Faculty Profiles - TOYOOKA Shinichi

Papers - TOYOOKA Shinichi

Division display 461 - 480 of about 940 ／ All the affair displays >>

Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer. Reviewed International journal

Hiroki Sato, Hiromasa Yamamoto, Masakiyo Sakaguchi, Kazuhiko Shien, Shuta Tomida, Tadahiko Shien, Hirokuni Ikeda, Minami Hatono, Hidejiro Torigoe, Kei Namba, Takahiro Yoshioka, Eisuke Kurihara, Yusuke Ogoshi, Yuta Takahashi, Junichi Soh, Shinichi Toyooka

Cancer science 109 ( 10 ) 3183 - 3196 2018.10

Language：English Publishing type：Research paper (scientific journal)

Compensatory activation of the signal transduction pathways is one of the major obstacles for the targeted therapy of non-small cell lung cancer (NSCLC). Herein, we present the therapeutic strategy of combined targeted therapy against the MEK and phosphoinositide-3 kinase (PI3K) pathways for acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC. We investigated the efficacy of combined trametinib plus taselisib therapy using experimentally established EGFR-TKI-resistant NSCLC cell lines. The results showed that the feedback loop between MEK/ERK and PI3K/AKT pathways had developed in several resistant cell lines, which caused the resistance to single-agent treatment with either inhibitor alone. Meanwhile, the combined therapy successfully regulated the compensatory activation of the key intracellular signals and synergistically inhibited the cell growth of those cells in vitro and in vivo. The resistance mechanisms for which the dual kinase inhibitor therapy proved effective included (MET) mesenchymal-epithelial transition factor amplification, induction of epithelial-to-mesenchymal transition (EMT) and EGFR T790M mutation. In further analysis, the combination therapy induced the phosphorylation of p38 MAPK signaling, leading to the activation of apoptosis cascade. Additionally, long-term treatment with the combination therapy induced the conversion from EMT to mesenchymal-to-epithelial transition in the resistant cell line harboring EMT features, restoring the sensitivity to EGFR-TKI. In conclusion, our results indicate that the combined therapy using MEK and PI3K inhibitors is a potent therapeutic strategy for NSCLC with the acquired resistance to EGFR-TKIs.

DOI： 10.1111/cas.13763

PubMed

researchmap

Low-risk donor lungs optimize the post-lung transplant outcome for high lung allocation score patients. Reviewed

Takeshi Kurosaki, Kentaroh Miyoshi, Shinji Otani, Kentaro Imanishi, Seiichiro Sugimoto, Masaomi Yamane, Motomu Kobayashi, Shinichi Toyooka, Takahiro Oto

Surgery today 48 ( 10 ) 928 - 935 2018.10

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The lung allocation score (LAS) has been generally recognized as a contributor to the overall survival in lung transplant candidates. However, donor-related risks have never been taken into consideration in previous research that validated the LAS. This study aimed to determine whether or not the role of the LAS as a predictor of the posttransplant outcome is influenced by the quality of the donor lungs. METHODS: We retrospectively reviewed 108 patients who underwent lung transplantation at Okayama University Hospital since 1998. The cohort was divided into two groups based on the lung donor score (DS; ≤ 4/> 4). Correlations between the LAS and posttransplant outcomes were investigated in both groups. RESULTS: In the high-DS group, an elevated LAS was strongly associated with posttransplant PaO2/FiO2 (p = 0.018). However, in the low-DS group, no correlation was found between them. There was no significant difference in the long-term survival according to the LAS in the low-DS group. The LAS effectively predicted the posttransplant outcome only when lungs with DS > 4 were transplanted; the LAS was not reliable if high-quality lungs were transplanted. CONCLUSION: Lung transplantation can be feasible and provides a survival benefit even for high-LAS patients if lungs from a low-risk donor are transplanted.

DOI： 10.1007/s00595-018-1670-7

PubMed

researchmap

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 2018.10

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 2018.10

肺癌におけるPrecision Medicineの現状と今後の展開肺癌のゲノム異常と治療の課題

豊岡伸一, 枝園和彦, 山本寛斉, 宗淳一, 冨田秀太

日本癌治療学会学術集会抄録集 56回 PD3 - 2 2018.10

非小細胞肺癌完全切除例に対する術後補助化学療法におけるERCC1の効果予測因子としての意義

中田昌男, 最相晋輔, 宗淳一, 奥村典仁, 中村廣繁, 山下素弘, 多田弘人, 森田智視, 豊岡伸一, 伊達洋至, 瀬戸内肺癌研究会

肺癌 58 ( 6 ) 516 - 516 2018.10

Myoepithelioma occurring in the posterior mediastinum harboring EWSR1 rearrangement: a case report. Reviewed International journal

Tomohiro Habu, Junichi Soh, Tomohiro Toji, Kazuhiko Shien, Eito Niman, Kei Namba, Hiroki Sato, Hiromasa Yamamoto, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Japanese journal of clinical oncology 48 ( 9 ) 851 - 854 2018.9

Language：English Publishing type：Research paper (scientific journal)

Myoepithelioma is a rare neoplasm usually occurring in the salivary glands or the mammary glands but also, more rarely, in the thoracic cavity. The diagnosis of myoepithelioma is based on the presence of histological and immunohistochemical characteristics of myoepithelioma, but in unusual locations, the diagnosis is challenging. For such cases, cytogenetic approaches have been developed as helpful tools for the diagnosis. We report a surgical case of 51-year-old woman with myoepithelioma occurring in the posterior mediastinum that harbored the Ewing sarcoma breakpoint region1 (EWSR1) gene rearrangement. To the best of our knowledge, this is the first report of a myoepithelioma occurring in the posterior mediastinum. In this case, the patient underwent the thoracoscopic surgery for a diagnostic tumorectomy and was diagnosed as myoepithelioma based on the following immunohistological findings. Considering the unusual location, we additionally performed a cytogenetic analysis to confirm the presence of the EWSR1 gene rearrangement, which is a genetic characteristic of myoepithelioma.

