Publications by authors named "Shyam Nathan"
Article Synopsis
- - Systemic sclerosis (SSc) is an autoimmune disease that leads to issues like blood vessel dysfunction, immune system problems, and widespread tissue scarring, but studying it has been tough due to a lack of relevant research models.
- - Researchers created an innovative in-vitro model using induced pluripotent stem cell-derived mesenchymal cells (iSCAR) to mimic the scarring seen in SSc, allowing for detailed investigation of gene expression tied to scarring at different stages.
- - The study confirms that the iSCAR model can be effectively used to test antifibrotic drugs, demonstrating responses to different compounds and revealing significant insights into the genes involved in both early and late stages of fibrosis.
Article Synopsis
- - LPA, produced by enzymes like autotaxin, activates specific receptors that promote pro-fibrotic signaling in the lungs of patients with idiopathic pulmonary fibrosis, leading to changes in basal cells of small airway epithelium.
- - Experiments showed that treating these basal cells with LPA resulted in significant signaling activity that increased the production of key proteins associated with tissue growth and fibrosis, such as CTGF and PDGFB.
- - The medium from LPA-treated basal cells stimulated the proliferation of normal human lung fibroblasts and raised their expression of collagen and other proteins, highlighting a interaction that may drive lung tissue remodeling in fibrosis.
Purpose: We previously identified small molecules that fit into a BRCA1-binding pocket within estrogen receptor-alpha (ERα), mimic the ability of BRCA1 to inhibit ERα activity ("BRCA1-mimetics"), and overcome antiestrogen resistance. One such compound, the hydrochloride salt of NSC35446 ("NSC35446.HCl"), also inhibited the growth of antiestrogen-resistant LCC9 tumor xenografts.
View Article and Find Full Text PDFContext: Resistance to conventional antiestrogens is a major cause of treatment failure and, ultimately, death in breast cancer.
Objective: The objective of the study was to identify small-molecule estrogen receptor (ER)-α antagonists that work differently from tamoxifen and other selective estrogen receptor modulators.
Design: Based on in silico screening of a pharmacophore database using a computed model of the BRCA1-ER-α complex (with ER-α liganded to 17β-estradiol), we identified a candidate group of small-molecule compounds predicted to bind to a BRCA1-binding interface separate from the ligand-binding pocket and the coactivator binding site of ER-α.