Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical and experimental findings on possible changes of the lymphocyte function during an immunosuppressive or cytostatic therapy respectively caused investigations to be made for explaining the connections existing between the influence of cellular immunoreaction and the use of different cytostatic regimes. Earlier findings on the influence of cellular immunoreaction after adding cytostatics to cultivated cells and investigations on the influence of the lymphocyte function in dependence on cytostatic therapy were used for comparison. Transformation and mitosis rates as well as necrosis rates and the result of macrophage migration inhibition are comparable parameters for influencing the lymphocyte function in children treated with cytostatics. Antimetabolites, vincristine, asparaginase and daunomycin will have less influence on the transformation rate as an expression of an immunosuppressive effect on only those cells responding in accordance with their kinetic phase. Cyclophosphamide will inhibit the transformation reaction more significantly. Examinations in children with different therapeutic regimes reveal a certain validity of therapy after the first statistical evaluation of the clinical material.
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PMID:[Studies on the effect of various kinds of cytostatic therapy on the cellular immune reaction in children with acute lymphatic leukemia]. 6 21

A number of therapeutic agents including L-asparaginase, Actinomycin-D, CCNU, Hydroxyurea, 5-FU, Cis-platinum, Cyclophosphamide, orchiectomy, Adriamycin and DES alone and in various combinations has been applied against the Dunning R-3327 rat prostatic adenocarcinoma subline G. We have found a parallel between the results of this study and those of similar therapeutic application to the human tumor. We conclude that this animal model may prove to be a useful screening system for agents against human prostatic cancer.
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PMID:Chemotherapy of the transplantable adenocarcinoma (R-3327) of the Copenhagen rat. 91 40

Over 20 cytoenzymochemical tests were carried out in 152 patients with different types of acute leukemia to estimate the effects of some antiblastic drugs such as L-asparaginase, Purinethol, Methotrexate, Endoxan, Vinchristine, Cytosine Arabinoside a.o. The patients selected for the study were carefully examined before treatment at different moments during and/or at the end of the treatment. The effects of these drugs on the blast cells were mild when the cellular populations had a low rate of nucleic acid synthesis, high glycogenic score and high amounts of lipids or an important oxidative enzymatic activity. The enzymatic prediction tests: the acid phosphate deviation test and the succinic dehydrogenase inhibition test including the variant suggested by some of the authors - the latic dehydrogenase inhibition test - gave satisfactory results only in certain cases of acute leukemia.
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PMID:Cytoenzymochemical effects of some antiblastic drugs and prediction of response to chemotherapy in acute leukemias. 105 33

Essentially all the drugs which are active against human leukemias and lymphomas are active against one type or another of the rodent leukemias and lymphomas. Leukemia L1210 has been generally the most successful screening tool for clinically active compounds. Leukemia P388, however, seems to be better in detecting active antibiotics and natural products and P1534 is particularly sensitive to the Vinca alkaloids, while L5178Y, EARAD, and 6C3HED are useful in detecting the activities of various asparaginase containing fractions. Cell cultures of these leukemias can demonstrate mechanism of drug action and quantitate resistance. Spontaneous AKR leukemia is a model of the advanced human disease. In these leukemias vincristine and prednisone produce a 4 log cell kill. Cytoxan and arabinosyl cytosine (Ara-C) are also effective. On the other hand drugs such as mercaptopurine (6MP) and methotrexate which are highly active in the maintenance phase of acute lymphocytic leukemia (ALL) and in L1210 have little or no activity against the AKR spontaneous system. Mouse leukemias can also detect schedule dependence, synergistic combinations, cross resistance, oral activity, and the ability of drugs to pass the blood brain barrier. A case in point is the Ara-C analog 2,2'-anhydro-arabinofuranosyl-5-fluorocytosine (AAFC) which is not schedule dependent, is active orally, is potentiated by thioguanine, and is effective against intracerebrally inoculated mouse leukemia. AAFC and its analogs might thus be a considerable improvement over Ara-C which is at the present time the most important component of the combination treatment of acute myelogenous leukemia (AML).
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PMID:Murine and human leukemias. 110 47

