start-ver=1.4 cd-journal=joma no-vol=117 cd-vols= no-issue=1 article-no= start-page=181 end-page=188 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC.
Methods A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer.
Results At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival.
Conclusions Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection. en-copyright= kn-copyright= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayamaMakio en-aut-sei=Hayama en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoRyujiro en-aut-sei=Sugimoto en-aut-mei=Ryujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakiYuho en-aut-sei=Maki en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkitaRiki en-aut-sei=Okita en-aut-mei=Riki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HiramiYuji en-aut-sei=Hirami en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MatsudaEisuke en-aut-sei=Matsuda en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SanoYoshifumi en-aut-sei=Sano en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsuuraMotoki en-aut-sei=Matsuura en-aut-mei=Motoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MizutaniHisao en-aut-sei=Mizutani en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=7 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=22 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=13 article-no= start-page=8727 end-page=8734 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background　The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissue has been related to the prognosis in various malignancies. Meanwhile, neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammation marker also has been associated with the prognosis in them. However, few reports have investigated the relationship between pulmonary metastases from sarcoma and these biomarkers.
Methods　We retrospectively recruited 102 patients undergoing metastasectomy for pulmonary metastases from uterine leiomyosarcoma at Okayama University Hospital from January 2006 to December 2019. TILs and TLSs were evaluated by immunohistochemical staining of surgically resected specimens of pulmonary metastases using anti-CD3/CD8/CD103/Foxp3/CD20 antibodies. NLR was calculated from the blood examination immediately before the most recent pulmonary metastasectomy. We elucidated the relationship between the prognosis and these factors. Because we considered that the status of tumor tissue and systemic inflammation were equally valuable, we also assessed the impact of the combination of TILs or TLSs and NLR on the prognosis.
Results　As for TILs, CD3-positive cells and CD8-positive cells were correlated with the prognosis. The prognosis was significantly better in patients with CD3-high group, CD8-high group, TLSs-high group, and NLR-low group, respectively. The prognosis of CD8-high/NLR-low group and TLSs-high/NLR-low group was significantly better than that of CD8-low/NLR-high group and TLSs-low/NLR-high group, respectively.
Conclusions　CD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma. en-copyright= kn-copyright= en-aut-name=MatsudaNaoki en-aut-sei=Matsuda en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataKazuma en-aut-sei=Iwata en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=HashimotoKohei en-aut-sei=Hashimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TojiTomohiro en-aut-sei=Toji en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= en-aut-name=TakahashiKatsuhito en-aut-sei=Takahashi en-aut-mei=Katsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=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 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 Pathology, 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Sarcoma Medicine, Center for Sarcoma Multidisciplinary Treatment, Kameda Medical Center 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= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e15077 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230717 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Percentage of low attenuation area on computed tomography detects chronic lung allograft dysfunction, especially bronchiolitis obliterans syndrome, after bilateral lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The percentage of low attenuation area (%LAA) on computed tomography (CT) is useful for evaluating lung emphysema, and higher %LAA was observed in patients with chronic lung allograft dysfunction (CLAD). This study investigated the relationship between the %LAA and the development of CLAD after bilateral lung transplantation (LT).
Methods: We conducted a single-center retrospective study of 75 recipients who underwent bilateral LT; the recipients were divided into a CLAD group (n = 30) and a non-CLAD group (n = 45). The %LAA was calculated using CT and compared between the two groups from 4 years before to 4 years after the diagnosis of CLAD. The relationships between the %LAA and the percent baseline values of the pulmonary function test parameters were also calculated.
Results: The %LAA was significantly higher in the CLAD group than in the non-CLAD group from 2 years before to 2 years after the diagnosis of CLAD (P < .05). In particular, patients with bronchiolitis obliterans syndrome (BOS) exhibited significant differences even from 4 years before to 4 years after diagnosis (P < .05). Significant negative correlations between the %LAA and the percent baseline values of the forced expiratory volume in 1 s (r = ?.36, P = .0031), the forced vital capacity (r = ?.27, P = .027), and the total lung capacity (r = ?.40, P < .001) were seen at the time of CLAD diagnosis.
