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

The medical and necropsy records of 41 cats diagnosed with nonlymphomatous hepatobiliary (NLHB) masses, including neoplasia and cysts, were reviewed. Overall, benign masses (n = 27) were more common than malignant ones (n = 14). The single most common malignancy was cholangiocellular carcinoma. The median age at diagnosis was significantly lower (P < .01) for cats with malignant rather than benign disease. Clinical signs associated with hepatobiliary neoplasia were usually vague and included lethargy, vomiting, and anorexia, often present for at least 2 weeks before presentation. Benign masses were an incidental finding in significantly more (P < .01) of the cases than were malignant masses. Median values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin were significantly higher (P < .05) in cats with malignant versus benign masses. The prognosis for malignant disease was poor, with 86% of the cats dying or being euthanatized during hospitalization. Cats with benign disease that underwent exploratory celiotomy were more likely to recover and warranted a more favorable prognosis than cats with malignant tumors. Factors associated with malignancy included age at presentation, presence of clinical signs at presentation, and specific serum chemistry changes.
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PMID:Nonlymphomatous hepatobiliary masses in cats: 41 cases (1972 to 1991). 783 94

Hepatic and renal subacute toxicity induced by the antineoplastic drugs chlorambucil, cisplatin, epirubicin and methotrexate and the steroid alkylating agent 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13, 17-lactam (p-[bis(2-chloroethyl) amino] phenyl) acetate was investigated in rats using serum biochemical parameters. Toxicological evaluation was performed in serum samples following the administration of dose regimens of the agents that were previously shown to be effective in suppressing malignant tumor growth or to prolong survival in tumor bearing animals. Hepatic and renal subacute toxicity was evaluated by measuring enzyme activity or concentrations of: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total cholesterol, gamma-glutamyltransferase, glucose, potassium, sodium, blood urea nitrogen and uric acid. The use of the above serum biochemical parameters indicated that the overall toxicity impact of the antitumor drugs was methotrexate < cisplatin < epirubicin < chlorambucil. The homo-azasteroid ester only transiently affected the biochemical parameters associated with renal toxicity, while it affected some of the biochemical parameters associated with hepatic toxicity, though to a significantly lower extent than the antitumor drugs.
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PMID:Evaluation of kidney and liver subacute toxicity of antitumor agents using serum biochemical parameters in rats. 790 82

Plachitin formed of both poly-N-acetyl-D-glucosamine (chitin) and cis-diamminedichloroplatinum (CDDP), was used as an arterial chemoembolization therapy against unresectable liver cancer. One gram of Plachitin contained 300 mg of CDDP. The Plachitin particle was 50-100 microns in diameter. Plachitin particles (50-100 mg) were injected via hepatic artery once or twice every week, and the total amount of 300 mg was considered one course of this therapy. The size and number of tumors were measured by computer tomography (CT). Pharmacokinetics of this drug was also assessed by serum and urine platinum (Pt) concentration. Three patients underwent the chemoembolization therapy using plachitin particles. Case 1 had multiple hepatocellular carcinomas. The tumor regression rate was 39% after two courses of this therapy. Serum alpha-fetoprotein (AFP) level decreased from 1,182 ng/ml to 300 ng/ml. Case 2 suffered from bile duct cystadenocarcinoma. After three courses of the therapy, the tumor regression rate was 84.4%. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 731 U/ml to 75 U/ml. Case 3 had synchronous multiple liver metastases from sigmoid colon cancer. The tumor regression rate was 77% after one course of the therapy. Carcinoembryonic antigen (CEA) and CA19-9 decreased from 406 ng/ml to 65 ng/ml and from 4,800 U/ml to 790 ng/ml, respectively. The response rate of the 3 cases was 66.7%. The peak levels of the serum Pt concentration of three patients were 0-0.4 microgram/g throughout the therapy, but peak urine Pt concentrations were observed during one course of the therapy of three patients ranging from 0.5 microgram/g to 3.2 micrograms/g, and decreased gradually for three weeks after the first course. Adverse effects of Plachitin particles for arterial chemoembolization were epigastralgia, nausea, fever, and elevation of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. These adverse effects were observed in all patients, but were transient. Catheter obstruction occurred in one patient (case 2). Cholecystitis, pancreatic pseudocyst, and duodenal ulcer were noticed in case 3. No renal hypofunction was observed. Plachitin might be a useful agent for arterial chemoembolization therapy for primary and secondary liver cancer.
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PMID:[Intraarterial chemoembolization therapy for unresectable liver cancer using plachitin particles]. 794 46

