Retroviral Interferon- α Gene Transfer Potentiates Paclitaxel against Ovarian Cancer Cells

Objective: To analyze the cytotoxic effects of paclitaxel following introduction of the retroviral interferon- α (IFN- α) gene into epithelial ovarian cancer cells.Design: Experimental molecular study.Setting: University hospital research center. Sample: Epithelial ovarian cancer cell lines OV-2774 and SKOV3. Empty vector was used as control.Methods: The cytotoxic effects of paclitaxel on ovarian cancer cells were studied prior to and after transfection with the retrovirus-mediated inteferon- α gene. RT/PCR of the interferon gene, cell survival and cell death were analyzed to assess retroviral interferon- α gene expression after transfection.Results: Paclitaxel inhibited cell growth in a dose dependent manner with half maximal inhibitory concentration (IC50) of 7.5 ng/ml. Retroviral inteferon- α gene transfer-transduced cells potentiated paclitaxel response against both ovarian cancer cell lines by 68%.Conclusion:  Retrovirus-mediated IFN- α gene transfer enhanced paclitaxel cytotoxicity on ovarian cancer cells. Retroviral IFN- α gene transfer in combination with paclitaxel may have significant clinical utility for the treatment of epithelial ovarian cancers

Sulforaphane Induces Cell Cycle Arrest, Migration, Invasion, and Apoptosis in Epithelial Ovarian Cancer Cells

Objectives: Isothiocyanates (ITC) has long been shown to demonstrate chemopreventive properties. Sulforaphane (SFN) is a major ITC present in broccoli and other cruciferous vegetables. We reviewed the current literatures of SFN on ovarian carcinoma cell lines. Methods: Studies were conducted on the effects of SFN on the growth of the OVCAR-3, MDAH 2774 and SKOV-3 ovarian carcinoma cell lines. Chuang et al. evaluated the effect of SFN on ovarian cancer cell cycles. Subsequently Chaudhuri et al. determined the specific pathway that was affected and Bryant et al. explored the signaling mechanisms through which SFN influences the cell growth and proliferation in ovarian cancer cell lines. Results: Chuang et al. showed a concentration dependent decrease in cell density. Analysis of cell cycle phase progression revealed a decrease in the cell populations in S and G2M phases, with an increase of G1 cell population, indicating a G1 cell cycle arrest. The degree of decrease in the replicating population was concentration and time dependent. These results clearly demonstrated an effect of SFN in inducing growth arrest and apoptosis in ovarian carcinoma cell lines. Chaudhuri et al. investigated the effects of sulforaphane on Akt signal transduction pathway. Both total Akt protein and active phosphorylated levels of Akt and phosphoinositide 3-kinase were significantly decreased in sulforaphane-treated ovarian cancer cell lines. Utilizing gene expression profile analysis, Bryant et al. showed SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions: SFN induced growth arrest and cell death in ovarian cancer cells in G1 cell cycle arrest. The Akt pathway was identified as the possible target for SFN. SFN suppresses growth of ovarian cancer cells in vitro by modulating cell cycle regulatory proteins and by enhancing apoptosis. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in ovarian cancer growth arrest, migration, and invasion

Multicystic Benign Cystic Mesothelioma Presenting as a Pelvic Mass

Background. Benign cystic mesothelioma (BCM) is a rare tumor that arises from the abdominal peritoneum with a predilection to the pelvic peritoneum. For this reason, it can often mimic gynecologic malignancies. Case. A 47-year-old perimenopausal female presented reporting several weeks of abdominal distention associated with abdominal tenderness and constipation. Computed tomography revealed a 24 cm multiloculated pelvic mass, and tumor markers were notable for an elevated CA-125. The patient was taken to the operating room for an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingoophorectomy, and removal of pelvic mass. Final pathologic evaluation revealed a benign cystic mesothelioma. Conclusion. Classically these tumors present as large multicystic masses with thin-walled septations and on preoperative evaluation BCM can mimic many different disease entities including ovarian malignancies and cystic lymphangioma. Often diagnosis can only be made at time of surgery

Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers.

BACKGROUND:High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools. METHODS AND FINDINGS:Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival. CONCLUSIONS:Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic dilemma and a potential critical inflection point in precision medicine. This study suggests that the use of personalized ctDNA biomarkers in gynecologic cancers can identify the presence of residual tumor while also more dynamically predicting response to treatment relative to currently used serum and imaging studies. Of particular interest, ctDNA was an independent predictor of survival in patients with ovarian and endometrial cancers. Earlier recognition of disease persistence and/or recurrence and the ability to stratify into better and worse outcome groups through ctDNA surveillance may open the window for improved survival and quality and life in these cancers

Undetectable levels of ctDNA following initial treatment are associated with improved survival.

<p>Kaplan–Meier analysis of progression-free (left panel) and overall survival (right panel) between individuals with undetectable (ctDNA = 0; blue lines) and detectable ctDNA (≥ 1; red lines). Significant differences in progression-free survival (p = 0.001) and overall survival (p = 0.0194) between undetectable and detectable groups.</p