ribozyme-mediated inhibition of 801-bp deletion-mutant epidermal growth factor receptor mrna expression in glioblastoma multiforme801 - bp deletion-mutant ribozyme-mediated抑制表皮生长因子受体信使rna表达多形性成胶质细胞瘤.pdfVIP

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ribozyme-mediated inhibition of 801-bp deletion-mutant epidermal growth factor receptor mrna expression in glioblastoma multiforme801 - bp deletion-mutant ribozyme-mediated抑制表皮生长因子受体信使rna表达多形性成胶质细胞瘤.pdf

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ribozyme-mediated inhibition of 801-bp deletion-mutant epidermal growth factor receptor mrna expression in glioblastoma multiforme801 - bp deletion-mutant ribozyme-mediated抑制表皮生长因子受体信使rna表达多形性成胶质细胞瘤

Molecules 2010, 15, 4670-4678; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Ribozyme-Mediated Inhibition of 801-bp Deletion-Mutant Epidermal Growth Factor Receptor mRNA Expression in Glioblastoma Multiforme Georg Karpel-Massler, Christian Rainer Wirtz and Marc-Eric Halatsch * Department of Neurosurgery, University of Ulm Medical School, Steinhövelstr 9, D-89075 Ulm, Germany; E-Mails: georg.karpel@uniklinik-ulm.de (G.K.-M.); rainer.wirtz@uniklinik-ulm.de (C.R.W.) * Author to whom correspondence should be addressed; E-Mail: marc-eric.halatsch@uniklinik-ulm.de; Tel: +49(0)731/500-55003; Fax: +49(0)731/500-55002. Received: 8 June 2010; in revised form: 28 June 2010 / Accepted: 29 June 2010 / Published: 30 June 2010 Abstract: The epidermal growth factor receptor (HER1/EGFR) is known to be disregulated in a large subgroup of glioblastoma multiforme cases. Disregulation of HER1/EGFR is related to malignant transformation and tumor growth in various human cancers, including malignant glioma. One mechanism that may lead to disregulated HER1/EGFR signaling is the intrinsic alteration of the receptor structure due to mutational changes. The most common mutant form of HER1/EGFR, named variant III (EGFRvIII), results from an 801 bp in-frame deletion in the DNA sequence encoding the extracellular ligand-binding domain. Independent of ligand–binding, EGFRvIII is constitutively activated and beyond external