A5010487754- Cancer-related gene regulation
- Esophageal Cancer Research and Treatment
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- Esophageal and GI Pathology
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Head and Neck Cancer Studies
- Gastric Cancer Management and Outcomes
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- Fibroblast Growth Factor Research
- Cancer Research and Treatments
- Helicobacter pylori-related gastroenterology studies
- Digestive system and related health
- NF-κB Signaling Pathways
- Kruppel-like factors research
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- Cancer Diagnosis and Treatment
- Skin and Cellular Biology Research
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Protein Kinase Regulation and GTPase Signaling
Penn State Milton S. Hershey Medical Center
2011-2025
Pennsylvania State University
2014-2024
University of Pennsylvania
2000-2023
UPMC Hillman Cancer Center
2023
Hershey (United States)
2014
Cancer Research Institute
2006-2012
Fox Chase Cancer Center
2010
The Wistar Institute
2010
Esophageal cancer is a prototypic squamous cell that carries poor prognosis, primarily due to presentation at advanced stages. We used human esophageal epithelial cells as platform recapitulate cancer, thereby providing insights into the molecular pathogenesis of cancers in general. This was achieved through retroviral-mediated transduction normal, primary epidermal growth factor receptor (EGFR), catalytic subunit telomerase (hTERT), and p53(R175H), genes are frequently altered cancer. These...
Transforming growth factor-beta (TGF-beta) is a potent inducer of epithelial to mesenchymal transition (EMT). However, it remains elusive about which molecular mechanisms determine the cellular capacity undergo EMT in response TGF-beta. We have found that both epidermal factor receptor (EGFR) overexpression and mutant p53 tumor suppressor genes contribute enrichment an EMT-competent subpopulation among telomerase-immortalized human esophageal cells during malignant transformation. EGFR...
Abstract Current nucleic acid delivery methods have not achieved efficient, non‐toxic of miRNAs with tumor‐specific selectivity. In this study, a new system based on light‐inducible gold–silver–gold, core–shell–shell (CSS) nanoparticles is presented. This delivers small therapeutics precise spatiotemporal control, demonstrating the potential for achieving selectivity and efficient miRNA mimics. The particles leverage photothermal heating metal due to local surface plasmonic resonance...
The esophageal epithelium is a prototypical stratified squamous that exhibits an exquisite equilibrium between proliferation and differentiation. After basal cells proliferate, they migrate outward toward the luminal surface, undergo differentiation, eventually slough due to apoptosis. identification characterization of stem responsible for maintenance remains elusive. Here, we employed Hoechst dye extrusion BrdU label–retaining assays identify in mice potential cell population localizes...
Barrett's esophagus is a premalignant condition whereby the normal stratified squamous esophageal epithelium undergoes transdifferentiation program resulting in simple columnar reminiscent of small intestine. These changes are typically associated with chronically exposed to acid and bile salts as result gastroesophageal reflux disease (GERD). Despite this well-defined epidemiologic association between esophagus, genetic that induce process keratinocytes have remained undefined.To begin...
Extrapituitary prolactin (Prl) is produced in humans and rodents; however, little known about its vivo regulation or physiological function. We now report that autocrine required for terminal mammary epithelial differentiation during pregnancy production regulated by the Pten–PI3K–Akt pathway. Conditional activation of PI3K–Akt pathway glands virgin mice either Akt1 expression Pten deletion rapidly induced accompanied synthesis milk despite absence lobuloalveolar development. Surprisingly,...
Barrett's esophagus (BE) is defined as an incomplete intestinal metaplasia characterized generally by the presence of columnar and goblet cells in formerly stratified squamous epithelium esophagus. BE known a precursor for esophageal adenocarcinoma. Currently, cell origin human has yet to be clearly identified. Therefore, we investigated role Notch signaling initiation metaplasia. Affymetrix gene expression microarray revealed that samples express decreased levels receptors (NOTCH2 NOTCH3)...
Esophageal squamous cell carcinoma (ESCC), which is the most common subtype of esophageal cancers, sixth leading cause cancer deaths worldwide with a five-year survival rate 19%. Identification efficient biomarkers for early detection and better understanding molecular mechanisms ESCC may offer reduced mortality. However, proper clinical diagnosis prognosis have not been defined yet. In presented study, we employed systematic integrative 'omics' strategy to reconstruct networks...
The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism, is one of the most commonly activated pathways human cancer. A for epithelial differentiation, however, has not been established. We previously reported that mice lacking Akt1, but Akt2, exhibit pronounced metabolic defect during late pregnancy lactation results from failure to upregulate Glut1 as well several lipid synthetic enzymes. Despite this defect, both Akt1-deficient Akt2-deficient normal...
The incidence of esophageal adenocarcinoma (EAC) is rising in the United States. An important risk factor for EAC presence Barrett esophagus (BE). BE replacement normal squamous epithelium with a specialized columnar response to chronic acid and bile reflux. However, emergence from keratinocytes has not yet been demonstrated. Our research focused on this. Wnt cyclooxygenase 2 (Cox2) are two pathways whose activation associated progression EAC, but their role tested experimentally. To explore...
Despite recent improvements in treatment for head and neck squamous cell carcinoma (HNSCC), half of all patients with a regional or advanced disease will die within 5 years from diagnosis. Therefore, identification mechanisms driving the aggressive behavior HNSCC is utmost importance. Because p120-catenin (CTNND1/P120CTN) downregulation PIK3CA mutations are commonly found HNSCC, objective this study was to identify their impact on fundamental processes metastasis, specifically, migration...
Abstract Introduction: The Notch receptor family regulates cell fates and may act as a tumor suppressor in the squamous epithelia. While differentiation is maintained esophageal carcinoma (ESCC) its precursor lesions, roles of biology remain elusive. Methods: Transformed human cells expressing EGFR, p53R175H cyclin D1 (EPC2-T) ESCC lines were stably transduced with ICN1, an active form NOTCH1 (N1) regulatable manner (Tet-On system). was inhibited by dominant negative mastermind-like1...
// Heather L. Lehman 1 , Michal Kidacki Joshua I. Warrick and Douglas B. Stairs Department of Pathology, The Pennsylvania State University College Medicine, Hershey, Pennsylvania, USA Correspondence to: Stairs, email: dbs18@psu.edu Keywords: p120-catenin; EGFR; NFkB; RhoA; ESCC invasion Received: October 27, 2017 Accepted: January 23, 2018 Published: 29, ABSTRACT Four out five patients diagnosed with esophageal squamous cell carcinoma (ESCC) will die within years. This is primarily a result...
Abstract Hidradenitis suppurativa ( HS ) is a chronic, inflammatory skin disease affecting the pilosebaceous units in axilla, groin and buttocks. While pathogenesis of not clear, mechanical stress exacerbates . In this study, we aimed to determine whether intracellular adhesive junctions may be aberrant patient skin. Strikingly, observed loss E‐cadherin p120ctn protein expression, two key adherens junction proteins, ~85% severe lesions. Moreover, expression was apparent non‐lesional from...
Protein kinases frequently play key roles in the normal regulation of growth and development eukaryotic organisms. As a consequence, aberrant expression or mutations this family molecules result transformation. Previously, we have conducted screen to identify protein that are expressed mouse during mammary gland breast cancer cell lines. We now describe molecular cloning, characterization Krct, novel serine/threonine kinase unrelated previously defined families kinases. At mRNA level, Krct...