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Clinicopathological and Molecular Analyses for Possible Correlation between Infertility Therapy and Development of Ocarian Cancer

Research Project

Project/Area Number 09470358
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

KONISHI Ikuo  Kyoto University, Gynecology and Obstetrics, Assistant Professor, 医学研究科, 講師 (90192062)

Co-Investigator(Kenkyū-buntansha) SAGAWA Norimasa  Kyoto University, Gynecology and Obstetrics, Associate Professor, 医学研究科, 助教授 (00162321)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥8,300,000 (Direct Cost: ¥8,300,000)
Keywordsovarian cancer / infertility / gonadotropin / Lh / hCG receptor / apoptosis / insulin-like growth factor-1 / ovarian surface epithelium / 不妊症治療 / hCG受容体 / IGF-1
Research Abstract

Possible relationship between infertility therapy and development of ovarian cancer has recently received much attention, and there have been case reports of ovarian carcinoma which occurred during ovulation-induction using gonadotropic agents. The aim of this research project is to clarify the clinicopathological characteristics of ovarian cancer in this setting, and to examine if gonadotropins affect ovarian cancer or ovarian surface epithelium, the histogenetic origin of epithelial ovarian carcinoma.
Analysis of our 6 cases and review of the literature revealed that ovarian carcinomas during or after ovulation-induction therapy are classified into 2 types : one is serous type carcinoma or LMP tumor. Clinically, such tumors suddenly appeared and are frequently associated with intraperitoneal metastases. Early detection of serous carcinoma is difficult even during the infertility treatment. Another type is clear cell or endometrioid carcinoma arising in endometriotic cyst. Early detect … More ion of this type carcinoma is possible by careful followup using transvaginal ultrasonography and MRI.
Our study demonstrated that ovarian surface epithelium (OSE) is immunoreactive for LH/hCG receptors. In the primary culture system of OSE, these cells exhibited specific binding capacity for hCG, and expressed mRNA of LH/hCG receptor gene. hCG not only enhanced the proliferative activity, but also inhibited apoptosis induced by serum-deprivation in OSE cells. Signal transduction of apoptotic inhibition by hCG occurred via up-regulation of insulin-like growth factor-i (IGF-1). These results suggest that gonadotropins are presumably involved in the behavior of OSE such as repair of the ovarian surface after ovulation.
An approximately half of ovarian carcinomas expressed LH/hCG receptor at both mRNA and protein levels. In ovarian cancer cell line (OVCAR3) expressing LH/hCG receptors, hCG inhibited cisplatin-induced apoptosis via up-regulation of IGE-1. Accordingly, gonadotropins may also play an important role in biological behavior and/or chemoresistance of ovarian cancer. In conclusion, our studies suggest the causal relationship between infertility therapy and ovarian cancer. Less

Report

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

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Komatsu T, et al.: "Adnexal masses : transvaginal US and Gadolinium-enhanced" Radiology. 198. 109-115 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi F, et al.: "Rapid growth of an ovarian clear cell carcinoma" Gynecol Oncol. 62. 309-313 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mandai M, et al.: "Messenger ribonucleic acid expression of LH/hCG receptor" Eur J Cancer. 33. 1501-1507 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuroda H, et al.: "Ovarian cancer in infertile women during or after" Int J Gynecol Cancer. 7. 451-457 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuroda H, et al.: "Human chorionic gonadotropin(hCG)inhibits cisplatin" Int J Cancer. 76. 571-578 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Konishi I, et al.: "Review : gonadotrophins and development of ovarian cancer" Oncology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小西郁生、万代昌紀: "図説産婦人科VIEW分子細胞生物学(“卵巣悪性腫瘍と癌遺伝子")" メジカルビュー社, 223(8) (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小西郁生、富樫かおり: "子宮内膜症の診断と治療(“子宮内膜症性嚢胞より発生する卵巣癌")" 真興交易医書出版, 309(15) (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Komatsu, T., Konishi, I., et al.: "Adnexal mass : comparison of transvaginal US and gadolinium-enhanced MR imaging assesment of intratumoral structure." Radiology. 198. 109-115 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi, F., Konishi, I., et al.: "Rapid growth of ovarian clear cell carcinomas expressing LH/hCG receptor arising from endometriosis during early pregnancy." Gynecol Oncol. 62. 309-313 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mandai, M., Konishi, I., et al.: "Messenger ribonucleic acid expression of LH/hCG receptor gene in human ovarian carcinomas." Eur J Cancer. 33. 1501-1507 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuroda, H., Konishi, I., et al.: "Ovarian cancer in infertile women during or after ovulation-induction therapy : expression of LH/hCG receptors and sex steroid receptors." Int J Gynecol Cancer. 7. 451-457 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuroda, H., Mandai, M., Konishi, I., et al.: "Human chrionic gonadotropin(hCG)inhibits cisplatin-induced apoptosis in ovarian cancer cells : possible role of up-regulation of insulin-like growth factor-1 by hCG." Int J Cancer. 76. 571-578 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Konishi, I., et al.: "Review : gonadotropins and development of ovarian cancer." Oncology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Komatsu T,et al.: "Adnexal masses:transvaginal US and Gadolinum-enhanced" Radiology. 198. 109-115 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi F,et al.: "Rapid growth of an ovarian clear cell carcinoma" Gynecol Oncol. 62. 309-313 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mandai M,et al.: "Messenger ribonucleic acid expression of LH/hCG receptor" Eur J Cancer. 33. 1501-1507 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuroda H,et al.: "Ovarian cancer in infertile women during or after" Int J Gynecol Cancer. 7. 451-457 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuroda H,et al.: "Human chorionic genadotropin(hCG)inhibits cisplatin." Int J Cancer. 76. 571-578 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Konishi I.et al.: "Review:gonadotropins and development of ovarian cancer" Oncology. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] 小西郁生、万代昌紀: "図説産婦人科VIEW分子細胞生物学(“卵巣悪性腫瘍と癌遺伝子")" メジカルビュー社, 223(8) (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小西郁生、富樫かおり: "子宮内膜症の診断と治療(“子宮内膜症性嚢胞より発生する卵巣癌")" 真興交易医書出版, 309(15) (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小西郁生: "不妊症治療と卵巣癌" 日本産科婦人科学会熊本地方部会雑誌. 41. 15-24 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mandai,M., et al.: "Messenger ribonucleic acid expression of LH/hCG receptor gene" European Journal of Cancer. 33. 1501-1507 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamamoto,S., et al.: "Expression of vascular endothelial growth factor (VEGF) in" British Journal of Cancer. 76. 1221-1227 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kuroda,H., et al.: "Ovarian cancer in infertile women during or after ovulation-" International Journal of Gynecological cancer. 7. 451-457 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kuroda,H., et al.: "Human chorinic gonadotropin inhibits cisplatin-induced apoptosis" International Journal of Cancer. (印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] 小西郁生, 富樫かおり: "子宮内膜症(“子宮内膜症性嚢胞より発生する卵巣癌の早期診断")" 真興交易医書出版, 15 (1997)

    • Related Report
      1997 Annual Research Report

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

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