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Induction of differentiation and tetraploidy by long-term treatment of C6 rat glioma cells with erucylphosphocholine
No full textInduction of differentiation represents a promising concept for chemotherapy of malignant gliomas, which are often refractory even to the combined treatment with surgery, irradiation and chemotherapy. Since anti-neoplastic alkyl-phosphocholines can induce differentiation of leukemic cell lines, the effects of the intravenously applicable alkyl-phosphocholine-derivative erucylphosphocholine (ErPC) on proliferation, morphology and differentiation of the rat glioma cell line C6 was examined in vitro. Short-term exposure to ErPC induced accumulation of the cells in the G2/M-phase of the cell cycle and apoptotic cell death. In contrast, continuous exposure of C6 rat glioma cells to sublethal ErPC doses (30 and 50 muM) caused both the formation of a slower growing tetraploid cell population and astrocytic differentiation. No resistance to in vivo obtainable ErPC concentrations was observed during this treatment. We conclude that ErPC-induced differentiation might be beneficial for a long-term adjuvant chemotherapy of low grade glioma
Alkylglycerol-mediated increase in drug delivery to the normal brain and to brain tumors in rats: Regulation of drug transfer and comparison with hypertonic mannitol and bradykinin
No full textThe mitochondrial pathway is central to erucylphosphocholine-mediated apoptosis in human glioma cell lines
No full textErufosine-induced apoptosis is blocked by peripheral-type benzodiazepine receptor (PBR) ligands in human glioma cells
No full textTransient and controllable opening of the blood-brain barrier to cytostatic and antibiotic agents by alkylglycerols in rats
No full textThe blood-brain barrier hinders progress in the chemotherapy of brain tumors due to insufficient penetration of anticancer drugs into the brain tissue. Short-chain alkylglycerols affect the physicochemical proper ties of biological membranes. The enhancement of the blood-brain barrier permeability by intra-arterial administration of alkylglycerols was investigated in tumor-free and C6 astroglioma bearing rats. The antineoplastic agents cisplatin and methotrexate and the antibiotics vancomycin and gentamicin were selectively injected into the right internal carotid artery in the absence and presence of various alkylmono-, alkyldi-, and alkyltri-glycerols. In normal rats the intra-arterial administration of the drugs without alkylglycerols resulted in low drug concentrations in brain tissue. In the presence of alkylglycerols (0.01-0.3 M) a reversible (within minutes) and concentration-dependent enrichment of the coinjected agents was found, preferentially in the ipsilateral hemisphere. The extent of drug accumulation in the brain was modified by changes in the chemical structure of the alkylglycerols. The effect increased with the chain length of the alkyl group, decreased with the number of glycerols, and varied from 2- to more than 230-fold compared to controls. In rats with C6 tumors 1-O-pentylglycerol increased the delivery of methotrexate 18-fold in the tumor, 28-fold in the surrounding brain, 18-fold in the contralateral brain, and 19-fold in the cerebellum compared to controls with methotrexate in the absence of pentyl-glycerol. In conclusion, the intra-arterial administration of alkylglycerols represents a novel and well controllable method for enhanced drug delivery to the brain and to brain tumors
Accidental cisplatin overdose in a child: Reversal of acute renal failure with sodium thiosulfate
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