研究者詳細 - 豊岡　伸一

論文 - 豊岡　伸一

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Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer. 査読国際誌

Kosuke Ochi, Ken Suzawa, Shuta Tomida, Kazuhiko Shien, Jui Takano, Shunsaku Miyauchi, Tatsuaki Takeda, Akihiro Miura, Kota Araki, Kentaro Nakata, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Tadahiko Shien, Masaomi Yamane, Kazuo Azuma, Yoshiharu Okamoto, Shinichi Toyooka

Biochemical and biophysical research communications 529 ( 3 ) 760 - 765 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors. MATERIALS AND METHODS: A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed. RESULTS: TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor. CONCLUSION: Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance.

DOI： 10.1016/j.bbrc.2020.06.077

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A phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with solid cancers harboring human epidermal growth factor receptor 2 amplification (JUPITER trial). 国際誌

Kenta Takahashi, Eri Ishibashi, Toshio Kubo, Yohei Harada, Hideyuki Hayashi, Masayuki Kano, Yasushi Shimizu, Hidekazu Shirota, Yukiko Mori, Manabu Muto, Chikashi Ishioka, Hirotoshi Dosaka-Akita, Hisahiro Matsubara, Hiroshi Nishihara, Naoko Sueoka-Aragane, Shinichi Toyooka, Akihiro Hirakawa, Ukihide Tateishi, Satoshi Miyake, Sadakatsu Ikeda

Medicine 99 ( 32 ) e21457 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. However, even if an actionable gene alteration is found, the incidence of HER2 amplification in these cancers is less than 5%. It is too difficult to conduct a conventional randomized, controlled trial in a rare fraction. Therefore, we have designed a organ-agnostic basket study, which covers a variety of solid cancers harboring HER2 amplification, in 1 study protocol. METHODS/DESIGN: This trial is a multicenter, single-arm, basket phase 2 study in Japan. Patients with solid cancers harboring HER2 amplification that have progressed with standard treatment, or rare cancers for which there is no standard treatment, will be eligible. Target cancers include bile duct, urothelial, uterine, ovarian, and other solid cancers where HER2 amplification is detected by comprehensive genomic profiling using next-generation sequencing technology. A total of 38 patients will be treated with combination therapy with trastuzumab and pertuzumab every 3 weeks until disease progression, unmanageable toxicity, death, or patient refusal. The primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, and duration of response. DISCUSSION: The aim of this trial is to evaluate the safety and efficacy of combination therapy with trastuzumab and pertuzumab in patients with locally advanced or metastatic, solid cancers harboring HER2 amplification. Instead of focusing on 1 organ type, our trial design uses a basket study focusing on HER2 amplification, regardless of the site or origin of the cancer. The results of our study will advance clinical and scientific knowledge concerning the treatment of locally advanced, rare solid cancers harboring HER2 amplification, using the combination of trastuzumab and pertuzumab. TRIAL REGISTRATION: This trial was registered in Japan Registry of Clinical Trials (jCRT) on February 25, 2019, as jRCT2031180150.

DOI： 10.1097/MD.0000000000021457

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The neutrophil-to-lymphocyte ratio as a novel independent prognostic factor for multiple metastatic lung tumors from various sarcomas. 査読

Hiromasa Yamamoto, Kei Namba, Haruchika Yamamoto, Tomohiro Toji, Junichi Soh, Kazuhiko Shien, Ken Suzawa, Takeshi Kurosaki, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Katsuhito Takahashi, Toshiyuki Kunisada, Takahiro Oto, Shinichi Toyooka

Surgery today 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Sarcomas are among the most refractory malignant tumors and often recur as pulmonary metastasis. Although the presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with the prognosis of several malignancies, the relationship between the NLR and sarcoma with pulmonary metastasis is unclear. We investigated the impact of the NLR in patients who underwent surgical resection for metastatic lung tumors from various sarcomas. METHODS: The subjects of this retrospective study were 158 patients with metastatic lung tumors from various sarcomas, who underwent initial pulmonary metastasectomy between 2006 and 2015. We examined the clinicopathological variables, including the NLR and the characteristics of surgical procedures. Survival was estimated by the Kaplan-Meier method and prognostic factors were evaluated by multivariate analysis. RESULTS: Multivariate analysis revealed significantly better survival of the group with an NLR < 2.26 immediately before the most recent pulmonary metastasectomy, in addition to such factors as the largest resected lesion being < 22 mm, a disease-free interval of > 2 years, and 3 or more pulmonary metastasectomies. CONCLUSION: The NLR immediately before the most recent pulmonary metastasectomy is a novel independent prognostic factor, which may be helpful when considering repeated pulmonary metastasectomy.

