Research on chemoradioresistance factors and novel molecular-targeted drugs for esophageal squamous cell carcinoma centering on MDM2

• Project/Area Number: 18K16296
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Tohoku University
• Principal Investigator: Okamoto Hiroshi 東北大学, 大学病院, 助教 (80732487)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 食道扁平上皮癌 / 化学放射線抵抗性 / Murine double minute 2 / Ki-67 / p16 / HO-1 / TXNRD1 / pMLKL / 化学放射線感受性 / p53 / 化学放射線感受性予測 / Murine Double Minute 2 / 分子標的薬

Outline of Final Research Achievements

In this study, using resected specimens of esophageal squamous cell carcinoma after definitive/preoperative CRT or preoperative chemotherapy, and pretreatment biopsy tissues evaluated mainly by immunohistochemical staining, and comparing with clinicopathological factors and clinical course, we identified Murine double minute 2 (MDM2), p16, p53, Ki-67, phosphorylated mixed lineage kinase domain-like protein (pMLKL), heme oxygenase-1 (HO-1), thioredoxin reductase 1 (TXNRD1) and others. It will lead to implementation in actual clinical practice, prospective clinical research, and construction of a multidisciplinary treatment strategy.

Academic Significance and Societal Importance of the Research Achievements

本研究により見出された治療効果予測のマーカーを用いて実際の臨床で治療前に予測できるかを前向き臨床試験として検証し、治療戦略へ組み込むことで、治療ガイドラインの策定に寄与し、また、患者にとって無駄な副作用や医療費の負担を軽減することができ、個々の患者に最適な治療法を提供することが可能となる。食道癌患者全体の予後改善にも寄与すると考えられ、医療費削減も含め社会に対する貢献度は大きい。さらなる臨床研究や、分子標的治療への発展、他の(化学)放射線療法を用いる肺癌、子宮頚癌、前立腺癌、脳腫瘍に対する研究への足掛かりになる可能性をも含んでいる。

