Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inosine dialdehyde (IdA), a new antitumor agent presently undergoing clinical evaluation in man, possesses two aldehyde groups that form stable complexes with a variety of biologic molecules containing amino groups. Complex formation of IdA with lysine, glycine, histidine, or bovine serum albumin (BSA) greatly reduces the cytotoxicity of IdA against L1210 leukemia in vitro. Complexes of IdA and BSA exhibit molecular weights ranging from 69,000 to greater than 800,000 as determined by Sephadex G-200 gel filtration, indicating that both aldehyde groups of IdA are functional and can cross-link protein molecules. The cross-linking of plasma proteins and the cross-linking of glycine to BSA were also observed. No interaction of IdA with nucleic acids, nucleic acid bases, or nucleosides was detected. The dialdehyde derivatives of other nucleosides also possessed cross-linking properties.
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PMID:Protein cross-linking properties of the antitumor agent inosine dialdehyde (NSC-118994). 103 30

Experiments were carried out in vitro using DNA polymerase and ribonucleotide reductase inhibitors to investigate their cytotoxicity to P388 murine leukemia sensitive (P388/S) and resistant (P388/R) to adriamycin (ADR). DNA polymerase inhibitors such as cytosine arabinoside (ara-C) and aphidicolin elicited comparative inhibition of DNA biosynthesis in both parental and ADR-resistant tumor cells. However, ribonucleotide reductase inhibitors such as hydroxyurea (HU) and caracemide were collaterally more sensitive to P388/R cells. Inosine diglycolaldehyde (Inox) was ineffective in showing such a response. Pretreatment with HU significantly increased intracellular ADR levels and inhibition of RNA biosynthesis by ADR in P388/R cells while, in P388/S cells, sequential or concurrent treatment with HU did not enhance intracellular ADR levels. Mechanisms underlying such an effect, implications due to reduced intracellular ATP levels in drug-resistant cells, and the possible utility of using ribonucleotide reductase as a target in drug-resistant tumors for the therapeutic benefit are discussed.
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PMID:Differential effect of collaterally sensitive antimetabolites on P388 murine leukemia sensitive and resistant to adriamycin in vitro. 251 59

A phase I trial of diglycoaldehyde (Inox) in children with leukemia established that the maximum tolerated dose of a 5-day schedule was 1.5 g/m2/day. A phase II study was undertaken by the Children's Cancer Study Group to evaluate the efficacy of this dose. Forty-seven children with acute leukemia refractory to conventional forms of therapy were entered in the study: 29 patients with acute lymphocyte leukemia/acute undifferentiated leukemia and 18 with acute nonlymphocytic leukemia. Inox was administered at a dose of 1.5 g/m2 as a 4-6 hour iv infusion daily for 5 days every 14 days. Toxic effects included myelosuppression, proteinuria, nausea, vomiting, diarrhea, local tissue reactions, hypocalcemia, transitory serum amylase elevation, and transitory hypotension. There was one life-threatening episode of drug-related renal toxicity. Of the 27 patients who received a minimum of two courses, partial remissions were observed in two patients with acute nonlymphocytic leukemia. Inox was inactive against advanced acute lymphocytic leukemia.
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PMID:Phase II evaluation of diglycoaldehyde (Inox) in children with acute leukemia: a children's cancer study group report. 742 52