Gastroenterology
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Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive and metastatic disease for which conventional treatments are of limited efficacy. A number of agents in development are potential anti-invasive and antimetastatic agents, including the Src kinase inhibitor dasatinib. The aim of this study was to assess the importance of Src in human PDAC and to use a genetically engineered mouse model of PDAC to determine the effects of dasatinib on PDAC progression. ⋯ This study confirms the importance of Src in human PDAC and shows the usefulness of a genetically engineered mouse model of PDAC for assessing the activity of potential antimetastatic agents and suggests that dasatinib should be evaluated further as monotherapy after resection of localized invasive PDAC.
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A variety of noninvasive molecular approaches to colorectal cancer screening are emerging with potential to improve screening effectiveness and user-friendliness. These approaches are based on the sensitive assay of molecular markers in stool, blood, and urine samples. ⋯ Validation of these technologies in average-risk populations are needed to establish their role for general colorectal cancer screening. This review addresses the biological rationale, technical advances, recent clinical performance data, and remaining issues with molecular screening for colorectal cancer.
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In patients with cirrhosis, hepatic encephalopathy (HE) has acute but reversible as well as chronic components. We investigated the extent of residual cognitive impairment following clinical resolution of overt HE (OHE). ⋯ In cirrhosis, episodes of OHE are associated with persistent and cumulative deficits in working memory, response inhibition, and learning.
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The molecular basis underlying visceral hypersensitivity in functional irritable bowel syndrome remains elusive, resulting in poor treatment effectiveness. Because alterations in spinal non-neuronal (astrocytic) glutamate reuptake are suspected to participate in chronic pain, we asked whether such processes occur in visceral hypersensitivity. ⋯ We identify spinal EAAT as a therapeutic target, and establish riluzole as a candidate to counteract gastrointestinal hypersensitivity in disorders such as irritable bowel syndrome.
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In this issue of Gastroenterology, the editors present 2 expert perspectives on the colorectal screening guidelines published in the May 2008 issue of the journal.