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)

Fostriecin is an antitumor antibiotic with marked activity against ovarian, breast, and lung cancer cell lines in the human tumor clonogenic assay. The mechanism of cytotoxicity in vivo is unknown; in vitro it has been shown to inhibit macromolecular synthesis, interact with the reduced folate carrier system, and inhibit topoisomerase II. Phase I testing of fostriecin in a daily for 5 days schedule has begun in cancer patients. A high-pressure liquid chromatographic method to measure fostriecin in plasma samples was developed using sulfaquinoxaline as an internal standard and ultraviolet detection (268 nm). The extraction efficiency is 70% and the sensitivity limit is 100 ng/ml. The pharmacokinetics of fostriecin were determined in six rabbits following intravenous injection of 12 mg/m2. The mean distribution space was 4.44 L/m2 and the mean plasma clearance was 302 ml/min/m2. The elimination half-life was 11.95 +/- 8.55 min. All rabbits exhibited a 10-60-fold increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that resolved within 48 h of drug administration.
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PMID:Determination of fostriecin pharmacokinetics in plasma using high-pressure liquid chromatography assay. 800 68

Previously identified prognostic factors in advanced colorectal cancer were tested in an independent population for their relationship to survival by univariate and multivariate analyses. The new population comprised 198 patients included in a randomised chemotherapy trial. The earlier identified prognostic variables were: (1) haemoglobin level (B-Hb), (2) disease-free interval, (3) Karnofsky performance status (KPS), (4) number of symptoms, and (5) whether the primary tumour was removed or not. In the new population, variables (1-3) had significant relationships to survival in both univariate and multivariate analyses, whereas variable (4) was significant only in the univariate analysis. Variable (5) was not significantly related to survival in any analysis. When a group of additional variables (white blood cell count, B-thrombocytes, S-creatinine and liver function tests) was included, S-aspartate aminotransferase (S-ASAT) was a strong predictor of survival. The independent predictive value of B-Hb, disease-free interval and KPS was confirmed in this study. S-ASAT might be an additional important prognostic factor in advanced colorectal cancer. However, the results of this study indicate that any new prognostic factor should be viewed as preliminary until verified in an independent population.
Eur J Cancer 1994
PMID:Appraisal of a model for prediction of prognosis in advanced colorectal cancer. 801 2

The pharmacokinetics and clinical activity of epirubicin were investigated in 16 patients with hepatocellular carcinoma (HCC) who received epirubicin at 75 mg/m2; the drug was given intravenously to 7 patients and via the hepatic artery to 9 patients (7 of whom also underwent embolisation). Lignocaine (1 mg/kg) was also given intravenously to 15 patients, and the metabolite monoethylglycinexylidide (MEGX) was measured as an indicator of liver function. Epirubicin clearance correlated with serum aspartate aminotransferase (AST), albumin and bilirubin values in patients treated intravenously or intraarterially. Although the route of administration did not affect the median total plasma clearance of epirubicin, early- and intermediate-phase clearance was higher following intraarterial administration. MEGX levels correlated with serum bilirubin levels but there was no correlation with albumin or AST values or epirubicin clearance. The rate of response to epirubicin was 3/13 (23%; 95% confidence interval, 8%-50%). Intravenous epirubicin was tolerated well, but intraarterial treatment was associated with significant morbidity. These data confirm that although current recommended dose adjustments are based primarily on serum bilirubin levels, altered epirubicin pharmacokinetics correlate more strongly with AST and albumin values than with serum bilirubin concentrations. However, at this dose and schedule, epirubicin has only modest activity against HCC.
Cancer Chemother Pharmacol 1994
PMID:Epirubicin in hepatocellular carcinoma: pharmacokinetics and clinical activity. 807 7

