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=25
cd-vols=
no-issue=11
article-no=
start-page=6269
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240606
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Sprouty-related enabled/vasodilator-stimulated phosphoprotein homology 1 domain containing 2 (SPRED2) is an inhibitor of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and has been shown to promote autophagy in several cancers. Here, we aimed to determine whether SPRED2 plays a role in autophagy in hepatocellular carcinoma (HCC) cells. The Cancer Genome Atlas (TCGA) Liver Cancer Database showed a negative association between the level of SPRED2 and p62, a ubiquitin-binding scaffold protein that accumulates when autophagy is inhibited. Immunohistochemically, accumulation of p62 was detected in human HCC tissues with low SPRED2 expression. Overexpression of SPRED2 in HCC cells increased the number of autophagosomes and autophagic vacuoles containing damaged mitochondria, decreased p62 levels, and increased levels of light-chain-3 (LC3)-II, an autophagy marker. In contrast, SPRED2 deficiency increased p62 levels and decreased LC3-II levels. SPRED2 expression levels were negatively correlated with translocase of outer mitochondrial membrane 20 (TOM20) expression levels, suggesting its role in mitophagy. Mechanistically, SPRED2 overexpression reduced ERK activation followed by the mechanistic or mammalian target of rapamycin complex 1 (mTORC1)-mediated signaling pathway, and SPRED2 deficiency showed the opposite pattern. Finally, hepatic autophagy was impaired in the liver of SPRED2-deficient mice with hepatic lipid droplet accumulation in response to starvation. These results indicate that SPRED2 is a critical regulator of autophagy not only in HCC cells, but also in hepatocytes, and thus the manipulation of this process may provide new insights into liver pathology.
en-copyright=
kn-copyright=
en-aut-name=WangTianyi
en-aut-sei=Wang
en-aut-mei=Tianyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=GaoTong
en-aut-sei=Gao
en-aut-mei=Tong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=
affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=autophagy
kn-keyword=autophagy
en-keyword=mitophagy
kn-keyword=mitophagy
en-keyword=SPRED proteins
kn-keyword=SPRED proteins
en-keyword=MAPK/ERK
kn-keyword=MAPK/ERK
en-keyword=mTOR
kn-keyword=mTOR
en-keyword=hepatocellular carcinoma
kn-keyword=hepatocellular carcinoma
END
start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=7
article-no=
start-page=394
end-page=407
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=The specific shapes of capillaries are associated with worse prognosis in patients with invasive breast cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Angiogenesis is considered essential for tumor progression; however, whether histological counting of blood vessel numbers, expressed as microvessel density (MVD), can be a prognostic factor in breast cancer remains controversial. It has been suggested that the specific morphology of blood vessels such as glomeruloid microvascular proliferation (GMP) is associated with clinical parameters. Here, we aimed to clarify the significance of MVD with revised immunohistochemistry and to identify new blood vessel shapes that predict prognosis in breast cancer. Four hundred and eleven primary breast cancer specimens were collected, and the sections were immunohistochemically stained with CD31 (single staining) and CD31 and Collagen IV (double staining). The prognosis of patients was examined based on the MVD value, and the presence of GMP and other blood vessels with other specific shapes. As a result, high MVD value and the presence of GMP were not associated with worse prognosis. By contrast, patients with deep-curved capillaries surrounding tumor cell nests (C-shaped) or excessively branched capillaries near tumor cell nests showed a significantly poor prognosis. The presence of these capillaries was also correlated with clinicopathological parameters such as Ki-67 index. Thus, the morphology of capillaries rather than MVD can be a better indicator of tumor aggressiveness.
en-copyright=
kn-copyright=
en-aut-name=SweHnin‐Wint‐Wint
en-aut-sei=Swe
en-aut-mei=Hnin‐Wint‐Wint
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
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=KomatsubaraYu
en-aut-sei=Komatsubara
en-aut-mei=Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=ShienTadahiko
en-aut-sei=Shien
en-aut-mei=Tadahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=
affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=angiogenesis
kn-keyword=angiogenesis
en-keyword=blood vessels
kn-keyword=blood vessels
en-keyword=breast cancer
kn-keyword=breast cancer
en-keyword=CD31 antigen
kn-keyword=CD31 antigen
en-keyword=immunohistochemistry
kn-keyword=immunohistochemistry
en-keyword=microvessel density
kn-keyword=microvessel density
en-keyword=survival analysis
kn-keyword=survival analysis
END
start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=10
article-no=
start-page=e174618
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240522
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro -tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph -circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC.
en-copyright=
kn-copyright=
en-aut-name=EainHtoo Shwe
en-aut-sei=Eain
en-aut-mei=Htoo Shwe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KawaiHotaka
en-aut-sei=Kawai
en-aut-mei=Hotaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NakayamaMasaaki
en-aut-sei=Nakayama
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OoMay Wathone
en-aut-sei=Oo
en-aut-mei=May Wathone
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=
en-aut-name=FukuharaYoko
en-aut-sei=Fukuhara
en-aut-mei=Yoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TakabatakeKiyofumi
en-aut-sei=Takabatake
en-aut-mei=Kiyofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=ShanQuisheng
en-aut-sei=Shan
en-aut-mei=Quisheng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SoeYamin
en-aut-sei=Soe
en-aut-mei=Yamin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OnoKisho
en-aut-sei=Ono
en-aut-mei=Kisho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NakanoKeisuke
en-aut-sei=Nakano
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=MizukawaNobuyoshi
en-aut-sei=Mizukawa
en-aut-mei=Nobuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=IidaSeiji
en-aut-sei=Iida
en-aut-mei=Seiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=NagatsukaHitoshi
en-aut-sei=Nagatsuka
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Universit
kn-affil=
affil-num=6
en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=11
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=12
en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=13
en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=14
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=72
cd-vols=
no-issue=11
article-no=
start-page=3787
end-page=3802
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230905
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.
