2025/07/31 更新

写真a

マキモト ゴウ
槇本 剛
Makimoto Go
所属
学術研究院医療開発領域 助教
職名
助教

学位

  • 医学博士 ( 2019年12月   岡山大学大学院医歯薬学総合研究科 )

研究キーワード

  • 肺癌

  • 呼吸器内科学

研究分野

  • ライフサイエンス / 呼吸器内科学

学歴

  • 岡山大学   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences  

    2014年4月 - 2019年12月

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  • 岡山大学   Medical School  

    2003年4月 - 2009年3月

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経歴

  • 岡山大学病院   呼吸器・アレルギー内科   助教

    2023年10月 - 現在

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  • 岡山大学病院   腫瘍センター   助教

    2022年6月 - 2023年9月

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  • 岡山大学病院   院内がん登録室   助教

    2021年4月 - 2022年5月

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  • 国立病院機構 岩国医療センター   呼吸器内科

    2019年10月 - 2021年3月

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  • 岡山大学病院   呼吸器・アレルギー内科   医員

    2014年4月 - 2019年9月

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  • 国立病院機構 岡山医療センター   呼吸器内科   後期研修医

    2012年4月 - 2014年3月

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  • 岡山ろうさい病院   内科   後期研修医

    2011年4月 - 2012年3月

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  • 国立病院機構 岡山医療センター   初期研修医

    2009年4月 - 2011年3月

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▼全件表示

所属学協会

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委員歴

  • 日本肺癌学会   中国・四国支部 評議員  

    2020年7月 - 現在   

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  • 日本癌治療学会   がん診療ガイドライン作成・改訂委員会 G-CSF適正使用ガイドライン改訂ワーキンググループ システマティックレビューチーム委員  

    2019年4月 - 現在   

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論文

  • Close Spatial Interactions between Cancer Cells and Cancer-Associated Fibroblasts Suppress Antitumor Immunity. 国際誌

    Yuto Naoi, Yumi Inukai, Tomoka Izumikawa, Joji Nagasaki, Takamasa Ishino, Youki Ueda, Yin Min Thu, Miho Fujiwara, Takahiro Baba, Go Makimoto, Ken Suzawa, Kazuhiro Okada, Ken-Ichi Yamamoto, Masakiyo Sakaguchi, Shuta Tomida, Yoshinobu Maeda, Shinichi Toyooka, Mizuo Ando, Yosuke Togashi

    Cancer immunology research   2025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)  

    Cancer-associated fibroblasts (CAFs) play immunosuppressive roles in the tumor microenvironment (TME). Specifically, they reportedly act as physical barriers preventing immune cell infiltration. However, the spatial relationships between CAFs and cancer cells in antitumor immunity remain unknown. In this study, we established three-dimensional (3D) constructs, in which the spatial relationships were controlled using a 3D bioprinter. Using these models, we found that the mixed distribution of fibroblasts (FBs) and cancer cells suppressed the antitumor immunity more than the surrounding distribution of FBs as physical barriers. The 3D construct with mixed distribution promoted transforming growth factor (TGF)-β and periostin (encoded by Postn gene) crosstalk, resulting in immunosuppression. Postn-knockdown in FBs decreased the TGF-β production in the mixed 3D construct and activated antitumor immunity both in vitro and in vivo. Clinically, patients with head and neck cancer or lung cancer showing mixed distribution of α-smooth muscle actin+ myofibroblast-like CAFs exhibited worse prognosis after programmed death protein-1 blockade therapies, and lower CD8+ T cell infiltration than those that had CAFs surrounding cancer cells. Overall, our findings suggest that the close interactions of CAFs and cancer cells facilitate immunosuppression, rather than the physical barriers created by CAFs, highlighting their potential as biomarkers and therapeutic targets for cancer immunotherapies based on spatial relationships. Furthermore, this study highlights the beneficial applications of 3D bioprinters.

    DOI: 10.1158/2326-6066.CIR-24-1144

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  • Colony-stimulating factor-1 receptor inhibitor augments osimertinib-induced anti-tumor immunity via suppression of macrophages in lung cancer harboring EGFR mutation. 国際誌

    Sachi Okawa, Shuta Tomida, Tadahiro Kuribayashi, Jun Nishimura, Takamasa Nakasuka, Atsuko Hirabae, Naofumi Hara, Hirofumi Inoue, Go Makimoto, Kiichiro Ninomiya, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Kadoaki Ohashi

    Molecular cancer therapeutics   2025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)  

    Persister cancer cells, which reversibly adapt to survive epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) treatment, contribute to the incurability of EGFR-mutant lung cancer. We previously reported that gefitinib induces CD8⁺ T cell-related tumor immunity in a genetically engineered mouse model (GEMM). This study investigates the tolerance of persister cancer cells to EGFR-TKI-induced tumor immunity in this model. Egfr-mutated lung cancer cells (C57BL/6/EgfrdelE748-A752) from GEMM were transplanted subcutaneously into wild-type C57BL/6J mice. Persistent tissues under osimertinib treatment were analyzed using digital spatial transcriptional profiling (DSP), immunohistochemical staining (IHC), and flow cytometry (FCM). The anti-tumor effect of osimertinib peaked at 14 days, leaving a small population of persister cancer cells. The number of PD-1⁺ CD8⁺ cells increased in the tumor microenvironment (TME), and CD8⁺ cell depletion attenuated the anti-tumor effect of osimertinib. DSP revealed upregulated expression of M2 macrophage-related genes in the TME of persister cancer cells. Consistently, IHC and FCM confirmed an increased number of CD206⁺ macrophages in the TME. Combining osimertinib with the colony-stimulating factor-1 receptor (CSF1R) inhibitor pexidartinib reduced CD206⁺ macrophages and enhanced the efficacy of osimertinib. Elevated granzyme or CD107 expression on CD8⁺ cells in the TME suggests that macrophages negatively affect osimertinib-induced anti-tumor immunity. M2-like macrophages may contribute to immune tolerance of persister cancer cells against EGFR-TKI-induced tumor immunity. A clinical trial evaluating combined osimertinib and CSF1R inhibitor therapy is warranted for Egfr-mutated lung cancer.

    DOI: 10.1158/1535-7163.MCT-25-0002

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  • Phase II Trial of LP-300 in Combination With Carboplatin and Pemetrexed in Never Smoker Patients With Relapsed Advanced Primary Adenocarcinoma of the Lung After Treatment With Tyrosine Kinase Inhibitors. 国際誌

    J Nicholas Bodor, Jonathan Dowell, Joseph Treat, Janakiraman Subramanian, Nihal Abdulla, Eric Lee, Kamlesh Sankhala, Chun-Hui Lee, Go Makimoto, Eisaku Miyauchi, Kartik Konduri, Hajime Asahina, Shuji Murakami, Yueh-Feng Wen, Yung-Hung Luo, Shan Yueh Chang, Reginald Ewesuedo, Jianli Zhou, Yasushi Goto

    Clinical lung cancer   2025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)  

    INTRODUCTION: Most patients with non-small cell lung cancer (NSCLC) who have never smoked possess tumors bearing tyrosine kinase oncogenes. While such tumors may exhibit robust responses to front-line tyrosine inhibitors (TKIs), disease progression is inevitable. Subsequent available therapies confer limited benefit, thus developing effective treatments for these patients remains a critical need. LP-300 is a novel compound that enhances chemotherapy sensitivity and inhibits the activity of tyrosine kinase oncogenes. Retrospective subset analyses of prior phase III studies found females and never-smokers, groups likely to have oncogene-driven tumors, obtained a considerable survival advantage with LP-300 combined with platinum-based chemotherapy as compared to chemotherapy alone. Prospective validation of these findings in patients with oncogene-driven NSCLC is needed. METHODS: The HARMONIC clinical trial, which is currently in progress, is a global, randomized, phase II study (NCT05456256) evaluating the 3-drug regimen of LP-300 with pemetrexed and carboplatin versus pemetrexed and carboplatin alone in 90 patients with advanced primary lung adenocarcinoma bearing tyrosine kinase oncogenes. Patient randomization is stratified by gender and favors the LP-300 containing arm (2-1). Patients must have tumors bearing tyrosine kinase actionable alterations (i.e. EGFR, ALK, ROS1, MET, RET, BRAF, or NTRK) and have prior TKI progression or intolerance. Primary endpoints are progression-free survival (PFS) and overall survival (OS). Secondary endpoints include objective response rate, duration of objective response, clinical benefit rate, and incidence of adverse events. CONCLUSION: This phase II trial is accruing patients at sites in the U.S, Japan, and Taiwan. Patient accrual is expected to be completed in the Fall of 2026.

    DOI: 10.1016/j.cllc.2025.05.013

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  • Remarkable Efficacy of Capmatinib in a Patient with Cancer of Unknown Primary with MET Amplification: A Case Report.

    Takaaki Tanaka, Go Makimoto, Ryohei Sumii, Rika Omote, Yayoi Ando, Kiichiro Ninomiya, Eiki Ichihara, Kadoaki Ohashi, Yoshinobu Maeda, Masahiro Tabata

    Internal medicine (Tokyo, Japan)   2025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)  

    This case report describes a 70-year-old female with cancer of unknown primary origin (CUP) who exhibited multiple distant lymph node metastases. Despite conventional chemotherapy (carboplatin and paclitaxel) and immunotherapy (nivolumab), disease progression was noted. Genomic profiling revealed MET amplification, leading to the administration of capmatinib, a selective MET tyrosine kinase inhibitor. The patient experienced substantial tumor reduction with dose adjustments due to adverse effects, indicating the potential efficacy of capmatinib in treating CUP with MET amplification.

    DOI: 10.2169/internalmedicine.5028-24

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  • A Prompt Diagnosis of Ascites and Dramatic Effect of Alectinib for Advanced Lung Adenocarcinoma Harboring EML4-ALK Fusion: A Case Report.

