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)

beta-L-(-)-2',3'-Dideoxy-3'-thiacytidine (3TC) is a cytosine nucleoside analog that potently inhibits the replication of human and duck hepatitis B viruses and human immunodeficiency virus through the activity of its 5'-triphosphate ester metabolite. The present study examined the intracellular decay of 3TC 5'-phosphates and tested strategies for modulating the cellular content of those nucleotides in primary cultures of duck hepatocytes and in human hepatoma 2.2.15 cells and CCRF-CEM T lymphoblasts. Inhibition by deoxycytidine of the 5'-phosphorylation of 3TC in duck hepatocytes confirmed that, as in mammalian cells, deoxycytidine kinase catalyzed 3TC activation. The 5'-mono, 5'-di-, and 5'-triphosphates of 3TC underwent monoexponential elimination from duck hepatocytes and 2.2.15 cells (half-lives, 3.6 to 8.0 h). Thymidine and fludarabine, which are agents that enhance the activity of deoxycytidine kinase, were tested in strategies for increasing the cellular content of 3TC 5'-phosphates. Coordinate treatment of cells with 3TC and thymidine (50 microM) increased the content of 3TC 5'-monophosphate in duck hepatocytes and the content of 3TC 5'-di- and 5'-triphosphates in 2.2.15 cells, but enhancement of 3TC 5'-phosphate levels in CCRF-CEM cells required a higher thymidine concentration (100 microM). Fludarabine (5 microM) did not affect the contents of 3TC 5'-di- and 5'-triphosphates in duck hepatocytes, but modestly increased the contents of those nucleotides in 2.2.15 cells and CCRF-CEM cells. Nitrobenzylthioinosine (NBMPR), an inhibitor of the es facilitated diffusion nucleoside transporter, reduced the level of entry of 3TC into 2.2.15 cells and abolished inward fluxes of thymidine, adenosine, and deoxycytidine. In 2.2.15 cells and CCRF-CEM cells, NBMPR reduced the formation of 3TC 5'-di- and 5'-triphosphates and reversed the thymidine- and fludarabine-induced increases in the formation of those nucleotides. NBMPR protected against the cytotoxicity of 3TC in CCRF-CEM cells, whereas thymidine potentiated that toxicity, apparently by enhancing the formation of 3TC 5'-triphosphate. Taken together, these results indicate that deoxycytidine kinase and the es nucleoside transporter are targets for manipulation of the metabolism and activity of 3TC.
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PMID:Modulation of the metabolism of beta-L-(-)-2',3'-dideoxy-3'-thiacytidine by thymidine, fludarabine, and nitrobenzylthioinosine. 914 44

This paper reviews our current understanding of hepatitis C infection in tropical countries. Since its discovery in 1989, hepatitis C has been recognized as an important disease in many tropical countries. In Egypt the prevalence in some sections of the population may-exceed 20%. In most tropical areas, however, the epidemiology of hepatitis C infection is poorly defined. There are clear variations in the distribution of genotypes in different areas and this may be one of the factors which influence the natural history of infection in different regions of the world. Routes of infection in tropical countries are poorly defined, most carriers having no clear risk factors for infection. There is some speculation that inadequate sterilization of medical equipment may be a route of infection in some areas. A combination of factors may result in an increased risk of hepatocellular carcinoma developing in patients from the tropics infected with hepatitis C and the prognosis may be worse due to co-infection with hepatitis B and human immunodeficiency virus, both of which may lead to accelerated liver disease. Prospects for disease control are poor due to the difficulty of developing a vaccine to the virus.
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PMID:Tropical aspects of viral hepatitis. Hepatitis C. 919 45

Cirrhosis is a frequent and severe event in the course of chronic hepatitis C, but it is unclear why some patients develop cirrhosis after a given period whereas others do not. We studied a large cohort of patients with chronic hepatitis C to determine the role of the route of transmission of hepatitis C virus (HCV) in the onset of cirrhosis. Six thousand six hundred sixty-four patients were enrolled in a nationwide survey of chronic hepatitis C in France. We first randomly defined a representative sample of 30 hospitals with medical units managing patients with HCV infection. All patients with chronic hepatitis C were enrolled if hepatitis C was diagnosed or treated in these units in 1991, 1992, or 1993. A questionnaire was filled in from the patients' charts and covered demographic data, risk factors for HCV infection, clinical and histological data, hepatitis B virus (HBV) and human immunodeficiency virus status, and alcohol intake. Descriptive statistics were prepared, and factors potentially related to the onset of cirrhosis were identified by means of univariate analysis followed by stepwise logistic regression analysis. Among the patients enrolled, 21.4% had biopsy-proven cirrhosis. Prevalence of cirrhosis markedly varied according to the route of transmission of HCV. It was significantly more frequent in blood recipients (23.4%) than in drug users (7.0%). Although the occurrence of cirrhosis was dependent on disease duration, it remained more frequent in blood recipients than in drug users for a given duration. Apart from the route of transmission, excessive alcohol intake was also associated with a higher risk of cirrhosis (34.9% vs. 18.2%; P < .001), and so was HBV infection (24.6% vs. 21.1%; P < .05). These factors acted independently of the route of transmission. Hepatocellular carcinoma was observed in 3.6% of all patients and in 17.8% of cirrhotic patients, and its occurrence was strongly and mainly related to the presence of cirrhosis. In conclusion, cirrhosis occurred in about 20% of the HCV-infected patients in this study and was more frequent in blood recipients than in drug users, independently of disease duration. Expected changes in the epidemiology of HCV infection might modify the risk of developing cirrhosis and, thereafter, cancer.
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PMID:Epidemiological factors affecting the severity of hepatitis C virus-related liver disease: a French survey of 6,664 patients. The Study Group for the Prevalence and the Epidemiology of Hepatitis C Virus. 925 63

