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Semireplication-competent vesicular stomatitis virus as a novel platform for oncolytic virotherapy

世界最新医学信息文摘 2015年第5期 245-245页

作者： Alexander Muik Catherine Dold Yvonne Gei Andreas Volk Marina Werbizki Ursula Dietrich dorothee von laer

Among oncolytic viruses, the vesicular stomatitis virus(VSV) is especially potent and a highly promising agent for the treatment of cancer. But, even though effective against multiple tumor entities in preclinical animal models, replicationcompetent VSV exhibits inherent neurovirulence, which has so far hindered clinical development. To overcome this limitation,replication-defective VSV vectors for cancer gene therapy have been tested and proven to be safe. However, gene delivery was inefficient and only minor antitumor efficacy was observed. Here, we present semireplicationcompetent vector systems for VSV(sr VSV), composed of two trans-complementing, propagation-deficient VSV vectors. The de novo generated deletion mutants of the two VSV polymerase proteins P(phosphoprotein) and L(large catalytic subunit), VSVΔP and VSVΔL respectively, were used mutually or in combination with VSVΔG vectors. These sr VSV systems copropagated in vitro and in vivo without recombinatory reversion to replication-competent virus. The sr VSV systems were highly lytic for human glioblastoma cell lines,spheroids, and subcutaneous xenografts. Especially the combination of VSVΔG/VSVΔL vectors was as potent as wild-type VSV(VSV-WT) in vitro and induced long-term tumor regression in vivo without any associated adverse effects. In contrast, 90% of VSV-WT-treated animals succumbed to neurological disease shortly after tumor clearance. Most importantly, even when injected into the brain, VSVΔG/VSVΔL did not show any neurotoxicity. In conclusion, sr VSVis a promising platform for virotherapeutic approaches and also for VSV-based vector vaccines, combining improved safety with an increased coding capacity for therapeutic transgenes, potentially allowing for multipronged approaches.

关键词： Vesicular stomatitis virus Oncolytic virus Virotherapy Malignant glioma

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Frequency and individual severity of arterial blood pressure changes in children and adolescents with attentiondeficit/hyperactivity disorder treated with methylphenidate hydrochloride: a prospective non-interventional study

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General Psychiatry 2020年第2期33卷 80-87页

作者： dorothee Busold-Hagenbeck Julia Elmenhorst Christoph Irtel von Brenndorff Reinhard Hilgers Martin Hulpke-Wette University Medical Centre Gottingen GottingenLower SaxonyGermany German Heart Centre Munich MunichBavariaGermany 3Medical Practice for Paediatric CardiologyBaden-Baden Baden-Wurttemberg Germany Departm ent of Medical Statistics University Medical Centre GottingenGottingenLower SaxonyGermany Medical Practice for Paediatric Cardiology GottingenLower SaxonyGermany

Background Attention-deficit/hyperactivity disorder(ADHD)is a common behavioural disorder in childhood.The psychostimulant methylphenidate hydrochloride(MPH)is one of the major pharmacological options for ADHD.MPH is known to result,on average,in a small increase in arterial blood pressure(BP).However,there are few clinical data regarding theindividual influences of MPH on BP among children and adolescents with ADHD.According to the European Union-wide standardised patient information sheet for MPH,BP changes>10 mm Hg compared with baseline values are Common'(ie,≥1%to10 mm Hg.The mean changes in systolic BP and diastolic BP were 0.87 mm Hg(95%Cl-1.75 mm Hg to 3.48 mm Hg)and 1.96 mm Hg(95%Cl 0.21 mm Hg to 3.7 mm Hg),respectively.The proportion of participants with initial prehypertension/hypertension was 54.55%.Conclusions In our sample with a high baseline rate of prehypertension/hypertension,BP changes>10 mm Hg during MPH therapy were more frequent than those indicated by the patient information sheet.Moreover,individual BP changes,including increases and decreases>10 mm Hg,resulted in a small average BP increase in the sample,thus reflecting neither the severity nor the direction of individ

关键词： severity prospective routine

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