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)

A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported upon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 consecutive weeks. These treatment regimens were well tolerated in the outpatient setting; no toxic deaths occurred, and none of the patients developed life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit significant increases in serum total bilirubin levels (mean peak +/- standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-limiting and life-threatening adverse reactions described upon IV rIL-2 therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha combination therapy as used in this study, can be given in the outpatient setting with good practicability and excellent safety.
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PMID:Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. Evidence of a risk-benefit advantage of subcutaneous therapy. 791 Jul 16

The authors measured immunoenzymatically circulating intercellular adhesion molecule-1 (cICAM-1) concentration in 135 patients with liver disease of either viral or toxic etiology: 13 had acute hepatitis; 58 had mild chronic liver disease; and 64 had cirrhosis (superimposed in 30 by hepatocellular carcinoma). Forty patients with extrahepatic diseases (19 with malignancies) and 28 healthy blood donors were tested as controls. One-way analysis of variance demonstrated a significant variability of cICAM-1 concentration among groups (F = 76.67, P < .0001), the highest value being recorded in acute hepatitis (Bonferroni's test for pairwise comparisons, P < .01). Total bilirubin showed a strong correlation with cICAM-1 (R = 0.766, P < .001). By stepwise multiple regression analysis the independent predictors of cICAM-1 concentration were chosen in the following order: total bilirubin; aspartate aminotransferase; cholinesterase; alpha-1-antitrypsin; and immunoglobulins. Thus, in addition to inflammation, cholestasis and decline of functioning hepatic mass may influence cICAM-1 concentration.
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PMID:Circulating intercellular adhesion molecule-1 (cICAM-1) concentration in liver disease. Relationship with cholestasis and functioning hepatic mass. 794 24

The acute intraperitoneal toxicities of chlorambucil and chlorambucil-spermidine conjugate have been compared, in mice. Both compounds were neurotoxic and also caused a prolonged fall in bodyweight and a depletion of lymphocyte numbers associated with a fall in the total leukocyte count and loss of spleen and thymus weight. Alanine aminotransferase and aspartate aminotransferase activities and blood urea nitrogen concentration were increased at 24 h after conjugate administration, but had returned to normal at 72 h. Chlorambucil significantly decreased blood urea nitrogen concentration for 72 h, but did not affect transferase activity. Tissue concentrations of conjugate were measurable in liver and kidney for 12 days and lung for 5 days after dosing. The toxicity of both compounds was cumulative. In mol/kg, the chlorambucil-spermidine conjugate was 10-fold more toxic than chlorambucil, on the basis of their neurotoxicity, but only 2- to 3-fold more toxic on the basis of their effects on lymphocyte depression. The increased toxicity of the conjugate does not improve its therapeutic index relative to chlorambucil.
Cancer Lett 1994 Oct 14
PMID:The comparative toxicity of chlorambucil and chlorambucil-spermidine conjugate to BALB/c mice. 795 40

Reduced or heterogeneous expression of E-cadherin has been demonstrated immunohistochemically in poorly differentiated carcinoma, which frequently shows weak intercellular adhesiveness and marked invasiveness. In vitro, not only reduced expression but also structural abnormalities of E-cadherin have been observed in human carcinoma cell lines which grow in a loosely adhering manner. To clarify the participation of structural abnormalities of E-cadherin in cancer invasion in vivo, sequence abnormalities were examined in the cadherin domain (exons 5, 6, 7 and 8) including the region essential for E-cadherin specific binding, using the polymerase chain reaction-single-strand conformation polymorphism method and direct sequencing in invasive lobular carcinoma of the breast, in which cancer cells become detached from each other and invade the stroma in a particularly scattered pattern. In 2 (10%) of the 20 cases examined, an identical sequence abnormality was detected in E-cadherin exon 7, i.e. a point mutation of codon 315 (AAT to AGT) which resulted in a single amino acid substitution (asparagine to serine). This mutation may abolish the E-cadherin-mediated cell-cell adhesion and be at least partly responsible for the weak intercellular adhesiveness and scattered histological pattern of the tumor.
Jpn J Cancer Res 1994 Oct
PMID:Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast. 796 Nov 5

The effects of four Diploptera punctata allatostatin peptides on the stomatogastric nervous system of the crab Cancer borealis were studied. All of the peptides had similar actions on the activity of neurons involved in rhythmic movements of the pyloric region of the stomach, decreasing the frequency of the pyloric rhythm in a dose-dependent manner. Diploptera allatostatin 3 (D-AST-3) was slightly more effective than the others. The absolute change in the frequency of the pyloric rhythm depended on the starting frequency, demonstrating that the effect of D-AST-3 depends on the preceding physiological state of the preparation. The largest decreases were observed when the starting frequency was slower than 0.8 Hz. Whole-mount immunocytochemistry with anti-Diploptera allatostatin 1 antibodies demonstrated the presence of allatostatin-like peptides in the paired commissural ganglia, the unpaired oesophageal ganglion and the stomatogastric ganglion, and in their connecting and motor nerves. Dense processes were labeled in the stomatogastric ganglion, 12-19 cell bodies and neuropil staining were found in each commissural ganglion, two cell bodies were stained in the oesophageal ganglion and two pairs of cell bodies, the gastropyloric receptor neurons, were stained in peripheral nerves.
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PMID:Allatostatin peptides in the crab stomatogastric nervous system: inhibition of the pyloric motor pattern and distribution of allatostatin-like immunoreactivity. 796 2

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


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