6 research outputs found
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Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain
Background:
Protein tyrosine kinases are important regulators of cellular homeostasis with tightly
controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory
constraints on kinase activity, can promote malignant transformation, and appear to be a major
determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase
domain, for example, have recently been identified in patients who showed clinical responses
to EGFR kinase inhibitor therapy.
Methods and Findings:
Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR)
kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR
coding sequence in glioma tumor samples and cell lines. We identified novel missense
mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/
8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene
dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells.
Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR
kinase inhibitors.
Conclusions:
Our results suggest extracellular missense mutations as a novel mechanism for oncogenic
EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for
treatment of glioblastoma
EFNS-ENS guidelines for the use of PCR technology for the diagnosis of infections of the nervous system
Background: Polymerase chain reaction (PCR) as a means to amplify nucleic acids has become an essential element in diagnosis of infections. It has evolved into a simple and rapid, easy- to- use approach. At present there are no published guidelines for the usage of PCR technology for the diagnosis of infections of the nervous system.
<p/>Methods: We reviewed the advantages and pitfalls of PCR in order to guide neurologists and infectious diseases experts in its application for the diagnosis of infections of the nervous system. Medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in May 2012. Recommendations were reached by consensus.
<p/>Recommendations: The reliability of PCR technology for the diagnosis of neurological infections is currently based on the pathogens. The main contribution of PCR is to the diagnosis of viral infections followed by bacterial CNS infections with the notable exception of tuberculous meningitis. Efficacy for the diagnosis of protozoal infections and helminthic infestations has also been established in many instances. Unfortunately, current molecular PCR technology is far from becoming routine in resource-poor countries where such infections are prevalent. Despite the importance of fungal infections in the context of the immune-compromised host, there is not enough data to recommend the routine use of PCR.
<p/>Conclusions: PCR technology is currently a reliable method for the diagnosis of viral and bacterial (except tuberculosis) infections, and only for some protozoal infections and helminthic infestations