Cyclosporin A abrogates pleiotropic drug resistance in certain experimental tumors. Its impact on drug-sensitive tumors has not been investigated. Our studies show that in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 cyclosporin A enhances daunorubicin inhibition of DNA synthesis in vitro and prolongs survival of host mice in vivo. Of particular interest is that cyclosporin A conve...

Both Adriamycin and daunorubicin undergo carbonyl reduction and glycosidic cleavage. We have investigated kinetic parameters of these reactions with several mam malian species including humans. Adriamycin and daunorubicin showed similar K values for reduction in all organs studied except those from rabbits. Both rabbit liver and kidney have a much lower K for Adriamycin reduction. In contrast t...

Unilamellar liposomes that retain their contents in the systemic circu lation can alter the pharmacokinetics of anticancer agents in favorable ways. It has long been recognized that certain liposome compositions will extravasate at sites of growing tumors and may increase the local drug concentration substantially above that achievable with a free drug. We report here that liposomes can alter t...

Chemotherapy-induced immunogenic cell death can favor dendritic cell (DC) cross-priming of tumor-associated antigens for T cell activation thanks to the release of damage-associated molecular patterns, including ATP. Here, we tested the hypothesis that in acute myeloid leukemia (AML), ATP release, along with its well-known immune stimulatory effect, may also contribute to the generation of an i...

1. Forssen EA, Ross ME. Daunoxome treatment of solid tumors: preclinical and clinical investigations. J Liposome Res 1994; 4:481-512. 2. Money-Kyrle JE, Bates E, Ready J, Gazzard BG, Phillips RH, Boag FC. Liposomal daunorubicin in advanced Kaposi’s sarcoma: a phase II study. Clin Oncol 1993; 5:367-371. 3. Michieli M, Damiani D, Ermacora A, Masolini P, Michelutti A, Baccarani M. Liposome encapsu...

Several stressors are known to influence epithelial tight junction (TJ) integrity, but the association between DNA damage and TJ integrity remains unclear. Here we examined the effects of daunorubicin and rebeccamycin, two anti-tumor chemicals that induce DNA damage, on TJ integrity in human intestinal epithelial cells. Daunorubicin and rebeccamycin dose-dependently enhanced transepithelial ele...

Vaults may contribute to multidrug resistance by transporting drugs away from their subcellular targets. To study the involvement of vaults in the extrusion of anthracyclines from the nucleus, we investigated the handling of daunorubicin by drug-sensitive and drug-resistant non-small lung cancer cells, including a green fluorescent protein (GFP)-tagged major vault protein (MVP)-overexpressing t...

Anthracycline antibiotics are potent anticancer drugs widely used in the treatment of solidtumors and hematological malignancies. Because of their extensive clinical use and their toxiceffect on normal cells, in the present study the effect of these drugs on multipotent hematopoieticbone marrow cells was investigated employing, viability tests, PARP cleavage, Hoechst 33258staining, DNA fragment...