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Effects of selenomethionine on acute toxicities from concurrent chemoradiation for inoperable stage Ⅲ nonsmall cell lung cancer

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World Journal of Clinical Oncology 2015年第5期6卷 156-165页

作者： Michael Mix Nithya Ramnath Jorge Gomez charles de groot Saju Rajan Shiva Dibaj Wei Tan Youcef Rustum Michael B Jameson Anurag K Singh department of Radiation Medicine Roswell Park Cancer Institute department of Medical Oncology University of Michigan department of Radiation Oncology Regional Cancer CentreWaikato Hospital department of Biostatistics and Bioinfor- matics Roswell Park Cancer Institute department of Cancer Biology Roswell Park Cancer Institute department of Oncology Regional Cancer CentreWaikato Hospital

AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine(SLM) with concurrent chemoradiation(CCRT) for Stage Ⅲ non-small cell lung cancer(NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its ***: Sixteen patients with stage Ⅲ NSCLC were accrued to this single arm, phase Ⅱ study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly Ⅳ paclitaxel 50 mg/m2 followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS: No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients(19%), pneumonitis in 0, leukopenia in 2(12.5%), and anemia in 1(6%); the latter two were significantly reduced when compared to the protocolstated expected rate of 35%(P = 0.045 for leukopenia, and P decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.

关键词： Selenium Chemoprotective Radioprotector Toxicity Radiotherapy

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Intra-arterial thrombolytics during endovascular thrombectomy for acute ischaemic stroke in the MR CLEAN Registry

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Stroke & Vascular Neurology 2023年第1期8卷 17-25页

作者： Sabine L Collette Reinoud P H Bokkers Aryan Mazuri Geert J LycklamaàNijeholt Robert J van Oostenbrugge Natalie E LeCouffe Faysal Benali charles B L M Majoie Jan Cees de groot Gert Jan R Luijckx Maarten Uyttenboogaart 无 department of Radiology Medical Imaging CentreUniversity Medical Centre GroningenUniversity of GroningenGroningenthe Netherlands department of Radiology Haaglanden Medical CentreThe Haguethe Netherlands department of Neurology Cardiovascular Research Institute Maastricht(CARIM)Maastricht University Medical CentreMaastrichtthe Netherlands department of Neurology Amsterdam UMCUniversity of AmsterdamAmsterdam NeuroscienceAmsterdamthe Netherlands department of Radiology Maastricht University Medical CentreMaastrichtthe Netherlands department of Radiology and Nuclear Medicine Amsterdam UMCUniversity of AmsterdamAmsterdam NeuroscienceAmsterdamthe Netherlands department of Neurology University Medical Centre GroningenUniversity of GroningenGroningenthe Netherlands On behalf of the MR CLEAN Registry investigators

Introduction The efficacy and safety of local intra-arterial(IA)thrombolytics during endovascular thrombectomy(EVT)for large-vessel occlusions is *** analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands(MR CLEAN)Registry,whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA *** In this observational study,we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR CLEAN Registry(March 2014-November 2017).The primary endpoint was favourable functional outcome,defined as an modified Rankin Scale score≤2 at 90 *** endpoints were reperfusion status,early neurological recovery and symptomatic intracranial haemorrhage(sICH).Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were *** Of the 2263 included patients,95(4.2%)received IA thrombolytics during *** IA thrombolytics administered were urokinase(median dose,250000 IU(IQR,193750-250000))or alteplase(median dose,20 mg(IQR,12-20)).No association was found between IA thrombolytics and favourable functional outcome(adjusted OR(aOR),1.16;95%CI 0.71 to 1.90).Successful reperfusion was less often observed in those patients treated with IA thrombolytics(aOR,0.57;95%CI 0.36 to 0.90).The odds of sICH(aOR,0.82;95%CI 0.32 to 2.10)and early neurological recovery were comparable between patients treated with and without IA *** primary and adjuvant revascularisation attempts,IA thrombolytics were more often administered for proximal than for distal *** outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation *** Local IA thrombolytics were rarely used in the MR CLEAN *** the relatively small st

关键词： arterial throm acute

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designing chimeric enzymes inspired by fungal cellulosomes

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Synthetic and Systems Biotechnology 2020年第1期5卷 23-32页

作者： Sean P.Gilmore Stephen P.Lillington charles H.Haitjema Randall de groot Michelle A.O'Malley department of Chemical Engineering University of CaliforniaSanta BarbaraSanta BarbaraCA93106United States MC 5080 University of CaliforniaSanta BarbaraCA93106-5080United States

Cellulosomes are synthesized by anaerobic bacteria and fungi to degrade lignocellulose via synergistic action of multiple enzymes fused to a protein *** templating key protein domains(cohesin and dockerin),designer cellulosomes have been engineered from bacterial motifs to alter the activity,stability,and degradation efficiency of enzyme *** a parts list for fungal cellulosomes from the anaerobic fungi(Neocallimastigomycota)was determined,which revealed sequence divergent fungal cohesin,dockerin,and scaffoldin domains that could be used to expand the available toolbox to synthesize designer *** this work,multi-domain carbohydrate active enzymes(CAZymes)from 3 cellulosome-producing fungi were analyzed to inform the design of chimeric proteins for synthetic cellulosomes inspired by anaerobic *** particular,Piromyces finnis was used as a structural template for chimeric carbohydrate active *** enzymes with retained properties were engineered by combining thermophilic glycosyl hydrolase domains from Thermotoga maritima with dockerin domains from Piromyces *** preserving the protein domain order from ***,chimeric enzymes retained catalytic activity at temperatures over 80°C and were able to associate with cellulosomes purified from anaerobic *** cellulosomes harbor a wide diversity of glycoside hydrolases,each representing templates for the design of chimeric *** conserving dockerin domain position within the primary structure of each protein,the activity of both the catalytic domain and dockerin domain was retained in enzyme *** further,the domain positioning inferred from native fungal cellulosome proteins can be used to engineer multi-domain proteins with non-native favorable properties,such as thermostability.

关键词： Cellulosome Dockerin Scaffoldin Anaerobic fungi Thermophile Enzyme

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