In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer.

UNLABELLED: Fenofibrate, an agonist of PPAR-alpha, in doses above 25 microM, inhibits proliferation and induces apoptosis in Ishikawa endometrial cancer cells. We show that these effects are potentiated by retinoic acid, an agonist of the retinoid-X-receptor. DNA content analysis shows that G1/S phase progression through the cell cycle is inhibited. Independent Component Analysis of gene microarray experiments demonstrated downregulation of Cyclin D1 (CCND1) and associated changes in cell cycle gene expression. Expression of PPAR-alpha mRNA was reduced by >75% using RNA-interference but this resulted in only minor changes in biological effects. A nude mouse model of endometrial carcinoma was used to investigate the effect of fenofibrate in vivo but failed to show consistent inhibition of tumour growth. CONCLUSION: The combination of fenofibrate and retinoic acid is a potent inhibitor of Ishikawa endometrial cancer cell growth in vitro

Intraoperative frozen section of ovarian tumors : a 6-year review of performance and potential pitfalls in an Australian Tertiary Referral Center

Objectives Intraoperative frozen section (IFS) offers a rapid test to guide the extent of surgery, which is essential for optimal treatment of ovarian cancer. This study evaluated the diagnostic performance and influence of IFS in the surgical management of ovarian tumors. Methods A retrospective review was conducted of IFS of adnexal lesions from 2008 to 2013, with diagnoses classified as benign, borderline, or malignant. The diagnostic performance of IFS was calculated, with a focus on primary epithelial tumors. In discordant cases, it was determined whether the results of the IFS influenced the nature of the primary surgery. Results There were 277 consecutive cases over the study period. The overall sensitivity for diagnosing malignant disease was 75.9% and the specificity was 100%. With a benign IFS result, there was a 6.25% (9/144) chance that the final diagnosis would be malignant, and a 7.6% (11/144) chance that the final diagnosis would be borderline, resulting in the potential for understaging. The predictive values for benign, borderline, and malignant IFS results were 86.1%, 66.6%, and 100%, respectively. For a borderline IFS result, there was a 33.3% chance that the final diagnosis would be malignant disease, and this was higher in older patients (53.3%). There were no instances of overdiagnosis in this series. Of 37 cases underdiagnosed, 19 received incomplete primary staging surgery guided by the IFS, and most of these were mucinous tumors. Conclusions Intraoperative frozen section is most valuable for its high specificity in diagnosing malignancy. It should be interpreted with caution in borderline tumors, particularly in older patients and in mucinous tumors. Overdiagnosis did not occur in this series; however, in younger patients, the limitations of IFS must be considered before surgery that would result in loss of fertility