Reactivity of p53 protein in canine transmissible venereal tumor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Carcinoma epidermóide de língua :correlação clínica, histológica e imuno-histoquímica

Oral squamous cell carcinoma is the most common malignant neoplasm in oral cavity. Several studies have been carried out to establish biologic behaviour criteria of this neoplasm. Thus, the purpose of this experiment was to performe a clinic, morphologic and immunohistochemical analysis, by the expression of cytokeratins 7, 10, 13, 14, 16 and 19 in 30 cases of tongue squamous cell carcinoma from the files of Dr. Luiz Antônio Hospital (Natal-RN). It was verifeid of the immunoexpression the correlation clinic estadiament and histologic gradation system proposed by Bryne (1998), in order to investigate the use of these intermediate filaments as an indicator of tumour progression. Data was collected from the patients file and it was observed that information regarding sex, age and race was resemble to the literature. Data obtained from disease evolution, clinic estadiament, metastasis and expression of cytokeratins 7, 10, 13, 14, 16 and 19 was submited to statistical analysis (Test K2), which showed that only the histologic gradation didn t demonstrated significant correlation to the clinic variables. The expression the cytokeratins presented variation in the analysed tumours. CK 10 expression showed significant correlation to metastasis, and the presence of CK 16 was related to disease evolution (obit/remission) and also with the T3 and T4 of TNM. These results evidenced that metastasis and TNM showed a good efficacy as a prognostic indicator. The histologic gradation proposed by Bryne (1998) didn t reflect the biologic behaviour of the studied tongue squamous cell carcinoma, and the analysis of some intermediate filaments of cytokeratins seems to reflect the biologic behaviour and agressivity of some oral squamous cell carcinoma

Estudo da expressão imuno-histoquímica das proteínas MMP-9, MMP-13 e TIMP-1 em ameloblastomas e tumores odontogênicos ceratocistos

Ameloblastomas and keratocystic odontogenic tumors (KOT) represent odontogenic lesions that, despite their benign nature, are distinguished by a distinct biological behavior, characterized by locally aggressive growth and recurrent episodes. The gnathic bone resorption caused by the growth of these lesions is a key to the expansion of the same, both being mediated by osteoclastic cells like enzymatic activity of various matrix metalloproteinases (MMPs) factor. The expression of stimulatory factors and inhibitors of bone resorption has been correlated with the development of these lesions, with emphasis to some MMPs such as collagenases and gelatinases and tissue inhibitors of metalloproteinases (TIMPs), among others. Based on the premise that stimulatory and inhibitory factors of osteolytic processes can be decisive for the growth rate of intraosseous odontogenic lesions, this experiment evaluated the immunoreactivity of MMP-9, -13 and TIMP-1 protein in the epithelium and mesenchyme of ameloblastoma and the KOT specimens, by a quantitative analysis of the immunoreactivity cells. Statistical analysis was performed using the Mann-Whitney and Wilcoxon tests with a significance level set at 5 %. Immunohistochemical expression of MMP-9, -13 and TIMP-1 was observed in 100% of cases both in the epithelium and in mesenchyme. The immunoreactivity in the epithelium of KOT and ameloblastomas revealed a predominance of score 3 for MMP-9 (p=0.382) and MMP-13 (p=0.069) and no statistically significance for TIMP-1, the latter being significantly higher immunoreactivity in ameloblastomas. In the mesenchyme, there was a higher score immunoreactivity of MMP-13 (p=0.031) in ameloblastomas in relation to KOT, whereas for MMP-9 and TIMP-1 no statistically significant difference (p=0.403 was observed, p=1.000). The calculation of the ratio of scores revealed expression of proteins in general, similarity of the lesions, a significant predominance of equal expression of TIMP-1 and MMP-9 was observed only in the epithelium of ameloblastoma. The marked immunostaining of MMP-9 , MMP-13 and TIMP-1 in epithelium and mesenchyme of the lesion indicate that these proteins involved in ECM remodeling required for tumor progression, however, specific differences in the expression of some of these proteins, are not sufficient to suggest differences in the biological behavior of ameloblastomas and KOTs

Expressão imuno-histoquimica da cicloxigenase-2 e p53 em cancinoma epidermóide oral

