UNIPROT:P17174 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transaminase enzymes, alanine (ALT) and aspartate transaminase (AST), have been reported to be raised and implicated to have prognostic value in hepatocellular carcinoma (HCC). Ki67, a marker of cellular proliferative activity, has also been noted to be increased in HCC. A study was conducted at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur to determine the possible association of proliferative activity, as determined by Ki67, with the transaminase enzymes. 31 cases of histologically diagnosed HCC who underwent tumour resection were retrieved from departmental archives. The patients' ages ranged between 40 to 79 years with a mean of 58.3 years. There was a male preponderance with M:F = 2.9:1. Ethnic Chinese formed 83.9% of the cases. 4 microm sections, cut from the formalin-fixed, paraffin-embedded tumour tissue block of each case, were immunohistochemically stained with Ki67 (DAKO monoclonal MIB-1) using the commercial DakoCytomation EnVision+System-HRP kit. The latest ALT and AST levels, assayed within 7 days prior to tumour resection, were retrieved from the patients' case records. 24 (77.4%) HCC demonstrated elevation of either ALT and/or AST. 27 (87.1%) HCC were immunopositive for Ki67. Ki67 immunoexpression was significantly correlated with raised transaminases (p<0.05). Hypothetically, the mechanism by which this phenomenon may occur may simply be release of transaminases due to destruction of hepatocytes by the cancer. Thus rising levels of the transaminases could signal a more rapid growth of the tumour and these routinely performed tests can be of prognostic value in management of HCC patients.
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PMID:Association of Ki67 with raised transaminases in hepatocellular carcinoma. 1929 19

Chemopreventive potential of Acacia nilotica bark extract (ANBE) against single intraperitoneal injection of N-nitrosodiethylamine (NDEA, 200mg/kg) followed by weekly subcutaneous injections of carbon tetrachloride (CCl(4), 3 ml/kg) for 6 weeks induced hepatocellular carcinoma (HCC) in rats was studied. At 45 day after administration of NDEA, 100 and 200mg/kg of ANBE were administered orally once daily for 10 weeks. The levels of liver injury and liver cancer markers such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (gamma-GT), total bilirubin level (TBL), alpha-feto protein (AFP) and carcinoembryonic antigen (CEA) were substantially increased following NDEA treatment. However, ANBE treatment reduced liver injury and restored liver cancer markers. ANBE also significantly prevented hepatic malondialdehyde (MDA) formation and reduced glutathione (GSH) in NDEA-treated rats which was dose dependent. Additionally, ANBE also increased the activities of antioxidant enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) in the liver of NDEA-administered rats. Eventually, ANBE also significantly improved body weight and prevented increase of relative liver weight due to NDEA treatment. Histological observations of liver tissues too correlated with the biochemical observations. HPLC analysis of ANBE showed the presence of gallic, protocatechuic, caffeic and ellagic acids, and also quercetin in ANBE. The results strongly support that A. nilotica bark prevents lipid peroxidation (LPO) and promote the enzymatic and non-enzymatic antioxidant defense system during NDEA-induced hepatocarcinogenesis which might be due to activities like scavenging of oxy radicals by the phytomolecules in ANBE.
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PMID:Potential chemoprevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by polyphenolics from Acacia nilotica bark. 1944 40

Solanum nigrum L. (SN) is a widespread plant and is regarded as a common relish in the east and the south of Taiwan. Our previous study has found that SN water extract (SNWE) alleviated carbon tetrachloride-induced liver damage in rats. However, the effects of SNWE on chemical-induced hepatic injury and hepatocarcinogenesis remain unclear. Therefore, this study aims to investigate the effects of SNWE on hepatic injury and hepatocarcinogenesis by using 2-acetylaminofluorene (AAF) and AAF/NaNO(2) treatment. The serum biomarkers for hepatic injury, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and gamma-glutamyl transferase, and for hepatocarcinogenesis, alpha-fetoprotein, were determined. Our results showed that AAF treatment led to a significant decrease of body weight and an increase of liver/body weight and serum biomarkers for hepatic injury and hepatocarcinogenesis. Interestingly, the SNWE supplement significantly lowered the liver/body weight and the biomarkers but did not affect the body weight. Further investigation revealed that a SNWE supplement increased the expression of glutathione S-transferase-alpha and -mu, the level of transcription factor for protection from oxidative stress, Nrf2, and the level of downstream targets regulated by Nrf2, including glutathione peroxidase, superoxide dismutase-1, and catalase. Moreover, the effects of SNWE on AAF/NaNO(2)-induced hepatoma were also investigated, and the findings revealed that SNWE suppressed the progression of the hepatoma and resulted in a great increase of the survival rate. Our findings indicate that the SNWE supplement significantly alleviated the AAF-induced hepatic injury and early hepatocarcinogenesis as well as the AAF/NaNO(2)-induced lethal hepatoma, which may result from the overexpression of glutathione S-transferases, Nrf2, and antioxidant enzymes.
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PMID:Solanum nigrum L. extract inhibits 2-acetylaminofluorene-induced hepatocarcinogenesis through overexpression of glutathione S-transferase and antioxidant enzymes. 1970 66

