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)

One of the major challenges facing gene therapy is the development of vectors targeting specific cell types. Restricting gene delivery to the relevant cell type leads to reduced T-cell responses to transgene products and prolonged gene expression. In this study, we demonstrate that vectors derived from human immunodeficiency virus (HIV) can be pseudotyped with Sendai virus fusion protein F. Such vectors transduced human hepatoma cells and primary human hepatocytes efficiently, but not non-liver cells. Several different approaches were also taken to significantly increase the titer of the pseudotyped vector. These studies may facilitate HIV vector-mediated gene delivery into liver in vivo.
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PMID:Preferential transduction of human hepatocytes with lentiviral vectors pseudotyped by Sendai virus F protein. 1202 61

Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease.
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PMID:Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics. 1208 18

1. End-stage liver disease associated with hepatitis C virus (HCV) infection has become the leading indication for liver transplantation in the United States. 2. Patients with end-stage liver disease caused by HCV may have such associated comorbidities as chronic alcoholism, steatosis, or coinfection with human immunodeficiency virus 1 or other hepatitis viruses. These comorbidities may accelerate disease progression. 3. As chronic hepatitis C progresses to cirrhosis, the risk for the development of hepatocellular carcinoma increases; this poses difficult management problems. 4. As patients who underwent transplantation for end-stage liver disease caused by HCV infection are followed up long term, it has become clear that patient and graft survival are decreased compared with HCV-negative patients or those with cholestatic liver disorders. 5. Risk factors associated with a worse outcome after transplantation include host, viral, donor, and posttransplantation factors. 6. Major challenges to be addressed in the future include delineation of the optimal antiviral therapy and how to handle the need to perform retransplantation on patients who develop graft dysfunction as a result of HCV recurrence.
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PMID:Hepatitis C: magnitude of the problem. 1236 91

We examined testing, referral, and treatment of patients with hepatitis C among HIV-infected patients in the Veterans Aging 3-Site Cohort Study by using patient- and provider-completed surveys and laboratory, pharmacy, and administrative records from the Department of Veterans Affairs electronic medical record. Of 881 human immunodeficiency virus-positive patients, 43% were coinfected with hepatitis C virus. Of these, 88 (30%) reported current alcohol consumption. Only one-third were counseled to reduce or stop alcohol consumption. Coinfected patients with indications for hepatitis C treatment had a high rate of contraindications, including both medical and psychiatric comorbidities. Of the 65 patients with indications for hepatitis C therapy and free of contraindications for treatment, only 18% underwent liver biopsy and 3% received IFN. Although treatment indications are common in this population, contraindications are also common. Health care providers are often unaware of alcohol consumption that may accelerate the course of hepatitis C, increase the risk of hepatocellular carcinoma, and reduce treatment efficacy.
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PMID:Testing, referral, and treatment patterns for hepatitis C virus coinfection in a cohort of veterans with human immunodeficiency virus infection. 1268 17

After the introduction of second generation ELISA and confirmatory tests clinically available, it was possible to determine that prevalence of infection with HCV was 98% among hemophiliacs exposed to factor VIII concentrates that weren't submitted to viral inactivation. Liver failure is 4.2 times more probable among patients also infected with HIV. The hepatocellular carcinoma studies show similar findings. They report a rate of 1.4 for every 1,000 hemophiliacs, and almost all patients have antibodies for hepatitis C virus. The studies with hemophiliacs exposed to unsafe blood products for HCV showed a significant increase in mortality from different liver diseases, as compared to control subjects. Mortality rate shows an important increase in the hemophiliacs also infected with human immunodeficiency virus. Combination therapy (ribavirin and interferon) doesn't seem to make a difference in the response rate as compared to patients without hemophilia. In spite of the best efforts to improve the safety of factor VIII concentrates, it has been impossible to eliminate the risk of transmission of other infective agents. That's why it seems that recombinant technology will be the answer in obtaining the concentrates.
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PMID:[Hepatitis C virus infection in patients with hemophilia]. 1271 60

