Previous studies conducted on the association between diabetes and the risk of endometrial cancer have reported controversial results that have raised a variety of questions about the association between diabetes and the incidence of this cancer. Thus, the aim of this systematic review and meta-analysis was to more precisely estimate the effect of diabetes on the risk of endometrial cancer incidence.All original articles were searched in international databases, including Medline (PubMed), Web of sciences, Scopus, EMBASE, and CINHAL. Search was done from January 1990 to January 2018 without language limitations. Also, logarithm and standard error logarithm relative risk (RR) were used for meta-analysis.A total of 22 cohort and case-control studies were included in this meta-analysis, of which 14 showed statistically significant associations between diabetes and risk of endometrial cancer. Diabetes was associated with increased risk of endometrial cancer (RR = 1.72, 95% CI 1.48-2.01). The summary of RR for all 9 cohort studies was 1.56 (95% CI 1.21-2.01), and it was 1.85 (95% CI 1.53-2.23) for 13 case control studies. The summary of RR in hospital-based studies was higher than other studies. Thirteen of the primary studies-controlled BMI as a confounding variable, and the combined risk of their results was 1.62 (95% CI 1.34-1.97).Diabetes seems to increases the risk of endometrial cancer in women, and this finding can be useful in developing endometrial cancer prevention plans for women having diabetes.

Hyperglycemia strongly affects endothelial function and activation, which in turn increases the risk of atherosclerotic cardiovascular disease. Among pharmacotherapies aimed at lowering blood glucose levels, glucagon-like peptide 1 receptor agonists (GLP-1RA) represent a class of drugs involved in the improvement of the endothelium damage and the progression of cardiovascular diseases. They show antihypertensive and antiatherosclerotic actions due at least in part to direct favorable actions on the coronary vascular endothelium, such as oxidative stress reduction and nitric oxide increase. However, cumulative peripheral indirect actions could also contribute to the antiatherosclerotic functions of GLP-1/GLP-1R agonists, including metabolism and gut microbiome regulation. Therefore, further research is necessary to clarify the specific role of this drug class in the management of cardiovascular disease and to identify specific cellular targets involved in the protective signal transduction. In the present review, we provide an overview of the effects of GLP-1RAs treatment on cardiovascular disease with particular attention on potential molecular mechanisms involving endothelium function on formation and progression of atherosclerotic plaque.© 2023. The Author(s).

Studies have showed that diabetes is one of the high risk factors of endometrial cancer; however, no reports describe the anti- or pro-cancer effect of a new kind of anti-diabetes drug, glucagon-like peptide-1 receptor agonist exenatide (exendin-4), on endometrial cancer. To investigate whether exenatide promotes or inhibits the growth of endometrial cancer, we used the subcutaneous human endometrial cancer cell Ishikawa xenografts in nude mouse model, and divided them into control group and exenatide-treated group. The tumor growth rate in exenatide group was slower than that in control group, and the apoptosis rate of exenatide group was higher than that in control group. In vitro, exendin-4 also attenuated Ishikawa cell viability and clone formation rate, but promoted cell apoptosis. There was an increase of phosphorylated-AMPK protein, a decrease of phosphorylated-mTOR protein both in vivo and in vitro after exenatide or exendin-4 treatment. Moreover, when treated with exendin-4 plus AICAR, an AMPK activator, cell apoptosis increased with higher ratio of phosphorylayed-AMPK/AMPK, lower ratio of phosphorylated-mTOR/mTOR and higher expression of cleaved caspase-3 than those in exendin-4 alone group, and the results were the opposite when treated with exendin-4 plus compound C, an AMPK inhibitor. Our results suggest that exenatide could attenuate the growth of endometrial cancer Ishikawa xenografts in nude mice, and AMPK may be the target of the mechanism.