Four hundred thirty patients with high-risk acute lymphoid leukemia were entered on the acute leukemia in childhood protocol (AlinC 12) of the Pediatric Division of the Southwest Oncology Group (now the Pediatric Oncology Group) between 1976 and 1979. This study was a prospective randomized comparison of two regimens that had as their primary differences: (1) an intensification period with Cytoxan (cyclophosphamide) and asparaginase after induction; (2) a period of intravenous methotrexate before initiating maintenance; and (3) in the regimen that had those two additions, triple-drug chemoprophylaxis of the central nervous system (CNS) using methotrexate, hydrocortisone, and cytosine arabinoside as compared to cranial irradiation and intrathecal methotrexate. All patients received vincristine and prednisone induction, 6-mercaptopurine and methotrexate maintenance, and vincristine and prednisone pulse intensification. There was no significant difference in the rate of bone marrow relapse. However, overall disease-free survival favored the arm with intensification and chemoprophylaxis because of a lesser incidence of extramedullary relapse. Thus, for treatment 1 versus treatment 3 the two-sided P values were for overall disease-free survival 0.16; bone marrow relapses 0.13; all CNS relapses 0.04; and all extramedullary disease relapses 0.013. It is concluded that intensification as delivered in this protocol protects against testicular relapse and that chemoprophylaxis is adequate prophylaxis against isolated CNS relapse.
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PMID:A comparison of two regimens for high-risk acute lymphocytic leukemia in childhood. A Pediatric Oncology Group Study. 291 Apr 21

The in vivo effects of several chemotherapeutic agents on the mitotic cycle of leukemic blasts in the bone marrow were evaluated by serial measurements of cells in mitosis and in deoxyribonucleic acid (DNA) synthesis as indicated by ability to incorporate tritiated thymidine or tritiated deoxyuridine. 28 studies were done in 23 children and 1 adult. The changes in the marrow after a single injection of L-asparaginase, hydrocortisone, cyclophosphamide, cytosine arabinoside, methotrexate, and an exchange transfusion (62% of the total blood volume) were evaluated. L-asparaginase and hydrocortisone were found to arrest the entry of cells into the S period. Cyclophosphamide appeared to inhibit DNA synthesis, arrest cells in mitosis, and inhibit the entry of cells into the S period. Cytosine arabinoside, and methotrexate inhibited DNA synthesis. During the period of time the cells were inhibited in the S phase by these two drugs, cells continued to enter the S period. Thus partial synchronization was achieved after these two drugs. An exchange transfusion had no consistent effect on the mitotic cycle, but partial synchronization in the S period was seen in one patient. To take advantage of the ability of cystosine arabinoside, to synchronize leukemic cells in the S phase, a second cycle-dependent drug was given at the time the leukemic blasts were synchronized. The second cycle-dependent drugs evaluated were vincristine, methotrexate, and cytosine arabinoside given by intravenous drip over a 12 hr period. Recruitment was found after cytosine arabinoside alone, and after prior synchronization with cytosine arabinoside and then the administration of either of these drugs. The results of these studies indicate that a greater therapeutic advantage can be achieved by a second cycle-dependent drug after synchronization than after the second drug alone.
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PMID:Synchronization and recruitment in acute leukemia. 528 86

Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor. Possibilities for further improvement of this protocol are discussed.
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PMID:Lasting engraftment of histoincompatible bone marrow cells in dogs. 626 56

