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Neuro-oncology/Neurofibromatosis
Brain tumors are the most common solid tumor in children, with nearly 2,500 new patients diagnosed every year, and are the leading cause of death due to cancer in children. The Neuro-Oncology Program at Children’s National Medical Center is recognized both nationally and internationally as a preeminent leader in the field of childhood brain tumor research and treatment. Nearly 10 percent of all the brain tumor patients diagnosed in the United States are treated at Children's by a highly skilled, multidisciplinary team that includes experts in pediatric neuro-oncology (Tobey J. MacDonald, MD, and Brian R. Rood, MD), neurology (Roger J. Packer, MD), neurosurgery (Derek Bruce, MD, John Myseros, MD, Amanda Yuan, MD), neuropathology (Maria Rita Santi, MD), and neuro-radiology (Louis-Gilbert Vézina, MD). At Children's, the Neuro-Oncology team provides state-of-the-art clinical care and delivery of the most advanced treatments and novel experimental therapeutics for childhood brain tumors through its active participation and leadership in the two largest national pediatric oncology groups, the Children’s Oncology Group and the Pediatric Brain Tumor Consortium.
In addition to clinical research and clinical therapeutic trials, the Neuro-Oncology team is engaged in cutting-edge laboratory research investigating the genetic causes, biology, immunology, and potential novel targeted treatments of these tumors:
Brain Tumor Biology and Immunology
Tobey J. MacDonald, MD, is working with Derek Bruce, MD, and Amanda Yaun, MD, in Neurosurgery to establish an orthotopic medulloblastoma brain tumor xenograft model to study brain tumor biology in vivo and conduct preclinical evaluations of novel drugs for the treatment of childhood brain tumors. Dr. MacDonald is also collaborating with Anamaris M. Colberg-Poley, PhD, and Stanislav Vukmanovic, MD, PhD, to elucidate the prevalence and role of herpes family viral infection of gliomas and the host immunologic response to medulloblastomas, respectively. Recently, Dr. MacDonald was elected to co-chair the Pediatric Brain Tumor Consortium (PBTC) Biology Committee.
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 CNS tumors while sparing normal cells.
Studies investigating brain tumor cells by Drs. MacDonald and Rood have implicated signaling through the epidermal growth factor (EGF) and platelet derived growth factor (PDGF) receptor pathways to be critical to the progression of childhood glioma and medulloblastoma. Dr. MacDonald has generated medulloblastoma cells deficient in PDGFR and Dr. Rood is investigating the relationship between the HIC-1 gene and regulation of the PDGFR ligand PDGFC to study the role of this receptor signaling pathway in medulloblastoma.
Genomics and Proteomics
A major strength of the Neuro-Oncology Program has been its work in being the first to identify key gene expression signatures related to the aggressive behavior of both pediatric gliomas and medulloblastoma using high-throughput microarray genomic expression profiling technology. Current work seeks to build on this strength and expand its collaborations with Maria Rita Santi, MD, in Neuropathology to perform high-throughput tissue microarray screening to identify additional novel protein biomarkers for therapeutic intervention in gliomas, medulloblastomas and other childhood brain tumors. Additional collaboration with the NIH and the Institute for Genomic Research (TIGR) laboratories further strengthens our initiative to dissect the key signaling pathways involved in childhood brain tumorigenesis. A significant new initiative at Children's in translational clinical neuro-oncology (Drs. Rood and MacDonald) during the past year stems from the NIH sponsored PBTC mandate to include innovative biologic studies with all clinical protocols to improve our understanding of brain tumor pathophysiology, discover new biomarkers and ultimately measure the efficacy of novel therapeutics. Given our research initiatives at Children's, this mandate has fostered the PBTC Brain Tumor CSF Proteomics Core Facility at Children's, which is utilizing MALDI-TOF-TOF analysis to generate protein spectra signatures of childhood brain tumors.
Related Links
Contact Information:
Nikkie Adesida
Children’s Research Institute
Center for Neuroscience Research
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-2389
202-476-4988 fax
nadesida@cnmcresearch.org
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