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

不孕症治疗与 Ocarian 癌发展之间可能相关性的临床病理学和分子分析

• 批准号: 09470358
• 负责人: KONISHI Ikuo
• 金额: $ 6.85万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470358/
• 关键词: ovarian 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

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

不孕治疗与卵巢癌发展之间的可能关系最近受到了很多关注，并且有一些病例报道使用促性腺激素在排卵期间发生卵巢癌。该研究项目的目的是阐明在这种情况下卵巢癌的临床病理学特征，并检查促性腺激素是否影响卵巢癌或卵巢表面上皮，这是上皮卵巢癌的组织遗传学起源。我们6例上皮卵巢癌的组织作用。对我们的6例的分析，并揭示了卵形的两种类型的卵巢癌 - 在卵巢癌中进行了两种类型，以下是卵巢癌 - 卵巢癌 - 卵巢癌 - 卵巢癌 - 在卵巢癌中 - 卵巢癌 - 癌或LMP肿瘤。在临床上，这种肿瘤突然出现，并且经常与腹膜内转移有关。即使在不孕治疗期间，也很难早日检测浆液性癌。另一种类型是在子宫内膜囊肿中产生的透明细胞或子宫内膜细胞癌。通过经阴道超声检查和MRI仔细随访，可以仔细随访，早期发现这种类型的癌的更多离子。我们的研究表明，对于LH/HCG受体，卵巢表面上皮（OSO）具有免疫反应性。在OSE的原代培养系统中，这些细胞暴露了HCG的特异性结合能力，并表达了LH/HCG受体基因的mRNA。 HCG不仅增强了增殖活性，而且还抑制了OSE细胞血清剥夺引起的凋亡。 HCG凋亡抑制的信号转移是通过上调胰岛素样生长因子-I（IGF-1）而发生的。这些结果表明，促性腺激素大概参与了OSE的行为，例如排卵后的卵巢表面修复。大约一半的卵巢癌在mRNA和蛋白质水平上表达LH/HCG受体。在表达LH/HCG受体的卵巢癌细胞系（OVCAR3）中，HCG通过上调IgE-1抑制了顺铂诱导的凋亡。据认为，促性腺激素也可能在卵巢癌的生物学行为和/或化学上发挥重要作用。总之，我们的研究表明，不孕治疗与卵巢癌之间存在因果关系。较少的

项目成果

Kuroda H, et al.: "Ovarian cancer in infertile women during or after" Int J Gynecol Cancer. 7. 451-457 (1997)

Kuroda H 等人：“不孕妇女期间或之后的卵巢癌”Int J Gynecol Cancer。

Mandai M, et al.: "Messenger ribonucleic acid expression of LH/hCG receptor" Eur J Cancer. 33. 1501-1507 (1997)

Mandai M 等人：“LH/hCG 受体的信使核糖核酸表达”Eur J Cancer。

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)

小西育夫、富樫香织：“子宫内膜异位症（“子宫内膜异位囊肿引起的卵巢癌的早期诊断”）”新光贸易伊绍出版社，15（1997）

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)

Mandai, M., Konishi, I., et al.：“人类卵巢癌中 LH/hCG 受体基因的信使核糖核酸表达。”

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)

Kuroda, H.、Mandai, M.、Konishi, I. 等人：“人绒毛膜促性腺激素 (hCG) 抑制顺铂诱导的卵巢癌细胞凋亡：胰岛素样生长因子 1 上调的可能作用