Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recently introduced enzyme immunoassay procedure for antibodies against the hepatitis-C virus (HCV) was used to test samples from 185 cases with hepatocellular carcinoma (HCC) and 432 hospital controls. The anti-HCV results were examined in conjunction with previously reported data from this study concerning hepatitis-B virus (HBV) serology, hepatitis-D virus (HDV) antibodies, presence of cirrhosis and tobacco smoking. There was evidence for interaction between HBV and HCV in the causation of HCC: as previously reported, the rate ratio (RR) linking the presence of anti-HCV to HCC among subjects positive for hepatitis-B surface antigen (HBsAg) was substantially higher than the corresponding RR among those negative for this marker; furthermore, among HCC patients positive for HBsAg, a high proportion (33/61) of those who were positive for hepatitis-Be antigen (HBeAg) or its antibody were positive for anti-HCV, whereas among HBsAg-positive controls who were also positive for HBeAg or its antibody, none was positive for anti-HCV (0/18; p less than 10(-4)). The anti-HCV-related RR for HCC was also higher among HCC patients with cirrhosis than among those without evidence of co-existing cirrhosis (RR 11.4 vs. 4.4; p = 0.06). In addition, there was some evidence of interaction between tobacco smoking and HCV in the origin of HCC; after controlling for age, sex and HBsAg status, the RR for subjects positive for anti-HCV was 6.8 among smokers but only 3.2 among non-smokers (p = 0.26). By contrast, there was no suggestion of an interaction between anti-HCV and anti-HDV, in agreement with the presumed minimal role, if any, of HDV in HCC etiology. These results support the notion that HCV is involved in the etiology of HCC by advancing, through a chronic liver disease process, carcinogenesis initiated by other factors.
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PMID:Epidemiologic assessment of interactions of hepatitis-C virus with seromarkers of hepatitis-B and -D viruses, cirrhosis and tobacco smoking in hepatocellular carcinoma. 165 59

The genetic factors involved in the multistep process of carcinogenesis can be divided at least into two major categories: 1. Mutated or lost genes, which may directly represent one step in the sequential process (tumour suppressor genes); inheritance of one tumour suppressor gene causes dominant expression of the carcinogenic phenotype (the dominant inheritance is described in the accompanying paper); 2. Other genes, which lead to conditions that favour the development of cancer and generally are inherited in a recessive fashion; they are the subject of this paper. Autosomal recessively inherited diseases, such as xeroderma pigmentosum, ataxia-telangiectasia, Bloom's syndrome and Fanconi's anaemia display increased genome instability (chromosomal fragility and/or DNA-repair deficiencies) and are associated in the homozygote and probably also in the heterozygote state with defined malignancies. Neoplasms particularly of the lymphoreticular system frequently occur in patients with genetically determined immunodeficiencies (e.g. severe combined immune deficiency or Wiskott-Aldrich syndrome). People differ due to their individual genetic constitution in their responses to various classes of carcinogens such as physical and chemical agents, to dietary habits, as well as to viruses. Furthermore, tumours are often found in patients displaying premature aging (e.g. Werner's syndrome). In addition, several metabolic abnormalities such as genetic syndromes featuring chronic liver disease, but also many other inherited metabolic conditions have cancer as a regular or frequent complication.
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PMID:Recessively inherited deficiencies predisposing to cancer. 219 May 29

Hepatocellular carcinoma (HCC) is among the 10 most common tumors in the world. However, incidence is not evenly distributed across the world. In many instances, the proximate cause for the tumor can be identified. Chronic hepatitis B infection is probably the most common cause, followed by chronic hepatitis C. Other important causes are alcoholic liver disease, hemochromatosis, alpha 1-antitrypsin deficiency, and other chronic liver diseases. Although proximate causes may be identifiable, pathogenesis remains uncertain. Factors that may be important include the presence of Aflatoxin B1 in food, genetic changes induced by the hepatitis B virus, and repeated rounds of necrosis and regeneration, also induced by hepatitis viruses. The genes involved and the mutations necessary for hepatic carcinogenesis are unknown, with the sole exception of the p53 gene, which is probably a late phenomenon. Screening for HCC is widely practiced despite the lack of evidence of improved survival. The screening tests used include alphafetoprotein levels and ultrasonography. Screening can identify small tumors; however, survival may not be improved, because the presence of cirrhosis may limit the number of patients who can undergo resections; recurrences or second primary tumors are common; and the presence of chronic liver disease means that survival may be limited anyway. There are many different forms of therapy available; unfortunately, most have not been compared in randomized controlled trials. Surgery remains the therapy of choice if feasible. All other therapy is palliative, including chemotherapy, chemoembolization, hepatic artery embolization, various forms of radiotherapy, and various forms of ablative therapy.
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PMID:Hepatocellular carcinoma. 753 16

