Background: Low-density lipoproteins levels are significant predictors of clinical outcomes in ovarian cancer (OvCa) patients. Despite American Diabetes Association (ADA) guidelines, suboptimal hyperlipidemia management is reported in women diagnosed with both OvCa and diabetes mellitus (DM). This study evaluated the impact of cholesterol drugs utilization and importance of following ADA guidelines on OvCa recurrence and survival. Methods: All DM patients newly diagnosed with OvCa between 2003 and 2010 at Roswell Park Cancer Institute were retrospectively reviewed (n=482). A total of 60 newly diagnosed OvCa patients having a form of diabetes at the time of cancer diagnosis were identified. Out of these, 14 patients were excluded due to presence of type 1 diabetes (n=6) or prior cancer history (n=8). The remaining 46 patients were included in the final analyses. Tumor pathology, outcomes, baseline co-morbidities and self-reported drug therapy were documented. Follow-up began at cancer diagnosis and ended with first confirmed recurrence and/or death. Cases lost to follow-up were censored at the date of last contact. To analyze categorical outcomes across different treatment groups, Fisher's exact test was used. All multivariate analyses were done using Cox proportional hazards models while accounting for age, weight, stage, histology, and cumulative comorbidity. A nominal significance level of 0.05 was used in all testing. Results: Average age at diagnosis and body mass index in this data set was 70±10 years and 34.76±7.07 kg/m2, respectively. Over three quarters of this population was diagnosed with advanced stage OvCa and 96% had a tumor grade of 2 or higher. Roughly two thirds of the tumors evaluated had a serous histology. Out of the cases reviewed, 52% did not receive any form of cholesterol management and 46% received a statin alone or in combination. After a median follow-up of 26.9 months, patients receiving statin monotherapy for cholesterol management were found to have improved recurrence (HR=0.17, 95% CI: 0.04 to 0.73, P=0.02); however, no impact on overall mortality was noted as compared to patients not receiving any cholesterol management medication. Conclusions: This study explored for the first time the association between statin utilization and prognosis in OvCa patients with DM. Given the identified benefit, reinforcing compliance with DM guidelines for hyperlipidemia management in OvCa patients deserves further attention. Our findings seed the beginning of a novel approach in personalized OvCa care. Citation Format: Michelle E. Amsler, Kristina A. Chmiel, Olesya Yaremko, Clare Carroll, Jingjing Yin, Terry Mashtare, Anthony Miliotto, Rachel Brightwell, Kunle Odunsi, Alice C. Ceacareanu. Statins use prevents ovarian cancer recurrence in women with diabetes mellitus. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-18. doi:10.1158/1538-7445.AM2013-LB-18
Adiponectin (ADP), a modulator of insulin actions, recently became an attractive therapeutic tool. We present here the effect of the first‐in‐class ADP receptor agonist (ADP355) on weight gain and biomarker patterns associated with long term high fat diet (HFD).Adult Sprague‐Dawley (SD) rats (n=23) were fed HFD (60% cal from fat) ad‐libitum for 15 weeks. ADP355 at 0.5mg/kg/dose, or saline was administered intraperitoneally every other day (n=3 each); weight gain, food intake, glucose (Glc) levels and blood biomarkers were assessed weekly. C‐reactive protein, glucagon, IL‐6, TNFα, amylin, insulin and leptin levels were measured by a multiplexed bead‐specific Luminex assay. The assays included 3 randomly selected matched controls. Results were assessed by student t‐test.After 15 weeks of treatment, the ADP355 group exhibited reduced weight gain (P<0.009), lower Glc levels (P=0.02), n=20, and significantly decreased glucagon (P<0.015) levels relative to control. While leptin levels increased, TNFα and amylin levels decreased significantly in the control group (P<0.002 for all). In the ADP355 group, leptin expression maintained a modestly increasing trend, however, no change was observed in the TNFα or amylin levels. In HFD fed SD rats, stimulation of the ADP receptor might be beneficial for weight gain prevention; however, our data do not support an anti‐inflammatory activity of ADP355 administration.
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