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

We have demonstrated that synthetic oligonucleotide representing glucocorticoid responsive element (GRE I) of MMTV inserted into the enhancerless early promoter of SV40 in p delta SVE-CAT expression vector, enhances transient expression of chloramphenicol acetyltransferase gene in HeLa and hepatoma cells cultivated in the presence of dexamethasone. The following changes in the structure of the core sequences (GTTACAAACTGTTCT) of the synthesized GRE eliminated its enhancing ability: i, changes in the left end of the core sequences from GTTACAAAATGTTCT to TCTTCAAACTGTTCT or to TACTCAAACTGTTCT; ii, the increase of gap between TGTTCT and the inverted repeat of this sequence. The above changes did not eliminate specific binding of glucocorticoid receptor to the synthetic oligonucleotides studied.
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PMID:Introduction of the glucocorticoid binding sequences into the expression vector p delta SVE-CAT and its effect on the CAT gene expression in mammalian cells. 179 99

The B6C3F1 mouse is used worldwide to gauge the carcinogenic hazard posed by chemicals to humans. An assessment of the ability of this rodent model to predict human neoplasia requires an evaluation of similarities and differences in the genetics of tumor formation between these two species. We examined 142 spontaneous and chemically-induced liver tumors isolated from the B6C3F1 mouse for losses of heterozygosity (LOH) at 78 polymorphic loci and compared these results to genetic changes known to occur in human hepatocellular carcinoma. Approximately a third of the 142 mouse tumors exhibited LOH, suggesting that tumor suppressor gene inactivation may be involved in the formation of mouse liver tumors. Most of the LOH observed was restricted to seven chromosome sites and most of the tumors that underwent LOH lost alleles from only one of those seven sites. The relatively few losses seen in these mouse tumors distinguished them from clinical stage human tumors in that, in the mouse tumors, interstitial deletions appeared more frequently than losses of whole chromosomes. Only four mouse tumors lost a whole chromosome. LOH occurred at loci of the mouse genome syntenic to areas of the human genome known to harbor the Wilms', retinoblastoma, APC, MCC and DCC tumor suppressor genes; these genes have never been associated with hepatocellular carcinomas. Losses observed on chromosomes 5 and 8 (syntenic to human chromosomes 4 and 16) suggest tumor suppressor genes that are common to hepatocellular carcinomas from both species, while losses on chromosome 9 suggest involvement of a previously unidentified tumor suppressor gene.
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PMID:Loss of heterozygosity in spontaneous and chemically induced tumors of the B6C3F1 mouse. 805 44

We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes.
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PMID:The putative tumor suppressor gene on chromosome 5q for hepatocellular carcinoma is distinct from the MCC and APC genes. 840 27

Microcirculation and molecular biology are the hottest topics in modern surgical research. In familial adenomatous polyposis the incidence of carcinoma can be assessed by the localisation of the PAC-gene mutation. Restorative proctocolectomy with ileoanal pouch represents the procedure of choice. The optimal age for the operation varies between 20 and 35 years according to the localisation of the mutation. RT-PCR directed to recently defined surface antigens allows for the sensitive detection of intraoperative tumor cell liberation. Due to tumor cell detection in the systemic circulation the perioperative administration of monoclonal antibodies must be advocated. A preciser definition of lymphogenic tumor spread underlines the importance of systematic lymphadenectomy in resection of the colon. The understanding of microcirculatory disorders has optimized surgical decision-making intra- and perioperatively: function of renal and hepatic microcirculation is a reliable parameter to predict graft quality already intraoperatively and to monitor therapeutic approaches to ischemia/reperfusion injury. Results in the therapy of acute pancreatitis could be improved by operating less and later. Analysis of pancreatic microcirculation resulted in an improvement of ICU-therapy in the early stages of the disease. Transplantation of the liver is limited to hepatocellular carcinoma when its localisation or the residual hepatic function after resection preclude curative excision. In addition liver transplantation should not be carried out in tumors larger than 5 cm or in patients with more than 3 tumor nodules. Liver resection for colorectal metastases is a standard procedure. A second resection of recurrent metastases is advocated since an identical median survival can be achieved compared to the primary resection (32 mo). The surgical treatment of non-colorectal liver metastases is under evaluation and should be restricted to oncological centers. Special aspects of backwashileitis in ulcerative colitis will be outlined concerning timing of colectomy, pouch construction, and follow-up.
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PMID:[State of the art: gastroenterologic surgery]. 1006 3

APC gene mutations have been demonstrated not only in colorectal carcinoma but also in a variety of human cancers. To define the possible role of mutations of the APC gene in hepatocarcinogenesis, we examined 46 pairs of hepatocellular carcinomas and corresponding non-tumorous liver tissue by polymerase chain reaction and single strand conformation polymorphism. All 46 hepatocellular carcinomas had no altered electrophoretic mobility to suggest the presence of APC gene mutation in the mutation cluster region. We also examined the possible loss of heterozygosity of APC and MCC gene loci by fragment length polymorphism analysis and by polymerase chain reaction. None of the cases showed a loss of heterozygosity at the APC and MCC gene loci. The results suggested that the possibility of APC and MCC as the gene defect in the genesis of human hepatocellular carcinoma may be very rare.
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PMID:Absence of APC gene mutation in the mutation cluster region in hepatocellular carcinoma. 1038 Nov 26

To determine the frequency of Wnt/Wingless beta catenin pathway alteration in human hepatocellular carcinoma, a beta catenin and APC gene mutation screening was performed in a series of 119 tumors. An activating beta catenin mutation in exon 3 was found in 18% of the cases. Among tumors lacking beta catenin mutation, no APC mutation has been evidenced in a subset of 30 cases tested. The correlation between beta catenin mutation status and chromosome segment deletions was studied on a set of 48 hyperploid tumors. Chromosome 1p, 4q and 16p deletions were significantly associated with the absence of beta catenin mutation (P<0.05). Furthermore the Fractional Allelic Loss was significantly smaller in the beta catenin mutated tumors than in the non-mutated tumors (0.12 versus 022). Taken together, these results suggest, the existence of two carcinogenesis mechanisms. The first mechanism implies a beta catenin activating mutation associated with a low rate of loss of heterozygosity. The second mechanism, operating in a context of chromosomal instability, would involve tumor suppressor genes.
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PMID:Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity. 1043 29

The activation of protooncogenes and inactivation of tumor suppressor genes in affected cells are considered as the core events that provide a selective growth advantage and clonal expansion during the multistep process of carcinogenesis. Somatic mutations, induced by exogenous or endogenous mechanisms, were found to alter the normal functions of the p53 tumor suppressor gene. p53 is the most prominent example of tumor suppressor genes because it is mutated in about half of all human cancer. In contrast to other tumor suppressor genes (like APC and RB), about 80% of p53 mutations are missense mutations that lead to amino acid substitutions in proteins and can alter the protein conformation and increase the stability of p53. These changes can also alter the sequence-specific DNA binding and transcription factor activity of p53. These abnormalities can abrogate p53 dependent pathways involved in important cellular functions like cell-cycle control, DNA repair, differentiation, genomic plasticity and programmed cell death. A number of different carcinogens have been found to cause different characteristic mutations in the p53 gene. For example, exposure to ultraviolet light is correlated with transition mutations at dipyrimidine sites; aflatoxin B(1) exposure is correlated with a G:C to T:A transversion that leads to a serine substitution at residue 249 of p53 in hepatocellular carcinoma; and exposure to cigarette smoke is correlated with G:C to T:A transversions in lung carcinoma. Therefore, measuring the characteristic p53 mutation load or frequency of mutated alleles in nontumorous tissue (before the clonal expansion of mutated cells), can generate hypotheses, e.g., providing a molecular linkage between exposure to a particular carcinogen and cancer, and identifying individuals at increased cancer risk.
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PMID:p53 mutation spectrum and load: the generation of hypotheses linking the exposure of endogenous or exogenous carcinogens to human cancer. 1051 75

Hepatocellular carcinoma (HCC) is linked etiologically to viruses (hepatitis B virus [HBV] and hepatitis C virus [HCV]), chemical carcinogens (i.e., aflatoxins), and other environmental and host factors causing chronic liver injury. Some hepatoblastomas may be linked to inherited gene mutations, but adult hereditary HCC appears to be rare. HCCs display gross genomic alterations, including DNA rearrangements associated with HBV DNA integration, loss of heterozygosity, and, less importantly, chromosomal amplifications and loss of imprinting. Many genes with somatic mutations have now been identified in these tumors. Most frequently involved genes are tumor suppressor genes such as p53, M6P/IGF2R, beta-catenin, p16INK4A, and retinoblastoma genes. Most identified mutations are somatic, but germline mutations of p16INK4A, APC, and BRCA2 have also been reported. Oncogenic activation of several cellular genes such as cyclin D and cyclin A have been described in HCC, but the possible implication of candidate viral oncogenes (i.e., X protein of HBV) is still debated. A comprehensive analysis of all the genetic changes described for HCC demonstrates that at least four different growth regulatory pathways are altered in these tumors. However, each pathway appears to be implicated in a limited fraction of these tumors, suggesting that HCCs are genetically heterogenous neoplasms. This genetic heterogeneity correlates with the heterogeneity of etiologic factors implicated in HCC.
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PMID:Genetic aspects of hepatocellular carcinogenesis. 1051 3

Since its discovery as a protein associated with the cytoplasmic region of E-cadherin, beta-catenin has been shown to perform two apparently unrelated functions: it has a crucial role in cell-cell adhesion in addition to a signaling role as a component of the Wnt/wg pathway. Wnt/wg signaling results in beta-catenin accumulation and transcriptional activation of specific target genes during development. It is now apparent that deregulation of beta-catenin signaling is an important event in the genesis of a number of malignancies, such as colon cancer, melanoma, hepatocellular carcinoma, ovarian cancer, endometrial cancer, medulloblastoma pilomatricomas, and prostate cancer. beta-catenin mutations appear to be a crucial step in the progression of a subset of these cancers, suggesting an important role in the control of cellular proliferation or cell death. The APC/beta-catenin pathway is highly regulated and includes players such as GSK3-beta, CBP, Groucho, Axin, Conductin, and TCF. c-MYC and cyclin D1 were recently identified as a key transcriptional targets of this pathway and additional targets are likely to emerge. Published 1999 John Wiley & Sons, Inc.
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PMID:beta-catenin signaling and cancer. 1058 Sep 87

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Hepatitis B virus and hepatitis C virus infections, exposure to aflatoxin, and excessive intake of alcohol have been identified as major risk factors. However, the molecular mechanisms underlying their development are still poorly understood. Recently, beta-catenin, one of the key components of the Wnt signaling pathway, has been found to be mutated in about 20% of HCCs, suggesting a role of the Wnt pathway in their development. In this study, we examined beta-catenin and APC mutations in 22 HCCs associated with HCV infection, using single-strand conformation polymorphism (SSCP) followed by direct DNA sequencing. beta-Catenin mutations were found in nine (41%) cases, but no APC mutations were found. beta-Catenin immunohistochemistry revealed nuclear accumulation of beta-catenin protein in all nine tumors with a beta-catenin mutation and two additional tumors without a mutation. These results suggest that activation of the Wnt signaling pathway by beta-catenin mutation contributes significantly to the hepatocellular carcinogenesis associated with HCV infection.
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PMID:Beta-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infection. 1059 7


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