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| 1 | Role of Sonic Hedgehog signaling during progression from inflammation to cancer in the stomach显示文摘Despite advances in treatment and the declining incidence,gastric cancer remains the second leading cause of cancer-related deaths in the world.Understanding the progression from inflammation to cancer in the stomach is crucial in the development of novel therapies and strategies for treating this disease.Chronic inflammation of the stomach is typically caused by Helicobacter pylori(H.pylori)and resulting lesions may lead to gastric cancer.During the progression from inflammation to cancer,the stomach epithelium changes with evidence of the disruption of normal epithelial cell differentiation and infiltrating inflammatory cells.Coincident with the development of atrophic gastritis and metaplasia,is the loss of the gastric morphogen Sonic Hedgehog(Shh).Given its critical role as a regulator of gastric tissue homeostasis,the disruption of Shh expression during inflammation correlates with the loss of normal epithelial cell differentiation,but this has only recently been rigorously tested in vivo using a unique mouse model of targeted gastric Shh deletion.While pre-neoplastic lesions such as atrophic gastritis and in-testinal metaplasia are associated with the loss of Shh within the acid-secreting glands of the stomach,there is a clear link between elevated Shh and signaling to gastric cancers.The current review focuses on the effects of aberrant Shh expression and its role in the development of gastric cancer,specifically in response to H.pylori infection. | Alexander E Sherman Yana Zavros | 2011 | World Journal of Gastrointestinal Pathophysiology2011，2，6： | 14 |
| 2 | Histamine 3 receptor activation mediates inhibition of acid secretion during Helicobacter-induced gastritis显示文摘AIM:To test the hypothesis that histamine 3 receptor (H3R)activation during Helicobacter infection inhibits gastric acid secretion in vivo and in vitro.METHODS:Helicobacter felis(H.felis)infected and uninfected C57Bl/6 mice were infused with either PBS or the H3 receptor antagonist thioperamide(THIO)for 12 wk.After treatment,mice were analyzed for morphological changes and gastric acid content.Total RNA was prepared from the stomachs of each group and analyzed for changes in somatostatin and gastrin mRNA abundance by real time-polymerase chain reaction(RTPCR).Location of H3 receptors in the stomach was analyzed by co-localization using antibodies specific for the H3 receptor and parietal cell marker H + ,K + -ATPase βsubunit. RESULTS:Inflammation and parietal cell atrophy was observed after 12 wk of H.felis infection.Interestingly, treatment with the H3R antagonist thioperamide(THIO) prior to and during infection prevented H.felis-induced inflammation and atrophy.Compared to the uninfected controls,infected mice also had significantly decreased gastric acid.After eradication of H.felis with THIO treatment,gastric acidity was restored.Compared to the control mice,somatostatin mRNA abundance was decreased while gastrin gene expression was elevated during infection.Despite elevated gastric acid levels, after eradication of H.felis with THIO,somatostatin mRNA was elevated whereas gastrin mRNA was suppressed.Immunofluorescence revealed the presence of H3 receptors on the parietal cells,somatostatin-secreting D-cells as well as the inflammatory cells. CONCLUSION:This study shows that during H.felis infection,gastric acidity is suppressed as a consequence of an inhibitory effect on the parietal cell by H3R activation.The stimulation of gastric mucosal H3Rs increases gastrin expression and release by inhibiting release of somatostatin. | Yana Zavros Nisreen Mesiwala Meghna Waghray Andrea Todisco Arthur Shulkes Juanita L Merchant | 2010 | World Journal of Gastrointestinal Pathophysiology2010，1，5： | 2 |
