Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: RECEPTOR ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; INHIBITOR ; proliferation ; tumor ; CELL ; CELL-PROLIFERATION ; FACTOR RECEPTOR ; Germany ; IN-VIVO ; INHIBITION ; KINASE ; THERAPY ; TYROSINE KINASE ; GENE ; GENES ; HYBRIDIZATION ; PROTEIN ; DRUG ; TUMORS ; LINES ; PATIENT ; LIGAND ; prognosis ; REDUCTION ; CONTRAST ; CELL-LINES ; GROWTH-FACTOR RECEPTOR ; PHOSPHORYLATION ; chromosome ; TARGET ; NO ; IN-SITU ; LESIONS ; AMPLIFICATION ; MUTATION ; METASTASIS ; PROSTATE-CANCER ; CELL-LINE ; LINE ; MUTATIONS ; HOMOLOG ; US ; LIGANDS ; TARGETS ; FLUORESCENCE ; POOR-PROGNOSIS ; SARCOMA ; fluorescence in situ hybridization ; PTEN ; TP53 ; EPIDERMAL-GROWTH-FACTOR ; ONCOLOGY ; TUMOR-SUPPRESSOR ; THERAPIES ; INCREASE ; EGFR ; cell proliferation ; LEVEL ; analysis ; SUPPRESSOR ; tumor suppressor gene ; NERVE ; USA ; DRUGS ; KINASE INHIBITOR ; epidermal growth factor receptor ; GROWTH-FACTOR-RECEPTOR ; receptor tyrosine kinase ; SOMATIC MUTATIONS ; comparison ; ErbB2 ; neurofibromatosis ; TARGETED THERAPY ; tumor suppressor ; EGF ; TRASTUZUMAB ; FACTOR-RECEPTOR ; growth factor ; MPNST ; NEU PROTOONCOGENE ; SCHWANN-CELLS
    Abstract: Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas with poor prognosis and limited treatment options. Evidence for a role of epidermal growth factor receptor (EGFR) and receptor tyrosine kinase erbB2 in MPNSTs led us to systematically study these potential therapeutic targets in a larger tumor panel (n=37). Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization analysis revealed increased EGFR dosage in 28% of MPNSTs. ERBB2 and three tumor suppressor genes (PTEN [phosphatase and tensin homolog deleted on chromosome 10], CDKN2A [cyclin-dependent kinase inhibitor 2A], and TP53 [tumor protein p53]) were frequently lost or reduced. Reduction of CDKN2A was linked to appearance of metastasis. Comparison of corresponding neurofibromas and MPNSTs revealed an increase in genetic lesions in MPNSTs. No somatic mutations were found within tyrosine-kinase-encoding exons of EGFR and ERBB2. However, at the protein level, expression of EGFR and erbB2 was frequently detected in MPNSTs. EGFR expression was significantly associated with increased EGFR gene dosage. The EGFR ligands transforming growth factor a and EGF were more strongly expressed in MPNSTs than in neurofibromas. The effects of the drugs erlotinib and trastuzumab, which target EGFR and erbB2, were determined on MPNST cell lines. In contrast to trastuzumab, erlotinib mediated dose-dependent inhibition of cell proliferation. EGF-induced EGFR phosphorylation was attenuated by erlotinib. Summarized, our data indicate that EGFR and erbB2 are potential targets in treatment of MPNST patients. Neuro-Oncology 10, 946-957, 2008 (Posted to Neuro-Oncology [serial online], Doc. D07-00250, July 23, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-053)
    Type of Publication: Journal article published
    PubMed ID: 18650488
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: ALPHA, C-KIT, DIAGNOSIS, ENGLAND, ESOPHAGUS, EXPRESSION, gastrointestinal, GASTROINTESTINAL STROMAL
    Abstract: Background: Gastrointestinal stromal tumors GIST) of the esophagogastric junction might pose a major problem to surgical resection. If locally advanced, extended or multivisceral resection with relevant procedural-specific morbidity and mortality is often necessary. Case presentation: We report a case of a patient with a locally advanced GIST of the esophagogastric junction who was treated by transhiatal resection of the lower esophagus and gastric cardia with reconstruction by interposition of segment of the jejunum (Merendino procedure). Prior to resection, downsizing of the tumor had successfully been achieved by treatment with imatinib mesylate for six months. Histological proof of GIST by immunohistochemical expression of c-KIT and/or PDGF alpha Receptor is crucial to allow embarking on this treatment strategy. Conclusion: A multimodal approach for an advanced GIST of the esophagogastric junction with preoperative administration of imatinib mesylate could avoid extended resection. The Merendino procedure might be considered as the reconstruction method of choice after resection of GIST at this location
    Type of Publication: Journal article published
    PubMed ID: 18394167
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: RECEPTOR ; CELLS ; EXPRESSION ; transcription ; ACTIVATION ; MUTATIONS ; POLYMERASE CHAIN-REACTION ; real-time PCR ; C-KIT ; IMATINIB MESYLATE ; THERAPEUTIC TARGET ; NERVE SHEATH TUMOR ; WILD-TYPE GISTS
    Abstract: Background: Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal tumors of the gastrointestinal tract. About 85% carry an activating mutation in the KIT or PDGFRA gene. Approximately 10% of GIST are so-called wild type GIST (wt-GIST) without mutations in the hot spots. In the present study we evaluated appropriate reference genes for the expression analysis of formalin-fixed, paraffin-embedded and fresh frozen samples from gastrointestinal stromal tumors. We evaluated the gene expression of KIT as well as of the alternative receptor tyrosine kinase genes FLT3, CSF1-R, PDGFRB, AXL and MET by qPCR. wt-GIST were compared to samples with mutations in KIT exon 9 and 11 and PDGFRA exon 18 in order to evaluate whether overexpression of these alternative RTK might contribute to the pathogenesis of wt-GIST. Results: Gene expression variability of the pooled cDNA samples is much lower than the single reverse transcription cDNA synthesis. By combining the lowest variability values of fixed and fresh tissue, the genes POLR2A, PPIA, RPLPO and TFRC were chosen for further analysis of the GIST samples. Overexpression of KIT compared to the corresponding normal tissue was detected in each GIST subgroup except in GIST with PDGFRA exon 18 mutation. Comparing our sample groups, no significant differences in the gene expression levels of FLT3, CSF1R and AXL were determined. An exception was the sample group with KIT exon 9 mutation. A significantly reduced expression of CSF1R, FLT3 and PDGFRB compared to the normal tissue was detected. GIST with mutations in KIT exon 9 and 11 and in PDGFRA exon 18 showed a significant PDGFRB downregulation. Conclusions: As the variability of expression levels for the reference genes is very high comparing fresh frozen and formalin-fixed tissue there is a strong need for validation in each tissue type. None of the alternative receptor tyrosine kinases analyzed is associated with the pathogenesis of wild-type or mutated GIST. It remains to be clarified whether an autocrine or paracrine mechanism by overexpression of receptor tyrosine kinase ligands is responsible for the tumorigenesis of wt-GIST
    Type of Publication: Journal article published
    PubMed ID: 21171987
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: pathology ; THERAPIES ; FAMILIES ; MEMBER ; NEW-YORK ; FAMILY ; EXPRESSION ; THERAPY ; EGFR ; GENETIC ALTERATION ; USA
    Type of Publication: Meeting abstract published
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...