Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To target gene expression to malignant hepatic cells, we have constructed recombinant retroviral vectors containing a reporter gene encoding nuclear beta-galactosidase (nls-LacZ) under transcriptional control of regulatory sequences from the rat alpha-fetoprotein (AFP) or human insulinlike growth factor II (IGFII) genes. The AFP and IGFII P3 promoters activate transcription during fetal development and are often reactivated in hepatocellular carcinoma (HCC). Infection of several cultured cell types with the retroviral vector containing the IGFII P3 sequence resulted in expression of the reporter gene in all cell lines tested, including those that do not produce IGFII. In contrast, selective expression was achieved by vectors containing the AFP transcriptional regulatory sequence. Nuclear beta-galactosidase activity was detectable in cells from lines that produce AFP, and not in cells that do not express the AFP gene. In most infected cell lines, retroviral RNA synthesis from the 5' LTR was inhibited, and deletion of the retroviral LTR enhancer did not change expression from either the IGFII P3-nls-LacZ or the AFP-nls-LacZ cassettes. After treatment of cells with 12-O-tetradecanoylphorbol-13-acetate and epidermal growth factor (EGF), the decrease in concentrations of endogenous AFP messenger RNA (mRNA) and nls-LacZ mRNA transcribed from the transferred AFP regulatory sequence were similar. In the context of an integrated provirus, the AFP transcriptional regulatory sequence is therefore subject to similar regulatory control as that of the endogenous gene. These data show that the AFP sequence, and not the IGFII P3 promoter we used, is suitable for targeting gene expression to malignant hepatic cells.
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PMID:Hepatoma cell-specific expression of a retrovirally transferred gene is achieved by alpha-fetoprotein but not insulinlike growth factor II regulatory sequences. 748 90

In Viet Nam cancer education has a low priority because of political and social factors. Knowledge about cancer staging and basic management principles is stagnated by restricted communication with foreign colleagues and by limitations of available techniques. Participation in either formal residency programs or conferences for continuing education outside Viet Nam is restricted to select individuals of high rank. Most foreign experience is gained from Russia or from the former Eastern-bloc nations. Available foreign textbooks and journals are limited to those published more than 20 years ago. Infectious diseases are the most significant health problem in Viet Nam and they indirectly contribute to the incidence of cancer, including the occurrence of hepatocellular carcinoma. A widespread epidemic of acquired immune deficiency syndrome (AIDS), acquired both outside and within the medical system, is another potential consequence of current health care practices. The need for an international exchange of scientific knowledge is dramatically reinforced through the identification of significant deficits in available medical care and the patterns of mortality in this restricted society.
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PMID:Cancer education in Viet Nam: a need for foreign input. 773 84

Our aim was to verify whether the presence of antibodies to HCV envelope protein might mark the occurrence of liver damage, as recently suggested in the literature. Sera from 104 patients (62 male, 42 female) were tested: 84 were positive and 20 were negative to a second generation enzyme immunoassay for anti-HCV antibodies; 51 patients had mild chronic liver disease (44 chronic hepatitis, seven steatosis), 43 had liver cirrhosis (superimposed by hepatocellular carcinoma in 18) and ten were asymptomatic anti-HCV positive subjects with normal liver function tests. Besides, all sera were tested by means of an enzyme immunoassay for the presence of serum antibodies to the synthetic peptide S24A (SIYPGHVSGH RMAWDMMMNW SPTA) derived from amino acids 307-330 of HCV polyprotein. Anti-S24A antibodies were detected in 40/84 sera positive and 1/20 negative at anti-HCV testing (Pearson chi 2 12.29; p = 0.005). Among anti-HCV positive sera, no significant difference existed in anti-S24A status with regard to clinical evidence of liver disease, ALT concentration or HCV RNA positivity. Thus, anti-S24A antibodies are detectable in approximately half of HCV-positive sera, but they do not seem to add significant clinical information to existing tests or to be useful as putative markers of viraemia.
Infection
PMID:Anti-envelope antibodies in anti-hepatitis C virus (HCV) positive patients with and without liver disease. 753 99

