Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data on ten variables and 16 biomarkers were obtained on 119 patients with newly diagnosed pulmonary cancer. The prognostic value of 16 biomarkers (alpha-1-antitrypsin [AAT], adrenocorticotropic hormone [ACTH], alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], human chorionic gonadotropin [HCG], immune complexes, immunoglobulins, N-terminal peptide of proopiomelanocortin [NTERM], and tumor-associated antibody [TAA]) was tested by adding these to the model of age, gender, stage, morphology, Feinstein's classification of symptoms, Karnofsky scale, leukocyte count, recent weight loss, and liver enzymes. Using Cox's regression method and a forward stepwise procedure, seven biomarkers (ACTH, AAT, AFP, calcitonin, HCG, TAA, and prolactin) entered the model. Elevated levels of cortisol and TAA were associated with longer survival. The selection of biomarkers by stepwise regression needs to be interpreted with caution, especially since the Z scores were found to be dependent on the particular variables included in the model. Furthermore, when dichotomized on maximum of the normal laboratory values, HCG and AFP were infrequently (2%) elevated. The lack of correlation among the biomarkers supports the hypothesis of random derepression of the genome of cancer cells. Further studies in improved modeling and the formulation of a biomarker index could enhance our understanding of the biology of cancer.
Cancer 1990 May 01
PMID:The use of biomarkers in the prediction of survival in patients with pulmonary carcinoma. 216 76

Ascitic fluid alpha 1-antitrypsin (AF-AAT) was compared with ascitic fluid total protein (AF-TP) and the serum-ascites albumin gradient (SAAG) in the differential diagnosis of ascites. The study included 82 consecutive patients of which 42 had cirrhosis, 8 hepatoma (with cirrhosis), and 27 malignant ascites (peritoneal 18, liver 9). The concentration of AF-AAT (milligrams per deciliter) was significantly elevated (P less than 0.001) in hepatoma (174 +/- 123), malignant liver disease (232 +/- 119) and peritoneal neoplasms (376 +/- 106) in comparison with cirrhotics (66 +/- 33). In separating ascites caused by cirrhosis or malignancy, AF-AAT (discriminating limit of 120 mg/dl) had a 96% sensitivity, 95% specificity, and 96% diagnostic efficacy, which was superior to the 87% observed for AF-TP and 86% for the SAAG. Similar results were obtained for the A/S AAT ratio but this test was not available in all patients. AF-AAT was particularly useful in patients with malignancy causing portal hypertension as assessed by SAAG (hepatoma, malignant liver disease). We conclude that AF-AAT may be a valuable parameter in the differential diagnosis of ascites.
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PMID:Ascitic fluid alpha 1-antitrypsin. 216 27

Sera of 260 patients with high serum aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1; AST)/alanine aminotransferase (L-alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2; ALT) ratio (greater than 2.0) and high serum AST (greater than 45 IU/1) were selected and tested for the presence of immunoglobulin complexed-AST, by using immunoprecipitation reaction and counterimmunoelectrophoresis. The macromolecular AST was confirmed by size-exclusion high-performance liquid chromatography (HPLC). 34 patients out of 260 were found to have AST-immunoglobulin complexes (13.1%). The classes of AST-linked immunoglobulins were identified to be alpha in 28 cases (82.4%, P less than 0.01), mixed type of alpha and gamma in 5 cases (14.7%) gamma in one case (2.9%). Positive frequency was the highest in liver malignancies, either primary (9/26, 34.6%) or metastatic (7/17, 42.2%), followed by other malignancies (6/55, 10.9%) and chronic liver diseases (4/22, 18.2%). Thus, it can be strongly suggested that the immunoglobulin A complexed-AST is frequently found in association with liver malignancies.
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PMID:Incidence and properties of aspartate aminotransferase-immunoglobulin complexes in patients with a high serum aspartate to alanine aminotransferase ratio. 220 38

