Updated on 2024/02/01

写真a

 
Hirose Takashi
 
Affiliation
Tamanagayama Hospital, Department of Pulmonary Medicine, Infectious Disease and Oncology, Clinical Professor
Title
Clinical Professor
External link

Papers

  • Thyroid transcription factor-1 (TTF-1) expression and the efficacy of combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapy in non-squamous non-small cell lung cancer. Reviewed International journal

    Hirokazu Iso, Kakeru Hisakane, Erika Mikami, Takahiro Suzuki, Satoru Matsuki, Kenichiro Atsumi, Kohji Nagata, Masahiro Seike, Takashi Hirose

    Translational lung cancer research   12 ( 9 )   1850 - 1861   2023.9

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    BACKGROUND: Thyroid transcription factor-1 (TTF-1) is expressed in approximately 70% of lung adenocarcinomas and is one of the most reliable makers to distinguish primary lung adenocarcinoma from metastatic disease. TTF-1-negative status is a poor prognostic factor, and TTF-1-negative lung adenocarcinoma is associated with poor efficacy of immune checkpoint inhibitor (ICI) monotherapy. However, the relationship between TTF-1 expression and the efficacy of ICI plus chemotherapy is still unclear. METHODS: We performed a retrospective analysis of 129 consecutive patients with advanced non-squamous non-small cell lung cancer (NS-NSCLC) treated with ICI monotherapy or ICI plus chemotherapy between January 2016 and December 2021. The expression of programmed death ligand-1 (PD-L1) and TTF-1 was also determined in cases for which no previous data were available. We then evaluated the association between TTF-1 expression status and treatment efficacy. RESULTS: Of the 129 cases, 33 were TTF-1-negative and 96 were positive. In the ICI monotherapy group (N=70), progression-free survival (PFS) was not significantly different between TTF-1-positive and negative patients (median 3.6 vs. 3.8 months, P=0.27); however, in patients with wild-type epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), a trend for worse PFS was observed in TTF-1-negative cases compared with those that were TTF-1-positive (median 3.8 vs. 4.5 months, P=0.088). Moreover, long-term efficacy of ICI monotherapy (>2 years) was not observed in the TTF-1-negative group. TTF-1-negative patients tended to have worse overall survival (OS) than TTF-1-positive patients (median 15.6 vs. 19.5 months, P=0.13). In the ICI plus chemotherapy group (N=59), TTF-1-negative patients tended to have better PFS and similar OS compared with TTF-1-positive patients (median 9.9 vs. 9.6 months, P=0.14; median 32.3 vs. 18.9 months, P=0.78). Long-term efficacy was generally observed in TTF-1-negative patients treated with atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP) (median PFS 22.5 months, median OS not reached). CONCLUSIONS: ICI monotherapy is generally less efficacious in TTF-1-negative NS-NSCLC patients, and clinicians should consider ICI plus chemotherapy in these cases. Our study suggests that ABCP is an optimal regimen for TTF-1-negative NS-NSCLC.

    DOI： 10.21037/tlcr-23-331

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  • 肺原発紡錘細胞癌に対してCBDCA+PTX+Nivolumab+Ipilimumabを投与し奏効した1例

    鈴木 貴大, 三上 恵莉花, 久金 翔, 渥美 健一郎, 廣瀬 敬, 永田 耕治, 清家 正博

    肺癌   63 ( 4 )   328 - 328   2023.8

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    Language：Japanese   Publisher：(NPO)日本肺癌学会  

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  • Standard versus low-dose nab-paclitaxel in previously treated patients with advanced non-small cell lung cancer: A randomized phase II trial (JMTO LC14-01). International journal

    Susumu Takeuchi, Kaoru Kubota, Shunichi Sugawara, Satoshi Teramukai, Rintaro Noro, Kei Fujikawa, Takashi Hirose, Shinji Atagi, Seigo Minami, Shinichiro Iida, Hiroshi Kuraishi, Tomoiki Aiba, Yuji Minegishi, Masaru Matsumoto, Masahiro Seike, Akihiko Gemma, Masaaki Kawahara