    Takahiro Baba, Hirofumi Inoue, Hiromi Matsuoka, Mio Kyakuno, Yusuke Yoshinaga, Tetsuya Takeguchi, Miho Fujiwara, Kotaro Yamada, Eri Nakamura, Ayako Morita, Naofumi Hara, Kiichiro Ninomiya, Hisao Higo, Masanori Fujii, Eiki Ichihara, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Yosuke Togashi, Go Makimoto

    Internal medicine (Tokyo, Japan)   2025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)  

    A 75-year-old never-smoker woman presented with dyspnea and loss of appetite. A mass was identified in the left upper lobe of the lung, and the patient was referred to our hospital. Despite the diagnosis of lung adenocarcinoma via bronchoscopy, ALK immunostaining was negative. Rapid weight gain and abdominal distension caused by ascites prompted fluid testing using the AmoyDx Pan Lung Cancer PCR Panel. EML4-ALK fusion was confirmed, and alectinib therapy was initiated immediately. The tumor size had decreased significantly, and the patient was discharged on day 34. This case highlights the necessity of multiplex genetic testing even when ALK immunostaining is negative.

    DOI: 10.2169/internalmedicine.5397-25

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  • Cancer-related alopecia and wig acquisition: how age, sex, and treatment affect patient choices. 国際誌

    Hideki Katayama, Eiki Ichihara, Ayako Morita, Go Makimoto, Shunsuke Kagawa, Ayano Ishii, Masahiro Tabata, Yoshinobu Maeda

    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer   33 ( 4 )   283 - 283   2025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)  

    PURPOSE: This study aimed to explore the prevalence and cost of wig purchases among patients with cancer in Okayama Prefecture, Japan, and examine the relationship between wig purchases and various demographic, social, and clinical factors. The findings aim to provide insights into appearance care and support systems for patients with cancer, particularly wig subsidies. METHODS: A survey was conducted between July and August 2023 among 3000 patients with cancer at 13 designated cancer care hospitals in Okayama Prefecture. Data on demographics, cancer treatment status, and wig purchase details were collected. Statistical analyses, including the Mann-Whitney U test, chi-square test, and logistic regression, were performed to identify factors significantly associated with wig purchases. RESULTS: Among the 863 respondents, 31.4% (271 patients) reported purchasing wigs. Factors significantly associated with wig purchase included young age (odds ratio [OR] = 1.04), female sex (OR = 1.61), and current cancer treatment (OR = 1.16). No significant correlation was found between wig purchase and household income, although higher-income patients tended to purchase more expensive wigs. CONCLUSION: The findings suggest that younger female patients with cancer and those undergoing treatment were more likely to purchase wigs, highlighting the importance of appearance care and the need for enhanced financial support for low-income patients.

    DOI: 10.1007/s00520-025-09318-8

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  • Efficacy of amivantamab, a bi-specific antibody targeting EGFR and MET, in ALK-rearranged non-small-cell lung cancer cell lines. 国際誌

    Tatsuya Nishi, Ayako Morita, Naofumi Hara, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yosuke Togashi, Yoshinobu Maeda, Eiki Ichihara

    Lung cancer (Amsterdam, Netherlands)   201   108415 - 108415   2025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: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are highly effective in treating ALK-rearranged non-small-cell lung cancer (NSCLC). However, at least 40% of patients develop acquired resistance during treatment. Adaptive or acquired resistance to ALK TKIs could be mediated through epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) signaling. Sixteen percent of acquired resistance cases are linked to bypass signaling. METHODS: In this study, we evaluated the effects of amivantamab, a bi-specific antibody targeting both EGFR and MET, on ALK-rearranged NSCLC cells. We investigated the effect of amivantamab on the ALK-rearranged NSCLC cell lines H3122, ABC-19, and ABC-11. RESULTS: Combining alectinib with amivantamab resulted in greater inhibition of cell growth inhibition in H3122 and ABC-19 cells compared to alectinib alone, but not in ABC-11 cells. EGFR TKI erlotinib showed similar efficacy in H3122 and ABC-19 cells, whereas MET TKI tepotinib was ineffective in both, suggesting that the efficacy of amivantamab is through EGFR inhibition. Unlike H3122 and ABC-19 cells, ABC-11 cells were resistant to EGFR/MET signaling inhibition. Interestingly, amivantamab enhanced alectinib efficacy against ABC-11 cells in the presence of peripheral blood mononuclear cells (PBMCs), despite showing no effect alone without PBMCs, suggesting action through non-signal inhibitory mechanisms. Finally, we treated alectinib-resistant cellswith alectinib, with or without amivantamab, and found that amivantamab restored the sensitivity of these cells to alectinib. CONCLUSION: The bi-specific antibody amivantamab, which targets EGFR and MET, enhanced the efficacy of alectinib through both signal and non-signal inhibitory mechanisms in ALK-rearranged NSCLC cells.

    DOI: 10.1016/j.lungcan.2025.108415

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  • Plasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer. 国際誌

    Tadahiro Kuribayashi, Rie Kinoshita, Kiichiro Ninomiya, Go Makimoto, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Shinichi Toyooka, Masakiyo Sakaguchi, Kadoaki Ohashi

    Scientific reports   15 ( 1 )   2577 - 2577   2025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)  

    Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital. The pre-treatment plasma levels of S100A8/A9 were analyzed. Eighty-one eligible patients were included (median age, 69 years). Sixty-two patients were men, 54 had adenocarcinoma, 74 had performance status (PS) 0-1, and 47 received ICIs as first-line treatment. The median time to treatment failure (TTF) for ICIs was 5.7 months, and the median overall survival (OS) was 19.6 months. The TTF and OS were worse in patients with high plasma S100A8/A9 levels (≥ 2.475 µg/mL) (median TTF: 4.3 vs. 8.5 months, p = 0.009; median OS: 15.4 vs. 38.0 months, p = 0.001). Multivariate analysis revealed that PS ≥ 2, liver metastasis, and high plasma S100A8/A9 levels were significantly associated with short TTF and OS. In conclusion, plasma S100A8/A9 level may have a limited effect on ICI therapy for NSCLC.

    DOI: 10.1038/s41598-025-87232-z

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  • A Prompt Diagnosis and Treatment of a Case of Nuclear Protein of the Testis Carcinoma Characterized by a Bronchial Lesion and High Serum Alpha-fetoprotein Level Following Genomic Testing.

    Hiroaki Matsuura, Go Makimoto, Naohiro Oda, Kiichiro Ninomiya, Hisao Higo, Masanori Fujii, Kammei Rai, Eiki Ichihara, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda

    Internal medicine (Tokyo, Japan)   63 ( 19 )   2655 - 2660   2024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)  

    Nuclear protein of the testis carcinoma (NUTC) is a rare and aggressive malignancy. We herein report a case of NUTC in the lung characterized by a bronchial lesion and elevated alpha-fetoprotein levels. A 35-year-old Japanese man presented to our institution with suspected advanced lung cancer based on a histological examination. Subsequently, next-generation sequencing (NGS) yielded a positive BRD4-NUTM1 fusion. In addition, positive NUT immunostaining of the lung biopsy specimen confirmed NUTC in the lungs. Systemic chemotherapy and radiotherapy showed a temporary response, with decreased serum alpha-fetoprotein levels. We highlight this case of a prompt diagnosis by NGS of NUTC in a young individual with a rapidly progressing tumor.

    DOI: 10.2169/internalmedicine.2938-23

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  • MET遺伝子増幅を認め、カプマチニブが著効した原発不明癌の1例

    槇本 剛, 田中 孝明, 住井 遼平, 表 梨華, 二宮 貴一朗, 安藤 弥生, 前田 嘉信, 田端 雅弘

    日本癌治療学会学術集会抄録集   62回   ICCJ3 - 3   2024年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌治療学会  

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  • A Case of Single-lung Transplant in a Patient with Mycobacterium avium Pulmonary Disease Successfully Treated with Amikacin Liposome Inhalation Suspension.

    Taichi Ozeki, Hisao Higo, Hiroki Omori, Shunta Mori, Shin Tanaka, Go Makimoto, Kiichiro Ninomiya, Akihiko Taniguchi, Masanori Fujii, Kentaro Miyoshi, Kammei Rai, Eiki Ichihara, Kadoaki Ohashi, Seiichiro Sugimoto, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Yoshinobu Maeda, Nobuaki Miyahara

    Internal medicine (Tokyo, Japan)   64 ( 7 )   1093 - 1096   2024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)  

    A 55-year-old man presented to our hospital with idiopathic pulmonary fibrosis (IPF). He was registered with the Japan Organ Transplant Network the following year due to disease progression. Treatment with clarithromycin, ethambutol, and rifampicin for complications of Mycobacterium avium pulmonary disease was initiated, but sputum conversion could not be achieved. The administration of an amikacin liposome inhalation suspension (ALIS) resulted in sputum conversion, and single-lung transplantation was performed. ALIS therapy was continued after lung transplantation, and no M. avium disease was observed for 15 months. ALIS may cause M. avium pulmonary disease with additional indications for lung transplantation.

    DOI: 10.2169/internalmedicine.3854-24

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  • Response to Imatinib in a Patient With Gastric Adenocarcinoma With KIT Q556_K558 In-Frame Deletion: A Case Report. 国際誌

    Kiichiro Ninomiya, Daisuke Ennishi, Kunio Okamoto, Midori Ando, Satoko Nakamura, Shuta Tomida, Yoshiyuki Ayada, Go Makimoto, Eiki Ichihara, Natsuko Okita, Shinichi Toyooka, Yoshinobu Maeda, Masahiro Tabata

    JCO precision oncology   8   e2400228   2024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)  

    Imatinib may be a useful targeted agent for patients with advanced gastric adenocarcinoma who have KIT mutations.

