Sensitization of ovarian cancer cells to cisplatin by genistein: the role of NF-kappaB.

BACKGROUND: Platinum-resistance (PR) continues to be a major problem in the management of epithelial ovarian cancer (EOC). Response to various chemotherapeutic agents is poor in patients deemed PR. Genistein, a soy isoflavone has been shown to enhance the effect of chemotherapy in prostate and pancreatic cancer cells in vitro and in vivo by reversing chemo-resistance phenotype. The goal of this study was to investigate the effects of combination therapy with genistein and cisplatin as well as other cytotoxic conventional chemotherapeutic agents in platinum-sensitive (PS) and resistant EOC cells. METHODS: The PS human ovarian cancer cell line A2780 and its PR clone C200 cells were pretreated with genistein, followed by the combination of genistein and either cisplatin, taxotere or gemcitabine. Cell survival and apoptosis was assessed by MTT and histone-DNA ELISA. Electrophoretic mobility shift assay (EMSA) was used to evaluate NF-kappaB DNA binding activity. Western blot analysis was performed with antibodies to Bcl-2, Bcl-xL, survivin, c-IAP and PARP. RESULTS: Reduction in cell viability, and corresponding induction of apoptosis was observed with genistein pretreatment followed by combination treatment with each of the drugs in both cell lines. The PS cell line was pretreated for 24 hours; in contrast, the PR cell line required 48 hours pretreatment to achieve a response. The anti-apoptotic genes c-IAP1, Bcl-2, Bcl-xL, survivin and NF-kappaB DNA binding activity were all found to be down-regulated in the combination groups. CONCLUSION: This study convincingly demonstrated that the current strategy can be translated in a pre-clinical animal model, and thus it should stimulate future clinical trial for the treatment of drug-resistant ovarian cancer.

Image-guided percutaneous cryotherapy for the management of gynecologic cancer metastases.

OBJECTIVE: To report the clinical response to image-guided percutaneous cryotherapy (IPC) for the palliative management of localized metastases in patients with gynecologic malignancies. METHODS: Institutional review board approval and patient consent were obtained. Gynecologic oncology patients were identified from our institution's cryotherapy database from August 2003 to August 2007. Cryotherapy was performed with 2.4 mm diameter probes (Endocare, Irvine, CA) with ultrasound or computerized tomography (CT) guidance under conscious sedation and local anesthesia. Follow-up was conducted by imaging studies and clinical encounters, using Response Evaluation Criteria in Solid Tumors (RECIST criteria). RESULTS: Twenty-eight ablation sessions were performed for 41 metastatic foci in 15 patients with gynecologic malignancies. Twelve patients had prior chemotherapy and 5 patients had prior radiation. Median follow-up was 317.5 days (range 95-1189). Median post-procedure pain score: 3/10 (range 0-5). Mean initial tumor size was 2.6 cm in maximal diameter. Median reduction in tumor diameter at 1 month was 21.4% (range 2-67.4%), at 3 months was 43.6% (range 16-80.4%), at 6 months was 54.7% (range (16.6-88.9%) and at 9 months was 58.2% (range 32-88.9%). Ten patients received concurrent chemotherapy, 8 had progression of disease at other sites and 2 had stable disease, while the cryotherapy site improved. One of 5 patients who had cryotherapy in the previously irradiated zone had recurrence. A liver capsule hematoma developed as an immediate complication in one patient and an enterocutaneous fistula developed in another. CONCLUSION: IPC is a well-tolerated, effective tool for local control of isolated metastatic foci as a single-modality treatment and for local control of symptomatic metastases in select patients undergoing systemic therapy for the management of gynecologic malignancies.

Clinical update of smooth muscle tumors of the uterus.

Smooth muscle tumors of the uterus represent a spectrum of diseases that range from benign leiomyoma to malignant leiomyosarcoma. The leiomyoma is the most common of these neoplasms. Clinically, it is important to fully understand the differences in clinical presentation, biologic behavior, and management for patients with benign leiomyoma, smooth muscle tumors of uncertain malignant potential, and leiomyosarcoma. The goal of this review is to present the most recent information about common smooth muscle tumors of the uterus including their etiology, histopathology, radiographic and clinical presentations, and available treatment options.