    Cancer medicine   12 ( 8 )   9133 - 9143   2023.4

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    BACKGROUND: Nab-paclitaxel (nab-PTX) has better transfer to tumor tissue than cremophor-based paclitaxel. It suggests that the optimum dose of nab-PTX might be lower than the dose and schedule that is widely used. We designed a randomized phase II trial to examine the clinical utility and safety of nab-PTX in patients with previously treated advanced non-small cell lung cancer (NSCLC). METHODS: Patients were randomly allocated (1:1) to receive nab-PTX monotherapy at 100 mg/m2 (group A) or 70 mg/m2 (group B). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). RESULTS: Finally, 81 patients were randomized. Similar results were observed in both groups for PFS (3.75 vs. 3.71 months), OS (13.50 vs. 16.13 months), or ORR (20.5% vs. 23.1%). The incidences of grade 3 or worse AEs were 57.5% in group A and 41.5% in group B. The proportion of serious side effects was 10.0% in group A and 4.9% in group B. CONCLUSION: Both standard dose and low dose of nab-PTX monotherapy are active for previously treated NSCLC patients with better safety profile. Therefore, nab-PTX 70 mg/m2 dose and schedule in the trial would be a reasonable option.

    DOI： 10.1002/cam4.5652

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  • 特発性器質化肺炎再発の背景因子と再発後のステロイド至適維持量

    渥美 健一郎, 久金 翔, 三上 恵莉花, 磯 博和, 松木 覚, 清家 正博, 廣瀬 敬

    日本呼吸器学会誌   12 ( 増刊 )   320 - 320   2023.3

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  • A Case of Pseudo-progression-like Pleurisy After Combined Treatment with Nivolumab and Ipilimumab for Lung Adenocarcinoma

    Terashima Yuto, Hisakane Kakeru, Atsumi Kenichiro, Terashi Naoki, Suzuki Ayana, Nagata Koji, Seike Masahiro, Gemma Akihiko, Hirose Takashi

    Haigan   62 ( 5 )   400 - 405   2022.10

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    Language：Japanese   Publisher：The Japan Lung Cancer Society  

    Background. The frequency of pseudo-progression caused by immune-checkpoint inhibitors in non-small cell lung cancer (NSCLC) is approximately 5%. Thus far, most reports of pseudo-progression in NSCLC have been due to immune-checkpoint inhibitor monotherapy. We report a case of pseudo-progression-like pleurisy after combined treatment with nivolumab and ipilimumab for lung adenocarcinoma. Case. A 70-year-old man with adenocarcinoma (pT3N0M1a, stage IVA) with pleural dissemination received combination therapy consisting of carboplatin, pemetrexed, nivolumab, and ipilimumab as first-line treatment. After treatment, he had fever, dyspnea, elevated CRP, and developed pleural effusion on the affected side. Thoracic drainage was subsequently performed. Abundant T lymphocytes with predominant CD4-positive cells infiltration were observed in pleural fluid cell-block specimens. Afterwards, his symptoms improved. No further accumulation of pleural effusion was observed, even though he continued receiving chemotherapy. Hence, he was diagnosed with pseudo-progression rather than an immune-related adverse event (irAE). Conclusion. This is the first report of pseudo-progression-like pleurisy in a lung cancer patient after combined nivolumab and ipilimumab treatment. It is important to distinguish pseudo-progression from irAE-induced pleurisy.

