PP272—Migraine and parthenolide inhibition of transient receptor potential ankyrin 1

2013 e103 emerged as a major complication of bortezomib therapy, which usually appears in the first courses of therapy with a number of sensory and painful symptoms, including reduced threshold to mechanical and cold stimuli. No satisfactory explanation or effective treatment exists for bortezomib-evoked CIPN. Patients (or Materials) and Methods: In this study, we evaluated whether TRPA1 acted as a critical mediator of CIPN by bortezomib or oxaliplatin in a mouse model system. Results: Our data demonstrated that CIPN hypersensitivity phenotype that was stably established by bortezomib could be transiently reverted by systemic or local treatment with the TRPA1 antagonist HC-030031. A similar effect was produced by the oxidative stress scavenger α -lipoic acid. Notably, the CIPN phenotype was abolished completely in mice that were genetically deficient in TRPA1, highlighting its essential role. Administration of bortezomib or oxaliplatin, which also elicits TRPA1-dependent hypersensitivity, produced a rapid, transient increase in plasma of carboxy-methyllysine, a byproduct of oxidative stress. Short-term systemic treatment with either HC-030031 or α -lipoic acid could completely prevent hypersensitivity if administered before the cytotoxic drug. Conclusion: Our findings highlight a key role for early activation/ sensitization of TRPA1 by oxidative stress by-products in producing CIPN. Furthermore, they suggest prevention strategies for CIPN in patients through the use of early, short-term treatments with TRPA1 antagonists. Disclosure of Interest: None declared

Diretrizes e procedimentos para publicação de trabalhos técnico-científicos na Embrapa Florestas.

bitstream/CNPF-2009-09/42431/1/Doc143.pdf1 CD-ROM

Paranaguá, Antonina e Curitiba, início do século XIX: reconstituindo espaços e a lógica de sua organização social

This paper is to develop a methodology to characterize the spatial distribution in the early nineteenth century, the urban residents enrolled in the Décima of Paranaguá, Antonina and Curitiba, three villages in southern province of São Paulo. Here are the problems faced and decisions made, almost always temporary and arbitrary. The result reached hypothetical plants of subdivisions and urban streets of those towns. From a database - developed mainly with the information Lista Nominativa de Habitantes - it was possible to characterize residents enrolled in the books of property tax Décima. Spatialising thematic data in plants, where they lived was possible to perceive the social group, your choices (or lack thereof), or realize their preferred sites, but not exclusive housing.O objetivo desse artigo é desenvolver uma metodologia para caracterizar a espacialização, no início do século XIX, dos moradores arrolados nas décimas urbanas de Paranaguá, Antonina e Curitiba, três vilas do sul da capitania de São Paulo. Apresentamos aqui os problemas enfrentados e decisões tomadas, quase sempre provisórias e arbitrárias. O resultado chegou a plantas hipotéticas dos loteamentos e arruamentos urbanos daquelas vilas. A partir de um banco de dados - elaborado principalmente com informações das Listas Nominativas de Habitantes -, foi possível caracterizar os moradores arrolados nos livros de imposto predial de Décima. Espacializando esses dados em plantas temáticas, foi possível perceber onde moravam os grupo sociais, suas escolhas (ou a falta delas), ou seja, perceber seus locais preferenciais, mas não exclusivos, de habitação

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope