The University of California, San Francisco (UCSF) is a major center for the treatment of patients with cancer of the central nervous system (CNS). Children represent approximately 25% of all new patients operated on and seen in consultation for the treatment of CNS malignancies. This proposal seeks to provide the resources necessary to bring together individuals who can build an integrated investigational program. The focus of this Program is fundamental research to provide insights important for understanding childhood brain tumors and translation of these advances into clinical management tools that will improve the care of children with brain tumors. We seek to provide an environment in which laboratory research emerges from the identification of clinically recognized opportunities and from which lines of investigation focused on improving patient care through the development of improved modalities for diagnosis and treatment are nurtured. The Program described in this proposal should become a focus for clinical, research, and training programs to improve the care of children with brain tumors. Dr. Mark Israel and Dr. Michael Edwards will direct a program that seeks to bridle the outstanding clinical and research resources at UCSF into a cohesive, synergistic research effort that integrates clinical and basic science activities. The institutional environment and the resources available at UCSF make it a particularly efficacious site for this undertaking. The Program includes a clinical project lead by Drs. Prados and Edwards that will be the intellectual focal point holding this Program together. Three laboratory research projects are also proposed by pediatricians who currently direct major research laboratories and are poised to include in their efforts studies focused on: 1) the pathogenesis of pediatric brain tumors, 2) the development of new markers to optimize currently available modalities of treatment, and 3) the response of pediatric nervous system tumors to biologically derived agents that can be expected to modify the clinical behavior of these malignancies. The resources requested in this proposal offer the opportunity to organize the care of pediatric brain tumor patients at UCSF around a research focus. An emphasis has been placed on developing the framework and mechanisms through which an integration of research identifying fundamental biological characteristics of these tumors and clinical investigations to capitalize upon these insights can be pursued. We believe this framework will nurture the cross-fertilization required for both the formulation of new ideas that emerge from clinical insights and the translation of these ideas into new treatment approaches and, eventually, prevention strategies.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory Grants (P20)
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Special Emphasis Panel (SRC (44))
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Prados, M D; Edwards, M S; Chang, S M et al. (1999) Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: results of a Phase II study. Int J Radiat Oncol Biol Phys 43:279-85
Russo, C; Fischbein, N; Grant, E et al. (1999) Late radiation injury following hyperfractionated craniospinal radiotherapy for primitive neuroectodermal tumor. Int J Radiat Oncol Biol Phys 44:85-90
Prados, M D; Edwards, M S; Rabbitt, J et al. (1997) Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen. J Neurooncol 32:235-41
Prados, M D; Wara, W; Edwards, M S et al. (1996) Treatment of high-risk medulloblastoma and other primitive neuroectodermal tumors with reduced dose craniospinal radiation therapy and multi-agent nitrosourea-based chemotherapy. Pediatr Neurosurg 25:174-81
Haas-Kogan, D A; Yount, G; Haas, M et al. (1996) p53-dependent G1 arrest and p53-independent apoptosis influence the radiobiologic response of glioblastoma. Int J Radiat Oncol Biol Phys 36:95-103
Yount, G L; Haas-Kogan, D A; Vidair, C A et al. (1996) Cell cycle synchrony unmasks the influence of p53 function on radiosensitivity of human glioblastoma cells. Cancer Res 56:500-6
Chang, S M; Fryberger, S; Crouse, V et al. (1995) Carboplatin hypersensitivity in children. A report of five patients with brain tumors. Cancer 75:1171-5
Cobbs, C S; Brenman, J E; Aldape, K D et al. (1995) Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res 55:727-30
Jensen, S; Paderanga, D C; Chen, P et al. (1995) Molecular analysis at the NF1 locus in astrocytic brain tumors. Cancer 76:674-7
Prados, M D; Wara, W M; Edwards, M S et al. (1995) The treatment of brain stem and thalamic gliomas with 78 Gy of hyperfractionated radiation therapy. Int J Radiat Oncol Biol Phys 32:85-91

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