced in Japan to improve surgical outcomes. This study reviewed the surgical outcomes after initial experience performing laparoscopic distal gastrectomy (LDG) and evaluated the improvement in surgical outcomes following accreditation as a QS.<br>
Methods: Eighty-seven consecutive patients who underwent LDG for gastric cancer by a single surgeon were enrolled in this study. The cumulative sum method was used to analyze the learning curve for LDG. The surgical outcomes were evaluated according to the two phases of the learning curve (learning period vs. mastery period) and accreditation (non-QS period vs. QS period).<br>
Results: The learning period for LDG was 48 cases. Accreditation was approved at the 67th case. The operation time and estimated blood loss were significantly reduced in the QS period compared to the non-QS period (230 vs. 270 min, p<0.001; 20.5 vs. 59.8 ml, p=0.024, respectively). Furthermore, the major complication rate was significantly lower in the QS period than in the non-QS period (0 vs. 10.6%, p=0.044).<br>
Conclusions: Experience performing approximately 50 cases is required to reach proficiency in LDG. After receiving accreditation as a QS, the surgical outcomes, including the complication rate, were improved.
en-copyright=
kn-copyright=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KagawaTetsuya
en-aut-sei=Kagawa
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakataNobuo
en-aut-sei=Takata
en-aut-mei=Nobuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KuwadaKazuya
en-aut-sei=Kuwada
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ShojiRyohei
en-aut-sei=Shoji
en-aut-mei=Ryohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MitsuhashiToshiharu
en-aut-sei=Mitsuhashi
en-aut-mei=Toshiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Shikoku Cancer Center
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Surgery, Okayama Red Cross Hospital
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Endoscopic surgical skill quantification system
kn-keyword=Endoscopic surgical skill quantification system
en-keyword=Qualified surgeon
kn-keyword=Qualified surgeon
en-keyword=Laparoscopic distal gastrectomy
kn-keyword=Laparoscopic distal gastrectomy
en-keyword=Gastric cancer
kn-keyword=Gastric cancer
en-keyword=Cumulative sum analysis
kn-keyword=Cumulative sum analysis
END

start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=4
article-no=
start-page=e0250643
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210422
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS.
en-copyright=
kn-copyright=

en-aut-name=OmoriToshinori
en-aut-sei=Omori
en-aut-mei=Toshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YamakawaYasuaki
en-aut-sei=Yamakawa
en-aut-mei=Yasuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OsakiShuhei
en-aut-sei=Osaki
en-aut-mei=Shuhei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HaseiJoe
en-aut-sei=Hasei
en-aut-mei=Joe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SugiuKazuhisa
en-aut-sei=Sugiu
en-aut-mei=Kazuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KomatsubaraTadashi
en-aut-sei=Komatsubara
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=FujiwaraTomohiro
en-aut-sei=Fujiwara
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YoshidaAki
en-aut-sei=Yoshida
en-aut-mei=Aki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KunisadaToshiyuki
en-aut-sei=Kunisada
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Gastric yolk sac Tumor-like carcinoma
kn-keyword=Gastric yolk sac Tumor-like carcinoma
en-keyword=Adenocarcinoma; Alpha-fetoprotein
kn-keyword=Adenocarcinoma; Alpha-fetoprotein
END

start-ver=1.4
cd-journal=joma
no-vol=7
cd-vols=
no-issue=1
article-no=
start-page=111
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Long-term survival without recurrence after surgery for gastric yolk sac tumor-like carcinoma: a case report
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Gastric yolk sac tumor (YST)-like carcinoma is extremely rare, and its prognosis is poor, because most patients have widespread metastases at the time of diagnosis. We report a case of gastric YST-like carcinoma with an adenocarcinoma component without metastases in which curative resection was performed. Case presentation A 77-year-old man complaining of melena and dizziness due to anemia was diagnosed with poorly differentiated adenocarcinoma in the gastric cardia, with a benign ulcer in the gastric body. He underwent total gastrectomy with D2 lymph node dissection for the tumor. Histological examination of the resected specimens revealed a mixture of reticular and glandular neoplastic components morphologically. In the reticular area, an endodermal sinus pattern and some Schiller-Duval bodies were confirmed. Gastric YST-like carcinoma with adenocarcinoma components, T2N0M0 Stage IB, was diagnosed. Immunohistochemical analysis showed that the YST was positive for carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and p53. In contrast, the adenocarcinoma was positive for p53 and negative for CEA and AFP. The patient remained healthy as of 7 years postoperatively, with no recurrence. Conclusions Routine medical examinations or endoscopic examinations for accidental symptom may be helpful for early diagnosis and good prognosis for gastric YST-like carcinoma, although the prognosis is generally poor.
en-copyright=
kn-copyright=

en-aut-name=UmedaHibiki
en-aut-sei=Umeda
en-aut-mei=Hibiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Gastric yolk sac Tumor-like carcinoma
kn-keyword=Gastric yolk sac Tumor-like carcinoma
en-keyword=Adenocarcinoma
kn-keyword=Adenocarcinoma
en-keyword=Alpha-fetoprotein
kn-keyword=Alpha-fetoprotein
END

start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=2
article-no=
start-page=231
end-page=238
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202104
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Long-term Survival with a Rare Advanced Primary Gastrointestinal Malignant Melanoma Treated with Laparoscopic Surgery/Immune Checkpoint Inhibitor
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Targeted therapies for malignant melanoma have improved patients’ prognoses. A primary gastrointestinal malignant melanoma is very rare, with no standard treatment strategy. We treated a 78-year-old Japanese female with advanced primary gastrointestinal melanoma of the descending colon and gallbladder. We administered a multidisciplinary treatment: surgical resection of the descending colon and gallbladder tumors, resection of the metastatic lymph nodes behind the pancreas head, and immune checkpoint antibody-blockade therapy (nivolumab) for ~4 years. PET/CT demonstrated no recurrent lesion for > 3 years.  Multidisciplinary therapies (e.g., surgery, chemotherapy, radiotherapy, target therapy, and immune checkpoint antibody-blockade therapy) can successfully treat primary gastrointestinal malignant melanoma.
en-copyright=
kn-copyright=

en-aut-name=EndoMotochika
en-aut-sei=Endo
en-aut-mei=Motochika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AsanoHiroaki
en-aut-sei=Asano
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakedaSho
en-aut-sei=Takeda
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HamadaYuki
en-aut-sei=Hamada
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KondoYoshitaka
en-aut-sei=Kondo
en-aut-mei=Yoshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Surgery, Mitoyo general Hospital
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=primary gastrointestinal melanoma
kn-keyword=primary gastrointestinal melanoma
en-keyword=laparoscopic surgery
kn-keyword=laparoscopic surgery
en-keyword=immune checkpoint antibody-blockade inhibitor
kn-keyword=immune checkpoint antibody-blockade inhibitor
END

start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=1
article-no=
start-page=102
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210128
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Extracellular vesicles shed from gastric cancer mediate protumor macrophage differentiation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background</br>
Peritoneal dissemination often develops in gastric cancer. Tumor-associated macrophages (TAMs) are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination, facilitating tumor progression. However, the mechanism by which macrophages differentiate into tumor-associated macrophages in the peritoneal cavity is not well understood. In this study, the interplay between gastric cancer-derived extracellular vesicles (EVs) and macrophages was investigated.</br>
Methods</br>
The association between macrophages and EVs in peritoneal ascitic fluid of gastric cancer patients, or from gastric cancer cell lines was examined, and their roles in differentiation of macrophages and potentiation of the malignancy of gastric cancer were further explored.</br>
Results</br>
Immunofluorescent assays of the ascitic fluid showed that M2 macrophages were predominant along with the cancer cells in the peritoneal cavity. EVs purified from gastric cancer cells, as well as malignant ascitic fluid, differentiated peripheral blood mononuclear cell-derived macrophages into the M2-like phenotype, which was demonstrated by their morphology and expression of CD163/206. The macrophages differentiated by gastric cancer-derived EVs promoted the migration ability of gastric cancer cells, and the EVs carried STAT3 protein.</br>
Conclusion</br>
EVs derived from gastric cancer play a role by affecting macrophage phenotypes, suggesting that this may be a part of the underlying mechanism that forms the intraperitoneal cancer microenvironment.
en-copyright=
kn-copyright=

en-aut-name=ItoAtene
en-aut-sei=Ito
en-aut-mei=Atene
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SakamotoShuichi
en-aut-sei=Sakamoto
en-aut-mei=Shuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KuwadaKazuya
en-aut-sei=Kuwada
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KajiokaHiroki
en-aut-sei=Kajioka
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YoshimotoMasashi
en-aut-sei=Yoshimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Extracellular vesicles
kn-keyword=Extracellular vesicles
en-keyword=Gastric cancer
kn-keyword=Gastric cancer
en-keyword=Tumor-associated macrophages
kn-keyword=Tumor-associated macrophages
en-keyword=Tumor microenvironment
kn-keyword=Tumor microenvironment
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=1
article-no=
start-page=1693
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210118
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.
en-copyright=
kn-copyright=

en-aut-name=KatsubeRyoichi
en-aut-sei=Katsube
en-aut-mei=Ryoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NishiwakiNoriyuki
en-aut-sei=Nishiwaki
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KobayashiTeruki
en-aut-sei=Kobayashi
en-aut-mei=Teruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KomotoSatoshi
en-aut-sei=Komoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SatoHiroaki
en-aut-sei=Sato
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KobayashiHisataka
en-aut-sei=Kobayashi
en-aut-mei=Hisataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=2
article-no=
start-page=879
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210117
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Real-Time Fluorescence Image-Guided Oncolytic Virotherapy for Precise Cancer Treatment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Oncolytic virotherapy is one of the most promising, emerging cancer therapeutics. We generated three types of telomerase-specific replication-competent oncolytic adenovirus: OBP-301; a green fluorescent protein (GFP)-expressing adenovirus, OBP-401; and Killer-Red-armed OBP-301. These oncolytic adenoviruses are driven by the human telomerase reverse transcriptase (hTERT) promoter; therefore, they conditionally replicate preferentially in cancer cells. Fluorescence imaging enables visualization of invasion and metastasis in vivo at the subcellular level; including molecular dynamics of cancer cells, resulting in greater precision therapy. In the present review, we focused on fluorescence imaging applications to develop precision targeting for oncolytic virotherapy. Cell-cycle imaging with the fluorescence ubiquitination cell cycle indicator (FUCCI) demonstrated that combination therapy of an oncolytic adenovirus and a cytotoxic agent could precisely target quiescent, chemoresistant cancer stem cells (CSCs) based on decoying the cancer cells to cycle to S-phase by viral treatment, thereby rendering them chemosensitive. Non-invasive fluorescence imaging demonstrated that complete tumor resection with a precise margin, preservation of function, and prevention of distant metastasis, was achieved with fluorescence-guided surgery (FGS) with a GFP-reporter adenovirus. A combination of fluorescence imaging and laser ablation using a KillerRed-protein reporter adenovirus resulted in effective photodynamic cancer therapy (PDT). Thus, imaging technology and the designer oncolytic adenoviruses may have clinical potential for precise cancer targeting by indicating the optimal time for administering therapeutic agents; accurate surgical guidance for complete resection of tumors; and precise targeted cancer-specific photosensitization.
en-copyright=
kn-copyright=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KishimotoHiroyuki
en-aut-sei=Kishimoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HoffmanRobert M.
en-aut-sei=Hoffman
en-aut-mei=Robert M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=AntiCancer, Inc.
kn-affil=
en-keyword=cancer cell cycle
kn-keyword=cancer cell cycle
en-keyword=fluorescent proteins
kn-keyword=fluorescent proteins
en-keyword=FUCCI
kn-keyword=FUCCI
en-keyword=imaging
kn-keyword=imaging
en-keyword=adenovirus
kn-keyword=adenovirus
en-keyword=oncolytic virotherapy
kn-keyword=oncolytic virotherapy
en-keyword=cancer stem cell
kn-keyword=cancer stem cell
en-keyword=mouse model
kn-keyword=mouse model
en-keyword=orthotopic
kn-keyword=orthotopic
END

start-ver=1.4
cd-journal=joma
no-vol=497
cd-vols=
no-issue=
article-no=
start-page=1
end-page=3
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210128
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Surgery is the only curative treatment option for pancreatic cancer, but patients often develop postoperative recurrence. Surgical invasiveness might be involved in the mechanism of recurrence. The associations among inflammation caused by surgery, neutrophils, and cancer metastasis were investigated. At first, neutrophil extracellular traps (NETs) were examined in clinical specimens, and NETs were observed around metastatic tumors. To explore how NETs were induced, neutrophils were cultured with pancreatic cancer or in cancer-conditioned medium. Neutrophils formed NETs when they were cultured with pancreatic cancer or even its conditioned medium. The effects of NETs on cancer cells were further investigated in vitro and in vivo. NETs induced the epithelial to mesenchymal transition in cancer cells and thereby promoted their migration and invasion. HMGB1 derived from NETs appeared to potentiate the malignancy of cancer cells. In a mouse model of liver metastasis with inflammation, NETs participated in the metastatic process by enhancing extravasation. Interestingly, thrombomodulin degraded HMGB1 and consequently inhibited the induction of NETs, thereby preventing pancreatic cancer metastasis to the liver. In conclusion, NETs interact reciprocally with pancreatic cancer cells, which play a pivotal role in inflammation-associated metastasis. Targeting NETs with thrombomodulin can be a novel strategy to improve the surgical outcome of pancreatic cancer patients.
en-copyright=
kn-copyright=

en-aut-name=KajiokaHiroki
en-aut-sei=Kajioka
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ItoAtene
en-aut-sei=Ito
en-aut-mei=Atene
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YoshimotoMasashi
en-aut-sei=Yoshimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SakamotoShuichi
en-aut-sei=Sakamoto
en-aut-mei=Shuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=HMGB1
kn-keyword=HMGB1
en-keyword=Epithelial to mesenchymal transition
kn-keyword=Epithelial to mesenchymal transition
en-keyword=Phorbol 12-myristate 13-acetate
kn-keyword=Phorbol 12-myristate 13-acetate
en-keyword=Ischemia-reperfusion model
kn-keyword=Ischemia-reperfusion model
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=11
article-no=
start-page=e0242223
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201112
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Short-term and long-term comparisons of laparoscopy-assisted proximal gastrectomy with esophagogastrostomy by the double-flap technique and laparoscopy-assisted total gastrectomy for proximal gastric cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background</br>
Although proximal gastrectomy (PG) is a recognized surgical procedure for early proximal gastric cancer, total gastrectomy (TG) is sometimes selected due to concern about severe gastroesophageal reflux. Esophagogastrostomy by the double-flap technique (DFT) is an anti-reflux reconstruction after PG, and its short-term effectiveness has been reported. However, little is known about the long-term effects on nutritional status and quality of life (QOL).</br> 
Methods</br>
Gastric cancer patients who underwent laparoscopy-assisted PG (LAPG) with DFT or laparoscopy-assisted TG (LATG) between April 2011 and March 2014 were retrospectively analyzed. Body weight (BW), body mass index (BMI), and prognostic nutritional index (PNI) were reviewed to assess nutritional status, and the Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 was used to assess QOL.</br> 
Results</br>
A total of 36 patients (LATG: 17, LAPG: 19) were enrolled. Four of 17 LATG patients (24%) were diagnosed with Stage ≥II after surgery, and half received S-1 adjuvant chemotherapy. BW and PNI were better maintained in LAPG than in LATG patients until 1-year follow-up. Seven of 16 LATG patients (44%) were categorized as “underweight (BMI<18.5 kg/m2)” at 1-year follow-up, compared to three of 18 LAPG patients (17%; p = 0.0836). The PGSAS-45 showed no significant difference in all QOL categories except for decreased BW (p = 0.0132). Multivariate analysis showed that LATG was the only potential risk factor for severe BW loss (odds ratio: 3.03, p = 0.0722).</br> 
Conclusions</br>
LAPG with DFT was superior to LATG in postoperative nutritional maintenance, and can be the first option for early proximal gastric cancer.
en-copyright=
kn-copyright=

en-aut-name=TsumuraTomoko
en-aut-sei=Tsumura
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakataNobuo
en-aut-sei=Takata
en-aut-mei=Nobuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ItoAtene
en-aut-sei=Ito
en-aut-mei=Atene
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=WatanabeMegumi
en-aut-sei=Watanabe
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KuwadaKazuya
en-aut-sei=Kuwada
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=
article-no=
start-page=1405
end-page=1417
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201105
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1) antibody have recently improved clinical outcome in certain cancer patients; however, osteosarcoma (OS) patients are refractory to PD-1 blockade. Oncolytic virotherapy has emerged as novel immunogenic therapy to augment antitumor immune response. We developed a telomerase-specific replication-competent oncolytic adenovirus OBP-502 that induces lytic cell death via binding to integrins. In this study, we assessed the combined effect of PD-1 blockade and OBP-502 in OS cells. The expression of coxsackie and adenovirus receptor (CAR), integrins αvβ3 and αvβ5, and programmed cell death ligand 1 (PD-L1) was analyzed in two murine OS cells (K7M2, NHOS). The cytopathic activity of OBP-502 in both cells was analyzed using the XTT assay. OBP-502-induced immunogenic cell death was assessed by analyzing the level of extracellular ATP and high-mobility group box protein B1 (HMGB1). Subcutaneous tumor models for K7M2 and NHOS cells were used to evaluate the antitumor effect and number of tumor-infiltrating CD8+ cells in combination therapy. K7M2 and NHOS cells showed high expression of integrins αvβ3 and αvβ5, but not CAR. OBP-502 significantly suppressed the viability of both cells, in which PD-L1 expression and the release of ATP and HMGB1 were significantly increased. Intratumoral injection of OBP-502 significantly augmented the efficacy of PD-1 blockade on subcutaneous K2M2 and NHOS tumor models via enhancement of tumor-infiltrating CD8+  T cells. Our results suggest that telomerase-specific oncolytic virotherapy is a promising antitumor strategy to promote the efficacy of PD-1 blockade in OS.
en-copyright=
kn-copyright=

en-aut-name=MochizukiYusuke
en-aut-sei=Mochizuki
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=DemiyaKoji
en-aut-sei=Demiya
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KureMiho
en-aut-sei=Kure
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KondoHiroya
en-aut-sei=Kondo
en-aut-mei=Hiroya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KomatsubaraTadashi
en-aut-sei=Komatsubara
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SugiuKazuhisa
en-aut-sei=Sugiu
en-aut-mei=Kazuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HaseiJoe
en-aut-sei=Hasei
en-aut-mei=Joe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YoshidaAki
en-aut-sei=Yoshida
en-aut-mei=Aki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KunisadaToshiyuki
en-aut-sei=Kunisada
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Sports Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Oncolys BioPharma, Inc,
kn-affil=

affil-num=12
en-affil=Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Oncolytic adenovirus
kn-keyword=Oncolytic adenovirus
en-keyword=hTERT
kn-keyword=hTERT
en-keyword=Immunogenic cell death
kn-keyword=Immunogenic cell death
en-keyword=ATP
kn-keyword=ATP
en-keyword=CD8
kn-keyword=CD8
END

start-ver=1.4
cd-journal=joma
no-vol=2021
cd-vols=
no-issue=14
article-no=
start-page=640
end-page=643
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201027
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Intracorporeal semi‐hand‐sewn Billroth I reconstruction in total laparoscopic distal gastrectomy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction</br>
Intracorporeal Billroth I (B‐I) reconstruction using an endoscopic linear stapler (ELS) is widely performed in total laparoscopic distal gastrectomy. However, conventional procedures require many ELSs for anastomosis. Here, we introduce the novel intracorporeal semi‐hand‐sewn (SHS) B‐I reconstruction.</br>
Materials and surgical technique</br>
After the transection of stomach and duodenum using ELS following adequate lymph node dissection, small entry holes were made on the anterior wall in the greater curvature of the stomach and the duodenal stump. The posterior walls of both the remnant stomach and the duodenum were attached with the ELS and fired to create the posterior wall of the B‐I anastomosis. All the transection line of the duodenum and one‐third of the transection line of the stomach were dissected; finally the anterior wall suturing at the anastomotic site was performed by the laparoscopic hand‐sewn technique.</br>
Discussion</br>
SHS procedure was performed for 17 gastric cancer patients. There were no intraoperative complications or conversions to open surgery. One intra‐abdominal abscess was observed although there was no anastomotic leakage. The median reconstruction time was 48 minutes (32‐63). The SHS procedure was safe, feasible, and economical, although it requires sufficient laparoscopic suturing and ligation skill.
en-copyright=
kn-copyright=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KuwadaKazuya
en-aut-sei=Kuwada
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakataNobuo
en-aut-sei=Takata
en-aut-mei=Nobuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=Kakiuchi Yoshihiko
en-aut-sei=Kakiuchi
en-aut-mei= Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=Noma Kazuhiro
en-aut-sei=Noma 
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Billroth I reconstruction
kn-keyword=Billroth I reconstruction
en-keyword=gastric cancer
kn-keyword=gastric cancer
en-keyword=laparoscopic distal gastrectomy
kn-keyword=laparoscopic distal gastrectomy
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=9
article-no=
start-page=2655
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200917
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=FUCCI Real-Time Cell-Cycle Imaging as a Guide for Designing Improved Cancer Therapy: A Review of Innovative Strategies to Target Quiescent Chemo-Resistant Cancer Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Progress in chemotherapy of solid cancer has been tragically slow due, in large part, to the chemoresistance of quiescent cancer cells in tumors. The fluorescence ubiquitination cell-cycle indicator (FUCCI) was developed in 2008 by Miyawaki et al., which color-codes the phases of the cell cycle in real-time. FUCCI utilizes genes linked to different color fluorescent reporters that are only expressed in specific phases of the cell cycle and can, thereby, image the phases of the cell cycle in real-time. Intravital real-time FUCCI imaging within tumors has demonstrated that an established tumor comprises a majority of quiescent cancer cells and a minor population of cycling cancer cells located at the tumor surface or in proximity to tumor blood vessels. In contrast to most cycling cancer cells, quiescent cancer cells are resistant to cytotoxic chemotherapy, most of which target cells in S/G2/M phases. The quiescent cancer cells can re-enter the cell cycle after surviving treatment, which suggests the reason why most cytotoxic chemotherapy is often ineffective for solid cancers. Thus, quiescent cancer cells are a major impediment to effective cancer therapy. FUCCI imaging can be used to effectively target quiescent cancer cells within tumors. For example, we review how FUCCI imaging can help to identify cell-cycle-specific therapeutics that comprise decoy of quiescent cancer cells from G1 phase to cycling phases, trapping the cancer cells in S/G2 phase where cancer cells are mostly sensitive to cytotoxic chemotherapy and eradicating the cancer cells with cytotoxic chemotherapy most active against S/G2 phase cells. FUCCI can readily image cell-cycle dynamics at the single cell level in real-time in vitro and in vivo. Therefore, visualizing cell cycle dynamics within tumors with FUCCI can provide a guide for many strategies to improve cell-cycle targeting therapy for solid cancers.
en-copyright=
kn-copyright=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HoffmanRobert M.
en-aut-sei=Hoffman
en-aut-mei=Robert M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=AntiCancer, Inc.
kn-affil=
en-keyword=cell cycle
kn-keyword=cell cycle
en-keyword=fluorescent proteins
kn-keyword=fluorescent proteins
en-keyword=FUCCI
kn-keyword=FUCCI
en-keyword=imaging
kn-keyword=imaging
en-keyword=targeted cancer therapy
kn-keyword=targeted cancer therapy
en-keyword=quiescent cancer cells
kn-keyword=quiescent cancer cells
en-keyword=decoy
kn-keyword=decoy
en-keyword=chemotherapy
kn-keyword=chemotherapy
END

start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=
article-no=
start-page=14
end-page=23
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Elimination of MYCN-Amplified Neuroblastoma Cells by Telomerase-Targeted Oncolytic Virus via MYCN Suppression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. High-risk NB is characterized by MYCN amplification and human telomerase reverse transcriptase (hTERT) rearrangement, contributing to hTERT activation and a poor outcome. For targeting hTERT-activated tumors, we developed two oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in which the hTERT promoter drives expression of the viral E1 gene for tumor-specific virus replication. In this study, we demonstrate the therapeutic potential of the hTERT-driven oncolytic adenoviruses OBP-301 and OBP-702 using four human MYCN-amplified NB cell lines (IMR-32, CHP-134, NB-1, LA-N-5) exhibiting high hTERT expression. OBP-301 and OBP-702 exhibited a strong antitumor effect in association with autophagy in NB cells. Virus-mediated activation of E2F1 protein suppressed MYCN expression. OBP-301 and OBP-702 significantly suppressed the growth of subcutaneous CHP-134 tumors. Thus, these hTERT-driven oncolytic adenoviruses are promising antitumor agents for eliminating MYCN-amplified NB cells via E2F1-mediated suppression of MYCN protein.
en-copyright=
kn-copyright=

en-aut-name=TanimotoTerutaka
en-aut-sei=Tanimoto
en-aut-mei=Terutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IedaTakeshi
en-aut-sei=Ieda
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NousoHiroshi
en-aut-sei=Nouso
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TaniMorimichi
en-aut-sei=Tani
en-aut-mei=Morimichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OyamaTakanori
en-aut-sei=Oyama
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NodaTakuo
en-aut-sei=Noda
en-aut-mei=Takuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=neuroblastoma
kn-keyword=neuroblastoma
en-keyword=MYCN
kn-keyword=MYCN
en-keyword=hTERT
kn-keyword=hTERT
en-keyword=adenovirus
kn-keyword=adenovirus
en-keyword=E2F1
kn-keyword=E2F1
END

start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=
article-no=
start-page=262
end-page=271
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Boosting Replication and Penetration of Oncolytic Adenovirus by Paclitaxel Eradicate Peritoneal Metastasis of Gastric Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Peritoneal metastasis is the most frequent form of distant metastasis and recurrence in gastric cancer, and the prognosis is extremely poor due to the resistance of systemic chemotherapy. Here, we demonstrate that intraperitoneal (i.p.) administration of a green fluorescence protein (GFP)-expressing attenuated adenovirus with oncolytic potency (OBP-401) synergistically suppressed the peritoneal metastasis of gastric cancer in combination with paclitaxel (PTX). OBP-401 synergistically suppressed the viability of human gastric cancer cells in combination with PTX. PTX enhanced the antitumor effect of OBP-401 due to enhanced viral replication in cancer cells. The combination therapy increased induction of mitotic catastrophe, resulting in accelerated autophagy and apoptosis. Peritoneally disseminated nodules were selectively visualized as GFP-positive spots by i.p. administration of OBP-401 in an orthotopic human gastric cancer peritoneal dissemination model. PTX enhanced the deep penetration of OBP-401 into the disseminated nodules. Moreover, a non-invasive in vivo imaging system demonstrated that the combination therapy of i.p. OBP-401 administration with PTX significantly inhibited growth of peritoneal metastatic tumors and the amount of malignant ascites. i.p. virotherapy with PTX may be a promising treatment strategy for the peritoneal metastasis of gastric cancer.
en-copyright=
kn-copyright=

en-aut-name=IshikawaWataru
en-aut-sei=Ishikawa
en-aut-mei=Wataru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OgawaToshihiro
en-aut-sei=Ogawa
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TabuchiMotoyasu
en-aut-sei=Tabuchi
en-aut-mei=Motoyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Oncolys BioPharma, Inc.
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=peritoneal metastasis
kn-keyword=peritoneal metastasis
en-keyword=adenovirus
kn-keyword=adenovirus
en-keyword=gastric cancer
kn-keyword=gastric cancer
en-keyword=intraperitoneal chemotherapy
kn-keyword=intraperitoneal chemotherapy
en-keyword=paclitaxel
kn-keyword=paclitaxel
en-keyword=oncolytic virus
kn-keyword=oncolytic virus
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=2
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200218
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Adenovirus serotype 5 (Ad5) is widely and frequently used as a virus vector in cancer gene therapy and oncolytic virotherapy. Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas.
en-copyright=
kn-copyright=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HaseiJoe
en-aut-sei=Hasei
en-aut-mei=Joe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=oncolytic adenovirus
kn-keyword=oncolytic adenovirus
en-keyword=hTERT
kn-keyword=hTERT
en-keyword=autophagy
kn-keyword=autophagy
en-keyword=GFP
kn-keyword=GFP
en-keyword=p53
kn-keyword=p53
END

start-ver=1.4
cd-journal=joma
no-vol=28
cd-vols=
no-issue=3
article-no=
start-page=794
end-page=804
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs.
en-copyright=
kn-copyright=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KumonKento
en-aut-sei=Kumon
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TsumuraTomoko
en-aut-sei=Tsumura
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HashimotoMasashi
en-aut-sei=Hashimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MorihiroToshiaki
en-aut-sei=Morihiro
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KubotaTetsushi
en-aut-sei=Kubota
en-aut-mei=Tetsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=AoyamaKatsuyuki
en-aut-sei=Aoyama
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=俊
kn-aut-sei=
kn-aut-mei=俊
aut-affil-num=12
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=MizuguchiHiroyuki
en-aut-sei=Mizuguchi
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University
kn-affil=

affil-num=15
en-affil=Oncolys BioPharma
kn-affil=

affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=immune checkpoint
kn-keyword=immune checkpoint
en-keyword=programmed death-1
kn-keyword=programmed death-1
en-keyword=oncolytic adenovirus
kn-keyword=oncolytic adenovirus
en-keyword=combined immunotherapy
kn-keyword=combined immunotherapy
en-keyword=immunogenic cell death
kn-keyword=immunogenic cell death
en-keyword=tumor infiltrating lymphocytes
kn-keyword=tumor infiltrating lymphocytes
en-keyword=CD8
kn-keyword=CD8
en-keyword=abscopal effect
kn-keyword=abscopal effect
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=16378
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=2019118
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment-colorectal cancer network 
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epithelial-mesenchymal transition (EMT) is a biological process by which epithelial cells acquire mesenchymal characteristics. In malignant tumors, EMT is crucial for acquisition of a mesenchymal phenotype with invasive and metastatic properties, leading to tumor progression. An inflammatory microenvironment is thought to be responsible for the development and progression of colorectal cancer (CRC); however, the precise role of inflammatory microenvironments in EMT-related CRC progression remains unclear. Here, we show the spatiotemporal visualization of CRC cells undergoing EMT using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drives red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-alpha, IL-1 beta, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. In vivo experiments further demonstrated the distribution of RFP-positive CRC cells in rectal and metastatic tumors. Our data suggest that the EMT imaging system described here is a powerful tool for monitoring EMT in inflammatory microenvironment-CRC networks.
en-copyright=
kn-copyright=

en-aut-name=IedaTakeshi
en-aut-sei=Ieda
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OkabayashiHiroki
en-aut-sei=Okabayashi
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KishimotoHiroyuki
en-aut-sei=Kishimoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=SaitouTakashi
en-aut-sei=Saitou
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=ImamuraTakeshi
en-aut-sei=Imamura
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine
kn-affil=

affil-num=14
en-affil=Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=4633
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=2019315
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PD-L1 expression combined with microsatellite instability/CD8+tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer 
en-copyright=
kn-copyright=

en-aut-name=MorihiroToshiaki
en-aut-sei=Morihiro
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KanayaNobuhiko
en-aut-sei=Kanaya
en-aut-mei=Nobuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KubotaTetsushi
en-aut-sei=Kubota
en-aut-mei=Tetsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AoyamaKatsuyuki
en-aut-sei=Aoyama
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KikuchSatoru
en-aut-sei=Kikuch
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NagasakaTakeshi
en-aut-sei=Nagasaka
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Pathology, Okayama University
kn-affil=

