NDLI: A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors.

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A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors.

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A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sun, Yanping Luster, Andrew D. Kieran, Mark W. Kung, Andrew L. Schmidt, Karl Segal, Rosalind A. Klein, Robyn S. Rubin, Joshua B. Chan, Jennifer A.
Description	Author Affiliation: Rubin JB ( Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.);
Abstract	The vast majority of brain tumors in adults exhibit glial characteristics. Brain tumors in children are diverse: Many have neuronal characteristics, whereas others have glial features. Here we show that activation of the Gi protein-coupled receptor CXCR4 is critical for the growth of both malignant neuronal and glial tumors. Systemic administration of CXCR4 antagonist AMD 3100 inhibits growth of intracranial glioblastoma and medulloblastoma xenografts by increasing apoptosis and decreasing the proliferation of tumor cells. This reflects the ability of AMD 3100 to reduce the activation of extracellular signal-regulated kinases 1 and 2 and Akt, all of which are pathways downstream of CXCR4 that promote survival, proliferation, and migration. These studies (i) demonstrate that CXCR4 is critical to the progression of diverse brain malignances and (ii) provide a scientific rationale for clinical evaluation of AMD 3100 in treating both adults and children with malignant brain tumors.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	23
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Neoplasms Drug Therapy Protein-Serine-Threonine Kinases Receptors, CXCR4 Antagonists & Inhibitors Animals Anti-HIV Agents Pharmacology Apoptosis Pathology Cell Division Cell Line, Tumor Chemokine CXCL12 Chemokines, CXC Biosynthesis Chemotaxis Glioblastoma Heterocyclic Compounds In Situ Nick-End Labeling Luciferases Metabolism Magnetic Resonance Imaging Medulloblastoma Mice Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Neoplasm Transplantation Proto-Oncogene Proteins Proto-Oncogene Proteins C-akt Time Factors Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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