Pleiotropic Chemotherapy to Abrogate Glioblastoma Multiforme Migration/Invasion.

Current clinical failure to cure primary glioblastoma multiforme in virtually all adult patients is due to genetic aberrations, molecular heterogeneity, and clonal evolution of tumor stem and differentiated cells within the core tumor, leading to their migration, invasion and proliferation in normal surrounding and in distant cerebral tissue sites. These factors are the causes of targeted drug resistance, inadequate surgical removal, and inadequate radio-therapeutic interventions. Resolution of this clinical conundrum may be found in administration of Withaferin A alone or in combination with pleiotropic drugs which address aberrant molecules and pathways promoting tumor cell motility, migration, invasion and proliferation.

Radiation-induced Demyelination and Remyelination in the Central Nervous System: A Literature Review.

Therapeutic radiation applied to the central nervous system concomitant with or followed by surgery and chemotherapy induces significant pathologic demyelination depending upon tumor volume, dosage, field of treatment, and age of patient, with consequent exacerbation of significant impairment of mental function including personality change, memory deficiencies, confusion, learning difficulties and dementia. These adverse clinical events may be ameliorated by the application of remyelinating measures including nutrition, supplements and pharmaceuticals prophylactically, concomitant with radiation or post-radiation treatment.

Distribution and Metabolism of Lipocurc™ (Liposomal Curcumin) in Dog and Human Blood Cells: Species Selectivity and Pharmacokinetic Relevance.

Background/aim: The aim of this study was to investigate the distribution of curcumin (in the form of Lipocurc™) and its major metabolite tetrahydrocurcumin (THC) in Beagle dog and human red blood cells, peripheral blood mononuclear cells (PBMC) and hepatocytes.

Materials And Methods: Lipocurc™ was used as the source of curcumin for the cell distribution assays. In vitro findings with red blood cells were also compared to in vivo pharmacokinetic data available from preclinical studies in dogs and phase I clinical studies in humans.

The Kynurenine Pathway: A Primary Resistance Mechanism in Patients with Glioblastoma.

The failure of chemotherapy and radiation therapy to achieve long-term remission or cure in patients with glioblastoma (GBM) is, in a large part, due to the suppression of the immune system induced by the tumors themselves. These tumors adapt to treatment with chemotherapy or radiation therapy by stimulating secretion of molecules that cause tryptophan metabolism to be disrupted. Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are produced, accelerating metabolism along the kynurenine pathway and resulting in excess levels of quinolinic acid, 3-hydroxyanthranilic acid and other neurotoxic molecules.

In Vitro Study of a Liposomal Curcumin Formulation (Lipocurc™): Toxicity and Biological Activity in Synovial Fibroblasts and Macrophages.

Background/aim: The polyphenol curcumin is produced in the rhizome of Curcuma longa and exhibits potent anti-inflammatory, antioxidant, and chemopreventive activities. Due to the fact that curcumin is poorly soluble in water, many delivery systems have been developed to improve its solubility and bioavailability achieving optimum therapeutic application. In this study, we evaluated the biological effects of a liposomal curcumin formulation (Lipocurc™) on human synovial fibroblasts (SW982) and mouse macrophages (RAW264).