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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of the various neoplastic manifestations of human immunodeficiency virus (HIV) and the variable period between HIV infection and the development of tumors related to acquired immunodeficiency syndrome (AIDS), it is possible that certain behaviors, toxins, genes, or infectious agents--particularly viruses--may act as cofactors in the pathogenesis of AIDS-related neoplasms. Most epidemiologic and laboratory investigations of possible cofactors have been directed toward Kaposi's sarcoma (KS), by far the most common AIDS-related tumor and one closely associated with male homosexual lifestyle in the U.S. Nonetheless, epidemiologic investigations of putative associations have not demonstrated any clear association between KS and particular viruses. Furthermore, laboratory investigations, both serologic and molecular/genetic, have failed to definitively implicate as cofactors for KS these viruses: cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses, pathogenic human papillomaviruses, or human herpes virus type 6. Investigations of a suggested association between EBV and AIDS-associated non-Hodgkin's (B cell) lymphomas (NHLs) have also been inconclusive. However, HIV may act as a cofactor in accelerating the development of hepatitis B-associated hepatocellular carcinoma. In summary, viral or other cofactors have not been definitely identified as cofactors in AIDS-related tumors.
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PMID:Possible cofactors for the development of AIDS-related neoplasms. 216 69

Using cloned Epstein-Barr nuclear antigen 1 (EBNA) and oriP elements from the Epstein-Barr virus (EBV) in conjunction with liver-specific growth media, we have constructed an EBNA-producing line of well-differentiated human hepatoma cells (Hep-EBNA-2) and appropriate EBV-oriP vectors. These vectors, pBEDC1 and pBEUG1, were maintained as free extrachromosomal elements only in cells that expressed the trans-acting EBNA protein. They were readily rescued from transfected Hep-EBNA-2 cells upon transformation of recA- Escherichia coli with cellular low-Mr DNA. They are true shuttle vectors in that they can propagate as free closed circular elements in both human Hep-EBNA-2 cells and E. coli. Finally, we have demonstrated the vector capability of our shuttle system by inserting into the SV40 expression cassette of pBEUG1 a large full-length cDNA encoding coagulation factor VIII. Our data clearly show that EBV-oriP episomes are able to stably propagate in an hepatic background and that neither high levels of EBNA protein nor multiple copy episomes significantly interfere with the expression of the set of hepatic functions that have been analyzed. These results are discussed in terms of gene amplification and cloning of genes that program liver differentiation.
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PMID:Construction of an EBNA-producing line of well-differentiated human hepatoma cells and of appropriate Epstein-Barr virus-based shuttle vectors. 254 32

Hepatitis non-A, non-B (HNANB) is due to one or more transmissible agents, probably viruses. Epidemiologically, HNANB is transmitted predominantly by transfusion of blood or plasma derivatives, and percutaneous inoculation, but a non-percutaneous transmission by the fecal-oral route is also established. However, despite 10 years of intense world-wide research, the transmissible agent, or agents, have not been identified and there are no serological assays for either an antigen or an antibody that can be used to detect this infection. The clinical diagnosis of HNANB remains, therefore, a diagnosis of exclusion mainly of hepatitis A and B, Epstein-Barr virus, cytomegalovirus and drug-induced liver disease. In contrast to hepatitis A and B, the clinical and biochemical course of HNANB tends to be less severe and the proportion of asymptomatic and anicteric cases is higher, but fulminant hepatitis and fatalities also occur. Typically, there is a fluctuating waxing and waning pattern of the serum aminotransferase activities in HNANB. HNANB has a relative high tendency to progress to a chronic stage. The exact frequency of HNANB-induced liver cirrhosis and convincing evidence for an association with hepatocellular carcinoma cannot be assessed, although the persistence of the infectious agent in chronic HNANB and the existence of a chronic asymptomatic carrier state have been proved. By light microscopy there is a broad morphologic spectrum of acute and chronic viral hepatitis, but no single pathognomonic lesion exists that allows a reliable distinction to be made of HNANB from hepatitis A and B. Electron microscopy of liver biopsy specimens of chimpanzees, experimentally infected with HNANB agents, permits the visualisation of cytoplasmic changes, which appear to be specific for infection with HNANB viruses. In human liver biopsy specimens from patients with HNANB, identical ultrastructural cytoplasmic changes could not consistently be demonstrated. In contrast, intranuclear aggregates of spherical and tubular particles measuring 20-29 nm, first described in experimental HNANB in chimpanzees, have been repeatedly demonstrated in acute and chronic HNANB in man. These nuclear particles have been considered as compelling evidence of human HNANB infection. The specificity has been challenged, however, by the demonstration of identical particles in other viral and non-viral hepatopathies and in liver biopsies of healthy volunteers. By immune electron microscopy, a multiplicity of virus-like particles are described in association with HNANB.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Hepatitis non-A, non-B: epidemiologic, clinical, serologic and morphologic aspects]. 258 79

