Estudo clínico-patológico do carcinoma epidermóide de língua e imunoistoquímico das proteínas BMP-2, BMPR-IA, BMPR-II e endoglina

Bone morphogenetic proteins (BMPs) are cytokines involved in proliferation and angiogenesis of many kind of human cancer. The present study analyzed the immunohistochemical expression of BMP-2, BMPR-II, BMPR-IA and endoglin (CD105) and their relationship with the biological behavior and local angiogenesis in tongue oral squamous cells carcinoma (SCC). The sample consisted of 25 cases of tongue SCC without metastasis, 25 tongue SCC with metastasis and 25 cases of Inflamatory Fibrous Hyperplasia (IFH).The histological grade of malignancy proposed by Bryne (1998), adapted by Miranda (2002) was used to classify all tongue SCC cases. Score 0 was attributed to absent-weak immunoexpression and score 1 for strong immunostaning and pattern of distribution was focal or diffuse. Microvessel counts (MVC) was established for CD105. Most of the patients with tongue SCC was male. The principal age in tongue SCC without metastasis was over 65 years and in tongue SCC with metastasis was between 45-65 years. There were predominance of stage II in TNM and in the specimens with high-grade, independent of studied group. For BMP-2, 56% of tongue SCC without metastasis and 72% tongue SCC with metastasis exhibited score 1 while the IFH showed secore 0 in 72% of the cases, with statistical association (p=0,007). Considering the BMPR-II, 52% of tongue SCC without metastasis exhibited score 0; 56% tongue SCC with metastasis and 60% IFH showed score 1. The majority cases of BMPR-IA demonstrated score 1 and 100% of CD105 exhibited strong immunoexpression in tongue SCC. Regarding the pattern distribution, it was noted a tendency to diffuse pattern for the proteins in all groups. The means of MVC were similar in tongue SCC without metastasis (32,91) and in tongue SCC with metastasis (32,05), however existed statistical difference with IFH (p<0,001). There was statistical association of BMP-2 expression with BMPR-II (p=0,008), BMPR-IA (p=0,006) and CD105 (p=0,046). An association between TNM and BMP-2 immunoexpression and their receptors was not detected, nevertheless this association was found with MVC (p=0,047) whose averages were higher for the stages II (35,97) e IV (35,69). No association between histological grading and these proteins was observed. This study suggests that the superexpression of BMP-2 signaling pathways acts on cell proliferation in tongue SCC and can be implicated with more invasive potential. Additionaly, the CD105 is a potent biological marker of neovascularization in this neoplasm and their association with BMP-2 and BMPR-IA receptor, showed that this type of cancer in BMP-2 is presented as pro-angiogenic in the metastatic process

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

Associação entre polimorfismos funcionais nos genes da MMP-7 e MMP-9 e o perfil clinicopatológico do carcinoma epidermóide de língua

Matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) modulate important functions strictly related to the development, invasion and metastasis of several human cancers among them the squamous cell carcinoma of the tongue (SCCT). However, individual genetic factors such as the functional single nucleotide polymorphisms (SNPs) influence the pattern of protein expression of these MMPs and thus may be related to the variability observed in the clinical behavior of patients with SCCT. In this context, the present cross-sectional study aimed to evaluate the association between the frequency of the functional SNPs MMP-7 -181 A/G and MMP-9 -1562 C/T and the clinical (age, gender and metastasis) and pathological (malignancy histological grading and immunohistochemistry expression) features of SCCT cases. Genotyping of these SNPs were performed by PCR-RFLP on DNA samples from 71 cases of SCCT and 60 individuals without cancer who constitute the control group. Among the results of this research, it was observed that the frequency of the polymorphic alleles MMP-7 -181 G and MMP-9 -1562 T in SCCT patients was 28% and 12%, respectively, and the frequency of the heterozygotes A/G (PR = 2.00; p < 0.001) and C/T (PR = 1.54; p = 0.014) were significantly higher in the patient group than in the controls. The prevalence of patients carrying the combination of SNPs studied was significantly associated with SCCT cases (PR = 2.00; p = 0.011) and metastasis (PR = 2.00; p < 0.001). Furthermore, with the frequency of SNPs analyzed, the age, gender, histological grading and immunoreactivity of MMP-7 and MMP-9 formed clinical and pathological parameters relevant to the identification of population subgroups more related to the development of SCCT and metastasis. Based on these results, it is suggested that the protein expression levels of MMP-7 and -9 substantially influence the balance between their pro- and anticancer biological functions and hence the clinicopathological profile of the 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