DOI： 10.1007/s00595-020-02093-5

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Fibrosis or Necrosis in Resected Lymph Node Indicate Metastasis Before Chemoradiotherapy in Lung Cancer Patients. 査読国際誌

Yuta Takahashi, Junichi Soh, Kazuhiko Shien, Hiromasa Yamamoto, Masaomi Yamane, Katsuyuki Kiura, Susumu Kanazawa, Hiroyuki Yanai, Shinichi Toyooka

Anticancer research 40 ( 8 ) 4419 - 4423 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIM: The histological features of lymph nodes (LNs) treated by chemoradiotherapy (CRT) in non-small cell lung cancer (NSCLC) have not been well studied. The purpose of this study was to evaluate the histological findings of LNs affected by CRT. PATIENTS AND METHODS: Among 107 clinically N2 NSCLC patients who underwent induction CRT followed by surgery from 1999 to 2017, 24 patients who received pathological evaluation of mediastinal LN before CRT were enrolled in this study. Postoperatively, we histologically reviewed all resected LNs (n=117) of the station evaluated before CRT. RESULTS: Fibrosis and/or necrosis were observed in all investigated LN stations. Histological observation of fibrosis and/or necrosis in the resected LNs after CRT indicated the presence of LN metastasis before CRT. CONCLUSION: The metastatic LNs that responded to CRT showed specific histological features, which enabled us to know the accurate clinical stage of the patient even though cancer cells were not found in the post-treated LNs.

DOI： 10.21873/anticanres.14447

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ウェットラボでのノンテクニカルスキル評価システムの有用性の検討

山根正修, 杉本誠一郎, 岡崎幹生, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) RO28 - 2 2020年8月

肉腫多発肺転移に対する肺切除術

山本寛斉, 諏澤憲, 三好健太郎, 大谷真二, 岡崎幹生, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) O44 - 7 2020年8月

進化する外科マネージメントセンターそれぞれの夢を実現するためのキャリアパス支援システム

菊地覚次, 黒田新士, 吉田龍一, 香川俊輔, 山根正修, 小谷恭弘, 笠原真悟, 豊岡伸一, 藤原俊義

日本外科学会定期学術集会抄録集 120回 SP - 8 2020年8月

外科系新専門医制度の発展・継続を加速する広域指導者養成プログラムの開発・運用

山根正修, 万代康弘, 伊野英男, 豊岡伸一

日本外科学会定期学術集会抄録集 120回 SSF - 2 2020年8月

自然気胸後の器質化期膿胸に対する醸膿胸膜切除術明瞭な臓側胸膜外層の同定に基づいた剥離

清水大, 三好健太郎, 松原慧, 山本治慎, 諏澤憲, 大谷真二, 山本寛斎, 岡崎幹生, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) MO59 - 10 2020年8月

肉腫多発肺転移に対する肺切除術

山本寛斉, 諏澤憲, 三好健太郎, 大谷真二, 岡崎幹生, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) O44 - 7 2020年8月

抗HMGB1抗体による肺虚血再灌流障害の抑制

中田憲太郎, 岡崎幹生, 清水大, 宮内俊作, 荒木恒太, 三浦章博, 塩谷俊雄, 諏澤憲, 三好健太郎, 大谷真二, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛弘, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) O47 - 4 2020年8月

気胸を合併し、発見された肺原発血管肉腫の1切除例

毛利謙吾, 岡崎幹生, 塩谷俊雄, 諏澤憲, 三好健太郎, 大谷真二, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) SP4 - 3 2020年8月

肺移植から学ぶ呼吸器外科学肺移植から学ぶゲノム医療

杉本誠一郎, 塩谷俊雄, 山本治慎, 田中真, 諏澤憲, 三好健太郎, 大谷真二, 山本寛斉, 岡崎幹生, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) S - 7 2020年8月

ロボット支援下肺葉切除術時の肺動脈損傷に対する対応

岡崎幹生, 諏澤憲, 塩谷俊雄, 三好健太郎, 大谷真二, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) V1 - 1 2020年8月

臨床的N0・病理学的リンパ節転移陽性肺がんに対する肺切除の現状

諏澤憲, 三好健太郎, 大谷真二, 山本寛斉, 岡崎幹生, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) O3 - 1 2020年8月

肺移植の問題点と改善策高度無気肺を合併したドナー肺による移植成績

塩谷俊雄, 杉本誠一郎, 山本治慎, 諏澤憲, 三好健太郎, 大谷真二, 山本寛斉, 岡崎幹生, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) PD1 - 3 2020年8月

右下肺静脈・左心房経由で左心室まで浸潤した小細胞肺癌に対する緊急手術の1例

岡崎幹生, 諏澤憲, 塩谷俊雄, 三好健太郎, 大谷真二, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) RV3 - 1 2020年8月

右下肺静脈・左心房経由で左心室まで浸潤した小細胞肺癌に対する緊急手術の1例

岡崎幹生, 諏澤憲, 塩谷俊雄, 三好健太郎, 大谷真二, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) RV3 - 1 2020年8月

ロボット支援下肺葉切除術時の肺動脈損傷に対する対応

岡崎幹生, 諏澤憲, 塩谷俊雄, 三好健太郎, 大谷真二, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) V1 - 1 2020年8月

ウェットラボでのノンテクニカルスキル評価システムの有用性の検討

山根正修, 杉本誠一郎, 岡崎幹生, 豊岡伸一

日本呼吸器外科学会雑誌 34 ( 3 ) RO28 - 2 2020年8月

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