2021/12/07 更新

写真a

クボ トシオ
久保 寿夫
KUBO Toshio
所属
岡山大学病院 助教
職名
助教
外部リンク

学位

  • 博士 ( 2013年3月   岡山大学大学院 )

  • 博士(病態制御科学) ( 2013年3月   岡山大学 )

研究キーワード

  • 高齢者

  • 肺癌

  • がんゲノム医療

  • 間質性肺炎

研究分野

  • ライフサイエンス / 腫瘍生物学

学歴

  • 岡山大学大学院     医歯薬学総合研究科

    2007年4月 - 2013年3月

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  • 岡山大学   医学部   医学科

    1996年4月 - 2002年3月

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経歴

  • 岡山大学   腫瘍センター   助教

    2013年12月 - 現在

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所属学協会

▼全件表示

 

論文

  • Marginal Zone Lymphoma and Lung Adenocarcinoma with an EGFR Exon 19 E746-S752del Mutation in a Patient with IgG4-related Disease

    Sachi Okawa, Kammei Rai, Nobuharu Fujii, Yuka Gion, Kiichiro Ninomiya, Yuka Kato, Akihiko Taniguchi, Toshio Kubo, Eiki Ichihara, Kadoaki Ohashi, Nobuaki Miyahara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Internal Medicine   60 ( 17 )   2831 - 2837   2021年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Internal Medicine  

    DOI: 10.2169/internalmedicine.6470-20

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  • Phase 3 Trial Comparing Nanoparticle Albumin-Bound Paclitaxel With Docetaxel for Previously Treated Advanced NSCLC

    Yasuto Yoneshima, Satoshi Morita, Masahiko Ando, Atsushi Nakamura, Shunichiro Iwasawa, Hiroshige Yoshioka, Yasuhiro Goto, Masafumi Takeshita, Toshiyuki Harada, Katsuya Hirano, Tetsuya Oguri, Masashi Kondo, Satoru Miura, Yukio Hosomi, Terufumi Kato, Toshio Kubo, Junji Kishimoto, Nobuyuki Yamamoto, Yoichi Nakanishi, Isamu Okamoto

    JOURNAL OF THORACIC ONCOLOGY   16 ( 9 )   1523 - 1532   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Introduction: We aimed to evaluate the efficacy and safety of nanoparticle albumin-bound (nab-) paclitaxel for previously treated patients with advanced NSCLC.Methods: In this randomized, open-label, noninferiority phase 3 trial, we enrolled patients with advanced NSCLC previously treated with cytotoxic chemotherapy. Patients were randomly allocated (1:1) to receive docetaxel (60 mg/m(2)) on day 1 or nab-paclitaxel (100 mg/m(2)) on days 1, 8, and 15 of a 21-day cycle. The primary end point was overall survival (OS) analyzed on an intention-to-treat basis.Results: Between May 22, 2015, and March 12, 2018, a total of 503 patients were randomly allocated to the treatment Median OS was 16.2 months (95% confidence interval [CI]: 14.4-19.0) for the 252 patients allocated to nab-paclitaxel and 13.6 months (95% CI: 10.9-16.5) for the 251 patients allocated to docetaxel (hazard ratio = 0.85, 95.2% CI: 0.68-1.07). Median progression-free survival was 4.2 months (95% CI: 3.9-5.0) for the nab-paclitaxel group versus 3.4 months (95% CI: 2.9-4.1) for the docetaxel group (hazard ratio = 0.76, 95% CI: 0.63-0.92, p = 0.0042). The objective response rate was 29.9% (95% CI: 24.0-36.2) for the nab-paclitaxel group and 15.4% (95% CI: 10.9-20.7) for the docetaxel group (p = 0.0002). Adverse events of grade greater than or equal to 3 included febrile neutropenia (5 of 245 patients [2%] in the nabpaclitaxel group versus 55 of 249 patients [22%] in the docetaxel group) and peripheral sensory neuropathy (24 [10%] versus 2 [1%], respectively).Conclusions: Nab-paclitaxel was noninferior to docetaxel in terms of OS. It should, thus, be considered a standard treatment option for previously treated patients with advanced NSCLC. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

    DOI: 10.1016/j.jtho.2021.03.027

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  • Pulmonary Aspergilloma and Allergic Bronchopulmonary Aspergillosis Following the 2018 Heavy Rain Event in Western Japan: A Case Report.

    Eri Ando, Takamasa Nakasuka, Toshio Kubo, Akihiko Taniguchi, Kiichiro Ninomiya, Yuka Kato, Eiki Ichihara, Kadoaki Ohashi, Kammei Rai, Katsuyuki Hotta, Masaomi Yamane, Nobuaki Miyahara, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 16-year-old boy with asthma participated in recovery volunteer work following the 2018 heavy rains in Japan. One month later, he experienced chest pain and dyspnea. Chest computed tomography revealed a cavity with a fungal ball, and Aspergillus fumigatus was detected in his bronchoalveolar lavage fluid. He was treated with voriconazole, but new consolidations appeared rapidly. He also experienced allergic bronchopulmonary aspergillosis. After prednisolone prescription, the consolidations improved; however, his asthma worsened. He underwent partial lung resection to avoid allergens, and his symptoms improved. We must recognize cases of infection after a disaster, especially in patients with chronic respiratory diseases.

    DOI: 10.2169/internalmedicine.7124-21

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  • Survival of chemo-naïve patients with EGFR mutation-positive advanced non-small cell lung cancer after treatment with afatinib and bevacizumab: updates from the Okayama Lung Cancer Study Group Trial 1404. 国際誌

    Takashi Ninomiya, Naoyuki Nogami, Toshiyuki Kozuki, Daijiro Harada, Toshio Kubo, Kadoaki Ohashi, Eiki Ichihara, Shoichi Kuyama, Kenichiro Kudo, Akihiro Bessho, Makoto Sakugawa, Nobukazu Fujimoto, Keisuke Aoe, Daisuke Minami, Keisuke Sugimoto, Nobuaki Ochi, Nagio Takigawa, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

    Japanese journal of clinical oncology   51 ( 8 )   1269 - 1276   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: In a phase I study, afatinib (30 mg/body daily) plus bevacizumab (15 mg/kg every 3 weeks) was well tolerated and showed favourable outcomes in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer. Herein, we report the 2-year progression-free survival, overall survival and safety profile of these patients. METHODS: Chemo-naïve patients with EGFR-mutant advanced non-small-cell lung cancer were enrolled. One group of patients received 40 mg afatinib daily and 15 mg/kg bevacizumab every 3 weeks (level 0) until disease progression or severe toxicity. Another group of patients received 30 mg afatinib daily and the same dose of bevacizumab (level 1). Dose-limiting toxicity was the primary endpoint, whereas long-term progression-free survival, overall survival and tolerability were secondary endpoints. Survival rates were estimated using the Kaplan-Meier method. RESULTS: The study included 19 patients (level 0: 5; level - 1: 14). Until the data cut-off date, seven patients continued the treatment, whereas 12 discontinued due to disease progression (n = 5) or toxicity (n = 7). The median PFS was 24.2 months, while the median overall survival was not reached. All patients developed adverse effects. Diarrhoea and skin rash were frequently observed as severe adverse events (grade 3). A secondary EGFR mutation (T790M) was detected in two patients after progression. CONCLUSIONS: Prolonged follow-up revealed that combination therapy with afatinib and bevacizumab might improve survival outcomes in EGFR-mutant advanced non-small-cell lung cancer patients and seems to be promising. TRIAL REGISTRATION: UMIN000015944.

    DOI: 10.1093/jjco/hyab084

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  • Secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs: A case report. 国際誌

    Kohei Taniguchi, Hiroyuki Yanai, Tatsuya Kaji, Toshio Kubo, Daisuke Ennishi, Akira Hirasawa, Tadashi Yoshino

    Journal of cutaneous pathology   48 ( 8 )   1069 - 1074   2021年8月

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    記述言語:英語  

    Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue. Although this tumor was previously reported as indolent, we report a case of secretory carcinoma of the skin with metastases and recurrence. The patient, a 31-year-old women, had a subcutaneous mass in the right axilla. The resected specimen contained a circumscribed mass, with proliferating tumor cells that exhibited prominent nucleoli. They exhibited glandular and papillary growth patterns and there were amphophilic secretions in the glands. Immunohistochemically, the tumor cells were positive for mammaglobin and S100. The tumor was surrounded by sweat glands and there was no mammary glandular tissue, suggesting that it was derived from axillary sweat glands. Accordingly, we made a diagnosis of secretory carcinoma of the skin. Four years after the operation, there were metastases in both lungs. The resected specimen revealed a tumor identical to that of the original skin tumor. Next-generation sequencing-based multiplex gene assay performed on the metastatic tissue revealed an ETV6-NTRK3 fusion gene. This is a rare case report of secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs.

    DOI: 10.1111/cup.14028

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  • SHP2 Inhibition Enhances the Effects of Tyrosine Kinase Inhibitors in Preclinical Models of Treatment-naïve ALK-, ROS1-, or EGFR-altered Non-small Cell Lung Cancer. 国際誌

    Hirohisa Kano, Eiki Ichihara, Hiromi Watanabe, Kazuya Nishii, Chihiro Ando, Takamasa Nakasuka, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Molecular cancer therapeutics   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    After molecular-targeted therapy, some cancer cells may remain that are resistant to therapies targeting oncogene alterations, such as those in the genes encoding the EGFR and anaplastic lymphoma kinase (ALK) as well as c-ros oncogene 1 (ROS1). The mechanisms underlying this type of resistance are unknown. In this article, we report the potential role of Src homology 2 domain-containing phosphatase 2 (SHP2) in the residual cells of ALK/ROS1/EGFR-altered non-small cell lung cancer (NSCLC). Molecular-targeted therapies failed to inhibit the ERK signaling pathway in the residual cells, whereas the SHP2 inhibitor SHP099 abolished their remaining ERK activity. SHP099 administered in combination with molecular-targeted therapy resulted in marked growth inhibition of cancer cells both in vitro and in vivo Thus, treatment combining an SHP2 inhibitor and a tyrosine kinase inhibitor may be a promising therapeutic strategy for oncogene-driven NSCLC.

    DOI: 10.1158/1535-7163.MCT-20-0965

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  • 腎門部に発生した粘液嚢胞腺癌の1例

    三宅 修司, 岩田 健宏, 長尾 賢太郎, 河田 達志, 富永 悠介, 定平 卓也, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 久保 寿夫, 柳井 広之, 那須 保友

    西日本泌尿器科   83 ( 1 )   14 - 14   2021年6月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 腎門部に発生した粘液嚢胞腺癌の1例

    三宅 修司, 岩田 健宏, 長尾 賢太郎, 河田 達志, 富永 悠介, 定平 卓也, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 久保 寿夫, 柳井 広之, 那須 保友

    西日本泌尿器科   83 ( 2 )   100 - 105   2021年6月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • A case of dramatic reduction in cancer-associated thrombus following initiation of pembrolizumab in patient with a poor performance status and PD-L1+ lung adenocarcinoma harboring CCDC6-RET fusion gene and NF1/TP53 mutations. 国際誌

    Takamasa Nakasuka, Kadoaki Ohashi, Hiromi Watanabe, Toshio Kubo, Shingo Matsumoto, Koichi Goto, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

    Lung cancer (Amsterdam, Netherlands)   156   1 - 4   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Pembrolizumab is a standard treatment for non-small cell lung cancer (NSCLC) with high-PD-L1 expression; however, its effect is dismal in patients with poor physical condition. Additionally, the effect of immunotherapy is generally limited in NSCLC harboring driver mutations such asEGFR, ALK, or RET gene aberrations. RESULTS: We report the beneficial effect of pembrolizumab in a patient with poor performance status and PD-L1+ lung adenocarcinoma with theCCDC6-RET fusion gene and co-occurring NF1/TP53 mutations, complicated by multiple cancer-associated thrombi and respiratory failure. CONCLUSIONS: Further studies are warranted to establish the role of co-occurring NF1/TP53 mutations as a positive predictive biomarker for pembrolizumab in NSCLC harboring RET fusion genes.

    DOI: 10.1016/j.lungcan.2021.03.022

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  • A novel osimertinib-resistant human lung adenocarcinoma cell line harbouring mutant EGFR and activated IGF1R. 国際誌

    Go Makimoto, Kiichiro Ninomiya, Toshio Kubo, Ryota Sunami, Yuka Kato, Eiki Ichihara, Kadoaki Ohashi, Kammei Rai, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Japanese journal of clinical oncology   51 ( 6 )   956 - 965   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: A third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is the standard treatment for patients with non-small cell lung cancer harbouring mutant EGFR. Unfortunately, these patients inevitably acquire resistance to EGFR-TKI therapies, including osimertinib. However, the mechanism associated with this resistance remains unclear. METHODS: A 63-year-old Japanese female with lung adenocarcinoma underwent right upper lobectomy (pT1bN2M0 pStage IIIA, EGFR Ex21 L858R). She manifested post-operative tumour recurrence with multiple lung metastases 8 months later and began gefitinib treatment. The lung lesions re-grew 15 months later, and EGFR T790M mutation was detected in the lung metastasis re-biopsy. She was administered osimertinib; however, it relapsed with pleural effusion 16 months later. We isolated cells from the osimertinib-resistant pleural effusion to establish a novel cell line, ABC-31. RESULTS: Although the EGFR L858R mutation was detected in ABC-31 cells, the T790M mutation was lost. ABC-31 cells were resistant to EGFR-TKIs, including osimertinib. Phospho-receptor tyrosine kinase array revealed activation of the insulin-like growth factor 1 receptor (IGF1R), whereas overexpression of the IGF1R ligand, IGF2, induced IGF1R activation in ABC-31 cells. Combination therapy using EGFR-TKIs and IGF1R inhibitor acted synergistically in vitro. She was re-administered osimertinib since EGFR-TKIs and IGF1R inhibitor combination therapy was impossible in clinical practice. This had a slight and short-lived effect. CONCLUSIONS: Taken together, we have successfully established a new osimertinib-resistant lung adenocarcinoma cell line with activated IGF1R. These ABC-31 cells will help develop novel therapeutic strategies for patients with lung adenocarcinoma resistant to specific treatment via IGF1R activation.

    DOI: 10.1093/jjco/hyab048

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  • VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers

    Hiromi Watanabe, Eiki Ichihara, Hiroe Kayatani, Go Makimoto, Kiichiro Ninomiya, Kazuya Nishii, Hisao Higo, Chihiro Ando, Sachi Okawa, Takamasa Nakasuka, Hirohisa Kano, Naofumi Hara, Atsuko Hirabae, Yuka Kato, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    CANCER SCIENCE   112 ( 5 )   1853 - 1864   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC.

    DOI: 10.1111/cas.14801

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  • VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers. 国際誌

    Hiromi Watanabe, Eiki Ichihara, Hiroe Kayatani, Go Makimoto, Kiichiro Ninomiya, Kazuya Nishii, Hisao Higo, Chihiro Ando, Sachi Okawa, Takamasa Nakasuka, Hirohisa Kano, Naofumi Hara, Atsuko Hirabae, Yuka Kato, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer science   112 ( 5 )   1853 - 1864   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC.

    DOI: 10.1111/cas.14801

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  • Dramatic Response to Carboplatin Plus Paclitaxel in Pancreatic Mucinous Cystadenocarcinoma with Liver Metastasis.

    Naohiro Oda, Masahiro Tabata, Masatoshi Uno, Yuzo Umeda, Hironari Kato, Toshio Kubo, Satoru Senoo, Takahito Yagi, Toshiyoshi Fujiwara, Yoshinobu Maeda, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mucinous cystic neoplasm (MCN) of the pancreas is a rare cystic tumor occurring in the pancreatic body and tail in young to middle-aged women that is pathologically characterized by an ovarian-like stroma. Chemotherapy for recurrent/advanced pancreatic MCN has been based on chemotherapy regimens for pancreatic ductal adenocarcinoma, but the prognosis is poor. We herein report a 37-year-old woman with pancreatic mucinous cystadenocarcinoma with liver metastasis that responded dramatically to carboplatin plus paclitaxel therapy (CBDCA + PTX). CBDCA + PTX may be a treatment option for recurrent/advanced pancreatic MCN with an ovarian-like stroma.

    DOI: 10.2169/internalmedicine.6730-20

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  • 【骨・軟部腫瘍のマネジメント(その1)】総論 診療体制 サルコーマセンター設立と腫瘍内科医との連携 集約化と地域連携

    国定 俊之, 中田 英二, 藤原 智洋, 久保 寿夫, 西森 久和, 田端 雅弘, 尾崎 敏文

    別冊整形外科   ( 79 )   7 - 12   2021年4月

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    記述言語:日本語   出版者・発行元:(株)南江堂  

    <文献概要>はじめに わが国では歴史的に整形外科が中心となって肉腫(サルコーマ)の治療方針を決め,主に手術と化学療法を担当してきた.一方,欧米では腫瘍内科が肉腫の化学療法を担当することが一般的であり,わが国の治療状況とは大きく異なる.肉腫治療例の増加とともに進行例が増加し,新規治療薬も開発され,整形外科医のみで治療していくことがむずかしくなってきた.また,化学療法以外にも,肉腫の診断,手術には多くの診療科の協力が必要で,多職種による集学的医療チームによる治療が重要である.当院では肉腫患者によりよい治療を提供する目的で,2014年4月に大学病院の診療部門としては日本ではじめてサルコーマセンターを設立した.本稿では,当院サルコーマセンターの活動を紹介する.

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600002&doc_link_id=10.15106%2Fj_besei79_7&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_7&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • Comparison of bronchoscopy and computed tomography-guided needle biopsy for re-biopsy in non-small cell lung cancer patients. 国際誌

    Hirohisa Kano, Toshio Kubo, Kiichiro Ninomiya, Eiki Ichihara, Kadoaki Ohashi, Kammei Rai, Katsuyuki Hotta, Masahiro Tabata, Takao Hiraki, Susumu Kanazawa, Yoshinobu Maeda, Katsuyuki Kiura

    Respiratory investigation   59 ( 2 )   240 - 246   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: New therapeutic drugs have been developed for non-small cell lung cancer (NSCLC), and the prognosis of advanced NSCLC patients has improved. However, resistance to these drugs is a concern, and re-biopsy is necessary to determine the mechanism of drug resistance. There are many reports about the protocols for re-biopsy, including techniques such as bronchoscopy and computed tomography-guided needle biopsy (CTNB); however, there is no consensus on which method is optimal. Therefore, we retrospectively reviewed the bronchoscopy and CTNB re-biopsies conducted at our hospital. METHODS: We retrospectively analyzed 79 cases of re-biopsies with bronchoscopy or CTNB in patients with NSCLC from January 2014 to December 2016 at our institute. RESULTS: Forty-nine cases of bronchoscopy and 30 cases of CTNB were taken for re-biopsy. The diagnostic rates of bronchoscopy and CTNB were 83.7% and 100%, respectively (p = 0.023). The complication rates of bronchoscopy and CTNB were 18.4% and 36.7%, respectively (p = 0.11), with a statistically significant difference in the incidence of pneumothorax (0% vs. 23.3%, respectively; p < 0.01). Pneumothorax required drainage in 6.7% of all CTNB cases. There were no fatalities in either group. CONCLUSIONS: CTNB showed a higher diagnostic rate; however, it was associated with a higher rate of complications such as pneumothorax. Hence, the optimal modality must be determined individually for each patient.

    DOI: 10.1016/j.resinv.2020.12.001

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  • Randomized study comparing mannitol with furosemide for the prevention of cisplatin-induced renal toxicity in non-small cell lung cancer: The OLCSG1406 trial. 国際誌

    Go Makimoto, Katsuyuki Hotta, Isao Oze, Kiichiro Ninomiya, Masamoto Nakanishi, Naofumi Hara, Hirohisa Kano, Hiromi Watanabe, Yusuke Hata, Kazuya Nishii, Takamasa Nakasuka, Junko Itano, Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Eiki Ichihara, Daisuke Minami, Akiko Sato, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Asia-Pacific journal of clinical oncology   17 ( 1 )   101 - 108   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: Evidence is lacking on the best standard method for forced diuresis to prevent cisplatin-induced nephrotoxicity. We compared the cisplatin-induced nephrotoxicity prevention effect of furosemide or mannitol in patients with advanced non-small cell lung cancer. METHODS: Patients with advanced non-small cell lung cancer suitable to receive cisplatin-containing regimen were randomly assigned to receive furosemide or mannitol with appropriate hydration. The primary endpoint was the proportion of ≥ grade 1 serum creatinine elevation in the first cycle. RESULTS: The trial was terminated early with 44 (22 per arm) of the planned 66 patients because of slow accrual. Patients' characteristics were well balanced with median baseline creatinine clearance of 98.0 and 95.1 mL/min in the furosemide and mannitol arms, respectively. In the first cycle, two (9%) and four (18%) patients developed grade 1 creatinine elevation (P = .66), respectively, despite no ≥ grade 2 toxicity. The median times to develop the worst creatinine score were 10 and 8 days, respectively. For all cycles, median times to recover to grade 0 were 56 and 20 days, respectively. The furosemide arm was characterized by relatively high urine output after cisplatin administration (900 vs 550 mL/h), low frequency of unplanned additional hydration (14% vs 32%), and high incidence of hyponatremia (18% and 5%) compared with the mannitol arm. Both arms showed similar progression-free survival and overall survival. CONCLUSION: The preventive effect of the two forced diuretics on cisplatin-induced nephrotoxicity was not significantly different. However, the two diuretics have some distinct types of clinical presentations.