From the seeds of the Yunnan bean, we purified an antifungal peptide using affinity chromatography on Affi-gel blue gel, FPLC-ion exchange chromatography on Mono S, and FPLC-gel filtration on Superdex 75. The antifungal peptide was adsorbed on Affi-gel blue gel at pH 7.8 and Mono S at pH 4.5. It exhibited a molecular mass of 6.5 kDa in both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its N-terminal sequence closely resembled defensin-related peptides. The peptide exerted antifungal activity toward the fungal species Fusarium oxysporum and Mycosphaerella arachidicola, with an IC50 of 2 microM for the former fungus and 10 microM for the latter. It manifested a weaker mitogenic activity toward murine splenocytes than Concanavalin A. It also displayed antiproliferative activity on a murine leukemia (L1210), a hepatoma (HepG2), and a murine leukemia (M1) cell line. It inhibited human immunodeficiency virus-1 reverse transcriptase with an IC50 of 200 microM.
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PMID:Gymnin, a potent defensin-like antifungal peptide from the Yunnan bean (Gymnocladus chinensis Baill). 1449 73

The X-linked hyper-IgM (XHIGM) syndrome is an uncommon primary immunodeficiency disease caused by mutations in the gene for CD40 ligand and characterized by normal or elevated serum IgM, reduced levels of IgG and IgA, and defective T-cell function. Because of its rarity, it has been difficult for any single investigator or institution to develop a comprehensive clinical picture of this disorder. Accordingly, a national registry was developed in the United States to provide demographic, genetic, immunologic, and clinical information on a relatively large number of patients with the XHIGM syndrome.A total of 79 patients from 60 unrelated families were registered between January 1997 and July 2002. The estimated minimal incidence was approximately 1/1,030,000 live births. All of the patients had significant IgG deficiency and most had IgA deficiency, but only one-half had elevated IgM levels. Most patients presented initially with a history of an increased susceptibility to infection including Pneumocystis carinii pneumonia. The average age of diagnosis was significantly earlier in patients born into a family with a previously affected individual. However, only one-third of the patients born into a family with a previously affected individual were diagnosed exclusively because of the presence of the positive family history before any clinical symptoms developed. Over half the patients developed symptoms of immunodeficiency and were diagnosed by 1 year of age, and over 90% by 4 years of age. The most prominent clinical infections were pneumonia (81% of patients), upper respiratory infections (49%) including sinusitis (43%) and recurrent otitis (43%), recurrent/protracted diarrhea (34%), central nervous system infections (14%), sepsis (13%), cellulitis (13%), hepatitis (9%), and osteomyelitis (1%). In addition to infections caused by encapsulated bacteria, opportunistic infections were relatively common and were caused by P. carinii, members of the herpes virus family (including cytomegalovirus), Cryptosporidium, Cryptococcus, Candida, Histoplasma, and Bartonella. Sclerosing cholangitis occurred in 5 patients and in 4 of these was associated with Cryptosporidium infection. Eight patients had died at the time of their entry into the Registry; 2 of pneumonia (1 P. carinii and 1 cytomegalovirus), 2 of encephalitis (1 ECHO virus and 1 cytomegalovirus), 2 of malignancy (both hepatocellular carcinoma), 1 of sclerosing cholangitis caused by Cryptosporidium, and 1 of hemolytic uremic syndrome.
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PMID:The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. 1466 87