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

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.
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PMID:Etoposide dosage and pharmacodynamics. 807 31

cis-Diamminedichloroplatinum (II) (cisplatin: CDDP) suppositories containing NaCl at different concentrations were prepared as a local chemotherapeutic agent for the treatment of uterine endometrial carcinoma and were administered to rabbits implanted with uterine VX2 tumor. The intrauterine CDDP histological level, as well as the antitumor effects and side effects of the suppositories to the liver and kidney were studied. The results showed high intrauterine tissue CDDP level in all suppository administrations. In particular, the NaCl-added suppositories enhanced the intrauterine CDDP level. As for antitumor effects, while the tumor growth rate of the NaCl-added suppository group was likely to be suppressed, the suppositories could not suppress tumor growth completely. The plasma platinum (Pt) level was 1.5 micrograms/ml or less and that of the liver and kidney was as low as 0.31 to 0.48 micrograms/g. No difference in levels depending on NaCl concentration was observed, nor was any abnormality found in the biochemical analysis including glutamate oxaloacetate transaminase (GOT) and blood urea nitrogen (BUN). Histopathological study revealed the degeneration of tumor cells in the NaCl-added suppository group. Minimal congestion and hemorrhage were observed in the endometria, possibly resulting from CDDP. By adding NaCl to CDDP suppositories, the uterine CDDP level and antitumor effects increased while no serious renal dysfunction was noted. Therefore, we conclude that NaCl-added CDDP suppositories are a useful local chemotherapy for endometrial carcinoma.
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PMID:A study of cis-diamminedichloroplatinum(II) suppositories for the treatment of rabbit uterine endometrial carcinoma. 836 53

A rare case of double primary tumors of the liver is reported. A 69-year-old male presented with fever and right upper quadrant pain. On admission blood culture grew Salmonella group B. Laboratory data showed leucocytosis, mild elevation of aspartate aminotransferase, alanine aminotransferase and sugar, positive-HBsAg, and normal range CEA and AFP. Abdominal sonography disclosed a well demarcated solid mass and another cystic lesion with a ragged wall in the left lobe of liver. Abdominal CT revealed a mixed density solid mass in the medial segment, and laterally located cystic mass with internal septa. A preoperative diagnosis of double tumors of the left lobe of the liver was made and the patient underwent a left hepatic lobectomy. Hepatocellular carcinoma and cystadenocarcinoma were diagnosed by histopathological examination. The patient has been well without tumor recurrence after one and a half year's follow-up.
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PMID:Double primary tumors of the liver. 838 67

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

Cyclophosphamide, and antineoplastic drug, and vitamin E, the common antioxidant present in the diet, were administered in separate dosages and in combination to animals (rats) with fibrosarcoma, metastatic tumor of the connective tissues, induced. The anticancer drug (20 mg/kg body weight) and the vitamin-E (400 mg/kg body weight) was administered for a period of 28 days from the day of tumor transplantation. The individual and the combined effects of these two substances were investigated by checking the growth of the tumor. Tumor markers like lactate dehydrogenase (LDH), serum glutamate pyruvate transminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), acid phosphatase, and alkaline phosphatase were analyzed for the changes in their concentration in serum, liver, and kidney to assess the success of the therapy. The increased level of the enzymes in the fibrosarcoma-suffering rats (GPII) was reduced by cyclophosphamide treatment (GP III) and vitamin E administration (GP IV). Among the treated groups, the combination therapy (GP V) showed greater efficacy in the treatment of fibrosarcoma than did individual administration, as there was more reduction in the levels of enzymes in Group V than those in to Groups III and IV. The enzyme levels were brought to near the normal level.
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PMID:Effect of administering cyclophosphamide and vitamin E on the levels of tumor-marker enzymes in rats with experimentally induced fibrosarcoma. 853 10

This study examined clinico-histopathologic differences between North American patients who developed hepatocellular carcinoma with and without cirrhosis. Histologic slides and clinical records of cases were reviewed. Cases were classified according to defined histopathologic criteria. Analyses were performed using appropriate tests. A total of 42.6% of cases were noncirrhotic. The trabecular type of hepatocellular carcinoma was the most common growth pattern in both groups. Patients with cirrhosis were significantly older, had high grade tumors, and local portal venous invasion significantly more often than patients without cirrhosis. Encapsulated tumors occurred in significantly more in patients without cirrhosis. Patients without cirrhosis survived longer than patients with cirrhosis (P < .0001) and had a better 5-year survival experience. On average, in patients with cirrhosis, serum aspartate transaminase and total serum bilirubin were significantly greater, and serum albumin was significantly lower. In general, hepatocellular carcinoma in North American patients with cirrhosis tended to be less well differentiated than those found among patients without cirrhosis. The pathology, natural history, and prognosis of this tumor is significantly influenced by the presence or absence of cirrhosis in the nonneoplastic liver, and the presence of cirrhosis portends a poorer prognosis.
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PMID:Hepatocellular carcinoma in cirrhotic and noncirrhotic livers. A clinico-histopathologic study of 804 North American patients. 856 Oct 84


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