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)

The anti-AIDS agent, AZT (3'-azido-3'-deoxythymidine), is mutagenic in a cultured human hepatoma cell line designated HepG2 at the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) locus. Using an exposure time of 3 hr, the number of mutants per 10(6) surviving cells increased as a function of AZT dose from 125 to 520. Chinese hamster ovary cells, in contrast, are not affected with respect to this endpoint when similar concentrations of AZT are used (i.e., 0.1 to 10 mg/ml). The aminothiol WR-151326 [3-(3-methylaminopropylamino) propanethiol dihydrochloride] was evaluated as a possible antimutagen for use with AZT. At a concentration of 4 mM, WR-151326 was added either concomitantly or following exposure of HepG2 cells to a 5 mg/ml concentration of AZT. Regardless of the treatment condition, WR-151326 was effective in reducing the mutagenic effects of AZT by about a factor of 2. Correcting for background mutations, the mutation frequencies determined were: AZT only for 3 hr, 110 x 10(-6) (S.E.M. +/- 6.0 x 10(-6)); AZT together with WR-151326 for 3 hr, 57 x 10(-6) (S.E.M. +/- 3.0 x 10(-6)); and AZT for 3 hr followed by WR-151326 for 3 hr, 68 x 10(-6) (S.E.M. +/- 5.0 x 10(-6)). This study demonstrates that AZT is mutagenic to a cell line of human origin and that WR-151326 can protect against this mutagenic process.
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PMID:Protection against AZT-induced mutagenesis at the HGPRT locus in a human cell line by WR-151326. 154 55

Patients with the acquired immunodeficiency syndrome are at risk to develop a variety of different cancers. Based on epidemiological data, Kaposi's sarcoma and non-Hodgkin's lymphoma have been clearly associated with infection by the human immunodeficiency virus (HIV). Additional cancers such as basal cell and squamous cell carcinomas, melanoma, and hepatocellular carcinoma have also been reported to be associated with a diagnosis of acquired immunodeficiency syndrome. A direct causal role of HIV has yet to be established for any of these cancers. We now report that transgenic mice carrying the HIV tat gene develop a high incidence of hepatocellular carcinoma after a long latency and that these changes in the liver are likely to be initiated by extrahepatic growth signals from the tat expressing cells in these mice. We predict that as acquired immunodeficiency syndrome patients begin to respond to therapy and show prolonged survival, such "secondary" malignancies induced by HIV will become increasingly prevalent.
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PMID:Liver cancer in transgenic mice carrying the human immunodeficiency virus tat gene. 174 42

In populations with non-HIV immunodeficiency, non-Hodgkin lymphoma and soft tissue sarcoma, especially Kaposi's sarcoma, are the most prominent tumours, but Hodgkin's disease, gastric carcinoma, squamous cell skin cancer, malignant melanoma, hepatoma, myeloid leukaemia and/or colorectal carcinoma have been linked in various studies. Population based cancer registries and cohort studies of HIV infected persons have generally failed to detect HIV related increases in total cancer incidence or in specific tumours other than non-Hodgkin lymphoma and Kaposi's sarcoma; however, associations with anal carcinoma, hepatoma and Hodgkin's disease have been suggested by some studies. Although not indicating increased risk, HIV induced immunosuppression has been linked to an acceleration of cervical and anal neoplasia and to increased aggressiveness of Hodgkin's disease with a relative excess of the mixed cellularity type. Advances in treatment for HIV infection will delay progression to AIDS and may allow an altered natural history to emerge, including the occurrence of excesses of additional cancer types.
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PMID:HIV infection and cancers other than non-Hodgkin lymphoma and Kaposi's sarcoma. 182 20

Serum from control or partially hepatectomized rats contains only two substances associated with stimulation of DNA synthesis in primary cultures of hepatocytes in serum free conditions. Hepatopoietin A is a large (105,000 kDa in monomeric form) heparin binding growth factor that is a heterodimer of two polypeptide chains (70,000 and 35,000 kDa). Another heparin binding growth factor, acidic FGF, also stimulates hepatocyte DNA synthesis but at a level comparable to half that of HPTA. These findings, along with recent observations of stimulation of liver growth and hepatoma formation in mice transgenic for the tat gene of the AIDS virus and overproducers of the heparin binding factor hst/KS3, raise the issue of the overall importance of different heparin binding growth factors in the control of hepatic growth regulation. Hepatopoietin B is a glycolipid that also acts as a complete hepatocytic mitogen. The role of the above substances as well as the role of norepinephrine, acting as a mitogenic trigger for stimulation of the rapid early phenomena associated with liver regeneration, is discussed.
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PMID:Hepatopoietins A and B and hepatocyte growth. 182 65

For developing countries, the cost-benefit of vaccination to control the hepatitis B virus (HBV) infection is great since the acute infection is generally subclinical and the benefit is the prevention of small numbers of cases of cirrhosis and hepatocellular carcinoma. Since the pattern of HBV infection in Africa is such that compared with southeast Asia, the infection occurs later in childhood and spread is horizontal rather than vertical. Investigation of method of spread of HBV may result in a means of control other than by vaccination. In the interim, due to the overlap in means by which HBV and human immunodeficiency virus (HIV) are spread, it could be worthwhile to take advantage of existing AIDS prevention programs to educate people about how to avoid both HBV and HIV infections.
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PMID:How AIDS forces reappraisal of hepatitis B virus control in sub-Saharan Africa. 167 Aug 83