    DOI: 10.1200/PO.24.00228

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  • A randomized, open-label phase II study on the preventive effect of goshajinkigan against peripheral neuropathy induced by paclitaxel-containing chemotherapy: The OLCSG2101 study protocol. 国際誌

    Naoki Nakamura, Go Makimoto, Takaaki Tanaka, Yuka Kato, Isao Oze, Toshiyuki Kozuki, Toshihide Yokoyama, Hirohisa Ichikawa, Shoichi Kuyama, Naofumi Hara, Yoshinobu Maeda, Katsuyuki Hotta

    Respiratory investigation   62 ( 5 )   897 - 900   2024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)  

    BACKGROUND: Paclitaxel (PTX) is an essential cytotoxic anticancer agent and a standard treatment regimen component for various malignant tumors, including advanced unresectable non-small cell lung cancer, thymic cancer, and primary unknown cancers. However, chemotherapy-induced peripheral neuropathy (CIPN) caused by PTX is a significant adverse event that may lead to chemotherapy discontinuation and deterioration of the quality of life (QOL). Although treatment modalities such as goshajinkigan (GJG), pregabalin, and duloxetine are empirically utilized for CIPN, there is no established evidence for an agent as a preventive measure. We designed a randomized phase II trial (OLCSG2101) to investigate whether prophylactic GJG administration can prevent the onset of CIPN induced by PTX. METHODS: This study was designed as a two-arm, prospective, randomized, multicenter phase II trial. The patients will be randomly assigned to either the GJG prophylaxis arm (Arm A) or the GJG non-prophylaxis arm (Arm B), using cancer type (lung cancer or not) and age (<70 years or not) as adjustment factors. A total of 66 patients (33 in each arm) will be enrolled. DISCUSSION: The results of this study may contribute to better management of CIPN, which can enable the continuation of chemotherapy and maintenance of the patient's QOL. ETHICS AND DISSEMINATION: Ethical approval was obtained from the certified review board of Okayama University (approval no. CRB21-005) on September 28, 2021. Results will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION: Japan Registry of Clinical Trials (registration number jRCTs061210047).

    DOI: 10.1016/j.resinv.2024.07.017

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  • Diagnosis and treatment of non-small cell lung cancer (NSCLC) harboring MET Ex14 skipping: have we met the desired drug? 国際誌

    Go Makimoto

    Translational lung cancer research   13 ( 6 )   1438 - 1443   2024年6月

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    記述言語:英語  

    DOI: 10.21037/tlcr-24-93

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  • Two Cases of Cytomegalovirus Colitis During the Treatment of Immune Checkpoint Inhibitor-Associated Colitis. 国際誌

    Masaya Iwamuro, Takehiro Tanaka, Go Makimoto, Eiki Ichihara, Sakiko Hiraoka

    Cureus   16 ( 6 )   e63308   2024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)  

    Herein, we outlined two case reports of patients who developed cytomegalovirus colitis following the initiation of corticosteroid therapy for colitis as a result of immune-related adverse events (irAEs). For both patients, endoscopic findings were similar to those observed for patients with irAE colitis but were devoid of the characteristic features associated with cytomegalovirus colitis, including punched-out ulcers. Given the therapeutic disparities between these two conditions, it is imperative to distinguish between these conditions in clinical practice. When addressing exacerbations or refractory manifestations of irAE-associated colitis, clinicians should remain vigilant with regard to the potential for cytomegalovirus infection, even in the absence of punched-out ulcers in the colorectum.

    DOI: 10.7759/cureus.63308

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  • Concomitant osimertinib and antituberculosis therapy in an elderly patient with EGFR-mutated lung cancer and pulmonary tuberculosis: A case report. 国際誌

    Hiroaki Matsuura, Hisao Higo, Tadahiro Kuribayashi, Akihiko Tamaoki, Takamasa Nakasuka, Mari Uno, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Nobuaki Miyahara, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Kadoaki Ohashi

    Thoracic cancer   15 ( 17 )   1390 - 1394   2024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)  

    The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well-established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89-year-old female, diagnosed with epidermal growth factor receptor (EGFR)-mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis.

    DOI: 10.1111/1759-7714.15324

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  • 肝切除後の難治性気管支胆汁瘻に対してEndobronchial Watanabe Spigotの挿入が感染制御に有効であった1例

    宇野 真梨, 槇本 剛, 藤 智和, 大森 洋樹, 肥後 寿夫, 本倉 優美, 田中 孝明, 森 俊太, 大西 桐子, 二宮 貴一朗, 頼 冠名, 市原 英基, 田端 雅弘, 宮原 信明, 堀田 勝幸, 大橋 圭明

    気管支学   46 ( Suppl. )   S337 - S337   2024年5月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器内視鏡学会  

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  • Effectiveness and safety of primary prophylaxis with G-CSF for lung cancer: a systematic review and meta-analysis to develop clinical practice guidelines for the use of G-CSF 2022

    Eiki Ichihara, Nobuaki Ochi, Go Makimoto, Kenichiro Kudo, Daijiro Harada, Yukinori Ozaki, Hiroshi Nishio, Kenji Tsuchihashi, Yuji Miura, Makoto Endo, Shingo Yano, Dai Maruyama, Tetsuhiro Yoshinami, Nobuyuki Susumu, Munetaka Takekuma, Takashi Motohashi, Mamoru Ito, Eishi Baba, Keita Uchino, Takahiro Kimura, Yutaro Kamiyama, Shinji Nakao, Shinobu Tamura, Hitomi Nishimoto, Yasuhisa Kato, Atsushi Sato, Toshimi Takano, Toshio Kubo

    International Journal of Clinical Oncology   29 ( 4 )   355 - 362   2024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 Science and Business Media LLC  

    BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is commonly administered to cancer patients undergoing myelosuppressive chemotherapy, especially when incidence rate of febrile neutropenia (FN) surpasses 20%. While primary prophylaxis with G-CSF has been proven effective in preventing FN in patients with cancer, there is limited evidence regarding its efficacy in specifically, lung cancer. Our systematic review focused on the efficacy of G-CSF primary prophylaxis in lung cancer. METHODS: We extracted studies on non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using the PubMed, Ichushi Web, and Cochrane Library databases. Two reviewers assessed the extracted studies for each type of lung cancer and conducted quantitative and meta-analyses of preplanned outcomes, including overall survival, FN incidence, infection-related mortality, quality of life, and musculoskeletal pain. RESULTS: A limited number of studies were extracted: two on NSCLC and six on SCLC. A meta-analysis was not conducted owing to insufficient data on NSCLC. Two case-control studies explored the efficacy of primary prophylaxis with G-CSF in patients with NSCLC (on docetaxel and ramucirumab therapy) and indicated a lower FN frequency with G-CSF. For SCLC, meta-analysis of five studies showed no significant reduction in FN incidence, with an odds ratio of 0.38 (95% confidence interval 0.03-5.56, P = 0.48). Outcomes other than FN incidence could not be evaluated due to low data availability. CONCLUSION: Limited data are available on G-CSF prophylaxis in lung cancer. Primary prophylaxis with G-CSF may be weakly recommended in Japanese patients with NSCLC undergoing docetaxel and ramucirumab combination therapy.

    DOI: 10.1007/s10147-024-02469-4

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    その他リンク: https://link.springer.com/article/10.1007/s10147-024-02469-4/fulltext.html

  • Protracted coronavirus disease 2019 after chimeric antigen receptor-T cell therapy successfully treated with sequential multidrug therapy. 国際誌

    Masahiro Yamashita, Hisao Higo, Nobuharu Fujii, Chiaki Matsumoto, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Kammei Rai, Eiki Ichihara, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Nobuaki Miyahara

    Respiratory medicine case reports   51   102104 - 102104   2024年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 56-year-old woman who received CD19 chimeric antigen receptor-T cell therapy for refractory diffuse large B-cell lymphoma developed severe coronavirus disease 2019 (COVID-19) and was treated with nirmatrelvir/ritonavir in April 2022. However, she experienced persistent fatigue and cough and fever in June. Computed tomography revealed bilateral ground-glass opacities (GGO), and the patient was treated with corticosteroids for organizing pneumonia after COVID-19. Partial improvement was observed, but new GGO appeared despite corticosteroid therapy. Genome analysis of severe acute respiratory syndrome coronavirus 2 detected Omicron variant BA.1.1.2, which was prevalent at the time of initial infection. The patient was diagnosed with protracted COVID-19 and was treated with remdesivir, molnupiravir, nirmatrelvir/ritonavir, and tixagevimab/cilgavimab. These treatments appeared to contribute to the improvement of protracted COVID-19.

    DOI: 10.1016/j.rmcr.2024.102104

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  • [Survival Mechanisms of Drug Tolerant Persister Cancer Cells against Targeted Anticancer Drugs].

    Masataka Taoka, Go Makimoto, Kadoaki Ohashi

    Gan to kagaku ryoho. Cancer & chemotherapy   50 ( 12 )   1239 - 1245   2023年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Persister cells constitute a subset of cancer cells that exhibit resistance to anticancer therapies. They evade anticancer drug-induced cell death by slowing down the cell cycle and transiently adapting to the drugs through multiple pathways. Subsequently, these persister cells function as reservoirs, leading cancer cells towards diverse and irreversible mechanisms of drug resistance. The causes of treatment resistance in persister cells have been reported to be primarily epigenetic changes, rather than irreversible genetic mutations. Acquisition of stem-like features, epithelial-to-mesenchymal transition, alterations in survival and apoptosis signaling, changes in metabolism, variations in the tumor microenvironment, and acquisition of immune escape mechanisms are reported to be involved in the survival of persister cells. Although various therapeutic interventions have been explored for each of these aspects, few have been clinically applied. In this article, we place a particular emphasis on EGFR lung cancer and persister cells. We discuss the reasons why EGFR tyrosine kinase inhibitors fail to achieve curative outcomes and consider the biological characteristics of persister cells. We also review an overview of potential therapeutic strategies to overcome persister cell-induced resistance.

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  • 扁平上皮癌転化を来したEGFR変異肺腺癌に対してサルベージ手術を施行した1例

    藤井 龍之介, 諏澤 憲, 柳光 剛志, 田中 真, 橋本 好平, 枝園 和彦, 三好 健太郎, 山本 寛斉, 岡崎 幹生, 杉本 誠一郎, 豊岡 伸一, 槇本 剛

    肺癌   63 ( 7 )   1005 - 1005   2023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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  • 扁平上皮癌転化を来したEGFR変異肺腺癌に対してサルベージ手術を施行した1例

    藤井 龍之介, 諏澤 憲, 柳光 剛志, 田中 真, 橋本 好平, 枝園 和彦, 三好 健太郎, 山本 寛斉, 岡崎 幹生, 杉本 誠一郎, 豊岡 伸一, 槇本 剛

    肺癌   63 ( 7 )   1005 - 1005   2023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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  • CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer. 国際誌

    Naofumi Hara, Eiki Ichihara, Hirohisa Kano, Chihiro Ando, Ayako Morita, Tatsuya Nishi, Sachi Okawa, Takamasa Nakasuka, Atsuko Hirabae, Masaya Abe, Noboru Asada, Kiichiro Ninomiya, Go Makimoto, Masanori Fujii, Toshio Kubo, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Translational lung cancer research   12 ( 10 )   2098 - 2112   2023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)  

    BACKGROUND: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance. METHODS: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC. RESULTS: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation. CONCLUSIONS: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC.

