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Brain Tumor Biology
Together with the Center for Cancer and Immunology Research (CCIR), the Divisions of Hematology/Oncology (Max Coppes, MD, PhD, Chief) and Neurology (Roger J. Packer, MD, Chief), have a particular interest in pediatric brain tumors, with both clinical and basic science research expertise enhancing progress in this area. As part of these investigations, we have used brain tumors as model systems for studies of cancer biology. Work in this field promises to fuel translational research and the ultimate application of the findings in cancer biology to brain tumor treatment.
Also, in the study of a related tumor, neuroblastoma, Stephan Ladisch, MD, has defined the role of the microenvironment in tumor progression and new prognostic factors in neuroblastoma in his National Institutes of Health (NIH) supported work, through investigation of ganglioside metabolism in these tumors. Tobey J. MacDonald, MD, has generated medulloblastoma cells deficient in Platelet Derived Growth Factor Receptor to study the role of this receptor in medulloblastoma and is collaborating with Maria Santi, MD, in Neuro-Pathology to perform high-throughput tissue microarray screening to identify additional novel biomarkers for therapeutic intervention in gliomas, medulloblastomas and other tumors. Additional collaboration with NIH and The Institute for Genomic Research (TIGR) laboratories further strengthens our initiative to dissect the key signaling pathways involved in childhood brain tumorigenesis.
Dr. MacDonald is also collaborating with Derrick Bruce, MD, and Amanda Yaun, MD, in Neurosurgery to establish the first orthotopic medulloblastoma brain tumor xenograft model with which to study brain tumor biology in vivo and conduct preclinical evaluations of novel drugs for the treatment of childhood brain tumors.
The goal of cancer therapies is to eliminate cancer cells completely while minimizing harm to normal cells. The difficulties are that treatments often have unwanted side-effects on normal cells and, even when the cancer is in remission, there is a chance that cancers can recur if some cancer cells escape treatment. Recent studies provide evidence that cancers are initiated by cells with properties similar to stem cells. These cells comprise a small percentage of the tumor cell population but can reconstitute the heterogeneous cell types of the original tumor. This suggests that cancer is caused by stem cell dysfunction. David M. Panchision, PhD, is investigating the relationship between improper stem cell regulation in the brain and the progression of cancer. With Brian R. Rood, MD, Dr. Panchision maintains a protocol to obtain brain tumor tissue samples directly from surgery. Stem cells and other progenitor cell types are isolated from these tumors and analyzed in culture, by flow cytometry and in an orthotopic NOD/SCID mouse xenograft model. The objective is to identify exploitable molecular targets to more selectively target Central Nervous System tumors while sparing normal cells.
For more information contact:
Stephan Ladisch, MD
Vice Chair
External Affairs, Department of Pediatrics
Children's Research Institute
Center for Cancer and Immunology Research
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-3898
202-476-3929 fax
sladisch@cnmc.org
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