Insulin-like growth factor I is a comitogen for hepatocyte growth factor in a rat model of hepatocellular carcinoma

Price, Julie; Kovach, Stephen J.; Johnson, Timothy S.; Koniaris, Leonidas G.; Cahill, Paul A.; Sitzmann, James V.; McKillop, Iain H.

doi:10.1053/jhep.2002.36158

Cited by 62 publications

(55 citation statements)

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“…Other studies have demonstrated a significant increase in IGF-2 mRNA expression in human cirrhotic liver, in liver cancers and in the peripheral blood of HCC, in human hepatoma cell lines, in comparison to that of normal adult liver (37)(38)(39)(40). This discrepancy may be attributed to the fact that in the present study we measured only the free IGF-2 levels in serum but not mRNA.…”

Section: Discussioncontrasting

confidence: 58%

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

et al. 2011

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Abstract. Hepatocellular carcinoma (HCC) contributes to 14.8% of all cancer mortality in Egypt, which has a high prevalence of hepatitis C virus (HCV). We have previously shown alterations in the insulin-like growth factor-1 (IGF-1) receptor signalling pathway during experimental hepatocarcinogenesis. The aim of this study was to determine whether serum levels of IGF-1, IGF-2 and IGFBP-3 can be used to discriminate between HCC and the stages of hepatic dysfunction in patients with liver cirrhosis assessed by the Child-Pugh (CP) score, and to correlate these levels with HCC stages. We recruited 241 subjects to the present study; 79 with liver cirrhosis, 62 with HCV-induced HCC and 100 age-matched controls. Results showed that serum levels of IGF-1, IGF-2 and IGFBP-3 were reduced significantly in cirrhosis and HCC patients in comparison to the controls, and that this reduction negatively correlated with the CP scores. However, only IGFBP-3 levels showed significant negative correlation with α-fetoprotein levels. The reduction in IGF-1 and IGFBP-3 but not IGF-2 levels was significant in HCC in comparison to patients with cirrhosis. None of the parameters significantly correlated with the HCC stage. IGFBP-3 levels discriminated between cirrhosis and HCC at a sensitivity of 87%, a specificity of 80% and a cut-off value of <682.6 ng/ ml. In conclusion, although our results showed that serum IGF-1, IGF-2 and IGFBP-3 are reduced with the progression of hepatic dysfunction, only IGFBP-3 may be considered as the most promising serological marker for the prediction of the development of HCC in the chronic HCV patients with liver cirrhosis.

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Section: Discussioncontrasting

confidence: 58%

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

et al. 2011

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“…Diabetes can lead to a fall in IGF-1 of endocrine origin. IGF-1 it been found that has a number of bioactivities including mediating action of growth hormone, increasing glucose taken by tissues, inhibiting hepatic glycogenesis, improving insulin sensitivity, decreasing oxidation of lipid, lowering free fatty acids, increasing nucleotide synthesis, proliferation and differentiation of cells [20][21][22][23][24][25] . These researches would inevitably help understand the molecular pathogenesis of disturbances of glucose, lipid, protein metabolism associated with diabetes, diabetic peripheral neuropathy and diabetic foot [4,[26][27][28] and probably might provide the premise of future molecular therapeutic intervention [29,30] .…”

Section: Discussionmentioning

confidence: 99%

Expression of liver insulin-like growth factor 1 gene and its serum level in rats with diabetes

Wang²,

Chen³

et al. 2004

WJG

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“…Mato's group demonstrated that knockout mice lacking this gene were predisposed to liver injury, exhibited increased expression of genes involved in cellular proliferation 158 , had impaired liver regeneration, had lower levels of SAMe, and spontaneously developed hepatocellular carcinomas 159,160 . S-nitrosylation of MAT I/III significantly decreased the levels of SAMe, and sensitized rat hepatocytes to enhanced proliferation 150,161,162 , which is mediated by hepatocyte growth factor scatter factor (HGF), and probably involves IGF-1 priming 163 . HGF is turned on by lower levels of SAMe 150 .…”

Section: S-nitrosylation Of Liver Methionine Adenosyltransferasementioning

confidence: 99%

Nitric Oxide and Cancer Development

et al. 2007

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Abstract:The role of nitric oxide (NO) in cancer development has become a very active research area. This review presents an overview of many studies that implicate an important role of NO in the development of cancer. These include results in experimental models as well as many observations made on NO and inducible nitric oxide synthase (iNOS) in human cancers. Our survey of the literature has allowed us to conclude that in general large levels of NO will kill cancer cells but paradoxically at intermediate to lower levels NO prevents cancer cell apoptosis and enhances tumor growth. This basic tenet has been demonstrated in many experimental models. The mechanistic basis of how intermediate levels of NO mediate tumor development is an active area of research and is the subject of this review. NO mediated S-nitrosylation of key enzymes and regulatory proteins plays a critical role. Key proteins S-nitrosylated which enhance tumor development include several caspases involved in apoptosis, PTEN the tumor suppressor protein, Bcl-2 the mitochondrial protein which protects from apoptosis, OGG1 the DNA repair protein and methionine adenosyl transferase the liver protein which synthesizes adenosylmethionine. The S-nitrosylation of these proteins enhances DNA mutations, prevents cancer cell apoptosis and enhances oncogenic cell growth. (J Toxicol Pathol 2007; 20: 77-92)

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Insulin-like growth factor I is a comitogen for hepatocyte growth factor in a rat model of hepatocellular carcinoma

Cited by 62 publications

References 50 publications

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

Expression of liver insulin-like growth factor 1 gene and its serum level in rats with diabetes

Nitric Oxide and Cancer Development

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