ABSTRACT
Background: NOTCH1 pathway activation has been recently described to be a key player in gastric carcinogenesis, enhance the survival and proliferation of cancer stem cells (CSCs) and mediate chemoresistance in several malignancies. Aim: This study investigated the correlation between NOTCH1 and CSC marker OCT4 (octamer binding transcription factor-4) expression and the clinicopathological properties, survival and treatment outcome in patients with gastric carcinoma (GC) receiving adjuvant chemotherapy. Materials and Methods: NOTCH1 and OCT4 were immunohistochemically detected in 50 post-operated specimens of GC. Patients' data regarding disease-free survival (DFS), overall survival (OS), and the response to the chemotherapy was statistically analyzed. Results: NOTCH1 and OCT4 overexpression was detected in 60% and 52% of GC tissues, respectively, and that was significantly higher than the rates in adjacent non-neoplastic gastric mucosa (P < 0.05). A significant correlation was detected between overexpression of NOTCH1 and OCT4 in GC and aggressive clinicopathological features; poor differentiation (P = 0.021, P = 0.037, respectively), depth of tumor invasion (P < 0.001 for both), TNM stage (P < 0.001 for both), lymph node metastasis (P = 0.002, P = 0.003, respectively) and distant metastasis (P < 0.001 for both). NOTCH1 was positively correlated with OCT4 (P = 0.002). Survival analysis disclosed that upregulation of NOTCH1 and OCT4 was associated with worse DFS (P = 0.013, P < 0.001, respectively) and OS (P < 0.001 for both). Overexpression of NOTCH1 and OCT4 correlated with poor response to chemotherapy (P = 0.013, P = 0.005, respectively) and worse clinical outcome. Conclusion: Combined detection of these proteins might disclose even better predictive value for shorter survival and resistance to chemotherapy.
ABSTRACT
TEMA: na infância a doença cerebrovascular (DCV) constitui condição rara em que a evolução a curto, médio e longo prazo tem merecido esclarecimentos. Neste sentido, a aplicação de técnicas comportamentais pode possibilitar melhor caracterização clínica, visando o planejamento e controle terapêutico eficientes. OBJETIVO: descrever em uma criança com DCV as manifestações audiológicas em dois momentos distintos da evolução clínica. MÉTODO: a criança, com diagnóstico comprovado de episódio único e unilateral de DCV, apresentando habilidades de linguagem e cognição satisfatórias, foi submetida a conjunto de testes convencionais e de processamento auditivo, incluindo a avaliação simplificada e as categorias de testes monóticos, dicóticos e de processamento temporal. Os dados obtidos foram pareados com criança normal destra, de mesmo sexo, idade e nível sócio-cultural. RESULTADOS: foi constatado comprometimento nas habilidades de memória auditiva e atenção seletiva em tarefas de integração e separação binaural para estímulos verbais e não-verbais. CONCLUSÃO: a evolução, embora favorável, se mostrou abaixo do esperado para a idade, quando comparado com seu par. A avaliação prospectiva da criança acometida por DCV possibilitou caracterizar o comportamento auditivo, definir seus parâmetros e a evolução do quadro audiológico.
BACKGROUND: cerebrovascular disease (CVD) during childhood is a rare condition; its short, medium and long-term characteristics deserve further investigation. The application of behavioral techniques may improve clinical characterization, thus rendering more efficient therapeutic planning and control. AIM: to describe the audiological manifestations in a child with CVD in two distinct moments of clinical follow-up. METHOD: the child, with a confirmed diagnosis of a single and unilateral episode of CVD, presenting satisfactory cognition and language skills, was submitted to a battery of conventional and auditory processing tests, which included a simplified evaluation as well as monotic, dichotic, and temporal processing tests. The obtained data was paired with those of a normal right-handed child, of the same gender, age and socio-cultural level. RESULTS: results indicate impairments in auditory memory as well as in selective attention during binaural separation and integration tasks for verbal and non-verbal stimuli. CONCLUSION: clinical development, although favorable, was below the average expected for the same age when compared to the control. The prospective evaluation of a child with DCV permitted the characterization of the auditory behavior, the definition of its parameters as well as the development of the audiological characteristics.