Squamous cell carcinoma is the most common malignant neoplasm in the oral cavity, accounting for more than 90% of all malignancies in this location. Cyclooxygenases (COX s) are key enzymes on arachidonic acid metabolism and prostaglandin synthesis, being expressed basically in two forms: the constitutive (COX-1) and the inducible (COX-2). Increased levels on the expression of COX-2 have been implicated in the pathogenesis tumor progression of various forms of human cancer, including oral squamous cell carcinoma, some of what suggesting a possible interaction between COX-2 and the protein expressed by the tumor suppressor gene p53, mutated in more than 50% of all human cancers. The mean of the present research consisted in analyze the correlation between the expression of COX-2 and p53, at the protein level, as well as evaluate the difference on the expression of these two proteins with the histological grading of malignancy. 34 cases of oral squamous cell carcinoma were selected and graded according to the histological grading system proposed by Bryne (1998) and the labeling indexes (LI s) for COX-2 and p53 evaluated using immunohistochemistry method. The results revealed that COX-2 was expressed in increased levels in most of the specimens, although there was no statistic significant correlation between LI s from COX-2 and p53 (p>0.05), and there were no statistical differences on the expression of these proteins between tumors of high and low grade of malignancy (p>0.05). Interestingly, the expression of COX-2 and p53 was detected in fragments of dysplastic oral epithelium adjacent to tumor areas, on basal and suprabasal layers. The absence of statistical correlation between the expression of COX-2 and p53 proteins do not rule ot the existence of a relation between them, were it may reflect the diversity of regulatory pathways between both, different direct and indirect inhibitory effects of COX-2 over p53, as well as the wide range of activation macheenisms for COX-2 and mutational status of the p53 gene Another conclusion point that the increased expression of COX-2 observed in oral squamous cell carcinomas suggest a role for this protein in the processes of pathogenesis and tumoral evolution of this malignant neoplasm

Avaliação imuno-histoquímica das galectinas-1, -3, -4 e -7 em carcinoma epidermóide de língua.

Several studies are carried out with aim to establish parameters to determine biologic behavior of oral squamous cell carcinoma, in order this neoplasm presents high rates of morbidity and mortality. The purpose of present research was to performe a clinic, morphologic and immunohistochemical analysis by the expression of galectins 1, 3, 4 and 7 in 65 cases of tongue squamous cell carcinoma, correlating this expression with clinics (outcome of the disease, metastasis and clinical staging) and morphologic parameters (malignancy histologic gradation system). The clinical and morphologic parameters analysed and expression of galectins 1, 3, 4 and 7 were submitted to statistical analysis (Qui2 test), observing that can be utilized as indicators of the biological behavior of the tongue squamous cell carcinoma. The galectin 1 was expressed in 87,7% of cases studied and it exhibit statistically significant correlation with metastasis (p=0,033) and clinical staging (p=0,016), it is located mostly in the citoplasm of the stomal cells. The immunoexpression of galectin 3 in 87,7% of cases was correlated with the presence of metastasis (p=0,033) and malignancy histological gradation system (p=0,031), observed, mostly of cases, in tongue squamous cell carcinoma of malignancy high grading. The galectin 4 showed no statistical significance to any of the parameters evaluated. The expression of galectin 7 in 73,8% of cases showed statistically significant correlation with the malignancy histologic grading (p=0,005), which is marking exclusively found in neoplastic epithelial cells, in the mostly of cases, it is found in cytoplasm and membrane (50%). The expressive immunopositivy of the galectins 1, 3 and 7, observed in this research, leads us to suggest a broad participation of these proteins in oral carcinogenesis, and its possible use as markers of biological behavior and tumor progression in cases of squamous cell carcinoma of the tongue

Avaliação da expressão imuno-histoquímica de marcadores de hipóxia em carcinoma epidermóide de língua

The tumor hypoxia modulates a series of genetic changes related to adaptive development, invasion and metastasis of various human cancers, among which squamous cell carcinoma of the tongue (SCCT). The objective of this study was to analyze clinical, morphological and immunohistochemical expression by HIF-1α, GLUT-1 and CA-IX in 57 cases of CEL and correlated this expression to clinical parameters and morphological. After a descriptive analysis of data on gender, age, race, and habits of patients, it was found that the results were consistent with the literature. The clinical and morphological parameters analyzed and the expression of these markers of hypoxia were subjected to statistical analysis (Qui2 test), verifying that they can be used as indicators of the biological behavior of CEL. Among the results of this study, we observed that the intensity of expression for HIF-1α, in most cases located in the cytoplasm and nucleus, statistically correlated with clinical staging (p = 0.011) and histological grading (p = 0.002). As for the relationship between the distribution of labeling for HIF-1α and metastasis, the chi-square (Qui2) showed that there was statistically significant differences between the groups (p = 0.040). 75.8% of the sample who had metastases, there was the predominance of diffuse marking. The immunoexpression cytoplasmic/membrane GLUT-1 showed a statistically significant correlation with the clinical stage (p = 0.002) and histological grading (p = 0.000). Concerning the location of markings for GLUT-1 tumor on the island, there was a predominance of peripheral marking specimens in most low-grade (78.6%). In the sample of high-grade, prevailed the location center/periphery (55.8%). According to the chi-square (Qui2), the location on the island of the tumor (p = 0.025) showed statistically significant difference in histological grading. The immunoreactivity of CA-IX, in most cases located in the membrane and cytoplasm, exhibited a statistically significant correlation with histological grading (p = 0.005). Based on these results, we can conclude a broad participation of these markers of hypoxia in oral carcinogenesis and its possible use as markers of biological behavior and tumor progression in CEL

