Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular epidemiological studies of populations at high risk for liver cancer have shown that hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure are two major risk factors for this disease. These etiological agents, combined with nutritional deficiencies, are important for the initiation and promotion of liver cancer in various parts of the world. In Qidong, People's Republic of China, liver cancer accounts for 10% of all adult deaths, and both HBV and AFB1 exposures are common. To study temporal and possible chemical-viral interactions in people, serum samples were collected during a longitudinal study designed to measure aflatoxin molecular biomarkers in residents of Daxin Township, Qidong City, People's Republic of China. In this study, the temporal modulation of aflatoxin adduct formation with albumin over multiple lifetimes of serum albumin was examined in both HBV-positive and HBV-negative people in two periods: September-December 1993 (wave 1) and June-September 1994 (wave 2). During the 12-week monitoring period of wave 1, 120 individuals (balanced by gender and HBV status) provided a total of 792 blood samples. AFB1-albumin adducts were detected in all but one of the serum samples. The range of binding detected by RIA in the Daxin population was 0.17-4.39 pmol AFB11/mg albumin with an overall mean +/- SD of 1.51 +/- 0.21 pmol AFB11/mg albumin. The mean +/- SD for weeks 0, 2, 4, 6, 8, 10 and 12 of wave 1 were 1.21 +/- 0.41, 1.58 +/- 0.70, 1.36 +/- 0.52, 1.71 +/- 0.44, 1.18 +/- 0.60, 2.00 +/- 0.59, and 1.68 +/- 0.34 pmol AFB1/mg albumin, respectively. During wave 2, 103 individuals from wave 1 provided a total of 396 blood samples collected monthly over wave 2, with mean +/- SD aflatoxin-albumin adduct levels of 1.19 +/- 0.37, 0.85 +/- 0.45, 0.89 +/- 0.28, and 0.61 +/- 0.15 pmol AFB1/mg albumin. Using linear regression models, the mean aflatoxin-albumin adduct levels increased (P < 0.05) during the 12 weeks of wave 1 and decreased (P < 0.05) over the 4 months of wave 2. Neither HBV surface antigen status nor gender modified either the baseline mean or the temporal trend. High-performance liquid chromatography confirmation was done on a subset of serum samples, and the results show an excellent association between the immunoassay data and high-performance liquid chromatography. Taken together, these data demonstrate that AFB1-albumin is a sensitive and specific biomarker for assessing exposure to this carcinogen in the population in Qidong.
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PMID:Temporal patterns of aflatoxin-albumin adducts in hepatitis B surface antigen-positive and antigen-negative residents of Daxin, Qidong County, People's Republic of China. 872 16

Four patients with advanced hepatocellular carcinoma were treated by repeated arterial infusion of zinostatin stimalamer (SMANCS). Every 4 weeks, 4 mg of SMANCS and 4 ml of Lipiodol were administered via the proper hepatic artery using an implantable arterial port. Three patients with advanced liver cirrhosis (Child B or C) could no longer be treated after 2 or 3 courses of SMANCS infusion because of hepatic failure. In the remaining patient also with compensated liver cirrhosis (Child A), a partial response was observed after 5 courses of chemo-infusion, but we discontinued infusion of SMANCS because of hepatic failure. To assess the usefulness of SMANCS for repeated arterial chemo-infusion by the port, we evaluated 103 patients with advanced HCC treated by Lipiodol emulsion mixed with 70 mg of epirubicin (EPI) using a port. An average course was 11 arterial infusions, and the overall response rate was 40%. One-year survival rates were 62% in Child A, 59% in Child B, and 53% in Child C. Compared with Child A and B patients, both elevation of serum total bilirubin levels and decrease of serum albumin levels were observed after 9 months in Child C patients. In conclusion, SMANCS may have more severe hepatic toxicity in comparison with Lipiodol emulsion mixed with EPI.
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PMID:[Repeated arterial infusion of zinostatin stimalamer using port for advanced hepatocellular carcinoma]. 951 84

