Global ETD Search

11	Novel 2-substituted isoflavones: A privileged structure approach to new agents for hormone-dependent breast cancer Kim, Young-Woo January 2003 (has links) No description available. hormone-dependent breast cancer estrogens isoflavones aromatase inhibitors selective estrogen receptor modulators 2-substituted isoflavones privileged structure
12	Estrogen receptor involvement in the response of human keratinocytes to ultraviolet B irradiation Farrington, Daphne L. January 2014 (has links) The signaling mechanisms involved in UVB-induced skin cancer are complex and although the scope of this work is inherently limited in focus, the findings may provide insight into how estrogen receptor signaling impacts cell growth, senescence, and apoptosis to protect keratinocytes. Additional signaling due to E2-activation of the estrogen receptor may provide back-up or redundant pathways in response to UVB. UVB Estrogen receptor Keratinocytes Skin -- Cancer Ultraviolet radiation Solar radiation Estrogen -- Receptors Selective estrogen receptor modulators Cells -- Growth Cells -- Aging Cells -- Death Apoptosis Keratinocytes
13	Design, Synthesis, and Process Chemistry Studies of Agents Having Anti-Cancer Properties Luniwal, Amarjit 26 May 2011 (has links) No description available. Chemistry Design Pharmaceuticals Pharmacy Sciences Drug Design Scale-up Synthesis Molecular docking studies Estrogen receptors Selective estrogen receptor modulators Breast Cancer Prostate Cancer Process Chemistry Glyceollins Pterocarpans Glycinol Benzofuran Dihydroxylation Isoprenylation
14	The effect of hypoxia on ER-β expression in the lung and cultured pulmonary artery endothelial cells Selej, Mona M.A. 12 March 2014 (has links) Indiana University-Purdue University Indianapolis (IUPUI) / 17-β estradiol (E2) exerts protective effects in hypoxia-induced pulmonary hypertension (HPH) via endothelial cell estrogen receptor (ER)-dependent mechanisms. However, the effects of hypoxia on ER expression in the pulmonary-right ventricle (RV) axis remain unknown. Based on previous data suggesting a role of ER-β in mediating E2 protection, we hypothesized that hypoxia selectively up-regulates ER-β in the lung and pulmonary endothelial cells. In our Male Sprague-Dawley rat model, chronic hypoxia exposure (10% FiO2) resulted in a robust HPH phenotype associated with significant increases in ER- β but not ER-α protein in the lung via western blotting. More importantly, this hypoxia-induced ER-β increase was not replicated in the RV, left ventricle (LV) or in the liver. Hence, hypoxia-induced ER-β up-regulation appears to be lung-specific. Ex vivo, hypoxia exposure time-dependently up-regulated ER-β but not ER-α in cultured primary rat pulmonary artery endothelial cells (RPAECs) exposed to hypoxia (1% O2) for 4, 24 or 72h. Furthermore, the hypoxia induced ER-β protein abundance, while not accompanied by increases in its own transcript, was associated with ER-β nuclear translocation, suggesting increase in activity as well as post-transcriptional up-regulation of ER-β. Indeed, the requirement for ER-β activation was indicated in hypoxic ER-βKO mice where administration of E2 failed to inhibit hypoxia-induced pro-proliferative ERK1/2 signaling. Interestingly, HIF-1α accumulation was noted in lung tissue of hypoxic ER-βKO mice; consistent with previously reported negative feedback of ER-β on HIF-1α protein and transcriptional activation. In RAPECs, HIF-1 stabilization and overexpression did not replicate the effects of ER- β up-regulation seen in gas hypoxia; suggestive that HIF-1α is not sufficient for ER-β up- regulation. Similarly, HIF-1 inhibition with chetomin did not result in ER-β down-regulation. HIF-1α knockdown in RPAECs in hypoxic conditions is currently being investigated. Hypoxia increases ER- β, but not ER-α in the lung and lung vascular cells. Interpreted in context of beneficial effects of E2 on hypoxic PA and RV remodeling, our data suggest a protective role for ER-β in HPH. The mechanisms by which hypoxia increases ER-β appears to be post-transcriptional and HIF-1α independent. Elucidating hypoxia-related ER-β signaling pathways in PAECs may reveal novel therapeutic targets in HPH. ER-β HIF-1α Right Ventricle Lung Pulmonary Artery Endothelial Cell Hypoxia Pulmonary Hypertension 17beta Estradiol Endothelial cells -- Research Selective estrogen receptor modulators Hypoxia (Water) -- Research Heart -- Right ventricle Heart --Left ventricle Western immunoblotting Pulmonary artery -- Research Cellular signal transduction Blood-vessels -- Diseases Phenotype -- Research
