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Dr. Madhav Nilakanth Mugale, M.V.Sc.,Ph.D.

Senior Scientist, Division Of Toxicology



LIVER CANCER:


Liver is primary organ involved in detoxification ingested material. Hepatocellular carcinoma (HCC) is the primary form of liver cancer that accounts for approx. 7 Lakhs deaths/year globally (WHO). Risk factors includes infection by hepatitis B and C viruses (HBV and HCV), chronic alcohol consumption, aflatoxin B1 (AFB1) exposure, non-alcoholic fatty liver disease (NAFLD) etc. including various chemical carcinogens. CYP2E1 enzyme is involved in the metabolic activation of carcinogens into genotoxic products which alkylate nucleic acids irreversibly in liver microsomes and recombinase systems. The enzyme transfers active electrons from reduced nicotinamide adenine dinucleotide phosphate (NADPH) or reduced nicotinamide adenine dinucleotide to oxygen to produce reactive oxygen species (ROS). CYP2E1-induced toxic metabolites coupled with oxidative stress from ROS are important mediators of liver injury.


The molecular mechanisms of the CYP2E1 gene in HCC are yet to be further explored to investigate novel therapeutic approaches for the treatment of HCC.









LUNG CANCER:


Most commonly affected system in the body is respiratory. The major types of lung cancer include adenocarcinoma, squamous cell carcinoma, small cell and large cell carcinoma. These include both non-small-cell lung cancer (NSCLC) 80% and small-cell lung cancer (SCLC) 20%. Lung cancer cells or normal adjacent cells express many growth factors, regulatory peptides and their receptors which leads to the development of some autocrine and paracrine growth stimulatory loops. A relevant proto-oncogene cerbB-2 (HER2/neu) is another growth factor receptor that encodes the protein of 185 kDa (p185neu) and cerbB-2 is expressed more in NSCLCs than the SCLCs. In viral oncogenesis ENV gene responble for progression and proliferation.


DIABETIC COMPLICATION(S):


Diabetes leads to number of complication in vascular system, leads to vital organ function impairment. One of the major complications of diabetes mellitus affecting ocular system due to chronic hyperglycaemia leading to irreversible retinal damage, and ultimately vision loss. Diabetic Retinopathy (DR) is characterized by complex inter-related pathophysiological mechanisms that includes genetic and epigenetic factors, increased production of oxidants, advanced glycosylation end products, secretion of various proinflammatory cytokines like TNF-α, IL-1β, IL-6 etc. Increase in adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) etc. along with the angiogenic factor, vascular endothelial growth factor (VEGF) have been found to be correlated with DR progression. Therefore, anti-VEGF therapy and other novel approaches can be used to understand and delineate the molecular pathways underlying the development of angiogenesis in DR using in vivo models. We contemplate translating the information gained from our research into strengthening current clinical medications and discovering novel therapeutic agents for the treatment of diabetic retinopathy.