Etoposide is a schedule-dependent cytotoxic drug with high single agent activity in small-cell lung cancer and lymphoma. Despite its clear dose-dependent myelosuppressive activity, dose-dependent evidence of its anti-tumour activity is harder to demonstrate. A number of reports have correlated haematological toxicity with pharmacokinetic and physiological parameters, which explains some of the variability in dynamic effects that exists between patients. Recent reports have also suggested that anti-tumour response may be related to plasma etoposide concentration. In our own studies we have investigated factors that influence the pharmacodynamic effects of etoposide, principally with regard to haematological toxicity, and these studies have highlighted a number of patient groups who are at risk. Impaired renal function causes a reduction in clearance of etoposide, resulting in increased systemic exposure and more profound myelotoxicity. A 30% dose reduction in this group is recommended to normalise the area under the plasma concentration-time curve (AUC). Patients with low serum albumin concentrations (< 35 g/l) also showed significantly worse haematological toxicity, but with no apparent change in total drug pharmacokinetics. There was, however, an increase in the free drug fraction in this group due to decreased protein binding, such that the free drug AUC was similar to that found in patients with renal dysfunction. This would also indicate that a dose reduction of around 30%-40% is required in this patient group. Patients with normal albumin levels but liver enzyme values (aspartate transaminase or gamma-glutamyl transpeptidase) more than 3 times the upper limit of normal also had a less marked but significant increase in neutropenia. In patients with normal organ function, age was the only significant factor in predicting the degree of leukopenia/neutropenia, and increasing age was also associated with decreasing drug clearance and an increase in drug AUC. A small dose reduction and/or careful monitoring is required in this patient group. Further studies are required to elucidate further the relationship between the pharmacokinetics of etoposide and its pharmacodynamics, particularly with regard to anti-tumor activity, and to determine the role of individualised therapy, based on a pharmacokinetic parameter, in reducing the dynamic variability and optimising the use of this drug.
Cancer Chemother Pharmacol 1994
PMID:Etoposide dosage and pharmacodynamics. 807 31

A prospective study of 187 patients with jaundice and 33 patients with unjaundiced cholestasis was carried out to evaluate the value of serum bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gammaglutamyl transferase (GGT), and leucine aminopeptidase (LAP) in the differential diagnosis between benign and malignant diseases causing jaundice and/or cholestasis. In the patients with malignant disease (n = 60), the mean serum bilirubin and ALP concentrations were significantly higher (p < 0.001) than in the patients with benign disease (n = 160). Serum LAP, ASAT, ALAT, or GGT levels did not show any significant differences. A stepwise discriminant analysis was carried out to evaluate the value of laboratory tests in predicting malignancy. The discrimination function is DF = bilirubin x 0.71 + ALP x 0.58 + ASAT x -0.24 + ALAT x 0.18 + LAP x 0.08 + GGT x -0.22. When the discriminant function was considered as a diagnostic score (DS), the sensitivity of it in detecting malignancy was 58% with a specificity of 89% and an efficiency of 81%. The DS of serum bilirubin and ALP reached the sensitivity of 61% with a 87% specificity and an efficiency of 79%. The post-test probability of malignant disease calculated by in this test combination was 69%. The LR+ was 4.8 and LR- 0.44. In conclusion, serum bilirubin and alkaline phosphatase seem to be the most potential tests of these laboratory tests in distinguishing benign and malignant causes of jaundice and/or cholestasis, high levels being suggestive of malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Value of serum alkaline phosphatase, aminotransferases, gamma-glutamyl transferase, leucine aminopeptidase, and bilirubin in the distinction between benign and malignant diseases causing jaundice and cholestasis: results from a prospective study. 809 35

The comparability of results for enzyme activity concentrations estimated with the methods recommended by the Scandinavian Committee on Enzymes(SCE) or the subcommittee on Enzymes of the European Committee for Clinical Laboratory Standards(ECCLS), and with the Kodak Ektachem methods, are discussed. As the Ektachem system in principle uses the IFCC methods at 37 degrees C as a reference, the results compare reasonably well for the alanine amino-transferase(ALAT), aspartate aminotransferase(ASAT), creatine kinase(CK) and gamma-glutamyltransferase(GT). The Ektachem reference method for lactate dehydrogenase(LD) is in principle the SCE method. The reasons for lower values with the SCE method are discussed. The interference on the Ektachem alkaline phosphatase (ALP) method from high concentrations of methotrexate(MTX) in serum, is shown. Results from our investigations on the interference by heparin in enzyme determinations on Ektachem are given. The problems with CK determinations in cancer patients regarding myocardial diseases are well known. When CK-BB is present in serum, the CK-B concentration is apparently lower using the Ektachem CK method than with use of the CK-MB slide, probably relating to the fact that chelator is omitted from the CK slide, while EGTA is supplied in the CK-MB slide. The user's dependence on the manufacturer for the choice of methods and the quality of the reagents, makes it important for laboratories and the Kodak Company to collaborate with the intention to continuously improve the Ektachem methodologies. The future possibilities of this technology seem to be nearly unlimited.
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PMID:Dry reagent technology. Kodak Ektachem 700 XR in clinical enzymology. 810 Oct 14

