Contribute to the understanding of both wound healing and embryonic development to help us design therapeutic strategies for birth defects and poor healing. The two histologically and physiologically distinct compartments of the mouse glandular gastric epithelium are: the proximal corpus/fundus mucosa characterized by the presence of acid-producing parietal cells, and the distal endocrine mucosa composed of enteroendocrine cells that secrete the hormone gastrin. Gast stimulates the parietal cells in the corpus to secrete acid. In addition, the hormone is considered to be a growth factor for the gastrointestinal tract, and on that basis has been implicated in gastrointestinal cancers. In the normal gastric corpus, Hedgehog ligands such as Sonic hedgehog are produced, but then decrease with chronic inflammation, loss of acid secretion, which leads to gastric metaplasia, a precursor lesion for gastric cancer. Nevertheless, Hh signaling remains active in gastric cancers, suggesting differences in the regulation of the Hh pathway in normal stomach compared to gastric carcinogenesis. We and others have analyzed the role of Hh signaling in the gastric corpus, but information on Hh signaling in the gastric antrum and its participation in antral tumor formation is scarce. In addition, Shh, the major Hh ligand expressed in the corpus, subsequently diminishes in the distal stomach despite persistent expression of Hh gene targets, e.g., Gli1 and Gli2, suggesting differential Hh signaling pathways operating in these two regions of the stomach. Gastric cancer is among the more prevalent cancers worldwide, with a survival rate of 27%. Interestingly, a shift in the most frequent site of gastric cancer from the distal stomach to the more proximal corpus and cardia has been observed over the past 10 years, possibly reflecting differences in cancer etiology and risk factors for these two regions of the stomach. Mouse AZ 960 side effects models of gastric tumorigenesis frequently exhibit changes in the gastric corpus/ fundus with little or no changes in the antrum. However to accurately compare the etiologic differences in cancer development between these two anatomic sites, further dissection of the mechanisms leading to hyperplasia and eventually tumorigenesis in the antrum is needed. Currently, different genetic models of antral cancer have been described and include loss of trefoil factor 1, aberrant activation of the gp130 cytokine receptor and loss of the hormone gastrin, yet none have examined a specific role for Hh signaling. Hh signaling is important for maintenance of the gastric mucosa. However it remains unclear whether deregulation of the Hh signal leads to preneoplastic changes and eventually gastric cancer. Therefore, the goal of our study was to determine if Hh signaling contributed to early preneoplastic changes in the antrum where the etiology of gastric cancers has not been well-established. Normal Shh expression is highest in the corpus and decreases in the antrum. In addition, expression during Helicobacter infection also reduces ligand expression especially in the corpus. These modifications have yielded marginal improvements, and novel approaches are needed to further enhance the sensitivity and reproducibility of IGRAs. Pathogen-associated molecular patterns are conserved microbial products with immunomodulatory properties. During infection, PAMPs are recognized by the innate immune cells via several families of pathogen recognition receptors of which the Toll-like receptor family is best characterized.