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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966-1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 +/- 17.5 years) and females (37.40 +/- 15.16 years) was significantly different (p < 0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96% vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumourous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (> 20 ng/ml) in 90% of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19,322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102,565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95% CI: [182.8, 19,952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade.
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PMID:Hepatitis B virus, alpha-fetoprotein synthesis, and hepatocellular carcinoma in Zaire. 128 Mar 14

In the current study we sought to elucidate the molecular mechanisms which might contribute to hepatocarcinogenesis in a hepatitis B virus (HBV) envelope transgenic mouse model in which chronic hepatocellular injury and inflammation lead to regenerative hyperplasia and eventually to the development of chromosomal abnormalities and hepatocellular carcinoma (HCC), thereby reiterating many of the pathophysiological events that occur prior to the development of HCC in chronic HBV infection in humans. We have previously demonstrated that HBV envelope gene expression is decreased in regenerating hepatocytes and preneoplastic nodules early in the disease process and that expression of alpha-fetoprotein and the multidrug transporter gene mdr-III is activated in the tumors that develop in this model, but not prior to tumor development. In the current study, we examined the structure and expression of a large panel of dominant acting oncogenes and tumor suppressor genes in the liver at all stages of the disease process in order to determine the extent to which they contribute to hepatocarcinogenesis in these transgenic mice. To our surprise, no changes were observed in the structure or function of any of these genes, many of which are commonly activated in other rodent models of hepatocarcinogenesis but rarely activated in human HCC. These findings suggest that the HBV transgenic mouse model is different from most other rodent models of hepatocarcinogenesis and that it may relate more closely to the events involved in HBV-induced human hepatocarcinogenesis, where generalized chromosomal abnormalities are common, while structural and functional changes in most of the commonly studied positive-acting oncogenes examined herein are not. Since p53 and RB mutations have recently been reported to be late events in human hepatocarcinogenesis, the structural integrity of the RB locus and the absence of p53 mutations in the HBV transgenic mouse model suggest that they may represent a relatively early stage of hepatocellular tumorigenesis and that further manipulation of this model is warranted in order to more fully reproduce the molecular-genetic events that characterize HBV-induced HCC in humans.
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PMID:Multiple oncogenes and tumor suppressor genes are structurally and functionally intact during hepatocarcinogenesis in hepatitis B virus transgenic mice. 131 29

We investigated whether replication-competent pre-C/C defective mutants of hepatitis B virus (HBV) are detectable in primary human hepatocellular carcinoma (HCC) tissues from patients of a geographic area endemic for such mutants. DNAs extracted from formalin-fixed paraffin-embedded HCC samples were checked for the presence of specific HBV DNA sequences using the polymerase chain reaction (PCR). Amplified pre-C regions from nine HCC samples were directly sequenced as were samples of nontumoral liver tissues from five of these patients. The data show that hypervariable distal pre-C sequences were present in all nine HCC samples; this high variability was dependent on point mutations, which led to amino acid substitutions in nearly all cases. Interestingly, seven of the nine HBV DNA-positive samples from HCC tissues (but not samples from peritumoral liver tissue) showed mutations leading to amino acid substitution at the level of a distal cysteine residue. No mutation generating a translationally defective pre-C/C region was detectable in the tumor samples. Otherwise, in four of the six nontumoral liver tissues available from the same patients, a pre-C sequence with an in-frame TAG stop codon was detectable, although in three cases as a component of mixed population.
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PMID:Sequence analysis of the hepatitis B virus pre-C region in hepatocellular carcinoma [HCC] and nontumoral liver tissues from HCC patients. 131 86

We report a 65-yr-old man with hepatitis B virus-related liver cirrhosis and biopsy-proven hepatocellular carcinoma who has undergone spontaneous regression. The tumor became impalpable, and was no longer detectable by ultrasonography and computed axial tomography, 5 and 30 months later. The alpha-fetoprotein level also decreased to normal range. The clinical course is silent, and the patient is alive and well 37 months after the initial diagnosis.
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PMID:Spontaneous regression of hepatocellular carcinoma. 131 72

Human papillomaviruses (HPV) have been linked causally to some human cancers such as cervical carcinoma. To determine whether any additional type of human malignancy contained HPV DNA, we examined 16 hepatocellular carcinoma (HCC) specimens by Southern blot technique and by polymerase chain reaction (PCR). One HCC contained HPV 16 DNA as demonstrated by both Southern blot and PCR. Two other HCC samples contained HPV 18-related nucleotide sequences by PCR but were negative by Southern blot of genomic DNA. HPV could have been carried via blood to the liver, thus indirectly supporting the presence of an HPV viremia. Our findings suggest that oncogenic HPV might constitute a cofactor acting synergistically with hepatitis B virus (HBV) in the development of the HCC in these patients. Alternatively, the presence of HPV in the tumor tissue might be the result of an opportunistic infection.
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PMID:Detection of human papillomavirus in primary hepatocellular carcinoma. 132 Mar 56

We have previously reported the identification of a hepatitis B virus (HBV) DNA integration in an intron of the cyclin A gene in an early hepatocellular carcinoma (HCC) and the isolation of human cyclin A cDNA. We have now constructed a cDNA library from the tumor and isolated several hybrid HBV-cyclin A cDNAs from it. The hybrid cDNAs encode an HBV-cyclin A fusion protein. In the chimeric protein, the N-terminus of cyclin A, including the signals for cyclin degradation, is deleted and replaced by viral PreS2/S sequences, transcription being initiated from the viral PreS2/S promoter. This chimeric protein is undegradable in an in vitro cyclin degradation assay. Northern blot analyses showed strong expression of the hybrid transcripts in the tumor, while cyclin A- or HBV-specific transcripts were not detected in the non-tumorous liver of the same patient. Thus, HBV DNA integration in the cyclin A gene resulted in a strong expression of hybrid HBV-cyclin A transcripts encoding a stabilized cyclin A. This chimeric protein may play an important role in the development of the tumor.
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PMID:Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma. 132 6

Twenty-three patients with minute hepatocellular carcinoma, defined as a solitary lesion less than or equal to 2 cm, underwent hepatectomy at our institute during the 10 years between January, 1979 and December, 1988. Hepatitis B surface antigen was positive in 4 patients and the preoperative serum alpha-fetoprotein level was within the normal range in 7 patients and slightly elevated (20-200 ng/mL) in 14 patients. Liver cirrhosis was present in 16 patients and chronic hepatitis in 6 patients. The diagnosis was first suspected from the results of periodic examinations, including echography and the measurement of alpha-fetoprotein, in all except one patient. Minor hepatic resection was performed in 22 patients, and lobectomy in one patient in whom the tumor was located centrally in the liver. Three patients died of hepatic failure in hospital following surgery, and the survival rates of the other 20 patients at 1, 3, and 5 years were 90, 79, and 61 percent, respectively. The prognostic factors that influenced long-term survival were investigated by comparing the survival curves. The only factor associated with a significant difference in survival was the severity of concomitant liver disease. Thus, severe cirrhosis is the main obstacle against the long-term survival of patients with minute hepatocellular carcinoma.
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PMID:Hepatic resection for minute hepatocellular carcinoma. 132 59

In persistent hepadnavirus infections, a distinctive feature of woodchuck hepatitis virus (WHV) is the coupling of frequent viral integrations into myc family genes with the rapid onset of primary liver tumors. We have investigated the patterns of WHV DNA insertion into N-myc2, a newly identified retroposed oncogene, in woodchuck hepatomas resulting from either natural or experimental infections. In both cases, integrated viral sequences were preferentially associated with the N-myc2 locus. In more than 40% of the woodchuck tumors analyzed, viral insertion sites were clustered in a 3-kb region upstream of N-myc2 or in the 3' noncoding region. Insertion of WHV sequences homologous to the human hepatitis B virus enhancers, either upstream or downstream of the N-myc2 coding domain, was associated with the production of normal N-myc2 mRNA or hybrid N-myc2-WHV transcripts, initiated at the normal N-myc2 transcriptional start site. Transient-transfection assays with different N-myc2-WHV constructs in HepG2 cells demonstrated that the viral enhancers could efficiently activate the N-myc2 promoter. These results, showing that cis activation of preferred cellular targets through enhancer insertion is a common strategy for tumor induction by WHV, emphasize the previously noted similarities between hepadnaviruses and nonacute oncogenic retroviruses.
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PMID:Hepadnavirus integration: mechanisms of activation of the N-myc2 retrotransposon in woodchuck liver tumors. 132 93

Liver cancer is a common neoplasm of man that is especially frequent in parts of the world where hepatitis B virus is endemic and high aflatoxin ingestion is experienced. Hepatocellular carcinoma (HCC) has a very aggressive behavior, is quite resistant to radiotherapy and chemotherapy and is often inoperable, all of which lead to a five-year patient survival of less than 5 percent. Studies in lower animals (e.g. fish, rats) lend themselves to preplanned manipulations aimed at answering specific questions which are intended to elucidate the biology of HCC. Information derived from these studies can be applied to the human condition with the hope of earlier diagnosis, improved treatment and possibly prevention. This review touches on selected areas of similarity and dissimilarity in the histology, histochemistry, metastasis, etiology and molecular biology of HCC in fish, rats and man.
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PMID:Hepatocellular neoplasia in fish, rats and man: a selected comparative review. 132 43

A personal view is presented reflecting some developments in human tumor virology during the past three decades. Since the discovery of the Epstein-Barr virus in 1964 members of additional viral groups have been linked to human tumors, e.g. hepatitis B virus, HTLV-1, and a number of different papillomavirus types. It became evident that the virus infection per se is not sufficient and that additional events modifying the host cell genome contribute to the development of virus-linked human cancers. At present approximately 15% of the worldwide cancer incidence can be linked to viral infections. The author describes his personal entry into the field and the research in his laboratory on human tumor viruses.
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PMID:Viruses in human tumors--personal reflections. 132 72


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