start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=4 article-no= start-page=295 end-page=297 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=The Efficacy of Rituximab in High-risk Renal Transplant Recipients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although graft survival following renal transplantation (RTx) has improved, outcomes following highrisk RTx are variable. Preexisting antibodies, including donor-specific antibodies (DSA), play an important role in graft dysfunction and survival. We have designed a study to investigate the safety and efficacy of anti-CD20 monoclonal antibodies (rituximab) in high-risk RTx recipients. Major eligibility criteria include: 1) major and minor ABO blood group mismatch, 2) positive DSA. Thirty-five patients will receive 200 mg/body of rituximab. The primary endpoint is the incidence of B cell depletion. This study will clarify whether rituximab is efficacious in improving graft survival in high-risk RTx recipients. en-copyright= kn-copyright= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KubotaRisa en-aut-sei=Kubota en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiokaTakashi en-aut-sei=Yoshioka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AriyoshiYuichi en-aut-sei=Ariyoshi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitagawaMasashi en-aut-sei=Kitagawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugiyamaHiroshi en-aut-sei=Sugiyama en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=end-stage renal disease kn-keyword=end-stage renal disease en-keyword=immunosuppression kn-keyword=immunosuppression en-keyword=kidney transplantation kn-keyword=kidney transplantation END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=4 article-no= start-page=299 end-page=302 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=A Phase II Clinical Trial Evaluating the Preventive Effectiveness of Lactobacillus Vaginal Suppositories in Patients with Recurrent Cystitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Urinary tract infections (UTIs) are the most common bacterial infections in women, and many patients experience frequent recurrence. The aim of this report is to introduce an on-going prospective phase II clinical trial performed to evaluate the preventive effectiveness of Lactobacillus vaginal suppositories for prevention of recurrent cystitis. Patients enrolled in this study are administered vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus every 2 days or 3 times a week for one year. The primary endpoint is recurrence of cystitis and the secondary endpoints are adverse events. Recruitment began in December 2013 and target sample size is 20 participants. en-copyright= kn-copyright= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UeharaShinya en-aut-sei=Uehara en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiiAyano en-aut-sei=Ishii en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoMasumi en-aut-sei=Yamamoto en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuhataRitsuko en-aut-sei=Mitsuhata en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Takamoto Atsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Kawasaki Hospital, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Center for innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=probiotics kn-keyword=probiotics en-keyword=lactobacilli kn-keyword=lactobacilli en-keyword=Lactobacillus crispatus kn-keyword=Lactobacillus crispatus en-keyword=urinary tract infection kn-keyword=urinary tract infection en-keyword=vaginal suppository kn-keyword=vaginal suppository END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=2 article-no= start-page=127 end-page=132 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20150803 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A prospective cohort study to define the clinical and pathological features of lung cancers harboring HER2 gene aberrations (the HER2-CS Study) and a phase II study of trastuzumab emtansine (recombinant) in patients with HER2-positive non-small cell lung cancer who recurred, progressed after standard chemotherapy, or were primarily refractory to standard chemotherapy kn-title=HER2異常等の低頻度の分子異常を有する非小細胞肺癌の臨床病理学的特徴を明らかにするための前向き観察研究（HER2-CS Study）と標準化学療法後再発・増悪または標準化学療法不応性のHER2陽性非小細胞肺癌患者を対象としたトラスツズマブエムタンシン（遺伝子組換え）の第2相試験 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name=木浦勝行 kn-aut-sei=木浦 kn-aut-mei=勝行 aut-affil-num=1 