    DOI: 10.21037/tlcr-23-99

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  • Severe Cytokine Release Syndrome and Immune Effector Cell-associated Neurotoxicity Syndrome in a Man Receiving Immune Checkpoint Inhibitors for Lung Cancer: A Case Report.

    Takaaki Tanaka, Masataka Taoka, Go Makimoto, Kiichiro Ninomiya, Hisao Higo, Masanori Fujii, Eiki Ichihara, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda

    Internal medicine (Tokyo, Japan)   63 ( 9 )   1261 - 1267   2023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)  

    A 55-year-old man with stage IV lung adenocarcinoma was treated with cisplatin, pemetrexed, nivolumab, and ipilimumab. Approximately 100 days after treatment initiation, he became disoriented and presented to the emergency department with a high fever. Blood tests revealed liver and kidney dysfunctions. Subsequently, the patient developed generalized convulsions that required intensive care. He was clinically diagnosed with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Organ damage was gradually controlled with immunosuppressive drugs, including steroids, and the patient was discharged. Successful treatment is rare in patients with CRS, including ICANS, during immune checkpoint inhibitor treatment for solid tumors.

    DOI: 10.2169/internalmedicine.2429-23

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  • Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer. 国際誌

    Chihiro Ando, Eiki Ichihara, Tatsuya Nishi, Ayako Morita, Naofumi Hara, Kenji Takada, Takamasa Nakasuka, Hiromi Watanabe, Hirohisa Kano, Kazuya Nishii, Go Makimoto, Takumi Kondo, Kiichiro Ninomiya, Masanori Fujii, Toshio Kubo, Kadoaki Ohashi, Ken-Ichi Matsuoka, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer science   2023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)  

    Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.

    DOI: 10.1111/cas.15958

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  • PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer. 国際誌

    Takamasa Nakasuka, Kadoaki Ohashi, Kazuya Nishii, Atsuko Hirabae, Sachi Okawa, Nahoko Tomonobu, Kenji Takada, Chihiro Ando, Hiromi Watanabe, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Hiromi Kumon, Yoshinobu Maeda, Katsuyuki Kiura

    Lung cancer (Amsterdam, Netherlands)   178   1 - 10   2023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)  

    OBJECTIVES: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored. MATERIALS AND METHODS: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined. RESULTS: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity. CONCLUSION: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME.

    DOI: 10.1016/j.lungcan.2023.01.018

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  • 肺膿瘍を合併し急速な増大を認めたが,迅速に診断しテポチニブが奏効したMET陽性肺癌の1例

    目瀬 優衣, 槇本 剛, 藤井 昌学, 市原 英基, 大橋 圭明, 木浦 勝行, 久保 寿夫, 田端 雅弘, 二宮 貴一朗, 堀田 勝幸

    肺癌   63 ( 1 )   68 - 69   2023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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  • COVID-19 Vaccine-Associated Lymphadenopathy Mimicking Regrowth of Axillary Lymph Node Metastasis of Lung Adenocarcinoma.

    Taku Noumi, Hiromi Watanabe, Kiichiro Ninomiya, Kadoaki Ohashi, Eiki Ichihara, Toshio Kubo, Go Makimoto, Yuka Kato, Masanori Fujii, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Hotta, Katsuyuki Kiura

    Acta medica Okayama   76 ( 5 )   593 - 596   2022年10月

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    記述言語:英語  

    We encountered a woman with re-enlarged axillary lymph nodes during a computed tomography (CT) scan for surveillance of lung adenocarcinoma with axillary lymph node metastasis at the initial diagnosis that had shrunk with standard chemotherapy. We first suspected cancer recurrence and considered a change in the chemotherapeutic regimen. However, after careful history taking regarding the timing of her Coronavirus Disease 2019 (COVID-19) vaccination, and subsequent careful, close follow-up, radiological shrinkage suggested a strictly benign cause. Especially in lung cancer with a medical history of axillary lymph node involvement, cliniciansshould be aware that vaccine-associated lymphadenopathy can mimic cancer recurrence and sometimesprompt serious misjudgment regarding a current treatment course and strategy.

    DOI: 10.18926/AMO/64041

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  • CD8+ T-cell responses are boosted by dual PD-1/VEGFR2 blockade after EGFR inhibition in Egfr-mutant lung cancer. 国際誌

    Kazuya Nishii, Kadoaki Ohashi, Shuta Tomida, Takamasa Nakasuka, Atsuko Hirabae, Sachi Okawa, Jun Nishimura, Hisao Higo, Hiromi Watanabe, Hirohisa Kano, Chihiro Ando, Go Makimoto, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Heiichiro Udono, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer immunology research   10 ( 9 )   1111 - 1126   2022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)  

    Epidermal growth factor receptor (EGFR) is the most frequently mutated driver oncogene in non-smoking-related, non-small-cell lung cancer (NSCLC). EGFR-mutant NSCLC has a non-inflamed tumor microenvironment (TME), with low infiltration by CD8+ T cells and, thus, immune checkpoint inhibitors, such as anti-programmed cell death-1 (anti-PD-1) have weak anti-tumor effects. Here, we showed that CD8+ T-cell responses were induced by an EGFR-tyrosine kinase inhibitor (TKI) in syngeneic Egfr-mutant NSCLC tumors, which was further pronounced by sequential dual blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2). However, simultaneous triple blockade had no such effect. PD-1/VEGFR2 dual blockade did not exert tumor-inhibitory effects without pre-treatment with the EGFR-TKI, suggesting that treatment schedule is crucial for efficacy of the dual blockade therapy. Pre-treatment with EGFR-TKI increased the CD8+ T-cell/regulatory T-cell (Treg) ratio, while also increasing expression of immunosuppressive chemokines and chemokine receptors, as well as increasing the number of M2-like macrophages, in the TME. Discontinuing EGFR-TKI treatment reversed the transient increase of immunosuppressive factors in the TME. The subsequent PD-1/VEGFR2 inhibition maintained increased numbers of infiltrating CD8+ T cells and CD11c+ dendritic cells. Depletion of CD8+ T cells in vivo abolished tumor growth inhibition by EGFR-TKI alone and the sequential triple therapy, suggesting that EGFR inhibition is a prerequisite for the induction of CD8+ T-cell responses. Our findings could aid in developing an alternative immunotherapy strategy in patients with cancers that have driver mutations and a non-inflamed TME.

    DOI: 10.1158/2326-6066.CIR-21-0751

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  • 大量喀血に対して気管支動脈塞栓術と気管支充填術が奏効したALK陽性肺癌の1例

    藤岡 佑輔, 田岡 征高, 槇本 剛, 栗林 忠弘, 松浦 宏昌, 下西 惇, 二宮 貴一朗, 肥後 寿夫, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 宮原 信明, 田端 雅弘, 木浦 勝行

    気管支学   44 ( Suppl. )   S307 - S307   2022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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  • First and repeat rebiopsy for detecting EGFR T790M mutation in non-small-cell lung cancer: CS-Lung-003 prospective observational registry study. 国際誌

    Kenichiro Kudo, Kazuya Nishii, Go Makimoto, Nobuhisa Ishikawa, Yukari Tsubata, Masahiro Kodani, Nobukazu Fujimoto, Masahiro Yamasaki, Tetsuya Kubota, Nagio Takigawa, Kazunori Fujitaka, Nobuhiro Kanaji, Takuo Shibayama, Junko Itano, Chihiro Ando, Katsuyuki Hotta, Katsuyuki Kiura

    Journal of cancer research and clinical oncology   148 ( 8 )   1869 - 1877   2022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)  

    PURPOSE: Osimertinib is still essential for the treatment of epidermal growth factor receptor (EGFR)-T790M-positive non-small-cell lung cancer (NSCLC) even in a relapsed setting, which suggests the importance of rebiopsy. The clinical value of repeat rebiopsy in patients with NSCLC who are T790M-negative on a first rebiopsy remains unclear. In this study, we examined the status of the first rebiopsy and evaluated the frequency of repeat rebiopsy of T790M-negative tumors detected by the first rebiopsy. METHODS: We reviewed 144 patients with NSCLC with major EGFR mutations, but not T790M, who received first- or second-generation EGFR tyrosine kinase inhibitors (TKIs), registered in the prospective, umbrella-type lung cancer patient registry (CS-Lung-003). RESULTS: Overall, 63 patients (44%) underwent the first rebiopsy. In the first rebiopsy, 51 (81%) and 12 (19%) of 63 underwent histological/cytological rebiopsy and liquid biopsy with the blood sampling, respectively. In the repeat rebiopsy, 23 (85%) and 4 (15%) of 27 underwent histological/cytological rebiopsy and liquid biopsy, respectively. The most frequently rebiopsied site was a pulmonary lesion (n = 24, 38.7%). Overall, 29 (46.0%) of 63 patients harbored the T790M mutation. Interestingly, a high detection rate of cancer cells did not necessarily indicate a high detection rate of the T790M mutation (p < 0.01). Among 34 patients with T790M-negative tumors confirmed on the first rebiopsy, 20 (58.8%) underwent repeat rebiopsies following interval therapy, revealing that seven (36.8%) had T790M-positive tumors. Osimertinib yielded median progression-free survival of 11.8 and 16.2 months in patients with the 790M mutation detected by the first rebiopsy and repeat rebiopsy, respectively. CONCLUSION: In our prospective cohort, the T790M mutation was detected in 46% of patients who underwent the first rebiopsy. Repeat rebiopsy may increase the ability to detect the T790M mutation positivity rate.

