Regulation of ovarian UT-OC-2 carcinoma cells by cytokines: effects on cell proliferation, activation of transcription factors and apoptosis.

BACKGROUND: It is known that immunologic factors are involved in the regulation of the growth of ovarian carcinoma and that granulocytes are often found on the site of ovarian cancer. Therefore, we chose to investigate the effects of cytokines on UT-OC-2 ovarian endometrioid adenocarcinoma cells in vitro. In order to investigate the molecular mechanisms involved, the activation of two key DNA-binding proteins, AP-1 and transcription factor NF-kappaB (NF-kappaB), was studied. Since DNA extracted from the UT-OC-2 cells showed fragmentation typical of apoptosis, we also studied the effects of cytokines on this event. METHODS: The effects of the studied cytokines on the proliferation of UT-OC-2 cells were investigated by (125)I-deoxyuridine incorporation. The activation of DNA-binding proteins was studied by electrophoretic mobility shift assay. Statistical analyses were performed by Student's t-test. RESULTS: Interferon alpha (IFN-alpha), transforming growth factor beta(1) (TGF-beta(1)), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) all had a significant inhibitory effect on cell proliferation. Granulocyte colony stimulating factor (GM-CSF) did not alter cell proliferation significantly. Transcription factors AP-1 and NF-kappaB were both found to be constitutively active in UT-OC-2 ovarian carcinoma cells. We were able to show that IFN-gamma, TGF-beta(1) and TNF-alpha all increased the binding activity of transcription factor AP-1 (AP-1). The binding activity of transcription factor NF-kappaB was not altered by any of the cytokines studied, with the exception of IFN-gamma. IFN-gamma had also a clear inhibitory effect on the apparent magnitude of apoptosis, whereas TNF-alpha and TGF-beta(1) showed no effect. CONCLUSION: The results of this study show that TNF-alpha, TGF-beta(1), and IFN-gamma are able to inhibit the proliferation of UT-OC-2 ovarian carcinoma cells. Activation of AP-1 seems to be involved in the growth-regulating processes induced by IFN-gamma, TGF-beta(1) and TNF-alpha; IFN-gamma is also able to increase the binding activity of NF-kappaB and inhibited apoptosis in ovarian cancer cells.

Activin B in patients with granulosa cell tumors: serum levels in comparison to inhibin.

BACKGROUND: Activins and inhibins are polypeptide hormones/growth factors of primarily gonadal origin. In the ovary, activins and inhibins are primarily synthesized by granulosa cells. Serum inhibin measurements have been used for the follow-up of patients with granulosa-cell tumors (GCT) after surgery. METHODS: We have employed a recently developed assay to study whether activin B (A) measurements can be used as a marker of progression of GCTs. Additionally, these measurements have been compared with simultaneously run inhibin measurements using a commercial assay. Serum samples of three patients suffering from GCTs (all stage Ia) were collected at primary surgery and at controls thereafter. RESULTS: In patient AM, serum inhibin levels have remained elevated while A levels are low; there has been no evidence of a residual tumor. In patient AR, there has been no clinical evidence of a residual tumor, and both serum A and inhibin levels have remained low. In patient PP, a residual tumor was found 6 years after primary surgery; at the time A levels were elevated, while inhibin levels remained low. CONCLUSION: We introduce A as a promising new marker for postoperative follow-up of patients suffering from GCTs.

Endometrial thermoablation for treatment of menorrhagia: comparison of two methods in outpatient setting.

BACKGROUND: Menorrhagia is one of the commonest reasons for gynecologic consultations. Inhibitors of fibrinolysis and non-steroidal anti-inflammatory drugs (NSAIDs) are generally used as therapy for the condition with an acceptable response in some patients. Endometrial ablation is one choice in patients suffering from menorrhagia. It can be performed in patients with no endometrial histological or anatomical pathology. In this method, the functional endometrial tissue is ablated under general anesthesia in an outpatient setting. METHODS: We compared two methods that are widely used in Finland (Menotreat and Cavaterm) in thermoablation of endometrial tissue in 31 patients that were randomized into two treatment groups. RESULTS: Endometrial ablation was effective in the treatment of menorrhagia in patients with normal endometrial structure. About 70% of the patients described the result of the treatment as 'very good'. Only one patient underwent a hysterectomy during the 6-month follow-up period because of problems related to uterine bleedings. The two methods were similar in efficacy and patient acceptance. CONCLUSIONS: Both thermoablation techniques were well accepted by our patients and showed similar and good efficacy and patient acceptance.

Self-adjusted postmenopausal hormone replacement therapy: effects on the biological and immunological profile of FSH and correlation to climacteric symptoms.

OBJECTIVE: The purpose of the present study was to evaluate the hormonal profile of patients of postmenopausal age during estrogen replacement therapy (ERT) with special reference to the serum levels of biologically active FSH (B-FSH) in a self-adjusted ERT model. DESIGN: The hormonal values found have been correlated to climateric symptoms reported by the patients (scored by the Kupperman menopausal index (KI)). METHODS: B-FSH was measured using an assay based on a cell system transfected permanently with FSH receptor cDNA. All women (n=32) applied estradiol percutaneously using 1 mg estradiol-17beta (E(2)) as an initial dose and were encouraged to increase the daily dose until they felt comfortable according to a specific scheme. Twelve of the 32 women were hysterectomized and treated, accordingly, with ERT only; 20 women received megestrol acetate monthly for 10 days. RESULTS: The initial average KI was 30 (range 10-54). A high degree of correlation (r=0.83; P<0.001) was observed between B-FSH and immunologically active FSH (I-FSH). Serum I-FSH and E(2) correlated negatively (r=-0.21; P<0.001); similarly, a negative correlation (r=-0.15; P<0.01) was observed between serum B-FSH and E(2) levels. Serum I-FSH and KI showed modest but significant positive correlation (r=0.13; P<0.01); a somewhat higher degree of correlation (r=0.19; P<0.005) was observed when B-FSH and KI were compared. E(2) showed positive correlation to serum sex-hormone binding globulin levels (r=0.22; P<0.001). CONCLUSIONS: This study shows that the transdermal self-adjusted hormone replacement therapy (HRT) model introduced is suitable for studies on endocrine changes during postmenopausal ERT. The finding of poor correlation between serum E(2) levels and KI emphasizes the importance of hormonal measurements during postmenopausal HRT.