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  • 1
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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; DOC08hnod302 /20080422/
    Publication Date: 2008-04-21
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
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    German Medical Science; Düsseldorf, Köln
    In:  77. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.; 20060524-20060528; Mannheim; DOC06hnod282 /20060424/
    Publication Date: 2006-04-25
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
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    German Medical Science; Düsseldorf, Köln
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 2; DOC097 /20060424/
    Publication Date: 2006-04-24
    Description: Die konfokale Laser Scanning Microscopy (LSM) liefert Informationen aus Epitheltiefen bis 0,5 mm. Ziel dieser ex vivo-Pilotstudie war es, die Anwendbarkeit dieser Methode für die Diagnostik des Kehlkopfkarzinoms und seiner Vorstufen zu prüfen.Die Untersuchungen wurden an 43 Larynxpräparaten von 26 Patienten (Alter: 35 bis 61 Jahre, durchschnittliches Alter: 51,9 ± 9,5 Jahre; 7 Frauen und 19 Männer), die sich im Zeitraum von Februar bis November 2005 einer Mikrolaryngoskopie wegen Larynxschleimhautveränderungen jedweder Genese unterzogen haben, vorgenommen. Die LSM-Befunde (Videos und Einzelbilder) wurden mit denen gesunder Larynxepithelien (Voruntersuchungen) und den histologischen Befunden verglichen. Folgende Kriterien wurden zur Charakterisierung der Malignität herangezogen: Vergrößerte und unterschiedlich geformte Zellen, Zellkluster, erhöhte Kern-Plasma-Relation, irreguläre Zellarchitektur, Verlust der Zellgrenzen.Die LSM ermöglicht die Darstellung der Basalzellschicht des Stimmlippenepithels, des Reincke-Raumes, des subepithelialen Raumes sowie dessen Gefäße. Ferner läßt sich das respiratorische Epithel der Supraglottis abgrenzen.Unter Verwendung der festgelegten Malignitätskriterien wurde für die Differenzierung von Dysplasie und benignen Tumoren vom Karzinom eine Sensitivität von 72.7% und eine Spezifität von 82,9% ermittelt. Mit der LSM wird eine Eindringtiefe bis zum subepithelialen Raum erreicht. Eine Differenzierung zwischen Entzündung, Dysplasie und Karzinom ist möglich. Die LSM stellt eine neue Technologie dar, die für den in vivo-Einsatz vorbereitet wird.
    Keywords: ddc: 610
    Language: German
    Type: article
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  • 4
    Keywords: THERAPY ; LUNG-CANCER ; adenocarcinoma ; SOCIETY ; GEFITINIB ; erlotinib
    Abstract: Detection of activating EGFR mutations in NSCLC is the prerequisite for individualised therapy with receptor tyrosine kinase inhibitors (TKI). In contrast, mutant downstream effector KRAS is associated with TKI resistance. Accordingly, EGFR mutation status is routinely examined in NSCLC specimens, but the employed methods may have a dramatic impact on the interpretation of results and, consequently, therapeutic decisions. Specimens with low tumour cell content are at particular risk for false-negative EGFR mutation reporting by sequencing with Sanger chemistry. To improve reliability of detecting clinically relevant mutant variants of EGFR and KRAS, we took full advantage of 454 deep sequencing and developed a two-step amplification protocol for the analysis of EGFR exons 18-21 and KRAS exons 2 and 3. We systematically addressed the sensitivity, reproducibility and specificity of the developed assay. Mutations could be reliably identified down to an allele frequency of 0.2-1.5 %, as opposed to 10-20 % detection limit of Sanger sequencing. High reproducibility (0-2.1 % variant frequency) and very low background level (0.4-0.8 % frequency) further complement the reliability of this assay. Notably, re-evaluation of 16 NSCLC samples with low tumour cell content 〈/=40 % and EGFR wild type status according to Sanger sequencing revealed clinically relevant EGFR mutations at allele frequencies of 0.9-10 % in seven cases. In summary, this novel two-step amplification protocol with 454 deep sequencing is superior to Sanger sequencing with significantly increased sensitivity, enabling reliable analysis of EGFR and KRAS in NSCLC samples independent of the tumour cell content.
