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  • 1
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    German Medical Science; Düsseldorf, Köln
    In:  56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC); 20050507-20050511; Strasbourg; DOCP116 /20050504/
    Publication Date: 2005-05-05
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Keywords: brain ; APOPTOSIS ; EXPRESSION ; IN-VITRO ; INHIBITOR ; proliferation ; CELL ; Germany ; human ; IN-VIVO ; KINASE ; PATHWAY ; PATHWAYS ; TYROSINE KINASE ; VITRO ; VIVO ; GENE ; GENE-EXPRESSION ; GENES ; GENOME ; RNA ; SURGERY ; LINES ; COMPLEX ; COMPLEXES ; MESSENGER-RNA ; INJECTION ; CELL-LINES ; SUPPRESSION ; TYROSINE KINASE INHIBITOR ; CANDIDATE GENE ; FORM ; TARGET ; gene expression ; resistance ; EFFICACY ; CELL-LINE ; SIGNALING PATHWAY ; SIGNALING PATHWAYS ; PHENOTYPE ; POLYMERASE-CHAIN-REACTION ; sensitivity ; TARGETS ; cell lines ; STAT1 ; signaling ; ANNOTATION ; polymerase chain reaction ; CANDIDATE GENES ; EGFR ; KINASE INHIBITORS ; glioblastoma multiforme ; GLIOBLASTOMA-MULTIFORME ; ADULT-RAT ; USA ; KINASE INHIBITOR ; epidermal growth factor receptor ; GLIOBLASTOMA ; GROWTH-FACTOR-RECEPTOR ; CANDIDATES ; POLYMERASE ; ASTROCYTES ; HUMAN GLIOMA-CELLS ; Genetic ; therapeutic ; THERAPEUTIC TARGET ; cellular response ; CELLULAR-RESPONSE ; TYROSINE ; Whole genome ; cRNA microarray ; erlotinib ; tyrosine kinase inhibition
    Abstract: Object. The authors have previously reported that erlotinib, an EGFR tyrosine kinase inhibitor, exerts widely variable antiproliferative effects on 9 human glioblastoma multiforme (GBM) cell lines in vitro and in vivo. These effects were independent of EGFR baseline expression levels, raising the possibility that more complex genetic properties form the Molecular basis of the erlotinib-sensitive and erlotinib-resistant GBM phenotypes. The aim of the present study was to determine candidate genes for mediating the cellular response of human GBMs to erlotinib. Methods. Complementary RNA obtained in cell lines selected to represent the sensitive, somewhat responsive, and resistant phenotypes were hybridized to CodeLink Human Whole Genome Bioarrays. Results. Expression analysis of 814 prospectively selected genes involved in major proliferation and apoptosis signaling pathways identified 19 genes whose expression significantly correlated with phenotype. Functional annotation analysis revealed that 2 genes (DUSP4 and STAT1) were significantly associated with sensitivity to erlotinib, and 10 genes (CACNG4, FGFR4, HSPA1B, HSPB1, NFATC1, NTRK1, RAC1, SMO, TCF7L1, and TGFB3) were associated with resistance to erlotinib. Moreover, 5 genes (BDNF, CARD6, FOSL1, HSPA9B, and MYC) involved in antiapoptotic pathways were unexpectedly found to be associated with sensitivity. Gene expressions were confirmed by quantitative polymerase chain reaction. Conclusions. Based on an analysis of gene expressions in cell lines with sensitive, somewhat responsive, and resistant phenotypes, the authors propose candidate genes for GBM response to erlotinib. The 10 gene candidates for conferring GBM resistance to erlotinib may represent therapeutic targets for enhancing the efficacy of erlotinib against GBMs. Five additional genes warrant further investigation into their role as putative cotargets of erlotinib. (DOI: 10.3171/2008.9.JNS08551)
    Type of Publication: Journal article published
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  • 3
    Keywords: ADHESION, ADHESION MOLECULE, BREAST, breast cancer, BREAST-CANCER, CANCER, CANCERS, carcinoma, CARCI
    Abstract: The L1 adhesion molecule (L1-CAM) is associated with impaired prognosis in many carcinomas. However, limited information about its expression in breast cancer tissue is available. Therefore, we carried out an analysis on L1 expression in primary breast cancers using a combination of Western blot, DNA-microarray analysis and immunohistochemistry. We observed L1 protein and mRNA overexpression in 14-15% of the carcinomas and this was confirmed by immunohistochemical staining. High L1 expression was associated with nodal involvement, high grading, human epidermal growth receptor 2 (Her-2), plasminogen activator inhibitor 1 (PAI-1) and vascular endothelial growth factor (VEGF) expression and a negative estrogen receptor (ER) status, but not with neuroendocrine markers. Moreover, patients with tumors showing high L1-CAM expression had a shorter disease-free and overall survival. Given the emerging functional role of L1 in promoting tumor cell migration, invasion, tumor growth and metastasis, our results suggest that L1 may have this function in breast cancer as well
    Type of Publication: Journal article published
    PubMed ID: 19787228
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  • 4
    Abstract: New technologies to generate, store and retrieve medical and research data are inducing a rapid change in clinical and translational research and health care. Systems medicine is the interdisciplinary approach wherein physicians and clinical investigators team up with experts from biology, biostatistics, informatics, mathematics and computational modeling to develop methods to use new and stored data to the benefit of the patient. We here provide a critical assessment of the opportunities and challenges arising out of systems approaches in medicine and from this provide a definition of what systems medicine entails. Based on our analysis of current developments in medicine and healthcare and associated research needs, we emphasize the role of systems medicine as a multilevel and multidisciplinary methodological framework for informed data acquisition and interdisciplinary data analysis to extract previously inaccessible knowledge for the benefit of patients.
    Type of Publication: Journal article published
    PubMed ID: 29497170
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  • 5
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  79. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20080430-20080504; Bonn; DOC08hnod612 /20080422/
    Publication Date: 2008-04-21
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 6
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The distribution of cell adhesion molecules in the normal human lung was investigated using antibodies to E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Lectin staining by Ulex europaeus type I agglutinin (UEA I) and immunohistochemistry for von Willebrand factor (vWF) was used to visualize a maximum of blood vessels per section. In the bronchial mucosa, staining for P-selectin was positive in ca 90%, and staining for E-selectin, VCAM-1, and ICAM-1 was positive in 40–70% of the vessels stained with UEA I. In the pulmonary circulation (vasa publica) ca 90% of non-capillary vessels stained by anti-vWF expressed P-selectin, 54% VCAM-1, 41% E-selectin, and only ca 20% ICAM 1. The alveolar capillaries were stained consistently by UEA I, but not by the panel of antibodies tested. The alveolar epithelium and, inconstantly, basal cells of the bronchial epithelium were positive for ICAM-1. The distribution pattern of inducible adhesion molecules in normal human lung tissue suggests that a permanent low-grade endothelial activation may exist in particular in the mucosa of the airways, which could be due to the normal antigen exposure via inhaled air.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0878
    Keywords: Mammary epithelium Ki-67 TUNEL Bcl-2 family Stem cell Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The expression of the apoptosis-related proteins Bcl-2 and Bax was investigated by immunohistochemistry in the normal non-lactating human mammary gland in relation to cell proliferation and apoptosis. In order to characterize individual Bax/Bcl-2-immunoreactive cells, the epithelial markers cytokeratin 14 and 19 and the macrophage marker CD 68 were used. Secretory-like differentiation of epithelial cells was characterized by histochemistry and lectin staining of surface glycoconjugates. Cell proliferation was exclusively found in glandular epithelial cells with broad contact to the ductular lumen, whereas nuclei with apoptosis-related DNA fragmentation were seen predominantly in basally located glandular epithelial cells and in myoepithelial cells. Weak immunoreactivity for Bcl-2 and Bax was present throughout all epithelia, suggesting a balance between pro- and antiapoptotic effects in the majority of epithelial cells. However, specific cells showed a strong staining for Bax or Bcl-2. The strongly Bcl-2-immunoreactive epithelial cells were not identical with proliferating cells, but they resembled them in configuration and in the luminal intraepithelial position. In contrast, the strongly Bax-positive epithelial cells had no or only a narrow contact to the ductular lumen. The different patterns of Bax/Bcl-2 immunoreactivity in specific glandular epithelial cells suggest that there are also different grades of susceptibility towards apoptotic stimuli in individual glandular epithelial cells. We conclude that specific Bax/Bcl-2 expression patterns could reflect particular cell differentiation states, and that the strongly Bcl-2-positive cells in part could represent epithelial stem cells.
    Type of Medium: Electronic Resource
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