Circulating tumor DNA detection in head and neck cancer: Evaluation of two different detection approaches

The use of non-invasive biomarkers such as circulating tumor DNA (ctDNA) in head and neck tumors may be of relevance in early diagnosis and eventually improved outcome. We evaluated two different approaches from two case series in Europe and South America including (i) targeted screening of ctDNA mutations, and (ii) detection of TP53 mutations in plasma and oral rinses without previous knowledge of mutational status in tumor samples. Targeted sequencing in 5 genes identified ctDNA mutations in plasma among 42% of HNSCC cases, 67% of who were early stage cases. No association was found between ctDNA mutation detection and overall survival. Sequencing of the entire coding region of the TP53 gene resulted in identification of TP53 mutations in 76% of tumor cases. However, concordance of mutation detection was low between tumor, oral rinses (11%) and plasma (2,7%) samples. Identification of 5 pathogenic TP53 mutations in oral rinses from 3 non-cancer controls gives additional evidence of mutation occurrence in individuals without a diagnosed cancer and presents an additional challenge for the development of ctDNA diagnostic assays. © 2017 Impact Journals LLC. All rights reserved

Saúde bucal e percepção sobre o atendimento odontológico em pacientes com transtorno psíquico moradores de residências terapêuticas Oral health and perceptions regarding dental care in patients with mental disorders living in therapeutic residences

Os pacientes portadores de transtornos psíquicos têm grande dificuldade de acesso ao tratamento dentário. Os problemas enfrentados vão desde a recusa dos profissionais em atender a essa clientela à inapropriada formação profissional dos mesmos. Este estudo, realizado em residências terapêuticas, objetivou avaliar as condições de saúde bucal dos moradores, assim como a percepção dos mesmos em relação ao atendimento odontológico recebido. Fizeram parte do estudo 38 indivíduos, sendo os dados coletados através de exame clínico e entrevista semiestruturada. A análise dos dados indicou elevado índice de cárie e de necessidade protética, com 42,5% dos indivíduos necessitando de prótese total e 30,3%, de próteses parciais. Com relação às condições periodontais, 28,5% dos elementos dentários apresentaram perda de inserção periodontal maior que 4 mm. Os dados da entrevistas foram averiguados pela análise de conteúdo temática, possibilitando a construção de duas categorias: associação de dor com a presença de dentes e o atendimento odontológico mutilador. A presença de saúde bucal foi associada à extração dentária, sendo esta a única solução para os incômodos na boca, indicando que, para esta população, ter saúde bucal é não ter dentes.<br>Patients with mental disorders have considerable difficulty in access to dental care, including the refusal of oral health professionals to offer care to this clientele and the inadequate professional training of oral health professionals regarding this issue. The present study was carried out in therapeutic residences in order to assess the oral health conditions of the residents as well as their perceptions regarding the dental care they have received. Thirty-eight individuals participated in the study. Data were collected through clinical examinations and a semi-structured interview. Data analysis revealed a high number of caries and the need for dentures, with 42.5% of the individuals needing complete dentures and 30.3% needing partial dentures. Regarding periodontal conditions, 28.5% of the dental elements exhibited losses of over 4 mm of periodontal insertion. Data from the interviews were submitted to content analysis, which enabled the establishment of two categories: the association of pain with the presence of teeth and mutilating dental care. Oral health was associated to dental extraction, which was considered the only solution to oral health disturbances, indicating that, for this population, oral health signifies not having teeth

Functional gene screening in embryonic stem cell implicates Wnt antagonism in neural differentiation.

The multilineage differentiation capacity of mouse embryonic stem (ES) cells offers a potential testing platform for gene products that mediate mammalian lineage determination and cellular specialization. Identification of such differentiation regulators is crucial to harnessing ES cells for pharmaceutical discovery and cell therapy. Here we describe the use of episomal expression technology for functional evaluation of cDNA clones during ES-cell differentiation in vitro. Several candidate cDNAs identified by subtractive cloning and expression profiling were introduced into ES cells in episomal expression constructs. Subsequent differentiation revealed that the Wnt antagonist Sfrp2 stimulates production of neural progenitors. The significance of this observation was substantiated by forced expression of Wnt-1 and treatment with lithium chloride, both of which inhibit neural differentiation. These findings reveal the importance of Wnt signalling in regulating ES-cell lineage diversification. More generally, this study establishes a path for rapid and direct validation of candidate genes in ES cells

Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney

During kidney development and in response to inductive signals, the metanephric mesenchyme aggregates, becomes polarized, and generates much of the epithelia of the nephron. As such, the metanephric mesenchyme is a renal progenitor cell population that must be replenished as epithelial derivatives are continuously generated. The molecular mechanisms that maintain the undifferentiated state of the metanephric mesenchymal precursor cells have not yet been identified. In this paper, we report that functional inactivation of the homeobox gene Six2 results in premature and ectopic differentiation of mesenchymal cells into epithelia and depletion of the progenitor cell population within the metanephric mesenchyme. Failure to renew the mesenchymal cells results in severe renal hypoplasia. Gain of Six2 function in cortical metanephric mesenchymal cells was sufficient to prevent their epithelial differentiation in an organ culture assay. We propose that in the developing kidney, Six2 activity is required for maintaining the mesenchymal progenitor population in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud