Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

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...

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

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

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

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.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(09)70025-7.pdf

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

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.

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MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma

Nat. Med. 8, 1186–1188 (2002) Because of space constraints, a reference was omitted from the text. The following sentence should have appeared after sentence 5 in paragraph 3: “However, Kaufmann et al. have described changes in gray matter structures in 12 narcoleptic patients10.” Subsequent references should be renumbered accordingly.

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Corrigendum: Hypothalamic gray matter changes in narcoleptic patients

Occlusion * Response: Adverse Effects of the Intraluminal Filament Model of Middle Cerebral Artery

COPYRIGHT © 2023 Bruun, Dietrich, Klingseisen and Bogdahn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Cellular CNS repair strategies, technologies and therapeutic developments

Editorial: Cellular CNS repair strategies, technologies and therapeutic developments

Antisense oligonucleotides (ODNs) are single-stranded, chemically-modified DNA-like molecules for the inhibition of gene translation by sequence-specific knockdown of mRNA through Watson–Crick hybridization. In general, their size ranges from 12 to 25 nucleotides in length, with the majority of ODNs being around 18–21 nucleotides. The natural phosphodiester backbone ODNs are rapidly degraded in biological fluids by ubiquitous nucleases. Therefore, a variety of heterocyclic modifications have been developed to strengthen base-pairing and thus stabilize the duplex formation between antisense ODN and their target mRNA. Antisense ODNs have been widely used for determining gene function, validation of drug targets and, finally, as novel therapeutics for human diseases. In this chapter, we will describe the development of antisense ODNs including their modifications, pharmacokinetics, and toxicity in animal models and humans, and their preclinical and clinical development in the therapy of human high-grade gliomas. The most advanced ODN in the therapy of high-grade gliomas is a phosphorothioate modified ODN (S-ODN), AP 12009 (trabedersen), which targets the mRNA encoding transforming growth factor beta2 (TGF-beta2). AP12009 is administered intratumorally using convection-enhanced delivery (CED). A randomized, controlled international Phase III study in recurrent or refractory anaplastic astrocytoma (SAPPHIRE) is planned to start in early 2009. Further antisense molecules targeting malignant glioma in clinical development are Affinitak, a PKC-alpha-S-ODN, and an ODN against IGF type I receptor for ex vivo use. In our opinion, antisense ODNs have potential for clinical applications in cancer patients even in a long-term perspective. They can be designed specifically against their target mRNA, are sufficiently stable in vivo and show first antitumor efficacy in human clinical trials with an excellent toxicity profile. Additionally, novel delivery techniques, like CED, may further improve their pharmacological profile making them superior to other DNA targeting strategies in humans.

Treatment of Malignant Gliomas with Antisense Oligonucleotides

Die Erfindung betrifft ein Melanom-inhibierendes Protein, fur dieses Protein codierende Nukleinsauresequenzen, Verfahren zur Gewinnung dieses Proteins sowie dessen Verwendung zur Herstellung eines Therapeutikums.

Ulrich Bogdahn

Papers

Corrigendum: Hypothalamic gray matter changes in narcoleptic patients

Occlusion * Response: Adverse Effects of the Intraluminal Filament Model of Middle Cerebral Artery

Editorial: Cellular CNS repair strategies, technologies and therapeutic developments

Treatment of Malignant Gliomas with Antisense Oligonucleotides

Melanom-inhibierendes protein