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Medicine and Health Sciences

Theses and Dissertations

Metformin

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Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik Jan 2022

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …


Modulation Of Electron Transport By Metformin In Cardiac Protection: Role Of Complex I, Ahmed Abdul Hussein Mohsin Jan 2018

Modulation Of Electron Transport By Metformin In Cardiac Protection: Role Of Complex I, Ahmed Abdul Hussein Mohsin

Theses and Dissertations

Modulation of mitochondrial complex I during reperfusion reduces cardiac injury. Complex I exists in two structural states: active (A) and deactive (D) with transition from A→D during ischemia. Reperfusion reactivates D→A with an increase in ROS production. Metformin preserves the D-Form. Our aim was to study the contribution of maintenance of deactivation of complex I during early reperfusion by metformin to protect against ischemia reperfusion injury. Our results showed that metformin decreased H9c2 cardiomyoblast apoptosis and total cell death following simulated ischemia for six hours followed by reoxygenation for twenty four hours compared to untreated cells. Reactive oxygen species (ROS) …


Metformin-Induced Pedf Expression Regulates Cell Proliferation And Lipid Metabolism In Prostate Cancer Cells, Miguel Angel Tolentino Aug 2013

Metformin-Induced Pedf Expression Regulates Cell Proliferation And Lipid Metabolism In Prostate Cancer Cells, Miguel Angel Tolentino

Theses and Dissertations

Prostate cancer (PCa) is one of the most common cancers in American males. A high fat diet and obesity accelerate PCa progression and increase the 1risk of death from disease. Epidemiological studies have indicated that PCa patients with type 2 diabetes have higher mortality rates than PCa patients without diabetes. Type 2 diabetics who are on metformin, a drug to control blood sugar levels, show a delay in PCa progression in comparison with PCa patients with type 2 diabetes who are not on metformin. It has been proposed that metformin inhibits proliferation via activation of AMP-activated protein kinase (AMPK) or …