Research Products

• [Journal Article] Correlation between TXNRD1/HO-1 expression and response to neoadjuvant chemoradiation therapy in patients with esophageal squamous cell carcinoma (2022)
  • Author(s): Ryujiro Akaishi, Fumiyoshi Fujishima, Hirotaka Ishida, Junichi Tsunokake, Takuro Yamauchi, Yusuke Gokon, Shunsuke Ueki, Toshiaki Fukutomi, Hiroshi Okamoto, Kai Takaya, Chiaki Sato, Yusuke Taniyama, Tomohiro Nakamura, Naoki Nakaya, Takashi Kamei, Hironobu Sasano
  • Journal Title: Esophagus Volume: 19 Issue: 3 Pages: 436-443
  • DOI: 10.1007/s10388-021-00904-3
  • Peer Reviewed
• [Journal Article] Definitive Chemoradiotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil for Advanced Cervical Esophageal Cancer: A Medium-Term Outcome (2022)
  • Author(s): Hiroshi Okamoto*, Yusuke Taniyama, Chiaki Ozawa, Ryohei Ando, Kozue Takahashi, Ryujiro Shinozaki, Michiaki Unno, Takashi Kamei
  • Journal Title: Asian Pacific Journal of Cancer Prevention Volume: 23 Issue: 2 Pages: 495-499
  • DOI: 10.31557/apjcp.2022.23.2.495
  • Peer Reviewed / Open Access
• [Journal Article] HO-1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy (2022)
  • Author(s): 4.Ryujiro Akaishi, Fumiyoshi Fujishima, Hirotaka Ishida, Junichi Tsunokake, Takuro Yamauchi, Yusuke Gokon,Shunsuke Ueki, Toshiaki Fukutomi, Hiroshi Okamoto, Kai Takaya, Chiaki Sato, Yusuke Taniyama1, Tomohiro Nakamura, Naoki Nakaya, Takashi Kamei, Hironobu Sasano
  • Journal Title: Cancer Reports Volume: 5 Issue: 3
  • DOI: 10.1002/cnr2.1477
  • Peer Reviewed / Open Access
• [Journal Article] p16 in highly malignant esophageal carcinomas: the correlation with clinicopathological factors and human papillomavirus infection (2021)
  • Author(s): Hirotaka Ishida, Atsuko Kasajima, Fumiyoshi Fujishima, Ryujiro Akaishi, Shunsuke Ueki, Yuto Yamazaki, Yoshiaki Onodera, Xin Gao, Hiroshi Okamoto, Yusuke Taniyama, Takashi Kamei, Hironobu Sasano
  • Journal Title: Virchows Archiv Volume: 478 Issue: 2 Pages: 219-229
  • DOI: 10.1007/s00428-020-02865-x
  • Peer Reviewed / Open Access
• [Journal Article] GR, Sgk1, and NDRG1 in esophageal squamous cell carcinoma: their correlation with therapeutic outcome of neoadjuvant chemotherapy (2020)
  • Author(s): Shunsuke Ueki, Fumiyoshi Fujishima, Takuro Kumagai, Hirotaka Ishida, Hiroshi Okamoto, Kai Takaya, Chiaki Sato, Yusuke Taniyma, Takashi Kamei, Hironobu Sasano
  • Journal Title: BMC Cancer Volume: 20 Issue: 1 Pages: 161-161
  • DOI: 10.1186/s12885-020-6652-7
  • Peer Reviewed / Open Access
• [Journal Article] Multiple carcinosarcomas of the esophagus with adeno-carcinomatous components: A case report (2020)
  • Author(s): Okamoto Hiroshi、Kikuchi Hiroshi、Naganuma Hiroshi、Kamei Takashi
  • Journal Title: World Journal of Gastroenterology Volume: 26 Issue: 17 Pages: 2111-2118
  • DOI: 10.3748/wjg.v26.i17.2111
  • Peer Reviewed / Open Access
• [Journal Article] Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for advanced cervical esophageal cancer. (2018)
  • Author(s): Hiroshi Okamoto, Yusuke Taniyama, Tadashi Sakurai, Takahiro Heishi, Jin Teshima, Chiaki Sato, Shota Maruyama, Ken Ito, Yu Onodera, Takuro Konno-Kumagai, Hirotaka Ishida, Takashi Kamei
  • Journal Title: Esophagus Volume: 15 Issue: 4 Pages: 281-285
  • DOI: 10.1007/s10388-018-0627-7
  • NAID: 40021670354
  • Peer Reviewed
• [Presentation] 進行頸部食道癌に対するDocetaxel, CDDP, 5-FU併用放射線療法 (2022)
  • Author(s): 岡本宏史、谷山 裕亮, 佐藤 千晃, 小澤洋平、小関健、堀江悠太、赤石隆二郎、山内拓郎、福富俊明、亀井尚
  • Organizer: 第76回 日本食道学会
• [Presentation] Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for advanced cervical esophageal cancer (2022)
  • Author(s): Hiroshi Okamoto, Yusuke Taniyama, Chiaki Sato, Toshiaki Fukutomi, Yohei Ozawa, Ken Koseki, Yuta Horie, Ryujiro Akaishi, Takuro Yamauchi, Takashi Kamei
  • Organizer: 18th International Society of Diseases of Esophagus
  • Int'l Joint Research
• [Presentation] 当院におけるT3b胸部食道癌に対する根治的化学放射線療法とサルベージ治療 (2022)
  • Author(s): 岡本宏史、谷山 裕亮, 佐藤千晃, 小澤洋平, 石田裕嵩, 小関健, 山内拓郎, 加藤伸史, 亀井 尚
  • Organizer: 第75回 日本胸部外科学会
• [Presentation] TXNRD1、HO-1の食道癌術前化学放射線療法患者での治療抵抗性及び予後の指標としての有用性 (2022)
  • Author(s): 赤石隆二郎、藤島史喜、山内拓郎、石田裕嵩、福富俊明、岡本宏史、佐藤千晃、谷山裕亮、亀井尚
  • Organizer: 第76回 日本食道学会
• [Presentation] 食道扁平上皮癌における Sgk1 発現と術前化学療 法治療効果との関連性 (2021)
  • Author(s): 植木 俊輔、藤島 史喜、小関 健、福富 俊明、岡本 宏史、高屋 快、佐藤 千晃、谷山 裕亮、亀井 尚、海 野 倫明、笹野 公伸
  • Organizer: 第121 回日本外科学会定期学術集会
• [Presentation] 食道扁平上皮癌における TXNRD1 と HO-1 発現 と術前化学放射線療法抵抗性についての関連 (2021)
  • Author(s): 赤石 隆二郎、藤島 史喜、石田 裕嵩、福富 俊明、岡本 宏史、高屋 快、佐藤 千晃、谷山 裕亮、海野 倫明、亀井 尚、笹野 公伸
  • Organizer: 第121 回日本外科学会定期学術集会
• [Presentation] 食道扁平上皮癌におけるGlucocorticoid receptorおよび関連因子発現の検討 (2020)
  • Author(s): 植木俊輔、藤島史喜、谷山裕亮、佐藤千晃、高屋快、岡本宏史、福富俊明、熊谷卓朗、亀井尚、笹野公伸
  • Organizer: 第74回日本食道学会学術集会
• [Presentation] 食道扁平上皮癌におけるネクロトーシスの免疫組織学的検討 (2020)
  • Author(s): 山内拓郎、藤島史喜、谷山裕亮、佐藤千晃、高屋快、岡本宏史、福富俊明、及川隆洋、亀井尚、笹野公伸
  • Organizer: 第74回日本食道学会学術集会
• [Presentation] Keap1-Nrf2制御系及びp62と化学放射線療法抵抗性についての検討 (2020)
  • Author(s): 藤島史喜、谷山裕亮、佐藤千晃、高屋快、岡本宏史、福富俊明、熊谷卓朗、笹野公伸、亀井尚
  • Organizer: 第74回日本食道学会学術集会
• [Presentation] 当科における頸部食道癌の治療成績の検討 (2019)
  • Author(s): 岡本宏史、谷山裕亮、櫻井直、日景允、佐藤千晃、高屋快、今野卓朗、氏家直人、海野倫明、亀井尚
  • Organizer: 日本消化器外科学会
• [Presentation] 当科の食道癌術後再発に対する治療の検討 (2019)
  • Author(s): 岡本宏史、谷山裕亮、櫻井直、日景允、佐藤千晃、高屋快、今野卓朗、氏家直人、小関健、亀井尚
  • Organizer: 日本食道学会
• [Presentation] 進行頸部食道癌に対するDocetaxel/CDDP/5-FU併用放射線療法(DCF-R)～FP-Rとの比較から (2018)
  • Author(s): 岡本 宏史、谷山 裕亮、櫻井 直、瓶子 隆弘、佐藤 千晃、高屋 快、伊東 賢、小野寺 優、今野 卓朗、亀井 尚
  • Organizer: 第72回日本食道学会学術集会
• [Presentation] Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for advanced cervical esophageal cancer (2018)
  • Author(s): Hiroshi Okamoto, Yusuke Taniyama, Tadashi Sakurai, Makoto Hikage, Jin Teshima, Chiaki Sato, Kai Takaya, Shota Maruyama, Ken Ito, Yu Onodera, Hirotaka Ishida, Takuro Konno, Takashi Kamei
  • Organizer: 16th World Congress of the International society of diseases of the esophagus
  • Int'l Joint Research