The clinical validity of the biomarker for the adjuvant chemotherapy in patients after curative resection for advanced gastric cancer

• Project/Area Number: 15K10114
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Iwate Medical University
• Principal Investigator: Koeda Keisuke 岩手医科大学, 医学部, 教授 (10285596)
• Co-Investigator(Kenkyū-buntansha): 西塚 哲 岩手医科大学, 医学部, 教授 (50453311)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胃癌 / 術後補助化学療法 / バイオマーカー / Helicobacter Pylori / ヘリコバクターピロリ / 胃がん

Outline of Final Research Achievements

From 13 institutes, we accumulated a retrospective cohort of 654 patients. We gave up the the NF-κB/JNK immunostaining, because we could not available the antibody of NF-κB/JNK immunostaining which we planned. So we switched an idea to existence of chronic inflammation to bring about activation of NF-κB and examined a correlation of H. pylori and prognosis. With the score-matched 222 patients in 2 groups (i.e, "surgery" or "surgery + S-1"), 5-year overall survival rate was 62% and 62% in H. pylori-positive or negative patients in surgery group; while 72% and 62% in H. pylori-positive or negative patients in S-1 group. These results indicate that the point of effect of H. pylori infection in gastric cancer treatment is chemotherapy. These clinical and epidemiological data including ourselves led us to formulate the following aims to clarify the immunological mechanisms to drive better outcome in the challenging gastric cancer treatment.

