Stratification of non-small cell lung cancer patients for therapy with epidermal growth factor receptor inhibitors: the EGFR fluorescence in situ hybridization assay

DNA fluorescence in situ hybridization (FISH) technology is used to study chromosomal and genomic changes in fixed cell suspensions and tissue block preparations. The technique is based on specific hybridization of small labeled DNA fragments, the probes, to complementary sequences in a target DNA molecule. Demand for FISH assays in formalin-fixed, paraffin-embedded tissues has been increasing, mainly in conditions in which diagnosis is not achieved in cell smears or tissue imprints, such as solid tumors. Moreover, the development of molecular targeted therapies in oncology has expanded the applicability of tests to predict sensitivity or resistance to these agents. The efficient use of tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) as therapeutical agents in advanced non-small cell lung cancer (NSCLC) depends on identification of patients likely to show clinical benefit from these specific treatments. The EGFR gene copy number determined by FISH has been demonstrated as an effective predictor of outcome from NSCLC patients to EGFR TKIs; however there are pending challenges for standardization of laboratory procedures and definition of the scoring system. This methodology article focuses on the EGFR FISH assay. It details the scoring system used in the studies conducted at the University of Colorado Cancer Center in which a significant association was found between increased EGFR copy numbers and clinical outcome to TKIs, and proposes interpretative guidelines for molecular stratification of NSCLC patients for TKI therapy

Identification of common fragile sites in chromosomes of 2 species of bat (Chiroptera, Mammalia)

In the karyotypes of the bat species Molossus ater and M molossus, spontaneous and bromodeoxyuridine (BrdU)- or aphidicolin (APC)-sensitive fragile sites were located. Four chromosome regions harbored APC-sensitive fragile sites: 1q9 and 8q4 in both M ater and M molossus, 3q3 in M ater, and 1p7 in M molossus. The fragile sites in 1q9 and 8q4 were also observed without induction in M molossus. BrdU-sensitive fragile sites were not detected. Despite observations in several other species, the fragile sites detected in Molossus are not coincident with the breakpoints involved in the chromosome rearrangements occurring in the evolution of 7 species of the Molossidae family

Chromosomal imbalances are uncommon in chagasic megaesophagus

<p>Abstract</p> <p>Background</p> <p>Chagas' disease is a human tropical parasitic illness and a subset of the chronic patients develop megaesophagus or megacolon. The esophagus dilation is known as chagasic megaesophagus (CM) and one of the severe late consequences of CM is the increased risk for esophageal carcinoma (ESCC). Based on the association between CM and ESCC, we investigated whether genes frequently showing unbalanced copy numbers in ESCC were altered in CM by fluorescence in situ (FISH) technology.</p> <p>Methods</p> <p>A total of 50 formalin-fixed, paraffin-embedded esophageal mucosa specimens (40 from Chagas megaesophagus-CM, and 10 normal esophageal mucosa-NM) were analyzed. DNA FISH probes were tested for <it>FHIT</it>, <it>TP63</it>, <it>PIK3CA</it>, <it>EGFR, FGFR1</it>, <it>MYC</it>, <it>CDKN2A, YES1 </it>and <it>NCOA3 </it>genes, and centromeric sequences from chromosomes 3, 7 and 9.</p> <p>Results</p> <p>No differences between superficial and basal layers of the epithelial mucosa were found, except for loss of copy number of <it>EGFR </it>in the esophageal basal layer of CM group. Mean copy number of <it>CDKN2A and </it>CEP9 and frequency of nuclei with loss of <it>PIK3CA </it>were significantly different in the CM group compared with normal mucosa and marginal levels of deletions in <it>TP63</it>, <it>FHIT, PIK3CA, EGFR, CDKN2A, YES </it>and gains at <it>PIK3CA, TP63, FGFR1, MYC, CDNK2A </it>and <it>NCOA3 </it>were detected in few CM cases, mainly with dilation grades III and IV. All changes occurred at very low levels.</p> <p>Conclusions</p> <p>Genomic imbalances common in esophageal carcinomas are not present in chagasic megaesophagus suggesting that these features will not be effective markers for risk assessment of ESCC in patients with chagasic megaesophagus.</p

A natureza regional das normas jus cogens

A presente pesquisa teve como foco a análise das normas jus cogens . Estas são as normas peremptórias do direito internacional, aquelas que devem ser obedecidas por todos os Estados da comunidade internacional, detendo, portanto, efeito erga omnes . Contudo, ainda paira muita insegurança jurídica acerca de tais normas tendo em vista a incerteza em relação ao seu conteúdo assim como as autoridades legítimas para reconhecê-las. Além destas duas incertezas, há um terceiro elemento que ainda não há resposta: podem as normas jus cogens ter um caráter regional? Poderiam existir normas cogentes aplicáveis a somente um continente, por exemplo? O objetivo desta pesquisa foi de justamente responder e elucidar se de fato as normas peremptóriasinternacionais poderiam ter um caráter regional ou não. Para responder tal pergunta, foi realizada a pesquisa jurisprudencial e doutrinária. A análise jurisprudencial foi usada tendo em vista que há inúmeras decisões internacionais que reconhecem tais normas. Por sua vez, a análise doutrinária foi utilizada tendo em vista o vasto espectro de opiniões no que concerne tais normas, tendo pouca unanimidade. Diante do método utilizado, foi verificado que não há a possibilidade de existirem normas jus cogens regionais tendo em vista a sua própria natureza e definição. Tais normas detém efeitos erga omnes , aplicáveis a todos os estados, visto que são as normasessenciais, basilares, do Direito Internacional. Diante desta característica, resta evidente que normas jus cogens regionais é um contra-senso em si. Por definição não podem existir, visto que estas são as normas que se aplicam a todos os Estados. Esta pesquisa, portanto, concluiu que, em virtude de sua própria natureza, as normas peremptórias do Direito Internacional não podem ter um caráter regiona

SIX1 (sine oculis homeobox homolog 1) (mammalian)

Review on SIX1 (sine oculis homeobox homolog 1) (mammalian), with data on DNA, on the protein encoded, and where the gene is implicated

Biologic and Genetics Aspects of Chagas Disease at Endemic Areas

The etiologic agent of Chagas Disease is the Trypanosoma cruzi, transmitted through blood-sucking insect vectors of the Triatominae subfamily, representing one of the most serious public health concerns in Latin America. There are geographic variations in the prevalence of clinical forms and morbidity of Chagas disease, likely due to genetic variation of the T. cruzi and the host genetic and environmental features. Increasing evidence has supported that inflammatory cytokines and chemokines are responsible for the generation of the inflammatory infiltrate and tissue damage. Moreover, genetic polymorphisms, protein expression levels, and genomic imbalances are associated with disease progression. This paper discusses these key aspects. Large surveys were carried out in Brazil and served as baseline for definition of the control measures adopted. However, Chagas disease is still active, and aspects such as host-parasite interactions, genetic mechanisms of cellular interaction, genetic variability, and tropism need further investigations in the attempt to eradicate the disease

Arquitetura hoteleira sob a ótica da sustentabilidade e da hospitalidade do espaço: um estudo sobre a aplicação dos conceitos de sustentabilidade e hospitalidade do espaço em projetos de hotéis

This present study aims to discuss the concept of both sustainability and hospitality into the context of city contemporary architecture which, in a certain way had been reinterpreted or asked in what is concerned to the concept of environmental sustainability. In this sense, the main goal of the research was to analyze two hotel projects in Santa Catarina, Brazil, been one of them configured as a small sized one and the other as a big hotel, where all the mentioned conditions had been manifested in a tight way and even had not been systematized into one of the hotel architecture samples, as a reference of sustainable and hospitable architecture. The methodology characterized by an initial bibliographic study, as well as documentary study, followed by a field research characterized by an intensive direct observation, as well as a group and systematic one, also considered both observation and questionnaires application (Marconi &amp; Lakatos, 2006) and it tried to rescue the history of hotel architecture in order to identify environmental sustainability contents, as well as hospitality ones, concerned to the constructed spaces, so that it would be possible, in a following moment, to analyze the hotel samples selected, which do manifest all the mentioned conditions. It was realized that considering its realities and sizes, both studied hotels do count with actions and elements that may be considered sustainable, as well as friendly environmental actions, what, doubtless, do provide hospitality in a certain way. Similarly, both hotels still have potentialities to be developed.El estudio debate los conceptos de sostenibilidad y hospitalidad del espacio en el contexto de la arquitectura de la ciudad contemporánea que fueron reinterpretados o cuestionados respecto al concepto de sostenibilidad ambiental. En este sentido, el objetivo de la investigación ha sido analizar dos proyectos de hoteles en Santa Catarina, uno de pequeño y otro de grande porte, en lo cual estas condiciones se presentan de forma puntual o no sistematizada en algunos ejemplares de la arquitectura hotelera, como referencia conceptual de la arquitectura sostenible y hospitalaria. La metodología caracterizada por una revisión de la literatura inicial, investigación documental, seguida de un estudio de campo también caracterizada por una observación directa intensiva, sistemática y en equipo, con prácticas de observación y aplicación de entrevistas (Marconi y Lakatos, 2006)  ha buscado rescatar la historia de la arquitectura hotelera para identificar los contenidos de sostenibilidad ambiental y de hospitalidad en el espacio construido, para posteriormente analizar los dos ejemplos de la arquitectura hotelera elegidos, que manifiestan estas condiciones. Por lo tanto, se ha realizado una revisión bibliográfica, y posteriormente el trabajo de campo que ha consistido en realización de entrevistas, formulario de observación y levantamiento del acervo bibliográfico. Se ha podido observar con la investigación que, según sus realidades y tamaños, ambos emprendimientos estudiados poseen acciones y elementos que pueden ser considerados sostenibles, como también acciones ambientalmente correctas, lo que, inevitablemente se puede considerar como acciones conducentes de hospitalidad. Por lo tanto, cuentan con potencialidades que pueden ser desarrolladas.Este estudo procura discutir os conceitos de sustentabilidade e hospitalidade do espaço no contexto da arquitetura da cidade contemporânea que, de alguma maneira foram reinterpretados ou questionados no que se refere ao conceito de  sustentabilidade  ambiental. Neste sentido, o objetivo principal da pesquisa foi analisar dois projetos de hotéis em Santa Catarina, um de pequeno porte e outro de grande porte, onde essas condições se manifestaram de forma estanques ou não sistematizadas em alguns exemplares da arquitetura hoteleira, como referência conceitual da arquitetura sustentável e hospitaleira. A metodologia caracterizada por um levantamento bibliográfico inicial, pesquisa documental, seguida de um estudo de campo caracterizado por uma observação direta intensiva, sistemática e em equipe, com práticas de observação e aplicação de entrevista (Marconi e Lakatos, 2006) procurou resgatar a história da arquitetura hoteleira para identificar conteúdos de sustentabilidade ambiental e de hospitalidade do espaço construído, para em seguida analisar os exemplares da arquitetura hoteleira selecionados, que manifestam estas  condições. Percebeu-se com o estudo que dentro de suas realidades e tamanhos, ambos os empreendimentos estudados contam com ações e elementos que podem ser considerados sustentáveis, bem como ações ambientalmente amigáveis, o que, inevitavelmente podem ser considerados como ações propiciadoras da hospitalidade. Da mesma forma, contam com potencialidades a serem desenvolvida