en-copyright=
kn-copyright=
en-aut-name=KawasakiKento
en-aut-sei=Kawasaki
en-aut-mei=Kento
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=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
ORCID=
en-aut-name=TakedaYasushige
en-aut-sei=Takeda
en-aut-mei=Yasushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MatsumotoHijiri
en-aut-sei=Matsumoto
en-aut-mei=Hijiri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NishimuraSeitaro
en-aut-sei=Nishimura
en-aut-mei=Seitaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KunitomoTomoyoshi
en-aut-sei=Kunitomo
en-aut-mei=Tomoyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
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=11
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=12
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=13
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=14
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=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=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
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=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=
en-keyword=Esophageal cancer
kn-keyword=Esophageal cancer
en-keyword=Cancer-associated fibroblasts
kn-keyword=Cancer-associated fibroblasts
en-keyword=Programmed cell death 1
kn-keyword=Programmed cell death 1
en-keyword=Program cell death ligand 1
kn-keyword=Program cell death ligand 1
en-keyword=Immune checkpoint inhibitors
kn-keyword=Immune checkpoint inhibitors
END
start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=11
article-no=
start-page=1562
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231024
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Novel Iron Chelators, Super-Polyphenols, Show Antimicrobial Effects against Cariogenic Streptococcus mutans
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Dental caries are an oral infectious disease that can affect human health both orally and systemically. It remains an urgent issue to establish a novel antibacterial method to prevent oral infection for a healthy life expectancy. The aim of this study was to evaluate the inhibitory effects of novel iron chelators, super-polyphenols (SPs), on the cariogenic bacterium Streptococcus mutans, in vitro. SPs were developed to reduce the side effects of iron chelation therapy and were either water-soluble or insoluble depending on their isoforms. We found that SP6 and SP10 inhibited bacterial growth equivalent to povidone-iodine, and viability tests indicated that their effects were bacteriostatic. These results suggest that SP6 and SP10 have the potential to control oral bacterial infections such as Streptococcus mutans.
en-copyright=
kn-copyright=
en-aut-name=Shinoda-ItoYuki
en-aut-sei=Shinoda-Ito
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OmoriKazuhiro
en-aut-sei=Omori
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=ItoTakashi
en-aut-sei=Ito
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NakayamaMasaaki
en-aut-sei=Nakayama
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=IkedaAtsushi
en-aut-sei=Ikeda
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=ItoMasahiro
en-aut-sei=Ito
en-aut-mei=Masahiro
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=TakashibaShogo
en-aut-sei=Takashiba
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Periodontics & Endodontics, Division of Dentistry, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=antimicrobial
kn-keyword=antimicrobial
en-keyword=iron chelator
kn-keyword=iron chelator
en-keyword=oral infection
kn-keyword=oral infection
en-keyword=Streptococcus mutans
kn-keyword=Streptococcus mutans
en-keyword=super-polyphenols
kn-keyword=super-polyphenols
END
start-ver=1.4
cd-journal=joma
no-vol=26
cd-vols=
no-issue=6
article-no=
start-page=1213
end-page=1223
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Diagnostic Utility of the PD-L1 Immunostaining in Biopsy Specimens of Patients with Biliary Tract Neoplasms
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Anti-programmed death 1/programmed death ligand 1 (PD1/PD-L1) antibodies have been successfully used as treatment agents for several solid tumors; however, it is difficult to predict their effectiveness. We evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue.
Methods Among 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. We performed immunohistochemical staining to investigate the PD-L1 expression in both resected and biopsy specimens. The percentage of the positively stained cells was calculated for subsequent use in the correlation investigation.
Results The biopsy methods were endoscopic retrograde cholangiopancreatography (ERCP) in 28 cases, percutaneous liver biopsy in 10 cases, and endoscopic ultrasound fine-needle aspiration in 7 cases. Among the 45 patients, when patients with > 10% positive tumor cells in surgically resected tissues were regarded as truly positive PD-L1, the positive and negative concordance rates between surgically resected tissues and biopsy samples were 56% (5/9) and 100% (36/36), respectively. With regard to the use of preoperative biopsy as a diagnostic tool, all (5/5) PD-L1-positive patients had a positive resected specimen. The accuracy of each biopsy method was as follows: ERCP, 89% (25/28); fine-needle aspiration, 86% (6/7); and liver biopsy, 100% (10/10).
Conclusions Biopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates.
en-copyright=
kn-copyright=
en-aut-name=MatsumotoKazuyuki
en-aut-sei=Matsumoto
en-aut-mei=Kazuyuki
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=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakakiAkinobu
en-aut-sei=Takaki
en-aut-mei=Akinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TakaharaMasahiro
en-aut-sei=Takahara
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoHironari
en-aut-sei=Kato
en-aut-mei=Hironari
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=YagiTakahito
en-aut-sei=Yagi
en-aut-mei=Takahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=
en-aut-name=OkadaHiroyuki
en-aut-sei=Okada
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, 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=
affil-num=6
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Programmed death ligand 1
kn-keyword=Programmed death ligand 1
en-keyword=Bile tract neoplasm
kn-keyword=Bile tract neoplasm
en-keyword=Biopsy specimen
kn-keyword=Biopsy specimen
en-keyword=Immunohistochemistry
kn-keyword=Immunohistochemistry
END
start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=11
article-no=
start-page=2971
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230530
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Conventional Cancer Therapies Can Accelerate Malignant Potential of Cancer Cells by Activating Cancer-Associated Fibroblasts in Esophageal Cancer Models
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors.
en-copyright=
kn-copyright=
en-aut-name=KomotoSatoshi
en-aut-sei=Komoto
en-aut-mei=Satoshi
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=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
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=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=KatsuraYuki
en-aut-sei=Katsura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=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=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
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=cancer-associated fibroblast
kn-keyword=cancer-associated fibroblast
en-keyword=chemotherapy
kn-keyword=chemotherapy
en-keyword=radiotherapy
kn-keyword=radiotherapy
en-keyword=esophageal cancer
kn-keyword=esophageal cancer
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
END
start-ver=1.4
cd-journal=joma
no-vol=24
cd-vols=
no-issue=5
article-no=
start-page=4996
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230305
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The downregulation of SPRED2, a negative regulator of the ERK1/2 pathway, was previously detected in human cancers; however, the biological consequence remains unknown. Here, we investigated the effects of SPRED2 loss on hepatocellular carcinoma (HCC) cell function. Human HCC cell lines, expressing various levels of SPRED2 and SPRED2 knockdown, increased ERK1/2 activation. SPRED2-knockout (KO)-HepG2 cells displayed an elongated spindle shape with increased cell migration/invasion and cadherin switching, with features of epithelial-mesenchymal transition (EMT). SPRED2-KO cells demonstrated a higher ability to form spheres and colonies, expressed higher levels of stemness markers and were more resistant to cisplatin. Interestingly, SPRED2-KO cells also expressed higher levels of the stem cell surface markers CD44 and CD90. When CD44(+)CD90(+) and CD44(-)CD90(-) populations from WT cells were analyzed, a lower level of SPRED2 and higher levels of stem cell markers were detected in CD44(+)CD90(+) cells. Further, endogenous SPRED2 expression decreased when WT cells were cultured in 3D, but was restored in 2D culture. Finally, the levels of SPRED2 in clinical HCC tissues were significantly lower than those in adjacent non-HCC tissues and were negatively associated with progression-free survival. Thus, the downregulation of SPRED2 in HCC promotes EMT and stemness through the activation of the ERK1/2 pathway, and leads to more malignant phenotypes.
en-copyright=
kn-copyright=
en-aut-name=GaoTong
en-aut-sei=Gao
en-aut-mei=Tong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=YangXu
en-aut-sei=Yang
en-aut-mei=Xu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=
en-aut-name=WangTianyi
en-aut-sei=Wang
en-aut-mei=Tianyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=
affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=epithelial-mesenchymal transition
kn-keyword=epithelial-mesenchymal transition
en-keyword=ERK1/2-MAPK
kn-keyword=ERK1/2-MAPK
en-keyword=tumorigenesis
kn-keyword=tumorigenesis
END
start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=2
article-no=
start-page=468
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230112
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Simple Summary Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate the possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo lung metastatic model. We found that highly metastatic TNBC cells have limited iron metabolism and can be more effectively targeted by iron chelators. Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate a possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo. Lung metastasis was further significantly reduced, leading to the hypothesis that iron metabolism between metastatic and non-metastatic cells may be different. An analysis of existing database demonstrated that the expression of iron-uptake genes was significantly suppressed in TNBC cells that metastasized to lymph nodes or lungs compared to those in primary tumors. A highly metastatic clone of the murine 4T1 TNBC cells (4T1-HM) did not proliferate well under iron-rich or iron-depleted conditions by iron chelators compared to a low-metastatic clone (4T1-LM). Bulk RNA-seq analysis of RNA from 4T1-HM and 4T1-LM cells suggested that the PI3K-AKT pathway might be responsible for this difference. Indeed, DFX suppressed the proliferation via the AKT-mTOR pathway in 4T1-HM and the human MDA-MB-231 cells, a human mesenchymal-like TNBC cell line. DFX also suppressed the growth of 4T1-HM tumors in comparison to 4T1-LM tumors, and reduced lung metastases after surgical resection of primary 4T1 tumors. These results indicated, for the first time, that highly metastatic TNBC cells have limited iron metabolism, and they can be more effectively targeted by iron chelators.
en-copyright=
kn-copyright=
en-aut-name=WangYuze
en-aut-sei=Wang
en-aut-mei=Yuze
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=ChenYuehua
en-aut-sei=Chen
en-aut-mei=Yuehua
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=HamadaYusuke
en-aut-sei=Hamada
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=LiChunning
en-aut-sei=Li
en-aut-mei=Chunning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=
affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=triple-negative breast cancer
kn-keyword=triple-negative breast cancer
en-keyword=iron metabolism
kn-keyword=iron metabolism
en-keyword=iron chelator
kn-keyword=iron chelator
en-keyword=phosphoinositide-3-kinase-protein kinase
kn-keyword=phosphoinositide-3-kinase-protein kinase
en-keyword=heterogeneity
kn-keyword=heterogeneity
en-keyword=metastasis
kn-keyword=metastasis
END
start-ver=1.4
cd-journal=joma
no-vol=72
cd-vols=
no-issue=5
article-no=
start-page=1285
end-page=1300
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221127
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pancreatic ductal adenocarcinoma (PDAC) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. However, the precise relationship between GEM-resistant PDAC and development of an immunosuppressive tumor microenvironment (TME) remains unclear. In this study, we investigated the immunosuppressive TME in parental and GEM-resistant PDAC tumors and assessed the therapeutic potential of combination therapy with the telomerase-specific replication-competent oncolytic adenovirus OBP-702, which induces tumor suppressor p53 protein and PD-L1 blockade against GEM-resistant PDAC tumors. Mouse PDAC cells (PAN02) and human PDAC cells (MIA PaCa-2, BxPC-3) were used to establish GEM-resistant PDAC lines. PD-L1 expression and the immunosuppressive TME were analyzed using parental and GEM-resistant PDAC cells. A cytokine array was used to investigate the underlying mechanism of immunosuppressive TME induction by GEM-resistant PAN02 cells. The GEM-resistant PAN02 tumor model was used to evaluate the antitumor effect of combination therapy with OBP-702 and PD-L1 blockade. GEM-resistant PDAC cells exhibited higher PD-L1 expression and produced higher granulocyte-macrophage colony-stimulating factor (GM-CSF) levels compared with parental cells, inducing an immunosuppressive TME and the accumulation of myeloid-derived suppressor cells (MDSCs). OBP-702 significantly inhibited GEM-resistant PAN02 tumor growth by suppressing GM-CSF-mediated MDSC accumulation. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation.
en-copyright=
kn-copyright=
en-aut-name=KajiwaraYoshinori
en-aut-sei=Kajiwara
en-aut-mei=Yoshinori
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=YamadaMotohiko
en-aut-sei=Yamada
en-aut-mei=Motohiko
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=FushimiTakuro
en-aut-sei=Fushimi
en-aut-mei=Takuro
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=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
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=10
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=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=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 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=
affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Pancreatic cancer
kn-keyword=Pancreatic cancer
en-keyword=Chemoresistance
kn-keyword=Chemoresistance
en-keyword=MDSC
kn-keyword=MDSC
en-keyword=GM-CSF
kn-keyword=GM-CSF
en-keyword=Oncolytic virus
kn-keyword=Oncolytic virus
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=9
cd-vols=
no-issue=11
article-no=
start-page=673
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Functional Blockage of S100A8/A9 Ameliorates Ischemia-Reperfusion Injury in the Lung
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=(1) Background: Lung ischemia-reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to identify the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. (2) Methods: Using a mouse hilar clamp model, the combination of RNA sequencing and histological investigations revealed that neutrophil-derived S100A8/A9 plays a central role in inflammatory reactions during lung IR injury. Mice were assigned to sham and IR groups with or without the injection of anti-S100A8/A9 neutralizing monoclonal antibody (mAb). (3) Results: Anti-S100A8/A9 mAb treatment significantly attenuated plasma S100A8/A9 levels compared with control IgG. As evaluated by oxygenation capacity and neutrophil infiltration, the antibody treatment dramatically ameliorated the IR injury. The gene expression levels of cytokines and chemokines induced by IR injury were significantly reduced by the neutralizing antibody. Furthermore, the antibody treatment significantly reduced TUNEL-positive cells, indicating the presence of apoptotic cells. (4) Conclusions: We identified S100A8/A9 as a novel therapeutic target against lung IR injury.
en-copyright=
kn-copyright=
en-aut-name=NakataKentaro
en-aut-sei=Nakata
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OkazakiMikio
en-aut-sei=Okazaki
en-aut-mei=Mikio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=SakaueTomohisa
en-aut-sei=Sakaue
en-aut-mei=Tomohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KomodaYuhei
en-aut-sei=Komoda
en-aut-mei=Yuhei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=ShimizuDai
en-aut-sei=Shimizu
en-aut-mei=Dai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=YamamotoHaruchika
en-aut-sei=Yamamoto
en-aut-mei=Haruchika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TanakaShin
en-aut-sei=Tanaka
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=MiyoshiKentaroh
en-aut-sei=Miyoshi
en-aut-mei=Kentaroh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=YamaneMasaomi
en-aut-sei=Yamane
en-aut-mei=Masaomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
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=16
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine
kn-affil=
affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine
kn-affil=
affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network
kn-affil=
affil-num=8
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=17
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=ischemia reperfusion injury
kn-keyword=ischemia reperfusion injury
en-keyword= S100A8/A9
kn-keyword= S100A8/A9
en-keyword=lung transplantation
kn-keyword=lung transplantation
en-keyword=damage-associated molecule patterns
kn-keyword=damage-associated molecule patterns
END
start-ver=1.4
cd-journal=joma
no-vol=24
cd-vols=
no-issue=1
article-no=
start-page=60
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220912
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Exosomal Wnt7a from a low metastatic subclone promotes lung metastasis of a highly metastatic subclone in the murine 4t1 breast cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Patients with triple-negative breast cancer (TNBC) often have poorer prognosis than those with other subtypes because of its aggressive behaviors. Cancer cells are heterogeneous, and only a few highly metastatic subclones metastasize. Although the majority of subclones may not metastasize, they could contribute by releasing factors that increase the capacity of highly metastatic cells and/or provide a favorable tumor microenvironment (TME). Here, we analyzed the interclonal communication in TNBC which leads to efficient cancer progression, particularly lung metastasis, using the polyclonal murine 4T1 BC model. Methods We isolated two 4T1 subclones, LM.4T1 and HM.4T1 cells with a low and a high metastatic potential, respectively, and examined the effects of LM.4T1 cells on the behaviors of HM.4T1 cells using the cell scratch assay, sphere-forming assay, sphere invasion assay, RT-qPCR, and western blotting in vitro. We also examined the contribution of LM.4T1 cells to the lung metastasis of HM.4T1 cells and TME in vivo. To identify a critical factor which may be responsible for the effects by LM.4T1 cells, we analyzed the data obtained from the GEO database. Results Co-injection of LM.4T1 cells significantly augmented lung metastases by HM.4T1 cells. LM.4T1-derived exosomes promoted the migration and invasion of HM.4T1 cells in vitro, and blocking the secretion of exosome abrogated their effects on HM.4T1 cells. Analyses of data obtained from the GEO database suggested that Wnt7a might be a critical factor responsible for the enhancing effects. In fact, a higher level of Wnt7a was detected in LM.4T1 cells, especially in exosomes, than in HM.4T1 cells, and deletion of Wnt7a in LM.4T1 cells significantly decreased the lung metastasis of HM.4T1 cells. Further, treatment with Wnt7a increased the spheroid formation by HM.4T1 cells via activation of the PI3K/Akt/mTOR signaling pathway. Finally, infiltration of alpha SMA-positive fibroblasts and angiogenesis was more prominent in tumors of LM.4T1 cells and deletion of Wnt7a in LM.4T1 cells markedly reduced angiogenesis. Conclusions We demonstrated, for the first time, that a low metastatic subclone can enhance lung metastasis of highly metastatic subclone via exosomal Wnt7a and propose Wnt7a as a molecular target to treat TNBC patients.
en-copyright=
kn-copyright=
en-aut-name=LiChunning
en-aut-sei=Li
en-aut-mei=Chunning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TianMiao
en-aut-sei=Tian
en-aut-mei=Miao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=WangYuze
en-aut-sei=Wang
en-aut-mei=Yuze
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KondoTakamasa
en-aut-sei=Kondo
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=YamamotoKen-Ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=
affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Breast cancer
kn-keyword=Breast cancer
en-keyword=Metastasis
kn-keyword=Metastasis
en-keyword=Exosomes
kn-keyword=Exosomes
en-keyword=Epithelial mesenchymal transition
kn-keyword=Epithelial mesenchymal transition
en-keyword=Tumor microenvironment
kn-keyword=Tumor microenvironment
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=12
cd-vols=
no-issue=1
article-no=
start-page=4819
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220321
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Under normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of beta-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS.
en-copyright=
kn-copyright=
en-aut-name=MiyaharaHiroyuki
en-aut-sei=Miyahara
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=HasegawaKosei
en-aut-sei=Hasegawa
en-aut-mei=Kosei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=YashiroMasato
en-aut-sei=Yashiro
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=
en-aut-name=TsukaharaHirokazu
en-aut-sei=Tsukahara
en-aut-mei=Hirokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=Department of Pediatrics, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of Pediatrics, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Pediatrics, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=41
cd-vols=
no-issue=1
article-no=
start-page=29
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220121
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background
Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. Here, we demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo.
Methods Three different pancreatic cancer line cells, BxPC3, PANC1, and PK8 cells were mixed with miPSCs and subcutaneously injected into immunodeficient mice. Tumors were evaluated by histological analysis and cells derived from iPSCs were isolated and selected from tumors. The isolated cells were characterized for cancer stem cell characters in vitro and in vivo as well as their responses to anticancer drugs. The impact of co-injection of iPSCs with cancer cells on transcriptome and signaling pathways of iPSCs was investigated.
Results The injection of miPSCs mixed with human pancreatic cancer cells into immunodeficient mice maintained the stemness of miPSCs and changed their phenotype. The miPSCs acquired CSC characteristics of tumorigenicity and self-renewal. The drug responses and the metastatic ability of CSCs converted from miPSCs varied depending on the microenvironment of cancer cells. Interestingly, transcriptome profiles of these cells indicated that the pathways related with aggressiveness and energy production were upregulated from the levels of miPSCs.
