Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver transplantation in malignancies must be confined to patients with potentially curable disease. The indication is widely accepted, however, in non-resectable tumors or in patients with cirrhosis that excludes major resection. Without treatment prognosis is extremely poor in these patients. In our own experience 12 out of 13 non-cirrhotic patients with hepatocellular carcinoma (HCC) died within 9 months, and 17 out of 19 cirrhotic patients died within the first year of non-curative or explorative surgery. None of our patients with HCC in non-cirrhotic livers has lived longer than 38 months, and those with cirrhotic livers more than 61 months even after curative resection. After liver transplantation 1-year survival rate was 54% in 14 patients with primary hepatic carcinomas (12 HCC, 2 CCC). In cirrhotic patients with large or infiltrating HCC the results of resection are worse than after grafting, at least in the Western World, so liver transplantation must be taken into consideration. The lack of grafts limits treatment by transplantation in these patients. Transplantation is only exceptionally indicated for patients with metastatic liver disease.
 ...
PMID:Primary hepatic malignancies: resection or liver transplantation? 216 24

Prognostically relevant factors and treatment were analysed in 103 patients suffering from primary epithelial liver tumors (88 HCC, 15 CCC). Ninety of them underwent operations: 14 liver transplantations, 32 resections, 44 explorative laparotomies. The resection rate was 38%, the 30-day mortality in transplantation 14%, in resection 22%. The 5-year survival after resection was about 25%. Liver transplantation resulted in 50% 1-year and 40% 2-year survival. Long-term prognosis was positively influenced by cirrhosis and formation of a tumor capsule. Indications for operative management depend only on extension of tumor growth and concomiting liver cirrhosis as biology of epithelial liver tumors is poorly understood.
 ...
PMID:[Prognosis and therapy of primary epithelial liver tumors. Evaluating a personal patient sample]. 217 93

In 94 patients liver transplantations for malignant tumors of the liver have been performed in this institution from 1972 to 1987. The long-term overall results in hepatic transplantation for irresectable tumors are disappointing in spite of good short-term palliation in most of the patients. Tumor recurrence is the rule. But individual long-living patients demonstrate the potentials of this treatment. Thus the crucial question will be a proper selection of patients. The relative suitability (in descending order of favorableness) of the kinds of tumors may range from HCC without cirrhosis, to central bile duct tumors, to HCC in cirrhosis, to CCC, and finally to secondaries. But this range can only give some probability for the success rate. More important is the tumor stage. Survival in lymph node-positive stages is by far worse than in lymph node-negative stages. The 6-month, 1-year, and 2-year actuarial survival data in our experience for lymph node-negative (lymph node-positive) HCC without cirrhosis are 83%, 75%, 75% (33%, 11%, 11%); in bile duct carcinomas in lymph node-negative stages (lymph node-positive) they are 6 months, 100% (40%); 1 year, 100% (13%); and 2 years, 83% (0%). Hepatic transplantation for selected tumor patients furthermore seems justified and is essential for a detailed analysis of the chance of different tumor types for success with this method of treatment.
 ...
PMID:Is there a place for liver grafting for malignancy? 245 Apr 17

In seven primary liver cancers (HCC 5, CCC 1, mixed 1), MR images (0.35 Tesla super-conducting) were compared with macroscopic appearances, and relaxation times (T1 and T2) with microscopic characteristics. MRI was able to reveal the gross appearance of five nodular lesions, but did not reveal one diffuse HCC and one nodular HCC with marked extracapsular extension. T2-weighted SE images could not demonstrate fibrous capsules around the tumor in four nodular HCCs. The T1 and T2 values of the tumors were longer than those of the surrounding liver parenchyma, and the T1 elongation corresponded roughly to the degree of necrosis and fibrosis within the tumors.
 ...
PMID:Magnetic resonance imaging (MRI) of primary liver cancer--MRI-pathologic correlation. 299 80

Hepatocytes cultured for extended periods of time lose the ability to express alcohol dehydrogenase and thus, the ability to efficiently oxidize ethanol. Therefore, it has been difficult to investigate the effects of chronic ethanol oxidation by hepatocytes in vitro. To circumvent this problem, we have inserted the coding region of an exogenous alcohol dehydrogenase gene into an hepatic cell line. Using the human hepatocellular carcinoma cell line, Hep G2, we have constructed an hepatic cell line that stably expresses alcohol dehydrogenase. These recombinant cells, termed HAD 73.1 cells, express approximately 40% of the alcohol dehydrogenase activity of freshly isolated rat hepatocytes. When the ethanol metabolizing ability of these cells was directly measured, the results indicated that not only were these cells able to metabolize ethanol at approximately 70% of the rate of freshly isolated rat hepatocytes but acetaldehyde concentrations of up to 50 microM were detected in the medium. Furthermore, the level of acetaldehyde produced during ethanol oxidation was augmented by cyanamide, an inhibitor of acetaldehyde oxidation, while the ability of these cells to metabolize ethanol was inhibited by pyrazole, an inhibitor of alcohol dehydrogenase. These results suggest that this in vitro system will be a valuable tool enabling detailed biochemical studies exploring the effects of chronic ethanol oxidation on the liver and the mechanisms of alcohol-induced hepatic cell injury.
 ...
PMID:Establishment of a recombinant hepatic cell line stably expressing alcohol dehydrogenase. 764 56