affil-num=8
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Clinical Oncology, Kawasaki Medical School
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=3
cd-vols=
no-issue=1
article-no=
start-page=96
end-page=103
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2018
dt-pub=20181011
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Multicenter retrospective study to evaluate the efficacy and safety of the double-flap technique as antireflux esophagogastrostomy after proximal gastrectomy (rD-FLAP Study)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=AIM:
As a result of the difficulty in effective prevention of gastroesophageal reflux, no standard reconstruction procedure after proximal gastrectomy (PG) has yet been established. The double-flap technique (DFT), or Kamikawa procedure, is an antireflux reconstruction procedure in esophagogastrostomy. The efficacy of DFT has recently been reported in several studies. However, these were all single-center studies with a limited number of cases.<br/>
METHODS:<br/>
We conducted a multicenter retrospective study in which patients who underwent DFT, irrespective of disease type and reconstruction approach, at each participating institution between 1996 and 2015 were registered. Primary endpoint was incidence of reflux esophagitis at 1-year after surgery, and secondary endpoint was incidence of anastomosis-related complications.<br/>
RESULTS:<br/>
Of 546 patients who were eligible for this study, 464 patients who had endoscopic examination at 1-year follow up were evaluated for reflux esophagitis. Incidence of reflux esophagitis of all grades was 10.6% and that of grade B or higher was 6.0%. Male gender and anastomosis located in the mediastinum/intra-thorax were independent risk factors for grade B or higher reflux esophagitis (odds ratio [OR]: 4.21, 95% confidence interval [CI]: 1.44-10.9, P = 0.0109). Total incidence of anastomosis-related complications was 7.2%, including leakage in 1.5%, strictures in 5.5% and bleeding in 0.6% of cases. Laparoscopic reconstruction was the only independent risk factor for anastomosis-related complications (OR: 3.93, 95% CI: 1.93-7.80, P = 0.0003).<br/>
CONCLUSION:<br/>
Double-flap technique might be a feasible option after PG for effective prevention of reflux, although anastomotic stricture is a complication that must be well-prepared for.
en-copyright=
kn-copyright=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ChodaYasuhiro
en-aut-sei=Choda
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OtsukaShinya
en-aut-sei=Otsuka
en-aut-mei=Shinya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=UeyamaSatoshi
en-aut-sei=Ueyama
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TanakaNorimitsu
en-aut-sei=Tanaka
en-aut-mei=Norimitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MuraokaAtsushi
en-aut-sei=Muraoka
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HatoShinji
en-aut-sei=Hato
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KimuraToshikazu
en-aut-sei=Kimura
en-aut-mei=Toshikazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TanakayaKohji
en-aut-sei=Tanakaya
en-aut-mei=Kohji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TanabeShunsuke
en-aut-sei=Tanabe
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KamikawaYasuaki
en-aut-sei=Kamikawa
en-aut-mei=Yasuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Surgery, Hiroshima City Hiroshima Citizens Hospital
kn-affil=

affil-num=3
en-affil=Department of Surgery, Fukuyama Medical Center
kn-affil=

affil-num=4
en-affil=Department of Surgery, Mihara Red Cross Hospital
kn-affil=

affil-num=5
en-affil=Department of Surgery, Kagawa Prefectural Center Hospital
kn-affil=

affil-num=6
en-affil=Department of Surgery, Kagawa Rosai Hospital
kn-affil=

affil-num=7
en-affil=Department of Surgery, Shikoku Cancer Center
kn-affil=

affil-num=8
en-affil=Department of Surgery, Okayama Saiseikai General Hospital,
kn-affil=

affil-num=9
en-affil=Department of Surgery, Iwakuni Clinical Center
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Surgery, Matsuda Hospital
kn-affil=

affil-num=17
en-affil=Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Kamikawa procedure
kn-keyword=Kamikawa procedure
en-keyword=antireflux surgery
kn-keyword=antireflux surgery
en-keyword=double‐flap technique
kn-keyword=double‐flap technique
en-keyword=esophagogastrostomy
kn-keyword=esophagogastrostomy
en-keyword=proximal gastrectomy
kn-keyword=proximal gastrectomy
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=2
article-no=
start-page=177
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190203
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy.
en-copyright=
kn-copyright=

en-aut-name=KatsuraYuki
en-aut-sei=Katsura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NinomiyaTakayuki
en-aut-sei=Ninomiya
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SatoHiroaki
en-aut-sei=Sato
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KomotoSatoshi
en-aut-sei=Komoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NarusakaToru
en-aut-sei=Narusaka
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TomonoYasuko
en-aut-sei=Tomono
en-aut-mei=Yasuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=XingBoyi
en-aut-sei=Xing
en-aut-mei=Boyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ChenYuehua
en-aut-sei=Chen
en-aut-mei=Yuehua
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=Kasai Tomonari
en-aut-sei=Kasai 
en-aut-mei=Tomonari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil= Shigei Medical Research Institute
kn-affil=

affil-num=11
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=School of Bioscience and Biotechnology, Tokyo University of Technology
kn-affil=

affil-num=17
en-affil= Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems
kn-affil=

affil-num=18
en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=combination therapy
kn-keyword=combination therapy
en-keyword=iron
kn-keyword=iron
en-keyword=stemness
kn-keyword=stemness
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=12
article-no=
start-page=e1671760
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= A solid tumor consists of cancer and stromal cells, which comprise the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are usually abundant in the TME, contributing to tumor progression. In cases of peritoneal dissemination of gastric cancer (GC), the contribution of intraperitoneal TAMs remains unclear. Macrophages from peritoneal washings of GC patients were analyzed, and the link between intraperitoneal TAMs and GC cells was investigated to clarify the interaction between them in peritoneal dissemination. Macrophages were predominant among leukocytes constituting the microenvironment of the peritoneal cavity. The proportion of CD163-positive TAMs was significantly higher in stage IV than in stage I GC. Co-culture with TAMs potentiated migration and invasion of GC. IL-6 was the most increased in the medium of in vitro co-culture of macrophages and GC, and IL-6 elevation was also observed in the peritoneal washes with peritoneal dissemination. An elevated concentration of intraperitoneal IL-6 was correlated with a poor prognosis in clinical cases. In conclusion, intraperitoneal TAMs are involved in promoting peritoneal dissemination of GC via secreted IL-6. TAM-derived IL-6 could be a potential therapeutic target for peritoneal dissemination of GC.
en-copyright=
kn-copyright=

en-aut-name=SakamotoShuichi
en-aut-sei=Sakamoto
en-aut-mei=Shuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KuwadaKazuya
en-aut-sei=Kuwada
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ItoAtene
en-aut-sei=Ito
en-aut-mei=Atene
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KajiokaHiroki
en-aut-sei=Kajioka
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=WatanabeMegumi
en-aut-sei=Watanabe
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KagawaTetsuya
en-aut-sei=Kagawa
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Gastric cancer
kn-keyword=Gastric cancer
en-keyword=tumor-associated macrophages
kn-keyword=tumor-associated macrophages
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
en-keyword=peritoneal dissemination
kn-keyword=peritoneal dissemination
END

start-ver=1.4
cd-journal=joma
no-vol=71
cd-vols=
no-issue=2
article-no=
start-page=127
end-page=133
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2017
dt-pub=201704
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Currently, chemoradiation is the most widely used nonsurgical treatment for esophageal cancer. However, some patients, particularly the very elderly or those with severe vital organ dysfunction, face difficulty with the chemotherapy component. We therefore examined the outcome of radiation therapy (RT) alone for patients with esophageal cancer at our facility. Between January 2005 and December 2014, 84 patients underwent RT at our hospital, and 78 of these patients received concomitant chemotherapy. The remaining 6 patients underwent RT alone; these patients were considered to be high-risk and to have no lymph node metastasis (stage I). Five of them received irradiation up to a curative dose: 4 showed a complete response (CR) and 1 showed a partial response (PR). Of the patients exhibiting CR, 3 are currently living recurrence-free, whereas 1 patient underwent endoscopic submucosal dissection (ESD) as salvage therapy for local recurrence, with no subsequent recurrence. High-risk stage I esophageal cancer patients can be treated radically with RT alone under certain conditions. In the future, to broaden the indications for RT monotherapy to include some degree of advanced cancers, a novel concurrent therapy should be identified.
en-copyright=
kn-copyright=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MaedaNaoaki
en-aut-sei=Maeda
en-aut-mei=Naoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TanabeShunsuke
en-aut-sei=Tanabe
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KatsuiKuniaki
en-aut-sei=Katsui
en-aut-mei=Kuniaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KatayamaNorihisa
en-aut-sei=Katayama
en-aut-mei=Norihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KanazawaSusumu
en-aut-sei=Kanazawa
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=esophageal cancer
kn-keyword=esophageal cancer
en-keyword=radiation therapy
kn-keyword=radiation therapy
en-keyword=high-risk patient
kn-keyword=high-risk patient
END

start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=5
article-no=
start-page=401
end-page=404
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201610
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Phase II Clinical Trial of the Efficacy and Safety of Short-term (3 days) Enoxaparin for the Prevention of Venous Thromboembolism after Gastric Cancer Surgery
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Although intermittent pneumatic compression (IPC) has become common as perioperative prophylaxis for venous thromboembolism (VTE) consisting of pulmonary thromboembolism (PE) and deep vein thrombosis (DVT), the prophylactic effect against VTE, especially lethal PE, is not yet satisfactory. Therefore, pharmacologic prophylaxis, such as with enoxaparin, is desirable. While the efficacy and safety of enoxaparin have been proven in several clinical trials, concern about bleeding with longterm (at least 7 days) use have potentially decreased its widespread adoption. We have launched a phase II study to evaluate the efficacy and safety of short-term (3 days) enoxaparin, in which a total of 70 gastric cancer patients undergoing gastrectomy will be recruited, and the primary endpoint is the incidence of DVT. This study could contribute to making pharmacologic prophylaxis for VTE more common.
en-copyright=
kn-copyright=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HinotsuShiro
en-aut-sei=Hinotsu
en-aut-mei=Shiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=venous thromboembolism
kn-keyword=venous thromboembolism
en-keyword=enoxaparin
kn-keyword=enoxaparin
en-keyword=short-term use
kn-keyword=short-term use
en-keyword=gastric cancer
kn-keyword=gastric cancer
en-keyword=surgery
kn-keyword=surgery
END

start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=3
article-no=
start-page=213
end-page=216
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201606
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Recurrence after Endoscopic Curative Resection of Mucosal Gastric Cancer Associated with an Adjacent Neoplastic Precursor Lesion
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 69-year-old man underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) at the lesser curvature in the angle of stomach. Histological examination revealed tub1, pM, ly0, v0, pLM(-), pVM(-), and the resection was considered curative. The scar after ESD was followed by esophagogastroduodenoscopy (EGD) and biopsy. Twenty months later, EGD showed an ulcerative lesion in the vicinity of the ESD scar, and histological examination of the biopsy specimen showed adenocarcinoma. A distal gastrectomy with lymph node dissection was then performed. Postoperative pathology showed tub1, pM, pN0, ly0, v0, and Stage 1A. Skip lesions were seen in the specimen resected by ESD, and the histological review confirmed so-called “dysplasia-like atypia” (DLA) between the lesions. It has been reported recently that in DLA, the dysplasia-like change involves only the bases of the pits, without upper pit or surface epithelium involvement, and it is said that the rate of DLA is higher in gastric cancer patients. We speculated that a precancerous lesion close to the resected cancer developed into a local recurrence.
en-copyright=
kn-copyright=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KubotaTetsushi
en-aut-sei=Kubota
en-aut-mei=Tetsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KuwadaKazuya
en-aut-sei=Kuwada
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KagawaTetsuya
en-aut-sei=Kagawa
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=dysplasia-like atypia
kn-keyword=dysplasia-like atypia
en-keyword=early gastric cancer
kn-keyword=early gastric cancer
en-keyword=endoscopic submucosal dissection
kn-keyword=endoscopic submucosal dissection
en-keyword=local recurrence
kn-keyword=local recurrence
END

start-ver=1.4
cd-journal=joma
no-vol=69
cd-vols=
no-issue=3
article-no=
start-page=173
end-page=176
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=201506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Prone-Position Thoracoscopic Ligation of the Thoracic Duct for Chyle Leak Following Radical Neck Dissection in a Patient with a Right Aortic Arch
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A chyle leak can occur as a complication after neck or chest surgery. Such a leak prolongs the hospital stay and is sometimes life-threatening. The treatment options are conservative management, interventional radiologic embolization, and surgery. Thoracoscopic ligation of the thoracic duct has emerged as a promising and definitive treatment. The case of a 65-year-old Japanese male patient with a rare congenital right aortic arch (typeⅢB1 of Edwardʼs classification) and a severe chyle leak that occurred after a total pharyngolaryngo-esophagectomy (TPLE) is described. The chyle leak was successfully managed by thoracoscopic ligation of the thoracic duct via a left-side approach with the patient in the prone position.
en-copyright=
kn-copyright=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MaedaNaoaki
en-aut-sei=Maeda
en-aut-mei=Naoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TanabeShunsuke
en-aut-sei=Tanabe
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=6
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=8
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=chyle leak
kn-keyword=chyle leak
en-keyword=thoracic duct
kn-keyword=thoracic duct
en-keyword=thoracoscopy
kn-keyword=thoracoscopy
en-keyword=prone position
kn-keyword=prone position
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20141219
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients.
en-copyright=
kn-copyright=

en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KishimotoHiroyuki
en-aut-sei=Kishimoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NagasakaTakeshi
en-aut-sei=Nagasaka
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=Robert M Hoffman
en-aut-sei=Robert M Hoffman
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=6
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=8
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=9
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=10
en-affil=
kn-affil=Oncolys BioPharma, Inc.