The disposition of total and non-protein-bound etoposide was investigated in 21 cancer patients receiving etoposide and cisplatin combination chemotherapy. Etoposide plasma concentrations were determined using a specific high-performance liquid chromatography (HPLC) method, and etoposide plasma protein binding was determined by equilibrium dialysis. The patients had a wide range of renal function (creatinine clearance, 32 to 159 mL/min/m2) and hepatic function (total bilirubin range, 0.3 to 21.5 mg/dL; aspartate aminotransferase [AST] range, 14 to 415 IU/L; serum albumin range, 2.7 to 4.1 g/dL). The mean etoposide total systemic clearance was not different in 15 patients with total bilirubin less than 1.0 mg/dL versus six patients with total bilirubin 1.1 to 21.5 mg/dL (18.7 +/- 5.9 mL/min/m2 v 26.4 +/- 10.7 mL/min/m2; t-test P = .06), with a trend toward higher total clearance in the patients with abnormal bilirubin values. However, the mean clearance of unbound etoposide was significantly lower in patients with increased total bilirubin (220 +/- 90 mL/min/m2 v 135 +/- 61 mL/min/m2; t-test P = .027). The fraction of etoposide unbound (fu) in plasma was significantly higher in patients with increased bilirubin (9% +/- 3% v 27% +/- 15%; t-test P = .002), explaining the trend toward higher total clearance in these patients. Etoposide clearance (total or unbound) in the 14 patients with measurable hepatic metastases was not different from the clearance in the seven patients without hepatic metastases. This study provides an explanation for why patients with increased bilirubin do not have lower total systemic clearance of etoposide, and indicates that such patients have a higher exposure to unbound etoposide. The results of ongoing pharmacodynamic studies of total and unbound etoposide in patients with increased bilirubin will determine the clinical relevance of altered etoposide protein binding.
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PMID:Changes in the clearance of total and unbound etoposide in patients with liver dysfunction. 223 Aug 75

We measured aminotransferase activity and vitamin B6 content in the livers of diabetic mice. Two different types of mice were used for the measurements, spontaneously non-obese diabetic (NOD) or alloxan-induced diabetic (Allo) mice, and control mice were either non-diabetic NOD or Institute of Cancer Research (ICR). The liver of diabetic mice had more aspartate aminotransferase (AST) activity than those of normal mice. The diabetic livers also had more vitamin B6 than did normal livers, and pyridoxamine (PM) levels were particularly high but pyridoxal (PL) levels were not. ICR livers showed hepatic alanine aminotransferase activities inversely correlated with blood glucose concentrations, while diabetic livers did not. The abundance of AST and B6 in the diabetic liver is consistent with the great need for gluconeogenic substrate there. This is understandable in that most aminotransferases require B6 vitamins, and especially the correlation between s-AST and PM levels was recognized in the diabetic liver. Conversely, the AST and PM levels were negatively correlated in normal mice. A metabolic shift towards gluconeogenesis apparently produces more B6 and PM while it induced holo-AST synthesis.
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PMID:Changes on levels of B6 vitamin and aminotransferase in the liver of diabetic animals. 237 34

