Loss of heterozygosity (LOH) in tumour suppressor genes in benign and malignant mixed odontogenic tumours

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Although molecular alterations are reported in different types of odontogenic tumours, their pathogenesis remains to be established. Loss of heterozygosity (LOH) studies allow the identification of minimal regions of deletions of known or putative tumour suppressor genes, the losses of which may promote neoplastic growth. The purpose of this study was to investigate LOH in a set of odontogenic mixed tumours. Tumour suppressor gene loci on 3p, 9p, 11p, 11q and 17p chromosomes were analysed in five samples of ameloblastic fibroma (AF), three samples of ameloblastic fibro-odontoma (AFO) and three samples of ameloblastic fibrosarcoma (AFS). The most frequently lost genetic loci were p53 (17p13, 62%) and CHRNB1 (17p13, 55%). LOH at the chromosome regions 3p24.3, 9p22 and 9p22-p21 was identified only in AFS. No sample showed LOH at the chromosomal loci 3p21.2 and 11q13.4. For the region 9p22-p13, LOH occurred in one sample of AFO. The fractional allelic loss (FAL) was calculated for each sample. The mean FAL of the benign lesions (i. e. AF and AFO) was 22%, whereas the mean FAL of the malignant lesions (i. e. AFS) was 74.6%. In conclusion, our results show a higher FAL in AFS compared to its benign counterparts and reveal a different pattern of LOH of tumour suppressor genes in AFS, which may regulate changes in tumour behaviour. J Oral Pathol Med (2012) 41: 389-393415389393Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Tendência de mortalidade do câncer de pulmão, traquéia e brônquios no Brasil, 1980-2003 Lung cancer, cancer of the trachea, and bronchial cancer: mortality trends in Brazil, 1980-2003

OBJETIVO: Descrever a tendência da mortalidade do câncer de pulmão, traquéia e brônquios por sexo e faixas etárias no Brasil. MÉTODOS: Para essa análise, utilizou-se o banco de dados do Sistema de Informações sobre Mortalidade de 1980 a 2003. A análise de tendência de mortalidade no Brasil e em estados selecionados foi realizada com o ajuste de modelos e utilização da técnica LOWESS para suavização das taxas. RESULTADOS: No Brasil, a taxa padronizada de mortalidade por câncer de pulmão, traquéia e brônquios passou de 7,21 em 1980 a 9,36 óbitos por 100 mil habitantes em 2003. A análise das taxas de mortalidade específicas mostra redução em homens entre 30 e 49 anos e entre 50 e 59 anos. Entre os homens de 60 a 69 anos ocorreu aumento das taxas entre 1980 até 1995, seguido de declínio. Entre homens acima de 70 anos e entre mulheres em todas as faixas etárias acima de 30 anos, a tendência é de aumento das taxas em todo o período analisado. CONCLUSÕES: a redução das taxas de mortalidade entre homens mais jovens pode ser o resultado das ações nacionais para a redução da prevalência do tabagismo no país nas décadas mais recentes, reduzindo a exposição nas coortes mais jovens. A manutenção de taxas elevadas de mortalidade em populações mais idosas deve-se a experiência do tabagismo passado. Quanto às mulheres, a elevação das taxas segue tendência mundial, também em função do aumento da prevalência do tabagismo entre mulheres nos anos recentes.<br>OBJECTIVE: To describe the mortality trends for lung cancer, cancer of the trachea, and bronchial cancer in relation to gender and age brackets in Brazil. METHODS: Data related to mortality between 1980 and 2003 were collected from the Brazilian Mortality Database. A trend analysis of mortality was carried out, nationwide and in selected states, using the LOWESS technique for rate smoothing and model adjustments. RESULTS: In Brazil, the standardized mortality rate for lung cancer, cancer of the trachea, and bronchial cancer increased from 7.21/100,000 inhabitants in 1980 to 9.36/100,000 inhabitants in 2003. Specific mortality rates decreased in males in the 30-49 and 50-59 age brackets. In the 60-69 age bracket, the rates for males increased from 1980 to 1995 and declined thereafter. There was a trend toward higher mortality rates in males over 70, as well as in females over 30, throughout the period evaluated. CONCLUSIONS: The decrease in the mortality rates in younger males might have resulted from recent national interventions aimed at reducing the prevalence of smoking and reducing exposure in younger cohorts. High mortality rates in older populations remained constant due to prior tobacco use. Increased mortality rates in females are a worldwide trend and are attributable to the recent increase in smoking prevalence in females

Investigation of Proliferative Activity in the Developing Human Tooth Using Ki-67 Immunostaining