affil-num=11
en-affil=
kn-affil=Department of Surgery, University of California

affil-num=12
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=endoscopic treatment
kn-keyword=endoscopic treatment
en-keyword=adenovirus
kn-keyword=adenovirus
en-keyword=colorectal cancer
kn-keyword=colorectal cancer
en-keyword=lymphatic metastasis
kn-keyword=lymphatic metastasis
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140528
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Fluorescence virus-guided capturing system of human colorectal circulating tumour cells for non-invasive companion diagnostics
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Molecular-based companion diagnostic tests are being used with increasing frequency to predict their clinical response to various drugs, particularly for molecularly targeted drugs. However, invasive procedures are typically required to obtain tissues for this analysis. Circulating tumour cells (CTCs) are novel biomarkers that can be used for the prediction of disease progression and are also important surrogate sources of cancer cells. Because current CTC detection strategies mainly depend on epithelial cell-surface markers, the presence of heterogeneous populations of CTCs with epithelial and/or mesenchymal characteristics may pose obstacles to the detection of CTCs. 


Methods We developed a new approach to capture live CTCs among millions of peripheral blood leukocytes using a green fluorescent protein (GFP)-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication (OBP-401, TelomeScan). 


Results Our biological capturing system can image epithelial and mesenchymal tumour cells with telomerase activities as GFP-positive cells. After sorting, direct sequencing or mutation-specific PCR can precisely detect different mutations in KRAS, BRAF and KIT genes in epithelial, mesenchymal or epithelial–mesenchymal transition-induced CTCs, and in clinical blood samples from patients with colorectal cancer. 


Conclusions This fluorescence virus-guided viable CTC capturing method provides a non-invasive alternative to tissue biopsy or surgical resection of primary tumours for companion diagnostics.
en-copyright=
kn-copyright=

en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MoriYoshiko
en-aut-sei=Mori
en-aut-mei=Yoshiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KishimotoHiroyuki
en-aut-sei=Kishimoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NagasakaTakeshi
en-aut-sei=Nagasaka
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=GoelAjay
en-aut-sei=Goel
en-aut-mei=Ajay
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=6
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=8
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=9
en-affil=
kn-affil=Oncolys BioPharma, Inc.

affil-num=10
en-affil=
kn-affil=Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center

affil-num=11
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=12
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
END

start-ver=1.4
cd-journal=joma
no-vol=19
cd-vols=
no-issue=23
article-no=
start-page=6495
end-page=6505
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20131201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Genetically Engineered Oncolytic Adenovirus Decoys and Lethally Traps Quiescent Cancer Stem-like Cells in S/G(2)/M Phases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose: Because chemoradiotherapy selectively targets proliferating cancer cells, quiescent cancer stem-like cells are resistant. Mobilization of the cell cycle in quiescent leukemia stem cells sensitizes them to cell death signals. However, it is unclear that mobilization of the cell cycle can eliminate quiescent cancer stem-like cells in solid cancers. Thus, we explored the use of a genetically-engineered telomerase-specific oncolytic adenovirus, OBP-301, to mobilize the cell cycle and kill quiescent cancer stem-like cells. 

Experimental Design: We established CD133(+) cancer stem-like cells from human gastric cancer MKN45 and MKN7 cells. We investigated the efficacy of OBP-301 against quiescent cancer stem-like cells. We visualized the treatment dynamics of OBP-301 killing of quiescent cancer stem-like cells in dormant tumor spheres and xenografts using a fluorescent ubiquitination cell-cycle indicator (FUCCI). 

Results: CD133(+) gastric cancer cells had stemness properties. OBP-301 efficiently killed CD133(+) cancer stem-like cells resistant to chemoradiotherapy. OBP-301 induced cell-cycle mobilization from G(0)-G(1) to S/G(2)/M phases and subsequent cell death in quiescent CD133(+) cancer stem-like cells by mobilizing cell-cycle-related proteins. FUCCI enabled visualization of quiescent CD133(+) cancer stem-like cells and proliferating CD133(-) non-cancer stem-like cells. Three-dimensional visualization of the cell-cycle behavior in tumor spheres showed that CD133(+) cancer stem-like cells maintained stemness by remaining in G(0)-G(1) phase. We showed that OBP-301 mobilized quiescent cancer stem-like cells in tumor spheres and xenografts into S/G(2)/M phases where they lost viability and cancer stem-like cell properties and became chemosensitive. 

Conclusion: Oncolytic adenoviralinfection is an effective mechanism of cancer cell killing in solid cancer and can be a new therapeutic paradigm to eliminate quiescent cancer stem-like cells.
en-copyright=
kn-copyright=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KishimotoHiroyuki
en-aut-sei=Kishimoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NagasakaTakeshi
en-aut-sei=Nagasaka
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=HoffmanRobert M.
en-aut-sei=Hoffman
en-aut-mei=Robert M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=2
en-affil=
kn-affil=Okayama Univ Hosp, Ctr Innovat Clin Med

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=10
en-affil=
kn-affil=Oncolys BioPharma Inc

affil-num=11
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=12
en-affil=
kn-affil=Univ Calif San Diego, Dept Surg

affil-num=13
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
END

start-ver=1.4
cd-journal=joma
no-vol=67
cd-vols=
no-issue=6
article-no=
start-page=333
end-page=342
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201312
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oncolytic Adenovirus-Induced Autophagy: Tumor-Suppressive Effect and Molecular Basis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Autophagy is a catabolic process that produces energy through lysosomal degradation of intracellular organelles. Autophagy functions as a cytoprotective factor under physiological conditions such as nutrient deprivation, hypoxia, and interruption of growth factors. On the other hand, infection with pathogenic viruses and bacteria also induces autophagy in infected cells. Oncolytic virotherapy with replication-competent viruses is thus a promising strategy to induce tumor-specific cell death. Oncolytic adenoviruses induce autophagy and subsequently contribute to cell death rather than cell survival in tumor cells. We previously developed a telomerase-specific replication-competent oncolytic adenovirus, OBP-301, which induces cell lysis in tumor cells with telomerase activities. OBP-301-mediated cytopathic activity is significantly associated with induction of autophagy biomarkers. In this review, we focus on the tumor-suppressive role and molecular basis of autophagic machinery induced by oncolytic adenoviruses. Addition of tumor-specific promoters and modification of the fiber knob of adenoviruses supports the oncolytic adenovirus-mediated autophagic cell death. Autophagy is cooperatively
regulated by the E1-dependent activation pathway, E4-dependent inhibitory pathway, and microRNA-dependent fine-tuning. Thus, future exploration of the functional role and molecular mechanisms underlying oncolytic adenovirus-induced autophagy would provide novel insights and improve the therapeutic potential of oncolytic adenoviruses.
en-copyright=
kn-copyright=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=
kn-affil=Center for Innovative Clinical Medicine, Okayama University Hospital

affil-num=2
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=oncolytic adenovirus
kn-keyword=oncolytic adenovirus
en-keyword=autophagy
kn-keyword=autophagy
en-keyword=E2F1
kn-keyword=E2F1
en-keyword=microRNA
kn-keyword=microRNA
END

start-ver=1.4
cd-journal=joma
no-vol=125
cd-vols=
no-issue=3
article-no=
start-page=195
end-page=199
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20131202
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis
kn-title=腫瘍融解アデノウイルスによるE2F1-マイクロRNA-7-EGFR経路を介したオートファジー細胞死の誘導分子機構
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=田澤大
kn-aut-sei=田澤
kn-aut-mei=大
aut-affil-num=1
ORCID=

en-aut-name=YanoSyuya
en-aut-sei=Yano
en-aut-mei=Syuya
kn-aut-name=矢野修也
kn-aut-sei=矢野
kn-aut-mei=修也
aut-affil-num=2
ORCID=

en-aut-name=YoshidaRyosuke
en-aut-sei=Yoshida
en-aut-mei=Ryosuke
kn-aut-name=吉田亮介
kn-aut-sei=吉田
kn-aut-mei=亮介
aut-affil-num=3
ORCID=

en-aut-name=YamasakiYasumoto
en-aut-sei=Yamasaki
en-aut-mei=Yasumoto
kn-aut-name=山崎泰源
kn-aut-sei=山崎
kn-aut-mei=泰源
aut-affil-num=4
ORCID=

en-aut-name=SasakiTsuyoshi
en-aut-sei=Sasaki
en-aut-mei=Tsuyoshi
kn-aut-name=佐々木剛
kn-aut-sei=佐々木
kn-aut-mei=剛
aut-affil-num=5
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=橋本悠里
kn-aut-sei=橋本
kn-aut-mei=悠里
aut-affil-num=6
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=黒田新士
kn-aut-sei=黒田
kn-aut-mei=新士
aut-affil-num=7
ORCID=

en-aut-name=OuchiMasaaki
en-aut-sei=Ouchi
en-aut-mei=Masaaki
kn-aut-name=大内正明
kn-aut-sei=大内
kn-aut-mei=正明
aut-affil-num=8
ORCID=

en-aut-name=OnishiTeppei
en-aut-sei=Onishi
en-aut-mei=Teppei
kn-aut-name=大西哲平
kn-aut-sei=大西
kn-aut-mei=哲平
aut-affil-num=9
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=宇野太
kn-aut-sei=宇野
kn-aut-mei=太
aut-affil-num=10
ORCID=

en-aut-name=KagawaSyunsuke
en-aut-sei=Kagawa
en-aut-mei=Syunsuke
kn-aut-name=香川俊輔
kn-aut-sei=香川
kn-aut-mei=俊輔
aut-affil-num=11
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=浦田泰生
kn-aut-sei=浦田
kn-aut-mei=泰生
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=藤原俊義
kn-aut-sei=藤原
kn-aut-mei=俊義
aut-affil-num=13
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学病院　新医療研究開発センター

