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Improvement of human tumor xenograft-mouse model as a preclinical evaluation system of new drugs discovered and developed by the novel strategy against cancer

Research Project

Project/Area Number 08458278
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

OHNISHI Yasuyuki  Cent. Inst. Exp. Anim. Lab. Oncology Head, 腫瘍研究室, 室長 (70201382)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Masato  Tokai Univ. Sch. Med. Dept. Pathol.Instractor, 医学部, 講師 (00164335)
HIOKI Kyoji  Cent. Inst. Exp. Anim. Animal Resource Ctr.Head, 飼育技術研究室, 室長 (80208735)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsxenograft / mouse / ribozyme / vascular endotherial growth factor / xenotransplantability / epidermal growth factor receptor / c-erb Bhuman neoplasm / C-erb B / 乳酸脱水素酵素ウイルス / GM-CSF / トランスジェニック / 血管内皮増殖因子 / P-glycoprotein / ヌードマウス / SCIDマウス / アイソフォーム / G-CSF / 腫瘍 / ヒト / オーソトピック移植 / P.glycoprotein / c-erbB-2 / ヒト型抗体 / DNAフィンガープリント
Research Abstract

In the recent strategy for treatment of cancer disease, concepts such as inhibition of oncogene activity, control of invasion and metastasis of cancer cells were attentioned as a novel target.To apply human tumor xenograft (HTX) model to the evaluation of new drugs which are discovered by those concepts, we improved host mouse and procedures of implantation of HTX.We also analyzed gene expression related to progress of carcinogenecity and malignancy of neoplasm.
We established double mutant mice for athymic nude (nu) and severe combined immune deficient (scid) genes.This allowed us that human skin was implanted more efficiently in the mice than in nude mouse.We first developed human skin grafted-mice using these double mutant mice, then HTX was implanted into the human skin.The tumor grew in the skin, and moreover focused in the liver of host mice.We established HTX-mouse model which overexpressed c-erbB-2/HER2 gene, and evaluated monoclonal antibody against C-ErbB-2/HER2 products.We analyzed expression of isoforms of vascular endothelial growth factor (EGER) gene in the HTXs, and found that expression of VEGF 189 in tumor tissue was related to xenotransplantability to SCID mice.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (46 results)

All Other

All Publications (46 results)

