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Carcinoma-associated fibroblasts (CAFs) that express α-smooth muscle actin (αSMA) contribute to cancer progression, but their precise origin and role are unclear. Using mouse models of inflammation-induced gastric cancer, we show that at least 20% of CAFs originate from bone marrow (BM) and derive from mesenchymal stem cells (MSCs). αSMA+ myofibroblasts(More)
The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Abstract Interferon-gamma (IFN-γ) mediates responses to bacterial infection and autoimmune disease but it is also an important tumor suppressor. IFN-γ is upregulated in the gastric mucosa by chronic Helicobacter infection; however, whether(More)
The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach(More)
Esophageal adenocarcinoma (EAC) arises from Barrett esophagus (BE), intestinal-like columnar metaplasia linked to reflux esophagitis. In a transgenic mouse model of BE, esophageal overexpression of interleukin-1β phenocopies human pathology with evolution of esophagitis, Barrett-like metaplasia and EAC. Histopathology and gene signatures closely resembled(More)
OBJECTIVE Stromal cell-derived factor-1 (SDF-1/CXCL12), the main ligand for CXCR4, is overexpressed in human cancer. This study addressed the precise contribution of SDF-1 to gastric carcinogenesis. DESIGN SDF-1 transgenic mice were created and a Helicobacter-induced gastric cancer model was used in combination with H/K-ATPase-IL-1β mice. Gastric tissue(More)
The gastrointestinal epithelium is characterized by a high turnover of cells and intestinal stem cells predominantly reside at the bottom of crypts and their progeny serve to maintain normal intestinal homeostasis. Accumulating evidence demonstrates the pivotal role of a niche surrounding intestinal stem cells in crypts, which consists of cellular and(More)
Esophageal adenocarcinoma (EAC), with its precursor lesion Barrett's esophagus (BE), accounts for 2% of all cancer-related deaths and has a very poor prognosis with a median survival of less than one year. In addition, the prevalence of BE is rapidly rising in the Western World, resulting in a large number of individuals " at risk " for this disease.(More)
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