There is an increased amount of evidence to suggest that viruses play important roles in the development of certain types of human tumors. These include the hepatitis B virus in hepatocellular carcinoma, human papillomaviruses in cervical cancer, Epstein-Barr virus in Burkitt's lymphoma and nasopharyngeal carcinoma, and human T-lymphotrophic virus in adult T cell leukemia and hairy cell leukemia. These pieces of evidence have accumulated from both clinical and basic studies which have shown that these viruses are involved in some stage of the carcinogenic process. Because of the rapid development of techniques and knowledge of molecular biology, most of the gene structures of these viruses and their products have been identified. These results make it possible to understand more clearly the route of infection and have facilitated the production of vaccines, using DNA-recombinant techniques. A significant decrease in the incidence of these types of cancers is expected through prevention programs conducted throughout the general population against these viruses within 10 to 20 years. These virus-related human cancers also provide us with a good opportunity to understand the basic mechanisms involved in the development of human cancers in general. In the present paper, these points are stressed in addition to describing the recent progress made in the study on virus-related human cancers.
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PMID:[Human cancers and viruses]. 287 42

This review examines some of the evidence which aetiologically implicates various DNA viruses (primarily papillomavirus, hepatitis B virus and Epstein-Barr virus) in certain human cancers (cervical carcinoma, primary liver cell carcinoma, Burkitt's lymphoma and nasopharyngeal carcinoma, respectively). The evidence includes: presence of viral DNA, RNA and proteins in tumours (and cell lines derived from them); occurrence of viruses with apparently different oncogenic potential; their ability to transform cell lines in vitro or cause tumours in animals; epidemiological and serological data. Factors which affect the progression to cancer are briefly considered as they illustrate that there are several stages in tumorigenesis. These factors include the immune system, irradiation, presence of other viruses or carcinogens and treatment. The lack of a single unique characteristic which defines a transformed cell would be expected from the multistep hypothesis and is related to the possible virus-cell interactions that can occur. These form a continuous spectrum ranging from productive infection of a permissive cell, through infection of a non-permissive cell, to the inability of a virus to infect a cell. This spectrum may reflect the absence of increasing numbers of cellular functions necessary for productive virus infection, with cell transformation occurring as a rare type of abortive infection. The evidence, especially for human papillomavirus, indicates that it is quite probable that particular DNA viruses are the causative agents for certain human cancers. Even so other factors can play decisive roles in tumorigenesis. Final aetiological proof will only be obtained when an anti-virus vaccine eradicates one form of human cancer.
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PMID:DNA viruses and human cancer. 329 39

