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)

Rat liver hyperplastic foci (HF) and hyperplastic nodules (HN) induced by diethylnitrosamine (DEN) according to the method of Solt and Farber were observed by light microscopy (LM) and scanning electron microscopy (SEM). Liver cirrhosis was not observed. HF, which were composed of basophilic hepatocytes arranged usually in two-cell-thick plates and occasionally one-cell-thick plates, were followed by early HN, which were composed of eosinophilic hepatocytes with enlarged nuclei and prominent nucleoli, at 4 weeks after DEN administration. SEM revealed that hepatocytes in HF had smooth surfaces and dilated bile canaliculi with a few short microvilli. Early HN (4 and 6 weeks) were composed of two-cell-thick plates of hepatocytes, whose intercellular surfaces were covered with numerous microvillous projections. Bile canaliculi were dilated and had numerous short microvilli. Late HN (6 and 8 months) were composed of eosinophilic hepatocytes, which were irregular in shape and size. Their nuclei were enlarged and nucleoli were prominent. Hepatocytes were arranged in two-cell-thick plates, but never in many-cell-thick plates. Bile canaliculi were larger than sinusoids. The bile canaliculi had numerous diverticula, but the zona occludens was present. Microvillous projections of intercellular surfaces of hepatocytes were more numerous than those of early HN. Fenestrae of the sinusoidal endothelium were lost in most parts. Kupffer cells were not seen in any stage of HN. HN progressed gradually toward hepatocellular carcinoma.
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PMID:Scanning electron microscopy of experimentally induced sequential alterations of rat liver hyperplastic nodules. 674 Feb 37

The aim of this study was to evaluate the effects of dietary iron on hepatocarcinogenesis in an animal model mimicking noncirrhotic genetic hemochromatosis. Iron overload may lead to liver cirrhosis and an increased risk of developing primary hepatocellular carcinoma. It is unknown if iron is of pathogenic importance for the carcinogenic process, or whether the increased cancer risk results solely from the cirrhotic process. We investigated the initiating, promoting, and mitogenic properties of carbonyl iron in the Solt-Farber model of chemical hepatocarcinogenesis. A diet supplemented with 2.5% to 3.0% carbonyl iron was either added to, or replaced, the initiating and promoting events in the model. None of the animals developed hepatic fibrosis. Hepatic iron was increased 6- to 13-fold in iron-treated animals, and predominantly located in periportal hepatocytes. Iron as an initiator did not increase the number of glutathione-S-transferase-Yp-positive foci. Iron reduced the number of foci when added to low-dose diethylnitrosamine plus partial hepatectomy, which may be explained by a delayed hepatic regeneration in iron-loaded liver. As a promoter, iron did not selectively induce proliferation of initiated cells. Added to a complete promotive regimen, iron decreased the volume density of preneoplastic nodules, possibly because of a mitostimulatory effect of iron on normal hepatocytes surrounding the nodules. Iron increased the hepatocyte labeling index and counteracted the mitoinhibitory effect of 2-acetylaminofluorene on regenerating liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of dietary iron on initiation and promotion in chemical hepatocarcinogenesis. 784 26

In animals, the combination of oxidative liver damage and inhibited hepatocyte proliferation increases the numbers of hepatic progenitors (oval cells). We studied different murine models of fatty liver disease and patients with nonalcoholic fatty liver disease or alcoholic liver disease to determine whether oval cells increase in fatty livers and to clarify the mechanisms for this response. To varying degrees, all mouse models exhibit excessive hepatic mitochondrial production of H(2)O(2), a known inducer of cell-cycle inhibitors. In mice with the greatest H(2)O(2) production, mature hepatocyte proliferation is inhibited most, and the greatest number of oval cells accumulates. These cells differentiate into intermediate hepatocyte-like cells after a regenerative challenge. Hepatic oval cells are also increased significantly in patients with nonalcoholic fatty liver disease and alcoholic liver disease. In humans, fibrosis stage and oval cell numbers, as well as the number of intermediate hepatocyte-like cells, are strongly correlated. However, cirrhosis is not required for oval cell accumulation in either species. Rather, as in mice, progenitor cell activation in human fatty liver diseases is associated with inhibited replication of mature hepatocytes. The activation of progenitor cells during fatty liver disease may increase the risk for hepatocellular cancer, similar to that observed in the Solt-Farber model of hepatocarcinogenesis in rats.
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PMID:Oxidative stress and oval cell accumulation in mice and humans with alcoholic and nonalcoholic fatty liver disease. 1450 39

To identify novel tumor-associated proteins, we analyzed the protein expression patterns from experimental hepatocellular carcinoma (HCC) that were induced using hepatocarcinogenesis models in rats. Rats were subjected to two previously described protocols of hepatocarcinogenesis using diethylnitrosamine as a carcinogen: the alternative Solt-Farber (aS&F) protocol, which induces HCC within 9 months, and Schiffer's model, which induces cirrhosis and multifocal HCC within 18 weeks. The patterns of protein expression from tumors and normal liver tissue were examined by SDS-PAGE and the bands identified at 33-34 kDa were analyzed by mass spectrometry. The prostaglandin reductase 1 (PTGR1) showed the highest number of peptides, with a confidence of level >99%. The increased expression of PTGR1 in tumors was confirmed in these two models by Western blotting and by increase in alkenal/one oxidoreductase activity (25-fold higher than normal liver). In addition, the gene expression level of Ptgr1, as measured by qRT-PCR, was increased during cancer development in a time-dependent manner (200-fold higher than normal liver). Furthermore, PTGR1 was detected in the cytoplasm of neoplastic cells in rat tumors and in 12 human HCC cases by immunohistochemistry. These analyses were performed by comparing the expression of PTGR1 to that of two well-known markers of hepatocarcinoma, Glutathione S-transferase pi 1 (GSTP1) in rats and glypican-3 in humans. The increased expression and activity of PTGR1 in liver carcinogenesis encourage further research aimed at understanding the metabolic role of PTGR1 in HCC and its potential application for human cancer diagnosis and treatment.
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PMID:Increased expression of prostaglandin reductase 1 in hepatocellular carcinomas from clinical cases and experimental tumors in rats. 2485 74