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71.
Detrimental effects of melanocortin‐1 receptor (MC1R) variants on the clinical outcomes of BRAF V600 metastatic melanoma patients treated with BRAF inhibitors 下载免费PDF全文
Michele Guida Sabino Strippoli Anna Ferretta Nicola Bartolomeo Letizia Porcelli Immacolata Maida Amalia Azzariti Stefania Tommasi Claudia Grieco Stefania Guida Anna Albano Vito Lorusso Gabriella Guida 《Pigment cell & melanoma research》2016,29(6):679-687
Melanocortin‐1 receptor (MC1R) plays a key role in skin pigmentation, and its variants are linked with a higher melanoma risk. The influence of MC1R variants on the outcomes of patients with metastatic melanoma (MM) treated with BRAF inhibitors (BRAFi) is unknown. We studied the MC1R status in a cohort of 53 consecutive BRAF‐mutated patients with MM treated with BRAFi. We also evaluated the effect of vemurafenib in four V600BRAF melanoma cell lines with/without MC1R variants. We found a significant correlation between the presence of MC1R variants and worse outcomes in terms of both overall response rate (ORR; 59% versus 95%, P = 0.011 univariate, P = 0.028 multivariate analysis) and progression‐free survival (PFS) shorter than 6 months (72% versus 33%, P = 0.012 univariate, P = 0.027 multivariate analysis). No difference in overall survival (OS) was reported, probably due to subsequent treatments. Data in vitro showed a significant different phosphorylation of Erk1/2 and p38 MAPK during treatment, associated with a greater increase in vemurafenib IC50 in MC1R variant cell lines. 相似文献
72.
Sara Santos de Carvalho Ana Cristina Sim?es e Silva Adriano de Paula Sabino Fernanda Cristina Gontijo Evangelista Karina Braga Gomes Luci Maria SantAna Dusse Danyelle Romana Alves Rios 《PloS one》2016,11(3)
Background
There is substantial evidence that chronic renal and cardiovascular diseases are associated with coagulation disorders, endothelial dysfunction, inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular diseases. Therefore, this study aimed to compare plasma levels of ultrassensible C-reactive protein (usCRP), PAI-1, D-dimer and TGF-β1 in patients undergoing HD with different ACE I/D polymorphisms.Methods
The study was performed in 138 patients at ESRD under hemodialysis therapy for more than six months. The patients were divided into three groups according to the genotype. Genomic DNA was extracted from blood cells (leukocytes). ACE I/D polymorphism was investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer, PAI-1 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA), and the determination of plasma levels of usCRP was performed by immunonephelometry. Data were analyzed by the software SigmaStat 2.03.Results
Clinical characteristics were similar in patients with these three ACE I/D polymorphisms, except for interdialytic weight gain. I allele could be associated with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and as ID had significantly higher levels of PAI-1 than those with II genotype. Other laboratory parameters did not significantly differ among the three subgroups (P = 0.033). Despite not reaching statistical significance, plasma levels of usCRP were higher in patients carrying the D allele.Conclusion
ACE I/D polymorphisms could be associated with changes in the regulation of sodium, fibrinolytic system, and possibly, inflammation. Our data showed that high levels of PAI-1 are detected when D allele is present, whereas greater interdialytic gain is associated with the presence of I allele. However, further studies with different experimental designs are necessary to elucidate the mechanisms involved in these associations. 相似文献73.