Conclusions
Our result suggests that cancer-inducing microenvironment in vivo could rewire the cell signaling and metabolic pathways to convert normal stem cells into CSCs.
en-copyright=
kn-copyright=
en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
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=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KumonKazuki
en-aut-sei=Kumon
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=FuXiaoying
en-aut-sei=Fu
en-aut-mei=Xiaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=Al KadiMohamad
en-aut-sei=Al Kadi
en-aut-mei=Mohamad
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SalomonDavid S.
en-aut-sei=Salomon
en-aut-mei=David S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=
affil-num=1
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Medical School, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University
kn-affil=
affil-num=8
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=9
en-affil=Mouse genetics program, Center for Cancer Research, National Cancer Institute
kn-affil=
affil-num=10
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=Cancer stem cells
kn-keyword=Cancer stem cells
en-keyword=iPSCs
kn-keyword=iPSCs
en-keyword=Conversion
kn-keyword=Conversion
en-keyword=Plasticity
kn-keyword=Plasticity
en-keyword=Tumorigenesis
kn-keyword=Tumorigenesis
en-keyword=Pancreatic cancer microenvironments
kn-keyword=Pancreatic cancer microenvironments
END
start-ver=1.4
cd-journal=joma
no-vol=7
cd-vols=
no-issue=1
article-no=
start-page=e148960
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220111
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Accumulating evidence has shown that cancer stroma and BM-derived cells (BMDCs) in the tumor microenvironment (TME) play vital roles in tumor progression. However, the mechanism by which oral cancer stroma recruits any particular subset of BMDCs remains largely unknown. Here, we sought to identify the subset of BMDCs that is recruited by cancer stroma. We established a sequential transplantation model in BALB/c nude mice, including (a) BM transplantation of GFP-expressing cells and (b) coxenografting of patient-derived stroma (PDS; 2 cases, designated PDS1 and PDS2) with oral cancer cells (HSC-2). As controls, xenografting was performed with HSC-2 alone or in combination with normal human dermal fibroblasts (HDF). PDS1, PDS2, and HDF all promoted BMDC migration in vitro and recruitment in vivo. Multicolor immunofluorescence revealed that the PDS coxenografts recruited Arginase-1(+)CD11b(+)GR1(+)GFP(+) cells, which are myeloid-derived suppressor cells (MDSCs), to the TME, whereas the HDF coxenograft did not. Screening using microarrays revealed that PDS1 and PDS2 expressed CCL2 mRNA (encoding C-C motif chemokine ligand 2) at higher levels than did HDF. Indeed, PDS xenografts contained significantly higher proportions of CCL2(+) stromal cells and CCR2(+)Arginase-1(+)CD11b(+)GR1(+) MDSCs (as receiver cells) than the HDF coxenograft. Consistently, a CCL2 synthesis inhibitor and a CCR2 antagonist significantly inhibited the PDS-driven migration of BM cells in vitro. Furthermore, i.p. injection of the CCR2 antagonist to the PDS xenograft models significantly reduced the CCR2(+)Arginase-1(+)CD11b(+)GR1(+) MDSC infiltration to the TME. In conclusion, oral cancer stroma-secreted CCL2 is a key signal for recruiting CCR2(+) MDSCs from BM to the TME.
en-copyright=
kn-copyright=
en-aut-name=OoMay Wathone
en-aut-sei=Oo
en-aut-mei=May Wathone
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KawaiHotaka
en-aut-sei=Kawai
en-aut-mei=Hotaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TakabatakeKiyofumi
en-aut-sei=Takabatake
en-aut-mei=Kiyofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=EguchiTakanori
en-aut-sei=Eguchi
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=OnoKisho
en-aut-sei=Ono
en-aut-mei=Kisho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=ShanQiusheng
en-aut-sei=Shan
en-aut-mei=Qiusheng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=
en-aut-name=YoshidaSaori
en-aut-sei=Yoshida
en-aut-mei=Saori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OmoriHaruka
en-aut-sei=Omori
en-aut-mei=Haruka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=SukegawaShintaro
en-aut-sei=Sukegawa
en-aut-mei=Shintaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NakanoKeisuke
en-aut-sei=Nakano
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=OkamotoKuniaki
en-aut-sei=Okamoto
en-aut-mei=Kuniaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=SasakiAkira
en-aut-sei=Sasaki
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=NagatsukaHitoshi
en-aut-sei=Nagatsuka
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=11
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=12
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=13
en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=14
en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=15
en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=35
cd-vols=
no-issue=
article-no=
start-page=71
end-page=86
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Spred2 controls the severity of Concanavalin A-induced liver damage by limiting interferon-gamma production by CD4(+) and CD8(+) T cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction: Mitogen-activated protein kinases (MAPKs) are involved in T cell-mediated liver damage. However, the inhibitory mechanism(s) that controls T cell-mediated liver damage remains unknown. Objectives: We investigated whether Spred2 (Sprouty-related, EVH1 domain-containing protein 2) that negatively regulates ERK-MAPK pathway has a biological impact on T cell-mediated liver damage by using a murine model. Methods: We induced hepatotoxicity in genetically engineered mice by intravenously injecting Concanavalin A (Con A) and analyzed the mechanisms using serum chemistry, histology, ELISA, qRT-PCR, Western blotting and flow cytometry. Results: Spred2-deficient mice (Spred2(-/-)) developed more sever liver damage than wild-type (WT) mice with increased interferon-gamma (IFNy) production. Hepatic ERK phosphorylation was enhanced in Spred2(-/-) mice, and pretreatment of Spred2(-/-) mice with the MAPK/ERK inhibitor U0126 markedly inhibited the liver damage and reduced IFN gamma production. Neutralization of IFNy abolished the damage with decreased hepatic Stat1 activation in Spred2(-/-) mice. IFN gamma was mainly produced from CD4(+) and CD8(+) T cells, and their depletion decreased liver damage and IFN gamma production. Transplantation of CD4(+) and/or CD8(+) T cells from Spred2(-/-) mice into RAG1(-/-) mice deficient in both T and B cells caused more severe liver damage than those from WT mice. Hepatic expression of T cell attractants, CXCL9 and CXCL10, was augmented in Spred2(-/-) mice as compared to WT mice. Conversely, liver damage, IFN gamma production and the recruitment of CD4(+) and CD8(+) T cells in livers after Con A challenge were lower in Spred2 transgenic mice, and Spred2-overexpressing CD4(+) and CD8(+) T cells produced lower levels of IFN gamma than WT cells upon stimulation with Con A in vitro. Conclusion: We demonstrated, for the first time, that Spred2 functions as an endogenous regulator of T cell IFNy production and Spred2-mediated inhibition of ERK-MAPK pathway may be an effective remedy for T cell-dependent liver damage.
en-copyright=
kn-copyright=
en-aut-name=SunCuiming
en-aut-sei=Sun
en-aut-mei=Cuiming
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
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=LiuQiuying
en-aut-sei=Liu
en-aut-mei=Qiuying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=CaoChen
en-aut-sei=Cao
en-aut-mei=Chen
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=YangXu
en-aut-sei=Yang
en-aut-mei=Xu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KunkelSteven L.
en-aut-sei=Kunkel
en-aut-mei=Steven L.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=
affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Pathology, University of Michigan Medical School
kn-affil=
affil-num=9
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Liver damage
kn-keyword=Liver damage
en-keyword=MAPK
kn-keyword=MAPK
en-keyword=Signal transduction and regulation
kn-keyword=Signal transduction and regulation
en-keyword=Gene-modified mice
kn-keyword=Gene-modified mice
en-keyword=Spred2
kn-keyword=Spred2
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=2021
dt-pub=2021814
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PolyI:C suppresses TGF-β1-induced Akt phosphorylation and reduces the motility of A549 lung carcinoma cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Backgrounds: Epithelial mesenchymal transition (EMT) is a critical process involved in the invasion and metastasis of cancer, including lung cancer (LC). Transforming growth factor (TGF)-β is one of factors capable of inducing EMT. Polyinosinic-polycytidylic acid (polyI:C), a synthetic agonist for toll-like receptor (TLR) 3, can enhance immune responses and has been used as an adjuvant for cancer vaccines; however, it remains unclear whether it influences other process, such as EMT. In the present study, we examined the effects of polyI:C on TGF-β-treated A549 human LC cells.
Methods and results: By in vitro cell proliferation assay, polyI:C showed no effect on the growth of A549 cells treated with TGF-β1 at the concentration range up to 10 μg/ml; however, it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-β1-induced Ak strain transforming (Akt) phosphorylation and increased phosphatase and tensin homologue (PTEN) expression without affecting the Son of mothers against decapentaplegic (Smad) 3 phosphorylation or the expression level of E-cadherin, N-cadherin or Snail, indicating that polyI:C suppressed cell motility independently of the ‘cadherin switching’. The Akt inhibitor perifosine inhibited TGF-β1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C.
Conclusion: PolyI:C has a novel function to suppress the motility of LC cells undergoing EMT by targeting the phosphatidylinositol 3-kinase /Akt pathway partly via PTEN and may prevent or reduce the metastasis of LC cells.
en-copyright=
kn-copyright=
en-aut-name=YamaguchiTakahiro
en-aut-sei=Yamaguchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
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=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TongGao
en-aut-sei=Tong
en-aut-mei=Gao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=
affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Toll-like receptors
kn-keyword=Toll-like receptors
en-keyword=cell migration
kn-keyword=cell migration
en-keyword= metastasis
kn-keyword= metastasis
en-keyword=epithelial mesenchymal transformation
kn-keyword=epithelial mesenchymal transformation
END
start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=8
article-no=
start-page=1831
end-page=1839
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210222
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Artificial intelligence supported anemia control system (AISACS) to prevent anemia in maintenance hemodialysis patients
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Anemia, for which erythropoiesis-stimulating agents (ESAs) and iron supplements (ISs) are used as preventive measures, presents important difficulties for hemodialysis patients. Nevertheless, the number of physicians able to manage such medications appropriately is not keeping pace with the rapid increase of hemodialysis patients. Moreover, the high cost of ESAs imposes heavy burdens on medical insurance systems. An artificial-intelligence-supported anemia control system (AISACS) trained using administration direction data from experienced physicians has been developed by the authors. For the system, appropriate data selection and rectification techniques play important roles. Decision making related to ESAs poses a multi-class classification problem for which a two-step classification technique is introduced. Several validations have demonstrated that AISACS exhibits high performance with correct classification rates of 72%-87% and clinically appropriate classification rates of 92%-98%.
en-copyright=
kn-copyright=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=IkedaHiroshi
en-aut-sei=Ikeda
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=SugitaniYoshiki
en-aut-sei=Sugitani
en-aut-mei=Yoshiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=SuitoHiroshi
en-aut-sei=Suito
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HuynhViet Quang Huy
en-aut-sei=Huynh
en-aut-mei=Viet Quang Huy
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KinomuraMasaru
en-aut-sei=Kinomura
en-aut-mei=Masaru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=HaraguchiSoichiro
en-aut-sei=Haraguchi
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=SakuramaKazufumi
en-aut-sei=Sakurama
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=Department of Pathology & Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Internal Medicine, Shigei Medical Research Hospital
kn-affil=
affil-num=3
en-affil=Advanced Institute for Materials Research, Tohoku University
kn-affil=
affil-num=4
en-affil=Advanced Institute for Materials Research, Tohoku University
kn-affil=
affil-num=5
en-affil=Advanced Institute for Materials Research, Tohoku University
kn-affil=
affil-num=6
en-affil=Division of Hemodialysis and Apheresis, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Kobayashi Medicine Clinic
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=anemia
kn-keyword=anemia
en-keyword=artificial intelligence
kn-keyword=artificial intelligence
en-keyword=chronic kidney disease
kn-keyword=chronic kidney disease
en-keyword=erythropoiesis-stimulating agents
kn-keyword=erythropoiesis-stimulating agents
en-keyword=hemodialysis
kn-keyword=hemodialysis
en-keyword=iron
kn-keyword=iron
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=74
cd-vols=
no-issue=6
article-no=
start-page=505
end-page=511
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202012
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=New Vascular-Access Intervention Assistance Plate Provides Good Operability and Safety by Preventing Accidental Falls: First Experience of 1,872 Cases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Vascular-access interventions are necessary for the continuation of hemodialysis, and they are performed under X-ray guidance. During interventions, patients’ accidental falls from the bed are a serious problem, and spe-cialized fixation systems for hemodialysis patients to prevent their falls from the bed have been lacking. We developed a new fixation plate made of polypropylene homopolymer and tested its ability to prevent such falls retrospectively. This plate, which we named the ‘vascular-access intervention assistance plate,’ offers functional features such as the concurrent fixation of the body and either arm and an arm space with serrations for fixing a forearm strap. We performed computer simulations to examine the strength of the plate, and we evaluated the efficacy of fall prevention by reviewing patients’ medical records. The results demonstrated that the functional design of the plate provides good operability via accurate concurrent fixations of the body and arm. The com-puter simulation analysis results indicated the plate’s sufficient strength. The medical records analysis revealed three accidental falls before the plate’s introduction (401 patients, 1,437 interventions), and none after plate introduction (683 patients, 1,872 interventions). Accidental falls were significantly prevented by use of the plate (p < 0.05). The dementia rate and type of procedure were not significantly different between the patients who fell and those who did not. This vascular-access intervention assisted plate provides good operability and safety by preventing accidental falls among hemodialysis patients.