    DOI: 10.1007/s00432-021-03893-z

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  • がん遺伝子パネル検査を行った胸腺がん5例の検討

    久保 寿夫, 二宮 貴一朗, 槇本 剛, 加藤 有加, 藤井 昌学, 市原 英基, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    日本呼吸器学会誌   11 ( 増刊 )   279 - 279   2022年4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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  • Identification of targetable kinases in idiopathic pulmonary fibrosis. 国際誌

    Hisao Higo, Kadoaki Ohashi, Shuta Tomida, Sachi Okawa, Hiromasa Yamamoto, Seiichiro Sugimoto, Satoru Senoo, Go Makimoto, Kiichiro Ninomiya, Takamasa Nakasuka, Kazuya Nishii, Akihiko Taniguchi, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Nobuaki Miyahara, Yoshinobu Maeda, Shinichi Toyooka, Katsuyuki Kiura

    Respiratory research   23 ( 1 )   20 - 20   2022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)  

    BACKGROUND: Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). METHODS: Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). RESULTS: Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. CONCLUSIONS: We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF.

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  • Massive hemoptysis in a post-operative patient with recurrent lung cancer successfully treated by the combination therapy of Endobronchial Watanabe Spigot and bronchial artery embolization 国際誌

    Masataka Taoka, Go Makimoto, Noriyuki Umakoshi, Kiichiro Ninomiya, Hisao Higo, Yuka Kato, Masanori Fujii, Toshio Kubo, Eiki Ichihara, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Respiratory Medicine Case Reports   38   101669 - 101669   2022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:Elsevier BV  

    A 76-year-old woman who was treated with lorlatinib for postoperative recurrent anaplastic lymphoma kinase-positive lung adenocarcinoma visited our hospital with massive hemoptysis. Chest computed tomography showed massive bleeding from the right upper lobe; however, the cause of bleeding was unclear. After bronchial artery embolization (BAE), bronchial occlusion was performed using an Endobronchial Watanabe Spigot (EWS) that was easily placed because BAE had reduced the bleeding volume. Treatment with BAE alone was inadequate; however, additional therapy with EWS after BAE successfully controlled the massive hemoptysis, especially in this patient who underwent lobectomy to prevent respiratory dysfunction.

    DOI: 10.1016/j.rmcr.2022.101669

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  • Successful and Prompt Treatment with Tepotinib for Lung Adenocarcinoma Harboring MET Exon 14 Skipping Mutation Combined with Lung Abscess Formation: A Case Report. 国際誌

    Go Makimoto, Atsushi Shimonishi, Kadoaki Ohashi, Kiichiro Ninomiya, Hisao Higo, Yuka Kato, Masanori Fujii, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Case reports in oncology   15 ( 2 )   494 - 498   2022年

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    記述言語:英語  

    Tepotinib, the novel MET-tyrosine kinase inhibitor, shows an antitumor effect for patients with non-small-cell lung cancer (NSCLC) harboring MET exon 14 skipping mutation. In January 2022, the AmoyDx® Pan Lung Cancer polymerase chain reaction Panel (AmoyDx® panel), which had a shorter turnaround time than the conventional test, was launched in Japan as a tepotinib companion test. We report a patient with an advanced MET-mutant NSCLC promptly diagnosed using the AmoyDx® panel and successfully treated with tepotinib. Although the patient's performance status (PS) worsened due to the rapid tumor progression and lung abscess formation, the tumor shrank immediately after tepotinib treatment with marked PS improvement.

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  • Dasatinib-induced massive left chylothorax in a patient with chronic myeloid leukemia. 国際誌

    Go Makimoto, Mahito Misawa, Yoshinobu Maeda, Katsuyuki Kiura

    Respiratory medicine case reports   37   101662 - 101662   2022年

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    記述言語:英語  

    Dasatinib, an effective second-generation tyrosine kinase inhibitor, is used to treat breakpoint cluster region-Ableson-positive chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphocytic leukemia. One common adverse event associated with dasatinib use is fluid retention, including pleural effusion. Chylothorax, however, is a rare adverse event. Although the precise mechanism of dasatinib-induced chylothorax is unclear, almost all cases involve right or bilateral chylothorax, and mostly occur within 5 years of dasatinib initiation. Here, we report a rare case of a patient with dasatinib-induced massive left chylothorax 10 years after dasatinib initiation, which improved after dasatinib termination and a switch to bosutinib.

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  • Carboplatin, pemetrexed, and pembrolizumab was effective for primary salivary gland-type lung adenocarcinoma diagnosed due to esophageal stricture: A case report

    Keita Kawakado, Tomoki Tamura, Masamoto Nakanishi, Go Makimoto, Yumiko Sato, Shoichi Kuyama

    Thoracic Cancer   12 ( 18 )   2513 - 2516   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:John Wiley and Sons Inc  

    DOI: 10.1111/1759-7714.14100

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  • Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR-mutant lung cancer with HIF-1 alpha/TGF-alpha expression

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

    ONCOLOGY LETTERS   22 ( 3 )   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)  

    DOI: 10.3892/ol.2021.12900

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  • Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR-mutant lung cancer with HIF-1α/TGF-α expression. 国際誌

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

    Oncology letters   22 ( 3 )   639 - 639   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)  

    Osimertinib, a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with lung cancer harboring EGFR T790M; however, acquired resistance is inevitable due to genetic and epigenetic changes in cancer cells. In addition, a recent randomized clinical trial revealed that the combination of osimertinib and bevacizumab failed to exhibit superior progression-free survival compared with osimertinib alone. The present study aimed to investigate the effect of triple therapy with osimertinib, bevacizumab and cetuximab in xenograft tumors with different initial tumor volumes (conventional model, 200 mm3 and large model, 500 mm3). The results demonstrated that osimertinib significantly inhibited tumor growth in both the conventional and large models; however, maximum tumor regression was attenuated in the large model in which hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-α (TGF-α) expression levels increased. Although the combination of osimertinib and bevacizumab exerted a greater inhibitory effect on tumor growth compared with osimertinib in the conventional model, the effect of this combination therapy was attenuated in the large model. TGF-α attenuated sensitivity to osimertinib in vitro; however, this negative effect was counteracted by the combination of osimertinib and cetuximab, but not osimertinib and bevacizumab. In the large xenograft tumor model, the triple therapy induced the greatest inhibitory effect on tumor growth compared with osimertinib alone and its combination with bevacizumab. Clinical trials of the triple therapy are required for patients with lung cancer with EGFR mutations and HIF-1α/TGF-α.

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  • Retrobulbar Optic Neuritis Induced by Pembrolizumab in a Patient with Lung Adenocarcinoma.

    Keita Kawakado, Tomoki Tamura, Masamoto Nakanishi, Go Makimoto, Shoichi Kuyama

    Internal medicine (Tokyo, Japan)   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)  

    Pembrolizumab is a monoclonal antibody with anti-tumor effects. Only a few reports have previously described retrobulbar optic neuritis induced by pembrolizumab. We herein report the case of a 64 -year-old man with advanced lung adenocarcinoma who received cisplatin, pemetrexed, and pembrolizumab combination therapy for six months. Following treatment, a visual field test showed a left central scotoma. Imaging studies showed left optic neuritis without brain metastasis. Blood tests showed an elevated serum creatinine level. He was diagnosed with retrobulbar optic neuritis and pembrolizumab-induced renal failure. After receiving corticosteroid treatment, his renal function rapidly improved. The optic neuritis improved somewhat, but it was not adequately resolved.

    DOI: 10.2169/internalmedicine.7425-21

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  • Heerfordt's Syndrome Associated with Trigeminal Nerve Palsy and Reversed Halo Sign.

    Go Makimoto, Keita Kawakado, Masamoto Nakanishi, Tomoki Tamura, Minori Noda, Satoko Makimoto, Yumiko Sato, Shoichi Kuyama

    Internal medicine (Tokyo, Japan)   60 ( 11 )   1747 - 1752   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)  

    Heerfordt's syndrome is a rare subtype of sarcoidosis and features a combination of facial palsy, parotid swelling, and uveitis, associated with a low-grade fever. Cases with two of three symptoms are called "incomplete Heerfordt's syndrome." Heerfordt's syndrome involving other cranial nerve symptoms is relatively rare. We herein report a case of incomplete Heerfordt's syndrome presenting with trigeminal nerve palsy and a reversed halo sign, a rare manifestation of pulmonary sarcoidosis. The histological diagnosis following a biopsy of the parotid gland and endobronchial ultrasound-guided trans-bronchial needle aspiration of the mediastinal lymph nodes was sarcoidosis. The symptoms and lung lesions improved after corticosteroid therapy.

    DOI: 10.2169/internalmedicine.6176-20

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  • Limited effect of afatinib in a non-small cell lung cancer patient harboring an epidermal growth factor receptor K860I missense mutation: A case report. 国際誌

    Tomoki Tamura, Keita Kawakado, Go Makimoto, Masamoto Nakanishi, Shoichi Kuyama

    Thoracic cancer   12 ( 11 )   1770 - 1774   2021年6月

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    記述言語:英語  

    Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are key drugs in the treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations; however, first-generation EGFR-TKIs, such as gefitinib and erlotinib, are not effective in patients with uncommon EGFR mutations. In contrast, efficacy of afatinib has been reported in some types of uncommon EGFR mutation such as G710X, L861Q. The effect of afatinib in NSCLC patients with the EGFR K860I mutation has been shown in vitro, but its clinical efficacy has not been demonstrated. Here, we report the experience of afatinib administration in an NSCLC patient with an EGFR K860I mutation. A 69-year-old woman presented with right hemiplegia and dysarthria. Multiple brain and lung tumors were observed. She underwent craniotomy and was diagnosed with lung adenocarcinoma. After stereotactic brain radiation therapy, cisplatin, pemetrexed, and bevacizumab combination therapy was initiated. Unfortunately, she was unable to continue chemotherapy as she had an intestinal perforation after two cycles. After five months, recurrence of multiple brain metastases and an increase in primary lung cancer were confirmed. Next-generation sequencing (NGS) was performed in a clinical trial, and an EGFR K860I mutation was detected in her tumor. Afatinib was administered and the primary lung tumor shrank, but multiple brain metastases were exacerbated. After irradiation of the brain, afatinib administration was continued. In conclusion, afatinib may show an effect in NSCLC patients with the EGFR K860I mutation, but its efficacy is limited.