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　整形外科学

affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=7
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=8
en-affil=
kn-affil=オンコリスバイオファーマ株式会社

affil-num=9
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=10
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=11
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=12
en-affil=
kn-affil=オンコリスバイオファーマ株式会社

affil-num=13
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学
en-keyword=アデノウイルス
kn-keyword=アデノウイルス
en-keyword=テロメラーゼ
kn-keyword=テロメラーゼ
en-keyword=マイクロRNA
kn-keyword=マイクロRNA
en-keyword=オートファジー
kn-keyword=オートファジー
en-keyword=EGFR
kn-keyword=EGFR
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=3
article-no=
start-page=314
end-page=325
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201303
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dual Programmed Cell Death Pathways Induced by p53 Transactivation Overcome Resistance to Oncolytic Adenovirus in Human Osteosarcoma Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Tumor suppressor p53 is a multifunctional transcription factor that regulates diverse cell fates, including apoptosis and autophagy in tumor biology. p53 overexpression enhances the antitumor activity of oncolytic adenoviruses; however, the molecular mechanism of this occurrence remains unclear. We previously developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301, that kills human osteosarcoma cells, but some human osteosarcoma cells were OBP-301-resistant. In this study, we investigated the antitumor activity of a p53-expressing oncolytic adenovirus, OBP-702, and the molecular mechanism of the p53-mediated cell death pathway in OBP-301-resistant human osteosarcoma cells. The cytopathic activity of OBP-702 was examined in OBP-301-sensitive (U2OS and HOS) and OBP-301-resistant (SaOS-2 and MNNG/HOS) human osteosarcoma cells. The molecular mechanism in the OBP-702-mediated induction of two cell death pathways, apoptosis and autophagy, was investigated in OBP-301-resistant osteosarcoma cells. The antitumor effect of OBP-702 was further assessed using an orthotopic OBP-301-resistant MNNG/HOS osteosarcoma xenograft tumor model. OBP-702 suppressed the viability of OBP-301-sensitive and -resistant osteosarcoma cells more efficiently than OBP-301 or a replication-deficient p53-expressing adenovirus (Ad-p53). OBP-702 induced more profound apoptosis and autophagy when compared with OBP-301 or Ad-p53. E1A-mediated miR-93/106b upregulation induced p21 suppression, leading to p53-mediated apoptosis and autophagy in OBP-702-infected cells. p53 overexpression enhanced adenovirus-mediated autophagy through activation of damage-regulated autophagy modulator (DRAM). Moreover, OBP-702 suppressed tumor growth in an orthotopic OBP-301-resistant MNNG/HOS xenograft tumor model. These results suggest that OBP-702-mediated p53 transactivation is a promising antitumor strategy to induce dual apoptotic and autophagic cell death pathways via regulation of miRNA and DRAM in human osteosarcoma cells. Mol Cancer Ther; 12(3); 314-25.
en-copyright=
kn-copyright=

en-aut-name=HaseiJoe
en-aut-sei=Hasei
en-aut-mei=Joe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SasakiTsuyoshi
en-aut-sei=Sasaki
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OsakiShuhei
en-aut-sei=Osaki
en-aut-mei=Shuhei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamakawaYasuaki
en-aut-sei=Yamakawa
en-aut-mei=Yasuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KunisadaToshiyuki
en-aut-sei=Kunisada
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YoshidaAki
en-aut-sei=Yoshida
en-aut-mei=Aki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OnishiTeppei
en-aut-sei=Onishi
en-aut-mei=Teppei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=11
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=12
en-affil=
kn-affil=Oncolys BioPharma Inc

affil-num=13
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=14
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
END

start-ver=1.4
cd-journal=joma
no-vol=7
cd-vols=
no-issue=6
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120615
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The hTERT Promoter Enhances the Antitumor Activity of an Oncolytic Adenovirus under a Hypoxic Microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin), in which the human telomerase reverse transcriptase (hTERT) promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5). In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen) or a hypoxic (1% oxygen) condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1 alpha and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells.
en-copyright=
kn-copyright=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KojimaToru
en-aut-sei=Kojima
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WatanabeYuichi
en-aut-sei=Watanabe
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=8
en-affil=
kn-affil=Oncolys BioPharma Inc

affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol

affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
END

start-ver=1.4
cd-journal=joma
no-vol=61
cd-vols=
no-issue=11
article-no=
start-page=1905
end-page=1916
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201211
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive breast and gastric cancers; however, acquired resistance presents a formidable obstacle to long-term tumor responses in the majority of patients. Here, we show the mechanism of resistance to trastuzumab in HER2-positive human cancer cells and explore the molecular sensitization by exogenous expression of HER2-extracellular domain (ECD) in HER2-negative or trastuzumab-resistant human cancer cells. We found that long-term exposure to trastuzumab induced resistance in HER2-positive cancer cells; HER2 expression was downregulated, and antibody-dependent cellular cytotoxicity (ADCC) activity was impaired. We next examined the hypothesis that trastuzumab-resistant cells could be re-sensitized by the transfer of non-functional HER2-ECD. Exogenous HER2-ECD expression induced by the stable transfection of a plasmid vector or infection with a replication-deficient adenovirus vector had no apparent effect on the signaling pathway, but strongly enhanced ADCC activity in low HER2-expressing or trastuzumab-resistant human cancer cells. Our data indicate that restoration of HER2-ECD expression sensitizes HER2-negative or HER2-downregulated human cancer cells to trastuzumab-mediated ADCC, an outcome that has important implications for the treatment of human cancers.
en-copyright=
kn-copyright=

en-aut-name=YoshidaRyosuke
en-aut-sei=Yoshida
en-aut-mei=Ryosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OnishiTeppei
en-aut-sei=Onishi
en-aut-mei=Teppei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SasakiTsuyoshi
en-aut-sei=Sasaki
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KishimotoHiroyuki
en-aut-sei=Kishimoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=2
en-affil=
kn-affil=Okayama Univ Hosp, Ctr Gene & Cell Therapy

affil-num=3
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=5
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=6
en-affil=
kn-affil=Okayama Univ, Dept Orthopaed Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=7
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=8
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=9
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=10
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=11
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci

affil-num=12
en-affil=
kn-affil=Okayama Univ, Dept Surg Gastroenterol, Grad Sch Med Dent & Pharmaceut Sci
en-keyword=HER2
kn-keyword=HER2
en-keyword=Extracellular domain
kn-keyword=Extracellular domain
en-keyword=Trastuzumab
kn-keyword=Trastuzumab
en-keyword=ADCC
kn-keyword=ADCC
en-keyword=Adenovirus
kn-keyword=Adenovirus
END

start-ver=1.4
cd-journal=joma
no-vol=125
cd-vols=
no-issue=1
article-no=
start-page=9
end-page=12
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Telomerase-specific virotherapy targeting lymph node micrometastasis of human cancer
kn-title=癌微小リンパ節転移を標的とするテロメラーゼ特異的制限増殖型ウイルス製剤の開発
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=KojimaToru
en-aut-sei=Kojima
en-aut-mei=Toru
kn-aut-name=児島亨
kn-aut-sei=児島
kn-aut-mei=亨
aut-affil-num=1
ORCID=

en-aut-name=WatanabeYuichi
en-aut-sei=Watanabe
en-aut-mei=Yuichi
kn-aut-name=渡邉雄一
kn-aut-sei=渡邉
kn-aut-mei=雄一
aut-affil-num=2
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=橋本悠里
kn-aut-sei=橋本
kn-aut-mei=悠里
aut-affil-num=3
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=黒田新士
kn-aut-sei=黒田
kn-aut-mei=新士
aut-affil-num=4
ORCID=

en-aut-name=YamasakiYasumoto
en-aut-sei=Yamasaki
en-aut-mei=Yasumoto
kn-aut-name=山崎泰源
kn-aut-sei=山崎
kn-aut-mei=泰源
aut-affil-num=5
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=矢野修也
kn-aut-sei=矢野
kn-aut-mei=修也
aut-affil-num=6
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=田澤大
kn-aut-sei=田澤
kn-aut-mei=大
aut-affil-num=7
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=宇野太
kn-aut-sei=宇野
kn-aut-mei=太
aut-affil-num=8
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=香川俊輔
kn-aut-sei=香川
kn-aut-mei=俊輔
aut-affil-num=9
ORCID=

en-aut-name=TanakaNoriaki
en-aut-sei=Tanaka
en-aut-mei=Noriaki
kn-aut-name=田中紀章
kn-aut-sei=田中
kn-aut-mei=紀章
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=浦田泰生
kn-aut-sei=浦田
kn-aut-mei=泰生
aut-affil-num=11
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=藤原俊義
kn-aut-sei=藤原
kn-aut-mei=俊義
aut-affil-num=12
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=2
en-affil=
kn-affil=オンコリスバイオファーマ

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=7
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=8
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=9
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=10
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=11
en-affil=
kn-affil=オンコリスバイオファーマ

affil-num=12
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学
en-keyword=telomerase
kn-keyword=telomerase
en-keyword=oncolytic adenovirus
kn-keyword=oncolytic adenovirus
en-keyword=lymph node metastasis
kn-keyword=lymph node metastasis
en-keyword=orthotopic colorectal cancer model
kn-keyword=orthotopic colorectal cancer model
en-keyword=<i>Alu</i> sequence
kn-keyword=<i>Alu</i> sequence
END

start-ver=1.4
cd-journal=joma
no-vol=119
cd-vols=
no-issue=10
article-no=
start-page=3172
end-page=3181
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2009
dt-pub=20091001
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A simple biological imaging system for detecting viable human circulating tumor cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The presence of circulating tumor cells (CTCs) in the peripheral blood is associated with short survival, making the detection of CTCs clinically useful as a prognostic factor of disease outcome and/or a surrogate marker of treatment response. Recent technical advances in immunocytometric analysis and quantitative real-time PCR have made it possible to detect a few CTCs in the blood; however, there is no sensitive assay to specifically detect viable CTCs. Here, we report what we believe to be a new approach to visually detect live human CTCs among millions of peripheral blood leukocytes, using a telomerase-specific replication-selective adenovirus expressing GFP. First, we constructed a GFP-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication (OBP-401; TelomeScan). We then used OBP-401 to establish a simple ex vivo method that was able to detect viable human CTCs in the peripheral blood. The detection method involved a 3-step procedure, including the lysis of rbc, the subsequent addition of OBP-401 to the cell pellets, and an automated scan using fluorescence microscopy. OBP-401 infection increased the signal-to-background ratio as a tumor-specific probe, because the fluorescent signal was amplified only in viable, infected human tumor cells, by viral replication. This GFP-expressing virus-based method is remarkably simple and allows precise enumeration of CTCs.
en-copyright=
kn-copyright=

en-aut-name=KojimaToru
en-aut-sei=Kojima
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WatanabeYuichi
en-aut-sei=Watanabe
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KyoSatoru
en-aut-sei=Kyo
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MizuguchiHiroyuki
en-aut-sei=Mizuguchi
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TanakaNoriaki
en-aut-sei=Tanaka
en-aut-mei=Noriaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=6
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Center for Gene and Cell Therapy, Okayama University Hospital

affil-num=8
en-affil=
kn-affil=Department of Obstetrics and Gynecology, Kanazawa University School of Medicine

affil-num=9
en-affil=
kn-affil=Department of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University

affil-num=10
en-affil=
kn-affil=Oncolys BioPharma Inc.

