DIPG
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DIPG CONSOURTIUM (DIPGC)
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Background

Diffuse intrinsic pontine glioma (DIPG) account for about 20% of pediatric brain tumors. Despite three decades of clinical research, the survival rate of children with high grade gliomas (HGG; WHO Grades III and IV) remains less than 10%.Diffuse intrinsic pontine gliomas (DIPGs) are high grade brainstem gliomas (BSGs) that remain uniformly fatal.Factors contributing to the lack of progress include challenges in surgical resection (inaccessibility to brainstem), poor availability of tissue, and lack of robust animal models of the disease.

We have taken two steps in order to overcome these obstacles and move rapidly towards molecular targeting and preclinical study of DIPGs.

First, we have formed a DIPG Consortium (DIPGC) that includes scientists from Johns Hopkins University (JHU), National Cancer Institute (NCI) and Children's National Medical Center (CNMC) in Washington DC.The aim of this consortium is to establish a DIPG biobank, share existing DIPG specimens and standardize DIPG specimen procurement and distribution amongst collaborators.

Second, DIPGC has obtained murine models of DIPG: the genetically engineered model that over expresses PDGF and two xenograft models that were recently generated at JHU and CNMC sites by orthotopic injection of postmortem DIPG tumor cells. Integrated genomic and proteomic characterizations of DIPG in humans and in murine models of DIPG are underway at DIPGC sites.

Our team includes three experts in the field of pediatric DIPG. All three centers have extensive experience in planning, overseeing, executing and analyzing experiments proposed in this study.

  • The Children's National Medical Center (CNMC) site is a world leader in expression profiling and is also equipped with the cutting edge protein profiling technologies.

  • The Johns Hopkins University (JHU) site has an established track record of basic and translational research on high-risk brain tumors. There is substantial expertise in the establishment and propagation of neurosphere cultures and tumor orthotopic xenograft models.

  • The Pediatric Neuro-Oncology Section of the National Cancer Institute (NCI) is considered a worldwide referral resource for DIPG patients. Initial studies on DIPG tumor tissue have been performed at the NCI in collaboration with Paul Meltzer, M.D., Ph.D., a renowned authority in gene expression analysis.

Tissue collection

The purpose of this study is to prospectively collect specimens from pediatric patients with diffuse intrinsic pontine glioma or brainstem glioma, either during therapy or at autopsy, in order to characterize the molecular abnormalities of this tumor.

Primary Outcome Measures:

  • Genome-wide expression patterns of RNA in tumor samples, normal brainstem tissue and cerebrospinal fluid using Affymetrix gene expression profiling

  • Validation of results of the genome-wide

  • Proteomic profiling of tumor, normal brainstem tissue and cerebrospinal fluid

  • Protein expression patterns as assessed by immunohistochemistry and western blot compared to normal brainstem tissue

  • Genome-wide analysis of tumor samples and normal brainstem tissue

  • In vitro and in vivo molecular analysis of collected samples

  • Collected samples will be used for in vitro analysis and generation of animal models.

External link to the tissue collection site (ClinicalTrials.gov) http://clinicaltrials.gov/ct2/show/NCT01106794

Javad Nazarian, PhD

Javad Nazarian is an investigator at the Center for Genetic Medicine in Children's National Medical Center, Washington DC and as an assistant professor in Integrative Systems Biology at the George Washington University.He received his PhD from the George Washington University in Genetic in 2005. His dissertation research involved molecular profiling of neuromuscular junctions using laser capture microdissection. His postdoctoral research involved protein profiling of pediatric brainstem tumors.

Dr. Nazarian's laboratory investigates establishing in vivo models of brainstem gliomas as well as generating the molecular profile of the disease. These include proteomics, genomics, microRNA and mRNA profiles. His multidisciplinary team includes members from Neurosurgery, Neurology, Oncology and Research departments. The team's ongoing research involves characterizing in vivo and in vitro models of brainstem gliomas, developing nanoparticles-mediated strategies for specific targeting of tumor cells, and assessment of non-hormonal steroids for treatment of pediatric brain tumors. External link to Dr.Nazarian's website at the George Washington University

Eric Raabe MD PHD 2010 Eric H. Raabe, MD, PhD

Eric Raabe, M.D., Ph.D., is an instructor in the Division of Pediatric Oncology and a physician-scientist at Johns Hopkins.

Raabe majored in neural science at Brown University and received his M.D. and Ph.D. from the University of Cincinnati College of Medicine. He completed his pediatric internship and residency at Children's Hospital of Philadelphia.

After spending a year working in Africa as part of the Baylor International Pediatric AIDS Initiative, Raabe joined Johns Hopkins as a pediatric oncology fellow. Working in the laboratory of Charles Eberhart in Neuropathology, Raabe established a human neural stem cell system to create genetically accurate models of pediatric brain tumors.

With an interest in neuro-oncology, Raabe see patients in the pediatric oncology outpatient clinic at Johns Hopkins.

He continues his research in the new Smith Building of the Wilmer Eye Institute in the Neuropathology Division, in collaboration with Charles Eberhart.

External link to Dr. Raabe's website at the Johns Hopkins School of Medicine

Portait Photo of Katherine Warren Kathy Warren, MD

Dr. Warren received her B.S. in Medical Technology in 1982 and her M.D. from Tufts University School of Medicine in 1990. She completed a residency in pediatrics at Children's National Medical Center, followed by a fellowship in pediatric oncology at the National Cancer Institute. She is board certified in pediatrics and pediatric hematology/oncology. Dr. Warren is a Tenure Track Investigator in the Pediatric Oncology Branch, specializing in neuro-oncology. Her research interests include performance of clinical trials, particularly in children with tumors of the central nervous system, non-invasive evaluation/imaging of the brain, and neurotoxicity resulting from tumors and their treatment.

External Link to Dr. Warren Website at the NCI







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