    DOI: 10.1111/ajco.13423

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  • レンバチニブが有効であった右上顎腺様嚢胞癌の一例

    西 達也, 西森 久和, 亀井 裕子, 二宮 貴一朗, 加藤 有加, 久保 寿夫, 堀田 勝幸, 田端 雅弘, 木浦 勝行, 前田 嘉信

    日本内科学会雑誌   110 ( Suppl. )   169 - 169   2021年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • Immune checkpoint inhibitor efficacy and safety in older non-small cell lung cancer patients. 国際誌

    Toshio Kubo, Hiromi Watanabe, Kiichiro Ninomiya, Kenichiro Kudo, Daisuke Minami, Etsuko Murakami, Nobuaki Ochi, Takashi Ninomiya, Daijiro Harada, Masayuki Yasugi, Eiki Ichihara, Kadoaki Ohashi, Kammei Rai, Keiichi Fujiwara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Japanese journal of clinical oncology   50 ( 12 )   1447 - 1453   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Immune checkpoint inhibitors offer longer survival than chemotherapy in several clinical trials for advanced non-small cell lung cancer. In subset analyses of clinical trials, immune checkpoint inhibitors extended survival in patients aged ≥65 years, but the effects in patients aged ≥75 years are controversial. We performed multicenter, collaborative and retrospective analyses of immune checkpoint inhibitor efficacy and safety in non-small cell lung cancer patients aged ≥75 years. METHODS: We retrospectively studied 434 advanced non-small cell lung cancer patients who received immune checkpoint inhibitors from December 2015 to December 2017, and retrospectively applied the Geriatric (G) 8 screening tool with medical records. RESULTS: Of the 434 patients who received immune checkpoint inhibitors, 100 were aged ≥75 years. Five patients with performance status 3 were omitted from the final analysis. Immune checkpoint inhibitors were given as a first-line treatment to 20 patients. The objective response rates, median progression-free survival rates and median survival times were 35.0%, 6.1 months and 10.7 months for first-line treatment, and 20.0%, 2.9 months and 14.7 months for second- or later-line treatments, respectively. The median modified G8 score was 11.0. The median survival time was longer in the high modified G8 (≥12.0) group than in the low modified G8 (≤11.0) group (18.7 vs. 8.7 months; P = 0.02). Likewise, the median survival time was 15.5 months (performance status 0-1) vs. 3.2 months (performance status 2) (P < 0.01). The grade ≥ 2 immune-related adverse events incidence was 36.8%. CONCLUSIONS: In this study, immune checkpoint inhibitors were effective and tolerable for patients aged ≥75 years. The modified G8 screening tool and performance status were associated with the outcome of older non-small cell lung cancer patients treated with immune checkpoint inhibitors.

    DOI: 10.1093/jjco/hyaa152

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  • Detection of epidermal growth factor receptor mutations in exhaled breath condensate using droplet digital polymerase chain reaction

    Kazuya Nishii, Kadoaki Ohashi, Tomoki Tamura, Kiichiro Ninomiya, Takehiro Matsubara, Satoru Senoo, Hirohisa Kano, Hiromi Watanabe, Naohiro Oda, Go Makimoto, Hisao Higo, Yuka Kato, Takashi Ninomiya, Toshio Kubo, Hiromasa Yamamoto, Shuta Tomida, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Yoshinobu Maeda, Katsuyuki Kiura

    ONCOLOGY LETTERS   20 ( 6 )   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    The detection of certain oncogenic driver mutations, including those of epidermal growth factor receptor (EGFR), is essential for determining treatment strategies for advanced non-small cell lung cancer (NSCLC). The current study assessed the feasibility of testing exhaled breath condensate (EBC) for EGFR mutations by droplet digital PCR (ddPCR). Samples were collected from 12 patients with NSCLC harboring EGFR mutations that were admitted to Okayama University Hospital between June 1, 2014 and December 31, 2017. A total of 21 EBC samples were collected using the RTube (TM) method and EGFR mutations (L858R, exon 19 deletions or T790M) were assessed through ddPCR analysis (EBC-ddPCR). A total of 3 healthy volunteer samples were also tested to determine a threshold value for each mutation. Various patient characteristics were determined, including sex (3 males and 9 females), age (range 54-81 years; median, 66 years), smoking history (10 had never smoked; 2 were former smokers), histology (12 patients exhibited adenocarcinoma), clinical stage (9 patients were stage IV; 3 exhibited post-operative recurrence) and EGFR mutation type (4 had L858R; 8 had exon 19 deletions; 8 had T790M). EBC-ddPCR demonstrated positive droplets in 8 of the 12 patients. The sensitivity and specificity of each mutation was as follows: 27.3 and 80.0% for EGFR L858R, 30.0 and 90.9% for EGFR Ex19del, and 22.2 and 100% for EGFR T790M. EBC-ddPCR analysis of EGFR mutations exhibited modest sensitivity and acceptable specificity. EBC-ddPCR is a minimally invasive and replicable procedure and may be a complementary method for EGFR testing in patients where blood or tissue sampling proves difficult.

    DOI: 10.3892/ol.2020.12256

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  • Detection of epidermal growth factor receptor mutations in exhaled breath condensate using droplet digital polymerase chain reaction. 国際誌

    Kazuya Nishii, Kadoaki Ohashi, Tomoki Tamura, Kiichiro Ninomiya, Takehiro Matsubara, Satoru Senoo, Hirohisa Kano, Hiromi Watanabe, Naohiro Oda, Go Makimoto, Hisao Higo, Yuka Kato, Takashi Ninomiya, Toshio Kubo, Hiromasa Yamamoto, Shuta Tomida, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Yoshinobu Maeda, Katsuyuki Kiura

    Oncology letters   20 ( 6 )   393 - 393   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The detection of certain oncogenic driver mutations, including those of epidermal growth factor receptor (EGFR), is essential for determining treatment strategies for advanced non-small cell lung cancer (NSCLC). The current study assessed the feasibility of testing exhaled breath condensate (EBC) for EGFR mutations by droplet digital PCR (ddPCR). Samples were collected from 12 patients with NSCLC harboring EGFR mutations that were admitted to Okayama University Hospital between June 1, 2014 and December 31, 2017. A total of 21 EBC samples were collected using the RTube™ method and EGFR mutations (L858R, exon 19 deletions or T790M) were assessed through ddPCR analysis (EBC-ddPCR). A total of 3 healthy volunteer samples were also tested to determine a threshold value for each mutation. Various patient characteristics were determined, including sex (3 males and 9 females), age (range 54-81 years; median, 66 years), smoking history (10 had never smoked; 2 were former smokers), histology (12 patients exhibited adenocarcinoma), clinical stage (9 patients were stage IV; 3 exhibited post-operative recurrence) and EGFR mutation type (4 had L858R; 8 had exon 19 deletions; 8 had T790M). EBC-ddPCR demonstrated positive droplets in 8 of the 12 patients. The sensitivity and specificity of each mutation was as follows: 27.3 and 80.0% for EGFR L858R, 30.0 and 90.9% for EGFR Ex19del, and 22.2 and 100% for EGFR T790M. EBC-ddPCR analysis of EGFR mutations exhibited modest sensitivity and acceptable specificity. EBC-ddPCR is a minimally invasive and replicable procedure and may be a complementary method for EGFR testing in patients where blood or tissue sampling proves difficult.

    DOI: 10.3892/ol.2020.12256

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  • Beneficial effect of erlotinib and trastuzumab emtansine combination in lung tumors harboring EGFR mutations. 国際誌

    Hiroe Kayatani, Kadoaki Ohashi, Kiichiro Ninomiya, Go Makimoto, Kazuya Nishii, Hisao Higo, Hiromi Watanabe, Hirohisa Kano, Yuka Kato, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Biochemical and biophysical research communications   532 ( 3 )   341 - 346   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is the standard therapy for non-small cell lung cancer (NSCLC) harboring EGFR mutations, but the resistance is inevitable. The drug-tolerant persister cancer cells are thought to be involved in the resistance. We recently reported that HER2 expression had a negative impact on time-to-treatment-failure in patients with EGFR mutant NSCLC. In this study, we hypothesized that HER2 might be a potential target for alternative combination therapy in NSCLC harboring EGFR mutations. In vitro study showed that the level of HER2 expression had no correlation with the sensitivity to EGFR-TKI, erlotinib but showed some correlation with HER2-inhibitor, ado-trastuzumab emtansine (T-DM1) in multiple EGFR-mutant lung cancer cell lines. In addition, HER2 expression was increased in persister cancer cells in 11-18 cell line harboring EGFR L858R or HCC827 cell line harboring EGFR exon 19 deletion after the exposure to erlotinib in vitro and in vivo. The combination of erlotinib and T-DM1 showed a superior inhibitory effect on cell proliferation compared with those of the erlotinib or T-DM1 alone in either 11-18 or HCC827 cells in vitro. The combination therapy also induced a significantly greater inhibitory effect on tumor growth in xenograft model in mice transplanted with either 11-18 or HCC827 cells compared with erlotinib alone or T-DM1 alone. No body weight loss was observed in these mice. These results suggested that the combination therapy with EGFR-TKI and T-DM1 might be a potentially promising strategy for treating lung cancer harboring EGFR mutations.

    DOI: 10.1016/j.bbrc.2020.07.055

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  • 遺伝性腫瘍-最新情報と今後の方向性 がん遺伝子パネル検査によるがん個別化医療と遺伝性腫瘍への実効果

    山本 英喜, 久保 寿夫, 冨田 秀太, 遠西 大輔, 豊岡 伸一, 平沢 晃

    日本癌学会総会記事   79回   S21 - 5   2020年10月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • Egfr改変肺癌マウスモデルを用いたAd-SGE-REICの抗腫瘍効果の検討

    中須賀 崇匡, 大橋 圭明, 西井 和也, 平生 敦子, 大川 祥, 安東 千裕, 原 尚史, 狩野 裕久, 渡邉 洋美, 二宮 貴一朗, 加藤 有加, 二宮 崇, 久保 寿夫, 頼 冠名, 市原 英基, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   528 - 528   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Egfr改変肺癌マウスモデルを用いたEGFR-TKI、抗VEGFR-2抗体と抗PD-1抗体併用療法の検討

    西井 和也, 大橋 圭明, 中須賀 崇匡, 平生 敦子, 大川 祥, 渡邉 洋美, 狩野 裕久, 原 尚史, 安東 千裕, 二宮 貴一朗, 加藤 有加, 二宮 崇, 久保 寿夫, 頼 冠名, 市原 英基, 堀田 勝幸, 田端 雅弘, 鵜殿 平一郎, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   531 - 531   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • SHP2阻害剤は遺伝子変異陽性肺癌細胞株における分子標的薬の効果を増強する

    狩野 裕久, 市原 英基, 大川 祥, 平生 敦子, 安東 千裕, 中須賀 崇匡, 原 尚史, 西井 和也, 渡邉 洋美, 二宮 貴一朗, 加藤 有加, 二宮 崇, 久保 寿夫, 頼 冠名, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   529 - 529   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 患者由来ROS1肺癌細胞株の樹立とcrizotinib耐性機序の検討

    渡邉 洋美, 狩野 裕久, 西井 和也, 原 尚史, 二宮 貴一朗, 加藤 有加, 久保 寿夫, 頼 冠名, 市原 英基, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   644 - 644   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 非小細胞肺癌領域における新規医薬品に基づく医薬品開発に係る臨床試験デザインについての検討

    加藤 有加, 堀田 勝幸, 二宮 貴一朗, 久保 寿夫, 頼 冠名, 市原 英基, 大橋 圭明, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   534 - 534   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 経気管支肺生検で病理学的に悪性所見が得られず、気管支洗浄液からEGFR遺伝子変異を検出した肺癌の検討

    高田 健二, 市原 英基, 尾関 太一, 西 達也, 西村 淳, 太田 萌子, 中村 尚季, 二宮 貴一朗, 加藤 有加, 二宮 崇, 久保 寿夫, 頼 冠名, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   651 - 651   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Egfr改変肺癌マウスモデルを用いたpersisterがん細胞に対する根治的薬物療法の開発

    大川 祥, 大橋 圭明, 原 尚史, 西井 和也, 中須賀 崇匡, 平生 敦子, 安東 千裕, 狩野 裕久, 渡邉 洋美, 二宮 貴一朗, 加藤 有加, 久保 寿夫, 頼 冠名, 市原 英基, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   644 - 644   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 左上顎洞腫瘤を契機に発見された左心室内への浸潤を伴う肺神経内分泌癌(小細胞癌)の集学的治療の一例

    平生 敦子, 加藤 有加, 西 達也, 岡崎 幹生, 二宮 貴一朗, 二宮 崇, 久保 寿夫, 頼 冠名, 市原 英基, 大橋 圭明, 山根 正修, 堀田 勝幸, 田端 雅弘, 豊岡 伸一, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   683 - 683   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 間質性肺炎症例におけるニンテダニブの発がん抑制効果についての後方視的検討

    西 達也, 久保 寿夫, 加藤 有加, 二宮 貴一朗, 谷口 暁彦, 八杉 昌幸, 池田 元洋, 市原 英基, 大橋 圭明, 頼 冠名, 尾形 佳子, 堀田 勝幸, 宮原 信明, 玄馬 顕一, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   743 - 743   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 抗がん抗原抗体を用いた免疫チェックポイント阻害薬の効果予測法の開発

    渡邉 洋美, 大橋 圭明, 西井 和也, 二宮 貴一朗, 加藤 有加, 久保 寿夫, 頼 冠名, 市原 英基, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   60 ( 6 )   723 - 723   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 経気管支肺生検で病理学的に悪性所見が得られず,気管支洗浄液からEGFR遺伝子変異を検出した肺癌の検討

    高田 健二, 市原 英基, 角南 良太, 西 達也, 大川 祥, 中村 尚季, 中須賀 崇匡, 狩野 裕久, 西井 和也, 渡邉 洋美, 二宮 貴一朗, 加藤 有加, 谷口 暁彦, 久保 寿夫, 頼 冠名, 大橋 圭明, 堀田 勝幸, 宮原 信明, 田端 雅弘, 木浦 勝行, 前田 嘉信

    気管支学   42 ( Suppl. )   S399 - S399   2020年6月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • 診断に苦慮した右肺異常陰影の1例

    高田 健二, 谷口 暁彦, 角南 良太, 大川 祥, 岩本 佳隆, 平生 敦子, 二宮 貴一朗, 久保 寿夫, 頼 冠名, 市原 英基, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 宮原 信明, 木浦 勝行

    岡山医学会雑誌   132 ( 1 )   46 - 46   2020年4月

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    記述言語:日本語   出版者・発行元:岡山医学会  

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  • Influence of age on the efficacy of immune checkpoint inhibitors in advanced cancers: a systematic review and meta-analysis. 国際誌

    Kiichiro Ninomiya, Isao Oze, Yuka Kato, Toshio Kubo, Eiki Ichihara, Kammei Rai, Kadoaki Ohashi, Toshiyuki Kozuki, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Katsuyuki Hotta

    Acta oncologica (Stockholm, Sweden)   59 ( 3 )   249 - 256   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift in the development of cancer treatment. However, it remains to be clarified whether the benefits that they confer differ according to patient age. We conducted a systematic review and meta-analysis to assess age differences in the benefits of ICI treatment.Methods: We systematically searched the PubMed database for randomised controlled trials of ICIs, including PD-1, PD-L1 and CTLA-4 inhibitors across multiple cancer types, such as melanoma, lung cancer and gastric cancer. We extracted trials including hazard ratios (HRs) for death stratified by patient age (cut-off age, 65 years). The primary objective of this study was to assess the difference in ICI efficacy between younger and older patients. We calculated pooled HRs and 95% confidence intervals (CIs) for younger and older cancer patients, and assessed data heterogeneity.Results: We identified 3999 studies in our search. Of these, 24 eligible randomised trials, including a total of 8157 (57%) younger and 6104 (43%) older cancer patients, fulfilled the criteria for our study and were thus further analysed. The pooled HRs of the younger and older patients were 0.76 (95% CI: 0.69-0.84) and 0.80 (95% CI: 0.71-0.86), respectively; the difference in ICI efficacy between younger and older cancer patients was not significant (p = .82). Regarding the PD-1 and PD-L1 inhibitors, the survival benefit was similar in both age groups (HR: 0.74; p = .96), whereas for the CTLA-4 inhibitors, there tended to be less survival benefit for older versus younger patients (HR: 0.90 and 0.77, respectively; p = .26).Conclusions: The survival benefit conferred by ICI was not age-dependent, amongst patients aged 65 years or younger. However, age-dependent benefits may vary amongst different types of ICIs.

    DOI: 10.1080/0284186X.2019.1695062

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  • Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden. 査読

    Makimoto G, Ohashi K, Tomida S, Nishii K, Matsubara T, Kayatani H, Higo H, Ninomiya K, Sato A, Watanabe H, Kano H, Ninomiya T, Kubo T, Rai K, Ichihara E, Hotta K, Tabata M, Toyooka S, Takata M, Maeda Y, Kiura K

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   14 ( 11 )   2009 - 2018   2019年11月

  • EGFR陽性非小細胞肺癌に対するアファチニブ/ベバシズマブ併用療法第I相試験 OLCSG1404 2年後解析

    野上 尚之, 上月 稔幸, 原田 大二郎, 二宮 崇, 久保 寿夫, 大橋 圭明, 久山 彰一, 工藤 健一郎, 別所 昭宏, 藤本 伸一, 青江 啓介, 柴山 卓夫, 南 大輔, 杉本 啓介, 越智 宜昭, 瀧川 奈義夫, 堀田 勝幸, 木浦 勝行

    肺癌   59 ( 6 )   721 - 721   2019年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 臨床的疑問より発した研究-Reverse translational research High tumor mutation burdenのALK陽性肺癌におけるアレクチニブ早期耐性について

    槇本 剛, 大橋 圭明, 冨田 秀太, 二宮 貴一朗, 久保 寿夫, 頼 冠名, 市原 英基, 堀田 勝幸, 田端 雅弘, 豊岡 伸一, 木浦 勝行

    肺癌   59 ( 6 )   571 - 571   2019年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 腫瘍免疫と微小環境 遺伝子改変EGFR変異肺癌マウスモデルの腫瘍免疫回避経路の検討

    西井 和也, 大橋 圭明, 槇本 剛, 渡邉 洋美, 狩野 裕久, 原 尚史, 中須賀 崇匡, 安東 千裕, 二宮 貴一朗, 加藤 有加, 二宮 崇, 久保 寿夫, 頼 冠名, 市原 英基, 堀田 勝幸, 田端 雅弘, 鵜殿 平一郎, 木浦 勝行

    肺癌   59 ( 6 )   567 - 567   2019年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Patients' preferences and perceptions of lung cancer treatment decision making: results from Okayama lung cancer study group trial 1406. 査読

    Makimoto G, Hotta K, Oze I, Ninomiya K, Nakanishi M, Hara N, Kano H, Watanabe H, Hata Y, Nishii K, Nakasuka T, Itano J, Ninomiya T, Kubo T, Ohashi K, Ichihara E, Minami D, Sato A, Tabata M, Maeda Y, Kiura K

    Acta oncologica (Stockholm, Sweden)   1 - 5   2019年10月

  • 肉腫におけるマイクロサテライト不安定性

    中田 英二, 国定 俊之, 長谷井 嬢, 西森 久和, 久保 寿夫, 田端 雅弘, 尾崎 敏文

    中国・四国整形外科学会雑誌   31 ( 3 )   319 - 319   2019年10月

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    記述言語:日本語   出版者・発行元:中国・四国整形外科学会  

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  • Programmed cell death-ligand 1 expression and efficacy of cisplatin-based chemotherapy in lung cancer: A sub-analysis of data from the two Okayama Lung Cancer Study Group prospective feasibility studies. 査読

    Nishii K, Hotta K, Ninomiya K, Kato Y, Ichihara E, Ohashi K, Ninomiya T, Kubo T, Rai K, Tabata M, Maeda Y, Kiura K

    Respiratory investigation   57 ( 5 )   460 - 465   2019年9月

  • SHP2阻害薬によるクリゾチニブのROS1陽性肺癌細胞阻害効果の増強(SHP2 inhibitor enhanced the effects of crizotinib in ROS1 rearranged lung cancer cell lines)

    狩野 裕久, 市原 英基, 原 尚史, 渡邉 洋美, 西井 和也, 槇本 剛, 二宮 貴一朗, 久保 寿夫, 頼 冠名, 大橋 圭明, 前田 嘉信, 木浦 勝行

    日本癌学会総会記事   78回   E - 3031   2019年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • The effect and safety of immune checkpoint inhibitor rechallenge in non-small cell lung cancer. 査読