Forty patients with chronic liver disease and HCC were analyzed for infection with hepatitis C (HCV) and hepatitis B (HBV) viruses. All patients were negative for HBsAg, 16 were alcoholics, 6 had previous blood transfusions and 18 had sporadic chronic hepatitis. Antibodies to HCV were determined by EIA 2nd generation. HBV-DNA was detected by PCR using primers of the precore region. Analysis of HCV-RNA was done with nested PCR amplifying the 5' non-coding region of the HCV genome, using primers complementary to nucleotides 1-20 and 305-320 and nested primers complementary to nucleotides 21-31 and 271-286 of the HCV-J1. Anti-HCV were positive in 35/40 patients (87.5%). HCV-RNA was detected by PCR in 34 patients (85%) all of them positive for the anti-HCV. HCV-RNA was detected in 70.5% of the alcohol abusers, in 100% of patients with history of transfusion(s) and 94.1% of patients with cryptogenic chronic liver disease. HBV-DNA was detected in only 2 patients. In conclusion, there is a high rate of HCV and a low rate of HBV viremia detected by PCR in Spanish patients with HCC HBsAg negative. No patient without anti-HCV presents HCV-RNA. Our results suggest that persistent HCV replication may play a role in hepatic carcinogenesis, as HBV-DNA could be found in only 5% of our HCC patients.
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PMID:Demonstration of HCV-RNA and HBV-DNA in the serum of HBsAg negative patients with hepatocellular carcinoma. 781 97

Chronic liver diseases, in particular chronic HBV and HCV infections, frequently progress to liver cirrhosis and HCC. The molecular events underlying hepatocarcinogenesis are not yet well defined. It appears likely, however, that HCCs result from a stepwise carcinogenesis: due to chronic liver disease there is liver cell necrosis, inflammation and regeneration with a high mitotic rate of liver cells. In this setting, chromosomal DNA rearrangements occur which may result in the activation of cellular oncogenes or inactivation of tumor suppressor genes. Viral genes or gene products as well as cofactors, such as alcohol or aflatoxins, may make a specific contribution to these molecular events. Apart from the molecular aspects of hepatocarcinogenesis, for clinical practice the implementation of measures to prevent or treat chronic liver diseases should reduce the incidence of HCCs, one the most frequent malignancies in some areas of the world.
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PMID:[Hepatocellular carcinoma: molecular biology aspects]. 784 55

Several biochemical events accompany and mediate the development of chronic liver disease and its evolution into cancer. Low plasma zinc and high copper levels have been observed in various liver diseases, such as liver cirrhosis and viral hepatitis, while increased oestradiol levels have been documented in chronic liver damage and hepatocellular carcinoma. We administered CCL4 intragastrically to 10 female Sprague Dawley rats for 30 weeks. All animals developed cirrhosis and four also developed hepatocellular carcinoma. Plasma levels of zinc, copper and oestradiol were significantly higher in the latter group than in animals with simple cirrhosis. Progesterone, AST and bilirubin showed a trend toward significant differences whereas testosterone and ALP levels were unchanged. These findings add to the evidence that sex hormones and trace elements are involved in the process of the development of chronic liver damage and carcinogenesis.
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PMID:Sex hormones and trace elements in rat CCL4-induced cirrhosis and hepatocellular carcinoma. 835 89

Hepatocellular carcinomas frequently occur in association with liver cirrhosis, as chronic liver disease is one of the most important factors in carcinogenesis. In addition to small hepatocellular carcinomas (less than 3 cm in diameter), recent reports of pathologic studies of resected specimens from cirrhotic liver describe associated small nodular lesions (i.e., regenerating nodule, adenomatous hyperplasia, and early hepatocellular carcinoma). In hepatocarcinogenesis of the cirrhotic liver, a regenerating nodule might be the first step in the development of hepatocellular carcinoma, going through phases of adenomatous hyperplasia and early hepatocellular carcinoma in a multistep fashion. We describe the pathologic characteristics of small hepatocellular carcinomas and associated nodular hepatic lesions and review the current concepts of the role of these associated lesions in carcinogenesis. We also discuss the imaging findings of these abnormalities, the efficacy of various imaging techniques for diagnosing them, and the importance of imaging in treatment planning.
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PMID:Small hepatocellular carcinomas and associated nodular lesions of the liver: pathology, pathogenesis, and imaging findings. 838 19