Antipyrine metabolism is widely used as an index of the drug-metabolizing reserve of the liver. It is well known that metabolism of this drug is impaired in subjects with acute hepatitis or cirrhosis, but conflicting data have been reported regarding patients with chronic postinfectious hepatitis or liver cancer. We studied conventional liver-function parameters and antipyrine metabolism (antipyrine per o.s. 18 mg/kg) in 518 subjects. One hundred and one patients had liver metastases (various primaries). Based on the number and size of lesions, the hepatic involvement was considered minimal in 47 and massive in 54 (groups B1 and B2, respectively). One hundred and two had chronic active hepatitis (CAH); 51 patients with histological evidence of fibrosis/early cirrhosis and 51 patients were without histological evidence of fibrosis/early cirrhosis. Ninety-two had histologically confirmed cirrhosis (group D), and the remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control group was composed of 103 subjects with healthy livers (group A). Antipyrine clearance (AP Cl) in CAH patients with fibrosis (0.246 +/- 0.98 mL/min per kg) was similar to that observed in patients with cirrhosis (0.223 +/- 0.148 mL/min per kg), and both values were significantly lower than that found in CAH patients without fibrosis (0.406 +/- 0.159 mL/min per kg, P < 0.01). Antipyrine clearance in patients with liver metastases (0.426 +/- 0.174 mL/min per kg) was similar to that of the healthy group (0.489 +/- 0.210 mL/min per kg). Cirrhotics and cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of impairment. Antipyrine clearance was positively correlated with serum albumin (r2 = 0.10, P = 0.01) and prothrombin time (r2 = 0.129, P < 0.01) in all groups, except those with liver metastases. In patients with CAH, the presence of fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of impairment in groups with liver metastases suggests that the functional hepatic reserve is maintained even in the presence of massive neoplastic invasion.
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PMID:Antipyrine clearance in chronic and neoplastic liver diseases: a study of 518 patients. 964 40

The insulin-like growth factor (IGF) axis has important autocrine, paracrine, and endocrine roles in the promotion of growth. Alterations of the IGF system have recently been implicated in the pathogenesis of several malignancies, but the relation to hepatocellular carcinoma (HCC) risk is unclear. To address this issue, we used an immunoradiometric assay to quantify IGF-1 levels in serum samples in a hospital-based, case-control study in Greece. The study subjects were all men and included 53 patients with HCC positive for hepatitis B and/or hepatitis C virus infections, 20 virus-negative HCC patients, 25 virus-negative patients with metastatic liver cancer (MLC), and 111 virus-negative control subjects. Data were analyzed by multiple linear regression, using IGF-1 as the dependent variable. The mean value of IGF-1 was 65.9 ng/ml among virus-positive HCC patients, 79.5 ng/ml among virus-negative HCC patients, 110.8 ng/ml among patients with MLC, and 174.7 ng/ml among hospital controls. After controlling for the degree of liver damage, as assessed by prothrombin time and serum albumin level, the reduction in IGF-1 level among HCC patients was found to be more than could be attributed to liver damage alone. This finding may have both diagnostic and pathophysiological implications.
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PMID:Insulin-like growth factor 1 in hepatocellular carcinoma and metastatic liver cancer in men. 1086 61

Mouse monoclonal antibodies were developed against a synthetic aflatoxin B(1) (AFB)-lysine-cationized bovine serum albumin conjugate. The isotype of one of these antibodies, IIA4B3, has been classified as immunoglobulin G1(lambda). The affinity and specificity of IIA4B3 were further characterized by a competitive radioimmunoassay. The affinities of IIA4B3 for AFB and its associated adducts and metabolites are ranked as follows: AFB-lysine > 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido)-9-hydroxy-AFB > AFB = 8,9-dihydro-8-(N(7)-guanyl)-9-hydroxy-AFB > aflatoxin M(1) > aflatoxin Q(1). IIA4B3 had about a 10-fold higher affinity for binding to AFB-lysine adduct than to AFB when (3)H-AFB-lysine was used as the tracer. The concentration for 50% inhibition for AFB-lysine was 0.610 pmol; that for AFB was 6.85 pmol. IIA4B3 had affinities at least sevenfold and twofold higher than those of 2B11, a previously developed antibody against parent AFB, for the major aflatoxin-DNA adducts 8,9-dihydro-8-(N(7)-guanyl)-9-hydroxy-AFB and 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido)-9-hydroxy-AFB, respectively. An analytical method based on a competitive radioimmunoassay with IIA4B3 and (3)H-AFB-lysine was validated with a limit of detection of 10 fmol of AFB-lysine adduct. The method has been applied to the measurement of AFB-albumin adduct levels in human serum samples collected from the residents of areas at high risk for liver cancer.
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PMID:Development of aflatoxin B(1)-lysine adduct monoclonal antibody for human exposure studies. 1137 85

