CB 33. REGULATION OF CERULOPLASMIN BY HYALURONAN IN GLIOMA PROGENITORS S. Tye, A. G. Gilg, J. Knapp, L. Olson, J. R. Bethard, C. A. Welsh, Z. Rumbolt, I. Takacs, B. P. Toole, and B. L. Maria, Charles P. Darby Childrens Research Institute, Healthcare University of South Carolina, Charleston, SC, USA The multicopper oxidase enzyme Ceruloplasmin was not long ago proven to be secreted by a desmoplastic infantile ganglioglioma that most likely arises from multipotent Trichostatin A price progenitor cells. The function of this review was to determine no matter whether Ceruloplasmin is regulated by hyaluro nan, a sizable polysaccharide that promotes anti apoptosis, invasion, and drug resistance in malignant cells. As a result of FACS examination, we isolated a side population of cells through the rat C6 glioma cell line that expressed ABCG2 and have been tremendously drug resistant by virtue of their BCRP efflux of chemotherapy, moreover, we isolated BCRP beneficial neurospheres through the U87 human glioma cell line.
C6SP cells cul tured on matrigel for 10 days expressed the two neuronal and glial markers. Shikimate Western blotting showed that C6SP cells and U87 neurospheres contained drastically even more Ceruloplasmin than their respective mother or father lines. Antagonizing hyaluronan/CD44 interactions by treating C6SP and U87 neurospheres with hyaluronan oligomers decreased Ceruloplasmin manufacturing. IL one beta increased Ceruloplasmin and HIF one alpha production in C6 cells greater than in IL six, and IL six increased Ceru loplasmin and HIF one alpha manufacturing more in C6SP. C6 and C6SP cells engrafted into the rodent central nervous strategy the two expressed abundant Ceruloplasmin. Taken with each other, these benefits suggest that glioma cells and their progenitor subpopulations express Ceruloplasmin in vitro and in vivo, Ceruloplasmin production in glioma progenitors is heavily depen dent on hyaluronan/CD44 interactions, and downstream from hyaluro nan/CD44 interactions, inflammatory mediators modulate Ceruloplasmin manufacturing differently in glioma progenitors.
Ongoing research will deter mine how hyaluronan mediated Ceruloplasmin production contributes to anti apoptosis, invasion, and drug resistance in glioma progenitor cells. CB 34. CYTOSTATIC Results OF ISOTYPE SELECTIVE AKT INHIBITOR CANDIDATES IN
MODEL PEDIATRIC BRAIN TUMORS Timothy Van Meter, Anil Kumar, Catherine Dumur, William C. Broaddus, and Gary Tye, Departments of Neurosurgery, Anatomy and Neurobiology, and Pathology, School of Medicine, Virginia Commonwealth University Health Systems, VA, USA Previous studies from our laboratories reported characterization of AKT isotype expression and activity in PNET and medulloblastoma cell lines an enhanced sensitivity to cisplatin induced cell death in the presence of micromolar doses of PH domain directed AKT inhibitors. We deter mined the growth suppressive results of AKT inhibitors that have been characterized for their isotype selectivity.