    DOI: 10.1111/1759-7714.13941

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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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  • Effect of Prophylactic Anti-emetics on Opioid-induced Nausea and Vomiting: A Retrospective Observational Cohort Study

    Tomoki Tamura, Keita Kawakado, G. O. Makimoto, Masamoto Nakanishi, Shoichi Kuyama

    IN VIVO   35 ( 3 )   1737 - 1742   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)  

    DOI: 10.21873/invivo.12432

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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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  • 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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  • Successful Treatment with Lorlatinib after the Development of Alectinib-Induced Liver Damage in ALK-Positive Non-Small-Cell Lung Cancer: A Case Report

    Go Makimoto, Keita Kawakado, Masamoto Nakanishi, Tomoki Tamura, Shoichi Kuyama

    CASE REPORTS IN ONCOLOGY   14 ( 1 )   197 - 201   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000513624

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  • Successful corticosteroid treatment of necrotizing sarcoid granulomatosis associated with tracheal lesion recurred after a surgical lung biopsy. 国際誌

    Go Makimoto, Keita Kawakado, Masamoto Nakanishi, Tomoki Tamura, Yumiko Sato, Shoichi Kuyama

    Respiratory medicine case reports   33   101402 - 101402   2021年

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    記述言語:英語  

    Necrotizing sarcoid granulomatosis (NSG) is a rare disease that presents with nodular lung lesions and necrosis. The pathology is consistent with sarcoidosis, but the necrosis can lead to a diagnosis of tuberculosis. Herein, we report a rare case of NSG that recurred four years after the initial diagnosis was made by surgical lung biopsy. A 51-year-old woman was initially referred to our hospital for the evaluation of multiple lung nodules. The pathological evaluation of a lung biopsy showed granulomas with necrosis and the infiltration of lymphocytes; thus, she was diagnosed with NSG. The lung nodules gradually improved after the diagnosis and we continued to follow her even though she did not require treatment. Four years after her initial diagnosis, she complained of back pain. Upon evaluation, we found that multiple lung nodules had recurred. Bronchoscopy also revealed a tracheal polypoid lesion, which showed granulomas with necrosis pathologically. Therefore, we diagnosed her with the recurrence of NSG. After the corticosteroid therapy, multiple lung nodules drastically improved. NSG patients should be carefully followed-up over several years, even if they do not require treatment.

    DOI: 10.1016/j.rmcr.2021.101402

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  • Successful transcatheter arterial embolization of asymptomatic aneurysm associated with left inferior phrenic artery-to-left pulmonary artery fistula: A case report. 国際誌

    Keita Kawakado, Takayuki Yabuki, Tatsuya Nishi, Masamoto Nakanishi, Go Makimoto, Tomoki Tamura, Shoichi Kuyama

    Respiratory medicine case reports   33   101444 - 101444   2021年

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    記述言語:英語  

    Cases of inferior phrenic artery-to-pulmonary artery fistulas and those complicated by massive hemoptysis have been rarely reported. A 38-year-old man presented to our hospital with a chief complaint of coughing. Computed tomography (CT) revealed a nodule in the left lower lobe, and contrast-enhanced CT showed inflow of contrast medium into the nodule. CT angiography detected an aneurysm associated with a left inferior phrenic artery-to-left pulmonary artery fistula. Transcatheter arterial embolization (TAE) was performed to prevent hemoptysis. Hemoptysis did not occur during the 2-year follow-up. We report a rare case of asymptomatic aneurysm associated with a left inferior phrenic artery-to-left pulmonary artery fistula, which was successfully treated using TAE to prevent hemoptysis.

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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.

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  • Anaplastic Lymphoma Kinase Fusion: A Review of Therapeutic Drugs and Treatment Strategies.

    Go Makimoto, Kadoaki Ohashi, Yoshinobu Maeda, Katsuyuki Kiura

    Acta medica Okayama   74 ( 5 )   371 - 379   2020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)  

    The prognosis of advanced non-small cell lung cancer (NSCLC) patients has improved in recent decades, especially for patients with an oncogenic driver mutation. Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are effective for patients with the echinoderm microtubule-associated protein-like 4-ALK fusion gene. Several ALK-TKIs have been established: the first-generation ALK-TKI, crizotinib; second-generation ALK-TKIs, alectinib and ceritinib; and third-generation ALK-TKI, lorlatinib. Some ALK-TKIs are effective for tumors that are resistant to other ALK-TKIs; however, as is known in epidermal growth factor receptormutant lung cancer, tumor resistance is inevitable. ALK-positive NSCLCs acquire resistance via various mechanisms, making it a heterogeneous disease. Therefore, it is necessary to develop next-generation treatment strategies, such as the use of next-generation ALK-TKIs for secondary mutations, or combination therapies with ALK-TKIs and other TKIs. In this review, we summarize the development and use of ALK-TKIs, prior pivotal clinical trials, and resistance mechanisms.

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  • Successful Desensitization Treatment with Osimertinib after the Development of Osimertinib-induced Urticaria in a Patient Undergoing Treatment for Non-small Cell Lung Cancer Harboring the EGFR T790M Mutation.

    Go Makimoto, Tatsuya Nishi, Keita Kawakado, Tomoka Nishimura, Tomoki Tamura, Kenichiro Kudo, Shoichi Kuyama

    Internal medicine (Tokyo, Japan)   59 ( 17 )   2161 - 2164   2020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)  

    Some patients discontinue receiving osimertinib for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) Thr790Met (T790M) mutation due to adverse its effects. We report a case of successful desensitization therapy after osimertinib-induced urticaria. An 85-year-old Japanese woman received osimertinib as third-line therapy for NSCLC with the EGFR T790M mutation. After two days, she developed urticaria of the lower extremities. We started osimertinib desensitization therapy at 0.1 mg/day, which was gradually increased to 40 mg/day. She continued osimertinib for >12 months without adverse effects. Desensitization therapy with osimertinib could be useful for patients experiencing osimertinib-induced urticaria.

    DOI: 10.2169/internalmedicine.4429-20

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  • Dramatic Response of Brain Metastasis from EGFR-mutation-positive NSCLC to Dacomitinib.

    Kenichiro Kudo, Keita Kawakado, Tomoka Kawajiri, Tatsuya Nishi, Go Makimoto, Tomoki Tamura, Shoichi Kuyama, Mitsune Tanimoto

    Internal medicine (Tokyo, Japan)   59 ( 14 )   1739 - 1740   2020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)  

    The central nervous system efficacy of dacomitinib, a key agent used in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC), is unclear. We herein present our experience in the use of dacomitinib for the treatment of multiple brain metastatic lesions from EGFR-mutation-positive NSCLC in an elderly patient. This case report demonstrates that dacomitinib can be an essential treatment option for patients with brain metastases.

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  • Successful Re-administration of Osimertinib in Osimertinib-induced Interstitial Lung Disease with an Organizing Pneumonia Pattern: A Case Report and Literature Review.

    Junko Itano, Hisao Higo, Kadoaki Ohashi, Go Makimoto, Kazuya Nishii, Katsuyuki Hotta, Nobuaki Miyahara, Yoshinobu Maeda, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   59 ( 6 )   823 - 828   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)  

    Osimertinib is the standard therapy for epidermal-growth-factor-receptor (EGFR)-mutant lung cancers. We herein report a case of osimertinib-induced interstitial lung disease (OsiILD) with an organizing pneumonia (OP) pattern and provide a literature-based review. Six months after osimertinib administration, a 75-year-old woman with right pleural carcinomatosis developed ILD with an OP pattern. After salvage chemotherapy, osimertinib with corticosteroid was successfully re-administered. A literature review suggested that 1) OsiILD with an OP pattern was rare but should be recognized, and 2) re-administration of osimertinib in OsiILD was successful in select patients. A criterion that determines whether a patient would benefit from re-administration is warranted.

    DOI: 10.2169/internalmedicine.3689-19

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

    Acta oncologica (Stockholm, Sweden)   59 ( 3 )   324 - 328   2020年3月

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

    Go Makimoto, Kadoaki Ohashi, Shuta Tomida, Kazuya Nishii, Takehiro Matsubara, Hiroe Kayatani, Hisao Higo, Kiichiro Ninomiya, Akiko Sato, Hiromi Watanabe, Hirohisa Kano, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Minoru Takata, Yoshinobu Maeda, Katsuyuki Kiura

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

    INTRODUCTION: The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. METHODS: Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction. RESULTS: ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes. CONCLUSIONS: High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy.

    DOI: 10.1016/j.jtho.2019.07.017

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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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  • 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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  • A Long-term Response to Nivolumab in a Case of PD-L1-negative Lung Adenocarcinoma with an EGFR Mutation and Surrounding PD-L1-positive Tumor-associated Macrophages.

    Hiromi Watanabe, Kadoaki Ohashi, Kazuya Nishii, Keisuke Seike, Go Makimoto, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   58 ( 20 )   3033 - 3037   2019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)  

    Anti-programmed cell death 1 (PD-1) antibodies have poor efficacy in epidermal growth factor receptor (EGFR)-mutated lung cancer. We herein report a 72-year-old man with programmed cell death-ligand 1 (PD-L1)-negative lung adenocarcinoma harboring an EGFR mutation that responded to nivolumab for more than 2 years. A pathological examination revealed infiltration of CD8-positive lymphocytes and macrophages expressing CD68, CD206, and PD-L1 into the PD-L1-negative tumor; CD206 expression is a marker of immunosuppressive tumor-associated macrophages (TAMs). The presence of PD-L1-positive TAMs in the tumor environment might be a predictor of a positive response to anti-PD-1 antibodies.