Conclusion: The %LAA on CT was associated with the development of CLAD and appears to have the potential to predict CLAD, especially BOS, after bilateral LT. en-copyright= kn-copyright= en-aut-name=KuboYujiro en-aut-sei=Kubo en-aut-mei=Yujiro 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=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HashimotoKohei en-aut-sei=Hashimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 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=11 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=12 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= en-keyword=bronchiolitis obliterans syndrome kn-keyword=bronchiolitis obliterans syndrome en-keyword=chronic lung allograft dysfunction kn-keyword=chronic lung allograft dysfunction en-keyword=computed tomography kn-keyword=computed tomography en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=restrictive allograft syndrome kn-keyword=restrictive allograft syndrome END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=8912 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of genetic loci associated with renal dysfunction after lung transplantation using an ethnic-specific single-nucleotide polymorphism array en-subtitle= kn-subtitle= en-abstract= kn-abstract=Renal dysfunction is a long-term complication associated with an increased mortality after lung transplantation (LT). We investigated the association of single-nucleotide polymorphisms (SNPs) with the development of renal dysfunction after LT using a Japanese-specific SNP array. First, eligible samples of 34 LT recipients were genotyped using the SNP array and divided into two groups, according to the presence of homozygous and heterozygous combinations of mutant alleles of the 162 renal-related SNPs. To identify candidate SNPs, the renal function tests were compared between the two groups for each SNP. Next, we investigated the association between the candidate SNPs and the time course of changes of the estimated glomerular filtration rate (eGFR) in the 99 recipients until 10 years after the LT. Delta eGFR was defined as the difference between the postoperative and preoperative eGFR values. Eight SNPs were identified as the candidate SNPs in the 34 recipients. Validation analysis of these 8 candidate SNPs in all the 99 recipients showed that three SNPs, namely, rs10277115, rs4690095, and rs792064, were associated with significant changes of the Delta eGFR. Pre-transplant identification of high-risk patients for the development of renal dysfunction after LT based on the presence of these SNPs might contribute to providing personalized medicine. en-copyright= kn-copyright= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki 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=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika 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=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 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=11 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=12 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=13 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=14 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 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=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 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=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=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 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 General Thoracic Surgery and Breast and Endocrinological Surgery, 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= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e14903 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diagnostic value of circulating microRNA-21 in chronic lung allograft dysfunction after bilateral cadaveric and living-donor lobar lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: MicroRNAs (miRNAs) involved in the pathogenesis of pulmonary fibrosis have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). We investigated the role of circulating miRNAs in the diagnosis of CLAD after bilateral LT, including cadaveric LT (CLT) and living-donor lobar LT (LDLLT).
Methods: The subjects of this retrospective study were 37 recipients of bilateral CLT (n = 23) and LDLLT (n = 14), and they were divided into a non-CLAD group (n = 24) and a CLAD group (n = 13). The plasma miRNA levels of the two groups were compared, and correlations between their miRNAs levels and percent baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) values were calculated from one year before to one year after the diagnosis of CLAD.
Results: The plasma levels of both miR-21 and miR-155 at the time of the diagnosis of CLAD were significantly higher in the CLAD group than in the non-CLAD group (miR-21, P = 0.0013; miR155, P = 0.042). The miR-21 levels were significantly correlated with the percent baseline FEV1, FVC, and TLC value of one year before and at the time of diagnosis of CLAD (P < 0.05). A receiver operating characteristic curve analysis of the performance of miR-21 levels in the diagnosis of CLAD yielded an area under the curve of 0.89.
Conclusion: Circulating miR-21 appears to be of potential value in diagnosing CLAD after bilateral LT. en-copyright= kn-copyright= en-aut-name=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio 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=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 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=9 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=10 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=11 ORCID= affil-num=1 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Chronic lung allograft dysfunction kn-keyword=Chronic lung allograft dysfunction en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=Living -donor lobar lung transplantation kn-keyword=Living -donor lobar lung transplantation en-keyword=Micro-RNA kn-keyword=Micro-RNA 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=12 cd-vols= no-issue=8 article-no= start-page=1195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Robotic Mediastinal Tumor Resections: Position and Port Placement en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to determine the optimal position and port placement during robotic resection for various mediastinal tumors. For anterior mediastinal tumors, total or extended thymectomy is commonly performed in the supine position using the lateral or subxiphoid approach. Although it is unclear which approach is better during robotic thymectomy, technical advantages of subxiphoid approach are beneficial for patients with myasthenia who require extended thymectomy. Partial thymectomy is performed in the supine position using a lateral approach. Superior, middle, and posterior mediastinal tumors are resected in the decubitus position using the lateral approach, whereas dumbbell tumor resection, which requires a posterior approach, can be performed in the prone position. The position and port placement should be chosen depending on the size, location, and aggressiveness of the tumor. In this study, we describe how to choose which of these different robotic approaches can be used based on our experience and previous reports. en-copyright= kn-copyright= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 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 Science 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 Science 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 Science 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 