Literature DB >> 18812968

CXCR4 expression is elevated in glioblastoma multiforme and correlates with an increase in intensity and extent of peritumoral T2-weighted magnetic resonance imaging signal abnormalities.

Charles B Stevenson1, Moneeb Ehtesham, Kathryn M McMillan, J Gerardo Valadez, Michael L Edgeworth, Ronald R Price, Ty W Abel, Khubaib Y Mapara, Reid C Thompson.   

Abstract

OBJECTIVE: With the objective of investigating the utility of CXCR4, a chemokine receptor known to mediate glioma cell invasiveness, as a molecular marker for peritumoral disease extent in high-grade gliomas, we sought to characterize the expression profile of CXCR4 in a large panel of tumor samples and determine whether CXCR4 expression levels within glioblastoma multiforme might correlate with radiological evidence of a more extensive disease process.
METHODS: Freshly resected tumor tissue samples were processed for immunohistochemical and quantitative polymerase chain reaction analyses to identify and quantify expression levels of CXCR4 and its corresponding ligand CXCL12. T1 postcontrast and T2-weighted magnetic resonance imaging brain scans were used to generate voxel signal intensity histograms that were quantitatively analyzed to determine the extent and intensity of peritumoral signal abnormality as a marker of disseminated disease in the brain.
RESULTS: CXCR4 expression was markedly elevated in Grade III and IV tumors compared with Grade II gliomas. Significantly, when patients with glioblastoma multiforme were segregated into two groups based on CXCR4 expression level, we observed a statistically significant increase in the intensity and extent of peritumoral magnetic resonance imaging signal abnormalities associated with CXCR4 high-expressing gliomas.
CONCLUSION: Our data confirm that high-grade gliomas robustly express CXCR4 and demonstrate a correlative relationship between expression levels of the CXCR4 receptor and the magnetic resonance imaging-based finding of a diffuse and more extensive disease process in the brain. CXCR4 expression status may, therefore, prove useful as a marker of disseminated disease in patients with glioblastoma multiforme.

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Year:  2008        PMID: 18812968      PMCID: PMC2602832          DOI: 10.1227/01.NEU.0000324896.26088.EF

Source DB:  PubMed          Journal:  Neurosurgery        ISSN: 0148-396X            Impact factor:   4.654


  32 in total

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5.  Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms.

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6.  Graphic analysis of microscopic tumor cell infiltration, proliferative potential, and vascular endothelial growth factor expression in an autopsy brain with glioblastoma.

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

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10.  CXCL12 in malignant glial tumors: a possible role in angiogenesis and cross-talk between endothelial and tumoral cells.

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Authors:  B J Carney; K Shah
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Review 2.  G protein-coupled receptors as oncogenic signals in glioma: emerging therapeutic avenues.

Authors:  A E Cherry; N Stella
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3.  The expression of P2X₇ receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas.

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4.  Expression of CXC-motif-chemokine 12 and the receptor C-X-C receptor 4 in glioma and theeffect on peritumoral brain edema.

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Review 5.  The role of the CXCR4 cell surface chemokine receptor in glioma biology.

Authors:  Moneeb Ehtesham; Elliot Min; Neil M Issar; Rebecca A Kasl; Imad S Khan; Reid C Thompson
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6.  The SDF-1 3'A genetic variation is correlated with elevated intra-tumor tissue and circulating concentration of CXCL12 in glial tumors: a study on Iranian anaplastic astrocytoma and glioblastoma multiforme patients.

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Review 7.  Use of FDA approved methamphetamine to allow adjunctive use of methylnaltrexone to mediate core anti-growth factor signaling effects in glioblastoma.

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8.  Survival and Proliferation of Neural Progenitor-Derived Glioblastomas Under Hypoxic Stress is Controlled by a CXCL12/CXCR4 Autocrine-Positive Feedback Mechanism.

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9.  A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion.

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10.  CXCR4 mediates the proliferation of glioblastoma progenitor cells.

Authors:  Moneeb Ehtesham; Khubaib Y Mapara; Charles B Stevenson; Reid C Thompson
Journal:  Cancer Lett       Date:  2008-11-12       Impact factor: 8.679

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