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Establishment of an appropriate metastasis model and a novel treatment for advanced human colorectal cancer using RAG2/common-γ double knockout mice

Research Project

Project/Area Number 12671208
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NAKAMURA Masataka (2002)  Human Gene Sciences Center, Professor, 疾患遺伝子実験センター, 教授 (30180392)

岡部 聡 (2000-2001)  東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (60242187)

Co-Investigator(Kenkyū-buntansha) YAMAGUCHI Noriko  Medical Research Institute, Instructor, 難治疾患研究所, 助手 (90251553)
OKABE Satoshi  Graduate School of Medical Science, Lecturer, 大学院・医歯学総合学研究科, 講師 (60242187)
中村 正孝  東京医科歯科大学, 疾患遺伝子実験センター, 教授 (30180392)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
KeywordsRAG2 / common-γ double knockout mouse / Liver metastasis model of human colorectal cancer / scid-hu mouse / endostatin / scid / hu mice / human endostatin
Research Abstract

The aim of this study is to establish an animal medel for immunothrerapeutic treatment of human colon cancer. Our results demonstrate that most of human colorectal cancer tissues remain alive in RAG2/common-γ knockout (DKO) mice, moreover, some of them invade into the muscular layer and lymphovascular channel in the flank, unlike with the ordinary immuno-compromised mice, nude mice and scid mice. These mice showed more foci of liver metastases than other mice after intrasplenic injection of the human colon cancer cell line, HT-29. Adaptation, invasion and liver metastasis of human colon cancer into several mice organs were more prevalent in DKO mice. Human colorectal cancer tissue implanted in the subcutaneous tissue of DKO mice showed the similar sensitivity to anti-cancer drugs in the HDRA method. Phenotypes of human colorectal cancer in DKO mice were kept as same as those before implantation. The effect of standard chemotherapeutics on MHC class I and CEA expression in colorectal cancer cell lines was determined. All anti-cancer drugs examined, when given at IC_50 values, induced expression of MHC class I in the human colon cancer cell line, COLO201. However, expression of CEA mRNA was only induced upon exposure to 5-FU. Regarding the in vivo studies in mice, the tumor size of colon26 was reduced only in response to treatment with CDDP, which also mediated the highest induction of MHC class I expression. These results indicate that cancer-specific immunotherapy may be synergistically effective when used in combination with systemic chemotherapy.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Funato, N.: "Basic helix-loop-helix transcription factor epicardin/pod-1/capsulin suppresses differentiation_by negative regulation of transcription"J. Biol. Chem.. 278. 7486-7493 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyazaki, S.: "Interleukin 2 receptor γ (γ_c) chain knockout mice show less regularity in estrous cycles but achieve normal pregnancy without fetal compromise"Am. J. Reprod. Immunol.. 47. 222-230 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayano, C.: "Accumulation of CD16^+ cells with secretion of Ksp37 in decidua at the end of pregnancy"Am. J. Reprod. Immunol.. 48. 57-62 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Michimata, T.: "Distribution of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict preganancy outcome following recurrent abortion"Am. J. Reprod. Immunol.. 47. 196-202 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirai, H.: "Agonistic effect of indomethacin on a prostaglandin D_2 receptor, CRTH2"J. Immunol.. 168. 981-985 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Michimata, T.: "Accumlation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D2-mediated manner"Mol. Human Reprod.. 8. 181-187 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S.: "Investigation into the usefulness and adverse events of CDDP, 5-FU, and dl-Leucovolin (PFL-therapy) for advanced colorectal cancer"J. Med. Dent. Sci.. 49. 77-84 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S.: "Clinicopathological study of mucous pooling referred to as mucinous component (MUC) in colorectal submucosal invasive carcinomas"J. Med. Dent. Sci.. 48. 69-78 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S.: "Ileosigmoid anastomosis with exclusion of transected ileal loop for intestinal fistula following total cystectomy of bladder cancer : Report of a case"J. Med. Dent. Sci.. 47. 243-246 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S.: "Abdominosacral repair for a rectovaginal fistula with anastomotic stenosis after low anterior resection : Report of a case"J. Med. Dent. Sci.. 48. 41-44 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Funato, N., Ohyama, M., Kuroda, T. & Nakamura, M.: "Basic helix-loop-helix transcription factor epicardin/pod-1/capsulin suppresses differentiation by negative regulation of transcription"J. Biol. Chem.. 278. 7486-7493 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyazaki, S., Tanebe, K., Sakai, M., Michimata, T., Tsuda, H., Fujimura, M., Nakamura, M., Kiso, I. & Saito, S.: "Interleukin 2 receptor γ (γc) chain knockout mice show less regularity in estrous cycles but achieve normal pregnancy without fetal compromise"Am. J. Reprod. Immunol.. 