Expressão imuno-histoquimica de proteínas relacionadas com a reabsorção óssea em carcinoma epidermoide de palato duro e língua

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Expressão imuno-histoquímica de metaloproteína em carcinoma epidermóide de lábio inferior e língua

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Expressão imuno-histoquímica da e-caderina e do CD44v6 em carcinoma epidermóide de lábio inferior e língua

The objective of this study was perform, by the streptoavidin-biotin technique, an immunohistochemical analysis of the E-cadherin and CD44v6 in 15 lower lip squamous cell carcinomas and 15 of tongue, with varied histologic gradation of malignidade, in order to establish a possible relation between the expression these proteins and the anatomical localization of the lesions, metastasis, as well as with the Bryne`s histolologic grading of malignancy system. It was not observed significant statistical association between the localization of the lesions and the malignancy score, however, had a significant correlation between the histologic parameters of malignancy gradation and the total score of malignancy, being that the parameter degree of keratinization presented the highest correlation (r = 0,844). Taking in consideration the anatomical localization of the lesions, it was not significant difference between the profile of expression and the amount of immunopositive cells for Ecaderina and CD44v6. To the metastasis variable, also it was not observed significant difference between the profile of expression and the amount of immunopositive cells for evaluated proteins. However, it was observed a statistical significant difference in relation to the scores of malignancy, being that the low score presented the highest values for the profile of expression and the amount of immunopositive cells for the E-caderina and the CD44v6. It was observed a statistically significant and negative correlation between the expression profile, the amount of E-cadherin and CD44v6 immunopositive cells and the total score of malignancy. Therefore, based in the results of this study, it was concluded that the expression of the immunohistochemical markers E-caderina and CD44v6 did not constitute histological indicator of aggressiveness for the patients with lower lip and tongue squamous cell carcinomas

Expressão imuno-histoquímica das integrinas α2ß1, α3ß, e α5ß1, em carcinoma epidermóide de lábio inferior e língua

The unpredictable biologic behavior of the oral squamous cells carcinoma has determined extensive research on the evolution of such tumor. Due to the existing relation between the outer cell matrix and the tumor cells, the integrins have been used as markers in the predictive study of the cell behavior. This study aims to analyze immunohistochemically the expression of the integrin α2β1, α3β1, and α5β1 connections for the collagen, the laminin and the fibronectin respectively in 15 cases of squamous cells carcinoma from the lower lip and 15 from the tongue, with different scores of malignance grading. A predominantly diffuse, cytoplasm and granular immunological marking was observed in the majority of the analyzed cases. According to the marking intensity, integrin α2β1 appeared positive in 80% of the lip and in 93,3% of the tongue cases. The immunological reactivity of integrin α3β1 was classified as positive in 60% of both the tongue and lip cases. For this integrin, 20% and 33.3% of the tongue and lip cases, respectively, were negative. In relation to integrin α5β1 the intensity was classified as positive in 53,3% of the cases and strongly positive in 46,7% of those located in the lip. In the tongue carcinomas, the intensity was positive in 46,7% of the cases and strongly positive in 53,3%. The statistic analysis did not show any significant differences or correlation of expression between these integrins nor between the anatomical sites or between different scores of malignancy grading. The expressive immunological marking of the integrins, α2β1, α3β1, and α5β1 in the studied cases of squamous cell carcinomas leads us to think of a great participation of these proteins in oral carcinogenesis; however, our results do not allow us to correlate its expression as an indicator of variations in the biological behavior of this neoplasia

Estudo in vitro dos efeitos da BMP-2 e do seu antagonista Noggin sobre a proliferação e migração celulares em carcinoma epidermóide de língua

Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in the oral cavity and reach a large number of individuals, has become an important public health problem. Studies have demonstrated changes in pathway components BMP in various types of cancers as prostate, colon, breast, gastric and OSCCs. Is the current knowledge that these proteins may exert pro-tumor effect in more advanced stages of neoplastic development coming to favor progression and invasion tumor. The inhibition of the signaling pathway BMP-2 through its antagonists, have shown positive results of antitumor activity and use of Noggin may be a novel therapeutic target for cancer. Given this evidence and the few studies with BMP-2, Noggin and OSCC, the objective of this research was to evaluate the effect of BMP-2 and its antagonist Noggin on proliferation and migration cell in line of cell cultures of human tongue squamous cell carcinoma (SCC25). The study was divided in three groups, a control group, where SCC25 cells suffered no treatment, a BMP-2 group, in which cells were treated with 100ng/ml of BMP-2 and a group of cells that were treated with 100ng/ml of Noggin. For the proliferation assay and cell cycle were established three time intervals (24, 48 and 72 hours). Proliferative activity was investigated by trypan blue and cell cycle analysis by staining with propidium iodide flow cytometry. The potential for migration / invasion of SCC25 cells was performing by a cell invasion assay using Matrigel in a 48-hour interval. The proliferation curve showed a higher proliferation in cells treated with BMP-2 in 72 hours (p < 0.05), and lower overgrowth and cell viability in Noggin group. Recombinant proteins favored a greater percentage of cells in cell cycle phase Go/G1 with a statistically significant difference in the interval of 24 hours (p < 0.05). BMP- 2 produced a greater invasion of cells studied as well as its antagonist Noggin inhibits invasion of cells (p < 0.05). Thus, these results indicate that BMP-2 promotes malignant phenotype, dues stimulates proliferation and invasion of SCC25 cells and, its antagonist Noggin may be an alternative treatment, due to inhibit the tumor progression

Perfil imuno-histoquímico do infiltrado inflamatório no front de invasão em carcicomas epidermóides de língua e lábio inferior

The progression of the oral squamous cells carcinomas (OSCCs) seems to suffer influence from related factors to the host, as local and systemic immunologic response, which are essential to the antineoplasic defenses. The purpose of this study was evaluate the local immunity in 30 tongue and 20 lower lip SCC by immunohistochemistry method, utilizing antibodies anti-CD3, CD4, -CD8, -CD25 e -ζ(zeta), which immunoexpressions were compared considering the anatomical localization, the intensity of the inflammatory infiltrate into the front of invasion and metastases. The CD4/CD8+ ratio was calculated for each case and associate with the mentioned variable, being the intensity of the inflammatory infiltrated also compared with the anatomical localization and metastase and for this the cases had been grouped in two categories: (n = 10) absent/scarce inflammatory infiltrate; and (n = 40) moderate/intense infiltrate. Fisher´s exact test was performed (α= 0.05) and it was not observed any significant correlation between these groups with anatomical sites and metastases. With regard to the immunoexpression, the CD3+, CD4+, CD8+ and CD25+ cells count was higher in the lower lip SCCs while the anti-ζimmunomarcation was more evident in the non metastatic cases. Through the statistical analyses, it was verified that the CD3 exhibited positive-significant correlation with the inflammatory infiltrate (p = 0.023). Furthermore, antibodies against CD8 and CD25 cells were also significantly correlated with the inflammatory infiltrate (p = 0.002 and 0.030, respectively) and with the anatomical site (p = 0.004 and p = 0.004) mainly in the lower lip SCCs. CD4/CD8 ratio did not show significant association with metastase nor with anatomical localization. We conclude that the inflammatory infiltrated of the Bryne s (1998) system did not constitute an indicator of aggressiveness in the tongue and lower lip SCCs analyzed and that clinical behavior of the SCCs studied was related in part to the immunohistochemical profile of infiltrated the inflammatory present in tumoral invasion front

Aprendizagem da língua japonesa apoiada por ferramentas computacionais: estudo e desenvolvimento do jogo Karuchā Ships Invaders