    Watanabe H, Kubo T, Ninomiya K, Kudo K, Minami D, Murakami E, Ochi N, Ninomiya T, Harada D, Yasugi M, Ichihara E, Ohashi K, Fujiwara K, Hotta K, Tabata M, Maeda Y, Kiura K

    Japanese journal of clinical oncology   49 ( 8 )   762 - 765   2019年8月

  • A phase I/II trial of weekly nab-paclitaxel for pretreated non-small-cell lung cancer patients without epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement. 査読

    Harada D, Kozuki T, Nogami N, Bessho A, Hosokawa S, Fukamatsu N, Hotta K, Ohashi K, Kubo T, Yoshioka H, Yokoyama T, Sone N, Kuyama S, Kudo K, Yasugi M, Takigawa N, Oze I, Kiura K

    Asia-Pacific journal of clinical oncology   15 ( 4 )   250 - 256   2019年8月

  • 災害ボランティア活動に参加した喘息患者の血痰精査中に発見された右胸部異常陰影の一例

    鹿谷 芳伸, 黒崎 毅史, 大谷 真二, 中田 憲太郎, 難波 圭, 諏澤 憲, 枝園 和彦, 久保 寿夫, 山本 寛斉, 岡崎 幹生, 杉本 誠一郎, 宗 淳一, 山根 正修, 大藤 剛宏, 豊岡 伸一

    岡山医学会雑誌   131 ( 2 )   113 - 113   2019年8月

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    記述言語:日本語   出版者・発行元:岡山医学会  

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  • Successful Treatment of Metastatic Urothelial Carcinoma after Accurate Diagnosis by Immunohistochemistry. 査読

    Makimoto G, Nishimori H, Kondo R, Yanai H, Sugimoto M, Oda N, Kubo T, Hotta K, Tabata M, Kiura K, Maeda Y

    Acta medica Okayama   73 ( 3 )   279 - 284   2019年6月

  • Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer. 査読

    Ichihara E, Hotta K, Ninomiya K, Kubo T, Ohashi K, Rai K, Tanaka H, Tabata M, Maeda Y, Kiura K

    Lung cancer (Amsterdam, Netherlands)   132   54 - 58   2019年6月

  • Chemoradiotherapy for locally advanced lung cancer patients with interstitial lung abnormalities. 査読

    Higo H, Kubo T, Makimoto S, Makimoto G, Ihara H, Masaoka Y, Ninomiya T, Ichihara E, Ohashi K, Sato A, Hotta K, Tabata M, Takigawa N, Maeda Y, Kiura K

    Japanese journal of clinical oncology   49 ( 5 )   458 - 464   2019年5月

  • Rapid and Long-term Response of Pulmonary Pleomorphic Carcinoma to Nivolumab. 査読

    Senoo S, Ninomiya T, Makimoto G, Nishii K, Kano H, Watanabe H, Hata Y, Kubo T, Tanaka T, Hotta K, Maeda Y, Kiura K

    Internal medicine (Tokyo, Japan)   58 ( 7 )   985 - 989   2019年4月

  • Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol. 査読

    Ninomiya T, Ishikawa N, Inoue K, Kubo T, Yasugi M, Shibayama T, Maeda T, Fujitaka K, Kodani M, Yokoyama T, Kuyama S, Ochi N, Ueda Y, Miyoshi S, Kozuki T, Amano Y, Kubota T, Sugimoto K, Bessho A, Ishii T, Watanabe K, Oze I, Hotta K, Kiura K

    Clinical lung cancer   20 ( 2 )   134 - 138   2019年3月

  • 非小細胞肺癌に対する免疫チェックポイント阻害剤の再投与についての後方視的検討

    渡邉 洋美, 久保 寿夫, 二宮 貴一朗, 工藤 健一郎, 南 大輔, 村上 悦子, 越智 宣昭, 原田 大二郎, 八杉 昌幸, 市原 英基, 大橋 圭明, 藤原 慶一, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    日本呼吸器学会誌   8 ( 増刊 )   267 - 267   2019年3月

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  • 免疫チェックポイント 高齢非小細胞肺癌に対する免疫チェックポイント阻害剤の効果と安全性に関する後方視的検討

    久保 寿夫, 渡邉 洋美, 二宮 貴一朗, 工藤 健一郎, 南 大輔, 村上 悦子, 越智 宣昭, 原田 大二郎, 八杉 昌幸, 市原 英基, 大橋 圭明, 藤原 慶一, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    日本呼吸器学会誌   8 ( 増刊 )   156 - 156   2019年3月

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  • 豪雨災害ボランティア後に肺アスペルギローマおよびABPAを発症した一例

    安東 愛理, 中須賀 崇匡, 久保 寿夫, 安東 千裕, 岩本 佳隆, 梅野 貴裕, 平生 敦子, 二宮 貴一朗, 谷口 暁彦, 頼 冠名, 市原 英基, 大橋 圭明, 宮原 信明, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    日本呼吸器学会誌   8 ( 増刊 )   355 - 355   2019年3月

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  • 肺動脈血栓塞栓症を合併した全身状態不良の肺腺癌に対しpembrolizumabが奏効した1例

    濱崎 友洋, 中須賀 崇匡, 大橋 圭明, 安東 千裕, 原 尚史, 梅野 貴裕, 岩本 佳隆, 板野 純子, 二宮 貴一朗, 二宮 崇, 谷口 暁彦, 久保 寿夫, 市原 英基, 堀田 勝幸, 宮原 信明, 田端 雅弘, 木浦 勝行, 前田 嘉信

    肺癌   59 ( 1 )   107 - 107   2019年2月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • ニボルマブによる尋常性乾癬・ぶどう膜炎の顕在化

    河野 和馬, 妹尾 賢, 大橋 圭明, 中須賀 崇匡, 安東 千裕, 原 尚史, 岩本 佳隆, 梅野 貴裕, 二宮 貴一朗, 谷口 暁彦, 二宮 崇, 久保 寿夫, 市原 英基, 頼 冠名, 片山 英樹, 堀田 勝幸, 宮原 信明, 田端 雅弘, 木浦 勝行, 前田 嘉信

    肺癌   59 ( 1 )   107 - 107   2019年2月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • MET or NRAS amplification is an acquired resistance mechanism to the third-generation EGFR inhibitor naquotinib 査読

    Kiichiro Ninomiya, Kadoaki Ohashi, Go Makimoto, Shuta Tomida, Hisao Higo, Hiroe Kayatani, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Scientific Reports   8 ( 1 )   1955   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Publishing Group  

    As a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimeritnib is the standard treatment for patients with non-small cell lung cancer harboring the EGFR T790M mutation
    however, acquired resistance inevitably develops. Therefore, a next-generation treatment strategy is warranted in the osimertinib era. We investigated the mechanism of resistance to a novel EGFR-TKI, naquotinib, with the goal of developing a novel treatment strategy. We established multiple naquotinib-resistant cell lines or osimertinib-resistant cells, two of which were derived from EGFR-TKI-naïve cells
    the others were derived from gefitinib- or afatinib-resistant cells harboring EGFR T790M. We comprehensively analyzed the RNA kinome sequence, but no universal gene alterations were detected in naquotinib-resistant cells. Neuroblastoma RAS viral oncogene homolog (NRAS) amplification was detected in naquotinib-resistant cells derived from gefitinib-resistant cells. The combination therapy of MEK inhibitors and naquotinib exhibited a highly beneficial effect in resistant cells with NRAS amplification, but the combination of MEK inhibitors and osimertinib had limited effects on naquotinib-resistant cells. Moreover, the combination of MEK inhibitors and naquotinib inhibited the growth of osimertinib-resistant cells, while the combination of MEK inhibitors and osimertinib had little effect on osimertinib-resistant cells. Clinical assessment of this novel combination (MEK inhibitors and naquotinib) is worth considering in osimertinib-resistant lung tumors.

    DOI: 10.1038/s41598-018-20326-z

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  • Atezolizumab Treatment Beyond Progression in Advanced NSCLC: Results From the Randomized, Phase III OAK Study. 査読

    Gandara DR, von Pawel J, Mazieres J, Sullivan R, Helland Å, Han JY, Ponce Aix S, Rittmeyer A, Barlesi F, Kubo T, Park K, Goldschmidt J, Gandhi M, Yun C, Yu W, Matheny C, He P, Sandler A, Ballinger M, Fehrenbacher L

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   13 ( 12 )   1906 - 1918   2018年12月

  • Study Protocol: Phase-Ib Trial of Nivolumab Combined With Metformin for Refractory/Recurrent Solid Tumors. 査読

    Kubo T, Ninomiya T, Hotta K, Kozuki T, Toyooka S, Okada H, Fujiwara T, Udono H, Kiura K

    Clinical lung cancer   19 ( 6 )   e861 - e864   2018年11月

  • Combined effect of cabozantinib and gefitinib in crizotinib-resistant lung tumors harboring ROS1 fusions. 査読

    Kato Y, Ninomiya K, Ohashi K, Tomida S, Makimoto G, Watanabe H, Kudo K, Matsumoto S, Umemura S, Goto K, Ichihara E, Ninomiya T, Kubo T, Sato A, Hotta K, Tabata M, Toyooka S, Maeda Y, Kiura K

    Cancer science   109 ( 10 )   3149 - 3158   2018年10月

  • 非小細胞肺癌に対する免疫チェックポイント阻害剤の再投与における効果と安全性に対する後方視的検討

    渡邉 洋美, 久保 寿夫, 二宮 貴一朗, 工藤 健一郎, 南 大輔, 村上 悦子, 越智 宣昭, 二宮 崇, 原田 大二郎, 八杉 昌幸, 市原 英基, 大橋 圭明, 藤原 慶一, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   58 ( 6 )   699 - 699   2018年10月

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  • デジタルPCR法による呼気濃縮液を用いたEGFR遺伝子診断法の検討

    西井 和也, 大橋 圭明, 田村 朋季, 妹尾 賢, 狩野 裕久, 渡邉 洋美, 小田 尚廣, 槇本 剛, 肥後 寿夫, 二宮 貴一朗, 加藤 有加, 南 大輔, 二宮 崇, 久保 寿夫, 堀田 勝幸, 田端 雅弘, 冨田 秀太, 豊岡 伸一, 前田 嘉信, 木浦 勝行

    肺癌   58 ( 6 )   597 - 597   2018年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 75歳以上の高齢非小細胞肺癌に対する免疫チェックポイント阻害剤の効果と安全性に対する後方視的検討

    久保 寿夫, 渡邉 洋美, 二宮 貴一朗, 工藤 健一郎, 南 大輔, 村上 悦子, 越智 宣昭, 二宮 崇, 原田 大二郎, 八杉 昌幸, 市原 英基, 大橋 圭明, 藤原 慶一, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   58 ( 6 )   523 - 523   2018年10月

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  • EGFR遺伝子変異陽性肺癌に対するタグリッソ再投与の有効性に関する検討

    市原 英基, 二宮 貴一朗, 久保 寿夫, 頼 冠名, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   58 ( 6 )   633 - 633   2018年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • EMT化を示すAlectinib耐性後の患者由来新規ALK肺癌細胞株の樹立とその耐性化の克服

    槇本 剛, 大橋 圭明, 佐藤 晃子, 渡邉 洋美, 二宮 貴一朗, 二宮 崇, 頼 冠名, 久保 寿夫, 市原 英基, 片山 英樹, 堀田 勝幸, 田端 雅弘, 豊岡 伸一, 前田 嘉信, 木浦 勝行

    肺癌   58 ( 6 )   599 - 599   2018年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 当院でニボルマブ投与開始し、長期的効果を認めた10症例の後方視的検討

    中須賀 崇匡, 渡邉 洋美, 久保 寿夫, 二宮 貴一朗, 二宮 崇, 頼 冠名, 市原 英基, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   58 ( 6 )   698 - 698   2018年10月

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  • Atezolizumab in Japanese Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer: A Subgroup Analysis of the Phase 3 OAK Study 査読

    Toyoaki Hida, Reiko Kaji, Miyako Satouchi, Norihiko Ikeda, Atsushi Horiike, Hiroshi Nokihara, Takashi Seto, Tomohisa Kawakami, Shintaro Nakagawa, Toshio Kubo

    Clinical Lung Cancer   19 ( 4 )   e405 - e415   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier Inc.  

    Atezolizumab is effective and well tolerated in pretreated advanced/metastatic non–small-cell lung cancer (NSCLC). We examined atezolizumab's efficacy and safety in 64 Japanese patients with NSCLC in the same setting via a subanalysis of the phase 3 OAK study. Atezolizumab improved overall survival versus docetaxel and was generally well tolerated, thus offering a potential NSCLC treatment for Japanese patients. Introduction: Atezolizumab, an anti–programmed death-ligand 1 (PD-L1) agent, is effective and well tolerated in patients with pretreated advanced non–small-cell lung cancer (NSCLC). We assessed its efficacy and safety in Japanese patients through subgroup analyses of the phase 3 OAK study (NCT02008227). Patients and Methods: Key eligibility criteria of this randomized, controlled, open-label, international study include locally advanced/metastatic NSCLC, ≥ 1 prior platinum-based chemotherapy, age ≥ 18 years, measurable disease (Response Evaluation Criteria in Solid Tumors v1.1), and Eastern Cooperative Oncology Group performance status 0 or 1. Atezolizumab 1200 mg or docetaxel 75 mg/m2 was provided intravenously every 3 weeks. Co-primary end points were overall survival (OS) in the intention-to-treat (ITT) population and those with ≥ 1% PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC
    TC1/2/3 or IC1/2/3). Results: Sixty-four ITT patients were Japanese
    19 had TC1/2/3 or IC1/2/3 status. In Japanese ITT patients, median OS in the atezolizumab arm (n = 36) was longer than the docetaxel arm (n = 28
    21.3 months [95% confidence interval (CI), 11.0-not estimable (NE)] versus 17.0 months [95% CI, 12.5-NE], respectively
    hazard ratio 0.80 [95% CI, 0.41-1.57]). In the TC1/2/3 or IC1/2/3 population, median OS was 21.3 months (95% CI, 15.0-NE) and NE in the atezolizumab (n = 11) and docetaxel (n = 8) groups, respectively (hazard ratio, 0.81 [95% CI, 0.22-3.05]). Atezolizumab was generally well tolerated, with no treatment-related deaths. Conclusion: Atezolizumab was effective and well tolerated in pretreated Japanese patients with NSCLC. Results are consistent with the primary analysis of OAK.

    DOI: 10.1016/j.cllc.2018.01.004

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  • 免疫チェックポイント阻害剤が次治療に与える影響についての後方視的検討

    渡邉 洋美, 久保 寿夫, 二宮 貴一朗, 工藤 健一郎, 南 大輔, 越智 宣昭, 原田 大二郎, 村上 悦子, 八杉 昌幸, 二宮 崇, 市原 英基, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 木浦 勝行

    日本がん免疫学会総会プログラム・抄録集   22回   144 - 144   2018年7月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • Randomized Phase II Study Comparing Mannitol with Furosemide for the Prevention of Renal Toxicity Induced by Cisplatin-based Chemotherapy with Short-term Low-volume Hydration in Advanced Non-small Cell Lung Cancer: The OLCSG1406 Study Protocol. 査読

    Makimoto G, Ichihara E, Hotta K, Ninomiya K, Oze I, Minami D, Ninomiya T, Kubo T, Ohashi K, Tabata M, Maeda Y, Kiura K

    Acta medica Okayama   72 ( 3 )   319 - 323   2018年6月

  • Clinical significance of repeat rebiopsy in detecting the EGFR T790M secondary mutation in patients with non-small cell lung cancer. 査読

    Ichihara E, Hotta K, Kubo T, Higashionna T, Ninomiya K, Ohashi K, Tabata M, Maeda Y, Kiura K

    Oncotarget   9 ( 50 )   29525 - 29531   2018年6月

  • フェンタニルとミダゾラム併用による気管挿管下での気管支鏡検査の苦痛度評価

    南 大輔, 瀧川 奈義夫, 二宮 崇, 久保 寿夫, 市原 英基, 大橋 圭明, 堀田 勝幸, 宮原 信明, 柴山 卓夫, 田端 雅弘, 木浦 勝行

    気管支学   40 ( Suppl. )   S189 - S189   2018年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • Second primary cancer in survivors of locally advanced non-small cell lung cancer treated with concurrent chemoradiation followed by surgery 査読

    Go Makimoto, Toshio Kubo, Isao Oze, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Junichi Soh, Shinichi Toyooka, Kuniaki Katsui, Nagio Takigawa, Mitsune Tanimoto, Katsuyuki Kiura

    Japanese Journal of Clinical Oncology   48 ( 3 )   287 - 290   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press  

    The standard treatment for patients with locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT), but surgical resection following induction CRT can extend overall survival in a select population. However, patients who survive longer are at risk of developing a second primary cancer (SPC). This is the first report to determine the incidence of SPC in survivors with LA-NSCLC after trimodal therapy. Between October 1997 and October 2013, 112 Stage III NSCLC patients underwent trimodal therapy in our hospital. The 5-year overall survival rate was 71.8%. SPC developed in 10 of the 112 patients 0.60-15.0 (median 5.49) years after initiating CRT. The observed incidence of SPC was 1.8 per 100 patient-years. Although trimodal therapy can prolong patient survival, the estimated incidence of SPC does not increase. A large prospective study with a longer follow-up time is required to determine the effects of trimodal therapy, including the development of SPC.

    DOI: 10.1093/jjco/hyy003

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  • A Phase II Study of Trastuzumab Emtansine in HER2-Positive Non–Small Cell Lung Cancer 査読

    Katsuyuki Hotta, Keisuke Aoe, Toshiyuki Kozuki, Kadoaki Ohashi, Kiichiro Ninomiya, Eiki Ichihara, Toshio Kubo, Takashi Ninomiya, Kenichi Chikamori, Daijiro Harada, Naoyuki Nogami, Taizo Hirata, Shiro Hinotsu, Shinichi Toyooka, Katsuyuki Kiura

    Journal of Thoracic Oncology   13 ( 2 )   273 - 279   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier Inc  

    Trastuzumab emtansine (T-DM1), an anti–erb-b2 receptor tyrosine kinase 2 (HER2) antibody-drug conjugate, has been shown to significantly improve survival in HER2-positive breast cancer. We report a phase II trial of T-DM1 monotherapy in relapsed NSCLC with documented HER2 positivity (an immunohistochemistry [IHC] score of 3+, both an IHC score of 2+ and fluorescence in situ hybridization positivity, or exon 20 mutation). This study was terminated early because of limited efficacy. The demographic characteristics in the 15 assessable patients were as follows: median age, 67 years
    male sex, 47%
    performance status of 0 to 1, 80%
    HER2 status IHC 3+, 33%
    HER status IHC 2+/fluorescence in situ hybridization–positive, 20%
    and exon 20 mutation, 47%. The median number of delivered cycles was 3 (range 1–11). One patient achieved a partial response with an objective response rate of 6.7% (90% confidence interval: 0.2–32.0). With a median follow-up time of 9.2 months, the median progression-free survival time and median survival time were 2.0 and 10.9 months, respectively. Grade 3 or 4 adverse events included thrombocytopenia (40%) and hepatotoxicity (20%) without any treatment-related deaths. T-DM1 had a limited efficacy for HER2-positive NSCLC in our cohort. Applying the concept of precision medicine to tumors appears challenging
    thus, additional molecular approaches are warranted.

    DOI: 10.1016/j.jtho.2017.10.032

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  • Potential influence of interleukin-6 on the therapeutic effect of gefitinib in patients with advanced non-small cell lung cancer harbouring EGFR mutations 査読

    Tomoki Tamura, Yuka Kato, Kadoaki Ohashi, Kiichiro Ninomiya, Go Makimoto, Hiroko Gotoda, Toshio Kubo, Eiki Ichihara, Takehiro Tanaka, Koichi Ichimura, Yoshinobu Maeda, Katsuyuki Hotta, Katsuyuki Kiura

    Biochemical and Biophysical Research Communications   495 ( 1 )   360 - 367   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier B.V.  

    Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a key therapy used for patients with EGFR-mutant non-small cell lung cancer (NSCLC), some of whom do not respond well to its therapy. Cytokine including IL-6 secreted by tumour cells is postulated as a potential mechanism for the primary resistance or low sensitivity to EGFR-TKIs. Fifty-two patients with advanced EGFR-mutant NSCLC who had received gefitinib were assessed retrospectively. The protein expression of IL-6 in the tumour cells was assessed by immunostaining and judged as positive if ≥ 50 of 100 tumour cells stained positively. Of the 52 patients, 24 (46%) and 28 (54%) were defined as IL-6-postitive (group P) and IL-6-negative (group N), respectively. Group P had worse progression-free survival (PFS) than that of group N, which was retained in the multivariate analysis (hazard ratio: 2.39
    95 %CI: 1.00–5.68
    p &lt
    0.05). By contrast, the PFS after platinum-based chemotherapy did not differ between groups P and N (p = 0.47). In cell line-based model, the impact of IL-6 on the effect of EGFR-TKIs was assessed. The combination of EGFR-TKI and anti-IL-6 antibody moderately improved the sensitivity of EGFR-TKI in lung cancer cell with EGFR mutation. Interestingly, suppression of EGFR with EGFR-TKI accelerated the activation of STAT3 induced by IL-6. Taken together, tumour IL-6 levels might indicate a subpopulation of EGFR-mutant NSCLC that benefits less from gefitinib monotherapy.

