Molecular biology of hepatocellular carcinoma and hepatitis B virus association.
ABSTRACT The involvement of the hepatitis B virus in the pathogenesis of hepatocellular carcinoma was initially suggested on the basis of epidemiological studies. In recent years several kinds of experimental evidence have supported this hypothesis; however, the role played by hepatitis B virus in hepatocarcinogenesis still needs to be elucidated. Several groups of researchers are presently involved in establishing whether hepatitis B virus makes a specific genetic contribution to carcinogenesis or predisposes to neoplastic transformation by causing chronic inflammation and cell regeneration. A comprehensive examination of the data available in the literature suggests that the two hypotheses may not be mutually exclusive.
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ABSTRACT: Wilms' tumour probably arises from embryonal kidney cells and occurs in both hereditary and sporadic forms. Knudson and Strong have suggested that both forms of the disease are initiated by two mutational events. In the case of the inherited form, cytogenetic evidence indicates that a germline deletion of chromosome band 11p13 may correspond to one of the two mutations. DNA mapping evidence is consistent with the notion that the tumour susceptibility gene (Wg) on chromosome 11 is actually recessive. Comings has proposed that the dominantly inherited tumours may arise by the inactivation or loss of a diploid pair of regulatory genes which normally suppress the expression of a structural transforming gene (Tg). It has recently been suggested that the N-myc oncogene may serve as a transforming gene in retinoblastoma, although no such gene has yet been identified in Wilms' tumour. We now report that in four cases of Wilms' tumour, insulin-like growth factor-II (IGF-II) transcripts are highly elevated compared with the adjacent normal kidney. In addition, we have mapped the gene for IGF-II to chromosome band 11p14.1, which is in the immediate vicinity of Wg. These findings suggest that IGF-II may be involved in the aetiology of Wilms' tumour.Nature 01/1985; 317(6034):258-60. · 38.60 Impact Factor
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ABSTRACT: Wilms' tumour (nephroblastoma) is an embryonal neoplasm occurring in hereditary and spontaneous forms. Both types show rearrangements of the short arm of chromosome 11. The germ line of children with the rare inherited triad of aniridia, genito-urinary abnormality and mental retardation carry a chromosome 11 that has a deletion in its short arm (band 11p13) and these children are at increased risk of developing Wilms' tumour. Neonates with the Beckwith-Wiedemann syndrome, in which there may be duplication of the 11p13-11p15 region, are similarly predisposed. In the spontaneous form of the tumour a deletion of the 11p14 band in tumour cells, but not in normal cells, has been reported, and the development of homozygosity for recessive mutations in the 11p region is implicated in the aetiology of Wilms' tumour. In view of these chromosomal rearrangements and because Wilms' tumour is histologically indistinguishable from the early stages of kidney development, we have now examined the expression of genes localized to 11p in Wilms' tumour and human embryonic tissue. In 12 sporadic tumours examined, the expression of the gene coding for insulin-like growth factor-II (IGF-II), localized to the 11p15 region, was markedly increased relative to adult tissues, but was comparable to the level of expression in several fetal tissues including kidney, liver, adrenals and striated muscle. This may reflect the stage of tumour differentiation, but could also contribute to the malignant process, as IGF-II is an embryonal mitogen.Nature 01/1985; 317(6034):260-2. · 38.60 Impact Factor
Article: The hepatitis B virus.[show abstract] [hide abstract]
ABSTRACT: DNA recombinant technology has radically changed hepatitis B virus (HBV) virology. The genetic organization, transcription and replication of the virus are basically understood, structures of integrated HBV sequences in hepatocellular carcinoma have been characterized, and new vaccines produced by recombinant DNA technique are being developed.Nature 317(6037):489-95. · 38.60 Impact Factor