Science kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=robot kn-keyword=robot en-keyword=robot-assisted thoracic surgery kn-keyword=robot-assisted thoracic surgery en-keyword=mediastinal tumor kn-keyword=mediastinal tumor en-keyword=thymectomy kn-keyword=thymectomy en-keyword=port placement kn-keyword=port placement END start-ver=1.4 cd-journal=joma no-vol=2022 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction. en-copyright= kn-copyright= en-aut-name=OchiKosuke en-aut-sei=Ochi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsudakaShimpei en-aut-sei=Tsudaka en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhuYidan en-aut-sei=Zhu en-aut-mei=Yidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 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=13 ORCID= en-aut-name=OkamotoYoshiharu en-aut-sei=Okamoto en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=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=Departments of Pharmacy, Okayama University Hospital 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=16 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=cancer-associated fibroblast kn-keyword=cancer-associated fibroblast en-keyword=drug resistance kn-keyword=drug resistance en-keyword=tranilast kn-keyword=tranilast END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=7297 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=One-step nucleic acid amplification for intraoperative diagnosis of lymph node metastasis in lung cancer patients: a single-center prospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer. en-copyright= kn-copyright= en-aut-name=NambaKei en-aut-sei=Namba en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=MiuraAkihiro en-aut-sei=Miura en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiYuta en-aut-sei=Takahashi en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyauchiShunsaku en-aut-sei=Miyauchi en-aut-mei=Shunsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArakiKota en-aut-sei=Araki en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=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=OtaniShinji en-aut-sei=Otani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 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=15 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=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 Pathology, Memorial Sloan Kettering Cancer Center 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 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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=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 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=Center for Comprehensive Genomic Medicine, 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= 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 General Thoracic Surgery and Breast and Endocrinological Surgery, 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 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=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= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=1 article-no= start-page=114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Survival and prognostic factors in patients undergoing pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes. Methods This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis. Results Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age >= 56 years, disease-free interval < 15 months, and size of metastasis (>= 27 mm) were associated with poor survival. Conclusion Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas. en-copyright= kn-copyright= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 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=9 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=10 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=11 ORCID= en-aut-name=TakahashiKatsuhito en-aut-sei=Takahashi en-aut-mei=Katsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=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 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=Center for Sarcoma Multidisciplinary Treatment, Department of Sarcoma Medicine, Kameda Medical Center kn-affil= affil-num=13 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=Retroperitoneal sarcoma kn-keyword=Retroperitoneal sarcoma en-keyword=Lung metastasis kn-keyword=Lung metastasis en-keyword=Metastasectomy kn-keyword=Metastasectomy END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=23 article-no= start-page=12809 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development en-subtitle= kn-subtitle= en-abstract= kn-abstract=Trastuzumab-emtansine (T-DM1) is a therapeutic agent molecularly targeting human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), and it is especially effective for MBC with resistance to trastuzumab. Although several reports have described T-DM1 resistance, few have examined the mechanism underlying T-DM1 resistance after the development of acquired resistance to trastuzumab. We previously reported that YES1, a member of the Src family, plays an important role in acquired resistance to trastuzumab in HER2-amplified breast cancer cells. We newly established a trastuzumab/T-DM1-dual-resistant cell line and analyzed the resistance mechanisms in this cell line. At first, the T-DM1 effectively inhibited the YES1-amplified trastuzumab-resistant cell line, but resistance to T-DM1 gradually developed. YES1 amplification was further enhanced after acquired resistance to T-DM1 became apparent, and the knockdown of the YES1 or the administration of the Src inhibitor dasatinib restored sensitivity to T-DM1. Our results indicate that YES1 is also strongly associated with T-DM1 resistance after the development of acquired resistance to trastuzumab, and the continuous inhibition of YES1 is important for overcoming resistance to T-DM1. en-copyright= kn-copyright= en-aut-name=FujiharaMiwa en-aut-sei=Fujihara en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhuYidan en-aut-sei=Zhu en-aut-mei=Yidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MamoriTomoka en-aut-sei=Mamori en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiokaRyo en-aut-sei=Yoshioka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UnoMaya en-aut-sei=Uno en-aut-mei=Maya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SuzukiYoko en-aut-sei=Suzuki en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AbeYuko en-aut-sei=Abe en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HatonoMinami en-aut-sei=Hatono en-aut-mei=Minami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KochiMariko en-aut-sei=Kochi en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IwamotoTakayuki en-aut-sei=Iwamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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=20 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Departments of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=19 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=20 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=YES1 kn-keyword=YES1 en-keyword=T-DM1 kn-keyword=T-DM1 en-keyword=dasatinib kn-keyword=dasatinib en-keyword=drug resistance kn-keyword=drug resistance END start-ver=1.4 cd-journal=joma no-vol=2021 cd-vols= no-issue=8 article-no= start-page=rjab336 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210814 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Robot-assisted thoracoscopic lobectomy for severe incomplete interlober fissure en-subtitle= kn-subtitle= en-abstract= kn-abstract=An incomplete interlobar fissure makes thoracoscopic lobectomy difficult