    DOI: 10.1016/j.bbrc.2017.10.175

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  • A phase I trial of afatinib and bevacizumab in chemo-naïve patients with advanced non-small-cell lung cancer harboring EGFR mutations: Okayama Lung Cancer Study Group Trial 1404. 査読

    Ninomiya T, Nogami N, Kozuki T, Harada D, Kubo T, Ohashi K, Kuyama S, Kudo K, Bessho A, Fukamatsu N, Fujimoto N, Aoe K, Shibayama T, Sugimoto K, Takigawa N, Hotta K, Kiura K

    Lung cancer (Amsterdam, Netherlands)   115   103 - 108   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.lungcan.2017.11.025

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  • Effects of (-)-epigallocatechin-3-gallate on EGFR- or Fusion Gene-driven Lung Cancer Cells 査読

    Yoshihiro Honda, Nagio Takigawa, Eiki Ichihara, Takashi Ninomiya, Toshio Kubo, Nobuaki Ochi, Masayuki Yasugi, Toshi Murakami, Hiromichi Yamane, Mitsune Tanimoto, Katsuyuki Kiura

    ACTA MEDICA OKAYAMA   71 ( 6 )   505 - 512   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    (-)-Epigallocatechin-3-gallate (EGCG) has been shown to bind to several receptors including epidermal growth factor receptor (EGFR). EGFR tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK) inhibitors are effective for non-small cell lung cancers harboring activating EGFR mutations and ALK or c-ros oncogene 1 (ROS1) fusion genes, respectively. We investigated the effects of EGCG on EGFR-or fusion gene-driven lung cancer cells such as PC-9, RPC-9, H1975, H2228 and HCC78. The five cell lines had similar sensitivity to EGCG. Phosphorylated (p) EGFR, pAkt and pErk in PC-9, RPC-9 and H1975 cells were suppressed by EGCG (50 or 100 mu M). EGCG also inhibited pALK in H2228, pROS1 in HCC78, and pErk and pAkt in both cell lines. All the xenograft tumors established using the 5 cell lines in EGCG-treated groups were significantly smaller than the tumors in the vehicle-treated groups. The numbers of tumor blood vessels of xenograft tissues in EGCG-treated mice were significantly lower than those in vehicle-treated mice. In conclusion, EGCG may be effective for EGFR-driven lung tumors irrespective of the presence of T790M, and for ALK or ROS1 fusion gene-driven lung tumors.

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  • 肺多形癌に対して免疫チェックポイント阻害薬が奏効した1例

    安原 かおり, 妹尾 賢, 二宮 崇, 久保 寿夫, 大橋 圭明, 市原 英基, 堀田 勝幸, 田端 雅弘, 木浦 勝行

    肺癌   57 ( 7 )   902 - 903   2017年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • EGFR G719A遺伝子変異を有する肺腺癌に対してニボルマブが奏効した1例

    高瀬 了輔, 板野 純子, 西井 和也, 二宮 崇, 市原 英基, 大橋 圭明, 堀田 勝幸, 木浦 勝行, 久保 寿夫, 田端 雅弘

    肺癌   57 ( 7 )   903 - 903   2017年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • A phase II trial of carboplatin plus S-1 for elderly patients with advanced non-small-cell lung cancer with wild-type epidermal growth factor receptor: The Okayama Lung Cancer Study Group Trial 1202 査読

    Shoichi Kuyama, Nobuaki Ochi, Akihiro Bessho, Katsuyuki Hotta, Genyo Ikeda, Daizo Kishino, Toshio Kubo, Daijiro Harada, Nobukazu Fujimoto, Masamoto Nakanishi, Takahiro Umeno, Toshiaki Okada, Kenichi Chikamori, Tomoko Yamagishi, Kadoaki Ohashi, Eiki Ichihara, Nagio Takigawa, Mitsune Tanimoto, Katsuyuki Kiura

    LUNG CANCER   112   188 - 194   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Introduction: S-1 is an oral fluoropyrimidine-based combination of tegafur, gimeracil, and oteracil potassium. Although the combination of S-1 with carboplatin is a first-line chemotherapy regimen for advanced non-small cell lung cancer (NSCLC), the efficacy and safety of the regimen in the elderly remain unknown.
    Methods: The patient inclusion criteria were previously untreated advanced NSCLC, wild-type epidermal growth factor receptor, aged 70 years or more, and a performance status (PS) of 0-2. The patients received oral S-1 (40 mg/m(2), twice daily) for 2 weeks and carboplatin (area under the curve: 5) on day 1 every 4 weeks as induction treatment. After four induction cycles, S-1 alone (40 mg/m(2), twice daily) was administered for 2 weeks every 4 weeks as a maintenance therapy until disease progression. The primary endpoint was the overall response rate (ORR), which was expected to exceed 20%, and the secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the toxicity profile. The associations between clinical outcomes and expression of genes such as thymidylate synthase and thymidine phosphorylase in the tumors were evaluated.
    Results: Thirty-three patients were enrolled between March 2013 and June 2015. The median age was 78 (range 70-89) years, and 51.5% had a PS of 0. The ORR was 30.3% (95% confidence interval (CI): 14.6-46.0) and the DCR 57.6% (95% CI: 40.7-74.4). Grade 3/4 toxicities included thrombocytopenia (42.4%), neutropenia (33.3%), and anemia (27.3%). There was one treatment-related death due to aspiration pneumonia following febrile neutropenia. The median PFS and OS were 134 days (95% CI: 79-173) and 479 days (95% CI: 250-571), respectively. Low thymidine phosphorylase expression was associated with the DCR (P &lt; 0.01).
    Conclusion: This study met the predesigned primary endpoint, and the regimen seems to be a favorable treatment option.

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  • EBUS-TBNA後の発熱および穿刺針洗浄培養における挿管チューブの有用性

    南 大輔, 瀧川 奈義夫, 沖 昌英, 坂 英雄, 二宮 崇, 久保 寿夫, 市原 英基, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 柴山 卓夫, 田端 雅弘, 木浦 勝行

    肺癌   57 ( 5 )   453 - 453   2017年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • T790M遺伝子変異検索における再・再生検の意義

    市原 英基, 堀田 勝幸, 二宮 崇, 久保 寿夫, 東恩納 司, 大橋 圭明, 佐藤 晃子, 田端 雅弘, 木浦 勝行

    肺癌   57 ( 5 )   420 - 420   2017年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Interstitial lung abnormalitiesを有する局所進行肺癌に対する放射線化学療法の検討

    肥後 寿夫, 久保 寿夫, 槇本 怜子, 井原 弘貴, 正岡 佳久, 二宮 崇, 市原 英基, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 田端 雅弘, 瀧川 奈義夫, 木浦 勝行

    肺癌   57 ( 5 )   499 - 499   2017年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list. 査読 国際誌

    Hisao Higo, Takeshi Kurosaki, Eiki Ichihara, Toshio Kubo, Kentaroh Miyoshi, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Nobuaki Miyahara, Katsuyuki Kiura, Shinichiro Miyoshi, Takahiro Oto

    Respiratory investigation   55 ( 4 )   264 - 269   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. METHODS: We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. RESULTS: Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. CONCLUSIONS: Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list.

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  • Triplet therapy with afatinib, cetuximab, and bevacizumab induces deep remission in lung cancer cells harboring EGFR T790M in vivo 査読

    Kenichiro Kudo, Kadoaki Ohashi, Go Makimoto, Hisao Higo, Yuka Kato, Hiroe Kayatani, Yasuko Kurata, Yoichiro Takami, Daisuke Minami, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Akiko Sato, Katsuyuki Hotta, Tadashi Yoshino, Mitsune Tanimoto, Katsuyuki Kiura

    MOLECULAR ONCOLOGY   11 ( 6 )   670 - 681   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment strategy for EGFR-mutant lung cancers; however, resistance usually occurs due to a secondary mutation, T790M, in EGFR. Combination therapy using afatinib and cetuximab has had good results in lung tumors harboring EGFR(T790M) mutations in clinical trials. The effect of bevacizumab, an antivascular endothelial growth factor (VEGF) antibody, combined with EGFR-TKIs has also been investigated. We hypothesized that the dose of afatinib and cetuximab could be reduced by combination with bevacizumab and that the triplet therapy may result in better tumor inhibition with tolerable toxicity. Using a xenograft mouse model with H1975-harboring EGFR(L858R) (+) (T790M) and RPC-9-harboring EGFR(19DEL+ T790M), we tested the efficacy of the triplet therapy with a modified dose of afatinib, cetuximab, and bevacizumab, and compared this therapy to single and double therapies. Triplet therapy with afatinib, cetuximab, and bevacizumab induced pathological complete remission in xenograft tumors with H1975 and RPC-9 cells versus tumors treated with single or double therapies. We saw no body weight loss in the mice. The triple therapy induced a significant reduction in CD31-positive vascular endothelial cells and increased cleaved caspase-3-positive cells in the tumors. This suggests that one mechanism underlying the deep remission could be suppression of neovascularization and induction of apoptosis by intensive inhibition of driver oncoproteins and VEGF. These results highlight the potential of afatinib, cetuximab, and bevacizumab to induce deep remission in tumors harboring EGFR T790M mutations. Therefore, clinical trials of this combination therapy are warranted.

    DOI: 10.1002/1878-0261.12063

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  • Erratum to "Frequent methylation and oncogenic role of microRNA-34b/c in small-cell lung cancer" [Lung Cancer 76 (1) (2012) 32-38]. 査読

    Tanaka N, Toyooka S, Soh J, Kubo T, Yamamoto H, Maki Y, Muraoka T, Shien K, Furukawa M, Ueno T, Asano H, Tsukuda K, Aoe K, Miyoshi S

    Lung cancer (Amsterdam, Netherlands)   108   254 - 255   2017年6月

  • Discomfort during bronchoscopy performed after endobronchial intubation with fentanyl and midazolam: a prospective study 査読

    Daisuke Minami, Nagio Takigawa, Hirohisa Kano, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Kadoaki Ohashi, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   47 ( 5 )   434 - 437   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Endobronchial intubation with fentanyl and midazolam might be recommended for an invasive bronchoscopic procedure.Although endobronchial intubation during a bronchoscopic examination is useful for invasive procedures, it is not routine practice in Japan. The present study evaluated discomfort due to endobronchial intubation using fentanyl and midazolam sedation during bronchoscopy.
    Thirty-nine patients were enrolled prospectively from November 2014 to September 2015 at Okayama University Hospital. Fentanyl (20 A mu g) was administered to the patients just before endobronchial intubation, and fentanyl (10 A mu g) and midazolam (1 mg) were added as needed during the procedure. A questionnaire survey was administered 2 h after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: excellent (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question ('Do you remember the bronchoscopic examination?') was also asked. Predefined parameters (blood pressure, heart rate, oxygen saturation and complications) were recorded.
    The enrolled patients included 22 males and 17 females; their median age was 70 (range: 28-88) years. The patients received a mean dose of 47.9 A mu g of fentanyl (range: 30-90 A mu g) and 2.79 mg of midazolam (range: 1-7 mg). In total, 28 patients (71.7%) agreed to undergo a second bronchoscopic examination; the mean levels of discomfort and for the re-examination were 2.07 points each. About 41% of the patients remembered the bronchoscopic examination. No severe complications were reported.
    Endobronchial intubation using fentanyl and midazolam sedation during an invasive bronchoscopic procedure might be recommended.
    UMIN000015578 in the UMIN Clinical Trials Registry.

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  • Optimal method for quantitative detection of plasma EGFR T790M mutation using droplet digital PCR system 査読

    Ken Suzawa, Hiromasa Yamamoto, Kadoaki Ohashi, Shinsuke Hashida, Shuta Tomida, Toshio Kubo, Yuho Maki, Junichi Soh, Kazunori Tsukuda, Katsuyuki Kiura, Shinichiro Miyoshi, Shinichi Toyooka

    ONCOLOGY REPORTS   37 ( 5 )   3100 - 3106   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Though patients with EGFR mutations are initially responsive to EGFR-tyrosine kinase inhibitors (TKIs), most tumors ultimately acquire resistance to EGFR-TKIs. The most frequently reported mechanism is EGFR T790M mutation. In this study, using a droplet digital PCR (ddPCR) system, we assessed optimal conditions for a mutation detection assay for EGFR T790M obtained from circulating cell-free DNA (cfDNA) in plasma. The advantages of locked nucleic acids (LNA) probe, short amplicon size, and blocking oligo using peptide nucleic acids (PNA) were assessed using control DNAs from cell lines to improve the sensitivity of mutation detection. T790M alleles were then analyzed using ddPCR in 59 plasma samples from 24 NSCLC patients with EGFR mutations, and compared to the T790M status which were determined thorough re-biopsies. The assessment of the optimal assay method revealed that the assay using the short amplicon can efficiently detect more fragmented-DNA. The LNA probe and PNA clamp contributed better separation between positive and negative droplets. This PNA-LNA-ddPCR clamp method can detect mutant alleles in the sample with a mutant allele content of 0.01%. In clinical plasma samples, T790M alleles were detected via ddPCR with a sensitivity of 42.8% and specificity of 97.3%. We established a highly-sensitive detection assay for the T790M allele using the PNA-LNA-ddPCR clamp method. ddPCR is a promising method for detecting non-invasive T790M mutation.

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  • フェンタニル、ミダゾラムによる鎮静下に行った気管支鏡検査の苦痛度評価試験

    南 大輔, 瀧川 奈義夫, 渡邉 洋美, 二宮 崇, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 田端 雅弘, 谷本 光音, 木浦 勝行

    気管支学   39 ( Suppl. )   S200 - S200   2017年5月

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  • Phase II Study of the EGFR-TKI Rechallenge With Afatinib in Patients With Advanced NSCLC Harboring Sensitive EGFR Mutation Without T790M: Okayama Lung Cancer Study Group Trial OLCSG 1403 査読

    Naohiro Oda, Eiki Ichihara, Katsuyuki Hotta, Kiichiro Ninomiya, Takashi Ninomiya, Toshio Kubo, Daisuke Minami, Toshi Murakami, Toshihide Yokoyama, Daijiro Harada, Shoichi Kuyama, Hirohisa Ichikawa, Koji Inoue, Daizo Kishino, Masaaki Inoue, Nagio Takigawa, Takuo Shibayama, Shingo Harita, Mitsune Tanimoto, Katsuyuki Kiura

    CLINICAL LUNG CANCER   18 ( 2 )   241 - 244   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CIG MEDIA GROUP, LP  

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first-line therapy for patients with EGFR-mutated nonesmall-cell lung cancer (NSCLC) have shown a significantly better objective response rate and progression-free survival than platinum doublet therapy. However, acquired resistance often occurs within 12 months. One of the potential strategies for treating acquired resistance in NSCLC is the readministration of EGFR-TKIs, a strategy that has mainly been evaluated using gefitinib or erlotinib. The aim of the present study is to investigate the efficacy and safety of EGFR-TKI readministration with afatinib in patients with advanced NSCLC harboring activating EGFR mutations without T790M. The primary endpoint is progression-free survival. The secondary endpoints include the objective response rate, disease control rate, overall survival, toxicity, and quality of life. A total of 12 patients will be enrolled in this trial. (C) 2016 Elsevier Inc. All rights reserved.

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  • Three-Arm Randomized Trial of Sodium Alginate for Preventing Radiation-Induced Esophagitis in Locally Advanced NoneSmall Cell Lung Cancer Receiving Concurrent Chemoradiotherapy: The OLCSG1401 Study Protocol 査読

    Kiichiro Ninomiya, Eiki Ichihara, Katsuyuki Hotta, Naoyuki Sone, Toshi Murakami, Daijiro Harada, Isao Oze, Toshio Kubo, Hisaaki Tanaka, Shoichi Kuyama, Daizo Kishino, Akihiro Bessho, Shingo Harita, Kuniaki Katsui, Mitsune Tanimoto, Katsuyuki Kiura

    CLINICAL LUNG CANCER   18 ( 2 )   245 - 249   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CIG MEDIA GROUP, LP  

    Concurrent chemoradiotherapy (CRT) is the standard of care for locally advanced nonesmall cell lung cancer (LA-NSCLC). However, this intensive therapy often causes severe esophagitis, which could deteriorate a patient's quality of life (QOL), leading to poor treatment compliance. Sodium alginate, approved in Japan for gastritis, is sufficiently highly viscous to remain in the esophageal mucosa, providing a protective effect in the esophagus. To investigate whether this compound has a preventive effect against severe esophagitis in patients receiving concurrent CRT, we plan a 3-arm randomized trial of sodium alginate with 2 different schedules versus water. The primary endpoint is set as the proportion of patients with grade &gt;= 3 esophagitis using the Common Terminology Criteria for Adverse Events, version 4.0. With stratification by institute, performance status, and percentage of the esophageal volume receiving &gt; 35 Gy, the patients will be randomly assigned to 1 of the following groups: sodium alginate initiated concomitantly with CRT (group A), sodium alginate initiated soon after the development of extremely mild esophagitis during CRT (group B), or water administered throughout CRT (group C). Assuming that the proportion of grade &gt;= 3 esophagitis would be 8% in groups A and B and 27% in group C, the required sample size would be 200 patients, with 70% power and 5% a. The secondary endpoints include QOL, the frequency of additional prescriptions of analgesics, treatment response, and survival. The results of the present study will clarify whether sodium alginate can prevent esophagitis in patients with LA-NSCLC undergoing CRT. (C) 2016 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.cllc.2016.08.001

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  • 腫瘍 疫学・基礎 EGFR変異を有する肺癌細胞株における第三世代EGFR-TKI耐性機序の検討

    二宮 貴一朗, 大橋 圭明, 槇本 剛, 肥後 寿夫, 萱谷 紘枝, 田村 朋季, 二宮 崇, 久保 寿夫, 市原 英基, 佐藤 晃子, 堀田 勝幸, 谷本 光音, 木浦 勝行

    日本呼吸器学会誌   6 ( 増刊 )   142 - 142   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • 原発性肺癌との鑑別を要した肺結核、結核性リンパ節炎の1例

    吉川 真生, 二宮 崇, 秦 雄介, 狩野 裕久, 妹尾 賢, 西井 和也, 渡邉 洋美, 久保 寿夫, 大橋 圭明, 市原 英基, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 田端 雅弘, 金廣 有彦, 木浦 勝行

    結核   92 ( 3 )   405 - 405   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本結核・非結核性抗酸菌症学会  

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  • 間質性肺疾患による脳死肺移植登録患者の臨床像と待機期間中早期死亡リスク因子の検討

    肥後 寿夫, 市原 英基, 黒崎 毅史, 久保 寿夫, 大橋 圭明, 勝田 知也, 洲脇 俊充, 宮原 信明, 三好 新一郎, 大藤 剛宏, 木浦 勝行

    日本呼吸器学会誌   6 ( 増刊 )   248 - 248   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • 進行膵癌に対するゲムシタビン+ナブパクリタキセル併用療法における薬剤性肺障害の検討

    久保 寿夫, 狩野 裕久, 妹尾 賢, 西井 和也, 秦 雄介, 渡邉 洋美, 二宮 崇, 市原 英基, 大橋 圭明, 佐藤 晃子, 加藤 博也, 堀田 勝幸, 宮原 信明, 田端 雅弘, 金廣 有彦, 木浦 勝行

    日本呼吸器学会誌   6 ( 増刊 )   183 - 183   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • 野生型EGFR遺伝子を有する高齢者未治療進行非小細胞肺癌に対するカルボプラチンとS-1併用療法の第2相試験(OLCSG1202)

    西井 和也, 二宮 貴一朗, 久保 寿夫, 久山 彰一, 別所 昭宏, 越智 宣敬, 堀田 勝幸, 瀧川 奈義夫, 谷本 光音, 木浦 勝行

    日本内科学会雑誌   106 ( Suppl. )   257 - 257   2017年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • Triplet therapy with afatinib, cetuximab, and bevacizumab induces deep remission in lung cancer cells harboring EGFR T790M in vivo. 査読

    Kudo K, Ohashi K, Makimoto G, Higo H, Kato Y, Kayatani H, Kurata Y, Takami Y, Minami D, Ninomiya T, Kubo T, Ichihara E, Sato A, Hotta K, Yoshino T, Tanimoto M, Kiura K

    Molecular oncology   11 ( 6 )   670 - 681   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/1878-0261.12063

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  • オシメルチニブ投与中に発症したうっ血性心不全の1例

    松尾 逸平, 渡邉 洋美, 市原 英基, 狩野 裕久, 妹尾 賢, 西井 和也, 秦 雄介, 二宮 崇, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   56 ( 7 )   1088 - 1088   2016年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 肺多形癌に対してnivolumabを投与中にニューモシスチス肺炎を発症した1例

    小柳 太作, 堀田 勝幸, 妹尾 賢, 狩野 裕久, 西井 和也, 秦 雄介, 渡邉 洋美, 二宮 崇, 大橋 圭明, 市原 英基, 佐藤 晃子, 木浦 勝行, 久保 寿夫, 田端 雅弘, 谷本 光音

    肺癌   56 ( 7 )   1087 - 1088   2016年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Potential influence of being overweight on the development of hepatic dysfunction in Japanese patients with EGFR-mutated non-small cell lung cancer undergoing gefitinib monotherapy: the Okayama Lung Cancer Study Group experience 査読

    Naohiro Oda, Katsuyuki Hotta, Hiroshige Yoshioka, Kenichiro Kudo, Eiki Ichihara, Yuka Kato, Kiichiro Ninomiya, Daisuke Minami, Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Akiko Sato, Nagio Takigawa, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

    CANCER CHEMOTHERAPY AND PHARMACOLOGY   78 ( 5 )   941 - 947   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Being overweight has been reported to induce hepatic dysfunction during cytotoxic chemotherapy. Severe hepatic dysfunction can also be observed during gefitinib monotherapy, leading to interrupted or discontinued treatment. However, whether being overweight is a risk factor during gefitinib therapy is unknown.
    We retrospectively reviewed 183 Japanese patients with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor-na &lt; ve non-small cell lung cancer (NSCLC) harboring EGFR mutations, who received gefitinib monotherapy between July 2007 and February 2014. We defined being overweight as having a body mass index (BMI) aeyen 25 kg/m(2) and assessed its potential relationship with aeyengrade 2 hepatic dysfunction.
    The patient demographics were as follows: 114 women; median age 72 years (range 42-95 years); BMI aeyen 25 kg/m(2), n = 32; performance status 0-1, n = 136; stage IIIB/IV, n = 141; and major EGFR mutations, n = 171. Hepatic dysfunction aeyengrade 2 during the gefitinib therapy was observed in 44 (24.0 %) patients, 22 (50.0 %) of whom interrupted or discontinued treatment. The median duration from gefitinib administration to the development of hepatic dysfunction was 56 days (range 6-1,352 days). Overweight patients were more likely to develop hepatic dysfunction aeyengrade 2 compared to non-overweight patients according to a multivariate analysis adjusted for several confounding factors (hazard ratio 2.24; 95 % confidence interval 1.01-4.95; p = 0.046).
    These results suggest that being overweight may induce hepatic dysfunction during gefitinib monotherapy in Japanese patients with EGFR-mutated NSCLC.

