We demonstrated the sensitivity profiles of pediatric tumor cells to every inhibitor class employing paired lumi nescent viability and apoptosis assays and IP kinase assays. Oligonucleotide microarray studies recommended novel candidate proteins involved inside the cell cycle in medulloblastoma that happen to be diminished by AKT inhibition during the administration of sublethal doses of inhibitors. We have now even more char acterized and validated these candidates by quantitative PCR in cell lines and clinical samples. AKT2 siRNA remedy of model cell lines sensitized this article DAOY and VC312 cells to cisplatin. Confocal immunofluorescence micros copy studies unveiled an association among active AKT and certain stages of mitosis. Our data recommend the results in the therapeutic inhibition of AKT as being a signifies of improving chemotherapeutic response is dependent upon activity toward the AKT2 isotype and that AKT inhibition may also have sustained cytostatic effects which can be exploited in vivo.
CB 35. NEUROFIBROMATOSIS one Reduction PROMOTES CXCL12 DEPENDENT GLIOMA Pomalidomide Growth BY DISABLING CXCR4 DESENSITIZATION Nicole M. Warrington,1 B. Mark Woerner,1 Arie Perry,3 Girish C. Daginakette,2 David H. Gutmann,two Joshua B. Rubin1,two,four, Departments of 1Pediatrics, 2Neurology, 3Pathology, 4Anatomy and Neurobiology, Washington University School of Medication, St Louis, MO, USA Astrocytoma formation in neurofibromatosis form one occurs preferentially along the optic pathway during the 1st decade of lifestyle. The molecular basis of this different pattern of gliomagenesis is unknown but seems to become dependent on elements derived through the surrounding brain microenvironment. We previously demonstrated that the chemokine CXCL12 is expressed in a temporal and anatomic pattern that correlates together with the growth of NF1 related gliomas and that CXCL12 uniquely promotes the growth of Nf1 /, but not wild type, astrocytes.
These information recommend that CXCL12 is a essential component present from the evolving tumor microenvironment that regulates

the expansion of Nf1 deficient astrocytes and facilitates NF1 linked glioma development. To additional evaluate this hypothesis, we determined the molecular basis from the differ ence between wild style and Nf1 / astrocyte responses to CXCL12 and found that Nf1 loss promoted growth responses to CXCL12 by inhibiting the desensitization with the CXCL12 G protein coupled receptor. Receptor desensitization is a negative regulatory process that limits the strength and duration of receptor signaling. Desensitization is initiated by ligand induced, G protein receptor kinase mediated, receptor phosphorylation. In this regard, CXCL12 remedy of wild form astro cytes induced a three fold increase in CXCR4 phosphorylation, which resulted in the brief suppression of intracellular cAMP levels.