and is predictive of morbidity after thoracoscopic lobectomy. This report demonstrates the robot-assisted thoracoscopic (RATS) lobectomy technique for patients with severe incomplete interlobar fissures. A fissureless approach was chosen for pulmonary resection. Near-infrared fluorescence imaging with intravenous indocyanine green (ICG) was used to detect the interlobar line after transection of the bronchus, pulmonary artery and vein. Interlobar fissure was identified and divided by robotic staplers. This combined technique using ICG and fissureless lobectomy made RATS lobectomy safe for patients with severe incomplete interlobar fissures. en-copyright= kn-copyright= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=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=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=296 cd-vols= no-issue= article-no= start-page=100524 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Covalent N-arylation by the pollutant 1,2-naphthoquinone activates the EGF receptor en-subtitle= kn-subtitle= en-abstract= kn-abstract=The epidermal growth factor receptor (EGFR) is the most intensively investigated receptor tyrosine kinase. Several EGFR mutations and modifications have been shown to lead to abnormal self-activation, which plays a critical role in carcinogenesis. Environmental air pollutants, which are associated with cancer and respiratory diseases, can also activate EGFR. Specifically, the environmental electrophile 1,2-naphthoquinone (1,2-NQ), a component of diesel exhaust particles and particulate matter more generally, has previously been shown to impact EGFR signaling. However, the detailed mechanism of 1,2-NQ function is unknown. Here, we demonstrate that 1,2-NQ is a novel chemical activator of EGFR but not other EGFR family proteins. We found that 1,2-NQ forms a covalent bond, in a reaction referred to as N-arylation, with Lys80, which is in the ligand-binding domain. This modification activates the EGFR?Akt signaling pathway, which inhibits serum deprivation?induced cell death in a human lung adenocarcinoma cell line. Our study reveals a novel mode of EGFR pathway activation and suggests a link between abnormal EGFR activation and environmental pollutant?associated diseases such as cancer. en-copyright= kn-copyright= en-aut-name=NakaharaKengo en-aut-sei=Nakahara en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamadaKyohei en-aut-sei=Hamada en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchidaTomoki en-aut-sei=Tsuchida en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbikoYumi en-aut-sei=Abiko en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=KumagaiYoshito en-aut-sei=Kumagai en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=6 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=9 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=epidermal growth factor receptor kn-keyword=epidermal growth factor receptor en-keyword=cell signaling kn-keyword=cell signaling en-keyword=chemical modification kn-keyword=chemical modification en-keyword=signal transduction kn-keyword=signal transduction en-keyword=apoptosis kn-keyword=apoptosis END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=5 article-no= start-page=431 end-page=433 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Giant Thymic Cyst Accompanied by Acute Mediastinitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=We encountered a rare case of thymic cyst accompanied by mediastinitis. A 39-year-old Japanese male presented with fever and chest pain. The chest CT revealed a mass composed of a lobular cystic lesion with inflammation, suggesting the onset of mediastinitis. A definitive histological diagnosis was not obtained, and we performed a thymectomy. Pathologically, the thymic cyst was accompanied by multiple cavities, mimicking thymic cysts, caused by the inflammatory abscess. The surrounding adipose tissue showed inflammatory cell infiltrations with chronic fibrosis. These findings indicate that clinicians should be aware that thymic cysts may cause severe mediastinitis. en-copyright= kn-copyright= en-aut-name=MiuraAkihiro en-aut-sei=Miura en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TojiTomohiro en-aut-sei=Toji en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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 Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= en-keyword=thymic cyst kn-keyword=thymic cyst en-keyword=multilocular thymic cyst kn-keyword=multilocular thymic cyst en-keyword=mediastinitis kn-keyword=mediastinitis END start-ver=1.4 cd-journal=joma no-vol=529 cd-vols= no-issue=3 article-no= start-page=760 end-page=765 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200827 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors.
Materials and methods
A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed.
Results
TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor.
Conclusion
Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance. en-copyright= kn-copyright= en-aut-name=OchiKosuke en-aut-sei=Ochi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=TakanoJui en-aut-sei=Takano en-aut-mei=Jui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyauchiShunsaku en-aut-sei=Miyauchi en-aut-mei=Shunsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiuraAkihiro en-aut-sei=Miura en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ArakiKota en-aut-sei=Araki en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 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=13 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=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=AzumaKazuo en-aut-sei=Azuma en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OkamotoYoshiharu en-aut-sei=Okamoto en-aut-mei=Yoshiharu 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 Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University kn-affil= affil-num=17 en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University kn-affil= affil-num=18 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Monensin kn-keyword=Monensin en-keyword=Epithelial-mesenchymal transition kn-keyword=Epithelial-mesenchymal transition en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=Drug repositioning kn-keyword=Drug repositioning en-keyword=Drug resistance kn-keyword=Drug resistance 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=2020 dt-pub=20200803 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The neutrophil-to-lymphocyte ratio as a novel independent prognostic factor for multiple metastatic lung tumors from various sarcomas en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose
Sarcomas are among the most refractory malignant tumors and often recur as pulmonary metastasis. Although the presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with the prognosis of several malignancies, the relationship between the NLR and sarcoma with pulmonary metastasis is unclear. We investigated the impact of the NLR in patients who underwent surgical resection for metastatic lung tumors from various sarcomas.
Methods
The subjects of this retrospective study were 158 patients with metastatic lung tumors from various sarcomas, who underwent initial pulmonary metastasectomy between 2006 and 2015. We examined the clinicopathological variables, including the NLR and the characteristics of surgical procedures. Survival was estimated by the Kaplan?Meier method and prognostic factors were evaluated by multivariate analysis.
Results
Multivariate analysis revealed significantly better survival of the group with an NLR??2 years, and 3 or more pulmonary metastasectomies.