Oxidants are suspected to represent important human carcinogens. They are mutagenic and may participate in the activation of proto-oncogenes and the inactivation of tumor suppressor genes. We have studied the capacity of hydrogen peroxide plus ferric chloride (FeCl3) to induce base pair changes in the hotspot codons 248 and 249 of the p53 tumor suppressor gene in human fibroblasts. In codon 248 (CGG) H2O2/FeCl3 only induced the transversion of G to C in the second position and the transition of G to A in the third position. No evidence was obtained for spontaneous or oxidant-induced deamination of 5-methylcytosine in the CpG dinucleotide of codon 248 since neither C to T transitions in the first position nor G to A transitions in the middle position were observed. H2O2/FeCl3 efficiently induced G to T transversions at both G-residues of codon 249 (AGG) and C to A transversions at the first position of codon 250 (CCC). It is evident that H2O2/FeCl3 possesses essentially the same mutagenic specificity for codons 249 and 250 of p53 as bulky carcinogens such as aflatoxin B1, benzo(a)pyrene or heterocyclic amines. In particular, it is not possible to eliminate oxidants from the list of candidate carcinogens which may be responsible for the high incidence of p53 codon 249 AGT mutations in hepatocellular carcinoma from certain areas of the world.
 ...
PMID:Oxy-radical induced mutagenesis of hotspot codons 248 and 249 of the human p53 gene. 803 11

Tumour (n = 338) and corresponding liver tissue (n = 276) of liver cell carcinoma (LCC) patients including 31 Asiatic cases was studied with immunohistochemical methods (IHC) for the expression of HBs (7MABs and 2 PABs), HBc, HBe, HBx, and preS antigens. HBV-DNA was detected with in situ hybridisation (ISH) employing digoxigenin-labeled DNA probes. Furthermore, polymerase chain reaction (PCR) was done for a part of the X-ORF (1542+, 1746-). Tumours from the European patients were fibrolamellar (FLC; n = 8), hepatocellular (HCC; n = 260), mixed hepatocellular/cholangiocellular (HCC/CCC; n = 23), and pure cholangiocellular carcinomas (CCC; n = 16). Of the Asiatic cases, 56.5% contained HBs in liver and 64.5% in tumour tissue, of the European cases these were 21.7% and 29.6%, respectively. HBc, HBe, and preS antigens were found only in few cases. HBV positive rates with ISH were 82.6% and 87.1% for Asiatic, and 45.3% and 51.7% for European cases, respectively. Altogether, 93.6% of the Asiatic and 64.2% of the European patients were positive for HBV with IHC or ISH. HCC/CCC and CCC showed slightly lower HBV positive rates than HCC. Over 90% of the cases had HBx in liver and tumour tissue. PCR revealed HBV positive rates of 73.2% for liver and 90.1% for tumour tissue irrespective of patients descent and tumour type. Thus, HBV seems to represent a pathogenetic factor for LCC in Western European patients irrespective of the tumour type. The existence of the "mixed tumours" HCC/CCC as well as the frequent HBV-positivity of tumours with cholangiocellular differentiation document that CCC belong to the category LCC.
 ...
PMID:[Pathogenetic role of HBV in liver cell carcinoma of Western European patients]. 860 Jun 76