  • [Publications] Tetsuji Tokunaga: "Is xenotransplantability of human colon cancers in SCID mice affected by angiogenetic factors?" J.Natl.Cancer Inst.90. 400-401 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masumi Yoshimura: "Chemotherapeutic profiles of human tumors implanted in SCID mice showing appeciable inconsistencies with those in nude mice" Expr.Anim.46. 153-156 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tetsuji Tokunaga: "Aberrant isoforme of vascular endothelial growth factor 189 expression is correlated with xenctransplantability of human esophageal cancer" Oncol.Rep.5. 1115-1118 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamazaki,Hitoshi: "Inhibition of tumor grawth by ribozyme-mediatal suppression of aberrant epilermal growth factor receptor gene expression" J.Natl.Cancer Inst.90. 581-587 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuyuki Ohnishi: "Re:Relationship between topotecan systemic exposure and tumor respoinse in human neuroblastoma xenografts" J.Natl.Cancer Inst.90. 1909-1910 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuyuki Ohnishi: "Practical role of genetic profiling and preserlation stock of human tumour exnogreft lines as a toal in animal experiments for antitumour drug evaluation" Lab.Anim.31. 169-176 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohnishi, Y., et al.: "Re : Relationship between topotecan systemic exposure and tumor response in human neuroblastoma xenografts." J.Natl. Cancer Inst. 90. 1909-19l0 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tokunaga, T., Oshika, Y., Ohnishi, Y., Ueyama, Y.and Nakamura, M.: "Response." J.Natl.Cancer Inst.90. 1747-1749 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamazaki, H., et al.: "M.Inhibition of tumor growth by ribozyme-mediated suppression of aberrant epidermal growth factor receptor gene expression." J.Natl. Cancer Inst.90. 581-587 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oshika, Y., et al.: "Growth stimulation of non-small cell ung cancer xenografts by granulocyte-macrophage colony-stimulating factor (GM-CSF)." Eur. J.Cancer. 34. 1958-1961 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kimura, M., et al: "Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer." cancer Res. 58. 2456-2460 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Goto, K., et al.: "Detection and typing of lactate dehydrogenase-elevating virus RNA from transplantable tumors mouse liver tissues and cell Iines using polymerase chain reaction." Lab.Anim.Sci.48. 99-102 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tokunaga, T., Nakamura, M., Oshika, Y., Ohnishi, Y.and Ueyama, Y.: "Is xenotransplantability of human colon cancers in SCID miuce affected by angiogenic factors? ." J.Natl. Cancer Inst.90. 400-401 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suto, R., et al.: "Multidrug resistance mediated by overexpression of P-glycoprotein in human osteosarcoma in vivo." Int. J.Oncology. 12. 287-291 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inaba, M., Ohnishi, Y., Ishii, H., Tanioka, Y., Yoshida, Y., Sudoh, K, Hakusui, H., Mizuno, N., Ito, K and Sugiyama, Y.: "Pharmacokinetics of CPT-11 in rhesus monkeys." Cancer Chemother. Pharmacol. 41. 103-108 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oshika, Y., et al.: "A human lung cancer xenograft producing granulocyte-colony stimulating factor and parathyroid hormone-related protein." Oncol. Rep. 5. 359-362 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tokunaga, T., et al.: "Aberrant isoforme of vascular endothelial growth factor 189 expression is correlated with xenotransplantability of human esophageal cancer" Oncol. Rep.5. 1115-1118 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshimura, M., et al.: "Quarantine for contaminated pathogens in transplantable human tumors or infections in tumor beaning mice." Expr. Anim.46. 161-164 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohnishi Y et al.: "Practical role of genetic profiling and preservation stock of human tumour xenograft lines as a tool in animal experiments for antitumour drug evaluation." Lab. Anim.31. 169-176 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshimura, et al.: "Chemotherapeutic profiles of human tumors implanted in SCID mice showing appreciable inconsistencies with those in nude mice." Expr. Anim. 46. 153-156 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takamiya, Y., et al.: "Murine P-glycoprotein on stromal vessels mediates multidrug resistance in intracerebral human glioma xenografts." Br.J.Cancer. 76. 445-450 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe, Y., et al.: "A xenograft line of human teratocarcinoma established by serial transplantation in severe combined immunodeficient (SCID) mice." APMIS. 105. 283-289 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsugu, A., et al.: "Localization of aberrant messenger RNA of epidermal growth factor receptor (EGFR) in malignant glioma." AntiCancer Res.17. 2225-2232 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe, Y., Ohnishi, Y., et al.: "P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo." Br.J.Cancer. 74. 1929-1934 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hioki, K, et al.: "Suppression of intestinal polyp development by low-fat and high-fiber diet in Apc^<c716> knockout mice." Carcinogenesis. 18. 1863-1865 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tokuda, Y., Ohnishi, Y., et al.: "In vitro and in vivo anti-tumor effects of a humanized monoclonal antibody against c-erbB-2 product." Br.J.Cancer. 73. 1362-1365 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe, Y., et al.: "Advantage of in vivo chemosensitivity assay to detect vincristine-resistance in a human epidermoid carcinoma xenograft." AntiCancer Res.16. 729-734 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inaba, M., et al.: "In vitro-in vivo correlation in anticancer drug sensitivity test using AUC-based concentrations and collagen gel droplet-embedded culture." Oncology. 53. 250-257 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuyuki, Ohnishi: "Re : Relationship between toputecan systemic exposuce and tumer responce in human neuroblastoma xenografts" J.Natl.Cancer Inst.90. 1909-1910 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tetsuji Tokunaga: "Aberrant isoforme of vasular endothelial growth factor 189 expression is correlated with xenetransplantability of human ecophaeeal cancer" Oncol.Rep.5. 1115-1118 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hitoshi Yamazaki: "Inhibition of tumor growth by ribozyme-mediated suppression of aberrant epdermal growth factor receptor gene expression" J.Natl.Cancer Inst.90. 581-587 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshiro Oshika: "Growth stimulation of non-small cell lung cancer xenografts by granulocyte-macrophage colory-stimulatinig factor(GM-CSF)" Eur.J.Cancer. 34. 1958-1961 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kazuo Goto: "Detection and typing of lactate dehydrogenase-elevating virus RNA from transplan table tumors, mouse llver tissues, and cells using polymerase chaln read" Lab.Anim.Sci.48. 99-102 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ryuji Suto: "Multidrag resistance medlated by overexpression of P-glycoprotein in human osteosarcoma in vivo" Int.J.Oncol.12. 287-291 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toknaga,T: "Is xenotransplantability of human colon cancers in SCID mice affected by angiogenic factors?" J.Natl.Cancer Inst.90. 400-401 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suto,R: "Multidrug resistance mediated by overexpression of P-glycoprotein in human osteosav coma in vivo" Int.J.Oncol.12. 287-291 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oshika,Y: "A human lung cancer renagraft producing granulocyte colony stimulating factor and parathyroid hormon-related protein" Oncol,Rep.5. 359-362 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Inaba,M: "Pharmacokinetics of CPT-11 in rhesus monkeys" Cancer Chemother.Pharmucol.41. 103-108 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takamiya,Y: "Murine P-glycoprotein on storomal vessels mediates multidrug resistance in intracerebral human alioma yenografte" Br.J.Cancer. 76. 445-450 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshimura,M: "Quarantin for contaminated pathogens in transplantable human tomors or infection in tumer bearing mice" Expr.Anim.46. 161-164 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takamiya,T.: "Murine P-glycoprotein on stromal vessels mediates multidrug resistance in intracelebral human glioma xenografts" Br.J.Cancer. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohnishi,Y.: "Practical role of genetic profiling and preservation stock of human tumour xenograft lines as a tail in animal experiment for antitumour drug evaluation" Lab.Anim.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshimura,M.: "Chemotherapeutic profiles of human tumors implanted in SCID mice showing appreciable inconsistencies with those in nude mice" Expr.Anim.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Abe,Y.: "P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo" Br.J.Cancer. 74. 1929-1934 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tokuda,Y.: "In vitro and in vivo anti-tumor effects of a humanized monoclonal antibody against c-erbB-2 product" Br.J.Cancer. 73. 1362-1365 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Abe,Y.: "Advantage of in vivo chemosensitivity assay detect vincristin-resistance in a human epidermoid carcinoma xenograft" AntiCancer Res.16. 726-734 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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