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name=堀田勝幸 kn-aut-sei=堀田 kn-aut-mei=勝幸 aut-affil-num=2 ORCID= en-aut-name=SatoAkiko en-aut-sei=Sato en-aut-mei=Akiko kn-aut-name=佐藤晃子 kn-aut-sei=佐藤 kn-aut-mei=晃子 aut-affil-num=3 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name=大橋圭明 kn-aut-sei=大橋 kn-aut-mei=圭明 aut-affil-num=4 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name=二宮崇 kn-aut-sei=二宮 kn-aut-mei=崇 aut-affil-num=5 ORCID= en-aut-name=MinnamiDaisuke en-aut-sei=Minnami en-aut-mei=Daisuke kn-aut-name=南大輔 kn-aut-sei=南 kn-aut-mei=大輔 aut-affil-num=6 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name=田端雅弘 kn-aut-sei=田端 kn-aut-mei=雅弘 aut-affil-num=7 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name=久保寿夫 kn-aut-sei=久保 kn-aut-mei=寿夫 aut-affil-num=8 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name=加藤有加 kn-aut-sei=加藤 kn-aut-mei=有加 aut-affil-num=9 ORCID= en-aut-name=HirataTaizo en-aut-sei=Hirata en-aut-mei=Taizo kn-aut-name=平田泰三 kn-aut-sei=平田 kn-aut-mei=泰三 aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=岡山大学病院 affil-num=2 en-affil= kn-affil=岡山大学病院 affil-num=3 en-affil= kn-affil=岡山大学病院 affil-num=4 en-affil= kn-affil=岡山大学病院 affil-num=5 en-affil= kn-affil=岡山大学病院 affil-num=6 en-affil= kn-affil=岡山大学病院 affil-num=7 en-affil= kn-affil=岡山大学病院 affil-num=8 en-affil= kn-affil=岡山大学病院 affil-num=9 en-affil= kn-affil=岡山大学病院 affil-num=10 en-affil= kn-affil=岡山大学病院 en-keyword=臨床研究中核病院 kn-keyword=臨床研究中核病院 en-keyword=国立研究開発法人日本医療研究開発機構 kn-keyword=国立研究開発法人日本医療研究開発機構 en-keyword=文部科学省橋渡し研究加速ネットワークプログラム kn-keyword=文部科学省橋渡し研究加速ネットワークプログラム en-keyword=HER2-CS study kn-keyword=HER2-CS study en-keyword=trastuzumab emtansine kn-keyword=trastuzumab emtansine citation=1) Ohnoshi T, Hiraki S, Kawahara S, Yamashita H, Yonei T, Ishii J, Egawa T, Kozuka A, Hiraki Y, Kimura I : Randomized trial comparing chemotherapy alone and chemotherapy plus chest irradiation in limited stage small cell lung cancer : a preliminary report. Jpn J Clin Oncol (1986) 16, 271-277. citation=2) Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry MC, Souhami RL, Brodin O, Joss RA, Kies MS, Lebeau B, Onoshi T, ?sterlind K, et al. : A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med (1992) 327, 1618-1624. citation=3) Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M : Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol (2004) 22, 3852-3859. citation=4) Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S, Watanabe Y, Sugimoto K, Shibayama T, Yonei T, Ueoka H, Takemoto M, et al. : Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer : OLCSG 0007. J Clin Oncol (2010) 28, 3299-3306. citation=5) EBMの手法による肺癌診療ガイドライン2014年版, 日本肺癌学会編, 金原出版, 東京 (2014) . citation=6) Kuyama S, Hotta K, Tabata M, Segawa Y, Fujiwara Y, Takigawa N, Kiura K, Ueoka H, Eguchi K, Tanimoto M : Impact of HER2 gene and protein status on the treatment outcome of cisplatin-based chemoradiotherapy for locally advanced non-small cell lung cancer. J Thorac Oncol (2008) 3, 477-482. citation=7) Mazi?res J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, Besse B, Blons H, Mansuet-Lupo A, Urban T, Moro-Sibilot D, Dansin E, et al. : Lung cancer that harbors an HER2 mutation : epidemiologic characteristics and therapeutic perspectives. J Clin Oncol (2013) 31, 1997-2003. citation=8) Suzuki M, Shiraishi K, Yoshida A, Shimada Y, Suzuki K, Asamura H, Furuta K, Kohno T, Tsuta K : HER2 gene mutations in non-small cell lung carcinomas : Concurrence with her2 gene amplification and her2 protein expression and phosphorylation. Lung Cancer (2015) 87, 14-22. citation=9) Remillard S, Rebhun LI, Howie GA, Kupchan SM : Antimitotic activity of the potent tumor inhibitor maytansine. Science (1975) 189, 1002-1005. citation=10) Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, Bl?ttler WA, Lambert JM, Chari RV, Lutz RJ, Wong WL, Jacobson FS, et al. : Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res (2008) 68, 9280-9290. citation=11) Weiler D, Diebold J, Strobel K, Aebi S, Gautschi O : Rapid response to trastuzumab emtansine in a patient with HER2-driven lung cancer. J Thorac Oncol (2015) 10, e16-17. END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=80 end-page=84 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=201110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A phase II study of amrubicin and topotecan combination therapy in patients with relapsed or extensive-disease small-cell lung cancer: Okayama Lung Cancer Study Group Trial 