Aberrations of the p53 and Rb tumour suppressor genes were examined in 12 human hepatocellular carcinoma (HCC)-derived cell lines from different geographic areas and 9 local HCCs by restriction fragment length polymorphisms (RFLP), polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and DNA sequencing. The relationships between genetic changes and hepatitis B virus (HBV) DNA integration in samples were compared. None of the cell lines and tumours showed structural changes in the Rb gene, while 6 cell lines and 2 tumours had mutation or deletion in exons 5 to 8 of p53. Mutations include an AGG --> AGT (Arg --> Ser) transversion at codon 249 in PLC/PRF/5 and Mahlavu, an AAT --> AAA (Asn --> Cys) transversion at codon 200 in TONG/HCC, an AAG --> GAG (Lys --> Glu) transition at codon 139 in HCC-T, a CAT --> CGT (His --> Arg) transition at codon 214 in SC4, and a CCC --> CTC (Pro --> Leu) transition at codon 250 in SC8. In Huh4, an 18-bp deletion from codon 264 to 270 resulted in loss of Leu-Gly-Arg-Asn-Ser-Phe from the amino acid sequences 265 to 270, whereas Hep3B had a 7-kb deletion after exon 7 of p53. Our data indicate that whereas Rb may not have pleiotropic effects on HCC, p53 aberrations are frequently involved in hepatocarcinogenesis. Further, HBV infection appears to be unrelated to the micro-genetic changes of p53. The G to T codon-249-mutation is consistent with HCCs arising from areas at high risk for both aflatoxin B1 (AFB1) exposure and HBV infection.
 ...
PMID:Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma. 877 41

1. Epoxide hydrolases form an enzyme family involved in the metabolism of a variety of xenobiotics including cytostatic drugs and carcinogens. Whether human microsomal epoxide hydrolase--one of the main members of the epoxide hydrolase family--is expressed in neoplasia of the liver has been the subject of a controversial discussion. 2. We therefore developed a quantitative immunohistochemical assay and monitored epoxide hydrolase expression in hepatocellular carcinomas (HCC, n = 20), cholangio-cellular carcinomas (CCC, n = 2) and liver metastases (n = 57) of tumours of various origins, and compared the expression intensities and patterns to normal liver tissue. 3. In normal liver tissue microsomal epoxide hydrolase displays expression of the constitutive type with non-zonal staining of all hepatocytes. 4. When using a quantitative immunohistochemical approach statistically significant differences in microsomal epoxide hydrolase expression were observed between normal tissue, hepatocellular carcinoma and liver metastases (mean optical density 2.35, 1.63 and 0.21 respectively, p = 2.9, 6.3 and 18.9). These data indicate differential expression in different types of liver neoplasm. 5. As microsomal epoxide hydrolase is involved in metabolism of different xenobiotics our findings may have implications for tumour progression.
 ...
PMID:Immunohistochemical assessment of human microsomal epoxide hydrolase in primary and secondary liver neoplasm: a quantitative approach. 885 25

Epidemiological evidence has been supporting a relationship between dietary aflatoxin B1 (AFB1) exposure, development of human primary hepatocellular carcinoma (HCC) and mutations in the p53 tumor suppressor gene. However, the correlation between the observed p53 mutations, the AFB1 DNA adducts and their activation pathways has not been elucidated. Development of relevant cellular in vitro models, taking into account species and tissue specificity, could significantly contribute to the knowledge of cytotoxicity and genotoxicity mechanisms of chemical procarcinogens, such as AFB1, in humans. For this purpose a non-tumorigenic SV40-immortalized human liver epithelial cell line (THLE cells) which retained most of the phase II enzymes, but had markedly reduced phase I activities was used for stable expression of the human CYP1A2, CYP2A6, CYP2B6 and CYP3A4 cDNA. The four genetically engineered cell lines (T5-1A2, T5-2A6, T5-2B6 and T5-3A4) produced high levels of the specific CYP450 proteins and showed comparable or higher catalytic activities related to the CYP450 expression when compared to human hepatocytes. The T5-1A2, T5-2A6, T5-2B6 and T5-3A4 cell lines exhibited a very high sensitivity to the cytotoxic effects of AFB1 and were approximately 125-, 2-, 2- and 15-fold, respectively, more sensitive than the control T5-neo cells, transfected with an expressing vector which does not contain CYP450 cDNA. In the CYP450-expressing cells, nanomolar doses of AFB1-induced DNA adduct formation including AFB1-N7-guanine, -pyrimidyl and -diol adducts. In addition, the T5-1A2 cells showed AFM1-DNA adducts. At similar levels of total DNA adducts, both the T5-1A2 and T5-3A4 cells showed, at codon 249 of the p53 gene, AGG to AGT transversions at a relative frequency of 15x10(-6). In contrast, only the T5-3A4 cells showed CCC to ACC transversion at codon 250 at a high frequency, whereas the second most frequent mutations found in the T5-1A2 cells were C to T transitions at the first and second position of the codon 250. No significant AFB1-induced p53 mutations could be detected in the T5-2A6 cells. Therefore, the differential expression of specific CYP450 genes in human hepatocytes can modulate the cytotoxicity, DNA adduct levels and frequency of p53 mutations produced by AFB1.
 ...
PMID:Aflatoxin B1-induced DNA adduct formation and p53 mutations in CYP450-expressing human liver cell lines. 923 Feb 70


1 2 3 4 Next >>