Potential of tumore suppressor FBXW7 as one of the therapeutic targets

2017 Fiscal Year Annual Research Report

• Project/Area Number: 15K10085
• Research Institution: Gunma University
• Principal Investigator: 横堀 武彦 群馬大学, 未来先端研究機構, 講師 (60420098)
• Co-Investigator(Kenkyū-buntansha): 堤 荘一 群馬大学, 医学部附属病院, 講師 (30323356) [Withdrawn] ; 宮崎 達也 群馬大学, 医学部附属病院, 講師 (70372349) ; 酒井 真 群馬大学, 医学部附属病院, 助教 (70420099) ; 桑野 博行 群馬大学, 大学院医学系研究科, 教授 (90186560) ; 緒方 杏一 群馬大学, 医学部附属病院, 助教 (10448897)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: FBXW7

Outline of Annual Research Achievements

腫瘍抑制因子FBXW7の発現意義を免疫染色法にて胃癌臨床検体で評価した。101症例の胃癌臨床検体を用いてFBXW7発現を解析した結果、FBXW7低発現群に予後不良症例が多い傾向を確認することができた(P=0.07)。この結果はFBXW7 mRNAを評価した以前の報告に矛盾しない結果であった。さらにHDAC阻害剤MS-275によるFBXW7発現誘導実験を行いFBXW7の発現誘導を確認することができた。
また、今回の検討で胃癌臨床検体だけでなく術前放射線化学療法を受けた食道扁平上皮癌患者の治療前生検検体におけるFBXW7発現の意義を免疫染色法で評価した。その結果、治療前にFBXW7発現が低下していた症例は有意に治療抵抗性を示し、病理学的治療効果判定で完全奏功症例が有意に少ないことが明らかとなった。この臨床検体での知見を再検証するためにin vitro解析も施行した。in vitro解析ではFBXW7と抗がん剤、放射線感受性の関係を明らかにするためにFBXW7を強制発現させたがん細胞株にCDDP, ネダプラチン、放射線照射を加え、そのFBXW7強制発現が細胞生存率に与える影響を評価した。その結果、腫瘍抑制因子FBXW7高発現癌細胞は有意に細胞生存が抑制されることが明らかとなった。これらのデータをまとめた論文はJournal of Surgical Oncology誌に2018年5月に受理となった。

