PW1.04. Inhibitors of microvesicle release with the potential to enhance effectivity of cancer chemotherapy

Introduction: Microvesicle (MV) release from tumour cells plays an important role in cancer drug resistance. It is essential that chemotherapeutic drugs are retained within target cells for increased effectiveness in inducing apoptosis. Microvesiculation influences drug retention so minimizing drug efflux is important. Based on MV biogenesis pathways, a range of potential inhibitors were tested. Methods: The NanoSight LM10 was used to analyse MV release from PC3 human prostate cancer cells. Cells were maintained in serumfree RPMI 1640. Washed cells were seeded in triplicate at 3.8105 cells/well initially treated with 300 mM BzATP for 1 h, and further 1 h with relevant concentrations of MV-inhibitors. MV count, annexin V staining and cell viability were assessed. Results: The numbers of MVs released were compared to control (BzATP alone). Up to 60% clear inhibition of MV release was shown with all reagents used. The maximum MV inhibition was with 500 mM ethylene glycol tetraacetic acid (EGTA) and 10 mM bisindolymaleimide I, resulting in 48 and 34%, respectively. Cell viability was 80% in all cases except for panthethine, which only resulted in 25%. Annexin V staining confirmed the vesicles identified were indeed MVs. Summary/ conclusion: EGTA and bisindolymaleimide I are potent inhibitors of MV release. Both novel and classic reagents described may be used individually or in combination. This could be similar to calpeptin and chloramidine, which enabled prostate cancer cells to sensitize to docetaxel treatment previously. This study extends the range of inhibitors that can be utilized to enhance novel combinatory treatment options

Chapitre 7. La CECA et les États-Unis, les années de retrouvailles (1952-1953)

En 1952, la mise en place de la Communauté Européenne du Charbon et de l’Acier à Luxembourg justifie l’envoi d’une représentation gouvernementale américaine composée de membres du service du Mutual Security Agency (msa). La msa, qui remplace l’Economic Cooperation Administration du Plan Marshall en 1951, a pour tâche de concrétiser les programmes d’assistance militaire au monde libre, ainsi que les programmes de défense économique. D’emblée, la représentation américaine affiche une approche t..