Vaccine therapy is now used in various infectious diseases. The hepatitis B virus (HBV) leads to chronic infection in around 5% of patients with a high risk of chronic active hepatitis which may result in cirrhosis and hepatocellular carcinoma. The partial efficacy of antiviral therapies (40% of sustained inhibition of HBV replication), their cost, the numerous side effects and the immune-mediated pathology of HBV infection explain the emergence of new immune therapies in treating HBV infection. Experimental and clinical arguments are in favor of vaccine therapy in HBV chronic infection. Thirty-two consecutive chronic HBsAg carriers with chronic hepatitis and detectable serum HBV DNA were given 3 standard injections of the GenHevac B vaccine at one month intervals. Six months after the first injection, 12 patients (37.5%) had undetectable HBV DNA while 3 others showed significant decrease in HBV DNA titers. Eight of these 15 responders received a standard course of alpha-interferon (5 MU thrice weekly subcutaneously for 4 months) and all still had undetectable HBV replication. By contrast, among 13 (of the 17) non responders to vaccine who were given alpha-interferon, only 3 stopped HBV replication. In summary, serum HBV DNA disappeared in 18 of the 32 patients (53.1%) who were given vaccine therapy, with or without interferon. Vaccination was uneventful. Active immune therapy against HBV appears as efficient and less expensive than antiviral therapies in stopping HBV replication. Such a result should be confirmed by controlled randomized trials.
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PMID:Immunotherapy of chronic hepatitis B by anti HBV vaccine. 764 80

The hepatitis C virus (HCV), a single-stranded RNA virus, is the major cause of posttransfusion hepatitis. HCV isolates differ in nucleotide and amino acid sequences. Nucleotide changes are concentrated in hypervariable regions and may be related to immune selection. In most immunocompetent persons, HCV infection is diagnosed serologically, using antigens from conserved regions. Amplification of RNA may be necessary to detect infection in immunosuppressed patients. Transmission by known parenteral routes is frequent; other means of spread are less common and may represent inapparent, percutaneous dissemination. Infection can lead to classical acute hepatitis, but most infected persons have no history of acute disease. Once infected, most individuals apparently remain carriers of the virus, with varying degrees of hepatocyte damage and fibrosis ensuing. Chronic hepatitis may lead to cirrhosis and hepatocellular carcinoma. However, disease progression varies widely, from less than 2 years to cirrhosis in some patients to more than 30 years with only chronic hepatitis in others. Determinants important in deciding outcome are unknown. Alpha interferon, which results in sustained remission in selected patients, is the only available therapy. Long-term benefits from such therapy have not been demonstrated. Prevention of HCV infection by vaccination is likely to be challenging if ongoing viral mutation results in escape from neutralization and clearance.
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PMID:Hepatitis C: progress and problems. 783 3

We have presented a working hypothesis showing the possible interrelations between proliferative, aproliferative and autoimmune disorders that may follow infection with lymphotropic herpesviruses. Aproliferative disorders in this context may also indicate immune or hematopoietic deficiency. Although this hypothesis can currently be best documented with the lymphotropic viruses (herpesviruses as well as similarly HTLV and HIV), the model may apply as well--with certain variations--to other viral infections such as with hepatitis virus B or C with acute or chronic infectious diseases, post-infectious arthritis, aplastic anemia, and other autoimmune liver diseases, as well as neoplastic diseases (hepatocellular carcinoma, chronic lymphocytic leukemia). The working hypothesis as depicted in Figure 2 permits a preview of which combinations of symptoms may occur in an individual disease independent of its initial classification and what clinical testing should be done respectively, and it also permits certain prognostic considerations. The above-mentioned transitions or combinations of various disease patterns have been repeatedly described in the medical literature (to refer to only a few examples: APL and MPD, HD and MDS, SLE and aplastic anemia, SLE and Kikuchi's disease; 23, 80-83). Finally the hypothesis can ideally serve as the basis for future planning of clinical research.
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PMID:A unifying concept of viral immunopathogenesis of proliferative and aproliferative diseases (working hypothesis). 789 76

Infection with hepadnaviruses and exposure to dietary aflatoxin are considered major risk factors in the development of hepatocellular carcinoma (HCC) both in humans and in animals. Recently, a broad range of mutations in the p53 tumor suppressor gene has been reported in human HCCs, predominantly from hepatitis B virus carriers in areas with either high or low levels of exposure to dietary aflatoxin. To determine whether p53 mutations are common to HCCs of hosts infected with related hepadnaviruses with and without treatment with aflatoxin, we studied the occurrence of mutations in the p53 gene in HCCs of ground squirrels and woodchucks with history of infection with ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus, respectively. Sequencing of wild type p53 genes from ground squirrels and woodchucks revealed remarkable homology between the two species with only a few amino acid differences in exons 4, 8, and 9. Using direct polymerase chain reaction sequencing, we analyzed the state of the p53 gene (exons 4-9) in 20 HCCs from ground squirrels (2 uninfected, 7 with past, and 11 with ongoing infection with GSHV) and in 11 HCCs from woodchucks persistently infected with woodchuck hepatitis virus. Five GSHV carrier and two uninfected ground squirrels received i.p. administration of aflatoxin B1. We detected only one mutation in the p53 gene of the tested animals. This mutation was located in codon 176 of exon 5 in the HCC of a GSHV-positive ground squirrel treated with aflatoxin. Mutation was caused by a G to T transversion in the second position of the codon, resulting in the replacement of cysteine with phenylalanine, and was accompanied by a tumor-specific loss of heterozygosity. p53 allelic amino acid variation with sequences coding for aspartic acid or asparagine was present in codon 61 in the variable region of exon 4 in both HCCs and nonneoplastic tissues of ground squirrels. In view of the considerably lower apparent rate of mutations in comparison to human HCCs, we suggest a less important role for aflatoxin in the induction of p53 mutations in HCCs of ground squirrels. Alternatively, etiological factors other than p53 mutations may be of greater significance in the development of HCC in ground squirrels and woodchucks.
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PMID:State of the p53 gene in hepatocellular carcinomas of ground squirrels and woodchucks with past and ongoing infection with hepadnaviruses. 792 76

Indeterminate pulmonary nodules (IPN) in transplant patients create a diagnostic and therapeutic challenge. Patients who are transplant candidates or have already undergone organ transplantation require diagnostic clarification of IPN which may represent oncologic and/or infectious disease processes. Between December 1991 and January 1993, we performed 43 needle-localized thoracoscopic resections (NLTR) on 40 patients for IPN considered too small for less invasive diagnostic techniques. Four of these patients were candidates for orthotopic liver transplantation (OLT) and required exclusion of either extrahepatic malignancy or pulmonary infection before proceeding with transplantation. The 5th patient had undergone OLT for an unresectable hepatocellular carcinoma, and NLTR confirmed the presence of pulmonary metastatic disease. Of the 4 OLT candidates, 2 had pathologically confirmed metastases from their primary hepatic malignancy and did not undergo transplantation. The remaining 2 OLT candidates had benign pulmonary processes (hamartoma, hyaline plaque) and underwent successful OLT. In all patients, the IPN was successfully identified with NLTR. There were no complications. NLTR is a reliable and well-tolerated method to diagnose IPN in transplant patients.
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PMID:Needle-localized thoracoscopic resections of small indeterminate pulmonary nodules in transplant patients. 794 43

The infectibility of the regenerating rat liver by ecotropic retroviruses was studied relative to the expression of the gene coding for the ecotropic retrovirus receptor (Ecor) that functions as a cationic amino acid transporter. It is known that the gene for the receptor is expressed in primary hepatocytes and hepatoma cells but is absent in adult liver cells. Isolation of a 2.85-kb cDNA for the rat Ecor suggested that the rat viral receptor is 97% homologous to the mouse viral receptor and that it contains the envelope-binding domain that determines the host range of ecotropic murine retroviruses. This explains the efficient infection of rat cells by ecotropic retroviruses. Since cell division is required for liver cells to be infected, we determined the susceptibility of the regenerating rat liver to infection at different time points after partial hepatectomy (0 to 24 h) in relation to the presence of receptor mRNA. Infection of the liver occurred only when the liver was exposed to virus 4 h after partial hepatectomy. This time course of infection paralleled expression of the gene for the Ecor, which was rapidly induced between 2 and 6 h during liver regeneration. However, expression of the dormant receptor gene in quiescent liver cells can be induced by insulin, dexamethasone, and arginine, indicating that cell division is not required for expression of the receptor gene in liver cells. A diet high in carbohydrate (low in protein) significantly increased the concentration of receptor mRNA in liver cells, indicating that hormones play a role in the regulation of expression of this gene in vivo. We conclude that the gene for the viral receptor is expressed in the regenerating and quiescent liver when the urea cycle enzymes are down regulated. The infection of the regenerating rat liver by ecotropic retroviruses at the time point of expression of the receptor gene supports the requirement of expression of this transporter for infection.
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PMID:Hormonal regulation of the gene for the type C ecotropic retrovirus receptor in rat liver cells. 810 22

The levels of natural antibody against Thomsen-Friedenreich (TF) antigen in sera of patients with various cancers and infectious diseases were examined by an enzyme-linked immunosorbent assay (ELISA) and compared with those of healthy donors. The levels of antibody against TF antigen in sera of patients with adenocarcinomas such as gastric, pancreatic and colorectal cancers were lower than those of patients with hepatoma, pyelonephritis and pneumonia. These findings may reflect the expression of TF-antigen in adenocarcinoma tissues.
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PMID:Natural antibody against Thomsen-Friedenreich antigen in sera of patients with carcinomas and infectious diseases. 815 84


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