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

In the presence of aplastic anemia (AA), therapeutic choices should be determined while taking into account not only changes for immediate improvement, but also both the risks for late-occurring complications and the following quality of life. We report here data concerning a long-term clinical survey (5 to 18 years with a median of 12 years) including 156 nongrafted patients receiving androgen therapy; all patients were alive more than 5 years after diagnosis (40% of patients included at time of diagnosis in our multicentric analysis). Between the 5th and the 13th year follow-up, 21 patients died of various causes either related to AA or to its treatment: 12 of infection or hemorrhage secondary to pancytopenia (6 relapses and 6 that had never been improved; 2 with paroxysmal nocturnal hemoglobinuria [PNH]); 5 of leukemia; 1 of a non-Hodgkin's lymphoma; 2 of late side effects following transfusion (1 acquired immunodeficiency syndrome and 1 chronic B hepatitis); and a single case of myocardial infarction (the latter could possibly result of androgen therapy). Thirteen patients in total developed PNH (among which 10 had clinical symptoms including 2 deaths, and 3 exhibited only biologic abnormalities). Few long-term side effects of androgens could be noticed. Adult height was normal in patients treated during childhood and so was young women's fertility. No malignant hepatoma occurred. This survey allows the recording of late spontaneous hematologic improvement (between 5 and 10 years of evolution). This occurred in 50% of patients that had remained cytopenic 5 years after diagnosis. Although bone marrow stem cell concentration remained abnormal after 10 years of evolution. 85% of patients had a normal red blood cell count, 80% a normal polymorphonuclear count, and 66% a normal platelet count. All patients who did not show late complications had an excellent quality of life.
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PMID:Long-term (5 to 20 years) Evolution of nongrafted aplastic anemias. The Cooperative Group for the Study of Aplastic and Refractory Anemias. 225 96

The effects of suramin, an antiparasitic agent, upon in vitro hepatitis B surface antigen production by the human hepatoma cell line PLC/PRF/5 and hepatitis B virus associated DNA polymerase activity in the serum of a chronically infected patient were examined. Treatment with suramin resulted in decreases in hepatitis B surface antigen production and hepatitis B-virus associated DNA polymerase activity. The decrease in hepatitis B surface antigen production was paralleled by a general decrease in hepatoma cell viability and cellular protein synthesis. Although the inhibitory effects of suramin for hepatitis B virus appear to be nonspecific as demonstrated in these two in vitro systems, the recently announced trial of suramin for the treatment of the acquired immunodeficiency syndrome should afford an unusual opportunity to evaluate the effectiveness of suramin in the treatment of chronic hepatitis B virus infection.
AIDS Res 1986 Feb
PMID:Effects of suramin on in vitro HBsAg production by PLC/PRF/5 cells and hepatitis B virus DNA polymerase activity. 242 68

In the United States, New York City has had the greatest number of subjects at risk of AIDS for the longest period of time. This population therefore serves as an indicator of changes in cancer risk which may emerge among persons at risk from AIDS. Using a proportional incidence method, we surveyed cancers occurring among single (a surrogate for homosexual) young men and married young men in Manhattan, the rest of New York City, and the remainder of New York State. The baseline period was established earlier to be 1973-76, during which time no cases of Kaposi's sarcoma were observed among single men in Manhattan. By 1985, the frequency of Kaposi's sarcoma in this group was increased 1,850-fold (compared with expected cases derived from other registries). In the same group, the increase of non-Hodgkin's lymphoma was 6.2-fold (p for trend less than 0.0001), with excesses of Burkitt's lymphoma and immunoblastic lymphoma being most noticeable. Diagnoses of Hodgkin's disease increased markedly in 1985 but not earlier. Since this pattern did not follow that of the AIDS epidemic in this area, we suggest that Hodgkin's disease is not an AIDS-associated tumor. Hepatoma was diagnosed more frequently in single young men during the 1980s but similar increases also were observed in married men and thus may be unrelated to AIDS. Thus, only Kaposi's sarcoma and non-Hodgkin's lymphoma appear to be AIDS-associated tumors, at least so far. With better treatment and longer survival, it remains possible that other tumors will emerge as part of the AIDS epidemic.
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PMID:Cancer among New York men at risk of acquired immunodeficiency syndrome. 273 9

Haemophilia B, or Christmas disease, is an inherited X-chromosome-linked bleeding disorder caused by a defect in clotting factor IX and occurs in about 1 in 30,000 males in the United Kingdom. Injection of factor IX concentrate obtained from blood donors allows most patients to be successfully managed. However, because of impurities in the factor IX concentrate presently in use, this treatment involves some risk of infection by blood-borne viruses such as non-A, non-B hepatitis and the virus causing acquired immune deficiency syndrome (AIDS). Because of the recent concern about the increasing incidence of AIDS amongst haemophiliacs, a factor IX preparation derived from a source other than blood is desirable. Here, we report that after introduction of human factor IX DNA clones into a rat hepatoma cell line using recombinant DNA methods, we were able to isolate small amounts of biologically active human factor IX.
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PMID:Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells. 298


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