    DOI: 10.1007/s00280-016-3146-z

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  • Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non-Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405) 査読

    Hideko Isozaki, Katsuyuki Hotta, Eiki Ichihara, Nagio Takigawa, Kadoaki Ohashi, Toshio Kubo, Takashi Ninomiya, Kiichiro Ninomiya, Naohiro Oda, Hiroshige Yoshioka, Hirohisa Ichikawa, Masaaki Inoue, Ichiro Takata, Takuo Shibayama, Shoichi Kuyama, Keisuke Sugimoto, Daijiro Harada, Shingo Harita, Toshiaki Sendo, Mitsune Tanimoto, Katsuyuki Kiura

    CLINICAL LUNG CANCER   17 ( 6 )   602 - 605   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CIG MEDIA GROUP, LP  

    Based on our preclinical study results, which showed that the activation of the hepatocyte growth factor/MET pathway is a potential mechanism of acquired resistance to alectinib, we launched the ALRIGHT (OLCSG1405 [alectinib-refractory nonesmall-cell lung cancer patients harboring the EML4-ALK fusion gene]), a phase II trial of the anaplastic lymphoma kinase (ALK)/MET inhibitor crizotinib in patients with nonesmall-cell lung cancer refractory to alectinib and harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene. Patients with ALK-rearranged tumors who have developed disease progression during alectinib treatment will receive crizotinib monotherapy until disease progression or the occurrence of unacceptable toxicity. The primary endpoint is set as the objective response rate, assuming that a response in 50% of eligible patients will indicate potential usefulness and that 15% would be the lower limit of interest (1-sided a of 0.05, b of 0.20). The estimated accrual number of patients is 9. The secondary endpoints include progression-free survival, overall survival, adverse events, and patient-reported outcomes. We will also take tissue samples before crizotinib monotherapy to conduct an exploratory analysis of ALK and hepatocyte growth factor/MET expression levels and gene alterations (eg, mutations, amplifications, and translocations). We will obtain information regarding whether crizotinib, which targets not only ALK, but also MET, can truly produce efficacy with acceptable safety profiles in ALK(+) non-small-cell lung cancer even in the alectinibrefractory setting. (C) 2016 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.cllc.2016.05.005

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  • 肺多形癌に対してnivolumabを投与し、抗腫瘍効果が得られた1例

    妹尾 賢, 狩野 裕久, 西井 和也, 秦 雄介, 渡邉 洋美, 二宮 崇, 久保 寿夫, 大橋 圭明, 市原 英基, 佐藤 晃子, 堀田 勝幸, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   56 ( 6 )   859 - 859   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 挿管チューブを使用したEBUS-TBNA後の発熱および穿刺針洗浄培養の後方視的検討

    南 大輔, 瀧川 奈義夫, 二宮 崇, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 柴山 卓夫, 宮原 信明, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   56 ( 6 )   511 - 511   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 脳転移を有する非小細胞肺がんに対するニボルマブの使用経験

    渡邉 洋美, 久保 寿夫, 狩野 裕久, 妹尾 賢, 西井 和也, 秦 雄介, 二宮 崇, 市原 英基, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   56 ( 6 )   800 - 800   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 非小細胞肺癌に対するre-biopsy 気管支鏡検査とCTガイド下生検との比較

    狩野 裕久, 久保 寿夫, 妹尾 賢, 西井 和也, 秦 雄介, 渡邉 洋美, 二宮 崇, 市原 英基, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   56 ( 6 )   512 - 512   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • A phase II study of topotecan and cisplatin with sequential thoracic radiotherapy in elderly patients with small-cell lung cancer: Okayama Lung Cancer Study Group 0102 査読

    Toshio Kubo, Keiichi Fujiwara, Katsuyuki Hotta, Toshiaki Okada, Shoichi Kuyama, Shingo Harita, Takashi Ninomiya, Haruhito Kamei, Shinobu Hosokawa, Akihiro Bessho, Tadashi Maeda, Toshiyuki Kozuki, Nobukazu Fujimoto, Kiichiro Ninomiya, Mitsuhiro Takemoto, Susumu Kanazawa, Nagio Takigawa, Masahiro Tabata, Mitsune Tanimoto, Hiroshi Ueoka, Katsuyuki Kiura

    CANCER CHEMOTHERAPY AND PHARMACOLOGY   78 ( 4 )   769 - 774   2016年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Purpose The treatment outcome in elderly patients with limited-disease small-cell lung cancer (LD-SCLC) remains poor. We carried out a phase II trial of split topotecan and cisplatin (TP) therapy and sequential thoracic radiotherapy for elderly LD-SCLC patients as a follow-up to our previous phase I trial.
    Methods In total, 30 patients aged 76 years or older, with untreated LD-SCLC were enrolled. Four courses of topotecan (1.0 mg/m(2), days 1-3) and cisplatin (20 mg/m(2), days 1-3) were administered, followed by thoracic radiotherapy (1.8 Gy/day, total of 45 Gy). The primary end point was the overall response rate (ORR).
    Results The trial was terminated early with 22 patients because of slow accrual. Their median age was 79 years. The median number of courses of chemotherapy administered was three, and the actual completion rate of the entire treatment course was 41 %. The ORR was 68 % with a 95 % confidence interval of 47-89 % (15/22 cases). The median progression-free survival and overall survival were 9.1 and 22.2 months, respectively. The main toxicity was myelosuppression, with grades 3-4 neutropenia (96 %), thrombocytopenia (50 %), and febrile neutropenia (32 %).
    Conclusions This regimen produced a favorable survival outcome, despite moderate-to-severe toxicity profiles. Further efforts are necessary to define an optimal regimen for elderly patients with limited SCLC.

    DOI: 10.1007/s00280-016-3135-2

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  • Common variable immunodeficiency患者に発症したEBウイルス関連多発平滑筋腫瘍の1例

    妹尾 賢, 田端 雅弘, 狩野 裕久, 西井 和也, 秦 雄介, 渡邉 洋美, 二宮 崇, 久保 寿夫, 大橋 圭明, 市原 英基, 佐藤 晃子, 堀田 勝幸, 木浦 勝行, 谷本 光音

    日本癌治療学会学術集会抄録集   54回   P62 - 10   2016年10月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • 肺 肺がんのトランスレーショナル・リサーチ EGFR遺伝子変異陽性NSCLCに対するGefitinib治療中の肝障害発現における過体重の影響

    小田 尚廣, 堀田 勝幸, 吉岡 弘鎮, 工藤 健一郎, 市原 英基, 加藤 有加, 二宮 貴一朗, 二宮 崇, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 瀧川 奈義夫, 田端 雅弘, 谷本 光音, 木浦 勝行

    日本癌治療学会学術集会抄録集   54回   WS59 - 2   2016年10月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • Safety and discomfort during bronchoscopy performed under sedation with fentanyl and midazolam: a prospective study 査読

    Daisuke Minami, Nagio Takigawa, Hiromi Watanabe, Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   46 ( 9 )   871 - 874   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Objective: Although sedation with fentanyl and midazolam during bronchoscopic examination is widely accepted in the USA and Europe, it is not routine practice in Japan. The objective of the present study was to evaluate sedation with fentanyl and midazolam during bronchoscopy.
    Methods: Thirty-seven patients were enrolled prospectively between November 2014 and July 2015 at Okayama University Hospital. Fentanyl (20 mu g) was administered to the patients just before the examination, and fentanyl (10 mu g) and midazolam (1mg) were added as needed during the procedure. A questionnaire was administered 2 hours after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: great (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question ('Do you remember the bronchoscopic examination?') was also used. Predefined matters for investigation (e.g. blood pressure, heart rate, oxygen saturation and complications) were recorded.
    Results: The enrolled patients included 13 males and 24 females; the median age was 67 (range: 31-87) years. The patients received a median dose of fentanyl of 45.4 mu g (range: 30-100 mu g) and midazolam of 2.56 mg (range: 1-10 mg). Twenty-six patients (70.2%) agreed to undergo a second bronchoscopic examination, and the average levels of discomfort and re-examination were 2.02 points for each. Only 37.8% of the patients remembered the bronchoscopic examination. No severe complications were reported.
    Conclusions: Sedation with fentanyl and midazolam during bronchoscopic examination should be recommended for use in Japan.

    DOI: 10.1093/jjco/hyw083

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  • Effect of Vandetanib on Lung Tumorigenesis in Transgenic Mice Carrying an Activating Egfr Gene Mutation 査読

    Masahiro Osawa, Kadoaki Ohashi, Toshio Kubo, Eiki Ichihara, Saburo Takata, Nagio Takigawa, Minoru Takata, Mitsune Tanimoto, Katsuyuki Kiura

    ACTA MEDICA OKAYAMA   70 ( 4 )   243 - 253   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Vandetanib (Zactima (TM)) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p&lt;0.01); resistance to vandetanib occurred at 20 weeks of age and the animals died from their lung tumors at about 28 weeks of age. These data suggest that vandetanib could suppress the progression of tumors harboring an activating EGFR mutation.

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  • 右肺門部腫瘤影の一例

    秦 雄介, 二宮 崇, 渡邉 洋美, 狩野 裕久, 西井 和也, 妹尾 賢, 加藤 有加, 谷口 暁彦, 南 大輔, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 宮原 信明, 田端 雅弘, 金廣 有彦, 谷本 光音, 木浦 勝行

    岡山医学会雑誌   128 ( 2 )   155 - 156   2016年8月

  • Activating alternative receptor tyrosine kinases induced alectinib-resistance in ALK rearranged non-small cell lung cancer cells 査読

    Isozaki Hideko, Ichihara Eiki, Yasugi Masayuki, Takigawa Nagio, Ohashi Kadoaki, Kubo Toshio, Ninomiya Takashi, Ochi Nobuaki, Minami Daisuke, Kudo Kenichiro, Kato Yuka, Kayatani Hiroe, Tamura Tomoki, Ninonniya Kiichiro, Higo Toshio, Makimoto Tsuyoshi, Sato Akiko, Hotta Katsuyuki, Matsumoto Kunio, Sendo Toshiaki, Tanimoto Mitsune, Kiura Katsuyuki

    CANCER RESEARCH   76   2016年7月

  • Endobronchial ultrasound-guided transbronchial needle aspiration of hilar and mediastinal lymph nodes detected on F-18-fluorodeoxyglucose positron emission tomography/computed tomography 査読

    Daisuke Minami, Nagio Takigawa, Naohiro Oda, Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Mitsumasa Kaji, Mitsune Tanimoto, Katsuyuki Kiura

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   46 ( 6 )   529 - 533   2016年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Endobronchial ultrasound-guided transbronchial needle aspiration is of diagnostic value in hilar/mediastinal (N1/N2) lymph node staging. We assessed the utility of endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients with N1/N2 lymph nodes detected on F-18-fluorodeoxyglucose positron emission tomography/computed tomography.
    Fifty lung cancer patients with N1/N2 disease on F-18-fluorodeoxyglucose positron emission tomography/computed tomography underwent endobronchial ultrasound-guided transbronchial needle aspiration for pathological lymph nodes between November 2012 and April 2015. The diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration, lymph node site and size, number of needle passes and complications were evaluated retrospectively from patients' medical records. Malignancy was defined as a maximum standardized uptake value (SUVmax) &gt; 2.5.
    The median longest diameter of the 61 lymph nodes (29 subcarinal, 21 right lower paratracheal, 6 left lower paratracheal, 4 right hilar and 1 upper paratracheal) was 23.4 mm (range: 10.4-45.7); the median number of needle passes was 2 (range: 1-5). There were no severe complications. A definitive diagnosis was made by endobronchial ultrasound-guided transbronchial needle aspiration in 39 patients (31 adenocarcinomas, 3 small-cell carcinomas, 2 squamous-cell carcinomas, 3 large-cell neuroendocrine carcinomas). In the remaining 11 patients, the diagnosis was indefinite: insufficient endobronchial ultrasound-guided transbronchial needle aspiration material was collected in two patients and non-specific lymphadenopathy was confirmed by endobronchial ultrasound-guided transbronchial needle aspiration or thoracotomy in the other nine patients. The mean lymph node SUVmax was 7.09 (range: 2.90-26.9) and was significantly higher in true-positive than in false-positive nodes (P &lt; 0.05, t-test). Non-specific lymphadenopathy was diagnosed by expert visual interpretation of F-18-fluorodeoxyglucose positron emission tomography/computed tomography images in five of the nine patients.
    Endobronchial ultrasound-guided transbronchial needle aspiration accurately diagnoses N1/N2 disease detected on F-18-fluorodeoxyglucose positron emission tomography/computed tomography.

    DOI: 10.1093/jjco/hyw023

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  • 肺クリプトコッカス症診断における迅速細胞診を用いた気管支鏡検査の有用性

    森近 大介, 南 大輔, 宮原 信明, 谷口 暁彦, 二宮 崇, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 金廣 有彦, 谷本 光音, 木浦 勝行

    気管支学   38 ( Suppl. )   S222 - S222   2016年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • RebiopsyにおいてEBUS-TBNAが有用であった3症例

    狩野 裕久, 南 大輔, 妹尾 賢, 西井 和也, 秦 雄介, 渡邉 洋美, 加藤 有加, 谷口 暁彦, 二宮 崇, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 宮原 信明, 田端 雅弘, 金廣 有彦, 谷本 光音, 木浦 勝行

    気管支学   38 ( Suppl. )   S263 - S263   2016年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • 呼吸器内視鏡の新技術 BIOEVALUATORを用いた迅速細胞診断を併用したEBUS-TBNAの組織診断

    南 大輔, 瀧川 奈義夫, 二宮 崇, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅彦, 谷本 光音, 木浦 勝行

    気管支学   38 ( Suppl. )   S176 - S176   2016年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • フェンタニルとミダゾラム併用による気管支鏡検査の苦痛度評価

    南 大輔, 瀧川 奈義夫, 二宮 崇, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    気管支学   38 ( Suppl. )   S245 - S245   2016年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • 自己免疫疾患合併肺癌の検討

    狩野 裕久, 久保 寿夫, 秦 雄介, 渡邉 洋美, 加藤 有加, 南 大輔, 二宮 崇, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 谷本 光音, 木浦 勝行

    日本呼吸器学会誌   5 ( 増刊 )   245 - 245   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • ボリュームアナライザーSYNAPSE VINCENTを用いたガイドシース併用気管支腔内超音波断層法の肺癌診断への導入効果

    南 大輔, 瀧川 奈義夫, 槇本 剛, 狩野 裕久, 秦 雄介, 渡邊 洋美, 中西 将元, 二宮 崇, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    気管支学   38 ( 2 )   153 - 153   2016年3月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • PET-CTで縦隔・肺門リンパ節陽性肺癌に対するEBUS-TBNAの有用性

    南 大輔, 瀧川 奈義夫, 槇本 剛, 狩野 裕久, 秦 雄介, 渡邉 洋美, 中西 将元, 加藤 有加, 二宮 崇, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    日本呼吸器学会誌   5 ( 増刊 )   187 - 187   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • Short-term low-volume hydration in cisplatin-based chemotherapy for patients with lung cancer: the second prospective feasibility study in the Okayama Lung Cancer Study Group Trial 1201 査読

    Kiichiro Ninomiya, Katsuyuki Hotta, Akiko Hisamoto-Sato, Eiki Ichihara, Hiroko Gotoda, Daisuke Morichika, Tomoki Tamura, Hiroe Kayatani, Daisuke Minami, Toshio Kubo, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   21 ( 1 )   81 - 87   2016年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    We previously reported the feasibility of short-term low-volume hydration in patients with advanced lung cancer who received cisplatin-based chemotherapy (Jpn J Clin Oncol 2013). We sought to determine the clinical usefulness of a more convenient hydration method, evaluating the safety and efficacy of shorter-term and lower-volume hydration.
    Chemona &lt; ve patients with advanced lung cancer who were a parts per thousand currency sign75 years and reserved an adequate renal function for cisplatin use (a parts per thousand yen60 mg/m(2)) were eligible. An intravenously administered hydration of 1700 ml in 3.5 h with 1500 ml of orally administered hydration was investigated. The primary endpoint was the proportion of patients without grade 2 or worse renal toxicity in the first cycle.
    A total of 45 patients were registered, all of whom were evaluable for renal toxicity. The median baseline creatinine score was 0.70 mg/dl, and the median cisplatin dose on day 1 was 75 mg/m(2). In the first cycle, one patient (2 %) developed grade 2 creatinine toxicity, and thus, the proportion of patients with less than grade 2 was 98 % (the lower limit of 95 % confidence interval; 93 %), which met the primary endpoint. Five patients (11 %) had grade 1 or greater nephrotoxicity, three of whom successfully recovered. The objective response rate was 24 % and median progression-free survival 5.8 months.
    This prospective study demonstrated the safety and efficacy of shorter-term lower-volume hydration.

    DOI: 10.1007/s10147-015-0860-1

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  • 放射線化学療法後に外科手術を行った局所進行非小細胞肺癌症例の長期フォローアップ解析

    槇本 剛, 久保 寿夫, 南 大輔, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 豊岡 伸一, 勝井 邦彰, 谷本 光音, 木浦 勝行

    日本内科学会雑誌   105 ( Suppl. )   192 - 192   2016年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • Efficacy of multimodal treatment for leptomeningeal metastases in a lung cancer harboring an EGFR mutation 査読

    Daisuke Morichika, Toshio Kubo, Hiroko Gotoda, Tomoki Tamura, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Kazuhiko Kurozumi, Mitsune Tanimoto, Katsuyuki Kiura

    ONCOTARGETS AND THERAPY   9   1753 - 1758   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:DOVE MEDICAL PRESS LTD  

    For lung cancer patients with epidermal growth factor receptor (EGFR) mutations, the advent of EGFR tyrosine kinase inhibitors (TKIs) has prolonged survival rates. Even though disease sites have been well controlled by EGFR-TKIs, some patients develop carcinomatous meningitis, which reduces their quality of life drastically. Although multidisciplinary approaches have improved patient survival and quality of life, the outcomes are not yet satisfactory. We report the case of a 54-year-old Japanese woman diagnosed with leptomeningeal metastases (LM) from a lung adenocarcinoma harboring an EGFR exon 21 L858R point mutation. She was treated with gefitinib for 2 months, and symptoms of LM emerged during the treatment period. Although the treatment was switched to erlotinib, disturbance of consciousness worsened because of progressive hydrocephalus. Because all extracranial lesions remained responsive to treatment, and the exon 20 T790M point mutation was not detected in cerebrospinal fluid, we placed a ventriculoperitoneal shunt. The patient's disturbed consciousness improved dramatically after the shunt was placed; however, the optic and auditory nerve impairments due to direct invasion of LM lesions into nerve canals persisted. Administration of bevacizumab subsequent to whole-brain radiotherapy reduced the cranial nerve impairment, and the patient survived for 10 months. In conclusion, a combination of erlotinib and ventriculoperitoneal shunt was effective for hydrocephalus, and the immediate administration of additional therapies, including bevacizumab and radiation therapy, was useful in a patient suffering from LM.