Research Products

• [Journal Article] Helicobacter pylori infection is associated with favorable outcome in advanced gastric cancer patients treated with S-1 adjuvant chemotherapy. (2018)
  • Author(s): Nishizuka SS, Tamura G, Nakatochi M, Fukushima N, Ohmori Y, Sumida C, Iwaya T, Takahashi T, Koeda K; Northern Japan Gastric Cancer Study Consortium.
  • Journal Title: J Surg Oncol Volume: - Issue: 5 Pages: 947-956
  • DOI: 10.1002/jso.24977
  • Peer Reviewed / Open Access
• [Journal Article] Colony Lysate Arrays for Proteomic Profiling of Drug-Tolerant Persisters of Cancer Cell. (2017)
  • Author(s): Kume K, Nishizuka SS.
  • Journal Title: Anal Chem Volume: 89 Issue: 17 Pages: 8626-8631
  • DOI: 10.1021/acs.analchem.7b01215
  • Peer Reviewed
• [Journal Article] Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil (2017)
  • Author(s): Ishida K, Ito C, Ohmori Y, Kume K, Sato KA, Koizumi Y, Konta A, Iwaya T, Nukatsuka M, Kobunai T, Takechi T, Nishizuka SS
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 2262-2262
  • DOI: 10.1038/s41598-017-02548-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Analysis of PI3K mutations and PI3K pathway proteins in advanced gastric cancer (2017)
  • Author(s): Ito C, Nishizuka SS, Ishida K, Uesugi N, Sugai T, Tamura G, Koeda K, Sasaki A
  • Journal Title: Journal of Surgical Research Volume: 212 Pages: 195-204
  • DOI: 10.1016/j.jss.2017.01.018
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 腹腔鏡下幽門保存胃切除術 (2016)
  • Author(s): 肥田圭介、佐々木 章
  • Journal Title: 日本外科学会雑誌 Volume: 117 Pages: 539-542
  • Peer Reviewed
• [Journal Article] Totally Laparoscopic Total Gastrectomy for Gastric Cancer at a Single Inst itutional Experience and Changes in Technique of Esophagojejunostomy. (2016)
  • Author(s): Umemura A, Koeda K, Fujiwara H, Chiba T, Otsuka K, Sasaki A
  • Journal Title: The Indian journal of surgery Volume: 78 Issue: 3 Pages: 249-253
  • DOI: 10.1007/s12262-016-1471-4
  • Peer Reviewed
• [Journal Article] Intracorporeal reconstruction after laparoscopic pylorus-preserving gastrectomy for middle-third early gastric cancer: a hybrid technique using linear stapler and manual suturing. (2016)
  • Author(s): Koeda K, Chiba T, Noda H, Nishinari Y, Segawa T, Akiyama Y, Iwaya T, Nishizuka S, Nitta H, Otsuka K, Sasaki A.
  • Journal Title: Langenbecks Arch Surg Volume: 401 Issue: 3 Pages: 397-402
  • DOI: 10.1007/s00423-016-1378-3
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] New era of integrated cancer biomarker discovery using reverse-phase protein arrays (2016)
  • Author(s): Nishizuka SS, Mills GB
  • Journal Title: Drug Metab Pharmacokinet. Volume: 31 Issue: 1 Pages: 35-45
  • DOI: 10.1016/j.dmpk.2015.11.009
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Systematic Protein Level Regulation via Degradation Machinery Induced by Genotoxic Drugs (2016)
  • Author(s): Kume K, Ishida K, Ikeda M, Takemoto K, Shimura T, Young L, Nishizuka SS.
  • Journal Title: J Proteome Res Volume: 15 Issue: 1 Pages: 205-15
  • DOI: 10.1021/acs.jproteome.5b00759
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Individualized Mutation Detection in Circulating Tumor DNA for Monitoring Colorectal Tumor Burden Using a Cancer-Associated Gene Sequencing Panel. (2016)
  • Author(s): Sato KA, Hachiya T, Iwaya T, Kume K, Matsuo T, Kawasaki K, Abiko Y, Akasaka R, Matsumoto T, Otsuka K, Nishizuka SS
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0146275-e0146275
  • DOI: 10.1371/journal.pone.0146275
  • Peer Reviewed / Open Access
• [Journal Article] Basic Studies on Locoregional Injection of a Newly Designed Chitin Sol (2016)
  • Author(s): Chiba T, Sugitachi A, Kume K, Segawa T, Nishinari Y, Ishida K, Noda H, Nishizuka S, Kimura Y, Koeda K, Sasaki A
  • Journal Title: 癌と化学療法 Volume: 42 Pages: 1561-3
  • Peer Reviewed
• [Presentation] Two-stage operation for marginally resectable advanced gastric cancer with pyloric stenosis (2017)
  • Author(s): Koeda K, Chiba T, Nishinari Y, Segawa T, Sasaki A
  • Organizer: 第89回日本胃癌学会
  • Place of Presentation: 広島
  • Year and Date: 2017-03-08
• [Presentation] ABSOLUTE, a phase 3trial of nanoparticle albumin-bound paclitaxel versus solbent-based paclitaxel in patients with pre-treated advanced gastric cancer: Efficacy and QOL results. (2017)
  • Author(s): Koeda K, Shitara K, Takashima A, Fujitani K, Tsujimoto H, Tsuji A, Oki E, Takagane A, Takagi M, Hamamoto Y, Baba H, Omuro Y, Okuda H, Nakano Y, Sugimoto N, Nakamura M, Imamura K, Ichikawa D, Kuwano h, Koizumi W
  • Organizer: 53rd ASCO Annual Meeting
  • Int'l Joint Research
• [Presentation] Microbiota and Chemotherapy: A Downstream Finding of RPPA Biomarker Screening (2017)
  • Author(s): Nishizuka S
  • Organizer: 7th Reverse-Phase Protein Array Global Workshop
  • Int'l Joint Research
• [Presentation] Improvements of esophagogastrostomy after laparoscopic proximal gastrectom y for upper-third early gastric cancer (2016)
  • Author(s): Koeda K, Chiba T, Nishinari Y, Sasaki A
  • Organizer: 15th World Congress of Endoscopic Surgery
  • Place of Presentation: Suzhou, China
  • Year and Date: 2016-11-09
  • Int'l Joint Research / Invited
• [Presentation] Gastric cancer treatment guideline in Japan (2016)
  • Author(s): Koeda K
  • Organizer: 第54回日本癌治療学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-20
  • Invited
• [Presentation] 高度肥満患者に対する腹腔鏡下幽門側胃切除術の問題点と対策 (2016)
  • Author(s): 肥田圭介、千葉 丈広, 西成 悠, 瀬川 武紀, 秋山 有史, 岩谷 岳, 西塚 哲, 木村 祐輔, 新 田 浩幸, 大塚 幸喜, 水野 大, 佐々木 章
  • Organizer: 第116回日本外科学会
  • Place of Presentation: 大阪
  • Year and Date: 2016-04-14
• [Presentation] 合併症ゼロを目指した腹腔鏡下胃切除鏡視下再建法の確立～Linear staplerとBurb ed suture deviceを用いた消化管再建～ (2015)
  • Author(s): 肥田圭介、千葉 丈広, 西成 悠, 瀬川 武紀, 秋山 有史, 岩谷 岳, 西塚 哲, 新田 浩幸, 大 塚 幸喜, 水野 大, 佐々木 章
  • Organizer: 第77回日本臨床外科学会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-26