Intrathecal liposomal cytarabine in relapsed or refractory infant and pediatric leukemias: the Children's Hospital of Philadelphia experience and review of the literature
ABSTRACT Intrathecal chemotherapy is integral to curing childhood leukemia; however, bioavailability is limited by the blood-brain barrier. Recently FDA-approved, intrathecal liposomal cytarabine (ITlipAC) increases drug concentration over time with fewer invasive procedures. We present a series of 4 children, including 2 infants, with relapsed central nervous system leukemia who went into remission using ITlipAC, with a review of the literature reporting ITlipAC use in children with relapsed leukemia. Drug-attributable side effects were observed more frequently in children with preexisting neurologic conditions and with adult dosing. Combined with other pediatric reports, our experience supports the efficacy of ITlipAC in pediatric and infant leukemic meningitis.
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Article: From the Sea to Anticancer Therapy[Show abstract] [Hide abstract]
ABSTRACT: Discovery, isolation, characterisation and pre-clinical and clinical trials of plant- or animal-derived drugs displaying pharmacological activities continue to develop and enlarge. Cancer chemotherapy is one of the most promising areas for these drugs. Since a very long time, nature has been an attractive source of potential medicinal agents for human use. The deep sea is becoming a novel and potently appealing source for new drugs, as well as shallow waters. This interest is mainly related to the terrific chemical diversity found in the vast number of plants and animal species, as well as in the microbial world. During the evolution, a rich source of biologically active compounds is developed in the depths of the sea, often reflecting ecological adaptation. Most of them (toxins) are developed to allow survival and flourishing acting against predators and parasites. Recent progress in Scuba diving, hi-tech/biotechnological and procedural advances in structure clarification, organic synthesis and biological assay determined the characterisation and preclinical/clinical evaluation of novel anticancer drugs. The aim of this review is to provide a description of their discovery, mode of action and clinical application.Current Medicinal Chemistry 08/2011; 18(23):3551-62. DOI:10.2174/092986711796642652 · 3.85 Impact Factor
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ABSTRACT: Classical chemotherapeutic agents such as mitotic inhibitors (spindle poisons), alkylating agents, antimetabolites, topoisomerase inhibitors, and anthracenediones (anthracyclines) inhibit DNA synthesis and mitosis, thereby killing or impeding the proliferation of rapidly dividing cells. During the last decade, targeted therapy has gained advantage over conventional treatment regimens, as it is more effective against cancer and also much less harmful to normal cells, thus minimizing the side-effects of chemotherapy. This type of treatment blocks the proliferation of cancer cells by inhibiting the function of specific targeted molecules needed for tumor growth and metastasis. Targeted therapy agents include monoclonal antibodies and small-molecule inhibitors, which most commonly target receptor and/or non-receptor tyrosine kinases. Most members of the BCL2 apoptosis-related family regulate cellular fate as a response to antineoplastic agents. Modulations at the mRNA and protein levels of these genes are usually associated with sensitivity or resistance of various types of cancer cells to chemotherapeutic drugs. Moreover, alterations in expression of BCL2-family members, induced by anticancer drug treatment, can trigger or simply facilitate apoptosis. In this review, we summarize information about changes in apoptosis-related gene expression caused directly or indirectly by antineoplastic agents, as well as about the impact of BCL2-family members on the chemosensitivity or chemoresistance of cancer cells.Anti-cancer agents in medicinal chemistry 06/2013; 14(3). DOI:10.2174/18715206113139990091 · 2.94 Impact Factor
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ABSTRACT: Biological barriers represent a stumbling block to the pharmacological treatment of lesions occurring in central nervous system or retina. The advent of nanodrugs was welcomed as a means to tide over and cross the barriers. Expectations, however, have not been completely fulfilled, as nanocarriers often accumulated at the endothelial frontier, rather than cross it over. The super-paramagnetism of iron oxide nanoparticles improved the diagnostic power of the magnetic resonance imaging and opened new perspectives. These nanoparticles, which can be addressed to the target organ by an external magnetic field, provide local imaging of the lesion, on-demand release of therapeutic agent, and subsequent imaging of the repair. Nanogels that present a sol–gel phase transition at body temperature are easy to inject and remain immobilized near the site of injection. There they promote prolonged and sustained release of drugs, or frame a shell for cell precursors to fully develop into mature neurons or glia.Handbook of Nanotoxicology, Nanomedicine and Stem Cell Use in Toxicology, 2014 edited by Saura C. Sahu and Daniel A. Casciano, 04/2014: chapter 13 - Part 2: pages 224-247; John Wiley & Sons, Ltd.., ISBN: 978-1-118-43926-5.