0401 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Backgrounds: Chemotherapy is a mainstay in the treatment of extensive-disease small-cell lung cancer (ED-SCLC), although the survival benefit remains modest. We conducted a phase II trial of amrubicin (a topoisomerase II inhibitor) and topotecan (a topoisomerase I inhibitor) in chemotherapy-na?ve and relapsed SCLC patients. Methods: Amrubicin (35 mg/m(2)) and topotecan (0.75 mg/m(2)) were administered on days 3-5 and 1-5, respectively. The objective response rate (ORR) was set as the primary endpoint, which was assessed separately in chemotherapy-na?ve and relapsed cases. Results: Fifty-nine patients were enrolled (chemotherapy-na?ve 31, relapsed 28). The ORRs were 74% and 43% in the chemotherapy-na?ve and relapsed cases, respectively. Survival data were also promising, with a median progression-free survival time and median survival time of 5.3 and 14.9 months and 4.7 and 10.2 months in the chemotherapy-na?ve and relapsed cases, respectively. Even refractory-relapsed cases responded to the treatment favorably (27% ORR). The primary toxicity was myelosuppression with grades 3 or 4 neutropenia in 97% of the patients, which led to grades 3 or 4 febrile neutropenia in 41% of the patients and two toxic deaths. Conclusion: This phase II study showed the favorable efficacy and moderate safety profiles of a topotecan and amrubicin two-drug combination especially in relapsed patients with ED-SCLC. en-copyright= kn-copyright= en-aut-name=NogamiNaoyuki en-aut-sei=Nogami en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChikamoriKenichi en-aut-sei=Chikamori en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShibayamaTakuo en-aut-sei=Shibayama en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KishinoDaizo en-aut-sei=Kishino en-aut-mei=Daizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HosokawaShinobu en-aut-sei=Hosokawa en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TamaokiAkihiko en-aut-sei=Tamaoki en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaritaShingo en-aut-sei=Harita en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UeokaHiroshi en-aut-sei=Ueoka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShinkaiTetsu en-aut-sei=Shinkai en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Department of Respiratory Medicine, NHO Shikoku Cancer Center affil-num=2 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital affil-num=3 en-affil= kn-affil=Department of Medicine, Chugoku Central Hospital affil-num=4 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital affil-num=5 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital affil-num=6 en-affil= kn-affil=Department of Respiratory Medicine, NHO Yamaguchi-Ube Medical Center affil-num=7 en-affil= kn-affil=Department of Medicine, NHO Minami-Okayama Medical Center affil-num=8 en-affil= kn-affil=Department of Respiratory Medicine, NHO Yamaguchi-Ube Medical Center affil-num=9 en-affil= kn-affil=Department of Respiratory Medicine, Okayama Red Cross Hospital affil-num=10 en-affil= kn-affil=Department of Respiratory Medicine, Okayama Institute of Health and Prevention affil-num=11 en-affil= kn-affil=Department of Medicine, Chugoku Central Hospital affil-num=12 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital affil-num=13 en-affil= kn-affil=Department of Respiratory Medicine, NHO Yamaguchi-Ube Medical Center affil-num=14 en-affil= kn-affil=Department of Respiratory Medicine, NHO Shikoku Cancer Center affil-num=15 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Topotecan kn-keyword=Topotecan en-keyword=Amrubicin kn-keyword=Amrubicin en-keyword=Chemo-naive kn-keyword=Chemo-naive en-keyword=Sensitive relapse kn-keyword=Sensitive relapse en-keyword=Refractory relapse kn-keyword=Refractory relapse END start-ver=1.4 cd-journal=joma no-vol=83 cd-vols= no-issue=1 article-no= start-page=30 end-page=36 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of AZD1480 in an epidermal growth factor receptor-driven lung cancer model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: STAT3 plays a vital role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment and is reported to be a critical mediator of the oncogenic effects of EGFR mutations. STAT3 activation is mediated through JAK family kinases. We investigated the effect of the JAK1/2 inhibitor AZD1480 on lung tumors induced by an activating EGFR mutation. Materials and methods: Three