Multi-dimensional interactome analyses of patient derived cancer xenograft model for personalized medicine system

• Project/Area Number: 26430097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Jichi Medical University (2016); Central Institute for Experimental Animals (2014-2015)
• Principal Investigator: Chijiwa Tsuyoshi 自治医科大学, 医学部, 講師 (70642180)
• Co-Investigator(Kenkyū-buntansha): 宮城 洋平 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, 総括部長 (00254194) ; 砂河 孝行 東京医科歯科大学, 難治疾患研究所, 特任助教 (40418637) ; 加藤 洋人 東京医科歯科大学, 難治疾患研究所, 助教 (60446549)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: がん患者由来ゼノグラフト / 疾患モデル / NOGマウス / インタラクトーム / 分子標的薬 / PDX

Outline of Final Research Achievements

In this study, we performed the interactome analyses of Patient-derived xenografts (PDX) linked with clinical information. It disclosed cancer-stroma interactions associated with molecular target drug efficiencies comprehensively. High interactions were confirmed by in-vivo drug sensitivity tests or clinical effectiveness of molecular target drugs. Efficient establishment procedures of PDX were also statistically confirmed among from our results. We also established PDXs from malignant pleural effusion. The PDXs from malignant pleural effusion are efficient and valuable as same as from surgical specimen. It is possible to establish serial PDXs of the same patient less-invasively. Our results appear to be reliable for clinical simulations of chemotherapy and will definitely assist in the selection of the most sensitive anti-cancer drug for each patient. The fast and efficient establishment of individual PDXs will contribute to personalized anti-cancer therapies.

Research Products

• [Journal Article] Study on AAV-mediated Gene Therapy for Diabetes in Humanized Liver Mouse to Predict Efficacy in Humans. (2016)
  • Author(s): Hashimoto H, Mizushima T, Ogura T, Kagawa T, Tomiyama K, Takahashi R, Yagoto M, Kawai K, Chijiwa T, Nakamura M, Suemizu H
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 478 Issue: 3 Pages: 1254-60
  • DOI: 10.1016/j.bbrc.2016.08.104
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of patient-derived cancer xenografts in immunodeficient NOG mice. (2015)
  • Author(s): Chijiwa T, Kawai K, Noguchi A, Sato H, Hayashi A, Cho H, Shiozawa M, Kishida T, Morinaga S, Yokose T, Katayama M, Takenaka N, Suemizu H, Yamada R, Nakamura Y, Ohtsu T, Takano Y, Imai K, Miyagi Y, Nakamura M
  • Journal Title: International Journal of Oncology Volume: 47 Issue: 1 Pages: 61-70
  • DOI: 10.3892/ijo.2015.2997
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Zinc finger protein 185 is a liver metastasis-associated factor of colon cancer. (2014)
  • Author(s): Furukawa D, Chijiwa T, Matsuyama M, Mukai M, Matsuo E, Nishimura O, Kawai K, Suemizu H, Hiraoka N, Nakagohri T, Yasuda S, Nakamura M
  • Journal Title: Molecular and Clinical Oncology Volume: 2 Issue: 5 Pages: 709-713
  • DOI: 10.3892/mco.2014.298
  • Peer Reviewed / Open Access
• [Presentation] Comprehensive and serial analyses of tumor-stroma interactions in individual PDX/NOG models contribute to personalized chemotherapy (2017)
  • Author(s): Chijiwa T, Haraguchi M, Komura D, Noguchi A, Shiozawa M, Katayama M, Miyao N, Matsui N, Tateishi Y, Suemizu H, Nakamura Y, Isagawa T, Katoh H, Ishikawa S, Nakamura M, Miyagi Y
  • Organizer: AACR International Conference on New Frontiers in Cancer Research
  • Place of Presentation: ケープタウン, 南アフリカ
  • Year and Date: 2017-01-18
  • Int'l Joint Research
• [Presentation] Establishment of patient-derived xenografts from malignant pleural effusion using NOG mice (2016)
  • Author(s): Chijiwa T, Haraguchi M, Isagawa T, Noguchi A, Katayama M, Miyao N, Yoshioka M, Matsui N, Tateishi Y, Suemizu H, Yamada R, Nakamura Y, Imai K, Komura D, Katoh H, Ishikawa S, Nakamura M, Miyagi Y
  • Organizer: ESMO Asia 2016
  • Place of Presentation: シンガポール
  • Year and Date: 2016-12-16
  • Int'l Joint Research
• [Presentation] Clinical significance of ZNF185 intracellular localization in pancreatic ductal carcinoma (2016)
  • Author(s): Furukawa D, Chijiwa T, Matsuyama M, Mukai M, Matsuo E, Nishimura O, Kawai K, Suemizu H, Nakagohri T, Yasuda S, Shimada K, Hiraoka N, Nakamura M
  • Organizer: AACR Annual Meeting 2016
  • Place of Presentation: ニューオーリンズ, アメリカ
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] Clinical applications of PDX/NOG models for personalized chemotherapy – possible use in chemo-sensitivity testing and clinical sequencing (2016)
  • Author(s): Chijiwa T, Isagawa T, Noguchi A, Sato H, Hayashi A, Cho H, Shiozawa M, Kishida T, Morinaga S, Yokose T, Katayama M, Takenaka N, Haraguchi M, Miyao N, Tateishi Y, Kawai K, Suemizu H, Yamada R, Nakamura Y, Imai K, Komura D, Ishikawa S, Nakamura M, Miyagi Y
  • Organizer: AACR special conference on Patient-Derived Cancer Models
  • Place of Presentation: ニューオーリンズ
  • Year and Date: 2016-02-11
  • Int'l Joint Research
• [Presentation] The valuable experimental model system "Cancer Xenopatient" established in NOG mice (2015)
  • Author(s): Chijiwa T, Kawai K, Noguchi A, Sato H, Hayashi A, Cho H, Shiozawa M, Kishida T, Morinaga S, Yokose T, Katayama M, Takenaka N, Suemizu H, Yamada R, Nakamura Y, Ohtsu T, Takano Y, Imai K, Miyagi Y, Nakamura M
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: フィラデルフィア
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Zinc finger protein 185 is a key molecule of liver metastasis in colon cancer (2014)
  • Author(s): Furukawa D, Chijiwa T, Matsuyama M, Mukai M, Matsuo E, Nishimura O, Kawai K, Suemizu H, Hiraoka N, Nakagohri T, Yasuda S, Nakamura M
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: サンディエゴ、アメリカ
  • Year and Date: 2014-04-05 – 2014-04-09