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71.
Colocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motility. 总被引:6,自引:0,他引:6
Sabine Gesierich Claudia Paret Dagmar Hildebrand Jürgen Weitz Kaspar Zgraggen Friedrich H Schmitz-Winnenthal Vaclav Horejsi Osamu Yoshie Dorothee Herlyn Leonie K Ashman Margot Z?ller 《Clinical cancer research》2005,11(8):2840-2852
PURPOSE: Patients with pancreatic adenocarcinoma have a poor prognosis due to the extraordinary high invasive capacity of this tumor. Altered integrin and tetraspanin expression is suggested to be an important factor. We recently reported that after protein kinase C activation, colocalization of alpha6beta4 with the tetraspanin CO-029 strongly supports migration of a rat pancreatic adenocarcinoma. The finding led us to explore whether and which integrin-tetraspanin complexes influence the motility of human pancreatic tumors. EXPERIMENTAL DESIGN: Integrin and tetraspanin expression of pancreatic and colorectal adenocarcinoma was evaluated with emphasis on colocalization and the impact of integrin-tetraspanin associations on tumor cell motility. RESULTS: The majority of pancreatic and colorectal tumors expressed the alpha2, alpha3, alpha6, beta1, and beta4 integrins and the tetraspanins CD9, CD63, CD81, CD151, and CO-029. Expression of alpha6beta4 and CO-029 was restricted to tumor cells, whereas alpha1, alpha2, alpha3, alpha6, beta1, and CD9, CD81, CD151 were also expressed by the surrounding stroma. CD63, CD81, and beta1 expression was observed at comparably high levels in healthy pancreatic tissue. alpha3beta1 frequently colocalized and coimmunoprecipitated with CD9, CD81, and CD151, whereas alpha6beta4 colocalized and coimmunoprecipitated mostly with CD151 and CO-029. Notably, protein kinase C activation strengthened only the colocalization of CD151 and CO-029 with beta4 and was accompanied by internalization of the integrin-tetraspanin complex, decreased laminin 5 adhesion, and increased cell migration. CONCLUSION: alpha6beta4 is selectively up-regulated in pancreatic and colorectal cancer. The association of alpha6beta4 with CD151 and CO-029 correlates with increased tumor cell motility. 相似文献
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Svjetlana Mohrmann Anna Maier-Bode Frederic Dietzel Petra Reinecke Natalia Krawczyk Thomas Kaleta Ulrike Kreimer Gerald Antoch Tanja N. Fehm Katrin Sabine Roth 《Breast care (Basel, Switzerland)》2022,17(2):159
BackgroundThe question of how to deal with B3 lesions is of emerging interest.MethodsIn the breast diagnostics of 192 patients between 2009 and 2016, a minimally invasive biopsy revealed a B3 lesion with subsequent resection. This study investigates the malignancy rate of different B3 subgroups and the risk factors that play a role in obtaining a malignant finding.ResultsThe distribution of B3 lesions after minimally invasive biopsy was as follows: atypical ductal hyperplasia (ADH), 7.3%; flat epithelial atypia (FEA), 7.8%; lobular neoplasia (LN), 7.8%; papilloma (Pa), 49.5%; phylloidal tumour (PT), 8.9%; radial sclerosing scar (RS), 3.1%; mixed findings, 10.4%; and other B3 lesions, 5.2%. Most B3 lesions were detected by stereotactic vacuum-assisted biopsy (44.3%), 36.5% by ultrasound-assisted biopsy, and 19.3% by magnetic resonance imaging-assisted biopsy. Most B3 lesions (55.2%) were verified by surgical resection, whereas 30.7% were downgraded to a benign lesion. About 14.1% of the cases were upgraded to malignant lesions, 9.4% to ductal carcinoma in situ and 4.7% to invasive carcinoma. In relation to individual B3 lesions, the following malignancy rates were found: 28.6% (ADH), 13.3% (FEA), 33.3% (LN), 12.6% (Pa), 5.9% (PT), and 0% (RS). The most important risk factor was increasing age. Postmenopausal status was considered an increased risk for an upgrade (p = 0.015). A known malignancy in the ipsilateral breast was a significant risk factor for a malignant upgrade (p = 0.003).ConclusionIncreasing knowledge about B3 lesions allows us to develop a “lesion-specific” therapy approach in the heterogeneous group of B3 lesions, with follow-up imaging for some lesions with less malignant potential and concordance with imaging or further surgical resection in cases of disconcordance with imaging or higher malignant potential. 相似文献
75.