    DOI： 10.2482/haigan.62.400

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  • Black pleural effusion caused by a pancreaticopleural fistula associated with autoimmune pancreatitis: A case report. International journal

    Keiki Miyadera, Kakeru Hisakane, Yuki Kato, Kenichiro Atsumi, Hiroki Ono, Shu Tanaka, Kaoru Kubota, Masahiro Seike, Akihiko Gemma, Takashi Hirose

    Medicine   101 ( 36 )   e30322   2022.9

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    RATIONALE: Black pleural effusion is a rare medical condition and a diagnostic marker. Pancreaticopleural fistula is one of the causes of black pleural effusion. Thus far, black pleural effusions caused by pancreaticopleural fistulae have mostly been reported in patients with alcohol-induced chronic pancreatitis. In this report, we present a case of black pleural effusion caused by a pancreaticopleural fistula associated with autoimmune pancreatitis. PATIENT CONCERNS AND DIAGNOSIS: A 59-year-old female without a history of alcohol drinking presented to our hospital with a chief complaint of dyspnea, as well as chest and back discomfort. She had left pleural effusion, and thoracentesis showed black pleural effusion. Computed tomography revealed the presence of encapsulated fluid from the pancreatic tail to the left pleural cavity, which was diagnosed as a pancreaticopleural fistula. It also showed diffuse pancreatic swelling. Serum testing showed a high IgG4 level (363 mg/dL). These findings led to the diagnosis of autoimmune pancreatitis. INTERVENTIONS AND OUTCOME: The patient underwent endoscopic pancreatic sphincterotomy and pancreatic duct stent placement and received treatment with steroids. After treatment, there was no further accumulation of pleural effusion observed. CONCLUSION: This is the first report of black pleural effusion due to a pancreaticopleural fistula associated with autoimmune pancreatitis. The characteristic appearance of black pleural effusion may assist diagnosis. We report this case to emphasize that autoimmune pancreatitis can be a cause of black pleural effusion.

    DOI： 10.1097/MD.0000000000030322

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  • A Case of Fulminant Type 1 Diabetes Mellitus After the Administration of Durvalumab for Small-cell Lung Cancer

    Terashi Naoki, Hisakane Kakeru, Miyadera Keiki, Kato Yuki, Terashima Yuto, Suzuki Ayana, Atsumi Kenichiro, Seike Masahiro, Gemma Akihiko, Hirose Takashi

    Haigan   62 ( 4 )   323 - 328   2022.8

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    Language：Japanese   Publisher：The Japan Lung Cancer Society  

    Background. Fulminant type 1 diabetes mellitus caused by immune checkpoint inhibitors is a rare adverse event. In lung cancer, several cases have been reported in non-small-cell lung cancer. We herein report a patient with small-cell lung cancer who developed fulminant type 1 diabetes mellitus after administration of durvalumab. Case. A 71-year-old man with extensive-stage small-cell lung cancer (cT4N3M1b, stage IVA) with no history of diabetes mellitus received combination therapy of carboplatin, etoposide, and durvalumab on May 20XX. He became aware of anorexia and fatigue on day 27. He was diagnosed with fulminant type 1 diabetes mellitus caused by durvalumab with hyperglycemia of 761 mg/dl, positive urine ketones, and urinary C-peptide of 3.9 μg/day on the second course of treatment (day 30). After his blood glucose level had been stabilized with insulin therapy, an additional three cycles of chemotherapy with carboplatin and etoposide were administered. A significant response was achieved, and the patient survived without disease progression. Conclusion. Fulminant type 1 diabetes mellitus caused by durvalumab for small-cell lung cancer is a rare but urgent immune-related adverse event that requires attention.

    DOI： 10.2482/haigan.62.323

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  • Eosinophilic chronic rhinosinusitis accompanied by asthma with dissimilar upper and lower airway responsiveness to mepolizumab and dupilumab: A case report

    Hosoya Kei, Komachi Taro, Hirose Takashi, Sato Kazuki, Okubo Kimihiro

    Journal of Immunology, Allergy and Infection in Otorhinolaryngology   2 ( 2 )   59 - 64   2022

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    Language：Japanese   Publisher：Japan Society of Immunology, Allergology and Infection in Otorhinolaryngology  

    Eosinophilic chronic rhinosinusitis (ECRS) is often associated with asthma and serves as a risk factor for frequent asthma exacerbation. Recent studies have reported the usefulness of biologics for management of ECRS and asthma in patients who are unresponsive to oral steroids.