en-copyright=
kn-copyright=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SakuramaKazufumi
en-aut-sei=Sakurama
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=HiramatsuSatoshi
en-aut-sei=Hiramatsu
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
affil-num=1
en-affil=Department of Pathology & Experimental Medicine, 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 Dialysis Access Center, Shigei Medical Research Hospital
kn-affil=
en-keyword=hemodialysis
kn-keyword=hemodialysis
en-keyword=fall accident
kn-keyword=fall accident
en-keyword=incident
kn-keyword=incident
en-keyword=vascular access
kn-keyword=vascular access
END
start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=10418
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200626
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Decreased miR-200b-3p in cancer cells leads to angiogenesis in HCC by enhancing endothelial ERG expression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Transcription factor ERG (erythroblast transformation-specific (ETS)-related gene) is essential in endothelial differentiation and angiogenesis, in which microRNA (miR)-200b-3p targeting site is expected by miRNA target prediction database. miR-200b is known decreased in hepatocellular carcinoma (HCC), however, the functional relation between ERG and miR-200b-3p, originating from pre-miR-200b, in HCC angiogenesis remains unclear. We investigated whether hepatocyte-derived miR-200b-3p governs angiogenesis in HCC by targeting endothelial ERG. Levels of miR-200b-3p in HCC tissues were significantly lower than those in adjacent non-HCC tissues. Poorly differentiated HCC cell line expressed lower level of miR-200b-3p compared to well-differentiated HCC cell lines. The numbers of ERG-positive endothelial cells were higher in HCC tissues than in adjacent non-HCC tissues. There was a negative correlation between the number of ERG-positive cells and miR-200b-3p expression in HCC tissues. Culture supernatants of HCC cell lines with miR-200b-3p-overexpression reduced cell migration, proliferation and tube forming capacity in endothelial cells relative to the control, while those with miR-200b-3p-inhibition augmented the responses. Exosomes isolated from HCC culture supernatants with miR-200b-3p overexpression suppressed endothelial ERG expression. These results suggest that exosomal miR-200b-3p from hepatocytes suppresses endothelial ERG expression, and decreased miR-200b-3p in cancer cells promotes angiogenesis in HCC tissues by enhancing endothelial ERG expression.
en-copyright=
kn-copyright=
en-aut-name=Moh-Moh-AungAye
en-aut-sei=Moh-Moh-Aung
en-aut-mei=Aye
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=ItoSachio
en-aut-sei=Ito
en-aut-mei=Sachio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KatayamaHiroshi
en-aut-sei=Katayama
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=
en-aut-name=OtaYoko
en-aut-sei=Ota
en-aut-mei=Yoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=YoshimuraTeizo
en-aut-sei=Yoshimura
en-aut-mei=Teizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=
affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Molecular medicine
kn-keyword=Molecular medicine
en-keyword=Tumour angiogenesis
kn-keyword=Tumour angiogenesis
END
start-ver=1.4
cd-journal=joma
no-vol=68
cd-vols=
no-issue=1
article-no=
start-page=57
end-page=62
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190731
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Prolonged warm ischemia exacerbated acute rejection after lung transplantation from donation after cardiac death in a mouse
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objective: In lung transplantation (LTx) from donation after cardiac death (DCD), the donor lungs are inevitably exposed to warm ischemic time (WIT) between the cardiac arrest and the initiation of cold preservation. We conducted this study to examine the effect of prolonged WIT on lung allograft rejection in a murine model of LTx from DCD.
Methods: Allogeneic BALB/c → B6 LTx from DCD was performed with a WIT of 15 min (WIT15 group, n = 5) or 60 min (WIT60 group, n = 5). Recipients were immunosuppressed by perioperative costimulatory blockade. The lung allografts were analyzed by histology and flow cytometry on day 7 after the LTx.
Results: Histologically, the rejection grade in the WIT60 group was significantly higher than that in the WIT15 group (3.4 ± 0.4 vs. 2.2 ± 0.2, P = 0.0278). Moreover, the intragraft CD8+ to CD4+ T cell ratio in the WIT60 group was significantly higher than that in the WIT15 group (2.3 ± 0.12 vs. 1.2 ± 0.11, P < 0.0001).
Conclusions: Prolonged WIT could exacerbate the severity of lung allograft rejection after LTx from DCD. Minimization of the WIT could improve the outcomes after LTx from DCD.
en-copyright=
kn-copyright=
en-aut-name=HiranoYutaka
en-aut-sei=Hirano
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=YamamotoSumiharu
en-aut-sei=Yamamoto
en-aut-mei=Sumiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OkadaMasanori
en-aut-sei=Okada
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OtaniShinji
en-aut-sei=Otani
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=
en-aut-name=YamaneMasaomi
en-aut-sei=Yamane
en-aut-mei=Masaomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=
en-aut-name=OtoTakahiro
en-aut-sei=Oto
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of General Thoracic Surgery, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Organ Transplant Center, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Organ Transplant Center, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Brain dead donor
kn-keyword=Brain dead donor
en-keyword=Donation after cardiac death
kn-keyword=Donation after cardiac death
en-keyword=Lung transplantation
kn-keyword=Lung transplantation
en-keyword=Organ preservation
kn-keyword=Organ preservation
en-keyword=Rejection
kn-keyword=Rejection
END
start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=1
article-no=
start-page=1
end-page=6
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202002
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Promising New Anti-Cancer Strategy: Iron Chelators Targeting CSCs
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Iron is a trace but vital element in the human body and is necessary for a multitude of crucial processes in life. However, iron overload is known to induce carcinogenesis via oxidative stress. Cancer cells require large amounts of iron for their rapid division and cell growth. Iron was recently found to play a role in cancer stem cells (CSCs); it maintains stemness during development. Iron also plays an important role in stemness by moderating reactive oxygen species. Thus, iron metabolism in CSCs is a promising therapeutic target. In this review, we summarize the roles of iron in cancer cells and CSCs. We also summarize anti-cancer therapeutic studies with iron chelators and describe our expectation of a new therapeutic strategy for CSCs on the basis of our findings.