OBJECTIVE. Severe (PiZZ) alpha(1)-antitrypsin (AAT) deficiency is a risk factor for liver disease, i.e. juvenile cirrhosis in infancy, and cirrhosis and hepatoma in adulthood. Little is known about the risk of liver disease in individuals with moderate (PiSZ) AAT deficiency. To investigate the natural course of AAT deficiency, a cohort of PiZZ and PiSZ individuals identified by the Swedish National neonatal screening programme in 1972-74 is followed regularly. The aim of this study was to compare liver function in this cohort with healthy control subjects aged 30 years. MATERIAL AND METHODS. Blood samples were obtained from 89 PiZZ, 40 PiSZ, and 84 control subjects (PiMM), and plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl (GT) transpeptidase were analysed. RESULTS. The mean values of all liver enzymes were within the normal range in all Pi subgroups. However, the mean AST was higher in the PiZZ and PiSZ subgroups than in the PiMM subgroup (p < 0.001), and the mean ALT was higher in the PiZZ individuals than in the controls (p < 0.05), while GT did not differ significantly among the Pi subgroups. The PiZZ women taking oral contraceptives had higher mean AST and ALT (p < 0.01) and GT (p < 0.05) than the control women taking oral contraceptives. CONCLUSIONS. At the age of 30 years, PiZZ and PiSZ individuals have normal plasma levels of the transaminases AST and ALT, although they are significantly higher than those in healthy control subjects. Use of oral contraceptives seems to influence liver enzymes in PiZZ women.
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PMID:The liver in 30-year-old individuals with alpha(1)-antitrypsin deficiency. 1989 86

We treated patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC) with polaprezinc and determined prospectively the effect on long-term outcome. 62 patients were enrolled. Of these, 32 were administered 1.0 g polaprezinc and the remainder were not administered polaprezinc. We measured the serum zinc concentrations using conventional atomic absorption spectrometry and conducted a prospective study to determine the long-term outcome of the polaprezinc therapy. Changes of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the polaprezinc administration group were significantly lower than those of the untreated group. The decrease in platelet count was clearly less than that of the untreated group. The factors that inhibited increases in serum zinc concentrations following administration of polaprezinc included low serum zinc concentration states. Furthermore, the reductions of AST and ALT levels in the low zinc group were significantly greater than those of the high zinc group. When the patients who were administered polaprezinc were divided into two groups whose zinc concentrations increased (zinc responders) or remained stable or decreased (zinc non-responders), the zinc responders had a clearly lower cumulative incidence of HCC than the zinc non-responders. We conclude zinc supplementation improved the long-term outcome in C-viral CH and LC patients.
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PMID:Zinc supplementation improves the outcome of chronic hepatitis C and liver cirrhosis. 1990 19

Many centers require a minimal graft to body weight ratio (GBWR) >or= 0.8 as an arbitrary threshold to proceed with right-lobe living donor liver transplantation (RL-LDLT), and there is often hesitancy about transplanting lower volume living donor (LD) liver grafts into sicker patients. The data supporting this dogma, based on the early experience with RL-LDLT at Asian centers, are weak. To determine the effect of LD liver volume in the modern era, we investigated the impact of GBWR on the outcome of RL-LDLT with a GBWR as low as 0.6 at the University of Toronto. Between April 2000 and September 2008, 271 adult-to-adult RL-LDLT procedures and 614 deceased donor liver transplants were performed. Twenty-two living donor liver transplantation (LDLT) cases with a GBWR of 0.59 to 0.79 (group A) were compared with 249 LDLT cases with a GBWR >or= 0.8 (group B) and with 66 full-graft deceased donor liver transplants (group C), who were matched 3:1 according to donor and recipient age, Model for End-Stage Liver Disease score, and presence of hepatitis C and hepatocellular carcinoma with the low-GBWR group. Portal vein shunts were not used. Markers of reperfusion injury [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], graft function (international normalized ratio and bilirubin), complications graded by the Clavien score, and graft and patient survival were compared. As expected, LD recipients had a significantly shorter cold ischemia time (94 +/- 43 minutes for A, 96 +/- 57 minutes for B, and 453 +/- 152 minutes for C, P = 0.0001). However, the peak AST, peak ALT, absolute decrease in the international normalized ratio, day 7 bilirubin level, postoperative creatinine clearance, complication rate graded by the Clavien score, and median hospital stay were similar in all groups. The rate of biliary complications was higher with LD grafts than deceased donor grafts (19% for A versus 10% for B and 0% for C, P = 0.2). Patient survival was similar in all groups at 1, 3, and 5 years (91% for A versus 89% for B and 93% for C at 1 year, 87% for A versus 81% for B and 89% for C at 3 years, and 83% for A versus 81% for B and 87% for C at 5 years, P = 0.63). A Cox proportional regression analysis revealed only hepatitis C virus as a risk factor for poorer graft survival and not GBWR as a continuous or categorical variable. In conclusion, we found no evidence of inferior outcomes with smaller size grafts versus larger size LD grafts or full-size deceased donor grafts. Further studies are warranted to examine the factors affecting the function of smaller grafts for living liver donation and thereby define the safe lower limits for transplantation.
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PMID:A graft to body weight ratio less than 0.8 does not exclude adult-to-adult right-lobe living donor liver transplantation. 1993 39

