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

The effects of eight antitumoral drugs known to cause anaphylactoid side effects in clinical use were studied in dogs. Blood pressure, heart rate, and blood and plasma histamine levels were monitored. L-asparaginase, methotrexate, 5-fluorouracil, bleomycin, and cisplatin had no effect on these parameters. Doxorubicin, Vehem (teniposide), and Vepeside (etoposide) induced hypotension, tachycardia, and a rise in histamine levels. In the cases of Vehem and Vepeside, the excipient (respectively, cremophor EL and tween 80) induced the same effects. These agents, like elliptinium, which had been previously studied, induce nonspecific histamine release--unlike the other drugs studied. The mechanism of clinically observed anaphylactoid side effects is discussed in the light of these findings.
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PMID:Study of histamine release induced by acute administration of antitumor agents in dogs. 245 32

The antitumor action of L-alanosine (NSC 153553) was investigated in murine leukemia P388 (P388/S), P388 resistant to adriamycin (P388/ADR), P388 resistant to vincristine (P388/VCR) and leukemia L5178Y sensitive to L-asparaginase (L5178Y/S). L-alanosine demonstrated good antineoplastic activity against P388/S and P388/ADR, whereas it showed better anticancer activity against P388/VCR and L5178Y/S at the various dose levels employed.
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PMID:Antitumor effect of L-alanosine (NSC 153553) on sensitive and resistant sublines of murine leukemias. 647 81

There is an ever-increasing number of therapeutics used to treat cancer. A recent publication listed 86 currently available antineoplastic medications. Despite this large number, hypersensitivity reactions are not common except with platinum compounds (cisplatin, carboplatin), epipodophyllotoxins (teniposide, etoposide), asparaginase, taxanes (paclitaxel), and procarbazine. Doxorubicin and 6-mercaptopurine are occasionally associated with hypersensitivity reaction. Comparable reactions with other chemotherapeutic agents are. uncommon; many are only anecdotal reports. Reactions associated with individual drugs are discussed in detail. The mechanisms responsible for most of these reactions are not known, as they have generally not been evaluated. The term "hypersensitivity" is widely used in the chemotherapy literature without a common definition. Hypersensitivity is defined here as an unexpected reaction with signs and symptoms not consistent with known toxicity of the drug. Most reactions are coincident with or within hours of drug administration. Almost all are associated with parenteral administration. Symptoms include flushing, alterations in heart rate and blood pressure, dyspnea and bronchospasm, back pain, fever, pruritus, nausea and all types of rashes. Some cases may be due to non-immune mediated release of histamine or cytokines, as many patients can subsequently tolerate re-exposure after pretreatment with steroids and antihistamine, and slow readministration of the drug. This is more compatible with a graded challenge, than desensitization and is generally successful for taxanes, less so for platinum compounds. In most cases hypersensitivity reactions are associated with the specific chemotherapeutic drug. Reaction rates may vary with different forms of the drugs, e.g. pegylated. Occasionally excipients such as Cremaphor EL may induce hypersensitivity reactions.
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PMID:Hypersensitivity reactions to chemotherapeutic drugs. 1272 96

We analysed the long-term outcome of the L86 protocol using L-asparaginase (L-asp), vincristine (VCR) and prednisolone (PSL), collectively known as LVP or L97 protocol using LVP along with pirarubicin hydrochloride (THP-ADR) for 97 patients with acute lymphoblastic leukemia (ALL) diagnosed between 1986 and 2002. No significant differences were seen in the two protocols regarding the complete remission (CR) rate or survival. Seventy-five of the 97 patients (77%) achieved a CR. The overall survival (OS) and disease-free survival (DFS) rates were 32.1% and 30.4% at 10 years, respectively. By univariate analysis, we identified seven adverse factors for DFS which included the L2 subtype by French-American-British classification, hepatosplenomegaly, a white blood cell count of more than 30 x 10(9)/L, a blast cell count of more than 10 x 10(9)/L in the peripheral blood, hemoglobin concentration greater than 10 g/dL, a serum lactate dehydrogenase value greater than twice the upper limit of normal and the presence of the Philadelphia chromosome (Ph). According to multivariate analysis, only the presence of Ph was a significant unfavourable factor for DFS and OS. In the 30 patients under 35 years of age without Ph, the OS in the 20 patients treated with L86 and in the 10 patients treated with L97 were 48 and 86%, respectively (P = 0.011). These results indicate that intensified chemotherapy, such as the L97 protocol that includes an anthracycline, might be beneficial for younger patients who are Ph-negative.
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PMID:Long-term outcome of L86 and L97 protocols for adult acute lymphoblastic leukemia. 1902 Oct 56

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, has a unique geographic distribution. Its pathology is characterized by marked angio-invasion and tissue necrosis. A typical NK-cell phenotype is usually present: CD2(+), CD3 epsilon+, CD56(+), cytotoxic molecules+ and Epstein-Barr virus (EBV)+. Magnetic Resonance Imaging helps to clearly define the local involvement. Positron Emission Tomography helps to demonstrate system spread. Various prognostic variables (International Prognostic Index or the Korean Prognostic Index) should be documented. This may include quantification of plasma EBV DNA. For localized nasal disease, radiotherapy is important, although chemotherapy is often added. Sustainable remission is observed in over half of these patients. For extra-nasal or disseminated disease, systemic chemotherapy becomes the mainstay and the prognosis is usually poor. Doxorubicin-containing regimens are not entirely satisfactory and L-asparaginase containing regimens are being investigated. Patients with poor prognostic features may be considered for an early autologous haematopoietic stem cell transplant. Allogeneic transplantation is efficacious but is associated with high transplant-related mortality.
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PMID:Advances in the management and monitoring of extranodal NK/T-cell lymphoma, nasal type. 1960 34

An enzyme-responsive drug delivery system was constructed from a pillar[5]arene-based polyethyleneglycol-substituted amphiphile which self-assembles into micelles in water. These micelles exhibit superior drug encapsulation capability, and display drug release behaviour in response to enzyme catalysis, in particular to L-asparaginase. Doxorubicin-loaded micelles show significant cytotoxicity against MCF-7 cancer cells.
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PMID:Enzyme-responsive pillar[5]arene-based polymer-substituted amphiphiles: synthesis, self-assembly in water, and application in controlled drug release. 2630 99