INTRODUCTION Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes. METHODS Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed. Kaplan-Meier curves were used to assess overall survival (OS) and disease-specific survival (DSS). RESULTS At a median follow-up duration of 102 (range 3–357) months, 53 (43.4%) patients experienced disease recurrence and 21 (17.2%) experienced disease progression. There was no significant difference in mortality between patients with and without diabetes mellitus. There was significant difference in OS between patients without diabetes mellitus, patients with diabetes mellitus on metformin and patients with diabetes mellitus but not on metformin (p = 0.033); patients with diabetes mellitus on metformin had the best prognosis. Metformin use was associated with significantly lower DSS (p = 0.042). Other oral hypoglycaemic agents, insulin or statins were not associated with disease recurrence or progression. CONCLUSION Metformin use was associated with improved oncological outcomes in patients with non-muscle-invasive bladder cancer treated with intravesical BCG. Prospective studies with larger patient populations are needed to validate the role of metformin as potential therapy for bladder cancer.
Study ObjectiveObesity‐related co‐morbidities pose a serious health care system burden. However, 30% of obese subjects do not present with cardiometabolic complications. Here we perform comprehensive lipidome and proteome analyses to identify inflammatory and cardiometabolic fingerprints that characterize metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) phenotypes.MethodsObese patients (BMI 35–50) donated plasma before undergoing bariatric surgery (clinicaltrial.gov NCT02322073). Patients were classified as MHO (n=5) versus MUO (n=9) according to International Diabetes Federation criteria. Metabolically healthy lean (MHL, n=14) subjects were age‐ and sex‐matched to the obese cohort. Plasma samples were analyzed for 480 protein biomarkers related to inflammation and cardiometabolic processes in a multiplexed array. Samples were also subjected to untargeted lipidomics and targeted oxylipin lipidomics analyses.ResultsGene‐ontology term analysis of the 15 proteins that were significantly decreased/elevated in MHO vs. MUO patients revealed differences in inflammation, metabolism, apoptosis and fibrosis signaling pathways. Furthermore, lipidomics show distinct differences in the lipid profile of MHO and MUO groups. The MUO group displayed increased levels of ceramides, which are implicated in development of insulin resistance and cardiovascular diseases. In contrast, the MHO group exhibited increased levels of anandamide and dihomo‐gamma‐linolenoyl ethanolamide, which are lipids associated with anti‐inflammatory effects. The MUO group also exhibited elevated levels of the cardiometabolic risk factor plasminogen activator inhibitor 1 (PAI‐1). Interestingly, MHO patients presented with increased levels of myeloblastin, which is a serine protease that degrades the PAI‐1–stabilizing protein vitronectin.ConclusionIn conclusion, we have performed a comprehensive lipidomic and proteomic fingerprinting of MHO and MUO subjects. Our analyses reveal clear stratification of the groups and identify lipid mediators that may be of possible therapeutic use as novel interventions for obesity‐associated pathophysiologies. Work is ongoing to explore the molecular mechanism by which the identified proteins and lipid mediators affect cardiometabolic health in obese patients.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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