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Comparative study of concentrations of antitumor agents in serum and tumor in nude mouse and human

Research Project

Project/Area Number 62570579
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionKeio University

Principal Investigator

KUBOTA Tetsuro  Keio University, Department of Medicine, Assistant, 医学部, 助手 (00118944)

Project Period (FY) 1987 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
KeywordsConcentration of antitumor agents / Human tumor xenografts / Surgical specimen / Nude mouse / Comparative pharmacology / ヌードマウス
Research Abstract

The pharmacokinetic comparison between nude mouse and human beings is important to use the human tumor xenografts - nude mouse system as a screening panel of newly developed antiunor agents. Mitomycin C (MMC), adriamycin (ADM), 5-fluorouracil (5-FU), cisplatin (DDP), DWA2114R (DWA) and carboplatin (CBDCA) were administered to nude mice bearing human tumor xenografts in maximum tolerated doses and to patinets with cancer in conventionally available doses in clinics. The concentrations of antitumor agents in serum and tumor were detected by bioassay for MMC and 5-FU, high performance liquid chromatography for ADM and atom absorption method for DDP, DWA and CBDCA.
The maximum serum concentration (Cmax in ug/ml) and concentration in tumor (T in ug/g) in nude mouse and human were as follows; mmc ADM 5-FU DDP DWA CBDCA Cmax in mouse 1.09 1.44 44.7 4.8 30.3 61.2 Cmax in human 0.84 0.42 85.4 2.2 24.0 6.5 T/Cmax% (mouse) 1.3 209.1 10.4 40.6 31.0 27.9 T/Cmax% (human) 0.9 354.6 3.1 42.9 30.7 10.4 T/Cmax ratio of each agent in mouse and human was similar to each other with a statistical significance at r = 0.996 (p 0.001).

Report

(4 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • Research Products

    (54 results)

All Other

All Publications (54 results)

