Glioblastoma multiforme is a uniquely resistant tumor to conventional surgery, radiation and chemotherapy. The 5-year disease free survival rate is greater than 2%. Virtually all of the deaths are due to progressive growth of tumor or the complication of treatment. For essentially all other human tumors there is a clearly recognizable local control rate following 60-70 Gy (at approximately 2 Gy per fraction) where tumors of comparable sizes are treated. The broad objective of the proposed research is to determine the extent to which the extraordinary resistance of GBMs is the consequence of: inherent cellular radiation resistance; unusually high numbers of Tumor Rescue Units per unit volume, micro-metabolic conditions which produce resistance (e.g., hypoxia) and or increase repair of radiation damage (e.g., high SH levels); rapid proliferation of tumor cells. The plan is to determine the values of the parameters alpha,beta, D(O), n, SF(2), and D for a large series of GBM and SCC cell lines. Concurrently, determine: the TCD-50-s, fractionation sensitivities, SF-6H, TRU numbers in xenografts, and the metabolic profile of these same xenografts. This latter planned work will require active collaboration with several investigators at other institutions with special technical capabilities and research interest in tumor pathophysiology. A secondary aim is to characterize the nude and scid mouse in terms of its residual immune reactivity after immune suppressive procedures (whole body irradiation, administration if immune suppressive agents, e.g., ALS, induction of immune tolerance, etc.).
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