A5089912608- TGF-β signaling in diseases
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Inflammatory mediators and NSAID effects
- Cancer-related gene regulation
- Estrogen and related hormone effects
- Cancer Immunotherapy and Biomarkers
- Neuropeptides and Animal Physiology
- Helicobacter pylori-related gastroenterology studies
- Gastric Cancer Management and Outcomes
- Cancer-related Molecular Pathways
- Barrier Structure and Function Studies
- Neuroendocrine Tumor Research Advances
- Cancer Research and Treatments
- Wnt/β-catenin signaling in development and cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Colorectal Cancer Surgical Treatments
- Cancer Mechanisms and Therapy
- Growth Hormone and Insulin-like Growth Factors
- Cancer Genomics and Diagnostics
Vanderbilt University Medical Center
2014-2024
Vanderbilt University
2012-2022
National Heart Foundation of Australia
2017
Vanderbilt-Ingram Cancer Center
1999-2015
Tennessee Oncology
2004-2015
Moffitt Cancer Center
2012
The University of Texas Southwestern Medical Center
2007
Breast Cancer Research Foundation
2006
Centre for Cancer Biology
2003-2005
VA Tennessee Valley Healthcare System
2003-2005
A considerable amount of evidence collected from several different experimental systems indicates that cyclooxygenase-2 (COX-2) may play a role in colorectal tumorigenesis. Large epidemiologic studies have shown 40-50% reduction mortality cancer persons taking aspirin or other nonsteroidal antiinflammatory drugs on regular basis. One property shared by all these is their ability to inhibit COX, key enzyme the conversion arachidonic acid prostaglandins. Two isoforms COX been characterized,...
A highly immunogenic C3H-derived UV-induced tumor was cotransfected with a murine transforming growth factor type beta 1 (TGF-beta 1) cDNA and neomycin-resistance gene. Stable clones were isolated used in vitro vivo to determine the effects of endogenously produced TGF-beta on cytolytic T-lymphocyte (CTL) responses. Tumor cells producing TGF-beta, though retaining expression for class I major histocompatibility complex molecules tumor-specific antigen, did not stimulate primary CTL responses...
A nontransformed rat jejunal crypt cell line (IEC-6) expresses transforming growth factor type beta 1 (TGF-beta 1) mRNA, secretes latent 125I-labeled TGF-beta competing activity into culture medium, and binds to specific, high-affinity (Kd = 3.7 pM) surface receptors. IEC-6 is markedly inhibited by 2 with half-maximal inhibition occurring between 0.1 1.0 ng of per ml. 1-mediated not associated the appearance biochemical markers enterocyte differentiation such as alkaline phosphatase...
<h3>Objective</h3> Claudin-1 expression is increased and dysregulated in colorectal cancer causally associates with the dedifferentiation of colonic epithelial cells, progression metastasis. Here, we have sought to determine role claudin-1 plays regulation intestinal homeostasis. <h3>Design</h3> We used a novel villin-claudin-1 transgenic (Cl-1Tg) mouse as model (with overexpression). The effect upon differentiation, lineage commitment Notch-signalling was determined using...
Small molecule inhibitors of signaling pathways have proven to be extremely useful for the development therapeutic strategies human cancers. Blocking tumor-promoting effects transforming growth factor-β (TGF-β) in advanced stage carcinogenesis provides a potentially interesting drug target intervention. Although very few TGF-β receptor kinase (TRKI) are now emerging preclinical studies, nothing is known about how these might regulate tumor-suppressive or TGF-β, when treatment during cancer...
Transforming growth factor alpha (TGF alpha) shares with epidermal (EGF) structural homology (35%), a common cell-surface membrane receptor alpha/EGF receptor), and nearly identical spectrum of biological activity, including inhibition gastric acid secretion. Herein, we report expression TGF mRNA in normal mucosa the adult guinea pig, rat, dog. was also detected matched surgically resected adjacent carcinoma from 10 patients, to benign ulcer an additional patient. protein quantitated by...
Oncogenic ras induces the expression of cyclooxygenase-2 (COX-2) in a variety cells. Here we investigated role transforming growth factor-β (TGF-β) Ras-mediated induction COX-2 intestinal epithelial cells (RIE-1). RIE-1 were transfected with an inducible Ha-RasVal12 cDNA and are referred as RIE-iRas addition 5 mmisopropyl-1-thio-β-d-galactopyranoside (IPTG) induced Ha-RasVal12, closely followed by increase COX-2. Neutralizing anti-TGF-β antibody partially blocked Ras-induced Combined...
The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in inflammatory states, and COX-2 overexpression plays a key role carcinogenesis. To understand mechanisms regulating expression, we examined its posttranscriptional regulation mediated through AU-rich element (ARE) within mRNA 3′-untranslated region (3′UTR). RNA binding studies, performed to identify ARE-binding regulatory factors, demonstrated translational repressor protein TIA-1 mRNA....
Transformation of epithelial cells is associated with loss cell polarity, which includes alterations in morphology as well changes the complement plasma membrane proteins. Rab proteins regulate polarized trafficking to and therefore represent potential regulators this neoplastic transition. Here we have demonstrated a tumor suppressor function for Rab25 intestinal neoplasia both mice humans. Human colorectal adenocarcinomas exhibited reductions expression independent stage, lower levels...
Metastatic recurrence is the leading cause of cancer-related deaths in patients with colorectal carcinoma. To capture molecular underpinnings for metastasis and tumor progression, we performed integrative network analysis on 11 independent human cancer gene expression datasets applied data from an immunocompetent mouse model as additional filter this biologic process. In silico one metastasis-related coexpression module predicted nuclear factor activated T-cell (NFAT) transcription factors...