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Study of multidrug-resistance mechanism and its overcoming in cutaneous mesenchymal malignant tumor

Research Project

Project/Area Number 10670814
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionOsaka Medical College

Principal Investigator

KUSAKABE Hidenari  Faculty of Medicine, Osaka Medical College Associate Professor, 医学部, 助教授 (00195421)

Co-Investigator(Kenkyū-buntansha) SAKATANI Shoko  Faculty of Medicine, Osaka Medical College Assistant Professor, 医学部, 講師 (20196075)
KIYOKANE Kimihiro  Faculty of Medicine, Osaka Medical College Professor, 医学部, 教授 (50085023)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsmesenchymal tumor / epithelioid sarcoma / multidurg resistance / lung resistance protein / sensitivity test / anticancer drug / LRP / 抗癌剤感受性検査 / 間葉性悪性腫瘍 / 多剤耐性 / actinomycin D
Research Abstract

The incidence of epithelioid sarcoma among cases with malignant soft tissue tumors is small, however, the rates of recurrence and metastasis of this type of sarcoma are high. To date, effective chemotherapy for advanced epithelioid sarcoma has not been established, furthermore, epithelioid sarcoma is known to exhibit multidrug resistance (MDR). The chemosensitivities of two cell lines established from epithelioid sarcoma to anticancer agents are examined in this study. The results showed that the ES-OMC-MN and SFT-8606 cell lines were resistant to vincristine (IC_<50>=1,190 nM and 872 nM, respectively) and adriamycin (IC_<50>=921 nM and 650 nM, respectively), but sensitive to actinomycin D (IC_<50><10 nM). The p-glycoprotein (p-Gp) and multidrug resistance gene 1 (MDRI) were not expressed in these cell lines, however, a high expression level of the lung resistance protein (LRP) was observed. The original tumor tissues from which the two cell lines were established were also found to be LRP-positive but not to express p- Gp. Their chemosensitivities to adriamycin of the cell lines, ES-OMC-MN and SFT- 8606, pretreated with 2.5 μg/ml anti-LRP antibody (LRP-56) were not significantly altered, however, the IC_<50> of vincristine became much smaller (IC_<50>=128 nM and 27 nM, respectively) than that in a non-pretreated cell line. It is thus suggested that the vincristine resistance in the two cell lines is LRP-mediated. Since cyclosporin A, known to be a modifier of p-Gp, also induced reversal of vincristine resistance in the ES-OMC- MN and SFT-8606 cell lines (IC_<50>=6.2 nM and 17 nM, respectively), it is suggested that cyclosporin A acts as a modifier against LRP.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Hidenari Kusakabe: "Expression of lung resistance protein in epithelioid sarcoma in vitro and in vivo"Archives of Dermatological Research. 292. 292-300 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 遠藤由紀子: "多発性骨転移を伴った乳房外Paget病の1例"Skin Cancer. 14. 311-315 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazu Nakano: "Acute monocytic leukemia presenting as cutaneous involvement"Dermatology. 199. 349-352 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hidenari KUSAKABE, Hiroshi IWASAKI, Kouichi SANO, Kimihiro KIYOKANE: "Expression of lung resistance protein in epithelioid sarcoma in vitro and vivo"Archives of Dermatological Research. 292. 292-300 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukiko ENDO, Takasi MATSUMURA, Utako ENOMOTO, Seiji MAESHIMA, Shoko SAKATANI, Hidenari KUSAKABE, Kimihiro KIYOKANE: "A case of extramammary Paget disease with multiple metastasis"Skin Cancer. 14. 311-315 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazu NAKANO, Hidenari KUSAKABE, Kimihiro KIYOKANE: "Acute monocytic leukemia presenting as cutaneous involvement"Dermatology. 199. 349-352 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hidenari Kusakabe: "Expression of lung resistance protein in epithelioid sarcoma in vitro and in vivo"Archives of Dermatological Research. 292. 292-300 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 窪田正昭: "Poroid hidradenoma"皮膚. 41・6. 675-678 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 土井久生: "Hidroacanthoma simplexとmalignant hidroacanthoma simplexの各1例とその免疫組織学的検討"皮膚. 42・1. 24-30 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 土井久生: "Arteriovenous hemangiomaの2例"皮膚. 42・4. 208-213 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 年名優美: "Toxic shock like syndromeの1例"皮膚. 42・4. 419-425 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 土井久生: "Basal cell carcinomaが隣接して存在したperifollicular fibromnの1例"皮膚. 42・5. 490-494 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Utako Enomoto: "Diffuse cutaneous mastocytosis responding to cyproheptadine"Clinical and Experimental Dermatology. 24. 16-18 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 米林 功二: "Bowenoid papulosisの1例"皮膚. 41. 199-203 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazu Nakano: "Acute monocytic leukemia presenting as cutaneous involvement"Dermatology. 199. 349-352 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 湊 恵美: "Human papilloma virus 16型を検出した外陰部巨大Bowen carcinomaの1例"皮膚. 41. 590-595 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 遠藤 由紀子: "多発性骨転移を伴った乳房外Paget病の1例"Skin Cancer. 14. 311-315 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hidenari Kusakabe: "Expression of lung resistance protein in epithelioid sarcoma in vitro and in vivo"Archives of Dermatological Research. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] 毛利 学: "カラーでみる口腔粘膜疾患の診かた"南江堂. 251

    • Related Report
      1999 Annual Research Report
  • [Publications] 土井 久生: "右足底部に発生したAcral lentiginous melanoma in situの1例" Skin Cancer. 12・3. 410-413 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 前島 精治: "陥凹性病変を呈した隆起性皮膚線維肉腫の1例" Skin Cance. 12・3. 445-448 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 藤田 美智子: "Necrobiosis lipoidicaの1例" 皮膚. 40・2. 147-150 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 米林 功二: "Relapsing polychondritisに合併した白癬菌性肉芽腫の1例" 皮膚. 40・4. 394-398 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中野 佳津: "粘液型脂肪肉腫の1例" Skin Cancer. 13・2. 167-170 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shoko Sakatani: "p53 Gene Mutations in Squamous Cell Carcinoma Occuring in Scars" The American Journal of Dermatopathology. 20・5. 463-467 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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