Reflections

 Good news for all the sufferers of atopic dermatitis. Incyte pharmaceuticals new drug- ruxolitinib cream was approved ( https://investor.incyte.com/press-releases/press-releases/2021/Incyte-Announces-U.S.-FDA-Approval-of-Opzelura-ruxolitinib-Cream-a-Topical-JAK-Inhibitor-for-the-Treatment-of-Atopic-Dermatitis-AD/default.aspx  ) by the FDA today (21st September 2021). OpzeluraTM is a topical cream whose active ingredient is a janus kinase inhibitor- ruxolitinib.  The cream is approved for 12 years and older for topical short-term non-chronic and non-continuous use in patients who are not immuno-compromised.  JAK-STAT pathway is a key cell signaling pathway involved in inflammation and itch. 

  Specific aims Mechanistic target for rapamycin (mTOR) has recently emerged as central regulator of cell metabolism with key role in cell proliferation and cancer development.  Our investigation of human follicular thyroid cancer (FTC) tissue samples demonstrated activation of mTOR along with p-CREB. Our transgenic mouse model of human FTC by protein kinase A (PKA) activation (due to knockdown of the regulatory subunit PRKAR1A gene implicated as tumor suppressor in human FTC), faithfully replicated the human FTC results with activation of mTOR and p-CREB. Examination of signaling pathways in our mouse model, we interestingly found activation of AMPK (Thr-172) which is not only an energy sensor but also termed as negative regulator of mTOR pathway. However, AMPK is also essential to prevent cellular apoptosis in cells subjected to various kinds of stress. We therefore hypothesize that activation of both AMPK and mTOR pathways are essential, balancing the cellular metabolic pat...

  Targeting AMPK and mTOR pathways in Atopic Dermatitis 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...

  RET/PTC3 Oncogene's Inflammatory Properties and Hashimoto's Thyroiditis   Various components of the ability to fight of infection in a host are collectively termed as immune system. Swelling, redness, pain and heat at the site of infection are hallmark of the active immune system and are defined as inflammation. Generally, more robust the inflammatory reaction is, the better it is for the host to clear the infection. Cancers are different as they are said to be actively causing the development of inflammation. The reason is that increased blood flow to the site of cancer brings more and more nutrients and other mediators which contradictorily help expand the cancer growth. We however believe that to be inaccurate, at best reflecting certain cancers only. We investigate papillary thyroid carcinoma (PTC) which is one of the most prevalent endocrine tumor known, accounting for about 85% of the thyroid malignancies. The incidence of thyroid cancers is on the rise too, in USA and...

  SCLEROSING MUCOEPIDERMOID CARCINOMA WITH EOSINOPHILIA OF THYROID (Failed Beheard application 😉) Research background and summary  What rare disease do you study?  A: SCLEROSING MUCOEPIDERMOID CARCINOMA WITH EOSINOPHILIA OF THYROID The general disease area of the rare disease you study. e.g. Immune/inflammatory disorder, metabolic disorder, neurodegenerative disorder, etc...  A: CANCER BIOLOGY/ INFLAMMATION Specific Aims (Less than 1000 words) This section should include background, hypothesis, specific aims, and significance.  A: 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 interest...