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Tumor cells grown in the presence of 1-O-alkyl-2-O-methylglycero-3-phosphocholine (AMG-PC) accumulated this ether lipid in their membranes. Depending on the cell type and the dose of the compound, up to 17% of the total phospholipids of the purified plasma membranes consisted of authentic AMG-PC. Extensive incorporation of the agent resulted in a decrease(More)
In our search for the mechanisms by which the drug 1-O-alkyl-2-O-methylglycero-3-phosphocholine (AMG-PC) inhibits tumor growth and metastasis, we have detected a metabolite, 1-O-alkyl-2-O-methylglycerol (AMG), in membranes of MO4 mouse fibrosarcoma cells grown in the presence of the drug. Synthetic AMG inhibited the activation of highly purified human(More)
Clinical use of anti-cancer alkylphospholipids is limited by gastrointestinal toxicity. However, new interest has emerged since it was shown that these drugs enhance the cytotoxic effect of conventional chemotherapy and radiotherapy in preclinical models. The aim of this study was to characterize the pharmacokinetic profile of perifosine, an oral analog of(More)
To improve nanoliposomal-doxorubicin (DoxNL) delivery in tumor cells using liposome membrane-incorporated short-chain sphingolipids (SCS) with selective membrane-permeabilizing properties. DoxNL bilayers contained synthetic short-chain derivatives of known membrane microdomain-forming sphingolipids; C8-glucosylceramide (C8-GluCer), C8-galactosylceramide(More)
BACKGROUND Phospholipase D (PLD) hydrolyzes phospholipids to generate phosphatidic acid (PA) and a free headgroup. PLDs occur as both intracellular and secreted forms; the latter can act as potent virulence factors. Exogenous PLD has growth-factor-like properties, in that it induces proto-oncogene transcription, mitogenesis and cytoskeletal changes in(More)
Diacylglycerol kinases (DGKs) metabolize diacylglycerol to phosphatidic acid. In T lymphocytes, DGKa acts as a negative regulator of TCR signaling by decreasing diacylglycerol levels and inducing anergy. In this study, we show that upon costimulation of the TCR with CD28 or signaling lymphocyte activation molecule (SLAM), DGKa, but not DGKz, exits from the(More)
Our improved understanding of the molecular processes that determine cellular sensitivity to ionizing radiation has accelerated the identification of new targets for intervention. Indeed, novel agents have become available for combined clinical use to overcome radioresistance and increase the therapeutic ratio of radiotherapy. Synthetic alkyl-phospholipid(More)
Alkyl-lysophospholipids have been shown to possess antitu-moral activity in animal and in human tumors. Among them, racemic 1-O-Å " tadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OCH3) had an antimetastatic effect in experimental tu mors. We investigated the effect of ET-18-OCH3 on invasion of MO4 mouse fibrosarcoma cells and on cellular activities(More)
1 XXX: name of the partner producing the report ™ TU/e, Philips, Agere or KPN Y: the number of the WorkPackage from which the report is originated ™ 1, 2, …, 8 DDD: distribution classification level ™ PUB (public), INT (internal), … NN: a (two) digit serial number associated to each partner, which is increased for each document created by the partner,(More)
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