Conclusion
The NLR immediately before the most recent pulmonary metastasectomy is a novel independent prognostic factor, which may be helpful when considering repeated pulmonary metastasectomy. en-copyright= kn-copyright= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NambaKei en-aut-sei=Namba en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=TojiTomohiro en-aut-sei=Toji en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=KurosakiTakeshi en-aut-sei=Kurosaki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 ORCID= en-aut-name=TakahashiKatsuhito en-aut-sei=Takahashi en-aut-mei=Katsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Diagnostic Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Multidisciplinary Treatment of Sarcoma, Department of Sarcoma Medicine, Kameda Medical Center kn-affil= affil-num=14 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=Metastatic lung tumor kn-keyword=Metastatic lung tumor en-keyword=Sarcoma kn-keyword=Sarcoma en-keyword=Metastasectomy kn-keyword=Metastasectomy en-keyword=Survival rate kn-keyword=Survival rate en-keyword=Neutrophil-to-lymphocyte ratio (NLR) kn-keyword=Neutrophil-to-lymphocyte ratio (NLR) END start-ver=1.4 cd-journal=joma no-vol=111 cd-vols= no-issue=3 article-no= start-page=849 end-page=856 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=YES1 activation induces acquired resistance to neratinib in HER2-amplified breast and lung cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Molecular-targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2-positive breast cancer. However, acquired resistance of various cancers to molecular-targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib-resistant cell lines from HER2-amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib-resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1-amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2-targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome. en-copyright= kn-copyright= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=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=MiyauchiShunsaku en-aut-sei=Miyauchi en-aut-mei=Shunsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ArakiKota en-aut-sei=Araki en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiuraAkihiro en-aut-sei=Miura en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NambaKei en-aut-sei=Namba en-aut-mei=Kei 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=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= affil-num=1 en-affil=Department of Clinical Pharmacy, 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 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=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 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=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=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 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 Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Clinical Pharmacy, 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= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=drug resistance kn-keyword=drug resistance en-keyword=lung cancer kn-keyword=lung cancer en-keyword=neratinib kn-keyword=neratinib en-keyword=YES1 kn-keyword=YES1 END start-ver=1.4 cd-journal=joma no-vol=110 cd-vols= no-issue=8 article-no= start-page=2549 end-page=2557 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acquired resistance mechanisms to afatinib in HER2-amplified gastric cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer treatment, especially that for breast and lung cancer, has entered a new era and continues to evolve, with the development of genome analysis technology and the advent of molecular targeted drugs including tyrosine kinase inhibitors. Nevertheless, acquired drug resistance to molecular targeted drugs is unavoidable, creating a clinically challenging problem. We recently reported the antitumor effect of a pan-HER inhibitor, afatinib, against human epidermal growth factor receptor 2 (HER2)-amplified gastric cancer cells. The purpose of the present study was to identify the mechanisms of acquired afatinib resistance and to investigate the treatment strategies for HER2-amplified gastric cancer cells. Two afatinib-resistant gastric cancer cell lines were established from 2 HER2-amplified cell lines, N87 and SNU216. Subsequently, we investigated the molecular profiles of resistant cells. The activation of the HER2 pathway was downregulated in N87-derived resistant cells, whereas it was upregulated in SNU216-derived resistant cells. In the N87-derived cell line, both MET and AXL were activated, and combination treatment with afatinib and cabozantinib, a multikinase inhibitor that inhibits MET and AXL, suppressed the cell growth of cells with acquired resistance both in vitro and in vivo. In the SNU216-derived cell line, YES1, which is a member of the Src family, was remarkably activated, and dasatinib, a Src inhibitor, exerted a strong antitumor effect in these cells. In conclusion, we identified MET and AXL activation in addition to YES1 activation as novel mechanisms of afatinib resistance in HER2-driven gastric cancer. Our results also indicated that treatment strategies targeting individual mechanisms of resistance are key to overcoming such resistance. en-copyright= kn-copyright= en-aut-name=YoshiokaTakahiro en-aut-sei=Yoshioka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiYuta en-aut-sei=Takahashi en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuriharaEisuke en-aut-sei=Kurihara en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgoshiYusuke en-aut-sei=Ogoshi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NambaKei en-aut-sei=Namba en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoHiroki en-aut-sei=Sato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi 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= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Bioinformatics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=afatinib kn-keyword=afatinib en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=HER2 kn-keyword=HER2 en-keyword=MET kn-keyword=MET en-keyword=YES1 kn-keyword=YES1 END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=7 article-no= start-page=627 end-page=640 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201907 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes. en-copyright= kn-copyright= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SumardikaI Wayan en-aut-sei=Sumardika en-aut-mei=I Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=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=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IiokaHidekazu en-aut-sei=Iioka en-aut-mei=Hidekazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SaitoKen en-aut-sei=Saito en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=RumaI Made Winarsa en-aut-sei=Ruma en-aut-mei=I Made Winarsa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoHiroki en-aut-sei=Sato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 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=15 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=16 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KuboMiyoko en-aut-sei=Kubo en-aut-mei=Miyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=PutrantoEndy Widya en-aut-sei=Putranto en-aut-mei=Endy Widya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MurakamiTakashi en-aut-sei=Murakami en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=LiuMing en-aut-sei=Liu en-aut-mei=Ming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HibinoToshihiko en-aut-sei=Hibino en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 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=26 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=27 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=6 en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=9 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=12 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=19 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Pediatrics, Dr. Sardjito Hospital/Faculty of Medicine, Universitas Gadjah Mada kn-affil= affil-num=21 en-affil=Department of Microbiology, Faculty of Medicine, Saitama Medical University kn-affil= affil-num=22 en-affil=Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University kn-affil= affil-num=23 en-affil=Department of Dermatology, Tokyo Medical University kn-affil= affil-num=24 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=25 en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=26 en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=27 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=4 article-no= start-page=327 end-page=330 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study about the Efficacy of Metformin to Immune Function in Cancer Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=A study to evaluate the effect of metformin on the immune system was commenced in July 2014. Metformin is one of the most commonly prescribed drugs for type 2 diabetes, and previous studies have reported that metformin has an anti-tumor effect. The aim of this study is to evaluate the efficacy of metformin on the immune system in human cancer patients in vivo. The primary outcome parameter will be the rate change in the population of CD8＋ T cells, which produce multiple cytokines. en-copyright= kn-copyright= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=EikawaShingo en-aut-sei=Eikawa en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= affil-num=1 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=metformin kn-keyword=metformin en-keyword=CD8＋ T cells kn-keyword=CD8＋ T cells en-keyword=cancer immunology kn-keyword=cancer immunology END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=23 end-page=26 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Preclinical Evaluation of MicroRNA-34b/c Delivery for Malignant Pleural Mesothelioma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The microRNA-34s (miR-34s) have p53 response elements in their 5?-flanking regions and demonstrate tumor-suppressive functions. In malignant pleural mesothelioma (MPM), we previously reported that expression of miR-34b and miR-34c (miR-34b/c) was frequently downregulated by methylation in MPM cell lines and primary tumors. The forced overexpression of miR-34b/c showed significant antitumor effects with the induction of apoptosis in MPM cells. In this study, we examined the in vivo antitumor effects of miR-34b/c using adenovirus vector on MPM. We subcutaneously transplanted NCI-H290, a human MPM cell line, into BALB/C mice and injected adenovirus vector expressing miR-34b/c, luciferase driven by the cytomegalovirus promoter (Ad-miR-34b/c or Ad-Luc), or PBS control into tumors over 5mm in diameter. A statistically significant growth inhibition of the tumor volume was observed in the Ad-miR-34b/c group from day 6 onward compared to the Ad-Luc group. The inhibition rate of Ad-miR-34b/c, compared to the tumor volume treated with Ad-Luc, was 58.6% on day 10 and 54.7% on day13. Our results indicate that adenovirus-mediated miR-34b/c gene therapy could be useful for the clinical treatment of MPM. en-copyright= kn-copyright= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=FukazawaTakuya en-aut-sei=Fukazawa en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuboTakafumi en-aut-sei=Kubo en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsanoHiroaki en-aut-sei=Asano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MuraokaTakayuki en-aut-sei=Muraoka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaNorimitsu en-aut-sei=Tanaka en-aut-mei=Norimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MakiYuho en-aut-sei=Maki en-aut-mei=Yuho 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=FurukawaMasashi en-aut-sei=Furukawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of General Surgery, Kawasaki Medical School affil-num=4 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=10 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=11 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=12 en-affil= kn-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=13 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=14 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=15 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=mesothelioma kn-keyword=mesothelioma en-keyword=microRNA kn-keyword=microRNA en-keyword=microRNA-34b/c kn-keyword=microRNA-34b/c en-keyword=p53 kn-keyword=p53 END start-ver=1.4 cd-journal=joma no-vol=82 cd-vols= no-issue=3 article-no= start-page=485 end-page=490 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. microRNA-34b/c (miR-34b/c), which plays an important role in the pathogenesis of MPM, is frequently downregulated by DNA methylation in approximately 90% of MPM cases. In this study, we estimated the degree of miR-34b/c methylation in serum-circulating DNA using a digital methylation specific PCR assay (MSP). Materials and methods: A real-time MSP assay was performed using the SYBR Green method. The melting temperature (Tm) of each PCR product was examined using a melting curve analysis. For a digital MSP assay, 40 wells were analyzed per sample. A total of 110 serum samples from 48 MPM cases, 21 benign asbestos pleurisy (BAP) cases, and 41 healthy volunteers (HVs) were examined. Results: Positive range of Tm value for miR-34b/c methylation was defined as 77.71-78.79 degrees C which was the mean 3 standard deviations of 40 wells of a positive control. The number of miR-34b/c methylated wells was counted per sample according to this criterion. The number of miR-34b/c methylated wells in MPM cases was significantly higher than that in BAP cases (P = 0.03) or HVs (P < 0.001). Advanced MPM cases tended to have higher number of miR-34b/c methylated wells than early MPM cases. Receiver-operating characteristic (ROC) curve analysis revealed that three number of miR-34b/c methylated wells per sample was the best cut-off of