Tailor-made molecular targeted chemoradiotherapy for esophageal cancer

• Project/Area Number: 24591958
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: FUJIWARA Hitoshi 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20332950)
• Co-Investigator(Kenkyū-buntansha): OTSUJI Eigo 京都府立医科大学, 医学研究科, 教授 (20244600) ; SOWA Yoshihiro 京都府立医科大学, 医学研究科, 准教授 (70315935)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 食道癌 / HDAC阻害剤 / 5-FU / 放射線

Outline of Final Research Achievements

Histone deacetylase (HDAC) inhibitors have been shown to enhance the effects of 5-fluorouracil (5-FU) against various cancer cells; however, no report has shown that an HDAC inhibitor may enhance the effects of 5-FU with radiation. Therefore, we investigated whether the novel HDAC inhibitor OBP-801/YM753 could enhance the effects of 5-FU with radiation on esophageal squamous carcinoma KYSE170 cells. The inhibition of the cell growth was significantly stronger with the combination of OBP-801/YM753 with 5-FU than with the 5-FU treatment only. Furthermore, inhibition of the colony formation was the most effective with the combined treatment of OBP-801/YM753, 5-FU, and radiation. Western blot analysis showed that OBP-801/YM753 suppressed the expression of thymidylate synthase induced by 5-FU. Therefore, this three-combined therapy is promising for patients with esophageal squamous carcinoma.

