Diabetes and cancer are prevalent diseases whose incidence is increasing globally. Diabetic women have a moderate risk increase in ovarian cancer, suggested to be due to an interaction between these two disorders. Furthermore, patients manifesting both diseases have associated worse prognosis, reduced survival and shorter relapse-free survival. According to current recommendations, incretin drugs such as Exenatide, a synthetic analog of Exendin-4, and Liraglutide are used as therapy for the type 2 diabetes (T2D). We studied the effects of GLP-1 and Exendin-4 on migration, apoptosis and metalloproteinase production in two human ovarian cancer cells (SKOV-3 and CAOV-3). Exendin-4 inhibited migration and promoted apoptosis through caspase 3/7 activation. Exendin-4 also modulated the expression of key metalloproteinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2). Vascular endothelial cells, which contribute to the formation and progression of metastasis, were also analyzed. TNF-α-stimulated endothelial cells from iliac artery after Exendin-4 treatment showed reduced production of adhesion molecules (ICAM-1 and VCAM-1). Additionally, incretin treatment inhibited activation of apoptosis in TNF-α-stimulated endothelial cells. In the same experiment, MMPs (MMP-1 and MMP-9), which are relevant for tumor development, were also reduced. Our study demonstrated that incretin drugs may reduce cancer cell proliferation and dissemination potential, hence limiting the risk of metastasis in epithelial ovarian cancer.

Summary: Introduction: Cardiovascular disease is the main cause of mortality and morbidity in the industrialized world. Incretin‐mimetic compounds such as exenatide are currently used in the treatment of type 2 diabetes.Aims: We investigated the effects of incretin drugs on apoptosis, adhesion molecule expression, and concentration of extracellular matrix (ECM) metalloproteinases under inflammatory conditions within the context of atherosclerotic plaque formation of both human coronary artery endothelial cells (hCAECs) and human aortic endothelial cells (hAoECs). TNF‐α‐stimulated hCAEC and hAoEC were treated with exenatide (1 and 10 nmol/L) and GLP‐1 (10 and 100 nmol/L) then evaluated for caspase 3/7 activity and assayed for protein levels of adhesion molecules sICAM‐1, sVCAM‐1, and P‐selectin. Concentrations of matrix metalloproteinases (MMPs) MMP‐1, MMP‐2, MMP‐9, and their inhibitors—tissue inhibitor of metalloproteinases (TIMPs), TIMP‐1, TIMP‐2 were also measured to evaluate the effects on extracellular matrix turnover within an inflammatory environment. Intracellular signaling pathways were evaluated via transfection of endothelial cells with a GFP vector under the NF‐κB promoter.Results: Our experimental data suggest that GLP‐1 receptor (GLP‐1R) agonists downregulate activation of NF‐κB and adhesion molecules ICAM and VCAM, but not P‐selectin, in both endothelial cell lines. Exendin‐4 and GLP‐1 modulate the expression of MMPs and TIMPs, with statistically significant effects observed at high concentrations of both incretins. Expressive modulation may be mediated by NF‐κB as observed by activation of the vector when stimulated under inflammatory conditions.Conclusion: These findings indicate that GLP‐1 analogs have anti‐inflammatory properties in endothelial cells that may play an important role in preventing atherosclerosis.

Introduction: Learning is essential and life-long for faculty and students. Often students and teachers use ineffective learning strategies and are not aware of evidence-based strategies. Methods: A multicenter, international, cross-sectional, online survey-based assessment of awareness of evidence-based learning strategies among health professions students (n = 679) and faculty (n = 205). Results: Students endorsed many study habits which violate evidence-based principles, including studying whatever is due soonest (389/679, 57%), failing to return to course material once a course has ended (465/679, 68%), and re-reading underlined or highlighted notes (298.679, 44%). While the majority of faculty surveyed (125/157, 80%) reported recommending effective study strategies for their students, most students (558/679, 82%) said they did not study the way they do because of instruction from faculty. The majority of faculty (142/156, 91%) and students (347/661, 53%) believe students have different learning styles. Discussion: The results of this study demonstrate health professions students continue to use many ineffective study strategies, and both students and faculty hold misconceptions about evidence-based learning. While planning a curriculum, medical educators should focus on teaching students how to learn and use higher order thinking procedures in addition to teaching content.

The strong association between diabetes mellitus type 2 and cancer is observed. The incidence of both diseases is increasing globally due to the interaction between them. Recent studies suggest that there is also an association between cancer incidence and anti-diabetic medications. An inhibitor of dipeptidyl-peptidase 4 (DPP-4), sitagliptin, is used in diabetes treatment. We examined the influence of sitagliptin alone or in combination with a cytostatic drug (paclitaxel) on the development of epithelial ovarian cancer cells and the process of metastasis. We examined migration, invasiveness, apoptosis, and metalloproteinases (MMPs) and their inhibitors’ (TIMPs) production in two human ovarian cancer cell lines. Sitagliptin induced apoptosis by caspase 3/7 activation in paclitaxel-treated SKOV-3 and OVCAR-3 cells. Sitagliptin maintained paclitaxel influence on ERK and Akt signaling pathways. Sitagliptin additionally reduced migration and invasiveness of SKOV-3 cells. There were distinct differences of metalloproteinases production in sitagliptin-stimulated ovarian cancer cells in both cell lines, despite their identical histological classification. Only the SKOV-3 cell line expressed MMPs and TIMPs. SKOV-3 cells co-treated with sitagliptin and paclitaxel decreased concentrations of MMP-1, MMP-2, MMP-7, MMP-10, TIMP-1, TIMP-2. The obtained data showed that sitagliptin used with paclitaxel may be considered as a possibility of pharmacological modulation of intracellular transmission pathways to improve the response to chemotherapy.