positivity of MPM with a 67% of sensitivity and a 77% specificity for prediction. The area under the ROC curve was 0.77. Conclusions: Our digital MSP assay can quantify miR-34b/c methylation in serum-circulating DNA. The degree of miR-34b/c methylation in serum-circulating DNA is associated with MPM, suggesting that this approach might be useful for the establishment of a new detection system for MPM. en-copyright= kn-copyright= en-aut-name=MuraokaTakayuki en-aut-sei=Muraoka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=AoeKeisuke en-aut-sei=Aoe en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HashidaShinsuke en-aut-sei=Hashida en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakiYuho en-aut-sei=Maki en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaNorimitsu en-aut-sei=Tanaka en-aut-mei=Norimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=FurukawaMasashi en-aut-sei=Furukawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=AsanoHiroaki en-aut-sei=Asano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KishimotoTakumi en-aut-sei=Kishimoto en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OtsukiTakemi en-aut-sei=Otsuki en-aut-mei=Takemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac SurgPathol affil-num=4 en-affil= kn-affil=Yamaguchi Ube Med Ctr, Natl Hosp Org, Dept Med Oncol & Clin Res affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=11 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=12 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=13 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg affil-num=14 en-affil= kn-affil=Okayama Rosai Hosp, Dept Resp Med affil-num=15 en-affil= kn-affil=Kawasaki Med Univ, Dept Hyg affil-num=16 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Surg en-keyword=Digital PCR kn-keyword=Digital PCR en-keyword=Malignant pleural mesothelioma kn-keyword=Malignant pleural mesothelioma en-keyword=microRNA kn-keyword=microRNA en-keyword=miR-34b/c kn-keyword=miR-34b/c en-keyword=Methylation kn-keyword=Methylation en-keyword=Circulating DNA kn-keyword=Circulating DNA END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=1 article-no= start-page=133 end-page=140 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of GLUT1 and Ki-67 expression on early-stage lung adenocarcinoma diagnosed according to a new international multidisciplinary classification en-subtitle= kn-subtitle= en-abstract= kn-abstract=High expression levels of glucose transporter isoform 1 (GLUT1) and Ki-67 are reportedly associated with malignancy-related clinicopathological factors in malignant tumors. Recently, a new histological IASLC/ATS/ERS classification for lung adenocarcinoma was proposed. In this study, we investigated the clinicopathological impact of GLUT1 and Ki-67 expression on early-stage lung adenocarcinoma classified according to the IASLC/ATS/ERS classification. One hundred and five patients with completely resected stage IA lung adenocarcinoma were retrospectively classified into two groups, a 'non-invasive type' (n=31) or an 'invasive type' (n=74), based on the IASLC/ATS/ERS classification. GLUT1 and Ki-67 expression status was evaluated using immunohistochemistry. The epidermal growth factor receptor (EGFR) and KRAS mutation status was determined using PCR-based assays. Positive GLUT1 and Ki-67 expression and EGFR and KRAS mutations were detected in 28 (27%), 33 (31%), 51 (49%) and 5 (8%) cases, respectively. Positive GLUT1 expression was significantly associated with a wild-type EGFR and mutant KRAS status. A multivariate analysis revealed that positive GLUT1 expression was independently associated with the 'invasive type'. In multivariate analyses for overall survival (OS) and disease-free survival (DFS), positive Ki-67 and GLUT1 expression was the only independent factor for a poor OS (P=0.012) and DFS (P=0.040), respectively. In addition, when stratified according to the GLUT1 and Ki-67 status, double-positive cases had the poorest DFS and OS times, compared with the other categories. Positive GLUT1 expression is associated with the invasive character of early-stage lung adenocarcinoma and with early disease relapse. Our results strongly suggest that GLUT1 and Ki-67 play important roles in acquiring biological malignant potential in early-stage lung adenocarcinoma. en-copyright= kn-copyright= en-aut-name=MakiYuho en-aut-sei=Maki en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IchimuraKouichi en-aut-sei=Ichimura en-aut-mei=Kouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=FurukawaMasashi en-aut-sei=Furukawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MuraokaTakayuki en-aut-sei=Muraoka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaNorimitsu en-aut-sei=Tanaka en-aut-mei=Norimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=AsanoHiroaki en-aut-sei=Asano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=2 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=3 en-affil= kn-affil=Okayama Univ Hosp, Dept Pathol affil-num=4 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=5 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=6 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=7 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=8 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=9 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=10 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=11 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=12 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg affil-num=13 en-affil= kn-affil=Okayama Univ Hosp, Dept Thorac Surg en-keyword=early-stage lung adenocarcinoma kn-keyword=early-stage lung adenocarcinoma en-keyword=glucose transporter isoform 1 kn-keyword=glucose transporter isoform 1 en-keyword=Ki-67 kn-keyword=Ki-67 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=26 end-page=31 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Strong anti-tumor effect of NVP-AUY922, a novel Hsp90 inhibitor, on non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=The anti-tumor activity of a newly developed Hsp90 inhibitor, NVP-AUY922 (AUY922), against non-small cell lung cancer (NSCLC) was examined. Twenty-one NSCLC cell lines were used, the somatic alterations of which were characterized. Cell proliferation was analyzed using a modified MTS assay. Expression of the client proteins was assessed using Western blotting. The cell cycle was analyzed using flow cytometry. The IC50 value of AUY922 for the NSCLC cell lines ranged from 5.2 to 860 nM (median, 20.4 nM). Based on previous data, cells with an IC50 of less than 50 nM were classified as sensitive cells and 19 of the 21 NSCLC cell lines were judged to be sensitive. The IC50 of five malignant pleural mesothelioma (MPM) cell lines revealed that the MPM cells had a significantly higher IC50 value (median, 89.2 nM; range, 22.2-24, 100 nM) than the NSCLC cells (p = 0.015). There was significant depletion of both the total and phosphorylated client proteins - EGFR, MET, HERZ and ART - at low drug concentrations (50-100 nM) in