| 3 | The Role of Sonic Hedgehog Reemergence During Gastric Cancer显示文摘 | Jason Martin Jessica M. Donnelly JeanMarie Houghton Yana Zavros | 2010 | Digestive Diseases and Sciences2010，，6： | 1 |
| 4 | Helicobacter pylori outer membrane protein 18 (Hp1125) induces dendritic cell maturation and function显示文摘 | Rathinavelu S Kao JY Zavros Y | 2005 | Helicobacter2005，10，5： | 1 |
| 5 | Interleukin-1 beta promotes gastric atrophy through suppression of sonic hedgehog显示文摘 | Waghray M Zavros Y Saqui-Salces M | 2010 | Gastrotenterology2010，138，2： | 1 |
| 6 | Reduced pepsin A processing of sonic hedgehog in parietal cells precedes gastric atrophy and transformation显示文摘 | Zavros Y Waghray M Tessier A | 2007 | J Biol Chem2007，282，33： | 1 |
| 7 | Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection显示文摘 | Zavros Y Paterson A Lambert J | 2000 | Dig Dis Sci2000，45，10： | 1 |
| 8 | The Role of Sonic Hedgehog Reemergence During Gastric Cancer显示文摘 | Jason Martin Jessica M. Donnelly JeanMarie Houghton Yana Zavros | 2010 | Digestive Diseases and Sciences2010，，6： | 1 |
| 9 | Hypergastrinemia in response to gastric inflammation supresses somatostatin 显示文摘 | Zavros Y Rieder G Ferguson A | 2002 | Am J Physiol Gastrointest Liver Physiol2002，282，1： | 1 |
| 10 | A model for integrative study of human gastric acid secretion显示文摘 | Joseph IM Zavros Y Merchant JL | 2003 | J Appl Physiol2003，94，4： | 1 |
| 11 | Helicobacter- pylori outer membrane protein 18 (Hpl125) induces dendritic cell maturation and function显示文摘 | Rathinavelu S Kao J Y Zavros Y | 2005 | Helicobact- er2005，10，5： | 1 |
| 12 | Helicobacter pylori outer membrane protein 18 (Hp1125) induces dendritic cell maturation and function显示文摘 | Rathinavelu S Kao JY Zavros Y | 2005 | Helicobacter2005，10，5： | 1 |
| 13 | Genetic or chemical hy- poehlorhydria is associated with inflammation that modulates parie- tal and G-cell populations in mice 显示文摘 | Zavros Y Rieder G Ferguson A | 2002 | Gastroenterology2002，122，1： | 1 |
| 14 | Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without helicobacter pylori infection 显示文摘 | Paterson A Lambert J | 2000 | Dig Dis Sci2000，45，10： | 1 |
| 15 | Interleukin- lbeta promotes gastric atrophy through suppression of Sonic Hedgehog显示文摘 | Waghray M Zavros Y Saqui-Salces M | 2010 | Gastroenterology2010，138，2： | 1 |
| 16 | Helicobacter pylori outer membrane protein 18 (Hp1125 )induces dendritic cell maturation and function显示文摘 | Rathinavelu S Kao J Y Zavros Y | 2005 | Helieobacter2005，10，5： | 1 |
| 17 | Genetic or chemical hypochlorhydria is associated with inflammation that modulates parietal and G-cell populations in mice 显示文摘 | Zavros Y Rieder G Ferguson A | 2002 | Gastroenterology2002，122，： | 1 |
| 18 | Helicobacter pylori outer membrane protein 18 (Hpl125) induces dendritic cell maturation and function显示文摘 | Rathinavelu S Kao J-Y Zavros Y | 2005 | Helicobacter2005，10，5： | 1 |
| 19 | Chronic gastritis in the hypochlorhydric gastrin - deficient mouse progresses to adenocarcinoma显示文摘 | Zavros Y Eaton KA Kang W | 2005 | Oncogene2005，24，14： | 1 |
| 20 | Helicobacter pylori outer membrane protein 18 (Hp1125 ) induces dendritic cell maturation and function 显示文摘 | Rathinavelu S Kao JY Zavros Y | 2005 | Helicobacter2005，10，5： | 1 |
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