A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells.

Cancer frequently develops resistance to the majority of chemotherapy treatments. This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors, specifically Canagliflozin (CAN), Dapagliflozin (DAP), Empagliflozin (EMP), and Doxorubicin (DOX), using in vitro experimentation. The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin (DOX) in MCF-7 cells. Interestingly, it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth. Notably, when these medications were combined with DOX, there was a considerable inhibition of glucose consumption, as well as reductions in intracellular ATP and lactate levels. Moreover, this effect was found to be dependent on the dosages of the drugs. In addition to effectively inhibiting the cell cycle, the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression. This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications, namely CAN, DAP, and EMP, on the responsiveness to the anticancer properties of DOX. The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

Assessing Adherence to Cardiac Monitoring Guidelines in Trastuzumab-Treated Breast Cancer Patients: Insights From a Tertiary Hospital.

INTRODUCTION: Breast cancer is a global health concern, with a significant portion of patients exhibiting human epidermal growth factor receptor 2 (HER2) overexpression. Trastuzumab is one of the pivotal therapies for HER2-positive breast cancer, but it carries the risk of cardiotoxicity. Guidelines for cardiac monitoring are essential to detect early signs of cardiotoxicity. However, adherence to these guidelines remains uncertain. METHOD: In this single-center retrospective cohort study, we analyzed data from 167 female patients diagnosed with HER2-positive breast cancer who were treated with trastuzumab. We meticulously assessed the level of adherence to cardiac monitoring guidelines and determined the incidence of trastuzumab-induced cardiotoxicity (TIC). Factors affecting adherence were subsequently investigated using appropriate statistical methods. RESULTS: Adherence to monitoring guidelines was only 31.7%. TIC incidence was 7.8%. Patients with concurrent use of cardiotoxic medications demonstrated higher adherence. A significant association was found between the number of trastuzumab doses and adherence. CONCLUSION: Adherence to monitoring guidelines was suboptimal. Those at a higher risk of cardiac issues showed greater adherence. Improved risk assessment methods are needed to individualize monitoring and intervention. Future research should focus on patient-centered, evidence-based monitoring to optimize the balance between cancer therapy and cardiac safety in the field of cardio-oncology.

Assessment of the Safety, Efficacy, and Benefit of Empagliflozin in Patients With Type 2 Diabetes Mellitus (T2DM) and Heart Failure With Reduced Ejection Fraction (HFrEF) at High Risk for Cardiovascular Events.

Background Since the increasing prevalence of type 2 diabetes mellitus (T2DM), heart failure coexisting with it has had a significant impact on clinical management and prognosis. Patients with T2DM and heart failure with reduced ejection fraction (HFrEF) have increased mortality and morbidity. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, is widely acknowledged to reduce cardiovascular risk in T2DM patients. We wanted to assess the composite outcomes of heart failure, cardiovascular death, and hospitalization following the start of empagliflozin therapy in the Saudi population. Methods This is a retrospective observational study conducted at King Fahad Armed Forces Hospital-Jeddah. We included patients aged 18 or older, male or female, with T2DM with HFrEF <40% and with a risk of cardiovascular events who were treated with empagliflozin 25 mg once daily as combination therapy and patients using other diabetic agents without empagliflozin as the comparative group. Results A total of 195 patients with T2DM and HFrEF who were at high risk for cardiovascular (CV) events were included in the study. Regarding gender, most of the patients (82.1%) were male with an average age of 61.28 ± 9.92. The patients were divided into 71 individuals who received empagliflozin and 124 who did not. When comparing the surgical procedure and comorbid status of the patients, coronary artery bypass graft (1.4%), coronary artery disease (5.6%), dyslipidemia (5.6%), and ischemic cardiomyopathy (0%) were found compared to the non-empagliflozin group. Meanwhile, hypertension was found to be 71.8% and ischemic heart disease was 50.7% in empagliflozin patients. Furthermore, only dyslipidemia differed significantly (p <0.001) between the empagliflozin and non-empagliflozin groups of patients. However, no significant differences were observed between the average low-density lipoprotein (p = 0.990) and high-density lipoprotein (p = 0.399). There was no significant difference observed in the primary outcome of CV deaths or hospital admission of patients between empagliflozin and non-empagliflozin. No deaths were reported in either of the comparative groups in our study. Conclusion In this study, there was no significant difference observed in hospital admission of the patients between the empagliflozin and non-empagliflozin groups. No cardiovascular mortality was reported in the study population. Further matched group comparative studies or placebo-controlled studies are required to compare the existing evidence of the impact of empagliflozin on T2DM patients with HFrEF and at high risk for CV deaths or hospital admission.