The emetic effects of five anticancer drugs, cyclophosphamide, nitrogen mustard-N-oxide, actinomycin D, 5-fluorouracil and L-asparaginase, and the effects of bilateral abdominal vagotomy and bilateral greater splanchnic nerve section or a 5-HT3 receptor antagonist on the emesis induced by these drugs were investigated in dogs. Cyclophosphamide (20 mg/kg, i.v.), nitrogen mustard-N-oxide (5 mg/kg, i.v.) and actinomycin D (50 micrograms/kg, i.v.) caused vomiting in dogs with a long latency period. 5-Fluorouracil (5 mg/kg, i.v.) and L-asparaginase (2000 K.U./kg, i.v.) failed to induce vomiting. Bilateral abdominal vagotomy and bilateral greater splanchnic nerve section completely inhibited the vomiting induced by the former three anticancer drugs. Furthermore, the vomiting was inhibited completely by intravenous administration of ICS205930 (2 x 0.1 mg/kg), a 5-HT3 receptor antagonist. These results suggest that activation of visceral afferents through 5-HT3 receptors mediates the vomiting induced by cyclophosphamide, nitrogen mustard-N-oxide and actinomycin D.
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PMID:Emetic effects of anticancer drugs and involvement of visceral afferent fibers and 5-HT3 receptors in dogs. 811 85

Cancer cells may frequently develop cross-resistance to structurally dissimilar chemotherapeutic agents. However, the molecular mechanisms for sensitivity and resistance of tumor cells towards chemotherapy are still partially understood. Antineoplasic drugs have been shown to induce apoptosis in chemosensitive leukemias and solid tumors. In this work, cross-resistance among vincristine (VCR), doxorubicin (DOX) and other antineoplasic agents commonly used in the treatment of leukemia such as etoposide (VP-16), methotrexate (MTX), cyclophosphamide (CTX), dexamethasone (DEX), cytarabine (Ara-C) and L-asparaginase on vincristine resistant (LBR-V160), doxorubicin resistant (LBR-D160) and sensitive (LBR-) murine leukemic T cell lines, was determined. The effect of antineoplasic agents was assayed by tritiated thymidine incorporation. Our results showed that VCR exhibited cross-resistance with DOX, VP-16, DEX and MTX, while DOX demonstrated cross-resistance with VCR, VP-16 and MTX. Ara-C failed to present cross-resistance with any cell line. Apoptosis induced by the above drugs on the same cell lines was analyzed by acridine orange and ethidium bromide staining, DNA hypoploidy (flow cytometry) and oligonucleosomal fragmentation of nuclear DNA showing that therapeutic concentrations of these chemotherapeutic agents induced apoptosis in the LBR- cell line. Our results demonstrated that, except for DEX, none of the drugs presenting cross-resistance were able to induce cell death on LBR-V 160 or LBR-D 160 cell lines.
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PMID:Correlation between decreased apoptosis and multidrug resistance (MDR) in murine leukemic T cell lines. 1169 8

Cyclophosphamide is an alkylating agent used as chemotherapy for cats with lymphoma, carcinomas and sarcomas. Clinical and pharmacokinetic studies of cyclophosphamide in normal and tumor-bearing cats have shown minimal toxicity and cyclophosphamide at clinically used dosages rarely requires dosage adjustment or treatment delays. Dose intensity appears important for treatment of most cancers; the aim of this study was to perform a modified dose escalation study of cyclophosphamide to establish the maximally tolerated dosage (MTD) for intravenous cyclophosphamide in cats. The dose limiting toxicity appeared to be neutropenia, and 30% of cats experienced grade 3 or grade 4 neutropenia at a cyclophosphamide dosage of 480mg/m2, which was determined as the MTD. Delayed neutropenia was observed commonly at higher dosages. Thrombocytopenia was less common than neutropenia, and always transient. Gastrointestinal toxicities were uncommon even at MTD. The recommended dosage for single agent cyclophosphamide in cats is 460mg/m2 with a post-treatment interval of three weeks, with hematology performed before any subsequent chemotherapy is administered. This dosage appears safe in combination with prednisolone and l-asparaginase; but has not been evaluated in combination with other chemotherapy agents, or with a post-treatment interval shorter than 3 weeks. Such combinations and shorter intervals are found in some protocols, so this recommended cyclophosphamide dose cannot be considered a direct substitute for cyclophosphamide dosages in existing protocols. There is a suggestion that inadequate renal function may exacerbate the myelosuppression of cyclophosphamide which should be further evaluated.
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PMID:Dosage escalation of intravenous cyclophosphamide in cats with cancer. 3050 42


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