Ulrich Bogdahn

Bio: Ulrich Bogdahn is an academic researcher from University of Regensburg. The author has contributed to research in topics: Neural stem cell & Neurogenesis. The author has an hindex of 67, co-authored 344 publications receiving 32279 citations. Previous affiliations of Ulrich Bogdahn include Hoffmann-La Roche & Volkswagen Foundation.

Versican isoform V1 regulates proliferation and migration in high-grade gliomas.

Abstract: Versican is a large chondroitin sulphate proteoglycan produced by several tumor cell types, including high-grade gliomas. Increased expression of distinct versican isoforms in the extracellular matrix plays a role in tumor cell growth, adhesion and migration. We have recently shown that transforming growth factor (TGF-beta)2, an important modulator of glioma invasion, interacts with versican isoforms V0/V1 during malignant progression of glioma in vitro. However, the distinct subtype of versican that modulates these effects could not be specified. Here, we show that transient down-regulation of V1 by siRNA leads to a significant reduction of proliferation and migration in glioblastoma cell lines and glioblastoma progenitor cells, whereas tumor cell attachment stays unaffected. We conclude that V1 plays a predominant role in modulating central pathophysiological mechanisms as proliferation and migration in glioblastoma. Considering that TGF-beta is a master regulator of glioma pathophysiology, and that V0/1 is induced by TGF-beta2, therapeutic regulation of V1 may induce meaningful effects on glioma cell migration not only in vitro, but also in vivo.

Effective silencing of EGFR with RNAi demonstrates non-EGFR dependent proliferation of glioma cells.

Abstract: The epidermal growth factor receptor (EGFR, ErbB1) is frequently dysregulated in a variety of solid human tumors, including malignant glioma. EGFR expression has been associated with disease progression, resistance to standard therapies and poor survival. The application of small interfering RNAs (siRNAs) has become an effective and highly specific tool to modulate gene expression, and a wide range of oncogenes have been silenced successfully. Here we show the siRNA-mediated down-regulation of EGFR in two established glioma cell lines with different EGFR expression levels (U373 MG, LN18). The expression of EGFR mRNA and protein was down-regulated by 70-90%. However, siRNA treatment had no inhibitory effect on cell proliferation, migration and activation status of EGFR-coupled signaling cascades. In accordance with these results, gene expression analysis with microarrays revealed only small, albeit specific changes in expression patterns. In conclusion, these data indicate that the specific down-regulation of EGFR might not be sufficient for a single agent therapeutic approach in malignant glioma.

Thrombolysis for stroke in the elderly.

Abstract: Introduction. Systemic thrombolysis with intravenous recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke had been licensed for patients up to 75 years in age in many European countries and was recently extended to 80 years. This age restriction results from the potential higher risk of cerebral bleeding in the elderly. The major rtPA trials included only 42 patients above 80 years showing a potential benefit from treatment. Further data is still rare.

Maintenance therapy with 13-cis retinoid acid in high-grade glioma at complete response after first-line multimodal therapy--a phase-II study.

Abstract: Background: Approximately 5% of patients with malignant glioma achieve complete response (CR) after first-line combined modality treatment. Although these patients will invariably suffer from tumor recurrence, they usually do not receive any further treatment to maintain remission. According to in vitro and in vivo clinical studies, 13-cis retinoic acid (cRA) may be a promising agent for maintenance therapy in these patients.

Karotisendarteriektomie und Karotisstenting Pilotstudie eines prospektiven, randomisierten und kontrollierten Vergleichs

Abstract: Fragestellung. In einer prospektiven, randomisierten und kontrollierten Pilotstudie werden die Karotisendarteriektomie und die Stenttherapie an einem Patientenkollektiv mit hochgradigen, symptomatischen Stenosen der extrakraniellen A. carotis interna miteinander verglichen. Methodik. Das Design der Studie sieht vor, dass symptomatische Patienten mit der Diagnose einer hochgradigen Stenose (≥70%) der A. carotis interna, die auf dem Boden einer DSA gesichert wurde, eingeschlossen werden. Vor und nach der Therapie finden wahrend der Hospitalisationsphase jeweils eine klinisch-neurologische Untersuchung, eine Duplexsonographie der Hals- und Hirngefase und eine MRT des Hirns statt. Das Nachsorgeprotokoll nach 1, 6 und 12 Monaten beinhaltet jeweils eine klinisch-neurologische Untersuchung und eine Duplexsonographie sowie nach 12 Monaten zusatzlich eine selektive Angiographie der behandelten Seite und eine weitere MRT des Hirns. Wahrend eines Zeitraums von 9 Monaten wurden bisher 23 von 137 wegen einer Karotisstenose behandelten Patienten in die Studie eingeschlossen, wobei 11 Patienten dem operativen Arm und 12 Patienten dem interventionellen Arm der Studie zugefuhrt wurden. Ergebnisse. Bei allen 23 Patienten wurde ein Primarerfolg ohne residuelle Stenose >30% erzielt, eine zerebrale Ischamie oder Todesfall traten nicht auf. Die bislang durchgefuhrten 18 Nachuntersuchungen (neurologische Untersuchung einschlieslich Duplexsonographie) bei insgesamt 13 Patienten (13 Kontrollen nach 30 Tagen, 5 Kontrollen nach 6 Monaten) ergaben keine relevante Restenosierung und keine zerebrale Ischamie. Schlussfolgerung. Bislang erwies sich die Stenttherapie in unserer Studie als komplikationsarmes Therapieverfahren. Aufgrund der geringen Patientenzahl kann zum jetzigen Zeitpunkt jedoch noch keine endgultige Bewertung erfolgen.

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Abstract: Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition

Abstract: The 3rd edition of the International Classification of Headache Disorders (ICHD-3) may be reproduced freely for scientific, educational or clinical uses by institutions, societies or individuals. Otherwise, copyright belongs exclusively to the International Headache Society. Reproduction of any part or parts in any manner for commercial uses requires the Society’s permission, which will be granted on payment of a fee. Please contact the publisher at the address below. International Headache Society 2013–2018. Applications for copyright permissions should be submitted to Sage Publications Ltd, 1 Oliver’s Yard, 55 City Road, London EC1Y 1SP, United Kingdom (tel: þ44 (0) 207 324 8500; fax: þ44 (0) 207 324 8600; permissions@sagepub.co.uk) (www.uk.sagepub.com). Translations

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial

Abstract: BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. METHODS: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. FINDINGS: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. INTERPRETATION: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. FUNDING: EORTC, NCIC, Nelia and Amadeo Barletta Foundation, Schering-Plough.

MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma

Abstract: background Epigenetic silencing of the MGMT (O 6 -methylguanine–DNA methyltransferase) DNArepair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. methods We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. results The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. conclusions Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.