Objective: The aim of this study was to investigate the proliferation of the developing human tooth germ and its surrounding tissues using Ki-67 immunostaining. Materials and Methods: Sections of mandibular dental arch tissues collected from 4 cadaveric human fetuses of 13, 16, 21 and 30 weeks of gestation were used. The immunoreactivity of Ki-67 in the tissue sections was assessed visually under a light microscope. Immunohistochemical controls were performed by replacing the primary antibody with phosphate-buffered saline or normal rabbit IgG. Results: The control sections did not display Ki-67 immunoactivity. Specimens of 13 weeks of gestation revealed intense Ki-67 immunostaining throughout the entire developing mandibular primary molars. At 16 weeks of gestation, immunostaining was observed in the inner enamel epithelium and dental papilla, in conjunction with the dental lamina showing decreased immunostaining. At 21 weeks, Ki-67 immunostaining was observed only in the inner enamel epithelium and dental papilla. The immunoreactivity of active ameloblasts and odontoblasts decreased, along with the proliferation capacity of the dental lamina. At 30 weeks, both enamel and dentin formation was observed along the cusped aspect of the tooth germ. Ameloblasts and odontoblasts were no longer immunoreactive in this region, while both types of cells were immunoreactive at the cervical regions of the crown. Dental lamina cells showed disintegration and were totally Ki-67-negative at 30 weeks of gestation. Conclusion: The Ki-67 immunoreactivity of the dental lamina decreased during intrauterine tooth development. Positive immunostaining was observed at specific sites in the enamel organ and dental papilla during the cap and bell stages. Copyright (C) 2007 S. Karger AG, Basel.WoSScopu

Tuberculose e silicose: epidemiologia, diagnóstico e quimioprofilaxia Tuberculosis and silicosis: epidemiology, diagnosis and chemoprophylaxis

A silicose, a mais prevalente das pneumoconioses, é provocada pela inalação de partículas de sílica cristalina. Indivíduos expostos à sílica, com ou sem silicose, apresentam risco aumentado de tuberculose e de micobacterioses não-tuberculosas. O risco de silicóticos desenvolverem tuberculose em relação a controles sadios varia de 2,8 a 39 vezes, em conformidade com a gravidade da doença de base. Têm sido estudados diferentes esquemas de quimioprofilaxia para tuberculose em silicóticos, todos com eficácia semelhante e com redução final de risco para cerca da metade em relação ao uso de placebo. São, no entanto, esquemas de longa duração, o que, acrescido dos possíveis efeitos colaterais (particularmente hepatotoxicidade), podem prejudicar a aderência. As diretrizes atuais recomendam a realização de prova tuberculínica e, se positiva, a instituição de quimioprofilaxia. São vários os esquemas possíveis, tanto em termos de drogas quanto de duração. Nossa recomendação é de que se use isoniazida na dose de 300 mg/dia (ou 10 mg/kg/dia) por seis meses para os indivíduos com silicose ou sadios com exposição superior a 10 anos, se forem reatores fortes à prova tuberculínica (induração > 10 mm). São necessários, no entanto, novos estudos para que indicações, drogas, doses e duração da profilaxia sejam definidas mais apropriadamente.<br>Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis) than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction to about one half of that obtained with placebo. Long-term regimens have potential side effects (particularly hepatotoxicity). In addition, the use of such regimens can jeopardize adherence to treatment. The current guidelines recommend that tuberculin skin tests be performed, and, if positive, that chemoprophylaxis be instituted. There are several possible regimens, varying in terms of the drugs prescribed, as well as in terms of treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10 mg/kg/day) for six months for patients with silicosis, as well as for healthy patients with periods of exposure to silica longer than 10 years and strongly positive tuberculin skin test results (induration > 10 mm). Nevertheless, further studies are necessary so that indications, drugs, doses and duration of chemoprophylaxis regimens can be more properly defined

Odontogenic Epithelium: Immunolabeling of Ki-67, EGFR and Survivin in Pericoronal Follicles, Dentigerous Cysts and Keratocystic Odontogenic Tumors

The aim of this study was to evaluate the biological profile of odontogenic epithelium by immunolabeling of epidermal growth factor receptor (EGFR), Ki-67 and survivin in keratocystic odontogenic tumors (KOT), dentigerous cysts (DC), and pericoronal follicles (PF). Immunohistochemical analysis was performed in 13 KOTs, 14 DCs and 9 PFs. Immunolabeling was analyzed in the basal and suprabasal layers of KOTs and DCs, and in the islands of odontogenic epithelium and/or reduced enamel epithelium of PFs. KOTs showed the highest proliferation rate among the three groups, mainly in suprabasal layers. EGFR immunolabeling was observed mainly in the cytoplasm in basal and suprabasal layers of KOTs and in the suprabasal layer of DCs. Immunolabeling in both membrane and cytoplasm was greater in PFs. In PFs, membrane-only staining was observed. Survivin immunolabeling showed a greater percentage of positive cells (scoring +++) in the suprabasal layer of KOTs. In DCs, both layers showed similar percentages of cells scoring +++; PFs showed the highest percentage of these cells. In KOTs, epithelial cells showed stimulus-independent neoplastic proliferative characteristics, suggesting the presence of a suprabasal proliferative compartment, maintained by inhibition of apoptosis. In DCs, the basal layer seemed to proliferate in response to stimulus. Although PFs showed low proliferative activity, the expression of EGFR indicates that some cells have a high capacity to respond to stimuli, which could probably explain the origin of odontogenic lesions