We report an incidental small hepatocellular carcinoma in a patient with chronic hepatitis C infection without cirrhosis. The existence of portal triads and the Meyenburg complexes within the lesion and atypical subnodules suggests that the carcinoma has arisen in the context of a macroregenerative nodule rather than the whole nodule being an early, spreading carcinoma. A growing body of evidence supports macroregenerative nodules as being precursor lesions in the development of hepatocellular carcinoma. Although they are generally thought of as being large cirrhotic nodules, this case suggests that they may be lesions that develop in the context of chronic liver disease, parallel to, but independently of, cirrhosis. Moreover, the development of carcinoma within the nodule suggests that macroregenerative nodules may play a role in carcinogenesis in noncirrhotic livers.
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PMID:A macroregenerative nodule containing multiple foci of hepatocellular carcinoma in a noncirrhotic liver. 839 Mar 98

Hepatitis B virus infection is associated with acute and chronic liver disease and the development of hepatocellular carcinoma (hcc). Several lines of evidence have suggested that hepatitis B virus X protein (HBx), which is a transcriptional trans-activator, plays a role in the process of liver carcinogenesis. We have investigated the expression of insulin-like growth factor I (IGF-I) receptor in human hepatocellular carcinoma cell lines using SNU368 cells containing HBx and SNU387 cells, which lack HBx gene transcript (J-G. Park et al., Int. J. Cancer, 62: 276-282, 1995), in an attempt to understand its possible relationship to the HBx-induced hcc. The binding of 125I-labeled IGF-I to the SNU368 cells was 5-fold higher than that of SNU387 cells. The Scatchard analysis of the binding data revealed a single class binding site for IGF-I with Kd of 7.6 and 8.8 nM and maximum binding capacities of 169 and 33 fmol/10(5) cells, respectively. Therefore, the difference observed in 125I-labeled IGF-I binding between SNU368 and SNU387 cells was due to an increase in the number of IGF-I binding sites with no change in affinity for the IGF-I receptor. An enhanced level of IGF-I receptors in SNU368 cells was also observed by fluorescence-activated cell sorting analysis using a monoclonal antibody against human IGF-I receptor, alpha IR3. The level of IGF-I receptor RNA and the basal IGF-I receptor gene promoter activity in SNU368 cells were 5 and 10 times higher than those observed in SNU387 cells, respectively. To substantiate further that HBx could transactivate the expression of the endogenous IGF-I receptor gene, Hep G2 cells were transiently transfected with a HBx expression vector. The transfection of Hep G2 cells with an HBx expression vector resulted in increased levels of IGF-I receptor RNA, promoter activity, and 125I-labeled IGF-I binding by 2.6-, 2.8-, and 2-fold, respectively. As a result of higher levels of IGF-I receptor, the mitogenic effect of IGFs (IGF-I and IGF-II) on SNU368 cells was 6 times higher than that of SNU387 cells. These results suggest that HBx may play a role in the process of hcc by activating IGF-I receptor gene expression.
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PMID:Increased expression of the insulin-like growth factor I (IGF-I) receptor gene in hepatocellular carcinoma cell lines: implications of IGF-I receptor gene activation by hepatitis B virus X gene product. 870 31

The measurement of somatic cell mutation may assist in the assessment of human cancer risk. The glycophorin A (GPA) assay, which measures the frequency of variant erythrocytes in persons with blood type MN, was used to directly assess in vivo mutability in 30 patients with hepatocellular carcinoma (HCC). HCC patients showed significantly increased frequencies of both hemizygous (MO) and homozygous (MM) variants, due to somatic loss of expression of the N allele, when compared with 27 patients with chronic liver disease and 21 healthy controls. The mean elevations of the MO and MM variant frequencies (VF) in HCC patients were 2-3-fold greater than the comparable VF in the control groups. The mean MO and MM VF in the patients with chronic liver disease was slightly elevated compared to that in healthy controls, but the difference was not significant. In the 19 anti-hepatitis C virus (HCV)-positive patients with a history of blood transfusion, significant linear relations between VF and the duration of HCV infection were observed for MO and MM. These data indicate a high background frequency of somatic mutations in HCC patients. The GPA assay may prove to be a useful estimation of the individual's risk of development of HCC.
Carcinogenesis 1997 Feb
PMID:Evidence for increased somatic cell mutations in patients with hepatocellular carcinoma. 905 41


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