Genilza Pereira de Oliveira Erika Cortez Graça Justo Araujo Katia Costa de Carvalho Sabino Fabiana Alves Neves Amélia Faustino Bernardo Simone Nunes de Carvalho Anibal Sanchez Moura Laís Carvalho Alessandra Alves Thole 《Cell and tissue research》2014,357(1):185-194
Bone marrow cells (BMCs) are the main type of cells used for transplantation therapies. Obesity, a major world health problem, has been demonstrated to affect various tissues, including bone marrow. This could compromise the success of such therapies. One of the main mechanisms underlying the pathogenesis of obesity is mitochondrial dysfunction, and recent data have suggested an important role for mitochondrial metabolism in the regulation of stem cell proliferation and differentiation. Since the potential use of BMCs for clinical therapies depends on their viability and capacity to proliferate and/or differentiate properly, the analysis of mitochondrial function and cell viability could be important approaches for evaluating BMC quality in the context of obesity. We therefore compared BMCs from a control group (CG) and an obese group (OG) of mice and evaluated their mitochondrial function, proliferation capacity, apoptosis, and levels of proteins involved in energy metabolism. BMCs from OG had increased apoptosis and decreased proliferation rates compared with CG. Mitochondrial respiratory capacity, biogenesis, and the coupling between oxidative phosphorylation and ATP synthesis were significantly decreased in OG compared with CG, in correlation with increased levels of uncoupling protein 2 and reduced peroxisome proliferator-activated receptor-coactivator 1α content. OG also had decreased amounts of the glucose transporter GLUT-1 and insulin receptor (IRβ). Thus, Western-diet-induced obesity leads to mitochondrial dysfunction and reduced proliferative capacity in BMCs, changes that, in turn, might compromise the success of therapies utilizing these cells. 相似文献
74.
Ying-Chao Lin Ai-Ru Hsieh Ching-Lin Hsiao Shang-Jung Wu Hui-Min Wang Ie-Bin Lian Cathy SJ Fann 《Journal of biomedical science》2014,21(1)
Background
Genome-wide association studies have been successful in identifying common genetic variants for human diseases. However, much of the heritable variation associated with diseases such as Parkinson’s disease remains unknown suggesting that many more risk loci are yet to be identified. Rare variants have become important in disease association studies for explaining missing heritability. Methods for detecting this type of association require prior knowledge on candidate genes and combining variants within the region. These methods may suffer from power loss in situations with many neutral variants or causal variants with opposite effects.Results
We propose a method capable of scanning genetic variants to identify the region most likely harbouring disease gene with rare and/or common causal variants. Our method assigns a score at each individual variant based on our scoring system. It uses aggregate scores to identify the region with disease association. We evaluate performance by simulation based on 1000 Genomes sequencing data and compare with three commonly used methods. We use a Parkinson’s disease case–control dataset as a model to demonstrate the application of our method.Our method has better power than CMC and WSS and similar power to SKAT-O with well-controlled type I error under simulation based on 1000 Genomes sequencing data. In real data analysis, we confirm the association of α-synuclein gene (SNCA) with Parkinson’s disease (p = 0.005). We further identify association with hyaluronan synthase 2 (HAS2, p = 0.028) and kringle containing transmembrane protein 1 (KREMEN1, p = 0.006). KREMEN1 is associated with Wnt signalling pathway which has been shown to play an important role for neurodegeneration in Parkinson’s disease.Conclusions
Our method is time efficient and less sensitive to inclusion of neutral variants and direction effect of causal variants. It can narrow down a genomic region or a chromosome to a disease associated region. Using Parkinson’s disease as a model, our method not only confirms association for a known gene but also identifies two genes previously found by other studies. In spite of many existing methods, we conclude that our method serves as an efficient alternative for exploring genomic data containing both rare and common variants.Electronic supplementary material
The online version of this article (doi:10.1186/s12929-014-0088-9) contains supplementary material, which is available to authorized users. 相似文献75.
In this article, we report the synthesis of Na2Sr1‐x(PO4)F:Eux phosphor via a combustion method. The influence of different annealing temperatures on the photoluminescence properties was investigated. The phosphor was excited at both 254 and 393 nm. Na2Sr1‐x(PO4)F:Eux3+ phosphors emit strong orange and red color at 593 and 612 nm, respectively, under both excitation wavelengths. Na2Sr1‐x(PO4)F:Eux3+ phosphors annealed at 1050°C showed stronger emission intensity compared with 600, 900 and 1200°C. Moreover, Na2Sr1‐x(PO4)F:Eux3+ phosphor was found to be more intense when compared with commercial Y2O3:Eu3+ phosphor. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
76.