Pentachlorophenol (PCP) induces liver cancer in mice, possibly due to covalent binding of PCP metabolites to critical macromolecules. In this work, covalent binding was related to PCP biotransformation and specific (cysteinyl) adducts of chlorinated quinones in liver and blood of Sprague-Dawley rats and B6C3F1 mice dosed with [(14)C]PCP. Using a sequential scheme of scintillation counting along with selective cleavage of cysteinyl adducts by Raney nickel, we quantified total radiobinding, total covalent binding, non-cysteinyl protein binding, and specific protein adducts in liver nuclei (Np), liver cytosol (Cp), hemoglobin (Hb), and serum albumin (Alb). Almost all of the radiobinding to Np (>98%) was attributed to covalent binding in both rats and mice. Regarding Cp, more covalent binding was observed in mice than in rats (100% versus 67%, P=0.015). Very little binding was attributed to serum Alb (rats 1.3%, mice 2.6%, P=0.046) or Hb (not detected in either species). These results indicate that the liver was the main organ for PCP metabolism and that relatively little of the dose of reactive metabolites became systemically available. Cysteinyl binding accounted for 76-91% of total covalent binding to Np and 68-76% of total covalent binding to Cp. In addition, five times more PCP was bioactivated in the livers of mice than in those of rats (2.14% of the dose bound to Cp in mice and 0.416% in rats). These results reinforce previous studies, suggesting that the liver was a target organ of PCP carcinogenicity and that mice were more susceptible to liver damage than rats. However, the sum of all quantified adducts accounted for only 7-8% of total cysteinyl binding to Np and 2% to Cp, suggesting that other uncharacterized binding species may be important to the toxicity of PCP.
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PMID:Fractionation of protein adducts in rats and mice dosed with [14C]pentachlorophenol. 1241 25

We have devised an original predictive residual index (PRI) using 99mTc diethylenetriaminepentaacetic acid galactosyl human serum albumin (99mTc-GSA) liver dynamic SPET for the pre-operative assessment of hepatectomy, including the prediction of residual liver function before hepatectomy. The aim of this study was to evaluate the usefulness of the PRI by using 99mTc-GSA liver dynamic SPET before and after percutaneous transhepatic portal embolization (PTPE) to induce compensatory hypertrophy of the remnant lobe, and to compare the results with the prognosis after hepatectomy. The subjects included eight patients with cholangiocellular carcinoma, five with gallbladder cancer, four with hepatocellular carcinoma and three with metastatic liver cancer. 99mTc-GSA liver dynamic SPET was performed immediately before and 2 weeks after PTPE. Dynamic SPET with 35 continuous rotations was performed to obtain the k-value according to the accumulation curve in each voxel (0.54 cm x 0.54 cm x 1.08 cm) of the liver immediately after a bolus injection of 185 MBq 99mTc-GSA. Each rotation consisted of 180 degrees turn in 64 steps in a 64 x 64 matrix. The acquisition time of each rotation was 35 s. We devised an original PRI by combining the k-value with functional liver volume which were measured by liver dynamic SPET. Hepatectomy was performed following the second SPET. The correlation between the PRI and post-operative patient prognosis was investigated retrospectively. The functional liver volume of the remnant lobe and the PRI significantly increased after PTPE compared with respective values before PTPE (P<0.005 and P<0.0001, respectively). Regarding the relationship between the PRI and the clinical course following surgery, post-operative complications were observed in only two patients. The PRI values of these two patients were 0.323 and 0.394. When the PRI was above 0.400, no patient had symptoms of hepatic failure. The results of this study suggest that, when the PRI value is above 0.400, there is a low probability of hepatic failure after hepatectomy. We conclude that the PRI devised in this study is useful in the pre-operative assessment of hepatectomy after PTPE.
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PMID:99mTc galactosyl human serum albumin liver dynamic SPET for pre-operative assessment of hepatectomy in relation to percutaneous transhepatic portal embolization. 1281

Although hepatitis C virus (HCV)-related cirrhosis has been suggested as a risk factor for intrahepatic cholangiocarcinoma (ICC), few sizeable studies have tested this hypothesis. We investigated ICC risk factors, with special reference to HCV infection. We conducted a hospital-based case-control study including 50 ICC patients and 205 other surgical patients without primary liver cancer. HCV seropositivity was detected in 36% of ICC patients and 3% of controls. By univariate analysis, the odds ratio (OR) for association of anti-HCV antibodies with development was 16.87 (95% confidence interval (CI), 5.69 to 50.00). History of blood transfusion or diabetes mellitus, elevated serum total bilirubin, elevated aspartate aminotransferase and alanine aminotransferase, decreased serum albumin and decreased platelet count were identified as other possible ICC risk factors. By multivariate analysis, anti-HCV antibodies (adjusted OR, 6.02; 95% CI, 1.51 to 24.1), elevated alanine aminotransferase, decreased serum albumin, and decreased platelet count were found to be independent risk factors for ICC development. As liver status worsened, the adjusted OR for ICC tended to increase. HCV infection is a likely etiology of ICC in Japan.
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PMID:Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma. 1524 96

The extracellular domain of the tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) may function as a soluble cytokine to selectively kill various cancer cells without toxicity to most normal cells. We constructed a series of recombinant adeno-associated virus (AAV) vectors expressing the extracellular domain of human TRAIL fused with signal peptides of human insulin, interferon, human growth hormone, and serum albumin and designated them as AAV-ISN-T, AAV-IFN-T, AAV-HGH-T, and AAV-Alb-T, respectively. Transduction of human SMMC-7721 liver cancer cells with AAV-ISN-T led to higher levels of TRAIL(95-281) protein expression in the cell culture media and produced more apoptosis of the cells in vitro than those with AAV-IFN-T, AAV-HGH-T, and AAV-Alb-T. The therapeutic potential of AAV-ISN-T was then evaluated in a transplanted mouse model established by injection of human liver cancer SMMC-7721 cells subcutaneously. Subsequent oral or intraperitoneal administration of AAV-ISN-T resulted in a rapid, high level and long time expression of soluble TRAIL in the sera and livers of the animals, as well as effective suppression of tumor growth, with no toxicity to normal hepatocytes. These data strongly suggest that it is possible to increase soluble TRAIL expression to make full use of tumoricidal activity of TRAIL as a therapeutic strategy. In conclusion, we provide evidence that oral administration of AAV-TRAIL might be an important alternative route with practical significance for cancer gene therapy.
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PMID:Oral adeno-associated virus-sTRAIL gene therapy suppresses human hepatocellular carcinoma growth in mice. 1631 90

Hepatitis B and C are diseases characterized by a high global prevalence, complex clinical course and limited efficacy of currently available antiviral therapy. Hepatitis B: local factors have a significant influence not only on the disease prevalence but also on the disease course. Vertical transmission of the infection in the areas of high prevalence results in perinatal infection, which universaly leads to the development of chronic disease. Factors associated with an increased risk of cirrhosis are older age, persistent viremia, coinfection with HCV, HDV and HIV, and consumption of alcohol, while the role of viral genotype is uncertain. Predictors of HCC development in cirrhotic liver are older age, male sex, alcohol abuse, exposure to aflatoxin, coinfection with HCV and HDV, continuously active inflammation, and potentially viral genotype. Survival predictors in cirrhotic patients are age, serum albumin, platelet count and splenomegaly as a reflection of portal hypertension. Hepatitis C: the risk of cirrhosis is low. Risk factors for cirrhosis are infection in older age, alcohol abuse, and coinfection with HBV and HIV. Obesity has negative impact on treatment efficacy.
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PMID:[Factors influencing clinical course of viral hepatitis]. 1638 Dec 33


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