To assess the risk factors, natural history, and eligibility for curative treatment of early-detected hepatocellular carcinoma (HCC), 385 hemophiliacs who were treated with blood or plasma derivates for at least 10 years and had persistently elevated aminotransferase values underwent an annual screening with an abdominal ultrasound examination and measurement of the serum alpha-fetoprotein (AFP) level. Of these, 355 had serum antibody to hepatitis C virus (anti-HCV), 29 had anti-HCV and hepatitis B surface antigen (HBsAg), and one had HBsAg alone; 141 had serum antibody to human immunodeficiency virus (anti-HIV). During 48 months of follow-up study, six patients developed HCC. All HCC patients had a HCV-related cirrhosis and had been exposed to HCV risk at a median age of 40 years. All patients had a multicentric tumor, which was not eligible for curative treatment. Univariate analysis showed age, cirrhosis, and baseline AFP levels to be significantly associated with an increased risk of HCC. By multivariate analysis, the risk of HCC was infinite in patients with cirrhosis, 31.0 for those with baseline AFP higher than 11 ng/mL, and 17.9 for those more than 45 years of age. In conclusion, the risk of cancer was greater for patients infected later in life, particularly those with cirrhosis and high AFP. Annual screening of hemophiliacs with ultrasound and AFP fails to identify potentially curable tumors because the diagnosis is made at a late stage of the disease.
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PMID:A prospective multicenter study of hepatocellular carcinoma in italian hemophiliacs with chronic hepatitis C. The Study Group of the Association of Italian Hemophilia Centers. 945 46

To investigate the possibility of using hepatitis B virus (HBV) as a vector, the tat gene from human immunodeficiency virus type 1 (HIV-1) was inserted into the full-length HBV genome in-frame with the polymerase (pol) open reading frame in the tether region and downstream of the preS1 promoter. We demonstrated that the tat gene was expressed with full activity in transactivating the HIV-1 long terminal repeat (LTR). The expression of the tat gene in the context of the HBV genome in chicken hepatoma and human cervical carcinoma cells, however, was not as efficient as that in human hepatoblastoma cells, which reflects the cellular and species specificity of promoters of hepadnaviruses. Detection of RNA expressed from this HBVtat recombinant revealed transcription of the tat gene by two promoters: the core/pol promoter and the preS1 promoter. A Pol-Tat fusion protein expressed by the core/pol promoter did not seem to contribute to the tat transactivation activity of the HBVtat recombinant since a frameshift mutation in the pol gene did not affect the recombinant tat function. The functional tat protein, therefore, was most likely expressed as a Tat-Pol fusion product. Endogenous polymerase assays showed that the pol protein expressed from the HBVtat recombinant was still active although at a reduced level. Hepatitis B surface antigens and e antigen produced from this recombinant were detected at similar levels as those produced from the wild type. Notably, the capability of forming complete HBV particles was still retained. These studies indicate the potential of constructing HBV as a replicative vector. We also showed that manipulation of a nonreplicative HBV vector was possible. Expression of the HBV polymerase could be completely eliminated and replication of the nonreplicative HBV recombinant could be supported by Pol transcomplementation.
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PMID:Development of replicative and nonreplicative hepatitis B virus vectors. 947 57

We are giving an overview over the clinical features and different therapeutic options of HIV associated malignancies. There are three AIDS-defining malignancies: - Kaposi's sarcoma - Non-Hodgkin's lymphoma (NHL) - cervical cancer. In Kaposi sarcoma there is a broad therapeutic spectrum from cryotherapy to systemic chemotherapy depending on the site and stage of the Kaposi sarcoma. In NHL early therapeutic intervention is necessary because of the fast progress of the tumor. The cervical cancer in HIV-infected women seems to be more aggressive than in non-infected and also needs early therapeutic intervention. Many other tumors seem to occur more frequently in patients with HIV infection: anorectal cancer, malignant testicular tumors, lung cancer, Hodgkin's lymphoma, basal cell carcinoma, squamous cell carcinoma, and even malignant melanoma. The cancer incidence in HIV-patients seems to be higher among nonblacks. Most of the immunodeficiency associated tumors are virus induced and they are accompanied by a persistent viral infection, including HHV-8 in Kaposi's sarcoma; Epstein Barr virus (EBV) in NHL; and human papillomavirus (HPV) in cervical cancer. But there are also types of virus induced tumors which are not frequently associated with HIV-infection like the primary hepatocellular carcinoma in patients with hepatitis B virus infection.
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PMID:Clinical manifestations and therapies of AIDS associated tumors. 950 54