    A man in his 70s was diagnosed with aspirin-induced asthma and chronic obstructive pulmonary disease approximately 5 years prior to presentation. Mepolizumab therapy was initiated owing to unresponsiveness to treatment including oral steroid administration. Asthma attacks reduced in frequency; however, oral steroids could not be withdrawn. The patient developed nasal symptoms following a 28-month course of mepolizumab therapy, which was therefore switched to dupilumab to improve sinusitis and asthma. The patient was diagnosed with severe ECRS based on a Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis score of 15, asthma, and biopsy proven evidence of nasal polyps. Nasal symptoms, except for olfactory dysfunction and sinusitis improved following 7-month dupilumab treatment; however, lung dysfunction and asthma persisted.

    Close interdisciplinary collaboration between Respiratory Medicine and Otorhinolaryngology is essential for accurate evaluation and treatment of patients with dissimilar responsiveness of the upper and lower respiratory tracts to treatment with the aforementioned medications.

    DOI： 10.24805/jiaio.2.2_59

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  • 免疫チェックポイント阻害剤投与後に発症した、免疫関連有害事象による副腎機能低下症の3例

    宮下 稜太, 中山 幸治, 齊藤 翔, 渥美 健一郎, 廣瀬 敬, 久保田 馨, 清家 正博, 弦間 昭彦

    肺癌   61 ( 7 )   992 - 992   2021.12

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  • A prospective, phase II trial of monotherapy with low-dose afatinib for patients with EGFR, mutation-positive, non-small cell lung cancer: Thoracic oncology research group 1632. International journal

    Rintaro Noro, Satoshi Igawa, Akihiro Bessho, Takashi Hirose, Tsuneo Shimokawa, Masanao Nakashima, Koichi Minato, Nobuhiko Seki, Takaaki Tokito, Toshiyuki Harada, Shinji Sasada, Shingo Miyamoto, Yosuke Tanaka, Naoki Furuya, Takayuki Kaburagi, Hideki Hayashi, Hirotoshi Iihara, Hiroaki Okamoto, Kaoru Kubota

    Lung cancer (Amsterdam, Netherlands)   161   49 - 54   2021.11

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    OBJECTIVES: Afatinib is an effective treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). However, the toxicity associated with this agent often leads to dose modifications. The aim of this study was to assess the efficacy, safety and plasma concentrations of low dose afatinib monotherapy in patients with EGFR mutation-positive NSCLC. PATIENTS AND METHODS: This was a multicenter, single-arm, open-label, phase II trial involving treatment-naïve patients with advanced EGFR mutation-positive NSCLC. From March 2017 to September 2018, 53 patients were enrolled from 21 institutions in Japan. Patients initially received afatinib 20 mg/day orally. For patients in whom the tumor progressed within stable disease, the investigators were able to increase the afatinib dose (10 mg increments). The primary endpoint was progression-free survival (PFS). The threshold and expected median PFS was 9.2 and 13.8 months, respectively. Additionally, the correlation of the plasma concentration of low-dose afatinib with clinical outcome and adverse events were evaluated. RESULTS: The median age of patients was 70 years (range: 37-85 years); 28 patients (52.8%) were females. The median duration of the follow-up was 20.8 months. The median PFS, and overall survival were 12.6 months (90% confidence interval [CI]: 9.7-14.3 months), and not reached, respectively. The primary endpoint was met. The objective response rate and disease control rate were 66.0% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9), respectively. Grade ≥ 3 adverse events occurred in 12 patients (22.6%), including diarrhea in four patients (7.5%). The rate of adverse events was lower than that observed in previous phase III studies of 40 mg afatinib. CONCLUSION: Based on its promising clinical efficacy and tolerability profile, monotherapy with low-dose afatinib should become one of the standard therapies for EGFR mutation-positive NSCLC.