    DOI: 10.2147/OTT.S95721

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  • 肺類上皮血管内皮腫の1例

    田中 晶平, 小田 尚廣, 佐藤 晃子, 宮原 信明, 狩野 裕久, 中西 将元, 秦 雄介, 槇本 剛, 久保 寿夫, 大橋 圭明, 二宮 崇, 堀田 勝幸, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行, 牧 佑歩, 宗 淳一, 豊岡 伸一, 三好 新一郎

    肺癌   55 ( 7 )   1127 - 1127   2015年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • III期肺腺癌に対する化学療法併用根治的外科切除から15年後に発症した放射線誘発軟部肉腫の1例

    中野 靖浩, 豊田 容輔, 大橋 圭明, 小田 尚廣, 槇本 剛, 久保 寿夫, 木浦 勝行, 谷本 光音, 山口 隆廣, 柳井 広之

    肺癌   55 ( 7 )   1128 - 1128   2015年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 薬疹、薬剤性肺炎を治療経過で認めた胸腺癌にnab-paclitaxel単剤療法が有用であった1例

    河合 三津保, 南 大輔, 槇本 剛, 中西 将元, 小田 尚廣, 豊田 容輔, 肥後 寿夫, 二宮 崇, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   55 ( 7 )   1126 - 1126   2015年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Downregulation of TBXAS1 in an iron-induced malignant mesothelioma model 査読

    Daisuke Minami, Nagio Takigawa, Yuka Kato, Kenichiro Kudo, Hideko Isozaki, Shinsuke Hashida, Daijiro Harada, Nobuaki Ochi, Masanori Fujii, Toshio Kubo, Kadoaki Ohashi, Akiko Sato, Takehiro Tanaka, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Mitsune Tanimoto, Katsuyuki Kiura

    CANCER SCIENCE   106 ( 10 )   1296 - 1302   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Malignant mesothelioma is an aggressive and therapy-resistant neoplasm arising from mesothelial cells. Evidence suggests that the major pathology associated with asbestos-induced mesothelioma is local iron overload. In the present study, we induced iron-induced mesothelioma in rats based on previous reports. Ten Wistar rats were given ferric saccharate and nitrilotriacetate i.p. for 5 days a week. Five of the ten rats exhibited widespread mesotheliomas in the peritoneum and tunica vaginalis. The tumor cells showed positive immunostaining for calretinin, wilms tumor-1, podoplanin and the oxidative DNA marker 8-hydroxy-2-deoxyguanosine. In three of the five rats with mesothelioma, array-based comparative genomic hybridization analysis identified a common chromosomal deletion mapped to the chromosomal 4q31 locus, which encompasses the TBXAS1 gene. Downregulation of the TBXAS1 gene was confirmed using quantitative PCR. TBXAS1 gene expression was also reduced in three of four human malignant pleural mesothelioma cell lines compared with normal bronchial epithelial cells. Immunohistochemistry revealed that TBXAS1 expression was weakly positive and positive in five and three out of eight human malignant mesothelioma samples, respectively. In conclusion, TBXAS1 gene expression was downregulated in rats with iron-induced mesothelioma. The relationship between iron overload and TBXAS1 downregulation should be pursued further.

    DOI: 10.1111/cas.12752

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  • EGFR-TKIによるクリゾチニブ耐性ROS1融合遺伝子陽性非小細胞肺癌細胞株の耐性克服

    加藤 有加, 大橋 圭明, 市原 英基, 工藤 健一郎, 磯崎 英子, 南 大輔, 久保 寿夫, 佐藤 晃子, 堀田 勝幸, 田端 雅弘, 瀧川 奈義夫, 谷本 光音, 木浦 勝行

    日本癌学会総会記事   74回   E - 1179   2015年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • 鉄誘発ラット悪性中皮腫モデルにおけるTBXAS1遺伝子発現の抑制

    南 大輔, 瀧川 奈義夫, 加藤 有加, 工藤 健一郎, 磯崎 英子, 二宮 崇, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 豊岡 伸一, 谷本 光音, 木浦 勝行

    日本癌学会総会記事   74回   P - 1040   2015年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • 当院における進行非小細胞肺癌患者に対するrebiopsyの検討

    狩野 裕久, 久保 寿夫, 南 大輔, 中西 将元, 槇本 剛, 秦 雄介, 渡邉 洋美, 加藤 有加, 二宮 崇, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   55 ( 5 )   457 - 457   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 当院呼吸器内科おけるペグフィルグラスチムの使用経験

    渡邉 洋美, 久保 寿夫, 中西 将元, 槇本 剛, 秦 雄介, 狩野 裕久, 加藤 有加, 南 大輔, 二宮 崇, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   55 ( 5 )   711 - 711   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 鉄誘発ラット悪性中皮腫モデルにおけるTBXAS1遺伝子発現の抑制

    南 大輔, 瀧川 奈義夫, 工藤 健一郎, 加藤 有加, 磯崎 英子, 原田 大二郎, 越智 宣明, 二宮 崇, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 豊岡 伸一, 谷本 光音, 木浦 勝行

    肺癌   55 ( 5 )   502 - 502   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Endobronchial ultrasound-guided transbronchial biopsy with or without a guide sheath for diagnosis of lung Cancer 査読

    Daisuke Minami, Nagio Takigawa, Daisuke Morichika, Toshio Kubo, Kadoaki Ohashi, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

    Respiratory Investigation   53 ( 3 )   93 - 97   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    Background: Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath (EBUS-GS) is widely used for diagnosing lung cancers
    however, the diagnostic yield varies widely. This study aimed to assess the efficiency of EBUS-GS. Methods: We retrospectively evaluated the results of 110 patients who underwent transbronchial biopsy (TBB) for diagnosis of peripheral lung cancer. Bronchoscopy with and without EBUS-GS was performed in 60 (group A) and 50 patients (group B), respectively
    their medical records were examined, and results from the two groups were compared by using the unpaired Student t-test. Results: The diagnostic sensitivity for lung cancer was 83.3% in group A and 68% in group B ( P=0.066) while using at least one of the following procedures: TBB, cytological brushing, and bronchial washing. The diagnostic sensitivity for lesions ≥20. mm was 86.4% in group A and 76.7% in group B ( P=0.263). Moreover, the diagnostic sensitivity for lesions 10-20. mm was 60% in group A and 14.2% in group B ( P=0.0004)
    the diagnostic sensitivity with TBB alone was 63.3% in group A and 44% in group B ( P=0.043). The diagnostic sensitivity with TBB alone for lesions ≥20. mm was 70.2% in group A and 44.8% in group B ( P=0.051). Moreover, the diagnostic sensitivity for lesions 10-20. mm in size was 45% in group A and 14.2% in group B with TBB alone ( P=0.115). Conclusion: EBUS-GS with TBB, brushing, and bronchial washing is effective in diagnosing lung cancers sized &lt
    20. mm.

    DOI: 10.1016/j.resinv.2014.10.003

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  • ガイドシース併用気管支腔内超音波断層法による経気管支肺生検で確定診断された悪性リンパ腫の2例

    肥後 寿夫, 南 大輔, 小田 尚廣, 豊田 容輔, 二宮 貴一朗, 槇本 剛, 谷口 暁彦, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 田端 雅弘, 金廣 有彦, 谷本 光音, 木浦 勝行

    気管支学   37 ( Suppl. )   S287 - S287   2015年5月

  • 腎移植後の免疫抑制療法に合併した肺クリプトコッカス症の診断にEBUS-GSが有用であった1例

    槇本 剛, 南 大輔, 宮原 信明, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    気管支学   37 ( 3 )   345 - 345   2015年5月

  • PET-CTにて縦隔、肺門リンパ節転移偽陽性の肺癌症例における超音波気管支鏡ガイド下針生検の有用性

    南 大輔, 瀧川 奈義夫, 小田 尚廣, 槇本 剛, 二宮 貴一朗, 豊田 容輔, 肥後 寿夫, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    気管支学   37 ( Suppl. )   S193 - S193   2015年5月

  • 気管支鏡検査における迅速細胞診の進歩と問題点 BIOEVALUATORを用いた迅速細胞診断を併用した超音波気管支鏡ガイド下針生検の有用性

    南 大輔, 瀧川 奈義夫, 槇本 剛, 小田 尚廣, 豊田 容輔, 二宮 貴一朗, 肥後 寿夫, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    気管支学   37 ( Suppl. )   S151 - S151   2015年5月

  • PET-CTにて縦隔・肺門リンパ節転移陽性の肺癌症例における超音波気管支鏡ガイド下針生検の有用性

    南 大輔, 瀧川 奈義夫, 小田 尚廣, 槇本 剛, 二宮 貴一朗, 豊田 容輔, 肥後 寿夫, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    気管支学   37 ( 3 )   345 - 345   2015年5月

  • A Phase II Trial of Gefitinib in Combination with Bevacizumab as First-Line Therapy for Advanced Non-Small Cell Lung Cancer with Activating EGFR Gene Mutations: The Okayama Lung Cancer Study Group Trial 1001 査読

    Eiki Ichihara, Katsuyuki Hotta, Naoyuki Nogami, Shoichi Kuyama, Daizo Kishino, Masanori Fujii, Toshiyuki Kozuki, Masahiro Tabata, Daijiro Harada, Kenichi Chikamori, Keisuke Aoe, Hiroshi Ueoka, Shinobu Hosokawa, Akihiro Bessho, Akiko Hisamoto-Sato, Toshio Kubo, Isao Oze, Nagio Takigawa, Mitsune Tanimoto, Katsuyuki Kiura

    JOURNAL OF THORACIC ONCOLOGY   10 ( 3 )   486 - 491   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Purpose: Whether bevacizumab enhances the effect of the epidermal growth factor receptor (EGFR) inhibitor gefitinib on EGFR mutant non-small cell lung cancers (NSCLCs) remains unknown. We conducted a phase II trial to investigate the efficacy and safety of gefitinib when combined with bevacizumab as first-line therapy in patients with advanced NSCLC harboring EGFR gene mutations.
    Methods: In this trial, 42 patients with a performance status of 0 to 2 received gefitinib (250 mg/d) and bevacizumab (15 mg/kg, every 3 weeks). The primary end point of this study was the 1-year progression-free survival (PFS) rate. We assumed that a 1-year PFS rate of 55% would indicate potential usefulness and that a 1-year PFS rate of 40% would constitute the lower limit of interest.
    Results: Forty-two patients were enrolled in the study with a median age of 73 (range 42-86) years. Activating EGFR gene mutations included exon 19 deletion (57%) and L858R point mutations in exon 21 (38%). The objective response rate was 73.8% and included two complete responses. The 1-year PFS rate and median PFS time were 56.7% (95% confidence interval [CI] 39.9-70.5) and 14.4 months (95% CI 10.1-19.2), respectively. The median PFS differed significantly between EGFR exon 19 deletion and the L858R point mutation (18.0 versus 9.4 months, respectively; p = 0.006). The median overall survival had not yet been reached. Severe adverse events included grade 3 skin rash (15%), hypertension (17%), aspartate transaminase/alanine aminotransferase elevation (17%), proteinuria (7%), intracranial hemorrhage (2%), and grade 4 perforation of the digestive tract (2%). There were no treatment-related deaths.
    Conclusion: Gefitinib in combination with bevacizumab as first-line therapy seems to be a favorable and well-tolerated treatment for patients with advanced NSCLC with activating EGFR gene mutations, especially those with EGFR exon 19 deletion mutations, although the primary end point was not met because the lower limit of the CI was less than 40%.

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  • Magnitude of the Benefit of Progression-Free Survival as a Potential Surrogate Marker in Phase 3 Trials Assessing Targeted Agents in Molecularly Selected Patients with Advanced Non-Small Cell Lung Cancer: Systematic Review 査読

    Katsuyuki Hotta, Yuka Kato, Natasha Leighl, Nagio Takigawa, Rabab Mohamed Gaafar, Hiroe Kayatani, Taizo Hirata, Kadoaki Ohashi, Toshio Kubo, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

    PLOS ONE   10 ( 3 )   e0121211   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background
    In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly selected patients with advanced non-small cell lung cancer (NSCLC), overall survival (OS) as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed.
    Methods and Findings
    We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs) or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed in molecularly selected patients and ten using an "all-comer" design). Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs) (0.99 vs. 1.04), the former exhibited greater progression-free survival-hazard ratios (PFS-HR) (mean, 0.40 vs. 1.01; P &lt; 0.01). A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%). The odds ratio for overall response was higher in trials with molecularly selected patients than in all-comer trials (mean: 6.10 vs. 1.64; P &lt; 0.01). An odds ratio of 3.40 for response afforded a sensitivity of 88% and a specificity of 90%.
    Conclusion
    The notably enhanced PFS benefit was quite specific to trials with molecularly selected patients. A PFS-HR cutoff of similar to 0.6 may help detect clinical benefit of molecular targeted agents in which OS is of limited use, although desired threshold might differ in an individual trial.

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  • BIOEVALUATORを用いた迅速細胞診断を併用したEBUS-TBNAの有用性

    槇本 剛, 南 大輔, 瀧川 奈義夫, 二宮 貴一朗, 小田 尚廣, 豊田 容輔, 肥後 寿夫, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    日本呼吸器学会誌   4 ( 増刊 )   216 - 216   2015年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • EGFR遺伝子変異を有する進行肺非小細胞癌に対する初回治療として、ゲフィチニブ、ベバシズマブ併用療法を行う第II相試験 岡山肺癌治療研究会OLCSG1001

    二宮 貴一朗, 工藤 健一郎, 加藤 有加, 市原 英基, 野上 尚之, 久山 彰一, 田端 雅弘, 久保 寿夫, 谷本 光音, 木浦 勝行, 岡山肺癌治療研究会

    日本内科学会雑誌   104 ( Suppl. )   191 - 191   2015年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • Programmed cell death protein 1 and programmed death-ligand 1 are expressed on the surface of some small-cell lung cancer lines 査読

    Hiromichi Yamane, Hideko Isozaki, Masami Takeyama, Nobuaki Ochi, Kenichiro Kudo, Yoshihiro Honda, Tomoko Yamagishi, Toshio Kubo, Katsuyuki Kiura, Nagio Takigawa

    AMERICAN JOURNAL OF CANCER RESEARCH   5 ( 4 )   1553 - 1557   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:E-CENTURY PUBLISHING CORP  

    Introduction: Programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) play a major role in suppressing the immune system during the formation of the PD-1/PD-L1 pathway, which transmits an inhibitory signal to reduce T cell activity. PD-L1 is often expressed in various malignant tumors. In contrast, PD-1 is generally observed in activated lymphocytes and myeloid-derived dendritic cells. Of the malignant cells, only Jurkat cells under special conditions and angioimmunoblastic T-cell lymphoma tissue cells express PD-1 on their surface. Methods: To clarify whether the PD-1/PD-L1 pathway participates in the immunotolerance of small-cell lung cancer (SCLC) cells, we examined the expressions of PD-1 and PD-L1 on the cell surface of SCLC cell lines using flow cytometry and reverse transcription polymerase chain reaction. Results: Among the four SCLC cell lines examined, only SBC-3 expressed both PD-1 and PD-L1. Conclusions: We demonstrated that both PD-1 and PD-L1 molecules were co-expressed on the surface of SCLC cells. Although the biological implications of this remain unclear, we speculate that PD-1 and its ligand on the SCLC cells may participate in the growth inhibition of tumor cells as reported in cytotoxic T cells.

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  • A phase II study of S-1 chemotherapy with concurrent thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer: The Okayama Lung Cancer Study Group Trial 0801 査読

    Keisuke Aoe, Nagio Takigawa, Katsuyuki Hotta, Tadashi Maeda, Daizo Kishino, Naoyuki Nogami, Masahiro Tabata, Shingo Harita, Toshiaki Okada, Toshio Kubo, Shinobu Hosokawa, Keiichi Fujiwara, Kenichi Gemba, Masayuki Yasugi, Toshiyuki Kozuki, Yuka Kato, Kuniaki Katsui, Susumu Kanazawa, Hiroshi Ueoka, Mitsune Tanimoto, Katsuyuki Kiura

    EUROPEAN JOURNAL OF CANCER   50 ( 16 )   2783 - 2790   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Background: Although thoracic irradiation (TRT) is a standard treatment for elderly patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treatment outcomes are poor. We previously reported a phase I trial combining S-1, an oral 5-fluorouracil derivative, and thoracic radiation, which yielded safe and effective outcomes.
    Methods: In this phase II trial, 30 patients aged 76 years or older with LA-NSCLC received S-1 (80 mg/m(2) on days 1-14 and 29-42) and TRT (60 Gy). The primary end-point was the response rate.
    Results: The median age and pre-treatment Charlson score were 79 years and 1, respectively. The mean proportions of the actual doses of S-1 and TRT delivered relative to the planned doses were 95% and 98%, respectively. Partial responses were observed in 19 patients (63%; 95% confidence interval: 45-82%), which did not attain the end-point. At a median follow-up time of 23.7 months, the median progression-free survival and median survival times were 13.0 months and 27.9 months, respectively. No difference in efficacy was observed upon stratification by tumour histology. Toxicities were generally mild, except for grade 3 or greater febrile neutropenia and pneumonitis in 7% and 10% of patients, respectively. No patient developed severe oesophagitis.
    Conclusions: Although the primary end-point was not met, concurrent S-1 chemotherapy and radiotherapy yielded favourable survival data. Also, the combined treatment was well-tolerated in elderly patients with LA-NSCLC. (c) 2014 Elsevier Ltd. All rights reserved.

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  • ガイドシース併用気管支腔内超音波断層法の肺癌診断への導入効果

    南 大輔, 瀧川 奈義夫, 二宮 貴一朗, 小田 尚廣, 豊田 容輔, 槙本 剛, 肥後 寿夫, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   54 ( 5 )   534 - 534   2014年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • ACTH産生胸腺神経内分泌腫瘍に合併したニューモシスチス肺炎の1例

    枝木 久典, 南 大輔, 二宮 貴一朗, 小田 尚廣, 豊田 容輔, 槇本 剛, 肥後 寿夫, 久保 寿夫, 大橋 圭明, 佐藤 晃子, 堀田 勝幸, 宮原 信明, 金廣 有彦, 田端 雅弘, 谷本 光音, 木浦 勝行, 小松原 基志, 稲垣 兼一

    肺癌   54 ( 4 )   260 - 260   2014年8月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • [Lung cancer: progress in diagnosis and treatments. Topics: III. Treatment; 4. Treatment of small cell lung cancer]. 査読

    Kubo T, Kiura K

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   103 ( 6 )   1322 - 1329   2014年6月

  • Fatal Candida Septic Shock During Systemic Chemotherapy in Lung Cancer Patient Receiving Corticosteroid Replacement Therapy for Hypopituitarism: A Case Report 査読

    Daisuke Morichika, Akiko Sato-Hisamoto, Katsuyuki Hotta, Katsuyoshi Takata, Noriko Iwaki, Koji Uchida, Daisuke Minami, Toshio Kubo, Mitsune Tanimoto, Katsuyuki Kiura

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   44 ( 5 )   501 - 505   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage IIIA. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (i) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (ii) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome.

    DOI: 10.1093/jjco/hyu019

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  • 気管支鏡検査で診断し外科的切除を行った肺原発悪性黒色腫の1例

    萱谷 紘枝, 南 大輔, 渡邉 元嗣, 山本 寛斉, 宗 淳一, 久保 寿夫, 堀田 勝幸, 田端 雅弘, 豊岡 伸一, 三好 新一郎, 谷本 光音, 木浦 勝行

    気管支学   36 ( 2 )   208 - 208   2014年3月

  • Effect of AZD1480 in an epidermal growth factor receptor-driven lung cancer model 査読

    Toshi Murakami, Nagio Takigawa, Takashi Ninomiya, Nobuaki Ochi, Masaaki Yasugi, Yoshihiro Honda, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Mitsune Tanimoto, Katsuyuki Kiura

    LUNG CANCER   83 ( 1 )   30 - 36   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    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 &lt;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 &lt;0.0001).
    Conclusion: AZD1480 may be effective against lung tumors driven by an activating EGER mutation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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  • Cisplatin-induced hyponatremia in malignancy: comparison between brand-name and generic formulation 査読

    Nobuaki Ochi, Hiromichi Yamane, Katsuyuki Hotta, Hiromi Fujii, Hideko Isozaki, Yoshihiro Honda, Tomoko Yamagishi, Toshio Kubo, Mitsune Tanimoto, Katsuyuki Kiura, Nagio Takigawa

    DRUG DESIGN DEVELOPMENT AND THERAPY   8   2401 - 2408   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:DOVE MEDICAL PRESS LTD  

    Introduction: Widespread use of generic drugs is considered to be indispensable if reductions in total health care costs are to be achieved, but the market share of such drugs remains low. In general, generic drugs have the same active ingredients as brand-name drugs, but this is not always the case. Thus, toxicity profiles may vary when brand-name and generic drugs are compared. We retrospectively investigated the incidence of hyponatremia in patients receiving brand-name cisplatin (CDDP) and a generic counterpart thereof.
    Methods: We reviewed the medical records of patients treated with brand-name CDDP (n=53) and a generic formulation (n=26), and compared the incidences of hyponatremia and renal toxicity. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. Differences between groups were evaluated using the Student's t-test, and the odds ratio for hyponatremia was estimated via logistic regression analysis.
    Results: Serum creatinine levels after chemotherapy increased significantly in both the brand-name and generic CDDP groups; no significant difference was evident between the two groups. Hyponatremia of grade 3 or above developed in 30.7% of the generic CDDP group compared to 15.1% of the brand-name CDDP group (P=0.011). Multivariate analysis showed that the use of generic CDDP increased the incidence of hyponatremia (odds ratio =5.661, 95% confidence interval =1.403-22.839; P=0.015).
    Conclusion: Oncologists should be aware that use of a generic CDDP might be associated with more hyponatremia than would use of brand-name CDDP.

