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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cis-dichlorodiammine platinum (CDDP) has recently been introduced for the treatment of human malignancies. CDDP belongs to the group of heavy metals and has nephrotoxicity, whose side effects limit the dose that can be used in patients. The urinary excretion of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), arylamidase (AA) activity and beta 2-microglobulin was determined in ovarian cancer patients receiving sequential combination chemotherapy with CDDP, adriamycin (ADM) and cyclophosphamide (CPA) (PAC chemotherapy) to evaluate the sensitivity of these indices for acute renal tubular damage and compared with the change in serum BUN, Cr and Ccr values. Increases in enzyme excretion after PAC chemotherapy were more often noticed and the urinary enzyme activity varied up to the 10.4-fold of the control, while serum BUN, Cr and Ccr values remained almost within normal limits. Enzyme excretion returned almost to the normal value in one week. A comparison between the urinary enzyme excretion especially AA value and serum BUN, Cr and Ccr values indicated that the serial determination of the urinary AA excretion pattern is more useful in detecting CDDP-induced nephrotoxicity than that of serum BUN, Cr and Ccr values.
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PMID:[Cisplatin and ovarian carcinoma--early detection of cisplatin-induced nephrotoxicity]. 404 May 42

The usefulness of a simple fluorometric assay for serum heat-stable alkaline phosphatase (HSAP) in the diagnosis and follow-up of ovarian cancer patients was evaluated. 50 percent of the patients with malignant ovarian tumors had serum HSAP-activities above the upper reference range. Active production of this tumor marker in malignant but not in benign ovarian tumors was demonstrated by analysing serum HSAP-activities in ovarian vein blood. After operation, serum HSAP-activities decreased in all cancer patients with elevated preoperative values. Our results suggest that fluorometric serum HSAP-assay may be a useful alternative method for the determination of this tumor marker especially in a clinical laboratory.
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PMID:Evaluation of the value of fluorometric serum heat stable alkaline phosphatase assay in patients operated on for ovarian tumors. 407 Sep 36

Serum lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT) and alkaline phosphatase (ALP) activities have been measured in 105 patients with ovarian cancer for periods of up to 4 years. The extent of the disease was assessed at laporotomy according to the FIGO classification. Chemotherapy was started one week after surgery, at which time 25% of patients had elevated LD, 29% elevated gamma GT and 21% elevated ALP. Of 51 patients who went into complete remission, 4% still showed elevated LD, 25% elevated gamma GT and 12% elevated ALP. Reactivation of tumour growth was apparent in 32 patients; there was a significant increase in the serum LD, gamma GT and ALP activities when remission and recurrence were first detected in 65%, 50% and 35% of patients respectively. With 14 patients, there was an unexplained increase in the activity of one or more of the enzymes 1-6 months prior to recurrence being detected; these changes may predict that chemotherapy is losing effect. During long-term remission, serum LD was increased in patients suffering from urinary tract infection or bladder dysfunction.
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PMID:Serum enzyme changes during chemotherapy for ovarian cancer. 612 35

A comparison of preoperative serum tumor markers (lactate dehydrogenase, lactate dehydrogenase isoenzymes, alpha-hydroxybutyrate dehydrogenase, alkaline phosphatase, aldolase, leucine aminopeptidase, cholinesterase, erythrocyte sedimentation reaction, carcinoembryonic antigen, alpha-fetoprotein, and beta 2-microglobulin) was made in 76 patients with ovarian or uterine cancer. Sixty-six patients with benign ovarian tumor served as control subjects. From analysis of each tumor marker the greatest positive results were obtained with the markers beta 2-microglobulin (57.1%), lactate dehydrogenase (53.1%), and hydroxybutyrate dehydrogenase (46.2%) for patients with carcinoma of the ovary. The use of these marker combinations in all ovarian cancer patients resulted in a marked increase of the positive rate from 57.1 to 85.2%. In stage I cases, the positive rate increased from 40.6 to 63.6%.
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PMID:Significance of serum tumor markers in patients with carcinoma of the ovary. 619 5

