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101.
Hairpin-structured phosphorothioate oligodeoxyribonucleotides containing a singlet oxygen-sensitive linker in the loop were prepared. These compounds do not bind complementary nucleic acids in the dark. Upon irradiation with red light in the presence of chlorine e6 the linker within these compounds is cleaved and a single-stranded oligodeoxyribonucleotide is produced. The latter compound is an efficient binder of complementary nucleic acids. This is the first example of ‘caged’ phosphorothioate oligodeoxyribonucleotides, whose nucleic acid binding ability is triggered by red light. 相似文献
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Sato F Jin Z Schulmann K Wang J Greenwald BD Ito T Kan T Hamilton JP Yang J Paun B David S Olaru A Cheng Y Mori Y Abraham JM Yfantis HG Wu TT Fredericksen MB Wang KK Canto M Romero Y Feng Z Meltzer SJ 《PloS one》2008,3(4):e1890
Background
Barrett''s esophagus predisposes to esophageal adenocarcinoma. However, the value of endoscopic surveillance in Barrett''s esophagus has been debated because of the low incidence of esophageal adenocarcinoma in Barrett''s esophagus. Moreover, high inter-observer and sampling-dependent variation in the histologic staging of dysplasia make clinical risk assessment problematic. In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett''s esophagus surveillance efficiency.Methods and Findings
We defined high-grade dysplasia as endpoint of progression, and Barrett''s esophagus progressor patients as Barrett''s esophagus patients with either no dysplasia or low-grade dysplasia who later developed high-grade dysplasia or esophageal adenocarcinoma. We analyzed 4 epigenetic and 3 clinical parameters in 118 Barrett''s esophagus tissues obtained from 35 progressor and 27 non-progressor Barrett''s esophagus patients from Baltimore Veterans Affairs Maryland Health Care Systems and Mayo Clinic. Based on 2-year and 4-year prediction models using linear discriminant analysis (area under the receiver-operator characteristic (ROC) curve: 0.8386 and 0.7910, respectively), Barrett''s esophagus specimens were stratified into high-risk (HR), intermediate-risk (IR), or low-risk (LR) groups. This 3-tiered stratification method retained both the high specificity of the 2-year model and the high sensitivity of the 4-year model. Progression-free survivals differed significantly among the 3 risk groups, with p = 0.0022 (HR vs. IR) and p<0.0001 (HR or IR vs. LR). Incremental value analyses demonstrated that the number of methylated genes contributed most influentially to prediction accuracy.Conclusions
This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barrett''s esophagus surveillance accuracy and efficiency. 相似文献103.
Abraham JM Cheng Y Hamilton JP Paun B Jin Z Agarwal R Kan T David S Olaru A Yang J Ito T Selaru FM Mori Y Meltzer SJ 《PloS one》2008,3(6):e2508
Cancers have been revealed to be extremely heterogenous in terms of the frequency and types of mutations present in cells from different malignant tumors. Thus, it is likely that uniform clinical treatment is not optimal for all patients, and that the development of individualized therapeutic regimens may be beneficial. We describe the generation of multiple, unique small peptides nine to thirty-four amino acids in length which, when labeled with the radioisotope (32)P, bind with vastly differing efficiencies to cell lines derived from different colon adenocarcinomas. In addition, the most effective of these peptides permanently transfers the (32)P radioisotope to colorectal cancer cellular proteins within two hours at a rate that is more than 150 times higher than in cell lines derived from other cancers or from the normal tissues tested. Currently, the only two FDA-approved radioimmunotherapeutic agents in use both employ antibodies directed against the B cell marker CD20 for the treatment of non-Hodgkin's lymphoma. By using the method described herein, large numbers of different (32)P-labeled peptides can be readily produced and assayed against a broad spectrum of cancer types. This report proposes the development and use of (32)P-labeled peptides as potential individualized peptide-binding therapies for the treatment of colon adenocarcinoma patients. 相似文献
104.