affil-num=11
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=12
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
END

start-ver=1.4
cd-journal=joma
no-vol=124
cd-vols=
no-issue=2
article-no=
start-page=105
end-page=110
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas
kn-title=テロメラーゼ依存性腫瘍融解ウイルス療法の骨・軟部肉腫に対する前臨床的検討
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=骨・軟部肉腫は, 一部に治療抵抗性で予後の悪い症例が存在するため, 新たな治療法の確立が重要な課題である.　我々は, 5型アデノウイルスを基本骨格として, テロメラーゼ活性に依存して増殖する腫瘍融解ウイルス（OBP-301）や, coxsackie and adenovirus receptor（CAR）陰性の腫瘍細胞に感染するファイバー改変型ウイルス（OBP-405）を用い, 骨・軟部肉腫細胞に対する抗腫瘍効果を検討した.　
　14種類の骨・軟部肉腫細胞株に対してOBP-301の細胞障害活性を検討し, 12種類の細胞株でOBP-301に感受性を認めた.　また, OBP-301の細胞障害活性はCARの発現と相関していた.　さらに, テロメラーゼ活性の低い細胞に対しても, 5型アデノウイルスの複製に必須のE1Aによりテロメラーゼ活性の増強効果がおこり, 強い抗腫瘍活性を示すことを明らかにした.　次に, 骨肉腫脛骨同所性移植動物モデルを作成しOBP-301を投与したところ, OBP-301投与群では対象群と比べて有意に腫瘍増殖を抑制した.　最後に, OBP-301に感受性を認めなかったCAR陰性細胞株に対してOBP-405を用いて検討し, OBP-405が有効に作用することを確認した.　
　OBP-301やOBP-405を用いたウイルス療法は, 骨・軟部肉腫に対する新たな治療法となる可能性がある.　
en-copyright=
kn-copyright=

en-aut-name=SasakiTsuyoshi
en-aut-sei=Sasaki
en-aut-mei=Tsuyoshi
kn-aut-name=佐々木剛
kn-aut-sei=佐々木
kn-aut-mei=剛
aut-affil-num=1
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=田澤大
kn-aut-sei=田澤
kn-aut-mei=大
aut-affil-num=2
ORCID=

en-aut-name=HaseiJo
en-aut-sei=Hasei
en-aut-mei=Jo
kn-aut-name=長谷井嬢
kn-aut-sei=長谷井
kn-aut-mei=嬢
aut-affil-num=3
ORCID=

en-aut-name=KunisadaToshiyuki
en-aut-sei=Kunisada
en-aut-mei=Toshiyuki
kn-aut-name=国定俊之
kn-aut-sei=国定
kn-aut-mei=俊之
aut-affil-num=4
ORCID=

en-aut-name=YoshidaAki
en-aut-sei=Yoshida
en-aut-mei=Aki
kn-aut-name=吉田晶
kn-aut-sei=吉田
kn-aut-mei=晶
aut-affil-num=5
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=橋本悠里
kn-aut-sei=橋本
kn-aut-mei=悠里
aut-affil-num=6
ORCID=

en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=矢野修也
kn-aut-sei=矢野
kn-aut-mei=修也
aut-affil-num=7
ORCID=

en-aut-name=YoshidaRyosuke
en-aut-sei=Yoshida
en-aut-mei=Ryosuke
kn-aut-name=吉田亮介
kn-aut-sei=吉田
kn-aut-mei=亮介
aut-affil-num=8
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=宇野太
kn-aut-sei=宇野
kn-aut-mei=太
aut-affil-num=9
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=香川俊輔
kn-aut-sei=香川
kn-aut-mei=俊輔
aut-affil-num=10
ORCID=

en-aut-name=MorimotoYuki
en-aut-sei=Morimoto
en-aut-mei=Yuki
kn-aut-name=森本裕樹
kn-aut-sei=森本
kn-aut-mei=裕樹
aut-affil-num=11
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=浦田泰生
kn-aut-sei=浦田
kn-aut-mei=泰生
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=藤原俊義
kn-aut-sei=藤原
kn-aut-mei=俊義
aut-affil-num=13
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=尾﨑敏文
kn-aut-sei=尾﨑
kn-aut-mei=敏文
aut-affil-num=14
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　整形外科学

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　整形外科学

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　整形外科学

affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　整形外科学

affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=7
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=8
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=9
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=10
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=11
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　整形外科学

affil-num=12
en-affil=
kn-affil=オンコリスバイオファーマ

affil-num=13
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=14
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　整形外科学
en-keyword=アデノウイルス
kn-keyword=アデノウイルス
en-keyword=肉腫
kn-keyword=肉腫
en-keyword=ALT
kn-keyword=ALT
en-keyword=ヒトテロメラーゼ逆転写酵素
kn-keyword=ヒトテロメラーゼ逆転写酵素
END

start-ver=1.4
cd-journal=joma
no-vol=123
cd-vols=
no-issue=2
article-no=
start-page=103
end-page=109
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2011
dt-pub=20110801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Radiosensitization by telomerase-dependent oncolytic adenovirus
kn-title=テロメラーゼ依存的腫瘍融解アデノウイルス製剤による 放射線感受性増強作用
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=DNA修復機能阻害は放射線感受性を増強させるため，DNA修復に関与する因子の阻害剤は放射線増感剤となり得る．我々の開発したテロメラーゼ依存的腫瘍融解アデノウイルス製剤OBP-301（テロメライシン）は，アデノウイルスE1B55kDaタンパクを介して細胞のDNA修復に重要な役割を果たすMRN複合体（Mre11，Rad50，NBS1）を分解する機能を有する．このMRN複合体の分解によりATM（ataxia-telangiectasia mutated）の活性化が抑制され結果的にDNA修復機構が阻害される．我々はOBP-301と放射線との併用が強力な相乗効果を生み出すことをマウスの皮下腫瘍モデルおよび食道癌同所性モデルにおいて証明した．これらの結果はOBP-301が将来有望な放射線増感剤となり得ることだけでなく，E1B55kDaタンパクを産生する腫瘍融解アデノウイルス製剤と放射線との併用が悪性腫瘍に対する有力な治療戦略となり得ることを示す．
en-copyright=
kn-copyright=

en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=黒田新士
kn-aut-sei=黒田
kn-aut-mei=新士
aut-affil-num=1
ORCID=

en-aut-name=FujiwaraToshiya
en-aut-sei=Fujiwara
en-aut-mei=Toshiya
kn-aut-name=藤原俊哉
kn-aut-sei=藤原
kn-aut-mei=俊哉
aut-affil-num=2
ORCID=

en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=白川靖博
kn-aut-sei=白川
kn-aut-mei=靖博
aut-affil-num=3
ORCID=

en-aut-name=YamasakiYasumoto
en-aut-sei=Yamasaki
en-aut-mei=Yasumoto
kn-aut-name=山崎泰源
kn-aut-sei=山崎
kn-aut-mei=泰源
aut-affil-num=4
ORCID=

en-aut-name=YanoSyuya
en-aut-sei=Yano
en-aut-mei=Syuya
kn-aut-name=矢野修也
kn-aut-sei=矢野
kn-aut-mei=修也
aut-affil-num=5
ORCID=

en-aut-name=UnoFutoshi
en-aut-sei=Uno
en-aut-mei=Futoshi
kn-aut-name=宇野太
kn-aut-sei=宇野
kn-aut-mei=太
aut-affil-num=6
ORCID=

en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=田澤大
kn-aut-sei=田澤
kn-aut-mei=大
aut-affil-num=7
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=橋本悠里
kn-aut-sei=橋本
kn-aut-mei=悠里
aut-affil-num=8
ORCID=

en-aut-name=WatanabeYuichi
en-aut-sei=Watanabe
en-aut-mei=Yuichi
kn-aut-name=渡辺雄一
kn-aut-sei=渡辺
kn-aut-mei=雄一
aut-affil-num=9
ORCID=

en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=野間和広
kn-aut-sei=野間
kn-aut-mei=和広
aut-affil-num=10
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=浦田泰生
kn-aut-sei=浦田
kn-aut-mei=泰生
aut-affil-num=11
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=香川俊輔
kn-aut-sei=香川
kn-aut-mei=俊輔
aut-affil-num=12
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=藤原俊義
kn-aut-sei=藤原
kn-aut-mei=俊義
aut-affil-num=13
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=7
en-affil=
kn-affil=岡山大学病院　遺伝子・細胞治療センター

affil-num=8
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=9
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=10
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=11
en-affil=
kn-affil=オンコリスバイオファーマ株式会社

affil-num=12
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学

affil-num=13
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学
en-keyword=アデノウイルス
kn-keyword=アデノウイルス
en-keyword=E1B55kDa
kn-keyword=E1B55kDa
en-keyword=MRN複合体
kn-keyword=MRN複合体
en-keyword=DNA修復
kn-keyword=DNA修復
en-keyword=放射線感受性
kn-keyword=放射線感受性
END

start-ver=1.4
cd-journal=joma
no-vol=122
cd-vols=
no-issue=3
article-no=
start-page=203
end-page=208
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2010
dt-pub=20101201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Development of novel detecting systems and therapies for micro cancer using replication-competent oncolytic adenovirus
kn-title=制限増殖型アデノウイルス製剤を用いた新たな微小がん病変の検出法の開発と治療への応用
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=KojimaToru
en-aut-sei=Kojima
en-aut-mei=Toru
kn-aut-name=児島亨
kn-aut-sei=児島
kn-aut-mei=亨
aut-affil-num=1
ORCID=

en-aut-name=HashimotoYuuri
en-aut-sei=Hashimoto
en-aut-mei=Yuuri
kn-aut-name=橋本悠里
kn-aut-sei=橋本
kn-aut-mei=悠里
aut-affil-num=2
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=香川俊輔
kn-aut-sei=香川
kn-aut-mei=俊輔
aut-affil-num=3
ORCID=

en-aut-name=TanakaNoriaki
en-aut-sei=Tanaka
en-aut-mei=Noriaki
kn-aut-name=田中紀章
kn-aut-sei=田中
kn-aut-mei=紀章
aut-affil-num=4
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=浦田泰生
kn-aut-sei=浦田
kn-aut-mei=泰生
aut-affil-num=5
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=藤原俊義
kn-aut-sei=藤原
kn-aut-mei=俊義
aut-affil-num=6
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器・腫瘍外科学

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器・腫瘍外科学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器・腫瘍外科学

