The basic research of preclinical simulation system for chemotherapy using "individual Cancer Xenografts"

• Project/Area Number: 25430098
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Central Institute for Experimental Animals
• Principal Investigator: KAWAI KENJI 公益財団法人実験動物中央研究所, その他部局等, 研究員 (30414064)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Masato 東海大学, 医学部, 教授 (00164335) ; 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, その他 (00254194)
• Co-Investigator(Renkei-kenkyūsha): MIYAGI Yohei 神奈川県立がんセンター, 臨床研究所, 部長 (00254194)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed(Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost : ¥4,000,000、Indirect Cost : ¥1,200,000); Fiscal Year 2015 : ¥1,950,000 (Direct Cost : ¥1,500,000、Indirect Cost : ¥450,000); Fiscal Year 2014 : ¥1,690,000 (Direct Cost : ¥1,300,000、Indirect Cost : ¥390,000); Fiscal Year 2013 : ¥1,560,000 (Direct Cost : ¥1,200,000、Indirect Cost : ¥360,000)
• Keywords: 疾患モデル / 個別化医療 / NOGマウス / NOG

Outline of Final Research Achievements

We established rapid and effective protocols for making individual Cancer Xenograft (iCX). In the iCXs, morphological characteristics, gene expression profiles, and genetic alteration patterns were all well preserved. In colorectal cancer iCXs, Collagen gel droplet embedded culture-drug sensitivity tests (CD-DST) were performed. The CD-DST results between original and iCX specimens were generally correlated (R2=0.01-0.89). The result of CD-DST using iCX was compatible with clinical effects of anti-cancer drug. Zinc finger protein 185 (ZNF185) is one of proteins selected from proteome analysis utilizing cancer xenograft models. We also analyzed the association between ZNF185 and the clinicopathological characteristics of colon cancer. ZNF185 expression was found to be an independent indicator of liver metastasis and prognosis in patients with colon cancer. Our iCXs with clinical information are a promising advance that may accelerate the development of anticancer therapies.

Research Products

• [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 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 Pages : 709-713
  • DOI: 10.3892/mco.2014.298
  • Peer Reviewed / Open Access
• [Journal Article] A versatile technique for the in vivo imaging of human tumor xenografts using near-infrared fluorochrome-conjugated macromolecule probes. (2013)
  • Author(s): Suemizu H, Kawai K, Higuchi Y, Hashimoto H, Ogura T, Itoh T, Sasaki E, Nakamura M.
  • Journal Title: PLoS One Volume : 8
  • DOI: 10.1371/journal.pone.0082708
  • Peer Reviewed
• [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
  • Place of Presentation: フィラデルフィア
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] NOGマウスによる高効率がん患者由来Xenograft株の樹立 (2013)
  • Author(s): 千々和剛、宮城洋平、川井健司、野口映、山田六平、末水洋志、高野康雄、中村雅登
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 大腸癌肝転移からのゼノグラフト作製とCD-DST法での抗がん剤感受性解析 (2013)
  • Author(s): 澤崎翔，塩澤学，赤池信，片山雄介，沼田幸司，樋口晃生，五代天偉，森永聡一郎，小嶋由香，川井健司，中村雅登，高野康雄，利野靖，益田宗孝，宮城洋平
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 京都