drug-sensitive cell lines. Cell-cycle analysis was performed for two sensitive cell lines, H1975 and H838. Following AUY922 treatment, an increase in the sub-G(0)-G(1) cell population, as well as appearance of cleaved PARP expression, indicated the induction of apoptosis. In conclusion, AUY922 was effective against most NSCLC cell lines, independent of the type of known molecular alteration, and appears to be a promising new drug for the treatment of NSCLC. (C) 2011 Elsevier Ireland Ltd. All rights reserved. en-copyright= kn-copyright= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=AndoMidori en-aut-sei=Ando en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaokaMunenori en-aut-sei=Takaoka en-aut-mei=Munenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AsanoHiroaki en-aut-sei=Asano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakiYuho en-aut-sei=Maki en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MuraokaTakayuki en-aut-sei=Muraoka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaNorimitsu en-aut-sei=Tanaka en-aut-mei=Norimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=FurukawaMasashi en-aut-sei=Furukawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamatsujiTomoki en-aut-sei=Yamatsuji en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NaomotoYoshio en-aut-sei=Naomoto en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Kawasaki Med Univ, Dept Gen Surg affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=9 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=10 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=11 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=12 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=13 en-affil= kn-affil=Kawasaki Med Univ, Dept Gen Surg affil-num=14 en-affil= kn-affil=Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci affil-num=15 en-affil= kn-affil=Kawasaki Med Univ, Dept Gen Surg affil-num=16 en-affil= kn-affil=Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci en-keyword=NSCLC kn-keyword=NSCLC en-keyword=Hsp90 kn-keyword=Hsp90 en-keyword=AUY922 kn-keyword=AUY922 en-keyword=EGFR kn-keyword=EGFR en-keyword=EGFR-TKI kn-keyword=EGFR-TKI en-keyword=Mesothelioma kn-keyword=Mesothelioma END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=32 end-page=38 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frequent methylation and oncogenic role of microRNA-34b/c in small-cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Small-cell lung cancer (SCLC) is an aggressive tumor with a dismal prognosis among primary lung cancers. MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human malignancy. The miR-34 family is comprised of tumor-suppressive miRNAs, and its reduced expression by methylation has been reported in various cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the alteration and tumor-suppressive impact of miR-34s in SCLC. The methylation of miR-34a and miR-34b/c was observed in 4 (36%) and 7 (64%) of 11 SCLC cell lines, respectively. Among the 27 SCLC clinical specimens, miR-34a and miR-34b/c were methylated in 4(15%) and 18 (67%), respectively. In contrast, 13 (28%) miR-34a methylated cases and 12 (26%) miR-34b/c methylated cases were found in 47 NSCLC primary tumors. The frequency of miR-34b/c methylation was significantly higher in SCLC than in NSCLC (p < 0.001). The expressions of miR-34s were reduced in methylated cell lines and tumors and restored after 5-aza-2'-deoxycytidine treatment, indicating that methylation was responsible for the reduced expression of miR-34s. Because the frequency of methylation was higher in miR-34b/c, we focused on miR-34b/c for a functional analysis. We examined the effect of miR-34b/c introduction on cell proliferation, migration and invasion. The transfection of miR-34b/c to two SCLC cell lines (H1048 and SBC5) resulted in the significant inhibition of cell growth, migration, and invasion, compared with control transfectants. Our results indicate that the aberrant methylation of miR-34b/c plays an important role in the pathogenesis of SCLC, implying that miR-34b/c may be a useful therapeutic target for SCLC. en-copyright= kn-copyright= en-aut-name=TanakaNorimitsu en-aut-sei=Tanaka en-aut-mei=Norimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuboTakafumi en-aut-sei=Kubo en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MakiYuho en-aut-sei=Maki en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MuraokaTakayuki en-aut-sei=Muraoka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=FurukawaMasashi en-aut-sei=Furukawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanoHiroaki en-aut-sei=Asano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AoeKeisuke en-aut-sei=Aoe en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=9 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=10 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=11 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=12 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci affil-num=13 en-affil= kn-affil=Natl Hosp Org Yamaguchi Ube Med Ctr, Dept Med Oncol affil-num=14 en-affil= kn-affil=Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci en-keyword=Methylation kn-keyword=Methylation en-keyword=MicroRNA kn-keyword=MicroRNA en-keyword=MicroRNA-34b/c kn-keyword=MicroRNA-34b/c en-keyword=Small cell lung cancer kn-keyword=Small cell lung cancer en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=p53 kn-keyword=p53 END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=1 article-no= start-page=162 end-page=167 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72 months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (449% vs. 90.0%, respectively; P=0.042). In a multivariate analysis. CD133 and ALDH1 negativity (P=0.047) and cN2-3 single station metastasis (P=0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy. en-copyright= kn-copyright= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=IchimuraKouichi en-aut-sei=Ichimura en-aut-mei=Kouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurukawaMasashi en-aut-sei=Furukawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MakiYuho en-aut-sei=Maki en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MuraokaTakayuki en-aut-sei=Muraoka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaNorimitsu en-aut-sei=Tanaka en-aut-mei=Norimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AsanoHiroaki en-aut-sei=Asano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=11 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=12 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=13 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=14 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Resp Med affil-num=15 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg en-keyword=NSCLC kn-keyword=NSCLC en-keyword=Cancer stem cell kn-keyword=Cancer stem cell en-keyword=CD133 kn-keyword=CD133 en-keyword=ALDH1 kn-keyword=ALDH1 en-keyword=Chemoradiotherapy kn-keyword=Chemoradiotherapy en-keyword=Induction therapy kn-keyword=Induction therapy END