Rat liver cytosolic sulfotransferase activity forms the highly reactive sulfuric acid ester of N-hydroxy-2-acetylaminofluorene (N-OH-2AAF), an ultimate carcinogen in 2-acetylaminofluorene (2AAF) hepatocarcinogenesis. A previous report demonstrated that 2AAF-induced liver hyperplastic nodules displayed a persistent loss of cytosolic N-OH-2AAF sulfotransferase activity following a hepatocarcinogenesis-producing regimen of 2AAF administration. As an initial step in examining the mechanism responsible for lowering N-OH-2AAF sulfotransferase activity, a monospecific polyclonal antibody to aryl sulfotransferase IV (AST IV) was produced and used in the assessment of AST IV as a candidate enzyme for liver cytosolic N-OH-2AAF sulfotransferase activity. Studies comparing the levels of N-OH-2AAF sulfotransferase activity of highly purified AST IV and rat liver cytosols with corresponding immunochemical analysis of AST IV contents demonstrated that there was sufficient AST IV activity in liver cytosols to indicate that it was the primary enzyme catalyzing cytosolic N-OH-2AAF sulfation. A subsequent immunochemical survey of nine extrahepatic tissues showed no detectable AST IV content and indicated that AST IV expression may be tissue specific. An immunochemical comparison of AST IV levels in control liver cytosols (high in sulfotransferase activity) with cytosols from 2AAF-derived hyperplastic nodules (low in sulfotransferase activity) or liver tumors (no sulfotransferase activity) showed low or no detectable levels, respectively, of AST IV. In addition, an immunochemical analysis of four rat hepatoma cell lines showed they contained no detectable levels of AST IV. These results suggested a strong correlation existed between a decrease in AST IV expression and tumor development. When the liver cytosols of rats taken from early, intermediate, and late stages of 2AAF carcinogenesis were analyzed for the development of a persistent loss of N-OH-2AAF sulfotransferase activity, a parallel loss of cytosolic N-OH-2AAF sulfotransferase activity and AST IV content was observed in rats which had proceeded from a stage of low risk to high risk for liver cancer. These findings indicated that (a) AST IV, a liver-specific enzyme, was the principle enzyme comprising cytosolic N-OH-2AAF sulfotransferase activity and (b) the decrease in sulfotransferase activity in nodules and tumors resulted from a decrease in the level of AST IV expression. Furthermore, it is suggested that a persistent decrease in AST IV expression may reflect a role for AST IV as part of a resistance phenotype in which transforming liver cells are able to escape the cytotoxic effects of highly reactive 2AAF metabolites and progress to cancer.
Cancer Res 1990 Sep 01
PMID:2-Acetylaminofluorene-mediated alteration in the level of liver arylsulfotransferase IV during rat hepatocarcinogenesis. 238 38

The aim of this study was to determine the mechanism by which bropirimine exerts its developmental toxicity. This drug is an immunomodulator and interferon inducer with antiviral and antitumor activities in experimental models. Timed-pregnant Upj:TUC(SD)spf (Sprague-Dawley) rats were given a single oral (gastric intubation) dose of bropirimine at 200 or 400 mg/kg (doses as high as 100 mg/kg/day have been employed in human cancer trials) on days 5, 6, 7, 8, 9, 10, 11, or 12 of gestation and in a second experiment on day 12, 13, 14, 15, 16, 17, 18, or 19 of gestation. The dams were killed 24 hours after dosing and their uterine contents examined. In a third experiment, bropirimine (400 mg/kg) was administered on day 4 of gestation and the uteri of different groups were examined on day 8, 9, 10, 11, or 12 of gestation. Serum progesterone levels were measured at sacrifice. In the first two experiments a battery of hematologic/clinical chemistry assays also were performed. In all three experiments, bropirimine-related maternal toxicity was observed; such toxicity was characterized by significant decreases in weight gain, relative to the concurrent vehicle controls, as well as significant differences in several blood parameters including platelets, white blood cells, alanine aminotransferase, and aspartate transaminase. In the first experiment, bropirimine treatment on day 11, but not day 12, resulted in significant decreases in the mean number of live embryos per litter. In the second experiment, significant decreases in the number of live fetuses per litter occurred 24 hours after dosing on day 18 (200 and 400 mg/kg groups) or day 19 (400 mg/kg group). Decreases in serum progesterone appeared to correlate well with the embryolethal effects seen after treatment between days 6 and 11 of gestation, but not with the fetal lethality seen when treatment was given on day 17 or 18. The decreases in serum progesterone levels found most likely were the result of a luteolytic effect, although it is unknown if bropirimine has a direct or indirect effect on the corpora lutea. In the third experiment, bropirimine treatment on day 4 of gestation resulted in only slight preimplantational losses, but significant decreases were found in mean number of live embryos per litter after day 9. Uterine decidual necrosis has been observed in the first experiment where bropirimine was given on day 11; however, treatment on day 4 resulted in an apparent decrease in decidual development but not necrosis.
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PMID:Variability in the developmental toxicity of bropirimine with the day of administration. 239 79

