Bladder cancer metformin

BACKGROUND: Docetaxel (DOCE) is a standard of care in metastatic castration-resistant prostate cancer (mCRPC). Several retrospective studies suggested a decrease in Prostate Cancer incidence and mortality with metformin (MET). MET has also demonstrated anti-tumor activity in Prostate Cancer preclinical models, with increased apoptosis when added to DOCE. We aimed at exploring the role of MET in combination with DOCE in mCRPC. PATIENTS AND METHODS: Non-diabetic mCRPC patients were randomly assigned to receive DOCE 75 mg/m2 every 21 days + prednisone (5 mg...

An important approach in tumor therapy is combining substances with different action mechanisms aiming to enhance the antineoplastic effect, decrease the therapeutic dosage, and avoid resistance mechanisms. Moreover, evaluating compounds already approved for the treatment of non-neoplastic diseases is promising for new antineoplastic therapies. Sodium dichloroacetate (DCA) reactivates oxidative phosphorylation in the cancer cell mitochondria, reducing apoptosis resistance in cancer cells. Furthermore, metformin inhibits the proliferation of tumor cells and CD133+ cancer -stem-like cells...

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. It can not only generate reactive oxygen species (ROS) to cause the chemical damage of tumor cells in the presence of enough oxygen but also promote the antitumor immunity of T cells through enhancing the production of interferon γ (IFN-γ). However, one phenomenon is ignored so far that the enhanced production of IFN-γ caused by PDT may significantly increase the expression of programmed death-ligand 1 (PD-L1) on the tumor cell membrane and thus could inhibit the immune killing effects of T cells...

In the last decade, cancer became the leading cause of death in the population under 65 in the European Union. Diabetes is also considered as a factor increasing risk of cancer incidence and mortality. Type 2 diabetes is frequently associated with being overweight and obese, which also plays a role in malignancy. Among biological mechanisms linking diabetes and obesity with cancer hyperglycemia, hyperinsulinemia, insulin resistance, increased levels of growth factors, steroid and peptide hormones, oxidative stress and increased activity of pro-inflammatory cytokines are listed...

Cyclophosphamide (CP) is a widely used anti-neoplastic drug; however, it leads to bladder dysfunction in the form of hemorrhagic cystitis that is a serious dose-limiting complication in cancer patients. We aimed to evaluate the protective effects of metformin (MET) in a mouse model of CP-related cystitis in parallel with its effect on CP-induced cytotoxicity in a breast cancer cell line, MDA-MB-231. Cystitis was induced by a single intraperitoneal injection of CP (300 mg/kg), and mice were administered MET, mesna, or vehicle treatment...

Bladder cancer is one of the most prevalent deadly diseases worldwide. Grade 2 tumors represent a good window of therapeutic intervention, whose optimization requires high resolution biomarker identification. Here we characterize energy metabolism and cellular properties associated with spreading and tumor progression of RT112 and 5637, two Grade 2 cancer cell lines derived from human bladder, representative of luminal-like and basal-like tumors, respectively. The two cell lines have similar proliferation rates, but only 5637 cells show efficient lateral migration...

OBJECTIVES: To evaluate if the obesity paradox, wherein obesity portends worse overall prognosis for a disease but improved outcomes for patients receiving immunotherapy, exists for patients receiving bacillus Calmette-Guérin (BCG) in a contemporary cohort. PATIENTS AND METHODS: We performed an Institutional Review Board-approved database review to identify patients with non-muscle-invasive bladder cancer (NMIBC) completing at least an induction course of BCG. Clinicopathological variables collected included: body mass index (BMI), medications, and diabetes mellitus (DM)...

BACKGROUND: While the chemoprevention effect of aspirin is well-established, the effects of metformin in cancer prevention is still controversial. This study is to investigate the use of aspirin, metformin, or the combination of both is associated with delayed cancer incidence. METHOD: This dataset is based on the electronic medical record of public hospitals in Hong Kong. Patients were classified into 1. aspirin user, 2. metformin user, 3. both aspirin and metformin user and 4...

Metformin is the first-line therapy for patients with type 2 diabetes, and its most common adverse effects are gastrointestinal. Lactic acidosis associated with metformin use is rare. Here, we report the case of a 77-year-old man with a medical history of diabetes (treated with metformin), hypertension, chronic alcohol abuse, and prostate and bladder cancer, who presented with abdominal pain, nausea, vomiting, and diarrhea for five days. He was admitted with severe metabolic acidosis due to metformin toxicity (metformin-associated lactic acidosis) with metformin level 23 mcg/mL (therapeutic range approximately 1-2 mcg/mL) in the setting of acute kidney failure due to acute pancreatitis and sepsis secondary to aspiration pneumonia...

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...

Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c and/or irregular blood glucose levels. Diabetic patients' mortality rates with COVID-19 are higher than those of cardiovascular or cancer patients. Recently, Bacillus Calmette-Guérin (BCG) vaccine has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to beta cells regeneration...

Bladder cancer (BC) is the sixth most common cancer in men. Moreover, chemotherapy for BC leads to various side effects. Metformin is known to induce apoptosis in vitro in many types of cancer. Furthermore, it has feasibility as a drug repositioning used for the treatment of cancer. The molecular mechanism of metformin mediating apoptosis in BC is still unclear. In this study, we showed that metformin stimulated the caspase-dependent apoptotic signaling pathway in T24 cells, a human BC cell line. Moreover, the induced apoptosis was partially inhibited by a general caspase inhibitor, z-VAD-fmk, which suggested that metformin-induced apoptosis in T24 cells is partially caspase-independent...

Gallbladder cancer is the most common biliary tract cancer with poor prognosis and wide variation in incidence rates worldwide, being very high in some countries in Latin America and Asia. Treatment of type 2 diabetes with metformin causes a reduction in the incidence of cancer. Till date, there are no reports on the anti-tumor effects of metformin in gall bladder cancer. Therefore, this study evaluated the effects of metformin on the proliferation of human gallbladder adenocarcinoma cells in vitro and in vivo, as well as explored the microRNAs associated with the anti-tumor effects of metformin...

BACKGROUND: An increasing number of studies have investigated associations of antidiabetes medications with cancer risk. Antidiabetes medications are classified by their mechanisms of action on tissues and organs. They potentially act as both causative and confounding factors in the temporal association of diabetes and cancer. AIM: To present the current evidence regarding both the carcinogenic and anti-carcinogenic effects of antidiabetes medications on cancer in humans...

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) is the most common neoplasm of the urinary tract and requires life-long invasive surveillance to detect disease recurrence. Currently, there are no effective oral therapies that delay disease recurrence or progression. We recently demonstrated that in mice, metformin accumulates unchanged in the urine. Urothelial cells are exposed to metformin concentrations ~ 240-fold higher than in serum. This was effective in the treatment of mouse bladder cancer models...

PURPOSE: To assess whether receipt of 5-alpha reductase inhibitors (5-ARIs) influences the findings on surgical pathology at the time of radical cystectomy (RC) and subsequent clinical outcomes. 5-ARIs may slow the progression of non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We retrospectively reviewed all patients who underwent RC at our institution between 2009 and 2017. Men were included who had urothelial cancer in the RC specimen. Patients with nonurothelial pathology or who had no cancer in the specimen were excluded...

PURPOSE: In 2011, France and Germany banned pioglitazone due to a concomitant risk for bladder cancer. There has been continued debate about this topic. Therefore, we present a detailed analysis of data from individual case safety reports of pioglitazone use (PG-ICSRs) associated with bladder cancer reported worldwide and in India. METHODS: Data from PG-ICSRs reported by the National Coordination Centre's Pharmacovigilance Programme of India, as well as over 131 World Health Organization member countries in the Uppsala Monitoring Centre's VigiLyze pharmacovigilance database system, from January 1, 1967, to March 4, 2018, were collected...

BACKGROUND: Metformin has been reported to function as the anti-tumor inhibiting the growth of different types of cancers, including bladder cancer. But there are few reports on the roles of Yap1, the key molecule of Hippo pathway, in the metformin induced inhibition of bladder cancer (BLCA). We are wondering if the inhibitory effect of metformin on bladder cancer is fulfilled via Yap1 and exploring the related mechanism. METHODS: MTS and colony formation assays were used to explore the cellular viabilities and proliferation of BLCA cells challenged by metformin at different concentrations, in vitro...

Biguanides, including metformin and phenformin, have emerged as promising anticancer agents. However, the high dose needed for their efficient anticancer properties restricts their clinical application. In an attempt to obtain higher active compounds than these parent compounds, pyrazole-containing biguanide derivatives were synthesized and screened for in vitro cytotoxicity against human cancer cell lines. Clonogenic assays and scratch wound healing assays demonstrated that these new derivatives profoundly inhibit cell proliferation and migration...

There is conflicting evidence regarding the association between metformin use and cancer risk in diabetic patients. During 2002-2012, we followed a cohort of 315,890 persons aged 21-87 years with incident diabetes who were insured by the largest health maintenance organization in Israel. We used a discrete form of weighted cumulative metformin exposure to evaluate the association of metformin with cancer incidence. This was implemented in a time-dependent covariate Cox model, adjusting for treatment with other glucose-lowering medications, as well as age, sex, ethnic background, socioeconomic status, smoking (for bladder and lung cancer), and parity (for breast cancer)...