TTF-1 Action on the Transcriptional Regulation of Cyclooxygenase-2 Gene in the Rat Brain

We have recently found that thyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor, is postnatally expressed in discrete areas of the hypothalamus and closely involved in neuroendocrine functions. We now report that transcription of cyclooxygenase-2 (COX-2), the rate limiting enzyme in prostaglandin biosynthesis, was inhibited by TTF-1. Double immunohistochemistry demonstrated that TTF-1 was expressed in the astrocytes and endothelial cells of blood vessel in the hypothalamus. Promoter assays and electrophoretic mobility shift assays showed that TTF-1 inhibited COX-2 transcription by binding to specific binding domains in the COX-2 promoter. Furthermore, blocking TTF-1 synthesis by intracerebroventricular injection of an antisense oligomer induced an increase of COX-2 synthesis in non-neuronal cells of the rat hypothalamus, and resulted in animals' hyperthermia. These results suggest that TTF-1 is physiologically involved in the control of thermogenesis by regulating COX-2 transcription in the brain

A efetividade do laser de HeNe 632,8 nm no reestabelecimento da integridade dos tecidos cutâneos em animais experimentais: revisão sistemática

O objetivo desta revisão sistemática foi analisar o efeito do laser de HeNe na cicatrização de feridas em ratos. Foram selecionados estudos experimentais que adotaram o laser HeNe para o tratamento de feridas agudas em ratos adultos saudáveis, com lesões induzidas por bisturi, nas bases de dados PubMed/MEDLINE, LILACS e SciELO. Foram utilizados os seguintes descritores: cicatrização de feridas e colágeno, de acordo com o MeSH e o DeCS, além dos unitermos laser HeNe e reparação da pele e seus equivalentes em inglês e espanhol. Três estudos foram incluídos na revisão sistemática, não sendo possível a realização de metanálise, devido à impossibilidade de comparação entre as metodologias dos estudos selecionados. Todos os estudos realizaram análise por meio de cortes histológicos das cicatrizes. A presença de falhas metodológicas nos três artigos dificultou a interpretação fidedigna dos dados encontrados. Os estudos destacaram uma redução na intensidade da resposta inflamatória e uma melhor organização das fibras colágenas no grupo irradiado. A terapia com laser HeNe mostrou boa resposta no reparo tecidual. No entanto, tais resultados devem ser analisados de modo criterioso, uma vez que há presença de heterogeneidade, principalmente em relação aos parâmetros adotados

Evaluating the SERCA2 and VEGF mRNAs as Potential Molecular Biomarkers of the Onset and Progression in Huntington's Disease

Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation of neurotrophic factors in several areas of the central nervous system and in peripheral tissues are hallmarks of Huntington\u2019s disease (HD). As there is no therapy for this hereditary, neurodegenerative fatal disease, further effort should be made to slow the progression of neurodegeneration in patients through the definition of early therapeutic interventions. For this purpose, molecular biomarker(s) for monitoring disease onset and/or progression and response to treatment need to be identified. In the attempt to contribute to the research of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing the HD mutation at different clinical stages of the disease and 54 sex- and agematched controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic reticulum-associated ATP2A2 calcium pump (SERCA2) and vascular endothelial growth factor (VEGF) in peripheral blood mononuclear cells (PBMCs) of manifest and premanifest HD subjects. Our results provide a potentially new candidate molecular biomarker for monitoring the progression of this disease and contribute to understanding some early events that might have a role in triggering cellular dysfunctions in HD

Prognostic value of thyroid transcription factor-1 in primary, resected, non-small cell lung carcinoma

Thyroid transcription factor-1 (TTF-1) is a 38-kDa nuclear protein expressed in thyroid follicular cells, in human fetal lung, and, after birth, in Type II epithelial cells of alveoli and in a subset of bronchial cells. Expression of TTF-1 was documented in neoplasms arising from cells that normally produce this transcription factor. In the present study, a series of surgically resected non-small cell lung carcinomas (NSCLCs) was evaluated for the expression of TTF-1 protein, and the correlation between TTF-1 expression and patient survival was retrospectively tested. Ninety-six patients with primary NSCLC underwent surgical resection between 1987 and 1992. All of the tissue specimens from these patients were examined for TTF-1 protein expression by immunohistochemical analysis. Tumor immunoreactivity for TTF-1 was categorized into three groups (-, +, and ++), according to the percentage of reactive cells. The relationship between TTF-1 expression and postsurgical survival was analyzed for 88 patients [60 squamous cell carcinomas (SCCs) and 28 adenocarcinomas (ACs)]. TTF-1 stain was always limited to nuclei. Of the 96 specimens of NSCLC, 59 (61%) were scored as -, 20 (21%) as +, and 17 (18%) as ++. TTF-1 expression was significantly higher in ACs than in SCCs (P < .0001). Survival curves among the -, +, and ++ groups were significantly different (log rank test, P = .04). Multivariate analysis showed that NSCLCs in the ++ group were associated with a poor prognosis (P = .009), independent of node (P = .01) or stage status (P = .0006). When subsets of patients with SCC and with AC were separately analyzed, TTF-1 was found to have an independent prognostic value only in patients with SCC (P = .04). The results of this study suggest that immunoreactivity for TTF-1 in NSCLC closely relates to clinical outcome, especially in patients with SCC

Combined analysis of MIB-1 and thyroid transcription factor-1 predicts survival in non-small cell lung carcinomas

The prognostic value of combined immunohistochemical analysis for the thyroid transcription factor-1 (TTF-1) and the proliferation marker MIB-1 was assessed in a consecutive series of non-small cell lung carcinomas (NSCLC). Tumor immunoreactivity for TTF-1 and MIB-1 was classified in three groups (-,+,+ +) and in two groups (-,+), respectively. Comparison across groups for TTF-1 reactivity showed significantly different survival curves (P = 0.04). In particular, the best prognosis was associated with a TTF-1 negative pattern, whereas the TTF-1 '++' cases showed the worst prognosis. A trend towards better prognosis was observed for MIB-1 negative cases (P = 0.09). Multivariate analysis confirmed independent prognostic significance of TTF-1 (P = 0.002), MIB-1 (P = 0.01) and pStage (P = 0.04). Accordingly, analysing TTF-1 and MIB-1 together, a better prediction of survival was obtained (P = 0.02), with the poorest prognosis for the 'TTF-1++/MIB-1+' cases. (C) 2001 Elsevier Science Ireland Ltd. All rights reserve