Methotrexate (MTX) accumulates in erythrocytes (ery) during weekly MTX administration, and the ery-MTX concentration reaches a steady state after 4-6 weeks. In order to study MTX accumulation and metabolism to polyglutamate derivatives in different age populations of red blood cells, we took erythrocytes from 12 children with ALL who were receiving maintenance treatment with MTX and 6-MP and separated them according to age on a discontinuous Percoll gradient. When the erythrocytes of these children were separated according to specific gravity a normal distribution was obtained. Age fractionation was confirmed by the exponential decline of the erythrocyte aspartate aminotransferase (ery-ASAT) and by the reticulocyte counts. The ery-MTX declined with increasing red blood cell age in an exponential manner no different from the decline of the ery-ASAT. The youngest population of red blood cells contained 2.3-5.9 (mean 3.8) times more MTX than the oldest population. By linear regression analysis the t1/2 of the ery-MTX was 19-79 days (mean 37 days). The ery-MTX t1/2 seemed to be directly related to the amount of MTX which had been metabolized to MTX-glu3-5. The decline of the ery-MTX was predominantly due to selective disappearance of MTX-glu1+2, whereas MTX-glu3-5 changed to a much lesser extent with advancing red blood cell age. The present investigation showed that steady-state ery-MTX concentration was determined by (1) the amount of MTX added to the circulation by the reticulocytes, (2) the in vivo loss predominantly of MTX with low numbers of glutamyl derivatives from erythrocytes, and (3) the loss of MTX from destroyed red blood cells. The observed in vivo disappearance of MTX from erythrocytes offers a possible explanation of the observation that the ery-MTX steady state was reached after 4-6 weeks of unaltered weekly MTX treatment.
Cancer Chemother Pharmacol 1988
PMID:In vivo decline of methotrexate and methotrexate polyglutamates in age-fractionated erythrocytes. 245 Jun 91

Alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) and aspartate aminotransferase (AsT) assays, as well as ultrasonography are the easiest and least expensive examinations to perform in the diagnosis of hepatic metastases. The 273 patients included in this series had cancer of the digestive tract. The diagnosis of presence or absence of liver metastases was made at surgery and was positive in 38 patients (14 per cent). A receiver operating characteristic (ROC) curve was drawn after computing the sensitivity (Se) and specificity (Sp) of each laboratory determination while the threshold indicating that the value was normal was incremented. The examinations were then compared in terms of Se, Sp, positive predictive value and negative predictive value. The threshold was determined on the ROC curve where less false-positive and more true-positive results were shown. According to predictive values, laboratory determinations could be classified in decreasing order of usefulness as: AP, LDH, GGT and AsT. Ultrasonography had a positive predictive value of 68 per cent a negative predictive value of 95 per cent, both figures being higher than those of any laboratory examination. These results suggest that ultrasonography has a higher diagnostic value than any of the enzyme assays in the detection of hepatic metastases. Moreover, ultrasonography provides morphological information which, in case of liver resection, may be useful to the surgeon.
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PMID:[Detection of hepatic metastasis of digestive cancers. Value of enzyme assays and ultrasonography]. 257 89

All cases of liver tumor referred to the King Faisal Specialist Hospital and Research Centre in Saudi Arabia during 2.5 years were reviewed. Hepatocellular carcinoma, 104 cases, was considerably more common than metastatic carcinoma with unknown primary, 15 cases. Lymphoma presenting as liver tumor occurred in three cases and there were no cases of cholangiocarcinoma. There were only two cases of benign tumor, both hemangioma. Hepatocellular carcinoma was characterized by a male predominance of 6:1, positive hepatitis B surface antigen in 60%, presentation with an enlarged, hard liver in over 90%, a systolic-diastolic bruit over the mass in 45%, a single highly echogenic lesion in the right lobe on ultrasound in 80%, and rapid progression. The serum AST (aspartate aminotransferase, serumglutamic oxalacetic transaminase [SGOT]) was abnormal in 97% and was higher than the alanine aminotransferase (ALT) in 93% of cases compared with 17% in 100 consecutive cases of chronic active hepatitis. Sixty-six percent of patients with hepatocellular carcinoma had serum AFP greater than 200 ng/ml. Excluding five cases of germ cell tumor (none involving the liver), and pregnant patients, serum AFP was less than 200 ng/ml in all other patients in whom it was measured between 1979 and 1981. A practical approach to the diagnosis of hepatocellular carcinoma is outlined. Biopsy does not appear to be indicated in many cases of advanced hepatocellular carcinoma.
Cancer 1985 Apr 01
PMID:Hepatic tumors in Saudi Arabia. A practical approach to diagnosis. 257 17


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