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

The effects of green tea extract (GTE) on exogenous and endogenous models of rat liver carcinogenesis using diethylnitrosamine (DEN) and a choline-deficient, L-amino acid-defined (CDAA) diet were studied. For the exogenous carcinogenesis study, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal dose of 200 mg/kg body weight of DEN, partially hepatectomized at week 3, and administered GTE at doses of 0, 0.01 and 0.1% in the drinking water from week 2 for 10 weeks. For the endogenous carcinogenesis study, rats were fed the CDAA diet and simultaneously given GTE for 12 weeks. All rats were killed at the end of week 12. After DEN-initiation, the apparent numbers of glutathione S-transferase placental form-positive foci, assayed as putative preneoplastic lesions, were decreased by the administration of GTE, though their sizes were not altered. In contrast, GTE did not significantly reduce the numbers of the lesions induced by the CDAA diet or affect their sizes. While the levels of 8-hydroxyguanine, a parameter of oxidative DNA damage, were reduced by the GTE administration in both experimental models, GTE did not protect against the CDAA-diet-associated liver tissue damage in terms of either histology or plasma marker enzyme levels. We conclude that, while GTE may be a possible chemopreventive agent for nitrosamine-initiated hepatocarcinogenesis in the absence of chronic hepatocyte damage, it does not significantly inhibit lesion development in hepatocarcinogenesis associated with the CDAA diet, a cirrhosis-associated model.
 ...
PMID:Inhibition by green tea extract of diethylnitrosamine-initiated but not choline-deficient, L-amino acid-defined diet-associated development of putative preneoplastic, glutathione S-transferase placental form-positive lesions in rat liver. 919 26

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.
 ...
PMID:Loss of the gene encoding mannose 6-phosphate/insulin-like growth factor II receptor is an early event in liver carcinogenesis. 929 14

Carcinogenesis is a multistep process. Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the genetic changes involved in cirrhosis are not known well. The present study was conducted to evaluate aberration of the retinoblastoma (RB) gene in HCC and adjacent non-tumorous liver using 22 patients with chronic liver damage accompanying HCC. The specimens obtained by microdissection from paraffin-embedded tissues were analyzed using an assay based on the polymerase chain reaction for highly polymorphic nucleotide sequences of microsatellites in the RB gene. Out of 22 cases, 15 showed constitutional heterozygosity for the microsatellite markers. In 11 (73.3%) of these 15 informative cases, the primary HCC foci showed loss of heterozygosity (LOH). In 8 of these 11 doubly informative (informative and LOH-positive in primary HCC) cases, LOH was found in 20 (64.5%) of 31 microdissected non-tumorous foci. All of the non-tumorous foci showing RB loss were cirrhotic lesions but there were no foci of chronic hepatitis. The remaining 4 cases without LOH in HCC foci showed no LOH in non-tumorous lesions. In our study, LOH of the RB gene was frequently observed in liver cirrhosis surrounding tumor.
 ...
PMID:Loss of heterozygosity of the retinoblastoma gene in liver cirrhosis accompanying hepatocellular carcinoma. 934 98