CD81 has been described as a putative receptor for hepatitis C virus (HCV); however, its role in HCV cell entry has not been characterized due to the lack of an efficient cell culture system. We have examined the role of CD81 in HCV glycoprotein-dependent entry by using a recently developed retroviral pseudotyping system. Human immunodeficiency virus (HIV) pseudotypes bearing HCV E1E2 glycoproteins show a restricted tropism for human liver cell lines. Although all of the permissive cell lines express CD81, CD81 expression alone is not sufficient to allow viral entry. CD81 is required for HIV-HCV pseudotype infection since (i) a monoclonal antibody specific for CD81 inhibited infection of susceptible target cells and (ii) silencing of CD81 expression in Huh-7.5 hepatoma cells by small interfering RNAs inhibited HIV-HCV pseudotype infection. Furthermore, expression of CD81 in human liver cells that were previously resistant to infection, HepG2 and HH29, conferred permissivity of HCV pseudotype infection. The characterization of chimeric CD9/CD81 molecules confirmed that the large extracellular loop of CD81 is a determinant for viral entry. These data suggest a functional role for CD81 as a coreceptor for HCV glycoprotein-dependent viral cell entry.
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PMID:CD81 is required for hepatitis C virus glycoprotein-mediated viral infection. 1472

Due to shared risk factors for transmission, coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a very common event. The prevalence of HCV infection among HIV-positive patients averages about 35% in the United States and Europe, but in clinical populations where there is a great prevalence of intravenous drug use as a risk factor for acquiring HIV, this value may be as high as 80-90%. Several studies have confirmed that HIV coinfection accelerates the natural course of chronic hepatitis C and an increased risk of liver cirrhosis, hepatocellular carcinoma, and decompensated liver disease has been found in coinfected subjects. Other studies have shown an increased risk of progression to acquired immunodeficiency syndrome (AIDS) and AIDS-related death among HIV-HCV-positive persons, suggesting that HCV coinfection may accelerate the course of HIV disease. In addition, hepatitis C may affect the management of HIV infection, increasing the incidence of liver toxicity associated with the antiretroviral regimens. The optimal therapeutic approach to HCV infection in HIV coinfected patients is still uncertain, because of the complex pathogenesis of both infections, potential drugdrug interactions, and the poor literature and information available about safety and efficacy of an interferon (IFN) and ribavirin combination in this clinical population. Available data show that the sustained virological response rates in coinfected persons treated with standard IFN plus ribavirin range from 18-40%, and several studies with pegylated IFN plus ribavirin are ongoing.
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PMID:Human immunodeficiency virus and hepatitis C virus coinfection: epidemiology, natural history, therapeutic options and clinical management. 1500 41

Spontaneous hepatobiliary tumors in non-human primates are uncommon. Here we report a case of hepatic carcinoma and a case of hepatic focal nodular hyperplasia (FNH) and myelolipoma in two captive chimpanzees. A 16-year-old male chimpanzee (4X0392) died after an 8-month history of hepatic amyloidosis and low-grade anemia. Necropsy findings included a hepatic neoplasm with highly pleomorphic hepatocytes arranged into irregular thickened trabeculae. The diagnosis was high-grade hepatocellular carcinoma. A second male chimpanzee (4X0080), 23 years of age, died suddenly of heart failure secondary to cardiomyopathy. An incidental finding at necropsy was a liver mass characterized by multinodularity, prominent fibrous septa, and biliary hyperplasia. These features were consistent with FNH. While 4X0392 had no history of experimental viral exposure, 4X0080 was vaccinated with inactivated hepatitis B virus, an attenuated hepatitis A virus, and was experimentally infected with hepatitis C virus and human immunodeficiency virus. A survey of the literature revealed 68 reported cases of hepatobiliary tumors in non-human primates, including 12 hepatocellular adenomas, eight cholangiocellular adenomas/cystadenomas, 22 hepatocellular carcinomas, seven cholangiocarcinomas, and seven gallbladder adenocarcinomas. The majority of reported cases have been in prosimians and Old World monkeys. Hepatic neoplasia is rare in chimpanzees. Only four hepatic neoplasms have been reported in chimpanzees, three of which were associated with viral hepatitis. FNH has not been previously described in any non-human primate.
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PMID:A case report of hepatocellular carcinoma and focal nodular hyperplasia with a myelolipoma in two chimpanzees and a review of spontaneous hepatobiliary tumors in non-human primates. 1506 32


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