A5089879911- Cancer-related Molecular Pathways
- Advanced Breast Cancer Therapies
- Ocular Oncology and Treatments
- Urinary Bladder and Prostate Research
- Mechanisms of cancer metastasis
- Prostate Cancer Treatment and Research
- Caveolin-1 and cellular processes
- Cancer Mechanisms and Therapy
- Synthesis and biological activity
- Pharmacogenetics and Drug Metabolism
- Lung Cancer Research Studies
- Estrogen and related hormone effects
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Hormonal Regulation and Hypertension
- Urological Disorders and Treatments
- Radiopharmaceutical Chemistry and Applications
- Mitochondrial Function and Pathology
- Hormonal and reproductive studies
- NF-κB Signaling Pathways
- Cellular Mechanics and Interactions
- Peptidase Inhibition and Analysis
- Pelvic floor disorders treatments
- Tissue Engineering and Regenerative Medicine
- Tannin, Tannase and Anticancer Activities
Thomas Jefferson University
2016-2024
University of Pennsylvania
2006-2023
Philadelphia University
2016
Children's Hospital of Philadelphia
2016
Sidney Kimmel Cancer Center
2016
California University of Pennsylvania
2012
Weizmann Institute of Science
2002
Indian Institute of Science Bangalore
1999
Abstract RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that multiple murine models of produces a prometastatic phenotype. Gene expression analyses showed regulation the cell motility receptor RHAMM by RB/E2F pathway was critical for epithelial–mesenchymal transition, motility, and invasion cells. Genetic modulation or pharmacologic inhibition activity sufficient necessary metastatic phenotypes induced prostate...
Purpose: The retinoblastoma tumor suppressor (RB), a key regulator of cell-cycle progression and proliferation, is functionally suppressed in up to 50% non-small cell lung cancer (NSCLC). RB function exquisitely controlled by series proteins, including the CyclinD-CDK4/6 complex. In this study, we interrogated capacity CDK4/6 inhibitor, palbociclib, activate function.Experimental Design Results: We employed multiple isogenic RB-proficient -deficient NSCLC lines interrogate cytostatic...
Partial bladder outlet obstruction in male rabbits causes detrusor smooth muscle hypertrophy and voiding dysfunction similar to that observed men with benign prostate hyperplasia. Using this model, we analyzed the protein expression ultrastructure of caveolae intermediate size filament following partial induced hypertrophy.Detrusor sections from body were processed for immunofluorescence electron microscopy. Western analysis was performed determine caveolin isoform-1, 2 3, proteins.Detrusor...
A comprehensive genomic and proteomic, computational, physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators internal anal sphincter (IAS) smooth muscle contractile phenotype basal tone. miRNA profiling, genome-wide expression, validation, network analyses were assess changes in mRNA expression IAS muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c,...
Expression of hepatic cytochromes P450 (CYP) in all species examined, including humans, is generally sexually dimorphic. We examined the sex-dependent expression CYP3A5 and hormone-regulated molecular mechanism(s) responsible for any dimorphism.
Perturbations in the retinoblastoma pathway are over-represented advanced prostate cancer; loss promotes bypass of first-line hormone therapy. Conversely, preliminary studies suggested that retinoblastoma-deficient tumors may become sensitized to a subset DNA-damaging agents. Here, molecular and vivo consequence status was analyzed models clinical relevance.Experimental work performed with multiple isogenic cancer cell lines (hormone sensitive: LNCaP LAPC4 cells resistant C42, 22Rv1 cells;...
A large number of mitochondrial proteins lack canonical mitochondrial-targeting signals. The bimodal transport cytochromes P450 (CYPs) to endoplasmic reticulum and mitochondria (MT), reported previously by us, likely represents one mode non-canonical protein targeting MT. Herein, we have studied the mechanism mouse MT-CYP1A1 gain insight into regulatory features evolutionary conservation mechanism. Mouse consists two NH2-terminal-truncated molecular species, +91A1 +331A1. Mutations Pro-2 →...
Cytochrome P450 (CYP)3A4 is the principal and most abundant human isoform of CYP responsible for metabolism more than 50% all consumed drugs innumerable endogenous compounds. Expression CYP3A4 sexually dimorphic regulated by combined actions GH glucocorticoids. In case rat, nearly CYPs are "intrinsically" or "inherently" dimorphic, meaning that expressed sex differences permanent irreversible. Using primary hepatocyte cultures derived from men women exposed to physiologic-like levels...
Protein kinase C (PKC)-potentiated inhibitory protein of 17 kDa (CPI-17) inhibits myosin light chain phosphatase, altering the levels phosphorylation and Ca2+ sensitivity in smooth muscle. In this study, we characterized CPI-17 promoter identified binding sites for GATA-6 nuclear factor kappa B (NF-κB). NF-κB upregulated expression cultured human mouse bladder muscle (BSM) cells an additive manner. was decreased upon silencing BSM from knockout (KO) mice. Moreover, force maintenance by...
The biochemical and molecular characteristics of cytochrome P4501A1 targeted to rat brain mitochondria was studied determine the generality targeting mechanism previously described for mitochondrial P450MT2 (P450MT2) from liver. In C6 glioma cells chronically exposed beta-naphoflavone (BNF), content reached 50 95% total cellular pool, respectively. 10 days BNF-treated purified over 85% purity using hydrophobic chromatography followed by adrenodoxin affinity binding. Purified consisted two...
The RB pathway plays a critical role in proliferation control that is commonly subverted tumor development. However, restoration of function can be elicited many cells by the inhibition CDK4/6 activity leads to dephosphorylation and subsequent repression E2F-mediated transcription. In this context, active RB/E2F complexes inhibit expression program coding genes promote cell cycle progression. non-coding RNA target downstream from could relevant for biology remain obscure. Here, miRNA gene...
Partial bladder outlet obstruction (pBOO)-induced remodeling of detrusor smooth muscle (DSM) is associated with the modulation cell signals regulating contraction. We analyzed DSM from obstructed murine urinary bladders for temporal regulation RhoA GTPase and Rho-activated kinase (ROCK), which are linked to Ca(2+) sensitization. In addition, effects equibiaxial stretch, a condition thought be pBOO-induced wall hypertrophy voiding frequency, on expression RhoA, ROCK, C-kinase-activated...
Purpose: Recent research has highlighted the mechanotransducer PIEZO2 as a crucial factor in lower urinary tract function, demonstrating associations with bladder compliance (BC), wall thickening, and elevated pressure. We explored hypothesis that <i>PIEZO2</i> expression may be associated dysfunction men outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH).Methods: The study included consecutive series of patients undergoing open prostatectomy for BPH at our...
A transcription suppressor element (sequence -481 to -320) containing a G-rich motif (designated GTG) and newly identified CAT-rich CATR) was previously shown modulate expression of the mouse cytochrome c oxidase Vb gene during myogenesis. Here, we show that GTG is critical for activation in both undifferentiated differentiated myocytes. Mutations CATR abolished repression myoblasts while limiting myotubes, suggesting contrasting functional attributes this DNA at different stages Results...
Caldesmon (CaD), a component of smooth muscle thin filaments, binds actin, tropomyosin, calmodulin, and myosin inhibits actin-activated ATP hydrolysis by myosin. Internal deletions the chicken CaD functional domain that spans from amino acids (aa) 718 to 731, which corresponds aa 512-530 including adjacent sequence in mouse CaD, lead diminished CaD-induced inhibition Transgenic mice with mutations five residues (Lys(523) Gln, Val(524) Leu, Ser(526) Thr, Pro(527) Cys, Lys(529) Ser), encompass...