Previously, we have reported that aspirin, a cyclooxygenase (COX) inhibitor, can prevent the fibrosis, cirrhosis and generation of oxidative DNA damage, and the associated development of glutathione-S-transferase placental form (GST-P)-positive preneoplastic liver nodules, caused by a choline-deficient, L-amino acid-defined (CDAA) diet in rats. In the present study, in order to elucidate the role of COX pathway in liver lesion-induction by a CDAA diet, the modulatory effects of other distinct chemical classes of COX inhibitors were examined. A long-acting example, piroxicam (PIRO) (at doses of 0.01, 0.02, 0.04 and 0.06%) and the short-acting ibuprofen (IBU) (at doses of 0.02, 0.04 and 0.06%) and indomethacin (IND) (at doses of 0.005 and 0.008%) were administered in the CDAA diet to male F344 rats, and animals were killed after 12 and 30 weeks. In another experiment, IND was given in drinking water at doses of 0.001, 0.002 and 0.004%. None of the inhibitors affected the development of fatty liver caused by a CDAA diet, but PIRO at doses higher than 0.04%, strongly inhibited the development of GST-P-positive and neoplastic nodules as well as fibrosis, cirrhosis and formation of 8-hydroxydeoxyguanosine (8-OHdG) adducts. IBU at the highest dose also exhibited similar but much less pronounced inhibitory effects. With IND, there was only a tendency for inhibition with no clear dose-dependence. The results together with our previous findings, indicate that relatively strong COX inhibitors, acting irreversibly like aspirin or for extended periods like PIRO, can prevent the endogenous hepatocarcinogenesis associated with a CDAA diet, although not the development of a fatty liver, suggesting that an augmented COX pathway might play key roles in the causation of liver lesions in this model.
Carcinogenesis 1997 Oct
PMID:Inhibition by piroxicam of oxidative DNA damage, liver cirrhosis and development of enzyme-altered nodules caused by a choline-deficient, L-amino acid-defined diet in rats. 936 1

Hepatitis C virus (HCV) infection causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. However, the mechanism of carcinogenesis by HCV is poorly understood. In this paper, the recent virological and molecular biological studies of HCV published in after 1996 were summarized including the past reported data. Major topics of the study are the biological functions of HCV proteins and the interaction between HCV proteins and cellular proteins. HCV replication and proliferation systems using human cultured cells were also described. The possible role of HCV for development of hepatocellular carcinoma is discussed.
 ...
PMID:[Hepatitis C virus as a causative agent of carcinogenesis--recent trends for study]. 939 12

Iron overload has been shown to impair the immune response of the liver, and induce hepatic fibrosis and cirrhosis. Opinions differ concerning the relative risk of developing hepatocellular carcinoma (HCC) in siderotic patients as compared with patients with hepatic fibrosis and cirrhosis and the possible mechanism of liver carcinogenesis in genetic hemochromatosis is still unknown. The purpose of this study is to assess hepatic iron overload, fibrosis and cirrhosis in liver tissue adjacent to hepatocellular carcinoma and in liver tissue of controls in population at risk for hepatocellular carcinoma. Liver tissue was available for examination in 147 biopsies with HCC collected in South Africa. As controls we used liver samples from 211 age and sex matched Africans who died in accidents. Tissue samples were processed routinely, stained with H and E, Sweet's reticulin, Masson's trichrome for fibrous tissue, Prussian blue for iron stain and immunohistochemically for HBsAg. Iron content was assessed with the method described by Brissot. Iron overload was detected in 42.1% of cancerous livers and in 43.7% of livers from controls. The presence of siderosis and iron content gradually increased with the age of studied similarly in cases and in controls. Cirrhosis was present in 32% of cancerous livers and was associated with iron overload in 13%. No cirrhosis and 6% of mild periportal fibrosis not related with siderosis was observed in controls. HBsAg was stainable in 80% of cancerous livers of patients below 25 years of age and in 40% of patients over 35 years. HBsAg in controls was positive in 9%. No relationship of HBsAg and amount of stainable iron in cancerous and livers of controls was found. In conclusion, African siderosis can not play important role in the etiopathogenesis of HCC.
 ...
PMID:Hepatic siderosis, fibrosis and cirrhosis: the association with hepatocellular carcinoma in high-risk population. 942