en-copyright=
kn-copyright=
en-aut-name=ChenYuehua
en-aut-sei=Chen
en-aut-mei=Yuehua
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=XingBoyi
en-aut-sei=Xing
en-aut-mei=Boyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=QiJiping
en-aut-sei=Qi
en-aut-mei=Jiping
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=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
affil-num=1
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Pathology, the First Affiliated Hospital of Harbin Medical University
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 Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cancer stem cell
kn-keyword=cancer stem cell
en-keyword=stemness
kn-keyword=stemness
en-keyword=iron
kn-keyword=iron
en-keyword=chelation
kn-keyword=chelation
en-keyword=chemotherapy
kn-keyword=chemotherapy
END
start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=3
article-no=
start-page=2756
end-page=2762
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=201909
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cancer stem cell induction from mouse embryonic stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Although cancers are often removed by surgery and treated by chemotherapy and/or radiation therapies, they often reoccur following treatment due to the presence of resistant residual cells such as cancer stem cells (CSCs). CSCs are characterized by their self-renewal, pluripotency, and tumorigenicity properties, and are promising therapeutic targets for the complete therapy of cancers; however, the number of CSCs in cancer tissue is typically too small to investigate fully. We have previously reported that CSCs could be established from induced pluripotent stem cells (iPSCs) using a conditioned medium during cancer cell culture. In the present study, mouse embryonic stem cells (mESCs) were observed to be converted to CSCs (mES-CSCs). This demonstrated that CSC induction does not exclusively occur following gene editing in somatic cells, and that conditioned medium from cancer cells may contain factors that can induce CSCs. Therefore, not only iPSCs but also mESCs, were demonstrated to be able to produce CSCs as one of the potentials of pluripotency of stem cells, suggesting that the conversion to CSCs is not specific to iPSCs. The resultant mES-CSCs would be also useful to generate tissue specific cancers and these naturally occurring cancers can contribute to drug screenings, but also undergo further investigation in order to reveal cancer mechanisms.
en-copyright=
kn-copyright=
en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MurakamiChikae
en-aut-sei=Murakami
en-aut-mei=Chikae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=El‑AaragBishoy
en-aut-sei=El‑Aarag
en-aut-mei=Bishoy
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IwasakiYoshiaki
en-aut-sei=Iwasaki
en-aut-mei=Yoshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
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=6
ORCID=
affil-num=1
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
affil-num=3
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=4
en-affil=Health Service Center, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems
kn-affil=
en-keyword=cancer stem cell
kn-keyword=cancer stem cell
en-keyword=conditioned medium
kn-keyword=conditioned medium
en-keyword=mouse embryonic stem cells
kn-keyword=mouse embryonic stem cells
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=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=54
cd-vols=
no-issue=11
article-no=
start-page=1019
end-page=1028
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190429
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The relationship between the PD-L1 expression of surgically resected and fine-needle aspiration specimens for patients with pancreatic cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=BACKGROUND:
Recently, therapeutic antibodies against programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) have shown promising clinical results for several solid tumors, including pancreatic cancer. In this study, we evaluated the relationship between the PD-L1 expression of surgical resected and fine-needle aspiration (FNA) specimens for patients with pancreatic cancer.
METHODS:
Of 121 patients who underwent endoscopic ultrasound-guided (EUS)-FNA before surgery for pancreatic cancer in an academic center, the 94 (78%) with adequate FNA specimens for a histological evaluation were retrospectively analyzed. All the patients had undergone upfront surgery without any chemotherapy or radiotherapy. We performed immunohistochemistry (IHC) staining to investigate the PD-L1 expression in both resected and FNA specimens. The positive-stained cells were counted, and their percentage was used for the investigation.
RESULTS:
Of the 94 patients, 16 (17%) and 11 (10%) were defined as positive on resected cancer specimens using cutoff points of 5% and 10% positively stained cancer cell counts, respectively. The concordance rates for the positive frequency of PD-L1 expression between resected and FNA specimens were 44% (7/16) and 55% (6/11) when the positivity was set to ≥ 5% and ≥ 10%, respectively. The concordance rates for the negative frequency of PD-L1 expression between two specimens were 97% (76/78) and 99% (82/83) when the positivity was set to ≥ 5% and ≥ 10%, respectively.
CONCLUSIONS:
Approximately, half of the patients with PD-L1 expression positive and almost all the patients with PD-L1 expression negative could be diagnosed on FNA specimens.
en-copyright=
kn-copyright=
en-aut-name=MatsumotoKazuyuki
en-aut-sei=Matsumoto
en-aut-mei=Kazuyuki
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=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakakiAkinobu
en-aut-sei=Takaki
en-aut-mei=Akinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TakaharaMasahiro
en-aut-sei=Takahara
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TanakaNoriyuki
en-aut-sei=Tanaka
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KatoHironari
en-aut-sei=Kato
en-aut-mei=Hironari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=HoriguchiShigeru
en-aut-sei=Horiguchi
en-aut-mei=Shigeru
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=FushimiSoichiro
en-aut-sei=Fushimi
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
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=13
ORCID=
en-aut-name=OkadaHiroyuki
en-aut-sei=Okada
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Department of Gastroenterology and HepatologyOkayama 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 Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=
kn-affil=
affil-num=6
en-affil=Department of PathologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical OncologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical OncologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of PathologyHimeji Red Cross Hospital
kn-affil=
affil-num=12
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical OncologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Immunohistochemistry
kn-keyword=Immunohistochemistry
en-keyword=PD-L1
kn-keyword=PD-L1
en-keyword=Pancreatic cancer
kn-keyword=Pancreatic cancer
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=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=
dt-pub=
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=血液透析用カテーテル留置位置の事前設定器具の開発
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= 血液透析分野では人口の高齢化に伴いカテーテルを用いた透析のニーズが高まっています。安全で効率よく透析を行うための正確なカテーテル留置には、医師の専門的な知識・技術が必要です。正確な位置に留置できなければ、正しく血液透析を行う事ができないだけはなく、医療事故を引き起こしたり、再留置時の透視装置の使用による患者さんへの被爆を増大させたり、高価な透析用カテーテル廃棄による医療費の無駄が生じます。
この問題を解決するために、私達はカテーテルの留置位置事前設定器具を考案し特許申請し、メディカルテクノおかやまの協力を得て、ケイ・テクノ社でプロトタイプを完成させました。この度、重井医学研究所附属病院で臨床研究を行い、安全性に問題なく、良好な留置成績を得る事ができました。今後は成果を学会、論文で発表すると共に、透析以外のカテーテルへの応用や海外展開も視野に事業化を進めていく予定です。
en-copyright=
kn-copyright=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=大原利章
kn-aut-sei=大原
kn-aut-mei=利章
aut-affil-num=1
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=櫻間教文
kn-aut-sei=櫻間
kn-aut-mei=教文
aut-affil-num=2
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=唐井利昌
kn-aut-sei=唐井
kn-aut-mei=利昌
aut-affil-num=3
ORCID=
affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科(医) 免疫病理学
affil-num=2
en-affil=
kn-affil=
affil-num=3
en-affil=
kn-affil=
en-keyword=人口透析
kn-keyword=人口透析
en-keyword=カテーテル
kn-keyword=カテーテル
en-keyword=留置器具
kn-keyword=留置器具
en-keyword=糖尿病
kn-keyword=糖尿病
en-keyword=手技
kn-keyword=手技
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