DOI： 10.1093/jjco/hyy100

PubMed

researchmap

Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients. Reviewed

Seiichiro Sugimoto, Masaomi Yamane, Shinji Otani, Takeshi Kurosaki, Shuji Okahara, Yukiko Hikasa, Shinichi Toyooka, Motomu Kobayashi, Takahiro Oto

Surgery today 48 ( 9 ) 848 - 855 2018.9

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Airway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes. METHODS: We reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT. RESULTS: The incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25). CONCLUSION: ACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

DOI： 10.1007/s00595-018-1663-6

PubMed

researchmap

HER増幅胃癌におけるアファチニブ耐性機序(Acquired resistant mechanism to afatinib in HER2 amplified gastric cancer cells)

吉岡貴裕, 枝園和彦, 難波圭, 冨田秀太, 山本寛斉, 宗淳一, 藤原俊義, 豊岡伸一

日本癌学会総会記事 77回 1449 - 1449 2018.9

EGFR変異陽性肺癌におけるLRIG1の抗腫瘍効果(Tumor-suppressive effect of LRIG1 in non-small cell lung cancer harboring mutant EGFR)

鳥越英次郎, 山本寛斉, 阪口政清, 難波圭, 佐藤博紀, 枝園和彦, 諏澤憲, 宗淳一, 冨田秀太, 佃和憲, 三好新一郎, 豊岡伸一

日本癌学会総会記事 77回 940 - 940 2018.9

がん転移抑制剤としての効果を有するS100A8/A9中和抗体の開発(Development of a novel S100A8/A9 neutralizing monoclonal antibody for suppression of cancer metastasis)

木下理恵, 山内明, 枝園和彦, 冨田秀太, 村田等, 豊岡伸一, 近藤英作, 阪口政清

日本癌学会総会記事 77回 1608 - 1608 2018.9

Inherited lung cancer syndromes targeting never smokers. Reviewed

Yamamoto H, Yatabe Y, Toyooka S

Translational lung cancer research 7 ( 4 ) 498 - 504 2018.8

病理病期IB〜IIIA期非小細胞肺癌完全切除症例に対する術後補助化学療法無作為化比較第3相試験(SLCG0401)

井上啓爾, 福田実, 竹之内光広, 一瀬幸人, 高森信三, 奥村典仁, 松尾恵太郎, 宗淳一, 豊岡伸一, 伊達洋至

肺癌 58 ( 4 ) 303 - 303 2018.8

Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms. Reviewed International journal

I Made Winarsa Ruma, Rie Kinoshita, Nahoko Tomonobu, Yusuke Inoue, Eisaku Kondo, Akira Yamauchi, Hiroki Sato, I Wayan Sumardika, Youyi Chen, Ken-Ichi Yamamoto, Hitoshi Murata, Shinichi Toyooka, Masahiro Nishibori, Masakiyo Sakaguchi

Cancers 10 ( 7 ) 2018.7

Language：English Publishing type：Research paper (scientific journal)

Embigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is involved in prostate and mammary gland development. As embigin's roles in cancer remain elusive, we studied its biological functions and interaction with extracellular S100A4 in prostate cancer progression. We found by a pull-down assay that embigin is a novel receptor for S100A4, which is one of the vital cancer microenvironment milleu. Binding of extracellular S100A4 to embigin mediates prostate cancer progression by inhibition of AMPK activity, activation of NF-κB, MMP9 and mTORC1 signaling, and inhibition of autophagy, which increase prostate cancer cell motility. We also found that embigin promotes prostate cancer growth, spheroid- and colony-forming ability, and survival upon chemotherapy independently of S100A4. An in vivo growth mouse model confirmed the importance of embigin and its cytoplasmic tail in mediating prostate tumor growth. Moreover, embigin and p21WAF1 can be used to predict survival of prostate cancer patients. Our results demonstrated for the first time that the S100A4-embigin/AMPK/mTORC1/p21WAF1 and NF-κB/MMP9 axis is a vital oncogenic molecular cascade for prostate cancer progression. We proposed that embigin and p21WAF1 could be used as prognostic biomarkers and a strategy to inhibit S100A4-embigin binding could be a therapeutic approach for prostate cancer patients.

DOI： 10.3390/cancers10070239

PubMed

researchmap

悪性胸膜中皮腫に対するREIC/Dkk-3遺伝子治療

山本寛斉, 諏澤憲, 枝園和彦, 宗淳一, 黒崎毅史, 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

日本がん免疫学会総会プログラム・抄録集 22回 146 - 146 2018.7