The purpose of this study was to elucidate the clinical significance of nitric oxide synthases (NOS), nitric oxide (NO) and tumor necrosis factor (TNF) in different types of ascites. NOS, NO and TNF in ascitic transudates of 21 patients with liver cirrhosis, ascitic exudate of 32 patients with liver cirrhosis and carcinogenesic ascites of 19 patients were measured by Griess, ELISA and colorimetric methods. Compares to the value in ascitic transudate of 21 patients with liver cirrhosis, NOS (7.32 +/- 3.13 nmol.min-1.g-1), NO (15.4 +/- 7.6 mumol/L) and TNF (331.7 +/- 121.2 mumol/L) in ascitic exudate of 32 patients with liver cirrhosis were significantly higher (P < 0.01). The NO (10.7 +/- 3.2 mumol/L) and TNF (185.6 +/- 84.1 mumol/L) in carcinogenesic ascites of 19 patients were between those in ascitic exudates and those in ascitic transudates of patients with liver cirrhosis (P < 0.05 or 0.01). The NOS activity was highest in carcinogenesic ascites. The decrease of 24h urine volume in patients with cirrhosis was relative to the increase of NO level in ascites. Those suggested that measurements of NOS, NO and TNF in ascites are helpful in differential diagnosis of ascites. The separation between NO level and NOS activity in ascites indicates that the ascites is carcinogenesis.
 ...
PMID:[Study of nitric oxide synthases, nitric oxide and tumor necrosis factor in different types of ascites]. 959 41

Hepatocellular carcinoma (HCC) frequently occurs in association with liver cirrhosis, as chronic liver disease is one of the most important factors in carcinogenesis. In addition to HCCs, recent reports of pathologic studies of resected specimens from cirrhotic liver describe associated small nodular lesions such as regenerative nodule, dysplastic nodule (adenomatous hyperplasia), and dysplastic nodule with subfocus of HCC (early HCC). In hepatocarcinogenesis of the cirrhotic liver, a regenerative nodule might be the first step in the development of HCC, going through phases of dysplastic nodule, early HCC and early advanced HCC in a multistep fashion. Fortunately, recent advances in various imaging techniques have facilitated the verification of these nodules. In this review, new nomenclature of small hepatocellular nodules, and detection and characterization of hepatic nodules in carcinogenesis with various imaging techniques are described with focus on the premalignant lesions and early stage of HCC. In addition, the efficacy of various imaging techniques for diagnosing them is discussed. Although the terms and definitions of these nodules are still variable and controversial, familiarity with the concept of these borderline lesions is important.
 ...
PMID:Hepatocarcinogenesis in liver cirrhosis: imaging diagnosis. 961 Jun 9

Radical treatment of the hepatocellular carcinoma (HCC) is complete surgical removal; it may be done by resection or total hepatectomy. Although multicentric carcinogenesis predicts that liver transplantation is likely adequate to treat both the hepatoma and the underlying cirrhosis, it doesn't seem justified in the advanced stages or in absence of end-stage liver disease and therefore liver resection remains the treatment of choice for radical cure of HCC. However, low resectability and high recurrence rate make surgery alone ineffective. Unresectable HCC may be converted to resectable by multimodality radiation/chemotherapy, and embolization of portal branch feeding tumour, improving the function of the nonembolized liver, can extend the surgical indications for HCC. Adjuvant chemoembolization has already shown to reduce recurrence rate after radical resection and it should be widely applied. In unresectable or not converted HCCs as well as in postoperative recurrence, alternative therapies, particularly as multimodality treatment, can improve survival rate. To date, multidisciplinary treatment of hepatocellular carcinoma, waiting for further studies on newer modalities (prevention and gene therapy, especially), represents the best way to improve long-term results.
 ...
PMID:[Multidisciplinary treatment of hepatocarcinoma]. 961 53

To understand the role of telomere dynamics in hepatocellular carcinogenesis, we examined the lengths of terminal restriction fragments (TRFs) in hepatocellular carcinoma (HCC) and surrounding tissues with chronic active hepatitis (CAH), liver cirrhosis (LC) and atypical adenomatous hyperplasia (AAH). The peak TRFs in all HCCs were significantly shorter than those of the surrounding tissues (CAH, LC). TRF in AAH was shortened and similar to that of HCC. Telomerase was examined in CAH, LC, AH, and HCC, and detected in high levels almost exclusively in HCCs. Interestingly, the intensity of telomerase activity in the AH was similar to that of HCC. Thus, the progressive shortening of telomere and the activation of telomerase may be a useful marker for the early detection of malignant progression in liver disease.
 ...
PMID:[Clinical significance of telomerase activity in precancerous lesion of the liver (adenomatous hyperplasia)]. 961 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>