Placental-type alkaline phosphatase was measured in sera, cyst, and ascites fluids, and from tumor extracts obtained from gynecologic cancer patients, particularly those with cancer of the ovary. A modified assay was used that depended on long incubation (20 to 24 hours) to measure the heat-stable, phenylalanine-sensitive placental isoenzyme. The concentration of enzyme in ascites and cyst fluids was markedly higher than in serum. Cyst fluid values were generally higher than ascites fluids from the same individual. The median enzyme levels for malignant cyst fluids were 50 times greater than for benign cyst fluids. When tumor tissue and fluids were available from the same patients, it was observed that the levels in each were proportional. Determination of this isoenzyme in serum did not give a useful index of tumor burden, as metastatic disease did not consistently result in elevated serum enzyme levels. When ovarian cancer patients were divided into two groups--those in whose sera placental-type phosphatase was elevated, and those in whom it was not--the presence of the enzyme in serum at the time of tumor diagnosis appeared to be a negative prognostic indicator, judged from survival data.
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PMID:Placental-type alkaline phosphatase in ovarian cancer fluids and tissues. 670 Aug 54

Two newly established murine monoclonal antibodies (MAbs), OVS1 and OVS2, to human ovarian mucinous cystadenocarcinoma were further characterized for diagnostic efficacy. The specific SA-1 antigen, purified from the tumor extract was identified as a glycoprotein of 29 kDa. A double determinant biotinstreptavidin alkaline phosphatase immunoassay system, containing OVS1 and OVS2 MAbs was used to determine the SA-1 levels in serum. The OVS1 MAb was used as a first antibody because of its high specificity of 96% while OVS2 MAb, with a lower specificity of 8% but greater sensitivity of 78%, was chosen as a second antibody. Matched sera of 64 healthy controls and 90 patients with definite diagnoses of 25 benign diseases, 14 nonovarian cancer and 51 ovarian cancer, were simultaneously measured together with CA 125 values. At cut-off levels of 220 and 360 units/ml, the SA-1 test showed 63% and 43% positive rates respectively in all types of ovarian cancer, compared to 65% and 57% positive rates for CA 125 at cut-off levels of 35 and 60 units/ml, respectively. Sensitivity for SA-1 at 220 units/ml cut-off level in mucinous ovarian cancer was 75% and increased significantly to 85% when the test was combined with CA 125 at 35 units/ml cut-off level. Furthermore, The combination of both tests significantly increased the positive rates to 86% in all types of early stage ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Establishment of OVS1 and OVS2 monoclonal antibodies recognizing human ovarian mucinous cystadenocarcinoma. 748 44

Intraperitoneal administration of liposomal valinomycin (MLV-VM) with cis-diamminedichloroplatinum(II) (cDDP) had significant antitumor activity against murine P388 leukemia and inhibited the growth of OVCAR-3 tumors in a nude mouse model of human ovarian cancer. This tumor is a teratoma originating in the ovary with pathogenesis and metastatic properties similar to those of human ovarian cancer. Drug was given to the mice once every 5 days for 4 doses beginning 1 day after i.p. implantation of 10(7) or 5 x 10(7) OVCAR-3 tumor cells. For P388 leukemia, drug was given i.p. once or on days 1 and 5 after tumor inoculation. Despite the use of low doses of MLV-VM, the antitumor activity of the combination [increase in life span (%T/C), 289%-294%] represents a 4-log cell kill over the additive effect of the two drugs, indicating a synergistic interaction between MLV-VM and cDDP. Likewise, low doses of the drug combination produced a synergistic interaction on human ovarian OVCAR-3 tumors, and tumor-free, long-term survivors were obtained. Combined therapy of liposome-incorporated valinomycin and cisplatin was well tolerated and produced no overlapping nephrotoxicity, although a decrease in liver enzyme markers (alkaline phosphatase and/or alkaline aminotransferase) with MLV-VM was observed. These results appear to suggest that MLV-VM with cDDP may have considerable potential for the treatment of ovarian cancer disseminated within the peritoneal cavity, although the frequency and sequence of drug administration may need to be improved.
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PMID:Combination chemotherapy of human ovarian xenografts with intraperitoneal liposome-incorporated valinomycin and cis-diamminedichloroplatinum(II). 828 24

