Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor (IGF) I and IGF-II were measured by radioimmunoassay in the sera of seven patients with acromegaly, 36 normal control subjects, 15 patients with chronic hepatitis, 15 patients with cirrhosis, 25 patients with hepatocellular carcinomas (HCCs) who did not have hypoglycemia, 20 patients with HCCs who did have hypoglycemia, and 10 patients with metastatic liver tumors. Both IGF-I and IGF-II levels decreased as liver disease progressed from the normal control stage to chronic hepatitis and cirrhosis, and both levels reflected the severity of liver disease. Patients with HCCs who had hypoglycemia had relatively higher IGF-II levels in their sera in comparison with those who did not have hypoglycemia (272 +/- 167.5 ng/ml vs 110.4 +/- 85.9 ng/ml [mean +/- SD], p less than 0.0005), despite the fact that those with hypoglycemia had more advanced liver cancer and had lower IGF-I levels in sera (16.7 +/- 14.1 ng/ml vs 46.8 +/- 47.9 ng/ml, p less than 0.002). It is possible that a labile IGF-II material is produced by the cancer cells of patients with hypoglycemia. This factor is reactive to the IGF-II receptor and partially cross-reacts with an antibody to IGF-II; it accounted for the mildly elevated levels of serum IGF-II. Hypoglycemia may be an integral effect of relatively elevated IGF-II like material and an advanced liver cancer. Also, higher serum alpha-fetoprotein (AFP) levels were more frequently found in patients with hypoglycemia who had relatively elevated IGF-II levels and short survivals.
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PMID:Radioimmunoassay of serum IGF-I and IGF-II in patients with chronic liver diseases and hepatocellular carcinoma with or without hypoglycemia. 246 May 70

This report shows that loss of heterozygosity at the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) locus occurred in 5/8 (63%) dysplastic liver lesions and 11/18 (61%) hepatocellular carcinomas (HCCs) associated with the high risk factors of hepatitis virus infection and liver cirrhosis. Mutations in the remaining allele were detected in 6/11 (55%) HCCs, including deletions in a polydeoxyguanosine region known to be a target of microsatellite instability. M6P/IGF2R allele loss was also found in cirrhotic tissue of clonal origin adjacent to these dysplastic lesions and HCCs, demonstrating that M6P/IGF2R inactivation occurs early in liver carcinogenesis. In conclusion, HCCs frequently develop from clonal expansions of phenotypically normal, M6P/IGF2R-mutated hepatocytes, providing further support for the idea that M6P/IGF2R functions as a liver tumor-suppressor gene.
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PMID:Loss of the gene encoding mannose 6-phosphate/insulin-like growth factor II receptor is an early event in liver carcinogenesis. 929 14

Insulin-like growth factor (IGF)-2 is overexpressed in hepatocellular carcinoma and accompanying dysplastic lesions. IGF-2 signalling is mediated through IGF-1 receptor (IGF-1R), while mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF-2R) controls pericellular levels of free IGF-2. We studied, by in situ hybridisation and immunohistology, 18 liver specimens with cirrhosis of different aetiology without neoplastic or dysplastic lesions. Immunohistology was also performed for insulin receptor IGF-1R and IGF-binding proteins 3 and 4. High focal levels of IGF-2 RNA were found in some hepatocytes of all livers with HBV- or HCV-induced cirrhosis (n=10), but in only one of the cirrhoses with nonviral aetiology (n=8). IGF-2 was overexpressed in biliary duct epithelial cells in one case. Compared with noncirrhotic liver, all cirrhotic specimens showed reduced hepatocellular expression of M6P/IGF-2R protein, which contrasted with enhanced expression in perisinusoidal cells. Immunostaining for the other antigens did not reveal significant differences. Upregulation of IGF-2 in some hepatocytes may lead to high focal IGF-2 levels sufficient to saturate local IGF-2 binding capacities, and may result in an increased susceptibility to cellular dedifferentiation and, ultimately, liver cancer. Downregulation of hepatocellular M6P/IGF-2R and upregulation of IGF-2 seem to be early events in hepatocarcinogenesis prior to the appearance of morphologically distinct dysplastic lesions. Elevated focal IGF-2 transcript levels may therefore indicate an increased risk for hepatocellular and cholangiocellular carcinomas.
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PMID:Focal overexpression of insulin-like growth factor 2 by hepatocytes and cholangiocytes in viral liver cirrhosis. 1261 83

Primary hepatocellular carcinoma (HCC) is one of the most common forms of malignant cancer with the fourth highest mortality rate worldwide. Major risk factors for the development of HCC include chronic infections with the hepatitis B or C virus, alcohol consumption, exposure to dietary aflatoxin B1, hereditary liver disease or liver cirrhosis of any etiology. Recent studies have discovered changes in the insulin-like growth factor (IGF) axis that affect the molecular pathogenesis of HCC, including the autocrine production of IGFs, IGF binding proteins (IGFBPs), IGFBP proteases, and IGF receptor expression. Characteristic alterations detected in HCC and hepatoma cell lines comprise the overexpression of IGF-II and the IGF-I receptor emerging as critical events in malignant transformation and growth of tumors. Simultaneous reduction of IGFBP expression and the increase in proteolytic cleavage of IGFBPs result in an excess of bioactive IGFs. Finally, defective functions of the IGF-II/mannose 6-phosphate receptor involved in degradation of IGF II, the activation of the growth inhibitor TGF-beta1, and the lysosomal targeting of cathepsin proteases capable to degrade extracellular matrix proteins may contribute to the development of HCC.
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PMID:The role of the IGF axis in hepatocarcinogenesis. 1471 Mar 47

Hepatocellular carcinoma is one of the most common malignant human tumors. Hepatocarcinogenesis is a multistep process with a multifactorial etiology. Chronic hepatitis B and hepatitis C virus infection, alcohol drinking and cirrhosis of any etiology are the major risk factors for hepatocellular carcinoma. Growth factors, their receptors and related proteins are involved in the process of malignant transformation. The IGF axis is involved in the proliferation and differentiation of normal, transformed and malignant hepatocytes. In the context of hepatocarcinogenesis, IGF-II has, in particular, been investigated thoroughly. Increased IGF-II bioavailability, protease activity of IGF-binding proteins and IGF-I receptor expression, decreased expression of IGF-II receptor and IGF-binding proteins are thought to contribute to hepatocellular carcinoma genesis. This review will first focus on the role of the IGF axis in hepatocarcinogenesis. In the second part it will emphasize circulating IGF-II levels in chronic liver disease and hepatocellular carcinoma, and diagnostic application of serum IGF-II level in both small and larger hepatocellular carcinoma.
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PMID:Insulin-like growth factor II in hepatocellular carcinoma. 2047 1

Soluble M6P/IGFIIR has the potential to be a significant carrier of IGF-II and mannose 6-P proteins in the circulation and play an important role as an antagonist to the cellular receptor. Evidence suggests that soluble receptor plays a role in fetal and childhood growth by opposing the growth stimulatory effects of IGF-II. Maternal serum levels of M6P/IGFIIR are elevated in late pregnancy and the IGF-II:soluble M6P/IGFIIR ratio in cord blood correlates strongly with weight at birth and placental weight suggesting an important role in fetal growth and development. However, elevated soluble receptor levels may also be indicative of disease in later life, such as liver cirrhosis and some tumor types and may be a useful marker for monitoring treatment and progression of the disease. Further investigation of the regulation of this soluble receptor in health and disease is required to fully elucidate its role in the circulation.
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PMID:Soluble M6P/IGFIIR in the circulation. 2652 57