9 research outputs found
Mapping and characterization of the amplicon near APOA2 in 1q23 in human sarcomas by FISH and array CGH
BACKGROUND: Amplification of the q21-q23 region on chromosome 1 is frequently found in sarcomas and a variety of other solid tumours. Previous analyses of sarcomas have indicated the presence of at least two separate amplicons within this region, one located in 1q21 and one located near the apolipoprotein A-II (APOA2) gene in 1q23. In this study we have mapped and characterized the amplicon in 1q23 in more detail. RESULTS: We have used fluorescence in situ hybridisation (FISH) and microarray-based comparative genomic hybridisation (array CGH) to map and define the borders of the amplicon in 10 sarcomas. A subregion of approximately 800 kb was identified as the core of the amplicon. The amplification patterns of nine possible candidate target genes located to this subregion were determined by Southern blot analysis. The genes activating transcription factor 6 (ATF6) and dual specificity phosphatase 12 (DUSP12) showed the highest level of amplification, and they were also shown to be over-expressed by quantitative real-time reverse transcription PCR (RT-PCR). In general, the level of expression reflected the level of amplification in the different tumours. DUSP12 was expressed significantly higher than ATF6 in a subset of the tumours. In addition, two genes known to be transcriptionally activated by ATF6, glucose-regulated protein 78 kDa and -94 kDa (GRP78 and GRP94), were shown to be over-expressed in the tumours that showed over-expression of ATF6. CONCLUSION: ATF6 and DUSP12 seem to be the most likely candidate target genes for the 1q23 amplification in sarcomas. Both genes have possible roles in promoting cell growth, which makes them interesting candidate targets
A propriedade sem registro : o contrato e aquisição da propriedade imóvel na perspectiva civil-contitucional
Orientador : Prof. Dr. Eroulths Cortiano JuniorTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Jurídicas, Programa de Pós-Graduação em Direito. Defesa: Curitiba, 12/08/2014Inclui referênciasResumo: Esta tese objetiva uma releitura da obrigatoriedade do registro nas aquisições da propriedade imóvel, a partir do reconhecimento do contrato como dotado de função social, que realiza, igualmente, a função social como liberdade de acesso aos bens. A propriedade imobiliária no Direito Civil brasileiro está qualificada como direito real, conforme o art. 1225, I, do Código Civil, e sua transferência negocial se orienta pelo sistema da separação parcial dos planos dos direitos obrigacionais e reais, o qual prevê a necessidade do contrato de transmissão (compra e venda, doação ou permuta) com posterior registro no Cartório Imobiliário, nos termos do art. 1245 e seguintes. A Constituição Federal de 1988 garante o direito de propriedade, que deve atender à sua função social, considerando-a como direito fundamental (art. 5.o, XXII e XXIII) e como princípio geral da ordem econômica (art. 170, II e III). A necessária interação entre o Direito Civil e a Constituição, sob a supremacia hierárquica desta, conduz a entender que o direito de propriedade atual, para além da literalidade do Código Civil, deve nortear-se pela sintonia entre ambos os diplomas legais, mas a partir da observação dos princípios e dos valores constitucionais. O Direito Civil-Constitucional surge, então, como uma opção de desenvolvimento do pensamento jurídico, que visa oferecer espaço de reflexão que supere a dogmática unicamente codificada, pois, com fundamento nos princípios e na axiologia constitucional, auxilia na ressignificação de institutos clássicos, como a propriedade e o contrato. O acesso à propriedade, então, pode ser considerado para além da letra da lei, o que permite relevar o registro, com a funcionalização do contrato que, a partir de sua teleologia, da solidariedade, da alteridade e da boa-fé, pode ser o elemento constitutivo da propriedade, com base no caso concreto. A aplicação direta e imediata da Constituição nas relações interprivadas favorece a ressignificação do contrato, que alçará significado de título suficiente para garantir o direito à propriedade (acesso). A complexidade e a pluralidade das relações sociais conduzem a uma transição do modelo abstrato e individualista da propriedade para o da propriedade concreta, que se constrói na funcionalização como liberdade(s) com vistas à realização das necessidade da pessoa concretamente considerada.Abstract: The aim of this thesis is to re-read the mandatory registration on acquisition of immovable property, from the social function of contract's recognition, which also performs its social function as freedom of access to assets. The immovable property in the Brazilian Civil Law is qualified as a real right, according to art. 1225, I, Civil Code, and its negotiating transferring is guided by the partial separation between obligations and real rights, which predicts the registration of transmission's contract (sale, donation or exchange) with the state registration authority, according to art. 1245 and on Civil Code. The 1988 Federal Constitution guarantees the right to property, which must meet its social function, considering it as a fundamental right (art. 5, XXII and XXIII) and as a general principle of economic order (art. 170, II and III). The necessary interaction between the civil law and the Constitution, under the hierarchical supremacy