Multidrug resistance (MDR) of cancer cells remains a major obstacle to favorable outcomes of treatment with many drugs, including doxorubicin. Most of the clinical trials failed to demonstrate the benefit of the drug efflux transporter P-glycoprotein (P-gp) inhibitors to circumvent P-gp-mediated drug resistance in vivo. The present study explored the therapeutic potential of combined treatment with liposomal doxorubicin, P-gp inhibitor quinine, and the photodynamic therapy (PDT) using indocyanine green (ICG) in the adenocarcinoma drug-resistant tumor model.
View Article and Find Full Text PDFAntitumor therapy in the elderly is particularly challenging due to multiple, often chronic diseases, poly-therapy, and age-related physiological changes that affect drug efficacy and safety. Furthermore, tumors may become more aggressive and drug-resistant with advanced age, leading to poor patient prognosis. In this study, we evaluated in mice bearing medulloblastoma xenografts the effect of age on tumor progression and tumor therapy.
View Article and Find Full Text PDFPurpose To compare both periablational and systemic effects of two mechanistically different types of ablation: thermal radiofrequency (RF) ablation and electroporative ablation with irreversible electroporation (IRE) in appropriately selected animal models. Materials and Methods Animal experiments were performed according to a protocol approved by the Animal Care Committee of Hebrew University. Female C57BL/6 mice (n = 165) were randomized to undergo either RF or IRE ablation of noncancerous normal liver.
View Article and Find Full Text PDFAims: To determine how the accumulation of drug in mice bearing an extra-hepatic tumor and its therapeutic efficacy are affected by the type of PEGylated liposomal doxorubicin used, treatment modality, and rate of drug release from the liposomes, when combined with radiofrequency (RF) ablation.
Materials And Methods: Two nano-drugs, both long-circulating PEGylated doxorubicin liposomes, were formulated: (1) PEGylated doxorubicin in thermosensitive liposomes (PLDTS), having a burst-type fast drug release above the liposomes' solid ordered to liquid disordered phase transition (at 42°C), and (2) non-thermosensitive PEGylated doxorubicin liposomes (PLDs), having a slow and continuous drug release. Both were administered intravenously at 8 mg/kg doxorubicin dose to tumor-bearing mice.
Recently, developing drug delivery systems exhibiting controlled drug release at the tumor sites emerged as an attractive option for enhancing anticancer therapeutic efficacy. It seems, however, unlikely that single agent therapies will prove effective enough against the myriad cells present within the malignancy. Therefore, next generation nanotherapeutics must not only find their way to the solid tumor but also must effectively destroy the diverse populations of cells promoting tumor growth.
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