    DOI: 10.2169/internalmedicine.2875-19

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  • EGFR-TKI acquired resistance in lung cancers harboring EGFR mutations in immunocompetent C57BL/6J mice. 国際誌

    Hisao Higo, Kadoaki Ohashi, Go Makimoto, Kazuya Nishii, Kenichiro Kudo, Hiroe Kayatani, Hiromi Watanabe, Hirohisa Kano, Kiichiro Ninomiya, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

    Lung cancer (Amsterdam, Netherlands)   136   86 - 93   2019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)  

    OBJECTIVES: Lung cancers harboring epidermal growth factor receptor (EGFR) mutations inevitably develop resistance to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Therefore, we sought to establish clinically relevant lung-cancer mouse models to achieve deep remission of cancers. MATERIALS AND METHODS: We previously established two transgenic lung-cancer mouse models harboring human EGFR exon 21 L858R substitution (hLR) and mouse Egfr exon 19 deletion (mDEL) in the C57BL/6 J background. Lung tumors from these two transgenic mouse strains were transplanted subcutaneously into BALB/c-nunu mice or C57BL/6 J mice. RESULTS: The transplanted tumors developed the ability to grow on the subcutaneous tissue, peritoneum, or lung of C57BL/6 J mice. While hLR tumors could grow only in C57BL/6 J mice carrying the transgene, mDEL tumors could grow in wild-type C57BL/6 J mice. The tumors maintained EGFR-dependency, and, thus, the EGFR-TKI gefitinib inhibited tumor growth; however, similar to human lung cancers, hLR and mDEL tumors acquired resistance in 60 and 200 days, respectively, following gefitinib administration. Secondary EGFR T790 M mutation in hLR tumors and secondary Egfr T792I mutation in mDEL tumors developed; however, no MET activation was detected. Accordingly, the third-generation EGFR-TKI osimertinib effectively inhibited gefitinib-resistant tumors in vivo. Furthermore, gefitinib-resistant tumors developed resistance to osimertinib in 100 days. CONCLUSION: These syngeneic lung-cancer mouse models harboring EGFR mutations are suitable for studying the drug-resistance mechanisms and the role of the tumor microenvironment. Further investigation with these mouse models is warranted for developing next-generation treatment strategies for lung cancer.

    DOI: 10.1016/j.lungcan.2019.08.019

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  • 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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  • Primary Resistance to Alectinib Was Lost after Bevacizumab Combined Chemotherapy in ALK-Rearranged Lung Adenocarcinoma. 国際誌

    Takamasa Nakasuka, Eiki Ichihara, Go Makimoto, Yoshinobu Maeda, Katsuyuki Kiura

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   14 ( 8 )   e168-e169   2019年8月

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  • Recent trends in the treatment of unresectable stage III non-small-cell lung cancer. 国際誌

    Go Makimoto, Katsuyuki Hotta, Katsuyuki Kiura

    Respiratory investigation   57 ( 4 )   330 - 336   2019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)  

    Approximately 20-25% of non-small-cell lung cancer (NSCLC) is diagnosed when the disease has progressed to clinical stage III. At this stage, and even if the cancer is considered unresectable, the treatment strategy should aim to achieve a cure. At the time of the initial diagnosis, it is necessary for medical oncologists to devise the best treatment strategy for each patient by composing a multidisciplinary treatment team including thoracic surgeons and radiation oncologists. In this review, we summarize prior pivotal clinical trials in unresectable clinical stage III NSCLC. Furthermore, we review very recent clinical trials evaluating the efficacy of immune checkpoint inhibitors in the treatment of NSCLC.

    DOI: 10.1016/j.resinv.2019.03.004

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  • Beneficial Effect of Osimertinib Readministration in Non-small-cell Lung Cancer Harboring an Epidermal Growth Factor Receptor (EGFR) Mutation with a History of Acquired Resistance to Osimertinib.

    Go Makimoto, Kadoaki Ohashi, Satoru Senoo, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   58 ( 11 )   1625 - 1627   2019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)  

    We herein report a case of the beneficial effect of osimertinib readministration in non-small-cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation. A 69-year-old non-smoking woman was diagnosed with advanced NSCLC harboring an EGFR exon19 deletion and T790M. She was treated with osimertinib for two years but eventually acquired resistance. After 1.5 years of salvage chemotherapies, osimertinib was re-administered. She has been effectively and safely treated with osimertinib readministration for over 10 months. A prospective study is warranted to evaluate the efficacy and safety of osimertinib readministration in NSCLC with EGFR mutations.

    DOI: 10.2169/internalmedicine.2152-18

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

    Go Makimoto, Hisakazu Nishimori, Reiko Kondo, Hiroyuki Yanai, Morito Sugimoto, Naohiro Oda, Toshio Kubo, Katsuyuki Hotta, Masahiro Tabata, Katsuyuki Kiura, Yoshinobu Maeda

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

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    記述言語:英語  

    Urothelial carcinoma usually presents with hematuria, but cases of multiple lymphadenopathy with elevated S-pancreas-1 antigen (SPan-1) levels have not been reported. A 62-year-old Japanese man with lymphadenopathies was diagnosed with an adenocarcinoma of unknown origin and transferred to our hospital for further diagnosis. Serum carbohydrate antigen 19-9 and SPan-1 levels were extremely elevated. Uroplakin III immunostaining was positive in the inguinal lymph node, and cystoscopy revealed the presence of invasive urothelial carcinoma. Treatment with cisplatin and gemcitabine promoted a complete metabolic response for > 4 years. The detection of uroplakin III and serum SPan-1 might help diagnose urothelial carcinoma.

    DOI: 10.18926/AMO/56873

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

    Hisao Higo, Toshio Kubo, Satoko Makimoto, Go Makimoto, Hiroki Ihara, Yoshihisa Masaoka, Takashi Ninomiya, Eiki Ichihara, Kadoaki Ohashi, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Nagio Takigawa, Yoshinobu Maeda, Katsuyuki Kiura

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

    INTRODUCTION: Although chemoradiotherapy for locally advanced lung cancer has the potential for cure, treatment is avoided in patients with interstitial lung disease because of the risk for severe radiation pneumonitis. Interstitial lung abnormalities (ILA) can be evaluated using high-resolution computed tomography (HRCT) to assess interstitial changes. In this study, we retrospectively examined the feasibility and efficacy of chemoradiotherapy for locally advanced lung cancer patients with ILA. METHODS: Patients who underwent chemoradiotherapy for locally advanced lung cancer at Okayama University Hospital between 2012 and 2015 were reviewed retrospectively. HRCT prior to treatment was evaluated by one pulmonologist and two radiologists using a sequential reading method. RESULTS: Of the 77 patients enrolled in this study, ILA was present in 25 (32.5%) and indeterminate ILA in 24 patients; 28 patients did not have ILA. Desaturation at rest (SpO2 < 95%) and honeycombing on HRCT were not observed in ILA patients. Only one patient with ILA had a low vital capacity (%VC < 80%). Severe radiation pneumonitis (≥Grade 2) occurred in 36.0% of the patients with ILA, but it was controllable; Grade 4 or 5 was not observed. Multivariate analysis showed that >25% of the lung volume receiving >20 Gy was risk factors of severe radiation pneumonitis, but ILA was not. The 2-year survival rates of patients with and without ILA were 56.8% and 74.1%, respectively, but the difference was not significant (P = 0.33). CONCLUSIONS: Chemoradiotherapy was feasible and effective in some patient population with ILA without desaturation, low VC and honeycombing on HRCT.

    DOI: 10.1093/jjco/hyz016

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

    Satoru Senoo, Takashi Ninomiya, Go Makimoto, Kazuya Nishii, Hirohisa Kano, Hiromi Watanabe, Yusuke Hata, Toshio Kubo, Takehiro Tanaka, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

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

    Pulmonary pleomorphic carcinoma (PPC) is a rare very aggressive subtype of non-small cell lung cancer. We herein report a case of PPC that showed a rapid response to nivolumab. The patient, whose multiple tumors had progressed very aggressively, was treated with nivolumab, an anti-programmed cell death-1 (PD-1) antibody. The tumors dramatically shrank after one cycle of nivolumab. The tumors were positive for programmed cell death ligand 1 (PD-L1). An immunohistochemical analysis revealed numerous PD-1+, CD68+ and CD206+ macrophages. This PD-1 antibody may be a good treatment option, especially in tumors that express PD-L1 and which show PD-1+ macrophage infiltration.

    DOI: 10.2169/internalmedicine.0890-18

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  • Long-term spontaneous remission with active surveillance in IgG4-related pleuritis: A case report and literature review. 国際誌

    Go Makimoto, Kadoaki Ohashi, Kohei Taniguchi, Junichi Soh, Akihiko Taniguchi, Nobuaki Miyahara, Shinichi Toyooka, Tadashi Yoshino, Yoshinobu Maeda, Katsuyuki Kiura

    Respiratory medicine case reports   28   100938 - 100938   2019年

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    記述言語:英語  

    Pleural effusion is a relatively rare feature of IgG4-related disease (IgG4-RD). Here, we report a case of a 72-year-old woman who presented with pleural effusion. Although the pleural adenosine deaminase level was increased, surgical biopsy of the pleura and left inguinal lymph node indicated that the effusion was due to IgG4-RD. Active surveillance was initiated because serum IgG4 and pleural effusion naturally decreased and then completely disappeared. The patient has shown no recurrence for >4 years. This case suggests that pleural biopsy can be used to distinguish IgG4-RD from tuberculosis; moreover, some cases with pleural effusion could improve without treatment.

    DOI: 10.1016/j.rmcr.2019.100938

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

    Yuka Kato, Kiichiro Ninomiya, Kadoaki Ohashi, Shuta Tomida, Go Makimoto, Hiromi Watanabe, Kenichiro Kudo, Shingo Matsumoto, Shigeki Umemura, Koichi Goto, Eiki Ichihara, Takashi Ninomiya, Toshio Kubo, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer science   109 ( 10 )   3149 - 3158   2018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)  

    The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has shown dramatic effects in patients with non-small cell lung cancer (NSCLC) harboring ROS1 fusion genes. However, patients inevitably develop resistance to this agent. Therefore, a new treatment strategy is required for lung tumors with ROS1 fusion genes. In the present study, lung cancer cell lines, HCC78 harboring SLC34A2-ROS1 and ABC-20 harboring CD74-ROS1, were used as cell line-based resistance models. Crizotinib-resistant HCC78R cells were established from HCC78. We comprehensively screened the resistant cells using a phosphor-receptor tyrosine kinase array and RNA sequence analysis by next-generation sequencing. HCC78R cells showed upregulation of HB-EGF and activation of epidermal growth factor receptor (EGFR) phosphorylation and the EGFR signaling pathway. Recombinant HB-EGF or EGF rendered HCC78 cells or ABC-20 cells resistant to crizotinib. RNA sequence analysis by next-generation sequencing revealed the upregulation of AXL in HCC78R cells. HCC78R cells showed marked sensitivity to EGFR-TKI or anti-EGFR antibody treatment in vitro. Combinations of an AXL inhibitor, cabozantinib or gilteritinib, and an EGFR-TKI were more effective against HCC78R cells than monotherapy with an EGFR-TKI or AXL inhibitor. The combination of cabozantinib and gefitinib effectively inhibited the growth of HCC78R tumors in an in vivo xenograft model of NOG mice. The results of this study indicated that HB-EGF/EGFR and AXL play roles in crizotinib resistance in lung cancers harboring ROS1 fusions. The combination of cabozantinib and EGFR-TKI may represent a useful alternative treatment strategy for patients with advanced NSCLC harboring ROS1 fusion genes.