Research Products

• [Journal Article] The novel HDAC inhibitor OBP-801/YM753 enhances the effects of 5-fluorouracil with radiation on esophageal squamous carcinoma cells (2014)
  • Author(s): Furutani A1, Sowa Y, Fujiwara H, Otsuji E, Sakai T
  • Journal Title: Oncol Res. Volume: 21 Issue: 5 Pages: 281-286
  • DOI: 10.3727/096504014x13890370410249
  • Peer Reviewed
• [Journal Article] Ibuprofen enhances TRAIL-induced apoptosis through DR5 upregulation. (2013)
  • Author(s): Todo M, Horinaka M, Tomosugi M, Tanaka R, Ikawa H, Sowa Y, Ishikawa H, Fujiwara H, Otsuji E, Sakai T
  • Journal Title: Oncol Rep. Volume: 30 Issue: 5 Pages: 2379-2384
  • DOI: 10.3892/or.2013.2713
  • Peer Reviewed
• [Journal Article] Prognostic impact of tumor IL-6 expression after preoperative chemoradiotherapy in patients with advanced esophageal squamous cell carcinoma. (2013)
  • Author(s): Yoneda M, Fujiwara H, Furutani A, Ikai A, Tada H, Shiozaki A, Komatsu S, Kubota T, Ichikawa D, Okamoto K, Konishi H, Murayama Y, Kuriu Y, Ikoma H, Nakanishi M, Ochiai T, Otsuji E.
  • Journal Title: Anticancer Res. Volume: 33 Pages: 2699-2705
  • Peer Reviewed
• [Journal Article] Overexpression of IL-6 by gene transfer stimulates IL-8-mediated invasiveness of KYSE170 esophageal carcinoma cells. (2013)
  • Author(s): Okamura S, Fujiwara H, Yoneda M, Furutani A, Todo M, Ikai A, Tada H, Okamura H, Umehara S, Shiozaki A, Kubota T, Komatsu S, Ichikawa D, Okamoto K, Ochiai T, Otsuji E.
  • Journal Title: Anticancer Res. Volume: 33 Pages: 1483-1489
  • Peer Reviewed
• [Journal Article] Time course of serum C-reactive protein levels during induction chemoradiotherapy and its correlation with treatment response and survival in patients with advanced esophageal squamous cell carcinoma (2013)
  • Author(s): Fujiwara H, Shiozaki A, Furutani A, Yoneda M, Kubota T, Komatsu S, Ichikawa D, Okamoto K, Murayama Y, Kuriu Y, Ikoma H, Nakanishi M, Ochiai T, Otsuji E
  • Journal Title: MOLECULAR AND CLINICAL ONCOLOGY Volume: 1 Issue: 3 Pages: 558-564
  • DOI: 10.3892/mco.2013.84
  • Peer Reviewed
• [Journal Article] COX-2 overexpression Induced by gene transfer reduces sensitivity of TE13 esophageal carcinoma cells to 5-fluorouracil and cisplatin (2013)
  • Author(s): Okamura H, Fujiwara H, Umehara S, Okamura S, Todo M, Furutani A, Yoneda M, Shiozaki A, Komatsu S, Kubota T, Ichikawa D, Okamoto K, Ochiai T, Sakakura C, Takahashi Y, Yoshimoto T, Otsuji E
  • Journal Title: Anticancer Res. Volume: 33 Pages: 537-542
  • Peer Reviewed
• [Journal Article] HGF regulates VEGF expression via the c-Met receptor downstream pathways, PI3K/Akt, MAPK and STAT3, in CT26 murine cells (2013)
  • Author(s): Matsumura A, Kubota T, Taiyoh H, Fujiwara H, Okamoto K, Ichikawa D, Shiozaki A, Komatsu S, Nakanishi M, Kuriu Y, Murayama Y, Ikoma H, Ochiai T, Kokuba Y, Nakamura T, Matsumoto K, and Otsuji E
  • Journal Title: Int J Oncol Volume: Vol. 42: no.2 Issue: 2 Pages: 535-542
  • DOI: 10.3892/ijo.2012.1728
  • Peer Reviewed
• [Journal Article] Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5-fluorouracil on human colon cancer cells (2013)
  • Author(s): Watanabe M, Sowa Y, Yogosawa M, Sakai T.
  • Journal Title: Cancer Sci. Volume: Epub ahead of print Issue: 6 Pages: 687-693
  • DOI: 10.1111/cas.12139
  • Peer Reviewed
• [Journal Article] PSK induces apoptosis through the inhibition of activated STAT3 in human esophageal carcinoma cells (2012)
  • Author(s): Umehara S, Shiozaki A, Otsuji E, et al
  • Journal Title: Int J Oncol Volume: 41 Pages: 61-66
  • DOI: 10.3892/ijo.2012.1454
  • Peer Reviewed
• [Journal Article] Perioperative outcomes of esophagectomy preceded by the laparoscopic transhiatal approach for esophageal cancer. (2012)
  • Author(s): Shiozaki A, Kokuba Y, Otsuji E, et al.
  • Journal Title: Diseases of the Esophagus Volume: (印刷中) Issue: 5 Pages: 470-478
  • DOI: 10.1111/j.1442-2050.2012.01439.x
  • Peer Reviewed
• [Journal Article] Retinoblastoma gene-independent G1 phase arrest by flavone, phosphatidylinositol 3-kinase inhibitor, and histone deacetylase inhibitor (2012)
  • Author(s): Tomosugi M, Sowa Y, Yasuda S, Tanaka R, te Riele H, Ikawa H, Koyama M, Sakai T
  • Journal Title: Cancer Sci. Volume: Vol. 103、 No. 12 Issue: 12 Pages: 2139-2143
  • DOI: 10.1111/cas.12012
  • Peer Reviewed
• [Journal Article] The anti-obesity drug orlistat promotes sensitivity to TRAIL by two different pathways in hormone-refractory prostate cancer cells. (2012)
  • Author(s): Jun Fujiwara, Yoshihiro Sowa, Mano Horinaka, Makoto Koyama, Miki Wakada, Tsuneharu Miki, Toshiyuki Sakai
  • Journal Title: International Journal of Oncology Volume: 40 Pages: 1483-1491
  • DOI: 10.3892/ijo.2012.1353
  • Peer Reviewed
• [Presentation] 食道がん細胞株に対するHDAC阻害剤OBP-801/YM753と放射線と5-FUの三者併用効果の検討
  • Author(s): 古谷 晃伸, 曽和 義広, 藤原 斉, 塩崎 敦, 窪田 健, 市川 大輔, 岡本 和真, 浦田 泰生, 酒井 敏行, 大辻 英吾
  • Organizer: 日本食道学会
  • Place of Presentation: 大阪
• [Presentation] HDAC阻害剤YM753(OBP-801)による食道がん細胞株における放射線と5FUの併用効果の増強
  • Author(s): 古谷 晃伸, 曽和 義広, 藤原 斉, 小西 博貴, 村山 康利, 小松 周平, 塩崎 敦, 栗生 宜明, 生駒 久視, 窪田 健, 中西 正芳, 市川 大輔, 岡本 和真, 浦田 泰生, 酒井 敏行, 大辻 英吾
  • Organizer: 日本外科学会
  • Place of Presentation: 福岡