Potential of tumore suppressor FBXW7 as one of the therapeutic targets

• Project/Area Number: 15K10085
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Gunma University
• Principal Investigator: Yokobori Takehiko 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) ; 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
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: FBXW7 / 消化器癌 / 腹膜播腫 / 胃癌 / HDAC阻害剤 / 腹膜播種

Outline of Final Research Achievements

We previously reported that the expression levels of FBXW7 in gastric cancer tissues were lower than those in non-cancerous tissues. Moreover, the gastric cancer patients with low FBXW7 expression have aggressive phenotypes of gastric cancer and poor prognosis compared to the high expression group. In this study we evaluated the FBXW7 protein expression using IHC. As a result, the low FBXW7 group had tendency of poor prognosis compared to the high expression group. Moreover, the FBXW7 induction by HDAC inhibitor MS-275 was validated in cancer cell lines. The cancer cell lines expressing highly FBXW7 were more sensitive to the anticancer drugs and radiation than control cells The therapeutic strategy to induce the FBXW7 expression by HDAC inhibitors might be a good for refractory gastric cancer patients.

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
  • 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 Issue: 2 Pages: 939-944
  • DOI: 10.21873/anticanres.12307
  • Peer Reviewed / Int'l Joint Research
• [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 (2018)
  • 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: 15 Pages: 3061-3067
  • DOI: 10.3892/ol.2017.7671
  • Peer Reviewed / Open Access
• [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
  • 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 Issue: 26 Pages: 42159-42172
  • 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 Issue: 13 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 Issue: 7 Pages: 12290-12300
  • 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 Issue: 9 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 Issue: 4 Pages: 1184-1190
  • DOI: 10.3892/ijo.2017.3899
  • Peer Reviewed
• [Journal Article] Establishment of a novel method to evaluate peritoneal microdissemination and therapeutic effect using luciferase assay. (2016)
  • Author(s): Takahashi R, Yokobori T, Osone K, Tatsuki H, Takada T, Suto T, Yajima R, Kato T, Fujii T, Tsutsumi S, Kuwano H, Asao T.
  • Journal Title: Cancer Science Volume: 107(3) Issue: 3 Pages: 341-346
  • DOI: 10.1111/cas.12872
  • Peer Reviewed / Open Access / Acknowledgement Compliant