We studied the cellular enzymatic defenses against anthracycline-induced free radical damage in the HL60 human myelogenous leukemia cell line and in its anthracycline-resistant subline, HL60/AR. Intracellular glutathione (GSH) levels and gamma-glutamyl transpeptidase activity were lower in HL60/AR than in HL60 cells. Glutathione-S-transferase (GST) and glutathione peroxidase activities were sim...

A major obstacle to the therapeutic use of anthracyclines, highly effective anticancer agents, is the fact that their administration results in dose-dependent cardiomyopathy. According to the currently accepted hypothesis, anthracyclines injure the heart by generating oxygen free radicals. The ability of pyridoxal isonicotinoyl hydrazone (PIH) and salicylaldehyde isonicotinoyl hydrazone (SIH) -...

high-dose extended-interval dosage (hded) regimen of aminoglycosides is now considered as the standard dosage strategy in sepsis. although safety and efficacy of this dosing regimen is well studied, but new experiments show increased the risk of resistance development associated with %t>mic less than 60% of the dosing interval following extended interval dosing. moreover, limited information is...

Resistance to chemotherapy and a high relapse rate highlight the importance of finding new therapeutic options for the treatment of acute myeloid leukemia (AML). Histone deacetylase (HDAC) inhibitors (HDACIs) are a promising class of drugs for the treatment of AML. HDACIs have limited single-agent clinical activities, but when combined with conventional or investigational drugs they have demons...

BACKGROUND/AIM In the search for new derivatives of anthracycline antibiotics, formamidinodaunorubicins containing in the amidine group either a morpholine moiety (DAUFmor) or a hexamethyleneimine moiety (DAUFhex) were synthesized. The biological effects of daunorubicin (DAU), DAUFmor and DAUFhex were compared. MATERIALS AND METHODS The experiments were performed on human acute lymphoblastic ...

Purpose With the advent of more aggressive cytotoxic chemotherapy regimens, the incidence of ocular toxicity due to these drugs is also on the rise. We report a case of Presumed Chemotherapy-Induced optic neuropathy and maculopathy secondary to treatment with cytarabine and daunorubicin for Acute Myeloid Leukaemia (AML). Case report A 50-year-old man with AML developed sudden decrease in visi...

Attempts to overcome multi-drug resistance in acute myeloid leukaemia (AML) have been limited by toxicities. To investigate the effect of reducing peak drug levels, we performed sequential phase II studies using continuous infusion daunorubicin and cytarabine without (AD) and then with ciclosporin (ADC) in older patients with AML. Untreated patients (age 56+ years) received daunorubicin (45 mg/...

Streptomyces peucetius, a microorganism that produces the anticancer drugs doxorubicin and daunorubicin, is itself resistant to the action of these drugs. The genes conferring resistance to doxorubicin and daunorubicin in S. peucetius have been sequenced (P. G. Guilfoile and R. Hutchinson, Proc. Natl. Acad. Sci. USA 88:8553-8557, 1991). Two open reading frames, drrA and drrB, were proposed to e...