15	<b>CHARACTERIZATION OF SERPINA1 IN ADULT SPINAL HOMEOSTASIS TO INFORM TREATMENT STRATEGIES</b> Neharika Bhadouria (17266174) 07 December 2023 (has links) <p dir="ltr">People suffering from COPD are also known to suffer from other musculoskeletal issues like fracture risk, back pain, etc. Intervertebral disc degeneration (IVD) is a prominent cause of back pain and inflammation, influenced by factors such as aging, sudden loading, and genetics. <i>SERPINA1</i>, a common genetic variant in individuals with chronic obstructive pulmonary disease (COPD), encodes the alpha-antitrypsin protein (AAT). AAT deficiency is also associated with IVD degeneration, bone loss, and gait impairment. Currently, AAT-deficient individuals receive costly and short-lived weekly AAT injections, with no established guidelines for managing IVD degeneration and osteoporosis. Our primary research objective was to examine the effects of <i>serpinA1a/c</i> using a mouse model with global knockout (KO) of <i>serpinA1a/c</i>, generated through CRISPR technology, on intervertebral discs (IVD) and bone. We found that global deletion of <i>serpinA1a/c</i> was found to cause IVD elastin degradation, leading to a loss of mechanical properties. Moreover, <i>serpinA1</i> was associated with increased bone-resorbing cells (osteoclasts) and a reduction in bone-forming cells (osteoblasts). Notably, sexual dimorphism was observed, with female IVDs exhibiting less degeneration than male counterparts, and <i>serpinA1a/c</i> KO mice were protected from mechanically-induced tail compression. Even in human IVDs, males expressed more AAT-1 compared to female IVDs. There are no FDA-approved drugs currently existing for IVD degeneration. Since IVD degeneration frequently occurs in individuals with osteoporosis, it shows a probable cross-talk happening between IVD and bone. In our study, we found the association of <i>serpinA1 </i>with estrogen receptor alpha and osteoclasts. Hence, we investigated the potential of raloxifene, an FDA-approved selective estrogen receptor modulator (SERM) typically prescribed to post-menopausal women for osteoporosis treatment, in averting IVD degeneration and improving mechanical characteristics in IVD. Our findings suggest that raloxifene injection may retard IVD degeneration induced by AAT deficiency, particularly in male mice. Furthermore, the latter study touched upon a conditional <i>serpinA1a</i> mouse model crossed with aggrecan-cre, specifically targeting <i>serpinA1a</i>-expressing cells in the IVD while sparing bone. Conditional <i>serpinA1a</i> deletion induced mild IVD degeneration without affecting bone loss. In summary, this study serves as a foundation for testing potential treatments for AAT patients with IVD degeneration and osteoporosis. It also provides compelling evidence for considering raloxifene as a treatment option for IVD degeneration in AAT-deficient patients experiencing IVD-related pain.</p> Genetically modified animals Animal structure and function Respiratory diseases Orthopaedics Pain Surgery Biomedical imaging Biomechanics SERPINA1 gene Raloxifene/pharmacokinetic Intervertebraldisc bone intervertebral disc injury Human intervertebral disc discogenic pain genetically modified animals Sex dimorphism aging behavioral assays Magnetic resonance Imaging Chronic obstructive pulmonary disease Spine biomechanics AAT-1 alpha-antitrypsin emphysema crosstalk treatment EVISTA tail disc lumbar disc tail compression FTIR QPCR Gene expression SerpinA1 isoforms lung conditional KO mice Global KO mice

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