  • [Publications] 稲田高男,久保田哲朗・他: "ヒト肺小細胞癌を用いたin vitro,in vivo制癌剤感受性試験ー併用化学療法についてー" 日本癌治療学会誌. 22. 1361-1366 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Konno,H.,Kubota,T.,et al.: "Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha fetoprotein monoclonal antibody" Cancer Research. 47. 4471-4477 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 久保田哲朗・他: "KM2210により著効が得られた再発乳癌の2例" 癌と化学療法. 14. 2556-2559 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Isobe,Y.,Kubota,T.,et al.: "Pharmacodynamic aspects of in vitro and in vivo chemosensitivity tests" Jpn.J.Cancer Res.78. 983-990 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 下山豊,久保田哲朗・他: "ヌ-ドマウス可移植性ヒト癌株に対するcisplatinとcarboplatinの抗腫瘍効果ー胃癌株を中心としてー" 癌と化学療法. 14. 2682-2687 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kikuyama,S.,Kubota,T.,et al.: "Cell kinetic study of human carcinomas using bromodeoxyuridine" Cell Tissue Kinetics. 21. 15-20 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 久保田哲朗ほか: "乳癌の内分泌療法" 乳癌の臨床. 2. 517-523 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yamada,Y.,Kubota,T.,et al.: "Human tumor clonogenic assay with reference to the clinical effect of chemotherapy" Surgical Research Communication. 4. 41-51 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 久保田哲朗ほか: "ホルモン依存性ヒト乳癌株Brー10を継代中に発生したホルモン非依存性腺癌Bxー1の性状と両腫瘍株の分離" 癌と化学療法. 15. 2081-2086 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota,T.,et al.: "Mode of action of busramustine on human breast carcinoma xenografts in nude mice" Japanese Journal of Cancer Research(Gann). 79. 1224-1229 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoue,S.,Kubota,T.: "Antitumor activity of quinocarmycin citrate(KWー2152)against human tumor xenografts serially transplanted into nude mice" Keio Jounal of Medicine. 37. 355-364 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 久保田哲朗ほか: "^<125>Iモノクロ-ナル抗体NCC-ST-433を用いたヒト肺小細胞癌の免疫画像診断ー基礎的検討" 癌と化学癌法. 16. 393-398 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota,T.,et al.: "Human breast carcinoma(ZRー75ー1)serially transplanted into nude mice-with reference to estradiol dependency and sensitivity to tamoxifen" Japanese Journal of Surgery. 19. 446-451 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota,T.,et al.: "Antitumor activity of KW2149 against human tumor xenografts serially transplanted into nude mice" Japanese Journal of Clinical Oncology. 19. 216-221 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 久保田哲朗ほか: "腫瘍マ-カ-を用いたtargetins療法ー基礎的検討ー" カルキノス. 2. 1351-1357 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 久保田哲朗ほか: "Human tumor clonogenic assayによる術後補助化学療法の選択" カルキノス. 3. 25-31 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Suto,A.,Kubota,T.,et al.: "MTT assay with reference to the clinical effect of chemotherapy" Journal of Surgical Oncology. 42. 28-32 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota,T.,et al.(分担執筆): "Experimental endocrinotherapy of hormone-dependent human breast carcinomas transplanted into nude mice in“Immune Deficient Animals"" Karger,Basel, 420 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 久保田哲朗(分担執筆): "“がん治療のあゆみ"新しいモノクロ-ナル抗体(NCCーSTー433)を用いた癌治療法の開発" 癌と化学療法社, 161 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota,T.,et al.: "The clinical usefulness of human xenografts in nude mice.In,Predicition of response to cancer therapy(ed.C.Hall)" Alan,R.Liss,New York, 213-225 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota,T.,et al.: "Immune-Deficient Animals in Experimental Medicine" Karger,Basel, 209-211 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Konno, H., Kubota, T., et al.: "Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha fetoprotein monoclonal antibody" Cancer Res., 47, 4471-4477, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Isobe, Y., Kubota, T., et al: "Pharmacodynamic aspects of in vitro and in vivo chemosensitivity test" Jpn. J. Cancer Res., 78, 983-990, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota, T., et al.: "Experimental endocrinotherapy of hormone-dependent human breast carcinomas transplanted into nude mice" Immune Deficient Animals 1987, Karger, Basel.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kikuyama, S., Kubota, T., et al.: "Cell kinetic study of human carcinomas using bromdeoxyuridine" Cell Tissue Kinetics, 21, 15-20, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yamada, Y., Kubota, T., et al.: "Human tumor clonogenic assay with reference to the clinical effect of chemotherapy" Surg. Res. Comm., 4 41-51, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota, T., et al.: "Mode of action of busramustine on human breast carcinoma xenografts in nude mice" Jpn. J. Cancer Res., 79, 1224-1229, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoue, S., Kubota, T., et al: "Antitumor activity of quinocarmycin citrate (KW-2152) against human tumor xenografts in nude mice" Keio J. Med., 37, 355-364, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota, T., et al.: "The clinical usefulness of human xenografts in nude mice" Prediction of response to Cancer Therapy, 1988 Alan, R. Liss, New York.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota, T., et al.: "Human breast carcinoma (ZR-75-1) serially transplanted into nude mice - with reference to estradiol dependency and tamoxifen sensitivity" Jpn. J. Surg., 19 446-451, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota, T., et al.: "Antitumor activity of KW2149 against human tumor xenografts serially transplanted into nude mice" Jpn. J. Clin. Oncol., 19, 216-221, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Suto, A., Kubota, T., et al.: "MTT assay with reference to the clinical effect of chemotherapy" J. Surg. Oncol., 42, 28-32, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kubota, T., et al.: "Immune-Deficient Animals in Experimental Medicine" Karger, Basel, 1989 P. 209-211.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 久保田哲朗,ほか: "^<125>Iモノクロ-ナル抗体NCC-ST-433を用いたヒト肺小細胞癌の免疫画像診断-基礎的検討" 癌と化学療法. 16. 393-398 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kubota,T.,et al.: "Human breast carcinoma(ZR-75-1)serially transplanted into nude mice-with reference to estradiol dependency and sensitivity to tamoxifen" Japanese Journal of Surgery. 19. 446-451 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kubota,T.,et al.: "Antitumor activity of KW2149 against human tumor xenografts serially transplanted into nude mice" Japanese Journal of Clinical Oncology. 19. 216-221 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 久保田哲朗,ほか: "腫瘍マ-カ-を用いたtargeting療法-基礎的検討-" カルキノス. 2. 1351-1357 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 久保田哲郎,ほか: "Human tumor clonogenic assayによる術後補助化学療法の選択" カルキノス. 3. 25-31 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suto,A.,Kubota,T.et al.: "MTT assay with reference to the clinical effect of chemotherapy" Journal of Surgical Onoclogy. 42. 28-32 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kubota,T.,et al.: "Immune-Deficient Animals in Experimental Medicine" Karger,Basel, 209-211 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kikuyama,S.;Kubota,T.;et al.: Cell Tissue Kinetics. 21. 15-20 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 久保田哲朗 他: 乳癌の臨床. 2. 517-523 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yamada,Y.;Kubota,T.;et al.: Surgical Research Communication. 4. 41-51 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 久保田哲朗 他: 癌と化学療法. 15. 2081-2086 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kubota,T.;et al.: Japanese Journal of Cancer Research(Gann). 79. 1224-1229 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Inoue,S.;Kubota,T.: Keio Journal of Medicine. 37. 355-364 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kubota,T.;et al.: "The clinical usefulness of human xenografts in nude mice.In,Predicition of response to cancer therapy" Alan,R.Liss, 213-225 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 稲田高男, 久保田哲朗 他: 日本癌治療学会誌. 22. 1361-1366 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Konno, H. ;Kubota, T. et al: Cancer Research. 47. 4471-4477 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 久保田哲朗 他: 癌と化学療法. 14. 2556-2559 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Isobe, Y. ;Kubota, T. et al.: Jpn. J. Cancer Res.78. 983-990 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 下山豊, 久保田哲朗 他: 癌と化学療法. 14. 2682-2687 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Kubota, T., et al.: "Experimental endocrinotherapy of hormone-dependent human breast carcinomas transplanted into nude mice in "Immune Deficient Animals"" Karger, Basel, 420 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 久保田哲朗 他: ""がん治療のあゆみ"新しいモノクローナル抗体(NCC-ST-433)を用いた癌治療法の開発" 癌と化学療法社, 161 (1987)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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