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器・腫瘍外科学

affil-num=5
en-affil=
kn-affil=オンコリスバイオファーマ

affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　消化器・腫瘍外科学
en-keyword=telomerase
kn-keyword=telomerase
en-keyword=oncolytic adenovirus
kn-keyword=oncolytic adenovirus
en-keyword=GFP
kn-keyword=GFP
en-keyword=micrometastasis
kn-keyword=micrometastasis
en-keyword=circulating tumor cell
kn-keyword=circulating tumor cell
END

start-ver=1.4
cd-journal=joma
no-vol=579
cd-vols=
no-issue=19
article-no=
start-page=4069
end-page=4075
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2005
dt-pub=20050801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The EGF (epidermal growth factor) receptor-tyrosine kinase inhibitor ZD1839 (Gefitinib, 'Iressa') blocks the cell signaling pathways involved in cell proliferation, survival, and angiogenesis in various cancer cells. TNF-related death apoptosis inducing ligand (TRAIL) acts as an anticancer agent. We investigated the antitumor effects of ZD1839 alone or in combination with TRAIL against human esophageal squamous cell cancer (ESCC) lines. Although all ESCC cells expressed EGF receptor at a protein level, the effect of ZD1839 on cell growth did not correlate with the level of EGFR expression and phosphorylation of EGF receptor protein in ESCC lines. ZD1839 caused a dose-dependent growth arrest at G0–G1 phase associated with increased p27 expression. As TE8 cells are resistant to TRAIL, we tested whether ZD1839 combined with TRAIL induced apoptosis of TE8 cells via the inhibition of EGF receptor signaling by ZD1839. ZD1839 inhibited the phosphorylation of Akt, and enhanced TRAIL-induced apoptosis via activation of caspase-3 and caspase-9, and inactivation of Bcl-xL. Our results indicated that ZD1839 has anti-cancer properties against human esophageal cancer cells. ZD1839 also augmented the anti-cancer activity of TRAIL, even in TRAIL-resistant tumors. These results suggest that treatment with ZD1839 and TRAIL may have potential in the treatment of ESCC patients.
en-copyright=
kn-copyright=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WatanabeTakanori
en-aut-sei=Watanabe
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TangoYasuhisa
en-aut-sei=Tango
en-aut-mei=Yasuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KawashimaTakeshi
en-aut-sei=Kawashima
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=UmeokaTatsuo
en-aut-sei=Umeoka
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NisizakiMasahiko
en-aut-sei=Nisizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TanakaNoriaki
en-aut-sei=Tanaka
en-aut-mei=Noriaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=2
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=3
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=4
en-affil=
kn-affil=Department of Surgery, Shiga University of Medical Science

affil-num=5
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=6
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=7
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=8
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=9
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
en-keyword=epidermal growth factor receptor
kn-keyword=epidermal growth factor receptor
en-keyword=ZD1839
kn-keyword=ZD1839
en-keyword=akt
kn-keyword=akt
en-keyword=esophageal squamous cell cancer
kn-keyword=esophageal squamous cell cancer
en-keyword=tumor necrosis factor-related apoptosis inducing ligand
kn-keyword=tumor necrosis factor-related apoptosis inducing ligand
END

start-ver=1.4
cd-journal=joma
no-vol=64
cd-vols=
no-issue=17
article-no=
start-page=6259
end-page=6265
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2004
dt-pub=20040901
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Visualization of intrathoracically disseminated solid tumors in mice with optical imaging by telomerase-specific amplification of a transferred green fluorescent protein gene
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Currently available methods for detection of tumors in vivo such as X-ray, computed tomography, and ultrasonography are noninvasive and have been well studied; the images, however, are not specific for tumors. Direct optical imaging of tumor cells in vivo that can clearly distinguish them from surrounding normal tissues may be clinically useful. Here, we describe a new approach to visualizing tumors whose fluorescence can be detected using tumor-specific replication-competent adenovirus (OBP-301, Telomelysin) in combination with Ad-GFP, a replication-deficient adenovirus expressing green fluorescent protein (GFP). Human telomerase reverse transcriptase is the catalytic subunit of telomerase, which is highly active in cancer cells but quiescent in most normal somatic cells. We constructed an adenovirus 5 vector in which the human telomerase reverse transcriptase promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site and showed that OBP-301 replicated efficiently in human cancer cells, but not in normal cells such as human fibroblasts. When the human lung and colon cancer cell lines were infected with Ad-GFP at a low multiplicity of infection, GFP expression could not be detected under a fluorescence microscope; in the presence of OBP-301, however, Ad-GFP replicated in these tumor cells and showed strong green signals. In contrast, coinfection with OBP-301 and Ad-GFP did not show any signals in normal cells such as fibroblasts and vascular endothelial cells. We also found that established subcutaneous tumors could be visualized after intraturnoral injection of OBP-301 and Ad-GFP. A549 human lung tumors and SW620 human colon tumors transplanted into BALB/c nu/nu mice were intraturnorally injected with 8 X 10(5) plaque-forming units of Ad-GFP in combination with 8 X 106 plaque-forming units of OBP-301. Within 3 days of treatment, the fluorescence of the expressed GFP became visible by a three-chip color cooled charged-coupled device camera in these tumors, whereas intraturnoral injection of Ad-GFP alone could not induce GFP fluorescence. Moreover, intrathoracic administration of Ad-GFP and OBP-301 could visualize disseminated A549 tumor nodules in mice after intrathoracic implantation. Our results indicate that intratumoral or intrathoracic injection of Ad-GFP in combination with OBP-301 might be a useful diagnostic method that provides a foundation for future clinical application.
en-copyright=
kn-copyright=

en-aut-name=UmeokaTatsuo
en-aut-sei=Umeoka
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawashimaTakeshi
en-aut-sei=Kawashima
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakiMasaki
en-aut-sei=Taki
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KyoSatoru
en-aut-sei=Kyo
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NagaiKatsuyuki
en-aut-sei=Nagai
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TanakaNoriaki
en-aut-sei=Tanaka
en-aut-mei=Noriaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=2
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=3
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=4
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=5
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=6
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=7
en-affil=
kn-affil=Department of Obstetrics and Gynecology, Kanazawa University School of Medicine

affil-num=8
en-affil=
kn-affil=Oncolys BioPharma, Inc.

affil-num=9
en-affil=
kn-affil=Oncolys BioPharma, Inc.

affil-num=10
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry

affil-num=11
en-affil=
kn-affil=Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
en-keyword=GFP
kn-keyword=GFP
en-keyword=adenovirus
kn-keyword=adenovirus
en-keyword=telomerase
kn-keyword=telomerase
en-keyword=replication
kn-keyword=replication
en-keyword=gene therapy
kn-keyword=gene therapy
END

start-ver=1.4
cd-journal=joma
no-vol=99
cd-vols=
no-issue=5-6
article-no=
start-page=667
end-page=672
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1987
dt-pub=19870630
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=A study on the galactosyltransferase activity of human gastric mucosa. Part 2. Gastric mucosal UDP galactosyltransferase activity of gastric ulcer patients and normal subjects.
kn-title=ヒト胃粘膜ガラクトース転移酵素の研究　第二編　胃潰瘍症例における検討
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Biopsied specimens of gastric mucosa of normal subjects and patients with gastric ulcer were obtained under routine gastrofiberscopy. UDP-galactosyltransferase activity was measured with the use of ovomucoid as a substrate. In endoscopically normal subjects, UDP-galactosyltransferase activity of the fundic gland area was significantly (p<0.01) higher than that of the pyloric gland area. In ulcer patients without anti-ulcer treatment, UDP-galactosyltransferase activity was elevated in the mucosa surrounding the ulcer at the healing stage and red scarring stage as compared with the corresponding area of non-ulcer individuals. However, under administration of an H(2)-blocker, the change in UDP-galactosyltransferase activity was not observed. These observations may suggest that (1) increased glycoprotein synthses may be a physiological response of the gastric mucosa to the ulcer and may promote ulcer healing, and that (2) the process of the H(2)-blocker induced ulcer healing may not be associated with the apparent increase in glycoprotein synthesis.
en-copyright=
kn-copyright=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=香川俊介
kn-aut-sei=香川
kn-aut-mei=俊介
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学第一内科学教室
en-keyword=gastric ulcer
kn-keyword=gastric ulcer
en-keyword=mucosal glycoprtein
kn-keyword=mucosal glycoprtein
en-keyword=UDP-galactosyltransferase
kn-keyword=UDP-galactosyltransferase
en-keyword=gastric mucosal atrophy
kn-keyword=gastric mucosal atrophy
en-keyword=H(2) blocker
kn-keyword=H(2) blocker
END

start-ver=1.4
cd-journal=joma
no-vol=99
cd-vols=
no-issue=5-6
article-no=
start-page=657
end-page=665
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1987
dt-pub=19870630
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=A study on the galactosyltransferase activity of human gastric mucosa Part 1. Assay conditions with ovomucoid as a substrate.
kn-title=ヒト胃粘膜ガラクトース転移酵素活性の研究　第一編　オボムコイドを基質とした測定法の基礎的検討
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The conditions assaying for UDP-galactosyltransferase in human gastric mucosa was studied. Ovomucoid without any pretreatment was employed as a substrate. The optimal pH was 6.8. Manganese, 2-mercaptoethanol and Triton X-100 were required for maximum enzyme activity. In the standard assay; 20 μl of enzyme solution was added to 30 μl of 50 mM MES buffer containing 5 mM 2-mercaptoethanol, 15 mM MnCl(2), 9.9mg protein/ml ovomucoid, 0.3 mM UDP-galactose, 1.7 μCi/ml UDP-[(3)H]-galactose and 1.5 mg/ml Triton X-100, and incubation was carried out at 37℃ for 20 min. [(3)H]-labelled ovomucoid was the only radioreactive reaction product detected. All galactose residue incorporated was liberated by β-galactosidase but not by α-galactosidase.
en-copyright=
kn-copyright=

en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=香川俊介
kn-aut-sei=香川
kn-aut-mei=俊介
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学第一内科学教室
en-keyword=human gastric mucosa
kn-keyword=human gastric mucosa
en-keyword=glycoprotein
kn-keyword=glycoprotein
en-keyword=UDP-galactosyltransferase
kn-keyword=UDP-galactosyltransferase
en-keyword=ovomuciod
kn-keyword=ovomuciod
en-keyword=N-acetylglucosamine
kn-keyword=N-acetylglucosamine
END

start-ver=1.4
cd-journal=joma
no-vol=120
cd-vols=
no-issue=3
article-no=
start-page=259
end-page=264
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2008
dt-pub=20081201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Virus-mediated oncolysis induces danger signals and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation
kn-title=腫瘍融解ウイルスによる細胞死であるオンコライシスは細胞内に danger signal を発生させ，プロテアソームアクチベーター(PA28)発現を増強することで細胞障害性Ｔリンパ球による免疫応答を活性化する
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=EndoYoshikatsu
en-aut-sei=Endo
en-aut-mei=Yoshikatsu
kn-aut-name=遠藤芳克
kn-aut-sei=遠藤
kn-aut-mei=芳克
aut-affil-num=1
ORCID=

en-aut-name=SakaiRyo
en-aut-sei=Sakai
en-aut-mei=Ryo
kn-aut-name=酒井亮
kn-aut-sei=酒井
kn-aut-mei=亮
aut-affil-num=2
ORCID=

en-aut-name=OuchiMasaaki
en-aut-sei=Ouchi
en-aut-mei=Masaaki
kn-aut-name=大内正明
kn-aut-sei=大内
kn-aut-mei=正明
aut-affil-num=3
ORCID=

en-aut-name=OnimatsuHideki
en-aut-sei=Onimatsu
en-aut-mei=Hideki
kn-aut-name=鬼松秀樹
kn-aut-sei=鬼松
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END