    Type of Publication: Journal article published
    PubMed ID: 23468066
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  • 5
    Keywords: EXPRESSION ; transcription ; TISSUE ; TUMORS ; IDENTIFICATION ; PATTERN ; SPECTRUM ; NAB2 ; STAT6 ; HEMANGIOPERICYTOMA
    Abstract: Recurrent somatic fusions of the two genes, NGFI-A-binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been recently identified to be presumable tumor-initiating events in solitary fibrous tumors. Herein, we evaluated a cohort of 52 solitary fibrous tumors/hemangiopericytomas by whole-exome sequencing (one case) and multiplex RT-PCR (all 52 cases), and identified 12 different NAB2-STAT6 fusion variants in 48 cases (92%). All 52 cases showed strong and diffuse nuclear positivity for STAT6 by IHC. We categorized the fusion variants according to their potential functional effects within the predicted fusion protein and found strong correlations with relevant clinicopathological features. Tumors with the most common fusion variant, NAB2ex4-STAT6ex2/3, corresponded to classic pleuropulmonary solitary fibrous tumors with diffuse fibrosis and mostly benign behavior and occurred in older patients (median age, 69 years). In contrast, tumors with the second most common fusion variant, NAB2ex6-STAT6ex16/17, were found in much younger patients (median age, 47 years) and represented typical hemangiopericytomas from deep soft tissue with a more aggressive phenotype and clinical behavior. In summary, these molecular genetic findings support the concept that classic pleuropulmonary solitary fibrous tumor and deep-seated hemangiopericytoma are separate entities that share common features but correlate to different clinical outcome.
    Type of Publication: Journal article published
    PubMed ID: 24513261
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  • 6
    Keywords: EXPRESSION ; GENE ; FUSION ; PATTERN ; CAVITY
    Abstract: AIMS: Sinonasal haemangiopericytoma (SN-HPC) is a rare sinonasal mesenchymal neoplasm of perivascular myoid cell origin. Solitary fibrous tumour (SFT) occurs only very rarely in the sinonasal tract. SFT and soft tissue HPC have been considered a single entity. Recently, recurrent gene fusions involving NAB2-STAT6 resulting in differential expression of STAT6 were characterized as central molecular events in SFT. However, no data exist for NAB2-STAT6 status or STAT6 expression in SN-HPC. METHODS AND RESULTS: We examined six SN-HPCs and two sinonasal SFTs by immunohistochemistry and RT-PCR for NAB2-STAT6 fusions. SN-HPC affected three females and three males (mean age: 72 years). They expressed smooth muscle actin, lacked strong CD34 reactivity and were negative for nuclear STAT6 expression. RT-PCR analysis confirmed the absence of NAB2-STAT6 fusions in all cases. Conversely, both sinonasal SFTs (in males aged 39 and 52 years) displayed classical features of pleuropulmonary and soft-tissue SFTs (uniformly CD34-positive with strong nuclear expression of STAT6). RT-PCR revealed NAB2-STAT6 fusions in both cases. CONCLUSIONS: These findings confirm the molecular and phenotypical distinctness of these two entities. While SN-HPC is a site-specific sinonasal neoplasm of as yet unknown molecular pathogenesis, sinonasal SFTs show phenotypical and molecular identity to their pleural/extrapleural counterparts.
