Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research.
View Article and Find Full Text PDFWe have developed an innovative tool, the Intelligent Catchment Analysis Tool (iCAT), designed to identify and address healthcare disparities across specific regions. Powered by Artificial Intelligence and Machine Learning, our tool employs a robust Geographic Information System (GIS) to map healthcare outcomes and disease disparities. iCAT allows users to query publicly available data sources, health system data, and treatment data, offering insights into gaps and disparities in diagnosis and treatment paradigms.
View Article and Find Full Text PDFAtherosclerosis is the main cause of death in men and women. This so-called "hardening of the arteries" results from advanced atherogenesis, the accumulation and death of subendothelial fat-laden macrophages (vascular plaque). The macrophages are attracted as the result of signals from injured vessels recruiting and activating cells to quell the injury by inflammation.
View Article and Find Full Text PDFRationale: Development of cervical squamous carcinoma (CXCA) is accompanied by changes in estrogen receptors (ERs, ERα and ERβ) and ezrin expression; however, reports have been conflicting. Using histologically documented staging of cervical biopsies, we determined ezrin and ER relationships during CXCA development.
Methods: Immunoreactive (ir) ezrin, ir-ERα, and ir-ERβ were studied in normal epithelium, carcinoma in situ/cervical intraepithelial neoplasia (CIN) 1 to 3, and local invasion or metastatic CXCA.
Objectives: We have shown that ezrin expression correlates with ovarian epithelial cancer (OVCA) cell proliferation and metastatic behavior. In this study, we evaluated ezrin expression in transformed ovarian superficial epithelial cells (OSE) in ovarian clefts and in culture.
Study Design: Immunohistochemistry and Western blotting for immunoreactive ezrin (ir-ezrin) in normal ovarian tissue, cultured OSE, and ovarian epithelial cancer cells.
Objective: To examine total ezrin expression (ezrin and phospho-ezrin) through the normal endometrial cycle and to correlate ezrin activation and localization with cytologic changes.
Design: Experimental laboratory study.
Setting: University medical centers.
Background: New data management models are emerging in multi-center clinical studies. We evaluated the incremental costs associated with decentralized vs. centralized models.
View Article and Find Full Text PDFRationale: The mechanism of atherogenesis includes leukocyte adhesion to endothelial cells followed by migration into the subendothelial space. The polysialylated neural cell adhesion molecules (PSA-nCAMs) are a group of hydrophilic neural cell adhesion molecule (NCAM) isoforms that inhibit NCAM: NCAM association, thereby blocking cell: cell adhesion. During previous studies, we demonstrated that sialylation of specific NCAMs are upregulated at proestrus in the rat and that PSA-nCAM is expressed by the rat vascular endothelium.
View Article and Find Full Text PDFOverexpression of Aurora-A kinase is commonly detected in many cancers, whereas the von Hippel-Lindau protein (pVHL) is frequently mutated or absent in renal cell carcinoma and is involved in the Ub proteasome complex, an important degradation pathway. In order to establish a link between Aurora-A overexpression and lack of pVHL protein, we hypothesized that pVHL regulates Aurora-A expression through a physical interaction. We present the first evidence, from both biological assays and computational biology techniques, that human pVHL binds strongly to Aurora-A kinase.
View Article and Find Full Text PDFJ Biomol Struct Dyn
February 2010
Quantum modeling of the N7(G) alkylation of guanine-cytosine (G-C) base pair by sulfur (HD) and nitrogen mustard (HN2) was performed by using the Density Functional Theory (DFT) BPW91/6-31G++DP procedure. The vibrational IR and Raman spectra are discussed with regard to the N7 position of guanine when electrophilic HD+ episulfonium and HN2+ aziridinium attack the G-C base pair. Thermodynamic and polarizability considerations are also presented.
View Article and Find Full Text PDFProtozoan parasites are a major threat to human health with millions of fatalities worldwide, especially in nonindustrialized countries. Currently, there is no cure for many of these parasitic diseases. Consequently, there is an imperative to find treatment targets and develop novel drugs based on the proteins encoded in the genomes of these parasites.
View Article and Find Full Text PDFEstrogen-induced synaptic plasticity (EISP) in the periventricular area (PVA) of the hypothalamus is necessary for the preovulatory gonadotropin surge. Because in situ enzymatic desialization of hypothalamic polysialylated (PSA) neural cell adhesion molecule (NCAM) blocked EISP, we examined the presence and amount of NCAM isotopes, PSA-NCAM, and sialylation enzymes in microdissected mouse hypothalamus tissues from proestrous afternoon [peak of estrogens and nadir of arcuate nucleus (AN) synapses] and metestrous morning (nadir of estrogens and highest AN synapses). Immunohistochemistry confirmed immunoreactive (ir) PSA-NCAM staining in the perineural spaces of the PVA.
View Article and Find Full Text PDFType 2 diabetes mellitus (T2DM) is characterized by three major metabolic abnormalities: impaired insulin-stimulated glucose uptake in muscle and adipose tissues, alterations in glucose-stimulated insulin secretion, and increased hepatic glucose production. Both genetic and environmental factors contribute to its development. The insulin gene (INS), insulin receptor gene (INSR), and insulin receptor substrate 1 gene (IRS1), identified by polymerase chain reaction and digestion with selected restriction enzymes PstI, NsiI, and BstnI, have been proposed as T2DM candidate genes.
