A5090559554- Prostate Cancer Treatment and Research
- TGF-β signaling in diseases
- Prostate Cancer Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Cancer Cells and Metastasis
- Urinary Bladder and Prostate Research
- Cancer-related Molecular Pathways
- Tissue Engineering and Regenerative Medicine
- Estrogen and related hormone effects
- Hormonal and reproductive studies
- FOXO transcription factor regulation
- Urological Disorders and Treatments
- Urologic and reproductive health conditions
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Lipid metabolism and biosynthesis
- Protease and Inhibitor Mechanisms
- Sexual Differentiation and Disorders
- Epigenetics and DNA Methylation
- Cell Adhesion Molecules Research
- Mathematical Biology Tumor Growth
- Fatty Acid Research and Health
- Mechanisms of cancer metastasis
- Inflammatory Biomarkers in Disease Prognosis
Louisiana State University in Shreveport
2024-2025
Louisiana State University Health Sciences Center Shreveport
2024
Louisiana State University
2024
Vanderbilt University Medical Center
2007-2023
NorthShore University HealthSystem
2015-2023
University of Chicago
2018-2023
Vanderbilt University
2010-2023
Vanderbilt-Ingram Cancer Center
2023
Breast Cancer Research Foundation
2023
John Wiley & Sons (United States)
2019
Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, mechanisms by which CAFs regulate cancer cell migration poorly understood. In this study, we show fibronectin (Fn) assembled mediates CAF–cancer association and directional migration. Compared with normal fibroblasts, produce an Fn-rich extracellular matrix anisotropic fiber orientation, guides cells to migrate directionally. align Fn increasing nonmuscle...
Abstract The present study explores the mechanisms by which human prostatic carcinoma-associated fibroblasts (CAF) induce tumorigenesis in initiated but nonmalignant epithelial cells (BPH-1). CAF express elevated levels of both transforming growth factor-β1 (TGF-β1) and stromal cell–derived factor-1 (SDF-1/CXCL12). TGF-β inhibits BPH-1 vitro, was found to be necessary for tumorigenic response CAF. This counterintuitive result suggested that signaling system involved other processes relating...
Carcinoma-associated fibroblasts (CAF) play a critical role in malignant progression. Loss of TGF-β receptor II (TGFβR2) the prostate stroma is correlated with prostatic tumorigenesis. To determine mechanisms by which stromal heterogeneity because loss TGFβR2 might contribute to cancer progression, we attenuated transforming growth factor beta (TGF-β) signaling subpopulation immortalized human model tumor In tissue recombination model, function 50% cell population resulted transformation...
The stromal microenvironment has key roles in prostate development and cancer, cancer-associated fibroblasts (CAFs) stimulate tumourigenesis via several mechanisms including the expression of pro-tumourigenic factors. Mesenchyme (embryonic stroma) controls organogenesis, some circumstances can re-differentiate tumours. We have applied next-generation Tag profiling to fetal human prostate, normal (NPFs) CAFs identify molecules expressed prostatic stroma. Comparison gene profiles a...
Abstract Autoimmune (AI) diseases can affect many organs; however, the prostate has not been considered to be a primary target of these systemic inflammatory processes. Here, we utilize medical record data, patient samples, and in vivo models evaluate impact inflammation, as seen AI diseases, on tissue. Human mouse tissues are used examine whether targeting inflammation limits prostatic hyperplasia. Evaluation 112,152 records indicates that benign hyperplasia (BPH) prevalence is...
Abstract Genetic changes in epithelial cells initiate the development of prostatic adenocarcinomas. As nascent tumors grow and undergo progression, tumor are intimately associated with stromal cells. Stromal within microenvironment acquire new properties, including capacity to promote phenotypic genetic progression adjacent Affymetrix microarrays were used identify 119 genes differentially expressed between normal-derived carcinoma-derived These included 31 encoding extracellular proteins...
Abstract Prostate cancer develops through a stochastic mechanism whereby precancerous lesions on occasion progress to multifocal adenocarcinoma. Analysis of human benign and prostate tissues revealed heterogeneous loss TGF-β signaling in the cancer-associated stromal fibroblastic cell compartment. To test hypothesis that progression is dependent responsive microenvironment, tissue recombination experiment was designed which ratio nonresponsive cells varied. Although 100% supported growth...
Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of invasive breast cancer which approximately half the patients will progress to cancer. Gaining better understanding DCIS progression may reduce overtreatment patients. Expression pro-inflammatory cytokine interleukin-6 increases with pathological stage and grade, associated poorer prognosis Carcinoma fibroblasts (CAFs), are present stroma known secrete cytokines promote tumor progression. We hypothesized that IL-6 paracrine...
Primary culture and animal cell-line models of prostate bladder development have limitations in describing human biology, novel strategies that describe the full spectrum differentiation from foetal through to ageing tissue are required. Recent advances biology demonstrate direct reprogramming somatic cells into pluripotent embryonic stem cell (ESC)-like is possible. These cells, termed induced (iPSCs), could theoretically generate adult tissue, providing an alternative strategy study...
Carcinoma-associated fibroblasts (CAF) are a heterogeneous group of cells within the tumor microenvironment (TME) that can promote tumorigenesis in prostate. By understanding mechanism(s) by which CAF contributes to growth, new therapeutic targets for management this disease may be identified. These studies determined whether unique sub-populations human prostate identified and functionally characterized.Single-cell RNA-seq primary followed unsupervised clustering was utilized generate cell...
Abstract Recent advancements in single-cell RNA sequencing (scRNAseq) have facilitated the discovery of previously unrecognized subtypes within prostate cancer (PCa), offering new insights into heterogeneity and progression. In this study, we integrated scRNAseq data from multiple studies, comprising publicly available cohorts generated by our research team, established H uman P rostate S ingle cell A tlas (HuPSA) M ouse (MoPSA) datasets. Through comprehensive analysis, identified two novel...
Cooperativity between oncogenic mutations is recognized as a fundamental feature of malignant transformation, and it may be mediated by synergistic regulation the expression pro- antitumorigenic target genes. However, mechanisms which oncogenes tumor suppressors coregulate downstream targets pathways remain largely unknown. Here, we used ChIP coupled to massively parallel sequencing (ChIP-seq) gene profiling in mouse prostates identify direct suppressor Nkx3.1. Further analysis indicated...
BACKGROUND Benign prostatic hyperplasia (BPH) is a common, chronic progressive disease. Inflammation associated with enlargement and resistance to 5α‐reductase inhibitor (5ARI) therapy. Activation of the nuclear factor‐kappa B (NF‐κB) pathway linked both inflammation ligand‐independent prostate cancer progression. METHODS NF‐κB activation androgen receptor variant (AR‐V) expression were quantified in transition zone tissue samples from patients wide range AUASS incidental BPH treated for low...
Abstract Acyl-CoA:diacylglycerol acyltransferase I (DGAT1) is a key enzyme in lipogenesis which increased metabolically active cells to meet nutrient requirements. DGAT1 has been recognized as an anti-obesity target; however, its role the tumor microenvironment remains unclear. We postulated that, prostate cancer (PCa) cells, augmented and growth are due expression leading microtubule-organizing center (MTOC) amplification. Thus, therapeutic targeting of potentially suppressive activity....
Abstract We have implemented a hybrid cellular automata model based on the structure of human prostate that recapitulates key interactions in nascent tumor foci between cells and adjacent stroma. Model simulations show how stochastic stroma may lead to structural suppression growth, modest proliferation, or unopposed growth. The incorporates aspects progression, including transforming growth factor-β (TGF-β), matrix-degrading enzyme activity, stromal activation. It also examines importance...