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Showing posts from 2016

Metabolic pathways and energy sources for tumors

Warburg's effect is quoted many times to describe the faulty metabolic pathways in tumor cells. Tumor cells which are rapidly dividing are known to create a hypoxic microenvironment which does not support glucose oxidation. Under these circumstances, glycolysis becomes a dominant metabolic pathway to generate energy for the rapidly dividing tumor cells. However, this may not be the complete story. In recent years, there has been a tremendous amount of work being done to explore the metabolic pathways involved in various tumors. All this now depicts a newer reality where glycolysis instead of being "The pathway" is now thought to be one of the pathways used by the tumor cells. Of interest are the protein metabolic pathways such as glutamine and proline pathways, The nucleic acid metabolic pathways and my present interest, the fatty acids pathways.  If we consider that alternative pathways such as fatty acid oxidation, protein metabolic pathways,  then all the proteins ...

Overdiagnosis and Thyroid cancer incidence

If you read about thyroid cancer, everyone agrees that its incidence is on the rise. In recent months, there has been lots of press coverage as how this increased thyroid incidence is due to overdiagnosis. To illustrate the overdiagnosis with an example, we need to take a look at South Korea. There was a huge increase in the incidence of thyroid cancer in South Korea which was blamed on overdiagnosis . But a recent review article on this topic cautions; not so fast . Thyroid cancers form about 2.1% of total cancer diagnoses worldwide, with women disproportionately affected, accounting for about 77% of the cases. The phenomenon of more women patients than men is unique to thyroid pathology and is also seen in Hashimoto's thyroiditis and Graves' disease. Majority of thyroid cancers are termed differentiated with two main subtypes, papillary thyroid cancers (PTC) and follicular thyroid cancers (FTC). The increased incidence of the thyroid cancer is mainly attributed to increas...

SCLEROSING MUCOEPIDERMOID CARCINOMA WITH EOSINOPHILIA OF THYROID

BACKGROUND                                                Sclerosing mucoepidermoid carcinoma with eosinophils of thyroid (SCEME) is a rare thyroid carcinoma. Although it is believed to take a slow, indolent approach to grow, the carcinoma can cause complications due to involvement of large part of the thyroid and neck. Apart from the involvement of thyroid gland, SCEME is also known to metastasize to different body parts, further complicating the prognostic outcome. The interesting part of the clinical picture is sclerosis and fibrosis of the involved part of the thyroid gland, and Hashimoto’s Thyroiditis (HT) in non-involved portion of the thyroid. The stroma shows infiltration of eosinophils, lymphocytes and plasma cells. SCEME has been found to be...

Targeting AMPK and mTOR pathways in Eczema

Targeting AMPK and mTOR pathways in Eczema   Rationale Eczema or atopic dermatitis is chronic inflammation of the skin characterized by numerous relapses. Eczematous patches, plaques, epidermal edema along with immunological cells in the infiltrate are the histologic features of eczema. It has been shown recently that CD4 and CD8 T-cells and the inflammatory cytokines such as IFN-γ, TNF-α, play a dominant role in the pathology of atopic dermatitis. Recent literature also suggests using biologics targeted to counter these pro-inflammatory cytokines. However, recently more focus has been put towards understanding the metabolic pathways of T-cell activation. Particular focus has been put in understanding the fatty acid metabolism involved in the T-cells.  It has been shown that T-cell activation leads to increased glucose uptake and activation of PI3K/AKT and mTOR pathway. Utilization of fatty acids for energy needs, i.e. using beta oxidation on the other hand leads to...