    DOI： 10.1016/j.lungcan.2021.08.007

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  • EGFR遺伝子変異陽性肺癌における繰り返し再生検の有効性とオシメルチニブの効果

    廣瀬 敬, 渥美 健一郎, 加藤 祐樹, 宮寺 恵希, 久金 翔, 久保田 馨, 清家 正博, 弦間 昭彦

    肺癌   61 ( 6 )   602 - 602   2021.10

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  • EGFR遺伝子変異陽性肺癌における繰り返し再生検の有効性とオシメルチニブの効果

    廣瀬 敬, 渥美 健一郎, 加藤 祐樹, 宮寺 恵希, 久金 翔, 久保田 馨, 清家 正博, 弦間 昭彦

    肺癌   61 ( 6 )   602 - 602   2021.10

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  • 既治療進行非小細胞肺癌に対するnab-paclitaxelの至適用量を検討するランダム化第II相試験(JMTO LC14-01)

    戸井 之裕, 武内 進, 菅原 俊一, 手良向 聡, 野呂 林太郎, 藤川 桂, 廣瀬 敬, 安宅 信二, 南 誠剛, 飯田 慎一郎, 倉石 博, 相羽 智生, 河原 正明, 峯岸 裕司, 松本 優, 清家 正博, 弦間 昭彦, 久保田 馨

    肺癌   61 ( 6 )   550 - 550   2021.10

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  • 黒色胸水を契機に診断された膵胸腔瘻の1例

    宮寺 恵希, 久金 翔, 加藤 祐樹, 渥美 健一郎, 大野 弘貴, 田中 周, 久保田 馨, 清家 正博, 弦間 昭彦, 廣瀬 敬

    日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会合同学会プログラム・抄録集   180回・246回   18 - 18   2021.9

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  • 黒色胸水を契機に診断された膵胸腔瘻の1例

    宮寺 恵希, 久金 翔, 加藤 祐樹, 渥美 健一郎, 大野 弘貴, 田中 周, 久保田 馨, 清家 正博, 弦間 昭彦, 廣瀬 敬

    日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会合同学会プログラム・抄録集   180回・246回   18 - 18   2021.9

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  • 特集 内科疾患の診断基準･病型分類･重症度 第1章 呼吸器 肺がん

    廣瀬 敬

    内科   127 ( 4 )   531 - 533   2021.4

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  • 間質性肺炎に伴う肺高血圧症に対する%FVC/%DLcoの有用性の検討

    渥美 健一郎, 田中 徹, 柏田 建, 田中 庸介, 齋藤 好信, 藤田 和恵, 廣瀬 敬, 清家 正博, 吾妻 安良太, 木村 弘, 弦間 昭彦

    日本呼吸器学会誌   10 ( 増刊 )   303 - 303   2021.4

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  • 間質性肺炎に伴う肺高血圧症に対する%FVC/%DLcoの有用性の検討

    渥美 健一郎, 田中 徹, 柏田 建, 田中 庸介, 齋藤 好信, 藤田 和恵, 廣瀬 敬, 清家 正博, 吾妻 安良太, 木村 弘, 弦間 昭彦

    日本呼吸器学会誌   10 ( 増刊 )   303 - 303   2021.4

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  • Atezolizumab併用化学療法中にANCA関連血管炎を発症した一例

    齊藤 翔, 中山 幸治, 宮下 稜太, 渥美 健一郎, 中里 玲, 金子 朋広, 永田 耕治, 清水 章, 久保田 馨, 清家 正博, 弦間 昭彦, 廣瀬 敬

    日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会合同学会プログラム・抄録集   179回・243回   22 - 22   2021.2

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  • 特集 いま知っておきたい! 内科最新トピックス 巻頭トピックス 保険収載された肺がん診療における遺伝子パネル検査とテイラーメイド治療

    廣瀬 敬

    内科   126 ( 3 )   330 - 332   2020.9

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  • 高齢者進行再発非小細胞肺癌に対する抗PD-1/PD-L1抗体の有効性と安全性の検討