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  • Afatinib Prolongs Survival Compared with Gefitinib in an Epidermal Growth Factor Receptor-Driven Lung Cancer Model 査読

    Takashi Ninomiya, Nagio Takigawa, Eiki Ichihara, Nobuaki Ochi, Toshi Murakami, Yoshihiro Honda, Toshio Kubo, Daisuke Minami, Kenichiro Kudo, Mitsune Tanimoto, Katsuyuki Kiura

    MOLECULAR CANCER THERAPEUTICS   12 ( 5 )   589 - 597   2013年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    An irreversible ErbB family blocker is expected to inhibit tumors with activating epidermal growth factor receptor (EGFR) mutations more strongly than reversible EGFR tyrosine kinase inhibitors and to overcome acquired resistance to the T790M secondary mutation. Eleven-week-old transgenic mice with Egfr exon 19 deletion mutation were treated with afatinib, gefitinib, or vehicle for 4 weeks. All mice were sacrificed at 15 weeks of age, and the number of superficial left lung tumors with a long axis exceeding 1 mm was counted. The afatinib-treated group had significantly fewer tumors than the vehicle group (P &lt; 0.01) and tended to have fewer tumors than the gefitinib-treated group (P = 0.06). Pathologically, gefitinib-treated mice had clearer, more nodular tumors than afatinib-treated mice. Immunoblotting showed that afatinib suppressed not only pEGFR but also pHER2, and induced apoptosis for longer periods than gefitinib. Subsequently, when each drug was administered 5 days per week until death, afatinib significantly enhanced mouse survival compared with gefitinib (median survival time: 456 days vs. 376.5 days; log-rank test, P &lt; 0.01). Finally, the combination of afatinib with bevacizumab was found to be superior to either drug alone in exon 19 deletion/T790M and L858R/T790M xenograft tumors. Overall, afatinib was more potent than gefitinib in tumors harboring an exon 19 deletion mutation, and the combination of afatinib with bevacizumab efficiently suppressed tumors harboring the T790M secondary mutation.

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  • 肋骨腫瘤を契機に発見された原発性肺癌と多発性骨髄腫合併の1例

    大亀 剛, 鷲尾 一浩, 二宮 貴一朗, 久保 寿夫, 岡田 俊明, 張田 信吾

    肺癌   53 ( 1 )   47 - 51   2013年2月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

    背景。多発性骨髄腫は形質細胞由来の悪性疾患で、しばしば肋骨などに孤立性の腫瘍を形成して発見されるが、肺癌に合併する症例は少ない。我々は、右肋骨腫瘍を契機に右肺上葉にも腫瘤を指摘し、手術時に行った生検で肋骨形質細胞腫と診断した1例を経験したので報告する。症例。73歳男性。発熱を主訴に近医受診した際に胸部X線撮影で異常影を指摘され、当院紹介となった。以前には同病変は指摘されていなかった。胸部CTで右肺尖部に肺癌を疑う15mmの結節と、右第5肋骨に6cm大の腫瘤を認めた。PET-CTでは両病変に異常集積を認めた。患者の意向で局所麻酔下での生検は行わない方針となり、診断・治療目的に手術を施行した。術中針生検にて肺尖部腫瘤は腺癌、肋骨腫瘤は形質細胞腫疑いの診断を得た。肺癌に対して右上葉切除ND2a-1を施行し手術終了した。右上葉肺腺癌pT1aN0M0 stage IAで、肋骨腫瘤は病理組織診断で形質細胞腫と診断された。当院血液内科にて全身精査を行い、血清IgGλ型M蛋白発現と骨髄中形質細胞増多を認めたため症候性多発性骨髄腫と診断された。結論。原発性肺癌と多発性骨髄腫の重複例の診断の契機として、肋骨形質細胞腫を呈していた例は国内で他に報告例がないため、若干の文献的考察を加えて報告した。(著者抄録)

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  • Subpopulation of small-cell lung cancer cells expressing CD133 and CD87 show resistance to chemotherapy 査読

    Toshio Kubo, Nagio Takigawa, Masahiro Osawa, Daijiro Harada, Takashi Ninomiya, Nobuaki Ochi, Eiki Ichihara, Hiromichi Yamane, Mitsune Tanimoto, Katsuyuki Kiura

    CANCER SCIENCE   104 ( 1 )   78 - 84   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Tumors are presumed to contain a small population of cancer stem cells (CSCs) that initiate tumor growth and promote tumor spreading. Multidrug resistance in CSCs is thought to allow the tumor to evade conventional therapy. This study focused on expression of CD133 and CD87 because CD133 is a putative marker of CSCs in some cancers including lung, and CD87 is associated with a stem-cell-like property in small-cell lung cancer (SCLC). Six SCLC cell lines were used. The expression levels of CD133 and CD87 were analyzed by real-time quantitative reverse transcription-polymerase chain reaction and flow cytometry. CD133+/- and CD87+/- cells were isolated by flow cytometry. The drug sensitivities were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Non-obese diabetic/severe combined immunodeficiency mice were used for the tumor formation assay. SBC-7 cells showed the highest expression levels of both CD133 and CD87 among the cell lines. CD133-/CD87-, CD133+/CD87-, and CD133-/CD87+ cells were isolated from SBC-7 cells; however, CD133+/CD87+ cells could not be obtained. Both CD133+/CD87- and CD133-/CD87+ subpopulations showed a higher resistance to etoposide and paclitaxel and greater re-populating ability than the CD133-/CD87- subpopulation. CD133+/CD87- cells contained more G0 quiescent cells than CD133-/CD87- cells. By contrast, CD133-/CD87- cells showed the highest tumorigenic potential. In conclusion, both CD133 and CD87 proved to be inadequate markers for CSCs; however, they might be beneficial for predicting resistance to chemotherapy. (Cancer Sci 2013; 104: 7884)

    DOI: 10.1111/cas.12045

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  • A case of primary lung cancer with synchronous costal plasmacytoma 査読

    Takashi Ohki, Kazuhiro Washio, Kiichiro Ninomiya, Toshio Kubo, Toshiaki Okada, Shingo Harita

    Japanese Journal of Lung Cancer   53 ( 1 )   47 - 51   2013年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Background. Multiple myeloma is a malignancy that derives from plasma cells. Some are diagnosed with a solitary plasmacytoma developing on spines, bones of the extremities or ribs, but few cases are reported that have multiple myeloma combined with primary lung cancer. We encountered a case of primary lung cancer with a solitary rib tumor, which was diagnosed as plasmacytoma. Case. A 73-year-old man found to have an asymptomatic tumor on the right 5th rib. This abnormal lesion was not pointed out before. Chest CT and PETCT showed a 15 mm sized tumor with spiculation and pleural indentation in the apex of the right lung (18F-FDG accumulation with the SUVmax of 7.93), and a 6 cm sized expansile tumor in the right 5th rib (18F-FDG accumulation with the SUVmax of 8.16). On operation, core needle biopsy was performed for these two tumors. Intraoperative rapid diagnosis was performed and we found the lung tumor was an adenocarcinoma, and the costal tumor was suspected to be a plasmacytoma. Subsequently, a right upper lobectomy ND2a-1 was performed by completely video-assisted surgery. The patient was given a diagnosis of primary lung adenocarcinoma (pT1aN0M0 stage IA) and a plasmacytoma of the right 5th rib. General examination was followed after the diagnosis, and a monoclonal gammopathy (IgG λ type) and an increase of plasma cells in the bone marrow were found, and symptomatic multiple myeloma was finally diagnosed. Conclusion. We report a rare case of primary lung cancer combined with symptomatic multiple myeloma which developed a single plasmacytoma on the rib. © 2013 The Japan Lung Cancer Society.

    DOI: 10.2482/haigan.53.47

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  • MicroRNA miR-34b/c enhances cellular radiosensitivity of malignant pleural mesothelioma cells. 査読

    Maki Y, Asano H, Toyooka S, Soh J, Kubo T, Katsui K, Ueno T, Shien K, Muraoka T, Tanaka N, Yamamoto H, Tsukuda K, Kishimoto T, Kanazawa S, Miyoshi S

    Anticancer research   32 ( 11 )   4871 - 4875   2012年11月

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  • S-1+Docetaxel併用療法が有効であった多発骨転移・播種性血管内凝固を合併した進行胃癌の1例

    二宮 貴一朗, 万波 智彦, 妹尾 賢, 鈴木 優子, 田村 朋季, 木村 耕介, 久保 寿夫, 増成 太郎, 岡田 俊明, 木口 亨, 瀬崎 伸夫, 張田 信吾, 中田 安成, 園部 宏

    癌と化学療法   39 ( 11 )   1719 - 1722   2012年11月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

    症例は69歳、女性。全身倦怠感と背部痛のため近医を受診し、著明な貧血と血小板減少を認め当院へ紹介となる。初診時の血液検査で播種性血管内凝固症候群(DIC)に陥っていた。胃内視鏡検査で噴門部小彎から体部小彎に4型病変を認め、生検では低分化型腺癌の診断であった。骨シンチグラフィで多発骨転移を認めた。胃癌に合併した骨髄癌症と考えられ、DICに対する補充療法、抗凝固療法を行うも病勢の悪化を続ける一方であり、そのため化学療法を施行した。S-1 80mg/m2を14日間内服、docetaxel(DOC)40mg/m2を1日目に点滴静注するS-1+DOC併用療法を施行し、治療開始より12日目にDICから離脱した。S-1+DOC併用療法は、胃癌骨髄癌症に対する重要な選択肢の一つとなる可能性がある。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J00296&link_issn=&doc_id=20121119410023&doc_link_id=%2Fab8gtkrc%2F2012%2F003911%2F024%2F1719-1722%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2012%2F003911%2F024%2F1719-1722%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • JAK2-related pathway induces acquired erlotinib resistance in lung cancer cells harboring an epidermal growth factor receptor-activating mutation 査読

    Daijiro Harada, Nagio Takigawa, Nobuaki Ochi, Takashi Ninomiya, Masayuki Yasugi, Toshio Kubo, Hiromasa Takeda, Eiki Ichihara, Kadoaki Ohashi, Saburo Takata, Mitsune Tanimoto, Katsuyuki Kiura

    CANCER SCIENCE   103 ( 10 )   1795 - 1802   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib and erlotinib, are effective for non-small cell lung cancer with activating EGFR mutations. However, even in patients with an initial dramatic response to such a drug, acquired resistance develops after 612 similar to months. A secondary mutation of T790M in EGFR and amplification of the MET gene account for this resistance; however, the mechanism(s) of approximately 30% of acquired resistance cases remain unknown. We established an erlotinib-resistant lung cancer cell line named PC-9/ER3 that harbors an EGFR mutation after continuously exposing PC-9 cells to erlotinib. PC-9/ER3 cells were 136-fold more resistant to erlotinib than the parental cells. Although the PC-9/ER3 cells did not carry the T790M mutation or MET amplification and had similar levels of phosphorylated (p) STAT3, pJAK2 increased in the resistant cells. It was found in the present study that 312 similar to h of exposure to erlotinib in both cell lines did not affect pJAK2 expression, but did result in increased pSTAT3 expression. pAkt in PC-9/ER3 cells was less suppressed than in PC-9 cells, although pEGFR and pMAPK were markedly suppressed in both cell lines. The combined treatment of erlotinib plus a JAK2 inhibitor (JSI-124) suppressed pAkt in PC-9/ER3 cells. Similarly, the combination of erlotinib plus JSI-124 or siRNA against JAK2 restored sensitivity to erlotinib in PC-9/ER3 cells. The combination of erlotinib plus JSI-124 was also effective for reducing PC-9/ER3 tumors in a murine xenograft model. Our results suggest that the activation of JAK2 partially accounts for acquired erlotinib resistance.(Cancer Sci, doi: 10.1111/j.1349-7006.2012.02363.x, 2012)

    DOI: 10.1111/j.1349-7006.2012.02363.x

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  • Disappearance of an activated EGFR mutation after treatment with EGFR tyrosine kinase inhibitors 査読

    Yoshihiro Honda, Nagio Takigawa, Soichiro Fushimi, Nobuaki Ochi, Toshio Kubo, Saeko Ozaki, Mitsune Tanimoto, Katsuyuki Kiura

    LUNG CANCER   78 ( 1 )   121 - 124   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    A 34-year-old Japanese woman presented with left supraclavicular lymph node swelling. Computed tomography scans revealed a mass on the left lower lobe, pulmonary nodules, and pleural effusion. A lymph node biopsy revealed large-cell carcinoma with an epidermal growth factor receptor (EGFR) deletion mutation, L747-T751 in exon 19. Although malignant pleural effusions carried the same EGFR mutation, progressive pleural effusions after treatment with chemotherapy, gefitinib, and erlotinib did not show any EGFR mutation. A cell line established from the pleural effusion 3 days before the patient expired also did not harbor the EGFR mutation. Histological sections of the lymph node of the patient were similar to those of the xenograft tumor of the cell line. There may be genetic heterogeneity in EGFR mutant tumors. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.lungcan.2012.07.003

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  • Frequent methylation and oncogenic role of microRNA-34b/c in small-cell lung cancer. 査読

    Tanaka N, Toyooka S, Soh J, Kubo T, Yamamoto H, Maki Y, Muraoka T, Shien K, Furukawa M, Ueno T, Asano H, Tsukuda K, Aoe K, Miyoshi S

    Lung cancer (Amsterdam, Netherlands)   76 ( 1 )   32 - 38   2012年4月

  • The anti-proliferative effect of heat shock protein 90 inhibitor, 17-DMAG, on non-small-cell lung cancers being resistant to EGFR tyrosine kinase inhibitor. 査読

    Kobayashi N, Toyooka S, Soh J, Yamamoto H, Dote H, Kawasaki K, Otani H, Kubo T, Jida M, Ueno T, Ando M, Ogino A, Kiura K, Miyoshi S

    Lung cancer (Amsterdam, Netherlands)   75 ( 2 )   161 - 166   2012年2月

  • STAT3 expression in activating EGFR-driven adenocarcinoma of the lung 査読

    Saburo Takata, Nagio Takigawa, Yoshihiko Segawa, Toshio Kubo, Kadoaki Ohashi, Toshiyuki Kozuki, Norihiro Teramoto, Motohiro Yamashita, Shinichi Toyooka, Mitsune Tanimoto, Katsuyuki Kiura

    LUNG CANCER   75 ( 1 )   24 - 29   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Bronchioloalveolar carcinoma (BAC) pattern is often seen at the margin of invasive adenocarcinomas. We investigated EGFR signaling abnormalities involved in the progression of adenocarcinoma. Fifty tumors were obtained from patients who underwent surgery for lung adenocarcinoma seen as dense areas in ground glass opacity on computed tomography. Six, 18, and 26 tumors &lt;1 cm, 1-2 cm, and &gt;= 2 cm in diameter, respectively, were analyzed. Of the 24 tumors &lt;= 2 cm in diameter, nine were preinvasive and 15 were invasive. EGFR, pAKT, and pMAPK were overexpressed in the center of the adenocarcinoma compared to the BAC component (p &lt; 0.01) by immunohistochemistry, while pSTAT3 expression was reversed (p = 0.017). In the tumors &lt;= 2 cm in diameter, pSTAT3 expression in the central area was higher in preinvasive tumors than in invasive tumors (p = 0.005). pSTAT3 was identified in the BAC component of 88% of the EGFR mutant (n = 17) and 82% of the wild-type tumors (n = 33). Transgenic mice expressing delE748-A752 EGFR and two lung cancer cell lines (PC-9 mutant and A549 wild-type EGFR) were also investigated. In transgenic mice, pSTAT3 was overexpressed in the BAC component around the adenocarcinoma center. Two lung cancer cell lines that overexpressed pSTAT3 were equally sensitive to a JAK2/STAT3 inhibitor (JSI-124). The role of STAT3 in the progression of adenocarcinoma should be further pursued. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.lungcan.2011.05.015

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  • A case of advanced gastric cancer with multiple bone metastases and disseminated intravascular coagulation successfully treated by combination chemotherapy of S-1 plus docetaxel 査読

    Kiichiro Ninomiya, Tomohiko Mannami, Satoru Seno, Yuko Suzuki, Tomoki Tamura, Kosuke Kimura, Toshio Kubo, Taro Masunari, Toshiaki Okada, Toru Kiguchi, Nobuo Sezaki, Shingo Harita, Yasunari Nakata, Hiroshi Sonobe

    Japanese Journal of Cancer and Chemotherapy   39 ( 11 )   1719 - 1722   2012年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

    Advanced gastric cancer (AGC) accompanied by disseminated intravascular coagulation (DIC) has a poor prognosis, and has no established therapy. Here, we report a case of a 69-year-old woman referred to our hospital due to severe anemia and thrombocytopenia. Esophagogastroduodenoscopy demonstrated an AGC in the cardiac part of the stomach, which was histologically diagnosed as poorly-differentiated adenocarcinoma. Bone scintigraphy showed multiple metastases to the bone marrow. Her diagnosis was DIC resulting from AGC, with multiple bone metastases. She underwent chemotherapy with the following regimen: 60 mg/m2 docetaxel (DOC) infusion on day 1 and daily oral administration of 100 mg/m2 S-1 for two weeks every three weeks. DIC subsided rapidly after initiation of the therapy and resolved in 12 days. She was discharged from the hospital 56 days after admission and survived 303 days. To our knowledge, this is the first case of AGC reported in the Japanese and English literature to obtain long-term survival in this setting. Combined chemotherapy of S-1 plus DOC may play an important role in the treatment of AGC developing DIC.