D. Lixandru P. Alexandru A. Mihai A. Roşca C. Ionescu-Tîrgovişte L.I. Braşoveanu 《Free radical research》2017,51(6):604-615
Aim: To investigate peripheral blood monocytes/macrophages (Mo/M?) paraoxonase 2 (PON2) in diabetes and the factors modulating its activity.Methods: One hundred and eighteen patients with newly diagnosed uncomplicated type 2 diabetes mellitus were compared regarding clinical, biochemical and oxidative stress parameters with 80 healthy subjects. The capacity of the peripheral blood mononuclear cells (PBMNC) to release pro-oxidants and to neutralise them was determined by measuring the respiratory burst (RB) and the intracellular antioxidant enzyme PON2. In vitro experiments were conducted on a differentiated monocytes cell line (dU937) that was exposed to serum deprivation followed by addition of isolated lipoproteins (VLDL or LDL).Results: Paraoxonase 2 activity in Mo/M? was significantly lower in type 2 diabetes patients (0.042?±?0.044 vs 0.165?±?0.133U lactonase activity/mg protein in controls, p?.0005) and decreased in the obese in all groups. It was inversely correlated to parameters of adiposity (BMI and Waist Circumference), of glucose control (blood glucose, fructosamine and HbA1c) and insulin resistance (HOMA-IR). In multivariate regression models, 15–34% of the PON2 variance was explained by diabetes. The in vitro addition of VLDL normalised the RB of serum deprived dU937 cells, S? (to 82?±?18% of the cells incubated with serum, S+) and PON2 activity (from 0.524?±?0.061 in S???to 0.298?±?0.048?U/mg protein). In contrast, when LDL was added, the RB remained lower (61?±?12% of S+, p?=?.03) and PON2 higher (0.580?±?0.030?U/mg protein, p?=?.003).Conclusions: The decrease in monocyte/macrophage PON2 enzymatic activity observed in type 2 diabetes cannot be totally explained by abdominal obesity and insulin resistance. The underlying molecular mechanisms need to be identified. 相似文献
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Transgenic switchgrass (Panicum virgatum L.) targeted for reduced recalcitrance to bioconversion: a 2‐year comparative analysis of field‐grown lines modified for target gene or genetic element expression 下载免费PDF全文
Alexandru Dumitrache Jace Natzke Miguel Rodriguez Jr Kelsey L. Yee Olivia A. Thompson Charleson R. Poovaiah Hui Shen Mitra Mazarei Holly L. Baxter Chunxiang Fu Zeng‐Yu Wang Ajaya K. Biswal Guifen Li Avinash C. Srivastava Yuhong Tang Charles Neal Stewart Jr Richard A. Dixon Richard S. Nelson Debra Mohnen Jonathan Mielenz Steven D. Brown Brian H. Davison 《Plant biotechnology journal》2017,15(6):688-697
Transgenic Panicum virgatum L. silencing (KD) or overexpressing (OE) specific genes or a small RNA (GAUT4‐KD, miRNA156‐OE, MYB4‐OE, COMT‐KD and FPGS‐KD) was grown in the field and aerial tissue analysed for biofuel production traits. Clones representing independent transgenic lines were established and senesced tissue was sampled after year 1 and 2 growth cycles. Biomass was analysed for wall sugars, recalcitrance to enzymatic digestibility and biofuel production using separate hydrolysis and fermentation. No correlation was found between plant carbohydrate content and biofuel production pointing to overriding structural and compositional elements that influence recalcitrance. Biomass yields were greater for all lines in the second year as plants establish in the field and standard amounts of biomass analysed from each line had more glucan, xylan and less ethanol (g/g basis) in the second‐ versus the first‐year samples, pointing to a broad increase in tissue recalcitrance after regrowth from the perennial root. However, biomass from second‐year growth of transgenics targeted for wall modification, GAUT4‐KD, MYB4‐OE, COMT‐KD and FPGS‐KD, had increased carbohydrate and ethanol yields (up to 12% and 21%, respectively) compared with control samples. The parental plant lines were found to have a significant impact on recalcitrance which can be exploited in future strategies. This summarizes progress towards generating next‐generation bio‐feedstocks with improved properties for microbial and enzymatic deconstruction, while providing a comprehensive quantitative analysis for the bioconversion of multiple plant lines in five transgenic strategies. 相似文献
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Kathryn E. Barry Liesje Mommer Jasper van Ruijven Christian Wirth Alexandra J. Wright Yongfei Bai John Connolly Gerlinde B. De Deyn Hans de Kroon Forest Isbell Alexandru Milcu Christiane Roscher Michael Scherer-Lorenzen Bernhard Schmid Alexandra Weigelt 《Trends in ecology & evolution》2019,34(2):167-180