The effect of heparin, a polyanionic glycosaminoglycan known to alter the function of many proteins, on insulin binding and bioactivity was studied. Cultured human lymphocytes (IM-9) were incubated with varying concentrations of heparin, then extensively washed, and 125I-labeled insulin binding was measured. Heparin at concentrations used clinically for anticoagulation (1-50 U/ml) inhibited binding in a dose-dependent manner; 50% inhibition of binding occurred with 5-10 U/ml. Scatchard analysis indicated that the decrease in binding was due to a decrease in both the affinity and the apparent number of available insulin receptors. The effect occurred within 10 min at 22 degrees C and persisted even after the cells were extensively washed. Inhibition of insulin binding also occurred when cells were preincubated with heparinized plasma or heparinized serum but not when cells were incubated with normal serum or plasma from blood anticoagulated with EDTA. By contrast, other polyanions and polycations, e.g., poly-L-glutamic acid, poly-L-lysine, succinylated poly-L-lysine, and histone, did not inhibit binding. Heparin also inhibited insulin binding in Epstein-Barr (EB) virus-transformed lymphocytes but had no effect on insulin binding to isolated adipocytes, human erythrocytes, or intact hepatoma cells. When isolated adipocytes were incubated with heparin, there was a dose-dependent inhibition of insulin-stimulated glucose oxidation and, to a lesser extent, of basal glucose oxidation. Although heparin has no effect on insulin binding to intact hepatoma cells, heparin inhibited both insulin binding and insulin-stimulated autophosphorylation in receptors solubilized from these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of heparin on insulin binding and biological activity. 354 43

Immunofluorescent staining of HeLa cells with rabbit antiserum raised against isolated HeLa cell nucleoli showed bright nucleolar fluorescence. Immunoprecipitation of nuclear extracts obtained from HeLa cells labelled with 35S-methionine or 32P-orthophosphate followed by gel electrophoresis of the precipitate revealed a major band of 90 kd. This antigen, called pp90, was judged to be responsible for the nucleolar fluorescence. Serine residues were predominantly phosphorylated in pp90. Similar nucleolar fluorescence was observed commonly in human cells derived from malignant tumors including acute lymphatic leukemia, adult T-cell leukemia, hepatitis B virus-associated hepatoma, adenocarcinoma, and in 5 lymphoid cells derived from Burkitt lymphoma but not in normal human lymphocytes or liver cells. In immunoprecipitation, 32P-labelled pp90 was commonly detected as the major component in all of those cells which showed nucleolar fluorescence. Resting human embryo lung (HEL) cells were negative for both nucleolar fluorescence and pp90 in immunoprecipitation, but turned positive when stimulated to grow, suggesting the involvement of pp90 in cell growth. Antigen pp90 was also induced in human lymphocytes and HEL cells by infection with Epstein-Barr virus in human cytomegalovirus, respectively, which are known to induce cell DNA synthesis in early stages of infection. A cross-reacting nucleolar antigen was detected in 2 monkey cells but not in 3 rodent cells tested.
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PMID:A human nucleolar antigen (pp90) associated with cell growth and its induction by Epstein-Barr virus and human cytomegalovirus. 609 64

The relationship between viruses and naturally occurring cancers, such as hepatocellular carcinoma and genital cancers, is of great importance to Africa. On the other hand, lymphomas, leukaemias and immunodeficiencies, although of less immediate public health importance, constitute an area of outstanding interest for research and their association with the Epstein-Barr virus (EBV) and the newly discovered human retroviruses merits world-wide attention. EBV-related malignancies in Africa include both Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC). Whether X-linked polyclonal lymphoproliferations exist in Africa remains an open question. The interrelationship between EBV, holoendemic malaria and genetic factors (oncogenes) has been deciphered in recent years, to make BL a kind of Rosetta stone for the understanding of multistage carcinogenesis. Although the role of EBV in the causation of NPC is not well understood, the viral capsid antigen (VCA) IgA test already allows both early detection of NPC in high-incidence areas and differential diagnosis in low-incidence areas. The question whether an EBV vaccine would be of value in African countries, in relation to EBV-associated malignancies, remains an open one. The diseases associated with the recently discovered human retroviruses (human T-lymphocyte leukaemia viruses: HTLVs) represent a new area for both research and public health assessment. Limited information is available today on the geographical distribution, age prevalence and association with disease in Africa of the different members of the retrovirus family (HTLV-1, HTLV-2, LAV/HTLV-3). The proportion of HTLV-related T-cell malignancies in different parts of Africa as well as the importance of immunodeficiencies caused by the different members of the retrovirus family remain to be determined. Typical acquired immunodeficiency syndrome (AIDS) appears to exist in Central Africa, especially Zaire, and HTLVs could be of public health importance if they cause severe forms of viral, bacterial or parasitic diseases through impairment of cell-mediated immunity. Africa, is and will long remain a continent of crucial importance with regard to the role of viruses in human malignancies and especially in haematopoietic proliferative disorders.
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PMID:Virus-associated lymphomas, leukaemias and immunodeficiencies in Africa. 610 Feb 86

