This study examined effects of aging on the cardiac response in vitro to daunorubicin, a cancer chemotherapeutic agent that causes cardiotoxicity. Left ventricular trabeculae carneae from adult (aged 6-9 months) and old (aged 24-28 months) Fischer 344 rats were placed in oxygenated, physiological buffer. Preparations were treated with daunorubicin (175 microM) or saline (controls) over a 210-mi...

Background: Although significant advances have been made in the treatment of cancer, a significant number of patients with acute lymphoblastic leukemia (ALL) show resistance to treatment. Thus, it is necessary to seek novel therapeutic agents to overcome this problem. Studies have indicated that the expression level of mouse double minute 2 (MDM2), a negative regulator of p53, is markedly eleva...

Unilamellar liposomes that retain their contents in the systemic circulation can alter the pharmacokinetics of anticancer agents in favorable ways. It has long been recognized that certain liposome compositions may increase the local drug concentration substantially above that achievable with a free drug. We report here that liposomes can alter the in vivo disposition of an entrapped drug not o...

mic enzyme that converts daunorubicm to a principal metabolite, daunorubicino!, in the presence of NADPH. This enzyme, found in mammalian tissues and studied in rat tissue preparations and normal human blood components, is also present in human leukemic myeloblasts. The enzymes from both normal and leukemic leukocytes require NADPH for activity, have similar kinetics and substrate saturation ch...

Our aim was to examine the molecular basis for acute effects of the anthracycline daunorubicin on cardiac ryanodine receptor (RyR2) channels and cardiac calsequestrin (CSQ2). Cardiotoxic effects of anthracyclines preclude their chemotherapeutic use in patients with pre-existing heart conditions. To address this significant problem, the mechanisms of anthracycline toxicity must be defined but at...

Through the use of drug-adapted tissue culture cells, correlations have been observed between the level of specific enzymes and drug resistance. Drug resistance, however, may be due to multiple factors. To test whether the activity of daunorubicin reducÃ-aseor NADPH diaphorase independ ently influences in vitro daunorubicin-induced Cytotoxicity, we developed somatic cell hybrid clones to partia...

Through the use of drug-adapted tissue culture cells, correlations have been observed between the level of specific enzymes and drug resistance. Drug resistance, however, may be due to multiple factors. To test whether the activity of daunorubicin reductase or NADPH diaphorase independently influences in vitro daunorubicin-induced cytotoxicity, we developed somatic cell hybrid clones to partial...

Eleven N-enamine derivatives of daunorubicin and of its 5-imino analogue as well as of doxorubicin have been synthesized and evaluated for antileukemic activity in vitro and in vivo. Comparison of biological activities of examined compounds with other enamine derivatives of daunorubicin, reported earlier by us, has indicated that the optimal activity is shown by N-(1-carboethoxypropen-1-yl-2)da...

Despite advances in the treatment of T‑cell acute lymphoblastic leukemia (T‑ALL), the outcome of T‑ALL treatment remains unsatisfactory, therefore, more effective treatment is urgently required. The present study examined the cytotoxicities of bortezomib in combination with daunorubicin against human Jurkat and Molt‑4 T‑ALL cells and primary T‑ALL cells. Compared with treatment alone, co‑exposu...