    Type of Publication: Journal article published
    PubMed ID: 24807787
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  • 7
    Keywords: EXPRESSION ; GENE ; VARIANTS ; FUSION ; BENIGN ; ANNOTATION ; GENOMES ; SOLITARY FIBROUS TUMOR ; DESMOID TUMORS ; FIBROMATOSIS
    Abstract: Sinonasal hemangiopericytoma (SN-HPC) is an uncommon, site-specific, low-grade mesenchymal neoplasm of probable perivascular myoid cell origin. In contrast to solitary fibrous tumors of soft tissue and sinonasal tract origin, SN-HPCs were recently shown to lack recurrent NAB2-STAT6 fusion variants. Other molecular alterations known to occur in some of soft tissue perivascular myoid cell neoplasms were also absent in SN-HPC; thus, the molecular pathogenesis of SN-HPCs remained unknown. Guided by whole-genome sequencing combined with RNA sequencing of an index case, we analyzed a total of six SN-HPCs for mutations within the amino-terminal region of the gene catenin (cadherin-associated protein), beta 1, 88 kDa (CTNNB1), encoding for beta-catenin. All six cases showed missense mutations, with amino acid substitutions clustering at positions 33 to 45, corresponding to the recognition site of the beta-catenin destruction complex. Similar CTNNB1 mutations have been described in a variety of epithelial and mesenchymal neoplasms. These mutations prevent beta-catenin phosphorylation and proteasomal degradation but promote its nuclear accumulation and subsequent increased transcription of Wingless-related integration site target genes. Consistent with these molecular findings, beta-catenin IHC showed consistent diffuse and strong nuclear staining of the tumor cells in all six SN-HPCs. Our results highlight, for the first time, CTNNB1 mutations as the likely initiating molecular events driving SN-HPC tumorigenesis, which places SN-HPC among the growing family of beta-catenin-driven mesenchymal neoplasms.
    Type of Publication: Journal article published
    PubMed ID: 25482924
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  • 8
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    German Medical Science; Düsseldorf, Köln
    In:  77. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.; 20060524-20060528; Mannheim; DOC06hnod314 /20060424/
    Publication Date: 2006-04-25
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 9
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    German Medical Science; Düsseldorf, Köln
    In:  77. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.; 20060524-20060528; Mannheim; DOC06hnod383 /20060424/
    Publication Date: 2006-04-25
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 10
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    German Medical Science; Düsseldorf, Köln
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 2; DOC052 /20060424/
    Publication Date: 2006-04-24
    Description: Eine offene Mastoidhöhle kann zu verschiedenen Problemen führen. Die Obliteration dieser stellt seit langem eine Herausforderung dar. Verschiedene Eigenmaterialien bzw. Fremdstoffen wie z.B.Hydrooxylapatit- und Trikalziumphosphatkeramik wurden zur Höhlenverkleinerung bereits verwandt. Neue, im Sol-Gel-Verfahren auf Kalziumphasphatbasis und Siliziumoxid gewonnene Materialien (Nano-Bone®) wurden bereits klinisch zur Knochenregeneration eingesetzt. Der Vorteil dieser neuen Materialien liegt - wie tierexperimentell nachgewiesen - in einer sehr guten Osteokonduktivität bei verbessertem Resorptionsverhalten. Andere Materialien wie z.B. Bio-Oss®, ein hoch poröses natürliches Knochenmineral, wiesen ähnliche positive Eigenschaften auf. Es gilt zu prüfen, ob die angegebenen Vorteile dieser neuen Materialien auch in der Mastoidchirurgie nutzbar sein könnten und somit die Diskussion um eine Höhlenobliteration neu beleben könnten. Am Tiermodel sollte geprüft werden, wie die neu entwickelten Materialien durch Ihre Porenstruktur die Ablagerung von körpereigenen Eiweißen und damit die Osteoneogenese beeinflussen. Dazu wurde an 30 narkotisierten Meerschweinchen die Bulla eröffnet und nach Entepithelisierung die eine Seite mit Nano-Bone® und die Gegenseite mit Bio-Oss® aufgefüllt. Die Entnahme der Bulla erfolgte jeweils an 5 Tieren nach einer, zwei, drei, vier, fünf und zwölf Wochen. In der histologischen Aufarbeitung wurde die Osteoblasten/klastentätigkeit bzw. die Osteoneogenese der verschiedenen Gruppen verglichen. Im Bereich der Narbe und der Bulla wurde das Gewebe auf Entzündungsreaktionen untersucht. Die Ergebnisse zeigen ermutigende Eigenschaften der neuen Materialien, so dass ihr Einsatz in der Ohrchirurgie durchaus sinnvoll erscheint.
    Keywords: ddc: 610
    Language: German
    Type: article
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