Research Products

• [Journal Article] Development of single nanometer-sized ultrafine oxygen bubbles to overcome the hypoxia-induced resistance to radiation therapy via the suppression of hypoxia-inducible factor-1α (2018)
  • Author(s): Iijima Misaki、Gombodorj Navchaa、Tachibana Yoshiaki、Tachibana Kohsuke、Yokobori Takehiko、Honma Kyoko、Nakano Takashi、Asao Takayuki、Kuwahara Ryusuke、Aoyama Kazuhiro、Yasuda Hidehiro、Kelly Matthew、Kuwano Hiroyuki、Yamanouchi Dai
  • Journal Title: International Journal of Oncology Volume: 印刷中 Pages: 印刷中
  • DOI: 10.3892/ijo.2018.4248
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High STMN1 Expression Is Associated with Tumor Differentiation and Metastasis in Clinical Patients with Pancreatic Cancer (2018)
  • Author(s): Suzuki K, Watanabe A, Araki K, Yokobori T, Harimoto N, Gantumur D, Hagiwara K, Yamanaka T, Ishii N, Tsukagoshi M, Igarashi T, Kubo N, Gombodorj N, Nishiyama M, Hosouchi Y, Kuwano H, Shirabe K.
  • Journal Title: Anticancer Research Volume: 38 Pages: 印刷中
  • DOI: 10.21873/anticanres.12307
  • Peer Reviewed
• [Journal Article] Correlation between high FBXW7 expression in pretreatment biopsy specimens and good response to chemoradiation therapy in patients with locally advanced esophageal cancer: A retrospective study (2018)
  • Author(s): Navchaa Gombodorj, Takehiko Yokobori, Naritaka Tanaka, Shigemasa Suzuki, Kengo Kuriyama, Yuji Kumakura, Tomonori Yoshida, Makoto Sakai, Makoto Sohda, Seded Baatar, Tatsuya Miyazaki, Masahiko Nishiyama, Ken Shirabe, and Hiroyuki Kuwano
  • Journal Title: Journal of Surgical Oncology Volume: accepted Pages: .
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Overexpression of karyopherin-alpha 2 in cholangiocarcinoma correlates with poor prognosis and gemcitabine sensitivity via nuclear translocation of DNA repair proteins (2017)
  • Author(s): Tsukagoshi Mariko、Araki Kenichiro、Yokobori Takehiko、Altan Bolag、Suzuki Hideki、Kubo Norio、Watanabe Akira、Ishii Norihiro、Hosouchi Yasuo、Nishiyama Masahiko、Shirabe Ken、Kuwano Hiroyuki
  • Journal Title: Oncotarget Volume: 8 Pages: 印刷中
  • DOI: 10.18632/oncotarget.15020
  • Peer Reviewed / Open Access
• [Journal Article] High STMN1 Expression is Associated with Cancer Progression and Chemo-Resistance in Lung Squamous Cell Carcinoma (2017)
  • Author(s): Bao Pinjie、Yokobori Takehiko、Altan Bolag、Iijima Misaki、Azuma Youko、Onozato Ryoichi、Yajima Toshiki、Watanabe Akira、Mogi Akira、Shimizu Kimihiro、Nagashima Toshiteru、Ohtaki Yoichi、Obayashi Kai、Nakazawa Seshiru、Bai Tuya、Kawabata-Iwakawa Reika、Asao Takayuki、Kaira Kyoichi、Nishiyama Masahiko、Kuwano Hiroyuki
  • Journal Title: Annals of Surgical Oncology Volume: 24 Pages: 4017～4024
  • DOI: 10.1245/s10434-017-6083-0
  • Peer Reviewed
• [Journal Article] Association of RAB5 overexpression in pancreatic cancer with cancer progression and poor prognosis via E-cadherin suppression (2017)
  • Author(s): Igarashi Takamichi、Araki Kenichiro、Yokobori Takehiko、Altan Bolag、Yamanaka Takahiro、Ishii Norihiro、Tsukagoshi Mariko、Watanabe Akira、Kubo Norio、Handa Tadashi、Hosouchi Yasuo、Nishiyama Masahiko、Oyama Tetsunari、Shirabe Ken、Kuwano Hiroyuki
  • Journal Title: Oncotarget Volume: 8 Pages: 印刷中
  • DOI: 10.18632/oncotarget.14703
  • Peer Reviewed
• [Journal Article] High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients (2017)
  • Author(s): Bai Tuya、Yokobori Takehiko、Altan Bolag、Ide Munenori、Mochiki Erito、Yanai Mitsuhiro、Kimura Akiharu、Kogure Norimichi、Yanoma Toru、Suzuki Masaki、Bao Pinjie、Kaira Kyoichi、Asao Takayuki、Katayama Ayaka、Handa Tadashi、Gombodorj Navchaa、Nishiyama Masahiko、Oyama Tetsunari、Ogata Kyoichi、Kuwano Hiroyuki
  • Journal Title: British Journal of Cancer Volume: 116 Pages: 1177～1185
  • DOI: 10.1038/bjc.2017.76
  • Peer Reviewed
• [Journal Article] High stathmin 1 expression is associated with poor prognosis and chemoradiation resistance in esophageal squamous cell carcinoma. (2017)
  • Author(s): Shigemasa Suzuki, Takehiko Yokobori, Bolag Altan, Keigo Hara, Daigo Ozawa, Naritaka Tanaka, Makoto Sakai, Akihiko Sano, Makoto Sohda, Halin Bao, Minoru Fukuchi, Tatsuya Miyazaki, Kyoichi Kaira, Takayuki Asao, Hiroyuki Kuwano
  • Journal Title: International Journal of Oncology Volume: 印刷中 Pages: 印刷中
  • DOI: 10.3892/ijo.2017.3899.
  • Peer Reviewed
• [Journal Article] High expression of carcinoembryonic antigen and telomerase reverse transcriptase in circulating tumor cells is associated with poor clinical response to the immune checkpoint inhibitor nivolumab (2017)
  • Author(s): Bao H、Bai T、Takata K、Yokobori T、Ohnaga T、Hisada T、Maeno T、Bao P、Yoshida T、Kumakura Y、Honjo H、Sakai M、Sohda M、Fukuchi M、Altan B、Handa T、Ide M、Miyazaki T、Ogata K、Oyama T、Shimizu K、Mogi A、Asao T、Shirabe K、Kuwano H、Kaira K
  • Journal Title: Oncology Letters Volume: 印刷中 Pages: 印刷中
  • DOI: 10.3892/ol.2017.7671
  • Peer Reviewed