Rita K. Schmutzler Bjrn Schmitz-Luhn Bettina Borisch Peter Devilee Diana Eccles Per Hall Judith Balmaa Stefania Boccia Peter Dabrock Günter Emons Wolfgang Gaissmaier Jacek Gronwald Stefanie Houwaart Stefan Huster Karin Kast Alexander Katalinic Sabine C. Linn Sowmiya Moorthie Paul Pharoah Kerstin Rhiem Tade Spranger Dominique Stoppa-Lyonnet Johannes Jozef Marten van Delden Marc van den Bulcke Christiane Woopen 《Breast care (Basel, Switzerland)》2022,17(2):208
BackgroundRisk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action.SummaryTherefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept. 相似文献
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Martin Ganssauge Helmut Wilhelm Karl-Ulrich Bartz-Schmidt Sabine Aisenbrey 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2009,247(12):1707-1710
Background
To report a case of nonarteritic anterior ischemic optic neuropathy (NA-AION) following intravitreal injection of bevacizumab (Avastin®).Methods
Interventional case report with an 18-month follow-up.Results
A 51-year-old male with pseudoxanthoma elasticum presented with NA-AION 2 weeks after treatment with intravitreal of bevazicumab (Avastin®) for choroidal neovascularisation secondary to angioid streaks. Except from a small optic disc without cupping he did not show further risk factors.Discussion
Risk of NA-AION should be taken into consideration when deciding for intravitreal application of drugs including anti-vascular endothelial growth factors (VEGF) agents like bevacizumab (Avastin®) in the treatment of retinal vascular diseases.78.
79.
JD Kuhlmann H Schwarzenbach P Wimberger M Poetsch R Kimmig S Kasimir-Bauer 《BMC cancer》2012,12(1):325
ABSTRACT: BACKGROUND: We recently showed that LOH proximal to M6P/IGF2R locus (D6S1581) in primary ovarian tumors is predictive for the presence of disseminated tumor cells (DTC) in the bone marrow (BM). For therapy-monitoring, it would be highly desirable to establish a blood-based biomarker. Therefore, we quantified circulating DNA (cirDNA) in sera of 63 ovarian cancer patients before surgery and after chemotherapy, measured incidence of LOH at four cancer-relevant chromosomal loci, correlated LOH with tumor cell spread to the BM and evaluated prognostic significance of LOH. Patients and Methods: cirDNA was fractionated into high- and low molecular-weight fraction (HMWF, LMWF) for LOH-profiling, utilizing PCR-based fluorescence microsatellite analysis. BM aspirates were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. RESULTS: cirDNA levels in the HMWF before surgery were predictive for residual tumor load (p=0.017). After chemotherapy, we observed a significant decline of cirDNA in the LMWF (p=0.0001) but not in the HMWF. LOH was prevalently detected in the LMWF with an overall frequency of 67 %, only moderately ablating after chemotherapy (45 %). Before surgery, LOH in the LMWF at marker D10S1765 and D13S218 significantly correlated with tumor grading and FIGO stage (p=0.033, p=0.004, respectively). In both combined fractions, LOH at D6S1581 additionally associated with overall survival (OS) (p=0.030). Moreover, solely LOH at D10S1765 in LMWF after therapy correlated with DTC in BM after therapy (p=0.017). CONCLUSION: We demonstrate the applicability and necessity of DNA-fractionation prior to analyzing circulating LOH and identify LOH at D10S1765 and D6S1581 as novel blood-based biomarkers for ovarian cancer, being relevant for therapy-monitoring. 相似文献
80.
Volkmar Müller Sabine Riethdorf Brigitte Rack Wolfgang Janni Peter A Fasching Erich Solomayer Bahriye Aktas Sabine Kasimir-Bauer Klaus Pantel Tanja Fehm 《Breast cancer research : BCR》2012,14(4):1-8