of this leads to understand that the current property law, beyond its literal meaning of the Civil Code, shall be guided by the line between the two enactments, but from the observation of constitutional principles and values.The Civil-constitutional Law arises, then, as an option for legal thinking development, which aims to provide a reflection space that overcomes the consolidated dogmatic, therefore, on the basis of principles and the constitutional axiology, assists in reframing classical institutes, as property and contract. The access to the property can then be considered beyond the letter of the law, which allows to release the register, with the functionalization's contract which, from its teleology, solidarity, alterity and good faith, may be the constituent element of the property, based on the case. The direct and immediate constitutional applying in privates relations cooperate to the contract redefinition, which obtain the sufficient title to guarantee the right to property (access). The complexity and plurality of social relations lead to a transition from abstract and individualistic model of property to concrete one which is constructed on functionalization as freedom (s) to intending to accomplish persons needs concretely considered
Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance
INTRODUCTION: Improving technologies for the detection and purification of bone marrow (BM) micrometastatic cells in breast cancer patients should lead to earlier prognosis of the risk of relapse and should make it possible to design more appropriate therapies. The technique used has to overcome the challenges resulting from the small number of target cells (one per million hematopoietic cells) and the heterogeneous expression of micrometastatic cell markers. In the present study, we have assessed the clinical relevance of current methods aimed at detecting rare disseminated carcinoma cells. METHODS: BM aspirates from 32 carcinoma patients were screened for the presence of micrometastatic cells positive for epithelial cell adhesion molecule and positive for cytokeratins, using optimized immunodetection methods. A comparison with data obtained for 46 control BM aspirates and a correlation with the clinical status of patients were performed. RESULTS: We developed a sensitive and efficient immunomagnetic protocol for the enrichment of BM micrometastases. This method was used to divide 32 breast carcinoma patients into three categories according to their epithelial cell adhesion molecule status. These categories were highly correlated with the recently revised American Joint Committee on Cancer staging system for breast cancer, demonstrating the clinical relevance of this simple and reliable immunomagnetic technique. We also evaluated immunocytochemical detection of cytokeratin-positive cells and cytomorphological parameters. Immunocytochemistry-based methods for the detection of BM micrometastases did not provide any information about the clinical status of patients, but helped to refine the immunomagnetic data by confirming the presence of micrometastases in some cases. We also tested a new density gradient centrifugation system, able to enrich the tumor fraction of BM specimens by twofold to threefold as compared with standard Ficoll methods. CONCLUSION: These improved methods for the detection of micrometastatic cells in patient BM should help clinicians to predict the clinical status of breast cancer patients at the time of surgery or treatment
Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling
Amplification of chromosome 1 sequences in lipomatous tumors and other sarcomas
Amplifications and gains involving 1q are common abnormalities in solid tumors. Recently, an amplicon originating from 1q21-23, containing the candidate oncogenes COAS1, COAS2 and COAS3 (Chromosome One Amplified Sequence) was identified. The presence, distribution and copy number level of extra COAS sequences were investigated in 48 bone and soft tissue tumor (BSTT) samples using metaphase FISH analysis. Amplification was seen in 27/48 (56%) samples. With few exceptions, all 3 genes were involved, but on average COAS2 exhibited higher copy numbers. The presence of extra COAS signals, irrespective of copy numbers, was found at similar frequencies in different histologic tumor subtypes. However, medium or high level amplification was common in lipomatous tumors but rare in other, nonlipomatous tumors (9/21 vs. 2/27 samples). The most common localization of extra COAS signals in lipomatous tumors was in supernumerary ring and giant marker chromosomes. Among nonlipomatous tumors, the distribution of extra COAS genes was more disperse, being located in various unidentified chromosomal structures, including double minutes, and only rarely in ring chromosomes. Because MDM2 is known to be amplified frequently in BSTTs, and in particular in atypical lipomatous tumors, cases with extra copies of COAS were studied also with an MDM2 probe. Twelve out of 18 lipomatous tumors had extra copies of both COAS and MDM2, and the 2 genes were found to be coamplified and interspersed exclusively in ring and giant marker chromosomes. Also 12 out of 18 nonlipomatous tumors exhibited simultaneous gain of COAS and MDM2, but colocalization in the same chromosome was less frequent. The role of the frequent coamplification of COAS, or some other yet unknown gene in the 1q21-23 region, and MDM2 remains to be elucidated