To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 microM, and concentrations of 7-OH-MTX declined triphasically, showing a t1/2 alpha value of 2.45 min, a t1/2 beta value of 30.5 min, and a terminal half-life (t1/2 gamma) of 240 min. The total clearance value was 14.5 ml min-1 kg, and the postdistributional volume of distribution (V beta) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.
Cancer Chemother Pharmacol 1994
PMID:Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat. 819 63

beta-2 microglobulin levels were measured in stored serum taken at presentation from 262 patients treated with combination chemotherapy for Kiel classification high-grade lymphoma at a single centre over a 15 year period. A significant association was found between elevated levels and advanced (Ann Arbor stage III or IV) disease or hepatic infiltration, but not with other sites of extranodal involvement or bulky disease. Patients with normal levels at presentation had a 70% remission rate with treatment compared to 37% of those with elevated levels (P < 0.001). With median follow up of 6 years duration of remission was significantly greater in patients with normal beta-2 microglobulin at presentation (plateau at 70%, compared to median remission of 19 months in those with raised levels, P < 0.001). Survival overall was also better in the group with normal levels (actuarial median 9 years compared to 1 year, P < 0.001). Multivariate analyses including treatment type, age, sex, B symptoms, stage, bulk, albumin, sodium, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and beta-2 microglobulin, placed beta-2 microglobulin among the three most influential independent variables for prediction of response rate, duration of remission and overall survival.
Br J Cancer 1993 Apr
PMID:Beta-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin's lymphomas. 847 38

Human recombinant tumor necrosis factor was administered to rats in small doses to determine whether it causes changes in the activity of liver enzymes similar to those observed in cancer growing extrahepatically. Intraperitoneal injection of increasing doses of tumor necrosis factor (20-100 micrograms/kg/day for 5 days) resulted in a 20-50% decrease in hepatic alanine aminotransferase (P < or = 0.05), a 10-20% decrease in aspartate aminotransferase (P < or = 0.04), and a 50-200% increase in alkaline phosphatase (P < or = 0.02). The activity of hepatic 5'-nucleotidase was unchanged. In the serum, there was no significant change in the activity of any of the enzymes. Histologically, there was no damage detectable by light or electron microscopic examination of the liver, and no evidence of biliary obstruction. However, in frozen liver sections stained histochemically for alkaline phosphatase, there was a dramatic increase in the activity of this enzyme in hepatocytes, which was confined to the bile canaliculi. There was also a 3- to 9-fold increase in the mitotic activity of hepatocytes. Comparable changes have been reported in the tumor-free liver of animals with cancer.
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PMID:Tumor necrosis factor induces enzymatic changes in liver comparable to those in extrahepatic cancer. 850 61

Molecules governing cellular interactions have been suggested to be involved in the spurious elevation of alpha 1-fetoprotein (AFP) in non-neoplastic liver disease. To explore this controversial issue, we measured AFP, circulating intercellular adhesion molecule 1 (cICAM-1), and common liver function tests in 111 patients (71 male, 40 female). Eighty-four patients had non-neoplastic chronic liver disease and 27 had hepatocellular carcinoma. The concentration of cICAM-1 was determined immunoenzymatically. In patients with non-neoplastic chronic liver disease, univariate analysis demonstrated a significant correlation between AFP and cholinesterase (R = -0.397, P < 0.001), aspartate aminotransferase (R = 0.421, P < 0.001), bilirubin (R = 0.231, P < 0.05) and cICAM-1 (R = 0.430, P < 0.001). Multivariate analysis among these variables and AFP indicated cICAM-1 to be the strongest independent predictor of AFP. We conclude that cICAM-1 compares favourably with liver function tests in predicting non-specific AFP variations in non-neoplastic chronic liver disease, suggesting a link between targeting of the inflammatory damage to the hepatocyte and development of neoplasia.
J Cancer Res Clin Oncol 1996
PMID:Circulating intercellular adhesion molecule 1 predicts non-specific elevation of alpha 1-fetoprotein. 864 48


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