View Article and Find Full Text PDFObjective: Depo-Provera is a contraceptive approved by the US Food and Drug Administration (FDA) since 1992 and used worldwide by more than 90 million women.
Aim Of Study: Despite the fact that progestins are endogenous hormones that are secreted by the body, its excess might lead to detrimental health effects. Whether progestins as contraceptives are friends or foes is a questionable matter.
Proper gonadal function requires coordinated (feedback) interactions between the gonads, adenohypophysis, and brain: the gonads elaborate sex steroids (progestins, androgens, and estrogens) and proteins (inhibin-activin family) during gamete development. In both sexes, the brain-pituitary gonadotrophin-regulating interaction is coordinated by estradiol through its opposing actions on pituitary gonadotrophs (sensitization of the response to gonadotrophin-releasing hormone [GnRH]) versus hypothalamic neurons (inhibition of GnRH secretion). This dynamic tension between the gonadotrophs and the GnRH cells in the brain regulates the circulating gonadotrophins and is termed reciprocal/negative feedback.
View Article and Find Full Text PDFTumor necrosis factor-alpha (TNF-alpha) and Fas ligand induce apoptosis by interacting with their corresponding membrane-bound death receptors and activating caspases. Since both systems share several components of the intracellular apoptotic cascade and are expressed by first trimester trophoblasts, it is unknown how these cells remain resistant to Fas ligand while sensitive to TNF-alpha. XAF1 (X-linked inhibitor of apoptosis (XIAP)-associated factor 1) is a proapoptotic protein that antagonizes the caspase-inhibitory activity of XIAP.
View Article and Find Full Text PDFCurr Protein Pept Sci
February 2007
Electrostatic and electrochemical properties of bio-molecules, such as proteins, are governed by energy parameters that are, in part dependent on its folding. Disruption of this process can lead to the development of complex, multisystem diseases whose presentation may be organ-dependent. Examples include cystic fibrosis, alpha-1 antitrypsin deficiency, and Alzheimer disease.
View Article and Find Full Text PDFThe purpose of this study is to determine the feasibility of the direct matrix-assisted laser desorption/ionization (MALDI) identification of proteins in fixed T47D breast cancer cells and murine brain tissues. The ability to identify proteins from cells and tissue may lead to biomarkers that effectively predict the onset of defined disease states, and their dynamic behavior could be an important hint for drug target discoveries. Direct tissue application of trypsin allows protein identification in cells and tissues, while maintaining spatial integrity and intracellular organization.
View Article and Find Full Text PDFProkaryotic organisms of the genus Mycoplasma are characterized by their small body and genome size containing a 0.6-1.35 M bp genome.
View Article and Find Full Text PDFThe risks of low bone mineral density, osteoporosis and fractures, are major concerns in postmenopausal women. Although postmenopausal hormone therapy is effective for reducing these risks, safety issues have been raised by the results of studies such as the Women's Health Initiative. Although there are scientifically valid reasons to be wary of the general applicability of the Women's Health Initiative findings, the study has underscored the continuing need for research into new forms of menopausal hormone therapy.
View Article and Find Full Text PDFSex steroids control cell movement and tissue organization; however, little is known of the involved mechanisms. This report describes the ongoing dynamic regulation by estrogen of the actin cytoskeleton and cell movement in human vascular endothelial cells that depends on rapid activation of the actin-regulatory protein moesin. Moesin activation is triggered by the interaction of the C-terminal portion of cell membrane estrogen receptor alpha with the G protein Galpha(13), leading to activation of the small GTPase RhoA and of the downstream effector Rho-associated kinase.
View Article and Find Full Text PDFFarm animal genomics is of interest to a wide audience of researchers because of the utility derived from understanding how genomics and proteomics function in various organisms. Applications such as xenotransplantation, increased livestock productivity, bioengineering new materials, products and even fabrics are several reasons for thriving farm animal genome activity. Currently mined in rapidly growing data warehouses, completed genomes of chicken, fish and cows are available but are largely stored in decentralized data repositories.
View Article and Find Full Text PDFComplete brain fixation can be achieved with transthoracic cardiac infusion without thoracotomy. Light and electron microscopy tissue sections reveal preservation of cytoplasmic and nuclear structure at all magnification levels. Punched samples were obtained from the fixed tissue specimens in precisely localized areas for study using electron microscopy.
View Article and Find Full Text PDFComplete archaeal genomes were probed for the presence of long (> or = 25 bp) oligonucleotide repeats (words). We detected the presence of many words distributed in tandem with narrow ranges of periodicity (i.e.
View Article and Find Full Text PDFWe have for the first time exposed estrogen's role in the epithelial ovarian cancer (OVCA) metastatic cascade and discovered that it is related to the induction of ezrin over-expression. 17beta Estradiol (E2) was administered to SKOV3 (ERalpha>beta) and DOV13 (ERalpha