Leandro F. Tarosso Mariana M. Sauer Sabri Sanabani Maria Teresa Giret Helena I. Tomiyama John Sidney Shari M. Piaskowski Ricardo S. Diaz Ester C. Sabino Alessandro Sette Jorge Kalil-Filho David I. Watkins Esper G. Kallas 《PloS one》2010,5(7)
Background
HIV-1-infected individuals who spontaneously control viral replication represent an example of successful containment of the AIDS virus. Understanding the anti-viral immune responses in these individuals may help in vaccine design. However, immune responses against HIV-1 are normally analyzed using HIV-1 consensus B 15-mers that overlap by 11 amino acids. Unfortunately, this method may underestimate the real breadth of the cellular immune responses against the autologous sequence of the infecting virus.Methodology and Principal Findings
Here we compared cellular immune responses against nef and vif-encoded consensus B 15-mer peptides to responses against HLA class I-predicted minimal optimal epitopes from consensus B and autologous sequences in six patients who have controlled HIV-1 replication. Interestingly, our analysis revealed that three of our patients had broader cellular immune responses against HLA class I-predicted minimal optimal epitopes from either autologous viruses or from the HIV-1 consensus B sequence, when compared to responses against the 15-mer HIV-1 type B consensus peptides.Conclusion and Significance
This suggests that the cellular immune responses against HIV-1 in controller patients may be broader than we had previously anticipated. 相似文献77.
Araújo LV Soares MA Oliveira SM Chequer P Tanuri A Sabino EC Ferreira JE 《Genetics and molecular research : GMR》2006,5(1):203-215
We developed a database system for collaborative HIV analysis (DBCollHIV) in Brazil. The main purpose of our DBCollHIV project was to develop an HIV-integrated database system with analytical bioinformatics tools that would support the needs of Brazilian research groups for data storage and sequence analysis. Whenever authorized by the principal investigator, this system also allows the integration of data from different studies and/or the release of the data to the general public. The development of a database that combines sequences associated with clinical/epidemiological data is difficult without the active support of interdisciplinary investigators. A functional database that securely stores data and helps the investigator to manipulate their sequences before publication would be an attractive tool for investigators depositing their data and collaborating with other groups. DBCollHIV allows investigators to manipulate their own datasets, as well as integrating molecular and clinical HIV data, in an innovative fashion. 相似文献
78.
Marta Ruiz‐Bermejo Celia Rogero César Menor‐Salván Susana Osuna‐Esteban José Ángel Martín‐Gago Sabino Veintemillas‐Verdaguer 《化学与生物多样性》2009,6(9):1309-1322
The complex salt named Prussian Blue, Fe4[Fe(CN)6]3?15 H2O, can release cyanide at pH>10. From the point of view of the origin of life, this fact is of interest, since the oligomers of HCN, formed in the presence of ammonium or amines, leads to a variety of biomolecules. In this work, for the first time, the thermal wet decomposition of Prussian Blue was studied. To establish the influence of temperature and reaction time on the ability of Prussian Blue to release cyanide and to subsequently generate other compounds, suspensions of Prussian Blue were heated at temperatures from room temperature to 150° at pH 12 in NH3 environment for several days. The NH3 wet decomposition of Prussian Blue generated hematite, α‐Fe2O3, the soluble complex salt (NH4)4[Fe(CN6)]?1.5 H2O, and several organic compounds, the nature and yield of which depend on the experimental conditions. Urea, lactic acid, 5,5‐dimethylhydantoin, and several amino acids and carboxylic acids were identified by their trimethylsilyl (TMS) derivatives. HCN, cyanogen (C2N2), and formamide (HCONH2) were detected in the gas phase by GC/MS analysis. 相似文献
79.
Francine Pazini Ricardo Menegatti José R. Sabino Carolina H. Andrade Gilda Neves Stela M.K. Rates François Noël Carlos A.M. Fraga Eliezer J. Barreiro Valéria de Oliveira 《Bioorganic & medicinal chemistry letters》2010,20(9):2888-2891
LASSBio-581 is a N-phenylpiperazine derivative designed for the treatment of schizophrenia. In this study, four strains of filamentous fungi were screened for their capabilities to biotransform LASSBio-581. Cunninghamella echinulata ATCC 9244 was chosen to scale up the biosynthesis of the p-hydroxylated metabolite of LASSBio-581. The chemical structure of the metabolite was confirmed by NMR, LC–MS and X-ray crystallography. Binding studies performed on brain homogenate indicated that the p-hydroxylated metabolite can be considered more selective for dopamine receptors than LASSBio-581, and, therefore, can be used to design new selective dopamine inhibitors. 相似文献