The immune system has evolved under Darwinian pressures as a defence against ubiquitous viruses. Immune surveillance against viral antigens protects the normal host. Individuals with inherited or acquired immune-deficiency disorders can become vulnerable to ubiquitous viruses and neoplasms can ensue, such as B-cell lymphoma, hepatocellular carcinoma, squamous-cell carcinoma, Kaposi's sarcoma, and carcinoma of the penis and uterine cervix. Immunodeficiency permits Epstein-Barr virus, hepatitis B virus, papillomavirus, herpes simplex virus, and cytomegalovirus to induce sustained target-cell proliferation. Each virus selects specific cellular targets bearing viral receptors and the infection leads to proliferation of the target cells rather than lysis. Various co-factors, including nutrition, exposure to tumour-promoting agents, parasitic infection, and ultraviolet light, may promote carcinogenesis. Depending on the type and severity of the immune deficiency, gradual proliferation may lead to evolution of a malignant clone. Conversion of polyclonal virally infected proliferating cells to give monoclonal malignancy is probably due to specific cytogenetic rearrangements which allow oncogene activation and endow an altered tumour cell with selective growth advantages over normal diploid cells. Prevention of viral oncogenesis may be possible by treatment of immune-deficient individuals with premalignant disorders. Immunotherapy and antiviral therapy may prevent progression of viral-induced proliferation to malignancy. The purpose of this paper is to discuss and evaluate the role of immune deficiency and viruses in the induction of malignancies commonly occurring in Africans residing in sub-Saharan Africa (Purtilo, 1976). The types of malignancies commonly occurring in this region are believed to be due to ubiquitous viruses. A failure of immune surveillance mechanisms to recognize viral antigens and abrogate proliferation of infected target cells predisposes to malignancy by increasing the chance of a proliferating cell undergoing a cytogenetic or molecular alteration which endows it with malignant characteristics. The immunological surveillance hypothesis has been elaborated during this century by Ehrlich, Thomas, Burnet, and Schwartz (reviewed by Purtilo & Linder, 1983). This hypothesis rests on several assumptions: that neoplastic cells possess unique tumour antigens: tumour antigens provoke an immune response in the host; and the immune response is protective and eliminates the tumour.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Squamous-cell carcinoma, Kaposi's sarcoma and Burkitt's lymphoma are consequences of impaired immune surveillance of ubiquitous viruses in acquired immune deficiency syndrome, allograft recipients and tropical African patients. 610 Feb 88

With the improved rapid sequencing techniques, the earlier sequence of U2 RNA of Novikoff hepatoma (Shibata et al, J. Biol. Chem. 250, 3909-3920, 1975) was reanalyzed and modified. The improved sequence of U2 RNA is 188 (or 189) nucleotides long and is in register with a characterized U2 RNA pseudogene (Denison et al, PNAS 78, 810-814, 1981) except for an 11 nucleotide sequence (nucleotides 147-157) which is absent from the pseudogene. From these results, a secondary structure of U2 RNA is proposed which is supported by the preferred cleavage sites with T1-RNase, RNase A and S1 nuclease. Isolated U2 RNA was cleaved by T1-RNase preferentially at positions 64 and 164, whereas U2 RNA in U2-snRNP was cleaved only at position 64, indicating that position 164 is protected in U2-snRNP. As with U1 RNA (Epstein et al, PNAS 78, 1562-1566, 1981) the 5'-end of isolated U2 RNA was not preferentially cleaved by T1-RNase.
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PMID:Primary and secondary structure of U2 snRNA. 679 40


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