Antidiabetic exendin-4 activates apoptotic pathway and inhibits growth of breast cancer cells

Exendin-4 is a GLP-1 analog used for the treatment of type 2 diabetes mellitus in its synthetic form. As women with diabetes have higher breast cancer incidence and mortality, we examined the effect of the incretin drug exendin-4 on breast cancer cells. The aim of the study is to investigate anticancer mechanism of exendin-4 in MCF-7 breast cancer cells. Cytotoxic effects of exendin-4 were determined by XTT assay. IC50 dose in MCF-7 cells were detected as 5 μM at 48th hour. Gene messenger RNA (mRNA) expressions were evaluated by real-time PCR. According to results, caspase-9, Akt, and MMP2 expression was reduced in dose group cells, compared with the control group cells. p53, caspase-3, caspase-8, caspase-10, BID, DR4, DR5, FADD, TRADD, PARP, PTEN, PUMA, NOXA, APAF, TIMP1, and TIMP2 expression was increased in dose group cells, compared with the control group cells. Effects of exendin-4 on cell invasion, colony formation, and cell migration were detected by Matrigel chamber, colony formation assay, and wound-healing assay, respectively. To conclude, it is thought that exendin-4 demonstrates anticarcinogenesis activity by effecting apoptosis, invasion, migration, and colony formation in MCF-7 cells. Exendin-4 may be a therapeutic agent for treatment of breast cancer as single or in combination with other agents. More detailed researches are required to define the pathways of GLP-1 effect on breast cancer cells because of the molecular biology of breast cancer that involves a complex network of interconnected signaling pathways that have role in cell growth, survival, and cell invasion. © 2015, International Society of Oncology and BioMarkers (ISOBM)

The association between central adiposity and autonomic dysfunction in obesity

Objective: To determine the relationship between central adiposity parameters and autonomic nervous system (ANS) dysfunction. Subjects and Methods: The study included 114 obese individuals without any cardiovascular risk factors. Weight (in kg), height (in m), and waist circumference (WC; in cm) were measured and body mass index was calculated. Echocardiographic examination was performed to measure left ventricular mass and epicardial fat thickness (EFT). All the participants underwent an exercise test and electrophysiological evaluation using electromyography. Heart rate recovery (HRR) at 1-5 min, R-R interval variation at rest and during hyperventilation, and sympathetic skin response were measured. Pearson's correlation analysis was used. Multiple linear regression analysis was used to identify the factors associated with autonomic dysfunction. Results: The HRR at 1-5 min was negatively correlated with WC and age (WC-HRR1: r = -0.32; WC-HRR2: r = -0.31; WC-HRR3: r = -0.26; WC-HRR4: r = -0.23; WC-HRR5: r = -0.21; age-HRR2: r = -0.32; age-HRR3: r = -0.28; age-HRR4: r = -0.41; age-HRR5: r = -0.42). Age was the only independent predictor of reduced HRR at 1-5 min. In addition, WC predicted a reduced HRR at 3 min. There were no significant associations between central obesity and electrophysiological parameters. EFT was not associated with ANS dysfunction. Conclusion: In this study, central adiposity and aging were associated with ANS dysfunction in obese individuals. The WC could be a marker of ANS dysfunction in obese individuals without any cardiovascular risk factors. The HRR assessment at a later decay phase could be more valuable for evaluating ANS function than during early recovery. © 2016 S. Karger AG, Basel

An examination by year of cases applied with caesarean hysterectomy because of placenta percreta in a tertiary centre: a retrospective cohort study

Objectives: To examine cases applied with caesarean hysterectomy because of placenta percreta by comparing changesin treatment strategies and complications according to year.Material and methods: A retrospective examination was made of 93 patients applied with caesarean hysterectomy witha diagnosis of placenta percreta in 5-year periods of 2005–2009, 2010–2014, and 2015–2019. Demographic characteristicswere recorded, and previous caesareans, history of myomectomy and curettage, gestational weeks, and infant birthweight.Intraoperative and postoperative findings were recorded as operating time, length of stay in hospital and Intensive Care Unit(ICU), transfusion requirement, the amount of erythrocyte suspension (ES) and fresh frozen plasma (FFP) transfused, and requirementfor massive transfusion. Anaesthesia type, complications, and the preferred skin-uterus incision were also recorded.Results: The 93 patients comprised 8 cases in the period 2005–2009, 23 in 2010–2014, and 62 in 2015–2019. The numberof previous caesarean procedures was observed to increase in parallel with these case numbers. A significant increase wasobserved in the gestational week of birth, and infant birthweight, and a decrease in operating times. In later years there wasseen to be a lower amount of ES and FFP transfused and fewer patients with massive transfusion. Preoperative diagnosisof placenta percreta, the highest preference for general anaesthesia, selection of midline vertical skin incision and uterinefundal incision were greatest in the period 2015–2019.Conclusions: In cases with placenta percreta, of which there is an increasing incidence, maternal and infant outcomescan be optimised with prenatal diagnosis and planned caesarean hysterectomy by a multidisciplinary team with optimalprenatal preparation