    清水 理光, 中道 真仁, 宮下 稜太, 宮寺 恵希, 村田 泰規, 菅野 哲平, 峯岸 裕司, 野呂 林太郎, 廣瀬 敬, 久保田 馨, 清家 正博, 弦間 昭彦

    肺癌   59 ( 6 )   731 - 731   2019.11

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  • 肺扁平上皮癌に合併したpulmonary tumor thrombotic microangiopathy(PTTM)の1剖検例

    清水 理光, 谷内 七三子, 戸塚 猛大, 恩田 直美, 村田 泰規, 廣瀬 敬, 細根 勝, 清家 正博, 久保田 馨, 弦間 昭彦

    肺癌   59 ( 2 )   184 - 185   2019.4

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  • Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. International journal

    Shigeaki Suzuki, Nobuhisa Ishikawa, Fumie Konoeda, Nobuhiko Seki, Satoshi Fukushima, Kikuko Takahashi, Hisashi Uhara, Yoshikazu Hasegawa, Shinichiro Inomata, Yasushi Otani, Kenji Yokota, Takashi Hirose, Ryo Tanaka, Norihiro Suzuki, Makoto Matsui

    Neurology   89 ( 11 )   1127 - 1134   2017.9

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    OBJECTIVE: To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan. METHODS: We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used. RESULTS: There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 women with a mean age of 73.5 ± 6.3 years. MG onset occurred in the early phase after nivolumab treatment and rapidly deteriorated. Nivolumab-related MG (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti-acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients' daily living activity. CONCLUSIONS: The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.

    DOI： 10.1212/WNL.0000000000004359

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Misc.

  • 術後プラチナ併用化学療法後の再発非小細胞肺癌に対するプラチナ併用化学療法±ICIの有効性と安全性の検討

    久金 翔, 戸塚 猛大, 高橋 聡, 谷内 七三子, 西島 伸彦, 渥美 健一郎, 小齊平 聖治, 神尾 孝一郎, 岡野 哲也, 弦間 昭彦, 清家 正博, 廣瀬 敬

    肺癌   62 ( 6 )   593 - 593   2022.11

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  • 術後プラチナ併用化学療法後の再発非小細胞肺癌に対するプラチナ併用化学療法±ICIの有効性と安全性の検討

    久金 翔, 戸塚 猛大, 高橋 聡, 谷内 七三子, 西島 伸彦, 渥美 健一郎, 小齊平 聖治, 神尾 孝一郎, 岡野 哲也, 弦間 昭彦, 清家 正博, 廣瀬 敬

    肺癌   62 ( 6 )   593 - 593   2022.11

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  • Nivolumab+Ipilimumab投与中に胸膜炎症状のpseudoprogressionを呈した胸膜播種を伴う肺癌の1例

    寺嶋 勇人, 渥美 健一郎, 寺師 直樹, 鈴木 彩奈, 久金 翔, 廣瀬 敬, 永田 耕治

    肺癌   62 ( 3 )   269 - 269   2022.6

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    Language：Japanese   Publisher：(NPO)日本肺癌学会  

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  • デュルバルマブ投与後に激症1型糖尿病を発症した小細胞肺癌の1例

    寺師 直樹, 久金 翔, 宮寺 恵希, 寺嶋 勇人, 鈴木 彩奈, 渥美 健一郎, 廣瀬 敬, 清家 正博, 弦間 昭彦

    肺癌   62 ( 2 )   139 - 139   2022.4

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  • COVID-19感染の回復期の白血球像の分析

    渥美 健一郎, 久金 翔, 鈴木 彩奈, 清家 正博, 弦間 昭彦, 廣瀬 敬

    第62回日本呼吸器学会学術集会   11 ( 増刊 )   234 - 234   2022.4

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  • 肺扁平上皮癌に対するPembrolizumab投与中に発症した耳介軟骨炎の1例