A previous report showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist (exenatide) induced apoptosis in endometrial cancer cells. However, the pathophysiological role of GLP-1R in endometrial cancer has not been fully elucidated. Here, we investigated the effects of the GLP-1R agonist liraglutide in endometrial cancer cells and examined the association between GLP-1R expression and clinicopathological characteristics in endometrial cancer patients.Human Ishikawa endometrial cancer cells were treated with different concentrations of liraglutide. To assess the effects of liraglutide, cell viability, colony formation, flow cytometry, Western blotting, and immunofluorescence assays were performed. Autophagy induction was examined by analyzing LC3 and p62 expression and autophagosome accumulation. Moreover, using a tissue microarray, we analyzed GLP-1R expression in 154 endometrial cancer tissue samples by immunohistochemistry.In accordance with the previous report, liraglutide inhibited Ishikawa cell growth in a dose-dependent manner. Liraglutide significantly induced autophagy, and phosphorylated AMPK expression was elevated. Immunohistochemical analysis revealed that GLP-1R expression was associated with positive estrogen receptor and progesterone receptor status, and higher GLP-1R expression was significantly correlated with better progression-free survival.The use of liraglutide to target autophagy in endometrial cancer cells may be a novel potential treatment for endometrial cancer. Furthermore, higher GLP-1R expression may be associated with better prognosis in endometrial cancer patients.

It has been reported that glucagon-like peptide-1 (GLP-1) agents have been associated with both the increased risk of cancer and inhibition of tumor growth and metastases. The aim of this study is to evaluate the effect of liraglutide on hepatocellular carcinoma cells - HepG2. Cytometry was used to evaluate mechanism related to decreased cell proliferation. Nuclear staining and morphometric analysis were also used to verify the process that was taking place after treatment with liraglutide, and in order to better understand the mechanism, TGF-β1 was performed. HepG2 cells decreased proliferation after liraglutide treatment without altering oxidative stress levels. Liraglutide was able to induce autophagy and senescence through the increase of TGF-β1 which possibly explains the growth decrease. We have demonstrated that liraglutide has an antiproliferative effect in HepG2 cells inducing autophagy and senescence by the increase of TGF-β1.Copyright © 2017 Elsevier B.V. All rights reserved.

In cancer treatment, the recurrent challenge of inducing apoptosis through conventional therapeutic modalities, often thwarted by therapy resistance, emphasizes the critical need to explore alternative cell death pathways. Ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides on cellular membranes, has emerged as one such promising frontier in oncology. Induction of ferroptosis not only suppresses tumor growth but also holds potential for augmenting immunotherapy responses and surmounting resistance to existing cancer therapies. This review navigates the role of ferroptosis in tumor suppression. Furthermore, we delve into the complex role of ferroptosis within the tumor microenvironment and its interplay with antitumor immunity, offering insights into the prospect of targeting ferroptosis as a strategic approach in cancer therapy.Copyright © 2024 Elsevier Inc. All rights reserved.

The process of cell division plays a vital role in cancer progression. Cell proliferation and error-free chromosomes segregation during mitosis are central events in life cycle. Mistakes during cell division generate changes in chromosome content and alter the balances of chromosomes number. Any defects in expression of TIF1 family proteins, SAC proteins network, mitotic checkpoint proteins involved in chromosome mis-segregation and cancer development. Here we discuss the function of organelles deal with the chromosome segregation machinery, proteins and correction mechanisms involved in the accurate chromosome segregation during mitosis.© 2022. The Author(s), under exclusive licence to Springer Nature B.V.

There is a strong association between hyperglycemia, oxidative stress, inflammation and the onset and progression of diabetes which causes a higher risk of cancer. This study investigated, the effect of concomitant use of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) with iron supplements in hyper-glucose conditions on the K-562 cell line.The effects of iron, ω-3 PUFAs, and a combination of both on K-562 cells were investigated under normal and high glucose conditions. The impact of these treatments was evaluated using multiple methodologies, including the MTT assay for cell viability, quantification of oxidative stress markers [total antioxidant capacity (TAC) and malondialdehyde (MDA)], and analysis of the cell cycle. Furthermore, the expression levels of TNFα and p53 mRNA were measured using Real-time PCR.The co-treatment of ω-3 PUFAs and iron in the presence of high glucose had notable effects, as evidenced by an increase in cell survival, resistance to imatinib chemotherapy, TNFαmRNA expression levels, MDA levels, and percentage of cells in the G2/S phase. Additionally, there was a decrease in the mRNA expression of p53 and TAC levels compared to treatment in the normal-glucose condition.Hyperglycemic conditions in conjunction with the combined treatment of theω-3 PUFAs and iron, led to reduced anticancer capacity, chemosensitivity, anti-inflammatory and antioxidant properties of the K-562 cells. These effects were found to be mediated by oxidative stress.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.