Efeitos da laserterapia na atividade biológica de células de carcinoma epidermóide de língua humano

The low level laser therapy (LLLT) has shown to be effective in promoting the proliferation of different cells in vitro, including keratinocytes, osteoblasts, endothelial cells and stem cells. It has been speculated that the biostimulatory effect of LLLT could cause undesirable enhancement of tumor growth in neoplastic diseases, since the malignant cells are more susceptible to proliferative stimuli. Within this context, this study evaluated the effect of LLLT on epidermoid carcinoma of the tongue cell line (SCC25) proliferation and invasion. Cultured cells were irradiated with an InGaAIP diode laser, 660nm, 30mW using two energy densities (0.5J/cm2 and 1.0J/cm2). Proliferative activity was assessed through trypan blue staining method and through cell cycle analysis using flow cytometry. The invasive potential was measured through cell invasion assay using matrigel. Cyclin D1, E-cadherin, -catenin and MMP-9 expressions were analyzed by immunofluorescence and flow cytometry and related to the investigated biological activities. Proliferation curve demonstrated that SCC25 irradiated with 1.0J/cm2 had the highest proliferative rate when compared to the control group and the group irradiated with 0.5J/cm2 (p<0.05). LLLT affected cell cycle distribution and energy density of 1.0 J/cm2 promoted a higher percentage of cells in S/G2/M phases, with statistically significant differences at 24h interval (p<0.05). LLLT, mainly with 1.0J/cm2, revealed significantly higher potential for invasion and influenced the expression of cyclin D1, E-cadherin, -catenin and MMP-9, promoting the malignant phenotype. In conclusion, our results indicate that LLLT has an important stimulatory effect on proliferation and invasion of SCC25 cells, likely due to altered expression of proteins associated with these processes

Fatores genéticos e ambientais envolvidos na carciogênese gástrica

RACIONAL: O câncer de estômago é o segundo tipo mais comum de neoplasia no mundo. A carcinogênese de estômago é processo de múltiplos passos, podendo manifestar-se em várias etapas como gastrite superficial, gastrite atrófica crônica, metaplasia intestinal, displasia e, finalmente, como um carcinoma. Essas condições costumam ser seqüenciais e ocorrer num período de muitos anos como resultado da exposição a uma variedade de fatores endógenos e exógenos, que causam alterações genéticas. Os recentes avanços da genética molecular têm mostrado que o acúmulo dessas várias anormalidades, incluindo a ativação de oncogenes e a inativação de genes supressores de tumores, resultam no desenvolvimento do câncer. Alterações genéticas descritas em carcinomas gástricos incluem amplificações e mutações dos genes c-ERBB2, K-RAS, c-MET e TP53. O ganho de cromossomos também foi encontrado em várias combinações com perda de outros cromossomos e pode estar associado com a expressão elevada de oncogenes, que contribuem com a progressão tumoral. CONCLUSÃO: Essas mudanças genéticas em carcinomas evidenciam o processo de múltiplas etapas da carcinogênese gástrica, por meio do acúmulo de uma série de alterações.

Busca de parceiros físicos por duplo-híbrido das proteínas ADAM23 e MX1, codificadas por genes metilados em câncer de cabeça e pescoço

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mielopatia infiltrativa por tumores não-hematológicos

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Expressão das metaloproteinases de matriz 2 e 9 em cães com linfoma: associação com fatores prognósticos

Pós-graduação em Cirurgia Veterinária - FCAV

Alterações no número de cópias genômicas em mastocitomas cutâneos caninos

Pós-graduação em Medicina Veterinária - FCAV

Identificação e caracterização de possiveis marcadores moleculares em carcinoma renal de células claras

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação de candidatos a marcadores moleculares envolvidos no carcinoma renal de células claras

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fibroblastos associados ao câncer e correlação com parãmetros patológicos em melanomas cutâneos caninos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)