    寺嶋 勇人, 渥美 健一郎, 寺師 直樹, 鈴木 彩奈, 久金 翔, 永田 耕治, 細矢 慶, 清家 正博, 弦間 昭彦, 廣瀬 敬

    日本内科学会関東地方会   676回   70 - 70   2022.3

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    J-GLOBAL

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  • 既治療進行非小細胞肺癌に対するnab-paclitaxelの至適用量を検討するランダム化第II相試験(JMTO LC14-01)

    戸井 之裕, 武内 進, 菅原 俊一, 手良向 聡, 野呂 林太郎, 藤川 桂, 廣瀬 敬, 安宅 信二, 南 誠剛, 飯田 慎一郎, 倉石 博, 相羽 智生, 河原 正明, 峯岸 裕司, 松本 優, 清家 正博, 弦間 昭彦, 久保田 馨

    肺癌   61 ( 6 )   550 - 550   2021.10

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    Language：Japanese   Publisher：(NPO)日本肺癌学会  

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  • ステロイドパルス治療が不応の特発性肺胞出血に対し血漿交換治療が奏功した一例

    岡村 賢, 恩田 直美, 中山 幸治, 村田 泰規, 久保田 馨, 清家 正博, 弦間 昭彦, 廣瀬 敬

    日本結核病学会関東支部学会・日本呼吸器学会関東地方会合同学会プログラム・抄録集   176回・236回   5 - 5   2019.9

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    Language：Japanese   Publisher：日本結核病学会関東支部学会・日本呼吸器学会関東地方会  

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  • 多彩な肺病変を呈し,診断に気管支鏡検査が有用であった急性型成人T細胞リンパ腫の1例

    矢嶋 知佳, 清水 理光, 村田 泰規, 谷内 七三子, 了徳寺 剛, 栗林 泰子, 尾崎 勝俊, 久保田 馨, 清家 正博, 弦間 昭彦, 廣瀬 敬

    気管支学   40 ( Suppl. )   S345 - S345   2018.5

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  • 長期間bevacizumab投与により効果が持続している3症例

    村田 泰規, 矢嶋 知佳, 清水 理光, 谷内 七三子, 廣瀬 敬, 久保田 馨, 清家 正博, 弦間 昭彦

    肺癌   58 ( 2 )   163 - 163   2018.4

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  • 化学療法の導入時期と生存期間の相関について

    村田 泰規, 矢嶋 知佳, 清水 理光, 谷内 七三子, 久保田 馨, 弦間 昭彦, 廣瀬 敬

    日本呼吸器学会誌   7 ( 増刊 )   243 - 243   2018.3

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  • 再発進行非小細胞肺癌に対するPD-1阻害剤投与後の殺細胞性抗癌剤の有効性と安全性の検討

    村田 泰規, 小林 由美子, 清水 理光, 谷内 七三子, 久保田 馨, 弦間 昭彦, 廣瀬 敬

    肺癌   57 ( 5 )   607 - 607   2017.9

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  • Nab-パクリタキセルによる二次治療により完全奏効に近い効果が維持された再発進行非小細胞肺癌の1例

    清水 理光, 宮 敏路, 高橋 彬彦, 小林 由美子, 久保田 馨, 弦間 昭彦, 廣瀬 敬

    癌と化学療法   44 ( 8 )   699 - 702   2017.8

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    Language：Japanese   Publisher：(株)癌と化学療法社  

    症例は62歳、女性。左下葉原発肺腺癌、cT2N2M1b、stage IV(脳転移)、EGFR遺伝子変異陰性の診断で脳転移切除後、カルボプラチン(AUC5)とペメトレキセド(500mg/m2)併用療法を6コース施行し、部分奏効(partial response:PR)が得られた。その後、ペメトレキセド単剤による維持療法を14コース施行後に原発巣の増大を認め、増悪(progressive disease:PD)と診断した。2014年1月より二次治療としてnab-パクリタキセル(100mg/m2)を開始したところ、完全奏効(complete response:CR)に近い奏効が得られ、約3年間40コース維持し、重篤な有害事象を認めていない。二次治療としてのnab-パクリタキセル単剤治療のエビデンスは十分ではないが、再発進行非小細胞肺癌に対し有効な治療選択肢の一つとなり得ると考えられた。(著者抄録)