    DOI: 10.1111/cas.13752

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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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  • 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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  • 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.

    Go Makimoto, Eiki Ichihara, Katsuyuki Hotta, Kiichiro Ninomiya, Isao Oze, Daisuke Minami, Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Acta medica Okayama   72 ( 3 )   319 - 323   2018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)  

    Although cisplatin-based chemotherapy shows a survival advantage compared to carboplatin for treating advanced non-small cell lung cancer, high-volume hydration and a long infusion time are necessary to avoid nephrotoxicity, and cisplatin-based chemotherapy has been difficult to administer in outpatient settings. A low-volume hydration method using mannitol or furosemide as forced diuresis was recently introduced, but there are no clear conclusions regarding which agent should be used. We describe our ongoing randomized phase II trial (the OLCSG1406 Study) evaluating the efficacy of forced diuresis. This study will clarify whether mannitol or furosemide is more suitable in cisplatin-based chemotherapy with low-volume hydration.

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

    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)  

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

    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 - 1955   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)  

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

    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)  

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

    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)  

    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 EGFRT790M 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 EGFRL858R+T790M and RPC-9-harboring EGFR19DEL+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 EGFRT790M mutations. Therefore, clinical trials of this combination therapy are warranted.

    DOI: 10.1002/1878-0261.12063

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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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  • 同時化学放射線療法後の手術により治療した局所進行性NSCLCの生存者における第二原発性癌(Second primary cancer in survivors of locally advanced NSCLC treated with concurrent chemoradiation followed by surgery)

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

    日本呼吸器学会誌   6 ( 増刊 )   345 - 345   2017年3月

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    記述言語:英語   出版者・発行元:(一社)日本呼吸器学会  

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  • Heerfordt's Syndrome Associated with a High Fever and Elevation of TNF-α.

    Go Makimoto, Nobuaki Miyahara, Mao Yoshikawa, Akihiko Taniguchi, Arihiko Kanehiro, Mitsune Tanimoto, Katsuyuki Kiura

    Acta medica Okayama   70 ( 4 )   273 - 7   2016年8月

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    記述言語:英語  

    Heerfordt's syndrome is a rare manifestation of sarcoidosis and is defined as a combination of facial palsy, parotid swelling, and uveitis, associated with a low-grade fever. We report a case of Heerfordt's syndrome presenting with a high fever and increased serum tumor necrosis factor alpha (TNF-α) levels. The patient had facial palsy, parotid swelling, uveitis, and swelling of the right supraclavicular and hilar lymph nodes. Corticosteroid therapy was initiated, and her symptoms soon resolved completely, in tandem with a decrease in TNF-α serum levels.

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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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  • 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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  • 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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  • 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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  • 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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  • 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

  • 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 )   350 - 350   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

  • 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

  • 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

  • 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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  • 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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  • Phrenic nerve paralysis as the initial presentation in pleural sarcomatoid mesothelioma. 国際誌

    Go Makimoto, Keiichi Fujiwara, Nobukazu Fujimoto, Ichiro Yamadori, Toshio Sato, Takumi Kishimoto

    Case reports in oncology   7 ( 2 )   389 - 92   2014年5月

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    記述言語:英語  

    A 74-year-old man was referred to our hospital because of persistent cough. A chest radiograph revealed an elevation of the right diaphragm. Computed tomography (CT) images revealed a small nodule localized on the right mediastinum. Five months later, the nodule had grown and was diagnosed as malignant pleural mesothelioma (MPM) by a CT-guided needle biopsy. The patient underwent combined chemotherapy, but the disease progressed rapidly and he passed away. On autopsy, microscopic findings and immunohistological examinations supported the diagnosis of sarcomatoid mesothelioma. Therefore, we diagnosed this rare case as localized sarcomatoid MPM showing phrenic nerve paralysis as an initial presentation.

    DOI: 10.1159/000363760

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  • nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic Carcinoma. 国際誌

    Go Makimoto, Keiichi Fujiwara, Hiromi Watanabe, Nobuhisa Kameyama, Mizuho Matsushita, Kammei Rai, Ken Sato, Toshiro Yonei, Toshio Sato, Takuo Shibayama

    Case reports in oncology   7 ( 1 )   14 - 7   2014年1月

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    記述言語:英語  

    We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF) injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma.

    DOI: 10.1159/000357938

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  • Diffuse parenchymal pulmonary amyloidosis showing an objective response to bortezomib-based chemotherapy.

    Hisao Higo, Keiichi Fujiwara, Hiromi Watanabe, Go Makimoto, Nobuhisa Kameyama, Mizuho Matsushita, Kammei Rai, Ken Sato, Tomoko Inomata, Kazutaka Sunami, Takuo Shibayama

    Internal medicine (Tokyo, Japan)   53 ( 16 )   1809 - 12   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 77-year-old woman was admitted because of bilateral hand numbness and dyspnea on exertion. Her serum IgG was increased, and a bone marrow aspiration analysis supported a diagnosis of multiple myeloma. Additionally, computed tomography scans of the chest showed bilateral ground glass attenuations, linear opacities, and consolidations. Transbronchial lung biopsy revealed Congo Red-positive amorphous eosinophilic deposits. She was therefore diagnosed with diffuse parenchymal pulmonary amyloidosis accompanied by multiple myeloma. Following combination chemotherapy including bortezomib, her serum monoclonal protein levels were normalized, and pulmonary function and oxygenation improved.

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  • Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial manifestation. 国際誌

    Go Makimoto, Yasuhiro Manabe, Chizuru Yamakawa, Daiki Fujii, Yasuko Ikeda-Sakai, Hisashi Narai, Nobuhiko Omori, Koji Abe

    Neurology international   4 ( 1 )   e5   2012年1月

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    記述言語:英語  

    We report 2 cases that were considered to be neuro-Sweet disease. They initially manifested with meningoencephalitis and no skin lesions, and rapidly improved with corticosteroid therapy. In both cases, patients complained of meningitic symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be positive over the clinical course. Cerebrospinal fluid analysis showed increased levels of lymphocytes and protein. In case #1, fluid-attenuated inversion recovery (FLAIR), magnetic resonance imaging (MRI) and diffusion-weighted images (DWI) showed high-intensity signals in the right dorsal medulla oblongata, bilateral dorsal midbrain, and left thalamus. In case #2, FLAIR and DWI showed high-intensity signals in the bilateral cerebellar cortex and left caudate nucleus. Symptoms and MRI images were markedly improved in both cases after corticosteroid pulse therapy. According to published diagnostic criteria, these 2 cases were considered possible neuro-Sweet disease. These cases suggest that the combination of meningoencephalitis and HLA specificity is important to consider the possibility of neuro-Sweet disease, even without skin lesions.

    DOI: 10.4081/ni.2012.e5

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  • Bilateral Pleural Effusions as an Initial Presentation in Primary Sjögren's Syndrome. 国際誌

    Go Makimoto, Michiko Asano, Nobukazu Fujimoto, Yasuko Fuchimoto, Katsuichiro Ono, Shinji Ozaki, Koji Taguchi, Takumi Kishimoto

    Case reports in rheumatology   2012   640353 - 640353   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by sicca symptoms. Interstitial pulmonary fibrosis and tracheobronchial sicca are the most common symptoms of pulmonary involvement in primary SjS, and they are rarely accompanied by serositis such as pleuritis or pericarditis. We report a case of SS presenting initially with bilateral pleural effusions. A 63-year old man was admitted to our hospital with a one-month history of cough, dyspnea, and right chest pain. Chest-computed tomography revealed bilateral pleural effusions. Serum anti-SS-A antibody titer was 1 : 256. Ophthalmological examination revealed a positive Schirmer test. Lip biopsy showed atrophy and plasmacytic infiltration of the salivary gland. Corticosteroid treatment was initiated. Pleural effusions were almost completely resolved by day 30. The patient has not experienced any recurrence.

    DOI: 10.1155/2012/640353

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共同研究・競争的資金等の研究

  • 自然転移発生モデルからひもとくALK融合遺伝子陽性肺癌の転移機構の解明

    研究課題/領域番号:25K19440  2025年04月 - 2028年03月

    日本学術振興会  科学研究費助成事業  若手研究

    槇本 剛

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

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  • ALK融合遺伝子陽性肺癌に対するアレクチニブの早期耐性機序の解明と根治戦略の開発

    研究課題/領域番号:22K16173  2022年04月 - 2025年03月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    槇本 剛

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 肺癌の治癒を目指すEGFR-TKI、抗EGFR抗体とベバシズマブ併用療法の効果

    研究課題/領域番号:16K19454  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    大橋 圭明, 槇本 剛, 西井 和也

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    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    第3世代EGFRチロシンキナーゼ阻害薬(TKI)はEGFRT 790M変異を有する肺癌における標準治療であるが、耐性化するため新規治療戦略が必要である。本研究では、オシメルチニブ、抗EGFR抗体セツキシマブと血管新生阻害薬ベバシズマブの3剤併用療法の効果を検討した。マウスモデルにて、低腫瘍量のゼノグラフトでは3剤併用療法の優越性は示されなかったが、腫瘍が進展した高腫瘍量のゼノグラフトでは3剤併用療法は、単剤、2剤併用療法に対してより強い抗腫瘍効果を示した。臨床試験で検討する価値のある有望な治療方法と考える。

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担当授業科目

  • 呼吸器系(臓器・系別統合講義) (2024年度) 特別  - その他

  • 腫瘍学 (2024年度) 特別  - その他

  • 血液・腫瘍・呼吸器内科学(基本臨床実習) (2024年度) 特別  - その他

  • 呼吸器系(臓器・系別統合講義) (2023年度) 特別  - その他

  • 腫瘍学 (2023年度) 特別  - その他

  • 血液・腫瘍・呼吸器内科学(基本臨床実習) (2023年度) 特別  - その他

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