47. 222-230 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayano, C., Koi, H., Ogawa, K., Nagat, K., Matsumoto, Y., Nakamura, M. & Aso, T.: "Accumulation of GD16^+ cells with secretion of Ksp37 in decidua at the end of pregnancy"Am. J. Reprod. Immunol.. 48. 57-62 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Michimata, T., Ogasawara, M. S., Tsuda, H., Suzumori, K., Aoki, K., Sakai, M., Fujimura, M., Nagata, K., Nakamura, M. & Saito, S.: "Distribution of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict preganancy outcome following recurrent abortion"Am. J. Reprod. Immunol.. 47. 196-202 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirai, H., Tanaka, K., Takano, S., Nakamura, M. & Nagata, K.: "Agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2"J. Immunol.. 168. 981-985 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Michimata, T., Tsuda, H., Sakai, M., Fujimura, M., Nagata, K., Nakamura, M. & Saito, S.: "Accumlation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D2-mediated manner"Mol. Human Reprod.. 8. 181-187 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S., Ishikawa, T., Tanami, H., Kuwabara, H., Fukahara, T., Udagawa, M., Ootsukasa, S., Arai, T., Maruyama, S., Murase, N., Yamashita, H., Iwai, T.: "Investigation into the usefulness and adverse events of CDDP, 5-FU, and dl-Leucovolin (PFL-therapy) for advanced colorectal cancer"J. Med. Dent. Sci.. 49. 77-84 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S., Ishikawa, T., Tanami, H., Kuwabara, H., Fukahara, T., Udagawa, M., Ootsukasa, S., Arai, T., Maruyama, S., Murase, N., Yamashita, H., Iwai, T.: "Clinicopathological study of mucous pooling referred to as mucinous component (MUC) in colorectal submucosal invasive carcinomas"J. Med. Dent. Sci.. 48. 69-78 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S., Ishikawa, T., Tanami, H., Kuwabara, H., Fukahara, T., Udagawa, M., Ootsukasa, S., Arai, T., Maruyama, S., Murase, N., Yamashita, H., Iwai, T.: "Abdominosacral repair for a rectovaginal fistula with anastomotic stenosis after low anterior resection : Report of a case"J. Med. Dent. Sci.. 48. 41-44 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S., Ishikawa, T., Tanami, H., Kuwabara, H., Fukahara, T., Udagawa, M., Ootsukasa, S., Arai, T., Maruyama, S., Murase, N., Yamashita, H., Iwai, T.: "Ileosigmoid anastomosis with exclusion of transected ileal loop for intestinal fistula following total cystectomy of bladder cancer : Report of a case"J. Med. Dent. Sci.. 47. 243-246 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Funato, N.: "Basic helix-loop-helix transcription factor epicardin/pod-1/capsulin suppresse differentiation by negative regulation of transcription"J. Biol. Chem. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyazaki, S.: "Interleukin 2 receptor γ (γ_c) chain knockout mice show less regularity in estrous cycles but achieve normal pregnancy without fetal compromise"Am. J. Reprod. Immunol. 47. 222-230 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hayano, C.: "Accumulation of CD16^+ cells with secretion of Ksp37 in decidua at the end of pregnancy"Am. J. Reprod. Immunol. 48. 57-62 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Michimata, T.: "Distribution of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict preganancy outcome following recurrent abortion"Am. J. Reprod. Immunol. 47. 196-202 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirai, H.: "Agonistic effect of indomethacin on a prostaglandin D_2 receptor, CRTH2"J. Immunol. 168. 981-985 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Michimata, T.: "Accumlation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D2-mediated manner"Mol. Human Reprod. 8. 181-187 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okabe, S.: "Investigation into the usefulness and adverse events of CDDP, 5-FU, and di-Leucovolin (PFL-therapy) for advanced colorectal cancer"J. Med. Dent. Sci.. 49. 77-84 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okabe, S.: "Clinicopathological study of mucous pooling referred to as mucinous component (MUC) in colorectal submucosal invasive carcinomas"J. Med. Dent. Sci.. 48. 69-78 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura, M: "Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2"J. Exp. Med.. 193. 255-261 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura, M: "A novel cell surface molecule of Th2 and Tc2 cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ cells during the early stage of pregnancy"Clin. Exp. Immunol.. 123. 105-111 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura, M: "A novel serum protein that is selectively produced cytotoxic lymphocytes"J. Immunol. 166. 6404-6412 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山下博典 他: "RAG2/γc ダブルノックアウトマウスを用いたヒト大腸癌実験モデルの作製"Biotherapy. 14巻1号. 54-56 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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