Aldoxorubicin and Temozolomide combination in a xenograft mice model of human glioblastoma.

Glioblastoma Multiforme (GBM) is still an incurable disease. The front-line Temozolomide (TMZ)-based therapy suffers from poor efficacy, underlining the need of new therapies. Preclinically, Aldoxorubicin (Aldox), a novel prodrug of Doxorubicin (Dox), has been successfully tested against GBM, encouraging the study of its association with other agents.

Morphine modulates doxorubicin uptake and improves efficacy of chemotherapy in an intracranial xenograft model of human glioblastoma.

Morphine may alter the permeability of Blood-Brain Barrier (BBB), enhancing the access of molecules normally unable to cross it, as Doxorubicin (Dox). In addition, morphine seems to mediate the uptake of Dox into the brain by its reduced efflux mediated by P-glycoprotein (P-gp). We evaluated the antitumor efficacy of Dox plus morphine treatment by an orthotopic glioblastoma xenograft model.

Blood-Brain Barrier and Breast Cancer Resistance Protein: A Limit to the Therapy of CNS Tumors and Neurodegenerative Diseases.

The treatment of brain tumors and neurodegenerative diseases, represents an ongoing challenge. In Central Nervous System (CNS) the achievement of therapeutic concentration of chemical agents is complicated by the presence of distinct set of efflux proteins, such as ATP-Binding Cassette (ABC) transporters localized on the Blood-Brain Barrier (BBB). The activity of ABC transporters seems to be a common mechanism that underlies the poor response of CNS diseases to therapies.

Mitochondria of a human multidrug-resistant hepatocellular carcinoma cell line constitutively express inducible nitric oxide synthase in the inner membrane.

Mitochondria play a crucial role in pathways of stress conditions. They can be transported from one cell to another, bringing their features to the cell where they are transported. It has been shown in cancer cells overexpressing multidrug resistance (MDR) that mitochondria express proteins involved in drug resistance such as P-glycoprotein (P-gp), breast cancer resistant protein and multiple resistance protein-1.

Delivery of doxorubicin across the blood-brain barrier by ondansetron pretreatment: a study in vitro and in vivo.

Doxorubicin (Dox) has got a limited efficacy in the treatment of central nervous system tumors because of its poor penetration through blood-brain barrier mediated by MDR efflux transporters. We investigated the possibility that ondansetron (Ond) enhances Dox cytotoxicity in cell lines interfering with P-glycoprotein and increases Dox concentration in rat brain tissues. The MDR phenotype was studied using human hepatocellular carcinoma cell line PLC/PRF/5 (P5 and P1(0.