Status of the light ion source developments at CEA/Saclay

ACC NIMInternational audienceSILHI (High Intensity Light Ion Source) is an ECR ion source producing high intensity proton ordeuteron beams at 95 keV. It is now installed in the IPHI site building, on the CEA/Saclay center. IPHI is a frontend demonstrator of high power accelerator. The source regularly delivers more than 130 mA protons in CWmode and already produced more than 170 mA deuterons in pulsed mode at nominal energy. The last beamcharacterisations, including emittance measurements, space charge compensation analysis and diagnosticimprovements, will be reported. Taking into account the SILHI experience, new developments are in progress tobuild and test a 5 mA deuteron source working in CW mode. This new source will also operate at 2.45 GHz andpermanent magnets will provide the magnetic configuration. This source, of which the design will be discussed,will have to fit in with the SPIRAL 2 accelerator developed at GANIL to produce Radioactive Ion Beams. TheH- test stand status is briefly presented here and detailed in companion papers.This work is partly supported by the European Commission under contract n°: HPRI-CT-2001-50021

Imatinib Mesylate Exerts Anti-Proliferative Effects on Osteosarcoma Cells and Inhibits the Tumour Growth in Immunocompetent Murine Models

Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma), a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1). Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma) and POS-1 (undifferentiated osteosarcoma). Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R), appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor status of patients