Global ETD Search

1	Perfil de expressão de microRNAs no esôfago de crianças portadoras de estenose cáustica Oliveira Junior, Wilson Elias de January 2018 (has links) Orientador: Erika Veruska Paiva Ortolan / Resumo: Introdução: Por volta de oitenta por cento dos acidentes envolvendo ingestão de cáusticos ocorrem em crianças. A estenose cáustica do esôfago é a sua principal complicação com grande morbidade. Lesões neoplásicas esofágicas podem desenvolver-se como uma complicação tardia desta estenose com um tempo médio de aparecimento entre o acidente e o desenvolvimento neoplásico de 15 a 30 anos. Considerando este risco, biopsias seriadas do esôfago são recomendadas com o objetivo de detecção precoce de displasias. Assim, um conhecimento abrangente da relação biológica entre cáusticos e neoplasia esofágica é de grande importância na identificação de novos biomarcadores que possibilitariam tratamento precoce. MicroRNAs (miRNAs) são RNAs pequenos, não codificadores de proteínas que regulam importantes processos celulares e têm se mostrado como robustos biomarcadores. O perfil global de expressão de miRNAs nesta população, seguida da identificação dos miRNA-alvo, pode levar à identificação da presença e magnitude do dano ao material genético em amostra de tecido esofágico obtido de pacientes portadores de estenose cáustica. Objetivos: Determinar o perfil global da expressão de miRNAs em células da mucosa esofágica de crianças portadoras de lesões por ingestão de cáusticos, com o objetivo de identificar miRNAs como biomarcadores associados a tumorigênese esofágica nesta população específica. Materiais e Métodos: Vinte e sete amostras esofágicas fixadas em formalina e embebidas em parafina (F... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: 80% of the caustic ingestions occur in children. Esophageal stricture is a major chronic complication with great morbidity. Esophageal neoplasms may develop as a late complication of caustic injury with a mean time between caustic ingestion and cancer development of 15-30 years. Serial biopsies are recommended aiming early detection of premalignant changes. Thus a comprehensive knowledge of biological relation between caustic and esophageal cancer is of major importance to identify the biomarkers that could enable an early treatment. MicroRNAs (miRNAs) are small non-coding RNA molecules and regulate key cellular processes during tumorigenesis and have been demonstrated as an useful diagnostic, prognostic and predictive biomarkers. Global miRNA expression profiling analysis in this population, followed by the identification of miRNA target genes, may lead to the identification of the presence and magnitude of damage to genetic material in a sample of esophageal tissue obtained from patients with caustic stenosis. Objectives: We aimed to identify global microRNA (miRNA) expression changes in cells of the esophageal mucosa from children with caustic lesions compared to paired macroscopic and microscopically normal esophageal tissue. Patient and Methods: 27 formalin fixed, paraffin embedded (FFPE) esophageal samples from 15 patients were divided into two groups according to the time elapsed after the injury (Group A: less than 5 years, Group B: more than 5 years). Tho... (Complete abstract click electronic access below) / Doutor estenose cáustica MicroRNAs. câncer de esôfago cirurgia pediátrica caustic stenosis miRNA profiling esophageal cancer pediatric surgery
2	Transcriptomic and Secretomic Profiling of Isolated Leukocytes Exposed to Alpha-Particle and Photon Radiation - Applications in Biodosimetry Howland, Matthew 09 September 2013 (has links) The general public is at risk of ionising-radiation exposure. The development of high-throughput methods to triage exposures is warranted. Current biodosimetry techniques are low-throughput and encumbered by time and technical expertise. Although there has been an emergence of gene-profiling tools for the purpose of photon biodosimetry, similar capacities do not exist for alpha-particle radiation. Herein is the first genomic study useful for alpha-particle radiation biodosimetric triage. This work has identified robust alpha-particle induced gene-based biomarkers in isolated, ex-vivo irradiated leukocytes from multiple donors. It was found that alpha-particle and photon radiation elicited similar transcriptional responses, which could potentially be distinguished by aggregate-signature analysis. Although no distinct genes were sole indicators of exposure type, clustering algorithms and principal component analysis were able to demarcate radiation type with some success. By comparing the biological effects elicited by photon and alpha-particle radiation, significant contributions have been made to the field of radiation biodosimetry. alpha-particle ionising radiation ionizing radiation gene response transcriptional response photon radiation biodosimetry dosimetry gene profiling miRNA profiling bio-plex
