Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraductal papillary neoplasia of the liver (IPNL) frequently presents gastrointestinal metaplasia with aberrant expression of MUC2 and MUC5AC and oversecretion of mucin into the ductal lumen. In this study, the involvement of CDX2, a homeodomain protein involved in the regulation of intestinal development and differentiation, in the expression of MUC2 was examined in mucinous intrahepatic cholangiocarcinoma (ICC) (n=7) and IPNL with hepatolithiasis (n=19) with comparison to conventional ICC (n=11), and intraductal papillary mucinous tumor and invasive ductal carcinoma of the pancreas (n=9 and 11, respectively). A total of 33 cases of hepatolithiasis, extrahepatic biliary obstruction and normal livers were used as the control. Immunohistochemically, both MUC2 and MUC5AC were frequently expressed in mucinous ICC and IPNL, while expression of MUC2 was not seen in conventional ICC. The nuclear expression of CDX2 was closely associated with the expression of MUC2 in mucinous ICC and IPNL. This intimate association of MUC2 and CDX2 was confirmed by double immunostaining. The cytoplasmic CDX2 expression was frequent in the mucinous and the conventional ICC and pancreatic carcinoma, irrespective of MUC2 and MUC5AC expression. CDX2 mRNA was detected in neoplastic cells showing cytoplasmic as well as nuclear expression of CDX2 by reverse transcriptase-polymerase chain reaction. One IPMT expressed MUC2 associated with nuclear CDX2 expression, while the other IPMT and conventional pancreatic carcinoma expressed MUC5AC only. Aberrant expression of CDX2 is closely related to the overexpression of MUC2 in mucinous ICC and IPNL associated with hepatolithiasia, suggesting its role in intestinal differentiation and its association with carcinogenesis in these tumors.
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PMID:Aberrant expression of CDX2 is closely related to the intestinal metaplasia and MUC2 expression in intraductal papillary neoplasm of the liver in hepatolithiasis. 1504 36

Hyperbilirubinemia is a common side effect of antiviral medications. The mechanisms underlying its development are multiple and unique to each therapy. During administration of antiviral medications, the hyperbilirubinemia observed in the absence of liver injury is most frequently manifested by isolated increases in the indirect-reacting fraction. Relevant mechanisms leading to indirect hyperbilirubinemia in this setting include hemolysis, decreased hepatic bilirubin clearance as a result of impairment of bilirubin conjugation, or circumstances in which both processes occur simultaneously. Underlying genetic susceptibilities may potentiate these side effects of antiviral therapy. Conjugated (direct-reacting) hyperbilirubinemia can be a consequence of generalized hepatocellular injury, selective cholestatic defects, biliary obstruction, or, rarely, genetic disorders of bilirubin transport. In the specific setting of antiviral therapy, preexisting liver disease or antiviral hepatotoxicity, such as is encountered with the use of the nucleoside and non-nucleoside human immunodeficiency virus reverse transcriptase inhibitors, are the most frequent causes of direct-reacting or mixed direct- and indirect-reacting hyperbilirubinemia. Modification in antiviral drug choice or dose may be required in cases of liver injury or of brisk hemolysis leading to significant anemia. The mild indirect hyperbilirubinemia associated with impairment in conjugation tends to be well tolerated and of little consequence. The decision to continue or discontinue antiviral therapy in the face of hyperbilirubinemia should be made after an assessment of the cause of the elevated bilirubin level and a thorough assessment of the risks and benefits of antiviral therapy.
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PMID:Hyperbilirubinemia in the setting of antiviral therapy. 1582 33

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase-PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC.
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PMID:MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer. 1847 1