Gaining a better understanding of how CD8+ T cells are activated in the liver, and in particular in chronic viral hepatitis, will give us more insight
into how to better generate effective therapies. We thank Dr. K. Reed Clarke for the preparation of the AAV vectors. “
“Abnormalities of gastrointestinal (GI) motor function contribute to a number of common clinical problems seen by gastroenterologists. Proper evaluation of patients with suspected functional gastrointestinal disorders and gastrointestinal motility disorders is important for correct diagnosis and an appropriate plan of treatment. This chapter discusses motility tests assessing esophageal, gastric, small intestinal, colonic, and anorectal function. The GI motility laboratory serves as an important station for patient evaluation and treatment
in gastroenterology. “
“The overall survival GS1101 of patients with hepatocellular carcinoma (HCC) remains poor, and the molecular pathogenesis remains incompletely defined in HCC. Here we report that increased expression of αB-Crystallin in human HCC predicts poor survival and disease recurrence after surgery. Multivariate analysis identifies αB-Crystallin EX 527 mouse expression as an independent predictor for postoperative recurrence and overall survival. We show that elevated expression of αB-Crystallin promotes HCC progression in Erastin vivo and in vitro. We demonstrate that αB-Crystallin overexpression fosters HCC progression by inducing epithelial-mesenchymal transition (EMT) in HCC cells
through activation of the extracellular-regulated protein kinase (ERK) cascade, which can counteract the effect of sorafenib. αB-Crystallin complexes with and elevates 14-3-3ζ protein, leading to up-regulation of ERK1/2 activity. Moreover, overexpression of αB-Crystallin in HCC cells induces EMT progression through an ERK1/2/Fra-1/slug signaling pathway. Clinically, our data reveal that overexpression of both αB-Crystallin and 14-3-3ζ correlates with the HCC poorest survival outcomes, and sorafenib response is impaired in patients with αB-Crystallin overexpression. Conclusion: These data suggest that the αB-Crystallin-14-3-3ζ complex acts synergistically to promote HCC progression by constitutively activating ERK signaling. This study reveals αB-Crystallin as a potential therapeutic target for HCC and a biomarker for predicting sorafenib treatment response. (HEPATOLOGY 2013) Hepatocellular carcinoma (HCC) is one of the major health problems worldwide.1 Because HCC is often diagnosed at an advanced stage, a large proportion of HCC patients display symptoms of intrahepatic metastases or postsurgical recurrence at the time of diagnosis. HCC is among the leading causes of cancer-related deaths in Asia, especially in China.