A series of extended length heterobifunctional coupling agents is described. The successive aminocaproic acid homologation of succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate, a known 9-atom long maleimide active ester linker, yielded 16-, 23-, and 30-atom long maleimide active ester homologues. The performance study of these coupling agents in automated microparticle enzyme immunoassays showed that, in the alpha fetoprotein assay, in which the linkers were employed in the construction of the alkaline phosphatase-antibody conjugates, the signal increased 64% when the length of the linker was incremented from 9 atoms to 23 atoms and 82% for the 30-atom long linker as compared with the 9-atom homologue. Similar improvements were observed in the performance of carbohydrate antigen, marker of ovarian cancer (CA-125), immunoassay where the linkers were used for conjugation of the capture antibody anti-CA-125 to the microparticle. Thus, a 300% signal improvement resulted when a 30-atom linker was used instead of the 9-atom homologue. The observed differences in the performance of the conjugates are interpreted as resulting from improved antibody binding and lowering of the steric hindrance of the complementarity-determined region of the antibody when longer coupling agents were used.
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PMID:Extended length heterobifunctional coupling agents for protein conjugations. 874 95

The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m(-2) (day 1), with ifosfamide dose 1.2 g m(-2) day(-1) (days 2-4) and cisplatin dose 30 mg m(-2) day(-1) (days 2-4). All 16 patients received 5.0 microg kg(-1) day(-1) G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 microg kg(-1) day(-1) rhIL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (> or = grade I) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.007). No relation was found between haematological toxicity and pharmacokinetic parameters of paclitaxel. Patients treated with rhIL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir), and the cisplatin dose intensity was higher (P=0.025). Six of the nine evaluable patients had a tumour response. The overall median progression-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as second-line treatment showed a low tolerability with unexpected mortality, while rhIL-3 administration tended to induce a more rapid platelet recovery.
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PMID:Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study. 904 28

The mechanism of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of amifostine are reviewed. Amifostine is a prodrug converted by alkaline phosphatase to the active sulfhydryl compound WR-1065. WR-1065 protects normal cells by scavenging free radicals, donating hydrogen ions to free radicals, depleting oxygen, and binding to active derivatives of antineoplastic agents. The immediate conversion of amifostine to WR-1065, its small volume of distribution, and the limited amount of drug and metabolite recovered in the urine suggest that amifostine is rapidly dephosphorylated and enters cells as its active metabolite. The selectivity of amifostine for normal tissue is hypothesized to be a results of the decreased vascularity of tumors, decreased activity of alkaline phosphatase in tumor cells, and pH dependence of WR-1065 uptake. In clinical studies, amifostine decreased the frequency of cisplatin-induced nephrotoxicity, ototoxicity, neurotoxicity, and myelosuppression. Amifostine has demonstrated an ability to decrease the hematologic toxicity of cyclophosphamide, carboplatin, mitomycin, and antineoplastic drug combinations. Amifostine has FDA-approved labeling for use in reducing cumulative renal toxicity in patients receiving repeat doses of cisplatin for advanced ovarian cancer and non-small-cell lung cancer. The recommended dose in adults is 910 mg/m2 administered as a 15-minute infusion 30 minutes before the start of chemotherapy. The major adverse effects of amifostine include hypotension and emesis. The benefits of amifostine must be weighted against its potential adverse effects, and the drug's impact on the efficacy of antineoplastics should be further investigated. Amifostine has shown promise in protecting non-malignant cells from the toxic effects of antineoplastics, apparently without compromising toxicity against cancer cells.
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PMID:Amifostine for protection from antineoplastic drug toxicity. 977 47


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