3	Transcriptomic and Secretomic Profiling of Isolated Leukocytes Exposed to Alpha-Particle and Photon Radiation - Applications in Biodosimetry Howland, Matthew January 2013 (has links) The general public is at risk of ionising-radiation exposure. The development of high-throughput methods to triage exposures is warranted. Current biodosimetry techniques are low-throughput and encumbered by time and technical expertise. Although there has been an emergence of gene-profiling tools for the purpose of photon biodosimetry, similar capacities do not exist for alpha-particle radiation. Herein is the first genomic study useful for alpha-particle radiation biodosimetric triage. This work has identified robust alpha-particle induced gene-based biomarkers in isolated, ex-vivo irradiated leukocytes from multiple donors. It was found that alpha-particle and photon radiation elicited similar transcriptional responses, which could potentially be distinguished by aggregate-signature analysis. Although no distinct genes were sole indicators of exposure type, clustering algorithms and principal component analysis were able to demarcate radiation type with some success. By comparing the biological effects elicited by photon and alpha-particle radiation, significant contributions have been made to the field of radiation biodosimetry. alpha-particle ionising radiation ionizing radiation gene response transcriptional response photon radiation biodosimetry dosimetry gene profiling miRNA profiling bio-plex
4	Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3) Guidi, Mònica 13 January 2009 (has links) Neurotrophins and their receptors are key molecules in the development of thenervous system. Neurotrophin-3 binds preferentially to its high-affinity receptorNTRK3, which exists in two major isoforms in humans, the full-length kinaseactiveform (150 kDa) and a truncated non-catalytic form (50 kDa). The twovariants show different 3'UTR regions, indicating that they might be differentiallyregulated at the post-transcriptional level. In this work we explore howmicroRNAs take part in the regulation of full-length and truncated NTRK3,demonstrating that the two isoforms are targeted by different sets of microRNAs.We analyze the physiological consequences of the overexpression of some of theregulating microRNAs in human neuroblastoma cells. Finally, we providepreliminary evidence for a possible involvement of miR-124 - a microRNA with noputative target site in either NTRK3 isoform - in the control of the alternativespicing of NTRK3 through the downregulation of the splicing repressor PTBP1. / Las neurotrofinas y sus receptores constituyen una familia de factores crucialespara el desarrollo del sistema nervioso. La neurotrofina 3 ejerce su funciónprincipalmente a través de una unión de gran afinidad al receptor NTRK3, del cualse conocen dos isoformas principales, una larga de 150KDa con actividad de tipotirosina kinasa y una truncada de 50KDa sin dicha actividad. Estas dos isoformasno comparten la misma región 3'UTR, lo que sugiere la existencia de unaregulación postranscripcional diferente. En el presente trabajo se ha exploradocomo los microRNAs intervienen en la regulación de NTRK3, demostrando que lasdos isoformas son reguladas por diferentes miRNAs. Se han analizado lasconsecuencias fisiológicas de la sobrexpresión de dichos microRNAs utilizandocélulas de neuroblastoma. Finalmente, se ha estudiado la posible implicación delmicroRNA miR-124 en el control del splicing alternativo de NTRK3 a través de laregulación de represor de splicing PTBP1. RISC complex retinoic acid renilla luciferase real-time quantitative PCR PTBP1 pri-miRNA pre-miRNA post-transcriptional regulation piRNA PicTar pGL4.13 PCR P-body p75NTR overexpression NTRK3 NTRK2 NTRK1 non-coding RNAs NGF neurotrophin neurotrophic signaling neuronal differentiation neurodevelopment neuroblastoma nervous system mRNA miRNA target prediction miRNA profiling miRNA mimic miRNA microarray miRNA inhibitor miRanda microRNA microarray luciferase assay Ingenuity Pathway Analysis (IPA) heLa cells gene silencing gene regulation full-length isoform (FL-NTRK3) firefly luciferase ERK disease dicer cancer development BDNF argonaute alternative splicing 3'UTR RNAhybrid RT-PCR SH-SY5Y cells siRNA standard error synaptic plasticity target validation TargetScan transfection translational repression TrkA TrkB TrkC truncated isoform (TR-NTRK3) tyrosine kinase (TK) western blot 575 61

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