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Ulrich Bogdahn

Other affiliations: Hoffmann-La Roche, Volkswagen Foundation, University of Bern  ...read more
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.


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Proceedings ArticleDOI
TL;DR: This study demonstrates, for the first time, that knockdown of LDH-A can decrease the RNA and protein level of TSP-1 and consecutively the processing of TGF-beta2.
Abstract: Introduction: Lactate dehydrogenase type A (LDH-A) is a key metabolic enzyme catalyzing pyruvate into lactate and is excessively expressed in several human tumors. Transforming growth factor-beta2 (TGF-beta2) is a key regulator of invasion in high-grade gliomas, partially remodeling the extracellular matrix (ECM) and inducing proteinases. Thrombospondin1 (THBS-1) is an extracellular protein important for activation and processing of TGF-beta2. A microarray of LDH-A knocked-down glioma cell RNA showed down regulation of THBS-1 and TGF-beta2. In this study, we tested the hypothesis that LDH-A influences TGF-beta2 activation by up regulation of THBS-1 leading to an enhanced migration of high-grade glioma in vitro. Methods: We performed LDH-A knock-down by transient transfection of glioma cells with small interfering RNA directed against LDH-A (siLDH-A). Expression levels of TGF-beta2 and THBS-1 in siLDH-A transfected cells were investigated using microarrays, RT-PCR, Western Blot and ELISA. Migration of transfected cells was investigated by Boyden Chamber and scratch assays. Results: siLDH-A suppresses TGF-beta2 in high-grade glioma and decreases the expression of THBS-1 on the RNA and protein level. THBS-1 leads to an increased level of activated TGF-beta2 in supernatants of siLDH-A treated cells. In migration assays, siLDH-A leads to a decreased migration of high-grade glioma cells. Discussion: We demonstrate, for the first time, that knockdown of LDH-A can decrease the RNA and protein level of TSP-1 and consecutively the processing of TGF-beta2. Additionally, knockdown of LDH-A decreases the RNA level of TGF-beta2. Both results may contribute to an enhanced level of TGF-beta2 and increased migration, given that LDH-A is expressed. An increased expression of LDH-A has been found in aerobic glycolysis, a mechanism well known from several human cancers. Recent paper showed that LDH-A is able to bind RNA. Thus we suppose LDH-A could influence the level of TGF-beta2 RNA by RNA stabilization. Together with our recent results that show that TGF-beta enhances migration in high-grade gliomas, we demonstrate a new panel of interactions between lactate metabolism and TGF-beta2 that might be crucial for glioma migration and possibly invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 55.

1 citations

Journal ArticleDOI
TL;DR: It is concluded that drug combination chemotherapy effects at the cellular level may be extremely heterogeneous.
Abstract: Combination chemotherapy is widely employed in clinical oncology; however, there is no generally accepted model to evaluate individual tumour susceptibility to a given drug combination protocol. We therefore investigated the drug interaction of ifosfamide (4-hydroxyperoxy-ifosfamide) and ACNU in a recently developed in vitro model of paired sequential combination chemotherapy in primary and metastatic malignant brain tumours. A long-term standard [6,3-3H]-thymidine-incorporation assay, employing a liquid scintillation counting protocol, was selected to assess the drug sensitivity of human tumours. In vitro drug exposures were derived from correlating in vivo-(systemic and CNS) and in vitro-pharmacokinetic drug parameters. In combination experiments tumour cells were treated sequentially by two drugs in both sequences: drug exposures were calculated for 2 h with a 1-h drug-free interval in between. "Cut-off" concentrations (maximum in vitro exposure doses) were calculated as 1.74 microM (for primary CNS tumours: 0.58 microM) for ifosfamide and 5.4 microM (for primary CNS tumours: 1.33 microM) for ACNU. Dose/response relations were derived from isotope incorporation rates after cells had grown for approximately five population doubling times. Combination isoboles were plotted after drug doses had been transformed into "equieffective doses", enabling comparison of drug combination effects. In all three glioblastomas (with CNS exposure dose) an additive or supra-additive effect could be observed in either sequence (in one tumour a biphasic additive isobole was found for both sequences). Out of three bronchial carcinomas (small-cell type, brain metastases) in two non-identical sequences a supra-additive effect was observed in two tumours, with antagonistic effects in the third tumour. In all three malignant melanomas and in one renal carcinoma antagonistic effects were observed, whereas in a second renal carcinoma supra-additive effects were demonstrated for both sequences. We conclude that drug combination chemotherapy effects at the cellular level may be extremely heterogeneous.

1 citations

Journal ArticleDOI
TL;DR: A 60-year-old male Caucasian patient who experienced a reversible sudden loss of vision of the right eye for 10 min followed by recurrent blurring of vision as well as dysarthria and numbness in the left face is presented.
Abstract: We present a rare case of internal carotid artery pseudoocclusion (ICAPO) in a 60-year-old male Caucasian patient who experienced a reversible sudden loss of vision of the right eye for 10 min followed by recurrent blurring of vision as well as dysarthria and numbness in the left face. The referring ophthalmologist admitted the patient for suspicious occlusion of the internal carotid artery causing anterior ischemic optic neuropathy (AION).

1 citations


Cited by
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Journal ArticleDOI
01 Mar 2013-Stroke
TL;DR: These guidelines supersede the prior 2007 guidelines and 2009 updates and support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition; emergency medical services activation, transport, and triage; through the initial hours in the emergency department and stroke unit.
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...

7,214 citations

Journal ArticleDOI
01 Jan 2018
TL;DR: 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 if the Society’s permission is granted.
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

6,269 citations

Journal ArticleDOI
TL;DR: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up, and a benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years.
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.

6,161 citations

Journal ArticleDOI
TL;DR: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylation of theMGMT promoter did notHave such a benefit and were assigned to only radiotherapy.
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.

6,018 citations