The substitution of amino acid (aa) 70 of arginine for glutamine and/or that of aa91 of leucine for methionine in the core protein in patients infected with hepatitis C virus (HCV) genotype 1b is associated with a poor response to pegylated interferon and ribavirin. Factors influencing these substitutions were sought in 1,097 patients infected with HCV-1b who had not received antiviral treatment. HCV variants with Arg70 and Leu91 (wild-type) decreased, while those with Gln70 and/or Met91 (mutant types) increased with age (P < 0.001). Of the 1,097 patients, 464 (42.3%) were infected with the Gln70 variant and the remaining 633 patients with the Arg70 variant. The proportion of patients with the Gln70 variant increased with the severity of liver disease (P < 0.001), elevated gamma-glutamyl transpeptidase (gamma-GTP) levels (P < 0.001) and a decrease in platelet count (P = 0.008). In univariate analysis patients with hepatocellular carcinoma, elevated aspartate aminotransferase (AST > or = 58 IU/L) and gamma-GTP (> or =61 IU/L), and decreased albumin levels (<3.9 g/dl) were more frequent in the patients with the Gln70 variant than the Arg70 variant (P = 0.003, 0.005, <0.001, and 0.031, respectively). In multivariate analysis HCC (odds ratio 1.829 [95% confidence interval 1.147-2.917]) and gamma-GTP > or =61 IU/L (1.647 [1.268-2.139]) increased the risk for the Gln70 variant. In conclusion, the substitution of amino aa70 of Arg for Gln in patients infected with HCV-1b increases with age, and it is associated with severe liver disease accompanied by elevated AST and gamma-GTP levels, as well as the development of hepatocellular carcinoma.
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PMID:Influence of amino-acid polymorphism in the core protein on progression of liver disease in patients infected with hepatitis C virus genotype 1b. 1995 Feb 30

The hepatotoxicity induced by valproic acid (VPA) has been described in many clinical studies and the related mechanism has been partly elucidated. The objective of this study is to investigate the hepatotoxicity and its underlying mechanism of valproic acid on human hepatoma carcinoma cell line HepG2. The cell viability was evaluated by 3-(4,5-dimethyltyiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the medium were detected using spectrophotometry. The gene expressions of cytochrome P450 1 A1 (CYP1A1), ATP-binding cassette transporter G1 (ABCG1) and carnitine palmitoyltransferase 1 (CPT1A), related to lipid transport and fatty acid metabolism, were measured by quantitative real-time reverse transcriptase-PCR. Treatment with valproate sodium obviously decreased the viability of HepG2 cells, accompanied by the increased leakages of ALT, AST and LDH in a dose-dependent manner. Furthermore, the gene expressions of CYP1A1, ABCG1 and CPT1A were almost up-regulated in the treated groups. In conclusion, these data suggest that VPA-induced hepatotoxicity was critically enhanced with the elevation of valproate sodium, which may be correlated with up-regulated gene expressions of CYP1A1, ABCG1 and CPT1A.
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PMID:Participation of lipid transport and fatty acid metabolism in valproate sodium-induced hepatotoxicity in HepG2 cells. 2037 Dec 85

The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient's age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P < 0.001 for all comparisons). HBV/D was the predominant genotype associated with HCC cases seen in India. The presence of different types of HBV mutations, age, sex, HBeAg status, and viral load was found to increase significantly the risk of HCC development in India.
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PMID:Hepatitis B virus BCP, Precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India. 2051 73

The aim of this study was to determine the clinicopathologic features and Hepatitis B virus genotypes in HBV-infected patients in the Upper Egypt. Eighty-three HBsAg-positive patients (28 carriers, 14 with chronic hepatitis, 32 with liver cirrhosis and 9 with hepatocellular carcinoma) were enrolled. Blood was collected and serum samples obtained were screened for Hepatitis markers genotyping was conducted for 6 HBV genotypes (A through F) using a method for genotyping HBV by primer specific polymerase chain reaction. Genotype D was the only genotype detected in different clinical forms of chronic HBV infection (carriers, chronic hepatitis, cirrhosis and hepatocellular carcinoma) and, in all patients who had elevated or normal alanine aminotransferase levels and in all ages. HBeAg was absent in 78 patients suggesting the presence of pre-core or core mutations. Positive correlation was found among serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), histological activity index and grade of hepatitis. This study provides the first indication about the clinicopathologic features of HBV-infected patients in the Upper Egypt. It also reports the predominance of genotype D in this region.
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PMID:Clinicopathologic features and genotyping of patients with chronic HBV infection in the Upper Egypt. 2071 6

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