Glycogen synthase kinase 3ß and cyclin D1 expression in cervical carcinogenesis.

OBJECTIVE: Glycogen synthase kinase 3ß (GSK3ß) is a pluripotent protein kinase involved in the development of cancers through regulation of numerous oncogenic molecules. Cyclin D1, an important regulator of G1 to S phase transition in various cells, is one of target proteins that GSK3ß regulate. Our objective was to assess the expression of GSK3ß and cyclin D1 in cervical neoplasm of different histologic grades and to identify their correlation in cervical carcinogenesis. METHODS: Immunohistochemical analysis of GSK3ß and cyclin D1 was performed in a total of 137 patients with 12 normal, 62 cervical intraepithelial neoplasia (CIN) (31 CIN1 and 31 CIN3) and 63 invasive cancers including 56 squamous cell carcinomas and 7 adenocarcinomas. RESULTS: The expression of GSK3ß increased in parallel with the lesion grade, while that of cyclin D1 decreased with severity of the lesion (P<0.001). There was a significant inverse correlation between GSK3ß and cyclin D1 expression in overall cervical neoplasia (Φ=-0.413, P<0.001). GSK3ß expression was higher in squamous cell carcinoma than in adenocarcinoma (P=0.049). CONCLUSION: These results suggest that the expressional increase in GSK3ß plays a role in cervical carcinogenesis and has inverse correlation with cyclin D1 expression in this process. In addition, GSK3ß expression appears to be associated with the histologic type of cervical cancer, especially squamous cell carcinoma.

Gonadotropin-releasing hormone-agonist induces apoptosis of human granulosa-luteal cells via caspase-8, -9 and -3, and poly-(ADP-ribose)-polymerase cleavage.

Gonadotropin-releasing hormone-agonist (GnRH-Ag) used in controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) has been known to directly affect apoptosis of human ovarian cells, but its mechanism is not clearly understood. Therefore, the purpose of the present study was to investigate whether caspase-8, -9, and -3 activation and poly-(ADP-ribose)-polymerase (PARP) cleavage are involved in the mechanism by which GnRH-Ag induces apoptosis in human granulosa-luteal cells. The prospective study was conducted in the research institute and clinical fertility center of university hospital. Human granulosa-luteal cells collected from IVF-ET patients were cultured and treated with 10-6 M GnRH-Ag or saline as a control. To access apoptosis in the cells, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay and DNA fragmentation analysis were preformed 24 h after treatment. Activity of caspase-8, -9, and -3 in the cells was examined using a fluorogenic substrate. Caspase-8, -9, and -3 activation and PARP cleavage were analyzed by Western blot. DNA fragmentation in the cells increased at concentrations over 10-6 M GnRH-Ag. In TUNEL assays, the rate of apoptotic cell formation in GnRH-Ag treatment increased significantly compared with that of saline treatment (p < 0.05). The activity of caspase-8, -9 and, -3 investigated using a fluorogenic substrate increased only in the apoptotic cells. In Western blot analysis, cells treated with GnRH-Ag revealed an increase in active forms of caspase-8, -9, and -3 compared with saline treatment. In addition, cleavage of PARP also increased in cells treated with GnRH-Ag. These results suggest that activation of caspase-8, -9, and -3 and cleavage of PARP might be involved in apoptosis of human granulosa-luteal cells induced by GnRH-Ag.

A case of ovarian pregnancy after ipsilateral partial salpingectomy.

We present a case report of an ovarian pregnancy after ipsilateral partial salpingectomy. A 19-year-old woman was admitted with vaginal bleeding and right lower abdominal pain. She had a history of right partial salpingectomy caused by a tubal pregnancy. The pregnancy test result was positive, and a right adnexal mass was identified by ultrasonography. Laparoscopy revealed a right ovarian pregnancy. Thus the possibility of ipsilateral ectopic pregnancy should be considered even when the patient has a history of salpingectomy total or partial.