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  • 経気管支肺生検にて診断したTS-1による薬剤性肺傷害の1例

    清水 理光, 名児耶 浩幸, 高橋 彬彦, 小林 由美子, 竹ヶ原 京志郎, 吉野 直之, 吾妻 安良太, 久保田 馨, 弦間 昭彦, 廣瀬 敬

    気管支学   39 ( Suppl. )   S305 - S305   2017.5

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  • 進行非小細胞肺癌に対する薬物療法の進歩と治療戦略

    廣瀬 敬

    日本医科大学医学会雑誌   12 ( 4 )   146   2016

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    Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)   Publisher：日本医科大学医学会  

    DOI： 10.1272/manms.12.146

    CiNii Research

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    Other Link： https://search.jamas.or.jp/link/ui/2017083053

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Research Projects

  • Elucidation of trans-activation mechanism from TRAIL receptor to EGFR

    Grant number：23590308  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    OHMORI Tohru, YAMAOKA Toshimitsu, HIROSE Takashi

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    Grant amount：\5200000 （ Direct Cost: \4000000 、 Indirect Cost：\1200000 ）

    We established EGFR-TKI-resistant non-small cell lung cancer (NSCLC) cell lines and found that these cell lines acquired collateral sensitivity to Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (about 70 times) as compared with parental cell line. In parental PC-9, anti-tumor effect of TRAIL was restricted, because TRAIL activates not only apoptotic signaling but also anti-apoptotic signaling through Akt/NFkB activation by cross talk signaling from TRAIL receptor to EGFR. In case of the resistant cell lines that overexpressed c-MET, the crosstalk signaling from TRAIL receptor to c-MET was not observed, and TRAIL-mediated Akt/NFkB activation was quite diminished. From these observations, EGFR-TKI/TRAIL combination is thought to be useful therapy for NSCLC.

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  • Association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced non-small cell lung cancer

    Grant number：23590648  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HIROSE Takashi

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    The orally administered erlotinib showed large interindividual variability in its pharmacokinetics. The aim of this study was to evaluate the association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced NSCLC. Plasma concentration of erlotinib was analyzed by high-performance liquid chromatography. The genotypes of ABCG2, ABCB1, ABCC2, CYP3A4, CYP3A5, CYP1A1, and CYP1A2 were analyzed by direct sequencing.
    There were no statistically significant association of pharmacokinetics or pharmacogenomics with toxicity, such as skin toxicity, diarrhea, stomatitis, liver injury, and interstitial lung disease (ILD) of erlotinib. However, one patient died of drug induced ILD was homozygous for ABCG2 C>A and showed the highest AUC. Additionally, Cmax was trend toward to higher in 4 patients with liver injury than those without (p=0.054). In conclusion, the homozygote of ABCG2 C>A could be associated with elevated erlotinib exposure and drug-induced ILD.

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  • The role of ADAM17 in squamous cell lung cancer

    Grant number：22501051  2010.10 - 2014.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    SIRAI Takao, YAMAOKA Toshimitsu, OHMORI Tohru, HIROSE Takashi, KADOKURA Mitsutaka, ADACHI Mitsuru

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    Grant amount：\3510000 （ Direct Cost: \2700000 、 Indirect Cost：\810000 ）

    Epidermal growth factor receptor (EGFR) overexpression and aberrant activation are frequently identified in non small cell lung carcinoma (NSCLC). Although EGFR-targeted therapies (i.e.: EGFR-TKIs, and anti-EGFR antibody) are used, the prognosis of NSCLC remains poor. ADAM17 induces activation of EGFR through EGF-like ligand cleavage. We hypothesized that the inflammatory cytokines and EGF-like ligands might up-regulate the expression of EGFR via ADAM17, leading to the resistance to EGFR-TKIs in squamous cell carcinoma of lung. These findings promisingly indicate additional therapeutic strategies and the understanding of tumorigenesis for NSCLC.

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