Noriyuki Akutagawa

Lysyl Oxidase and MMP-2 Expression in Dehydroepiandrosterone-Induced Polycystic Ovary in Rats

Abstract Polycystic ovary syndrome (PCOS) is characterized by cystogenesis; however, the cause of this cystogenesis is unknown. At ovulation, preovulatory collagenolytic activities in the ovarian follicles increase and various proteinases are needed to degrade the tissues surrounding the follicles. To clarify the roles of enzymes in collagen degradation of the follicular wall of polycystic ovary (PCO) in relation to the cystogenesis, we examined expression of lysyl oxidase (LOX), which initiates cross-link formation of the collagen and elastin in the extracellular matrix, and expression of matrix metalloproteinases (MMPs) in ovaries of model rats with PCO induced by dehydroepiandrosterone (DHEA) compared with MMP expression in control rats. DHEA treatment increased LOX mRNA expression to more than three times the control value (P < 0.01). MMP-2 mRNA expression in control rats was threefold greater than that in the DHEA-induced group (P < 0.05). Expression of both latent and active forms of MMP-2 in controls was more than twice that in the DHEA-induced group (P < 0.05) as shown by Western blotting, and expression of the active form of MMP-2 was also twice as high in the controls as in the DHEA-treated group (P < 0.05) as shown by zymography. Our results suggest that depression of MMP-2 activity and increased LOX expression may be one of the causes of the cystogenesis of PCO.

Expression of vascular endothelial growth factor and E-cadherin in human ovarian cancer: association with ascites fluid accumulation and peritoneal dissemination in mouse ascites model.

Ascites formation and peritoneal dissemination are critical problems in patients with advanced ovarian cancer. Vascular endothelial growth factor (VEGF), also known as angiogenic growth factor, is a potent mediator of peritoneal fluid accumulation and angiogenesis of tumors. E‐Cadherin is an adhesion molecule that is important for cell‐to‐cell interaction. To elucidate the molecular mechanism of ascites formation and peritoneal dissemination of ovarian cancer, we examined the expression of VEGF and E‐cadherin in different ovarian cancer cell lines and utilized nude mice to compare the biological characteristics of ovarian cancer cells. Three human ovarian cancer cell lines (AMOC‐2, HNOA and HTBOA) were used in this study. Expression of genes was analyzed by northern blotting and RT‐PCR methods. AMOC‐2 expressed E‐cadherin, but not VEGF. HNOA expressed VEGF without E‐cadherin expression. HTBOA expressed both VEGF and E‐cadherin. Each human ovarian cancer model revealed a specific feature. The AMOC‐2 mouse had a single large peritoneal tumor without ascites or remarkable peritoneal dissemination. HTBOA and HNOA mice had bloody ascites and marked peritoneal dissemination. Introduction of VEGF antisense into HTBOA cells could inhibit the ascites formation. It is suggested that VEGF is important for the ascites formation via the increased vascular permeability effect. The deregulation of E‐cadherin expression might be involved in the peritoneal dissemination. These molecules are important for the formation of specific features of advanced ovarian cancer. Ovarian cancer cell lines that had different gene expression patterns produced nude mouse human ovarian cancer models with different characteristics.

A case of ovarian actinomycosis

Background: Pelvic actinomycosis is uncommon and often presents as a complication of an intrauterine device (IUD). A diagnosis of actinomycosis can be made from the finding of sulfur granules within inflammatory exudate on histologic examination after surgery. However, it may be possible to diagnose actinomycosis before surgery by finding Actinomyces-like organisms on Papanicolaou smears. Case: A 41-year-old woman had been diagnosed as having a pelvic abscess, and bilateral salpingo-oophorectomy was performed. She had been an IUD user for 6 years. Actinomyces-like organisms were detected in her previous Papanicolaou cervical smears. If the patient had been treated when the Actinomyces-like organisms were detected by Papanicolaou smears, the serious ovarian actinomycosis might have been avoided. Conclusion: We suggest that routine cervical examinations are important for women who are IUD users.

A Case of a Screlosing Stromal Ovarian Tumor That Expresses VEGF

A case of a sclerosing stromal tumor (SST) of the ovary is presented. One of the tumors characteristics was its high vascularity. On immunohistochemical staining, the vascular endothelial growth factor (VEGF) was positive for both cellular and edematous areas in the tumor. VEGF was thought to be a factor that affected the clinicopathological features of this tumor.