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  • 異種移植マウスモデルを利用したゲフィチニブ獲得耐性における肝細胞増殖因子(HGF)の関与

    柏原 宏美, 市原 英基, 高田 三郎, 大橋 圭明, 大澤 昌宏, 久保 寿夫, 武田 洋正, 藤井 昌学, 頼 冠名, 瀧川 奈義夫, 谷本 光音, 木浦 勝行

    肺癌   49 ( 5 )   697 - 697   2009年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 非喫煙関連肺癌マウスモデルにおけるvandetanibの化学予防効果

    久保 寿夫, 大橋 圭明, 大澤 昌宏, 武田 洋正, 市原 英基, 藤井 昌学, 柏原 宏美, 瀧川 奈義夫, 谷本 光音, 木浦 勝行

    肺癌   49 ( 5 )   659 - 659   2009年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Chemopreventive Effects of Gefitinib on Nonsmoking-Related Lung Tumorigenesis in Activating Epidermal Growth Factor Receptor Transgenic Mice 査読

    Kadoaki Ohashi, Nagio Takigawa, Masahiro Osawa, Eiki Ichihara, Hiromasa Takeda, Toshio Kubo, Seiki Hirano, Tadashi Yoshino, Minoru Takata, Mitsune Tanimoto, Katsuyuki Kiura

    CANCER RESEARCH   69 ( 17 )   7088 - 7095   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Twenty-five percent of all lung cancer cases are not attributable to smoking. Epidermal growth factor receptor (EGFR) mutations, which are involved in similar to 50% of nonsmoker lung cancer, are positively correlated with responsiveness to gefitinib, and inversely correlated with smoking history. Activating EGFR mutations play a critical role in the carcinogenesis of nonsmoking-related lung cancer. To investigate the chemopreventive effects of gefitinib on nonsmoking-related lung cancer, we generated transgenic mice expressing EGFR L85SR in type II pneumocytes constitutively using the surfactant protein-C promoter. The transgenic mice invariably developed atypical adenomatous hyperplasia at age 4 weeks and multifocal adenocarcinoma of varying sizes at age 7 weeks. Notably, the expression levels of phosphorylated and total ErbB2, ErbB3, and thyroid transcription factor-1 were elevated in the transgenic mice compared with wild-type controls at age 3 weeks. Administration of gefitinib to 3-week-old transgenic mice for I week before carcinogenesis reduced the amount of phosphorylated EGFR in the lungs of the mice to the baseline level. Gefitinib (5 mg/kg/d; n = 5, 5, and 15) or vehicle (n = 5, 5, and 15) was administered to transgenic mice from age 3 to 8, 13, and 18 weeks, respectively. The numbers of lung tumors in the control and gefitinib-treated groups were 1.75, 5.8, 10.2, and 0 (P &lt; 0.05), respectively. No fatal toxic events occurred in either group, and gefitinib inhibited tumorigenesis completely in this mouse model. These results suggest the utility of molecular targeted chemoprevention against nonsmoking-related lung cancer. [Cancer Res 2009;69(17):7088-95]

    DOI: 10.1158/0008-5472.CAN-08-4205

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  • ゼノグラフトモデルでのゲフィチニブに対する腫瘍の感受性における肝細胞増殖因子の効果(Effect of hepatocyte growth factor on tumors sensitive to gefitinib in a xenograft model)

    柏原 宏美, 市原 英基, 高田 三郎, 大橋 圭明, 大澤 昌宏, 久保 寿夫, 武田 洋正, 藤井 昌学, 頼 冠名, 瀧川 奈義夫, 谷本 光音, 木浦 勝行

    日本癌学会総会記事   68回   479 - 479   2009年8月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • 非喫煙者肺癌マウスモデルにおけるバンデタニブによる化学予防効果(Chemopreventive effect of vandetanib on tumorigenesis in a mouse model of non-smoking related lung cancer)

    久保 寿夫, 大橋 圭明, 大澤 昌宏, 武田 洋正, 市原 英基, 藤井 昌学, 柏原 宏美, 瀧川 奈義夫, 谷本 光音, 木浦 勝行

    日本癌学会総会記事   68回   75 - 75   2009年8月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • Efficacy of a Lumbo-peritoneal Shunt for Meningeal Carcinomatosis Refractory to Gefitinib Treatment 査読

    Toshio Kubo, Nagio Takigawa, Katsuyuki Kiura, Ayumi Nishida, Nobuaki Ochi, Hiromi Kashihara, Shigeki Umemura, Akiko Hisamoto, Mitsune Tanimoto

    ANTICANCER RESEARCH   29 ( 7 )   2759 - 2760   2009年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT INST ANTICANCER RESEARCH  

    A 51-year-old female presented with left facial palsy. She had adenocarcinoma of the lung with multiple brain metastases. The primary tumor regressed after treatment with gefitinib, however, neurological symptoms progressed rapidly because of meningeal carcinomatosis, when a deletion mutation in exon 19 of the epidermal growth factor receptor in cells from her cerebrospinal fluid was detected. After performing lumbo-peritoneal shunting, her symptoms improved dramatically and she had been well without peritoneal dissemination for 15 months, continuing gefitinib treatment. Finally, she died 18 months after lumbo-peritoneal shunting. A T790M acquired-resistance mutation in exon 20 of the epidermal growth factor receptor was found from her mesenteric lymph nodes and cerebrospinal fluid at autopsy. A lumbo-peritoneal shunt might be considered for meningeal carcinomatosis refractory to gefitinib treatment without an emergence of a T790M mutation.

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  • 変異EGFRトランスジェニックマウスに対するvandetanibの有用性

    大澤 昌宏, 大橋 圭明, 久保 寿夫, 市原 英基, 高田 三郎, 瀧川 奈義夫, 田端 雅弘, 谷本 光音, 木浦 勝行

    肺癌   48 ( 5 )   476 - 476   2008年10月

  • 限局型小細胞肺癌(LD-SCLC)に対する化学放射線療法における早期奏効の臨床的意義

    藤井 昌学, 堀田 勝幸, 藤原 義朗, 久保 寿夫, 武田 洋正, 柏原 宏美, 大澤 昌宏, 大橋 圭明, 市原 英基, 高田 三郎, 平木 章夫, 瀧川 奈義夫, 田端 雅弘, 木浦 勝行, 谷本 光音

    肺癌   48 ( 5 )   417 - 417   2008年10月

  • 喫煙と関連性が低い肺癌マウスモデルに対するゲフィチニブの化学予防効果(Chemopreventive Effect of Gefitinib on Smoking-unrelated Lung Cancer Mouse Model)

    大橋 圭明, 大澤 昌宏, 久保 寿夫, 武田 洋正, 市原 英基, 堀田 勝幸, 平木 章夫, 瀧川 奈義夫, 吉野 正, 田端 雅弘, 高田 穣, 木浦 勝行, 谷本 光音

    日本癌学会総会記事   67回   90 - 90   2008年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • 限局型小細胞肺癌(LD-SCLC)に対する化学放射線療法における早期奏効の臨床的意義

    藤井 昌学, 堀田 勝幸, 藤原 義朗, 久保 寿夫, 武田 洋正, 柏原 宏美, 大澤 昌宏, 大橋 圭明, 市原 英基, 高田 三郎, 瀧川 奈義夫, 田端 雅弘, 木浦 勝行, 谷本 光音, 平木 章夫

    肺癌   48 ( 4 )   367 - 367   2008年8月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • [Coinfection with Mycoplasma pneumoniae and Chlamydophila pneumoniae in a middle-aged adult]. 査読

    Kubo T, Takigawa N, Tanimoto Y, Ichihara E, Tabata M, Miyahara N, Kanehiro A, Kiura K, Tanimoto M

    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society   45 ( 10 )   808 - 811   2007年10月

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MISC

  • AYA世代発症の肉腫・希少がんに対するがん遺伝子プロファイリング検査の意義

    山本英喜, 河内麻里子, 十川麗美, 二川摩周, 浦川優作, 井上博文, 井上博文, 遠西大輔, 久保寿夫, 中田英二, 田端雅弘, 亀田雅博, 黒住和彦, 柳井広之, 嶋田明, 平沢晃, 平沢晃

    日本遺伝性腫瘍学会学術集会プログラム・抄録集   26th   2020年

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  • がん遺伝子パネル検査によるがん個別化医療と遺伝性腫瘍への実効果

    山本英喜, 山本英喜, 久保寿夫, 冨田秀太, 遠西大輔, 豊岡伸一, 豊岡伸一, 平沢晃

    日本癌学会学術総会抄録集(Web)   79th   2020年

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  • 災害ボランティア活動に参加した喘息患者の血痰精査中に発見された右胸部異常陰影の一例

    鹿谷 芳伸, 黒崎 毅史, 大谷 真二, 中田 憲太郎, 難波 圭, 諏澤 憲, 枝園 和彦, 久保 寿夫, 山本 寛斉, 岡崎 幹生, 杉本 誠一郎, 宗 淳一, 山根 正修, 大藤 剛宏, 豊岡 伸一

    岡山医学会雑誌   131 ( 2 )   113 - 113   2019年8月

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  • The effect and safety of an immune checkpoint inhibitor rechallenge in non-small cell lung cancer.

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  • Immune checkpoint inhibitor efficacy and safety in elderly non-small cell lung cancer patients.

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  • EGFR遺伝子変異陽性肺癌に対するオシメルチニブ再投与の有効性に関する検討

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  • Acquired resistance to the third-generation EGFR inhibitor ASP8273 is associated with MET or NRAS gene amplifications in preclinical models

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  • A comprehensive analysis of autopsied specimens and patient-derived cell lines in ALK-positive lung cancers with rapid acquired resistance to alectinib

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  • Impact of atezolizumab (atezo) treatment beyond disease progression (TBP) in advanced NSCLC: Results from the randomized phase III OAK study.

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  • The effect of nivolumab treatment for central nervous system metastases in non-small cell lung cancer.

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  • Chemoradiotherapy (CRT) for locally-advanced (LA) lung cancer patients with interstitial lung abnormalities (ILA).

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  • Phase I/II Trial of Carboplatin, nab-Paclitaxel and Bevacizumab for Advanced Non-Squamous Non-Small Cell Lung Cancer: Results of Phase I Part

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  • Interleukin-6 as potential predictive marker for therapeutic effect of Gefitinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations

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  • Combination effect of anti-VEGFR-2 antibody with erlotinib on EGFR mutant non-small cell lung cancer

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  • AXL and EGFR signaling mediate resistance to Crizotinib in non-small cell lung cancer cells harboring the ROS1 fusion gene

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  • Association with consolidation chemotherapy after concurrent chemoradiotherapyfollowed by surgery and the disease free survival in patients with stage III non-small cell lung cancer (NSCLC).

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  • 分子標的薬耐性 EML4-ALK融合遺伝子陽性肺癌におけるアレクチニブの耐性機序解明

    磯崎 英子, 市原 英基, 大橋 圭明, 堀田 勝幸, 瀧川 奈義夫, 八杉 昌幸, 二宮 崇, 久保 寿夫, 佐藤 晃子, 南 大輔, 細川 忍, 別所 昭宏, 千堂 年昭, 谷本 光音, 木浦 勝行

    肺癌   55 ( 5 )   400 - 400   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Interleukin-6 Is a Valuable Predictive Marker for Therapeutic Effect of Gefitinib in Patients with Advanced NSCLC Harboring EGFR Mutations

    Yuka Kato, Katsuyuki Hotta, Tomoki Tamura, Takehiro Tanaka, Koichi Ichimura, Kadoaki Ohashi, Toshio Kubo, Eiki Ichihara, Mitsune Tanimoto, Katsuyuki Kiura

    JOURNAL OF THORACIC ONCOLOGY   10 ( 9 )   S646 - S647   2015年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE INC  

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  • ケア 外来化学療法の問題点を解決 外来化学療法を受ける患者の自己管理日記帳の活用状況の調査

    福武 恵, 西本 仁美, 久山 めぐみ, 黒明 安子, 槇枝 亜希, 小幡 優子, 水田 裕美, 西森 久和, 久保 寿夫, 田端 雅弘

    日本癌治療学会誌   50 ( 3 )   2722 - 2722   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • Both programmed cell death protein 1 and programmed death-ligand 1 molecules can be expressed on the cell surface of small-cell lung cancer

    Hiromichi Yamane, Hideko Isozaki, Nobuaki Ochi, Kenichiro Kudo, Yoshihiro Honda, Tomoko Yamagishi, Toshio Kubo, Katsuyuki Kiura, Nagio Takigawa

    CANCER RESEARCH   75   2015年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2015-1323

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  • Phase II study of topotecan and cisplatin with sequential radiotherapy in elderly small cell lung cancer patients (Okayama Lung Cancer Study Group; OLCSG 0102).

    Toshio Kubo, Shingo Harita, Toshiaki Okada, Haruhito Kamei, Shinobu Hosokawa, Tadashi Maeda, Toshiyuki Kozuki, Keiichi Fujiwara, Katsuyuki Hotta, Nagio Takigawa, Mitsune Tanimoto, Katsuyuki Kiura

    JOURNAL OF CLINICAL ONCOLOGY   33 ( 15 )   2015年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • 【臨床研究中核病院から】 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

    木浦 勝行, 堀田 勝幸, 佐藤 晃子, 大橋 圭明, 二宮 崇, 南 大輔, 田端 雅弘, 久保 寿夫, 加藤 有加, 平田 泰三

    岡山医学会雑誌   127 ( 2 )   2015年

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  • 肺全摘後症候群に伴う急性呼吸不全に対して胸腔内ガス注入療法が著効した1例

    妹尾 賢, 久保 寿夫, 二宮 貴一朗, 岡田 俊明, 鷲尾 一浩, 張田 信吾

    日本呼吸器学会誌   4 ( 6 )   2015年

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  • 肺癌のチェックポイント阻害剤

    久保 寿夫, 木浦 勝行

    呼吸器内科   27 ( 6 )   2015年

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  • 【いま知っておきたい! 内科最新トピックス】(第1章)呼吸器 ALK陽性肺がんの第二世代治療薬とその問題とは

    木浦 勝行, 久保 寿夫

    内科   116 ( 6 )   2015年

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  • アレクチニブ

    木浦勝行, 久保寿夫

    分子呼吸器病   19 ( 1 )   2015年

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  • 経気管支肺生検にて悪性リンパ腫と確定診断された4例

    小田尚廣, 南大輔, 瀧川奈義夫, 槙本剛, 二宮貴一郎, 豊田容輔, 肥後寿夫, 久保寿夫, 大橋圭明, 佐藤晃子, 堀田勝幸, 宮原信明, 金廣有彦, 田端雅弘, 谷本光音, 木浦勝行

    気管支学   37 ( 3 )   2015年

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  • MET阻害薬の最新知見 (特集 肺癌分子標的治療薬の最新情報)

    久保 寿夫, 木浦 勝行

    呼吸器内科   26 ( 2 )   106 - 110   2014年8月

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    記述言語:日本語   出版者・発行元:科学評論社  

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    その他リンク: http://search.jamas.or.jp/link/ui/2015002336

  • Factors affecting PS deterioration at the time of relapse after the first-line EGFR-TKI therapy in EGFR-mutant advanced NSCLC

    Tomoki Tamura, Katsuyuki Hotta, Hiroko Gotoda, Yuka Kato, Eiki Ichihara, Toshio Kubo, Mltsune Tanimoto, Katsuyuki Kiura

    JOURNAL OF CLINICAL ONCOLOGY   32 ( 15 )   2014年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • Time trend in the survival advantage in phase III trials investigating molecular targeted agents for advanced non-small cell lung cancer (NSCLC) during the past decade

    Yuka Kato, Katsuyuki Hotta, Hiroe Kayatani, Toshio Kubo, Kadoaki Ohashi, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

    JOURNAL OF CLINICAL ONCOLOGY   32 ( 15 )   2014年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • 超音波気管支鏡ガイド下針生検(EBUS-TBNA)におけるBIOEVALUATOR(R)を使用した迅速細胞診断の有用性

    南大輔, 瀧川奈義夫, 森近大介, 二宮貴一朗, 後藤田裕子, 萱谷絋枝, 田村朋季, 久保寿夫, 佐藤晃子, 堀田勝幸, 宮原信明, 金廣有彦, 田端雅弘, 谷本光音, 木浦勝行

    気管支学   36 ( 2 )   2014年

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  • 肺癌診断におけるガイドシース併用気管支腔内超音波断層法の導入効果

    南大輔, 瀧川奈義夫, 二宮貴一朗, 森近大介, 後藤田裕子, 萱谷絋枝, 田村朋季, 久保寿夫, 佐藤晃子, 堀田勝幸, 宮原信明, 金廣有彦, 田端雅弘, 谷本光音, 木浦勝行

    気管支学   36   2014年

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  • 超音波気管支鏡ガイド下針生検(EBUS-TBNA)におけるBIOEVALUATORを使用した迅速細胞診断の効果

    二宮貴一朗, 南大輔, 瀧川奈義夫, 森近大介, 後藤田裕子, 萱谷絋枝, 田村朋季, 久保寿夫, 佐藤晃子, 堀田勝幸, 宮原信明, 金廣有彦, 田端雅弘, 谷本光音, 木浦勝行

    気管支学   36   2014年

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  • EGFR-TKI使用中に生じた癌性髄膜炎に対し,脳脊髄液-腹腔内シャントが奏効した2症例の検討

    森近大介, 久保寿夫, 萱谷紘枝, 後藤田裕子, 田村朋季, 二宮貴一郎, 南大輔, 大橋圭明, 佐藤晃子, 堀田勝幸, 田端雅弘, 谷本光音, 木浦勝行

    日本肺癌学会総会号   55th   2014年

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  • 当院における進行肺腺癌に対するPemetrexedの抗腫瘍効果とEML4-ALK融合遺伝学の関連性についての検討

    二宮貴一朗, 妹尾賢, 田村朋季, 久保寿夫, 三宅剛平, 岡田俊明, 張田信吾

    日本臨床腫瘍学会学術集会プログラム・抄録集   10th   2012年

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  • Role of ERK reactivation mediated by Src in acquired resistance to gefitinib in non-small cell lung cancer with EGFR mutation

    Nobuaki Ochi, Nagio Takigawa, Kadoaki Ohashi, Hiromasa Takeda, Masanori Fujii, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Mitsune Tanimoto, Katsuyuki Kiura

    CANCER RESEARCH   71   2011年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2011-724

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  • Vascular endothelial growth factor receptor tyrosine kinase inhibitor inhibited mutated epidermal growth factor receptor-driven tumors ex vivo and in vivo

    Toshio Kubo, Kadoaki Ohashi, Masahiro Osawa, Hiromasa Takeda, Eiki Ichihara, Takashi Ninomiya, Nagio Takigawa, Shingo Harita, Yasunari Nakata, Mitsune Tanimoto, Katsuyuki Kiura

    CANCER RESEARCH   71   2011年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2011-3681

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  • Effect of afatinib on lung cancer burden induced by an exon 19 EGFR mutation in transgenic mice

    Takashi Ninomiya, Nagio Takigawa, Toshio Kubo, Masayuki Yasugi, Yoshihiro Honda, Daisuke Minami, Toshi Murakami, Eiki Ichihara, Mitsune Tanimoto, Katsuyuki Kiura

    CANCER RESEARCH   71   2011年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2011-3566

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  • JAK2/STAT3 induces erlotinib-resistance in lung cancer cells harboring EGFR-activating mutations

    Daijiro Harada, Daijiro Harada, Nagio Takigawa, Kadoaki Ohashi, Eiki Ichihara, Toshio Kubo, Hiromasa Takeda, Hiromi Kashihara, Katsuyuki Hotta, Mitsune Tanimoto, Katsuyuki Kiura

    CANCER RESEARCH   71   2011年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2011-717

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  • 「肺小細胞癌に対する予防的全脳照射」 特集 小細胞肺癌治療の現況と展望.

    久保寿夫, 木浦勝行

    呼吸器科   16 ( 4 )   286 - 291   2009年

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  • DNA methylation in small lung adenocarcinoma withbronchioloalveolar carcinoma components.

    Kubo T, Yamamoto H, Ichimura K, Jida M, Hayashi T, Otani H, Tsukuda K, Sano Y, Kiura K, Toyooka S

    Lung Cancer   65 ( 3 )   328 - 332   2009年

  • P-44 肺癌細胞株におけるCD133の発現(基礎研究,第49回日本肺癌学会総会号)

    田尾 裕之, 久保 寿夫, 大谷 弘樹, 冨山 浩司, 山本 寛斎, 山根 正修, 豊岡 伸一, 大藤 剛宏, 佐野 由文

    肺癌   48 ( 5 )   2008年10月

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    記述言語:日本語   出版者・発行元:日本肺癌学会  

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  • 中年成人に発症したマイコプラズマ肺炎とクラミドフィラ肺炎の重複感染

    久保寿夫, 瀧川奈義夫, 谷本 安, 市原英基, 田端雅弘, 宮原信明, 金廣有彦, 木浦勝行, 谷本光音

    日本呼吸器学会誌   45 ( 10 )   808 - 811   2007年

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講演・口頭発表等

  • Phase II trial of carboplatin, nab-paclitaxel and bevacizumab for advanced non-squamous non-small cell lung cancer (CARNAVAL study; TORG1424/OLCSG1402)

    久保 寿夫

    ESMO Asia Annual Meeting  2019年11月23日 

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    記述言語:英語   会議種別:ポスター発表  

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  • 高齢非小細胞肺癌に対する免疫チェックポイント阻害剤の効果と安全性に関する後方視的検討

    久保 寿夫

    第59回日本呼吸器学会学術講演会  2019年4月13日 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Immune checkpoint inhibitor efficacy and safety in elderly non-small cell lung cancer patients.

    久保 寿夫

    ESMO Annual Meeting  2018年10月20日 

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    記述言語:英語   会議種別:ポスター発表  

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  • Phase Ib trial of nivolumab combined with metformin for refractory/recurrent solid tumors

    久保 寿夫

    ASCO Annual Meeting  2018年6月3日 

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    記述言語:英語   会議種別:ポスター発表  

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  • 治療歴を有するNSCLC患者に対するatezolizumabの第3相臨床試験(OAK)における日本人部分集団解析

    久保 寿夫

    第58回日本肺癌学会学術集会  2017年10月14日 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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共同研究・競争的資金等の研究

  • 治間質性肺炎合併肺癌に対する新規治療戦略の開発-化学予防の観点から-

    2018年04月 - 2020年03月

    日本学術振興会  科学研究費若手研究 

    久保 寿夫

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    担当区分:研究代表者  資金種別:競争的資金

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担当授業科目

  • 呼吸器系(臓器・系別統合講義) (2021年度) 特別  - その他

  • 腫瘍学 (2021年度) 特別  - その他

  • 血液・腫瘍・呼吸器内科学(基本臨床実習) (2021年度) 特別  - その他

  • 血液・腫瘍・呼吸器内科学I(演習・実習) (2021年度) 特別  - その他

  • 血液・腫瘍・呼吸器内科学I(講義・演習) (2021年度) 特別  - その他

  • 血液・腫瘍・呼吸器内科学II(演習・実習) (2021年度) 特別  - その他

  • 血液・腫瘍・呼吸器内科学II(講義・演習) (2021年度) 特別  - その他

  • 血液・腫瘍・呼吸器内科学(基本臨床実習) (2020年度) 特別  - その他

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