The goal of this application is to develop a coordinated research center focused on pediatric brain tumors. A sizable multidisciplinary clinical program dedicated to prospective investigation forms the basis for establishing a directed effort in laboratory science. Central to the development of a scientific program is the commitment of resources to recruit one or more basic science faculty to study mechanisms of neoplastic development and/or therapeutic response in childhood brain tumors. To initiate the basic science component, we have identified institutional laboratories recognized for research in pediatric solid tumors. Investigators' efforts will be directed toward fundamental scientific and therapeutic questions in pediatric malignant gliomas. These activities are identified in the Basic Research Component as projects (1) examining the mechanisms of radiation-induced drug resistance, utilizing xenograft pediatric brain tumor cell cultures developed in the Core program as well as in vivo tissue obtained sequentially during protocol therapy, (2) exploring the use of computer- aided image analysis systems to assess treatment-induced single cell DNA damage, and (3) studying molecular mechanisms of alkylator resistance. The Core Components provides (1) a xenograft facility to develop in vivo models of pediatric malignant gliomas and (2) administrative coordination of the laboratory and clinical activities, a mechanism to identify and recruit basic science faculty for this effort and support to facilitate tissue acquisition and handling neuropathology correlation, biostatistical design and analysis, and data management. The proposed 3-year developmental program will provide a coordinated clinical and laboratory investigation effort focused on molecular and therapeutic pharmacology in pediatric malignant gliomas. At the conclusion of the feasibility period, the level of basic and clinical research will warrant support as a brain tumor research center.
| Marathi, U K; Howell, S R; Ashmun, R A et al. (1996) The Fanconi anemia complementation group C protein corrects DNA interstrand cross-link-specific apoptosis in HSC536N cells. Blood 88:2298-305 |
| Qian, X; von Wronski, M A; Brent, T P (1995) Localization of methylation sites in the human O6-methylguanine-DNA methyltransferase promoter: correlation with gene suppression. Carcinogenesis 16:1385-90 |
| Houghton, P J; Cheshire, P J; Hallman 2nd, J D et al. (1995) Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels in protracted schedules to mice bearing xenografts of human tumors. Cancer Chemother Pharmacol 36:393-403 |
| Kingsley, P B (1995) Magnetic field gradients and coherence-pathway elimination. J Magn Reson B 109:243-50 |