EGFR tyrosine kinase inhibitor-resistant cell lines (RPC-9, PC-9/Van-R and PC-9/ER3) established from PC-9 harboring an EGFR exon19 deletion mutation were used. Growth inhibition was measured using an MIT assay. Effects of AZD1480 were also evaluated in the xenograft model and in the EGFR transgenic mice model. Protein expressions were assessed by immunoblotting and immunohistochemistry. Group differences were compared using Student's t-test. To evaluate the efficacy of AZD1480 on survival, AZD1480 or vehicle was administered orally from 7 weeks of age of the transgenic mice. Overall survival curves were calculated using the Kaplan-Meier method. Results: The sensitivities of resistant and parent cells to AZD1480 were similar in vitro. AZD1480 (30 or 50 mg/kg/day, per os) reduced angiogenesis and revealed significant tumor regression in a mouse xenograft model: Subsequently, the transgenic mice were treated with AZD1480 (30 mg/kg/day) or vehicle alone. The numbers of lung tumors (long axis exceeding 1 mm) in the AZD1480-treated group and control group were 0.37 +/- 0.18 and 2.25 +/- 0.53 (p <0.001), respectively. AZD1480 treatment suppressed pSTAT3, pJAK1, pJAK2 and angiogenesis. The median survival time in the AZD1480-treated group (217 days) was significantly greater than that in the control group (106 days) (log-rank test, p <0.0001). Conclusion: AZD1480 may be effective against lung tumors driven by an activating EGER mutation. en-copyright= kn-copyright= en-aut-name=MurakamiToshi en-aut-sei=Murakami en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasugiMasaaki en-aut-sei=Yasugi en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HondaYoshihiro en-aut-sei=Honda en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune 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= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=2 en-affil= kn-affil=Kawasaki Med Univ, Dept Gen Internal Med 4 affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=4 en-affil= kn-affil=Kawasaki Med Univ, Dept Gen Internal Med 4 affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=11 en-affil= kn-affil=Okayama Univ Hosp, Dept Allergy & Resp Med en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Oncogene addiction kn-keyword=Oncogene addiction en-keyword=EGFR kn-keyword=EGFR en-keyword=JAK2 kn-keyword=JAK2 en-keyword=STAT3 kn-keyword=STAT3 en-keyword=Transgenic mice kn-keyword=Transgenic mice END start-ver=1.4 cd-journal=joma no-vol=322 cd-vols= no-issue=1 article-no= start-page=168 end-page=177 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Src mediates ERK reactivation in gefitinib resistance in non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=To study epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms, we established a novel gefitinib-resistant lung cancer cell line derived from an EGFR-mutant non-small cell lung cancer cell line (PC-9) pretreated with 4-(methylnitrosamino)1-(3-pyridy1)-1-butanone (designated PC9-GR). We found that gefitinib substantially suppressed the EGFR signaling pathway, whereas ERK was reactivated after several hours in PC9-GR but not in PC-9. The combination of gefitinib with ERK inhibition (by U0126) restored gefitinib susceptibility in PC9-GR, but PI3K-Akt inhibition with LY294002 did not. Although the levels of phosphorylated Src were up-regulated simultaneously with ERK reactivation, neither ERK suppression using U0126 nor an ERK-specific siRNA induced Src phosphorylation. Furthermore, dual inhibition of EGFR and Src restored gefitinib sensitivity in PC9-GR in vitro and in vivo. In conclusion, our results indicate that Src-mediated ERK reactivation may play a role in a novel gefitinib resistance mechanism, and that the combined use of gefitinib with a Src inhibitor may be a potent strategy to overcome this resistance. en-copyright= kn-copyright= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasugiMasayuki en-aut-sei=Yasugi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=2 en-affil= kn-affil=Kawasaki Hosp, Kawasaki Med Sch, Dept Gen Internal Med 4 affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=9 en-affil= kn-affil=Okayama Univ Hosp, Dept Resp Med en-keyword=EGFR kn-keyword=EGFR en-keyword=Src kn-keyword=Src en-keyword=ERK kn-keyword=ERK en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Gefitinib kn-keyword=Gefitinib en-keyword=Resistance kn-keyword=Resistance 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