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Cytopathologic study of intrinsic and acquired drug resistance of human ovarian cancer -the role of YB-1 and cMOAT/MRP2 gene-

Research Project

Project/Area Number 12671612
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyushu University

Principal Investigator

HIRAKAWA Toshio  Kyushu University Hospital, Lecturer, 医学部附属病院, 講師 (20218770)

Co-Investigator(Kenkyū-buntansha) SONODA Kenzo  Kyushu University Hospital, Assistant Professor, 医学部附属病院, 助手 (30294929)
KOBAYASHI Hiroaki  Kyushu University Hospital, Assistant Professor, 医学部附属病院, 助手 (70260700)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
KeywordsOvarian cancer / Drug resistance / YB-1 / cMOAT1 / MRP2 / MRP1 / MRP3 / MRP-2 / P糖蛋白 / MRP-1 / MRP-3
Research Abstract

Purpose: The aim of the first study was to elucidate the association between nuclear YB-1 and cisplatin resistance in human ovarian cancer using cultured cell lines and surgical specimens. Methods: Intracellular YB-1 localization was examined by Western blot analysis for both cisplatin sensitive and resistant human ovarian cancer cell lines. Moreover, 35 pairs of surgical specimens derived from primary and matched recurrent ovarian cancers of the same patient were evaluated for their nuclear YB-1 expression by immunohistochemical staining. Results: Western blot analysis for nuclear and cytoplasmic extracts indicated that cisplatin-resistant cells showed much higher nuclear YB-1 expression than sensitive parental cells. Immunohistochemical analysis showed that 10 paired cases turned from negative nuclear YB-1 in primary lesions to positive nuclear YB-1 in recurrent lesions, whereas only two paired cases showed a reverse turn from positive to negative. Conclusion: The expression of YB-1 … More might be a useful predictive marker indicating cisplatin sensitivity and/or a target molecule to treat recurring ovarian cancers by cisplatin-based second-line chemotherapy.
Purpose: The aim of the second study was to characterize patients with unfavorable clinical outcome by the relative mRNA levels of ABC transporter expression in their tumor samples and to examine whether relative mRNA levels of each of the ABC transporter can be a useful predictor of progression-free survival in advanced ovarian carcinoma. Methods: We examined tumor samples taken from 30 patients with primary serous papillary adenocarcinoma of the ovary for the expression of MDR1, MRP1, MRP2, and MRP3 mRNA using real-time reverse transcription-PCR, and we evaluated its correlation with clinical outcome. All 30 patients were divided into three groups according to clinical outcome after debulking surgery and platinum-based chemotherapy: 8 patients were classified into the unfavorable group; 11 were classified into the favorable group; and 11 were classified into intermediate group. Results: The relative mRNA levels of MRP1 and MRP3 were significantly different among the three groups, and the mRNA levels of MRP1 and MRP3 in the unfavorable group were significantly higher than those in the favorable group by multiple comparison. The relative mRNA levels of MRP1 expression were significantly correlated with those of MRP3 expression. In the 30 patients with serous papillary adenocarcinoma, univariate and multivariate analysis demonstrated that the high relative mRNA levels of MRP1 expression were significantly correlated with a short period of progression-free survival. Conclusion: In patients with advanced ovarian serous adenocarcinoma, these results suggest that increased levels of coordinated MRP1 and MRP3 mRNA expression in their tumor samples characterize patients with an unfavorable outcome. Furthermore, a higher level of MRP1 mRNA expression can be a candidate for a useful predictor of a shorter period of progression-free survival. Less

Report

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

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Yahata H, et al.: "Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer"J Cancer Res Clin Oncol. 128巻. 621-626 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohishi Y, et al.: "ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma"Clin Cancer Res. 8巻. 3767-3775 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yahata H, et al.: "Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer"J Cancer Res Clin Oncol. 128. 621-626 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohishi Y, et al.: "ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma"Clin Cancer Res. 8. 3767-3775 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sonoda K. et al.: "The clinical significance and function of tumor-associated antigen RCAS1"Proceedings of the twelfth Fukuoka International Symposium on Perinatal Medicine. 66-69 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogawa S, et al.: "Prognostic significance of microvessel density, vascular cuffing and vascular endothelial growth factor expression in ovarian carcinoma: a special review for clear cell adenocarcinoma"Cancer Lett. 176巻. 111-118 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yahata H, et al.: "Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer"J Cancer Res Clin Oncol. 128巻. 621-626 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohishi Y, et al.: "ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma"Clin Cancer Res. 8巻. 3767-3775 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hachisuga T, Fukuda K, Iwasaka T, Hirakawa T, et al.: "Endometrioid adenocarcinomas of the uterine corpus in women younger than 50 years of age can be divided into two distinct clinical and pathologic entities based on anatomic location"Cancer. 2578-2584 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hachisuga T, Fukuda K, Hirakawa T, Kawarabayashi T: "The effect of nulliparity on survival in endometrial cancer at different ages"Gynecol Oncol. 122-126 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okugawa k, Hirakawa t, Fukushima K: "Relationship between age, histological type, and size of ovarian tumors"Int J Gynecol Obstet. 45-50 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K Sonoda, et al.: "The clinical significance of tumor-associated antigen RCAS1 expression in the normal, hyperplastic and malignant uterine endometrium"Gynecologic Oncology. 79. 424-429 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K Ohshima,K Sonoda, et al.: "Expression of RCAS1 and FASL in human trophoblasts and uterine glands during pregnancy : the possible role in immune privilege"Clinical and Experimental Immunology. (In press). (2001)

    • Related Report
      2000 Annual Research Report

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

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