In a retrospective study of a 12-year period (1981-1992) liver histology was analyzed in 227 autopsied patients infected with the human immunodeficiency virus. Normal histology could only be documented in 29 patients (13%). In the majority of cases (56%) uncharacteristic changes were seen such as steatosis (34%), hemosiderosis (10%) or non-specific reactive hepatitis (7%). The finding of hepatic peliosis obtained in 4 patients was not associated with inflammatory liver changes, especially infections from Rochalimaea. Within a wide range of opportunistic infections recorded in 50 patients (22%), hepatitis caused by Cytomegalovirus (8%), Toxoplasma gondii (5%), Leishmania donovani (1%), Cryptococcus neoformans and Pneumocystis carinii (each 0.5%) was diagnosed. Among 16 cases (7%) of mycobacterial liver infections typical mycobacteria were found in two patients and atypical mycobacteria in 14 patients, respectively. In 23 patients (10%) chronic viral hepatitis, caused by HBV (7%) or HCV infections (3%), respectively, was observed. Hepatitis was typed as mild only in each 5 patients with HBV or HCV infection, whereas the remaining cases showed a transition towards cirrhosis. Two patients with HBV-associated cirrhosis developed hepatocellular carcinoma. The remaining 32 malignant liver tumors represented secondary neoplasms, including 13 cases of non-Hodgkin's lymphomas.
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PMID:[Liver changes in AIDS. Retrospective analysis of 227 autopsies of HIV-positive patients]. 964 44

Injection drug use is the single most important risk factor for acquiring hepatitis C virus (HCV) infection. Injection drug users acquire this infection rapidly after initiating injection practices, and up to 90% of them are chronically infected with HCV. HCV infection is a major cause of chronic liver disease, and persons infected with HCV are at risk for chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma, and they risk transmitting HCV infection to others. Preventive measures for HCV infection are limited. The heterogeneous nature of HCV and its ability to undergo rapid mutation appear to prevent the development of an effective neutralizing immune response, obstructing development of a vaccine. Prevention of HCV infection must rely on educational and programmatic efforts aimed at preventing drug use, providing substance abuse treatment for persons who inject illicit drugs, and encouraging safer injection practices. These efforts should include messages about the risk and prevention of all blood-borne pathogens, including HCV, hepatitis B virus, and human immunodeficiency virus.
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PMID:The importance of preventing hepatitis C virus infection among injection drug users in the United States. 966 17

Immunodeficiency, be it congenital, therapeutic, or infectious in origin, increases the risk of certain, but not all, types of cancer. A common feature of these cancers is that specific infectious agents appear to be important in their etiology, not only in immunodeficient subjects but also in the general population. People with acquired immunodeficiency syndrome (AIDS) are at an increased risk of Kaposi's sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, squamous cell carcinoma of the conjunctiva, and childhood leiomyosarcoma. It is striking that most of these cancers have been associated with specific human herpesvirus (HHV) infections: HHV-8 with Kaposi's sarcoma and the closely related Epstein-Barr virus with non-Hodgkin's lymphoma, Hodgkin's disease, and possibly also with childhood leiomyosarcoma. Moreover, similar associations between these viruses and cancer have been found, albeit inconsistently, in people who are not immunosuppressed. Further research is needed to establish whether the risk of other cancers is also increased in people with AIDS, although, if so, the cancers are likely to be rare or to have comparatively small associated relative risks. Existing evidence suggests that there may be no marked increase in the risk of two common cancers that are known to be caused by infectious agents--hepatocellular carcinoma and invasive carcinoma of the uterine cervix. The apparent lack of an increase in invasive cervical cancer is unexpected and needs further investigation, especially since the prevalence of cervical infection with human papillomaviruses and of low-grade preneoplastic changes in the cervical epithelium is increased in women with AIDS. With the prospect of improved survival in people with AIDS, the effect of immunosuppression on cancer is likely to become an increasingly important issue.
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PMID:Overview of the epidemiology of immunodeficiency-associated cancers. 970 94

Cutaneous horn and squamous cell carcinoma (SCC) in situ (i.e., Bowen's disease) were documented concurrently in a cat. The cat had multiple, crusted lesions and a cutaneous horn on the right dorsal lumbar area. All the crusted cutaneous lesions were diagnosed as SCC in situ. Other findings included the presence of a thymoma and hepatoma. This cat was tested, and results were negative for feline leukemia and feline immunodeficiency viruses. At necropsy (eight months after the initial diagnosis was made) the hepatoma had ruptured, resulting in exsanguination and death.
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PMID:Cutaneous horn and squamous cell carcinoma in situ (Bowen's disease) in a cat. 982 83


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