The use of technology tools for teaching and learning has grown increasingly in our daily life. In this context, a branch that has had tremendous growth is the area of teaching and learning language through computational tools. The study of CALL (Computer Assisted Language Learning), accomplished in this research, aims to evaluate existing tools in this context, focused specifically on the Japanese language; and from this study, accomplish the development of a new computational tool that can assist teaching/learning of the Japanese language. As results, we present a wide survey on the subject in various technologies/devices, as well as the complete development process of a new tool, the Karuchā Ships Invaders game, that proposes to teach basic concepts of the language, blended with entertainment, and still, focusing on the Brazilian students of Japanese language audience. We will present all the concept phases of the game and its evolution through the research, as well as an interface evaluation. Still, we present proposal and validation of a method to evaluate motivational aspects of computational tools with educational focus, and results extracted from an experiment accomplished with prospective users

O ensino da língua portuguesa na televisão: uma análise através do programa afinando a língua

The present dissertation aims to an approach of the teaching of Portuguese language on television, trying to find how possible is the contribution of this communication media in the sense to give a higher classroom dynamism and to excite the students for that subject. The TV show Afinando a Língua (roughly, putting the language in tune ), a Canal Futura feature, have as one of these main purpose be shown on the classrooms as a tool that could enlarge the possibilities of a subject often took as particularly difficult. Blocked by the traditional grammatical teaching, the Portuguese lessons have been for years pictured as hermetic and far from the Brazilian speakers reality. So, people create myths around the language that earns adjectives as complicate and inaccessible and that Brazilians can t speak the Portuguese really good, because it only happens in Portugal, the original country of the language. These myths start exactly because the teaching orientation take their basis only on the standard language, in fact just one of the language variations by the way, anywhere in the world dictated by ancestral rules, once produced in Portugal. The regular school don t accept the Portuguese variation as a natural fact for a huge country as Brazil, with almost 190 million people, regarding it as a wrong way of talking. The repression that follows the students from the early school days make them repel the language supposedly learned at school. In fact, they normally face it as something unfamiliar, different from the language that they have use to learn at home, from the family and neighbors Instead of giving new possibilities for the language learning, the television, a powerful audiovisual device, only reinforces the idea that everyone, in any life situation, should talk the standard Portuguese, turning its back to the learning acquired much earlier that any person reach the school. This conservative attitude brings almost no changes, between the shows that try to teach the idiom and the traditional Portuguese lessons, wasting valuable tools that could lead to the possibility to open the classroom to the outside world, and to the wider knowledge of the differences from each Brazilian region culture, a positive attitude that could much enlarge the cultural and linguistic students universe

Saberes docentes, alfabetização, respeito à infância: a criança de 6 anos no ensino fundamental

Éste trabajo se inserta en el ámbito de los cambios en la Enseñanza Fundamental (EF) brasileño que, por la Ley Federal n.º 11.114/2005 anticipa el EF para seis años de edad, y de la Ley n.º 11.274/2006 que amplia el mismo nivel de enseñanza de ocho para nueve años Tales cambios tienen sido respaldados por el argumento de la importancia de se anticipar y promover un mayor acceso a la educación y garantizar una permanencia bien sucedida del alumno en la etapa obligatoria de la Educación Básica. La inclusión de los niños de seis años en el EF puede ser considerada una conquista en el ámbito de las políticas públicas brasileñas destinadas a la educación de niños. Sin embargo, la sencilla simples anticipación/ampliación de matrículas en el EF puede constituirse en más una forma de exclusión, si no fueren garantizadas las condiciones necesarias para se ofrecer una educación de calidad que considere las peculiaridades de una práctica pedagógica de alfabetización con niños más jóvenes. Evidentemente, muchos son los factores que pueden influenciar la calidad de la educación y el tratamiento escolar financiamiento, gestión, organización del espacio escolar pero la acción del profesor, en ése sentido, es un factor primordial entre otros determinantes. Así pensando, definimos como objetivo de éste trabajo investigar saberes docentes requeridos de el profesor para el desarollo de una práctica pedagógica que tiene por meta la apropiación de la lengua escrita, por el niño de seis años recién-ingresa en la Enseñanza Fundamental respetando su condición de ser niño . Para tanto, en el ámbito del enfoque cualitativo de la encusta, realizamos un estudio de caso en dos instituciones públicas: Escola Municipal Professora Emilia Ramos y Centro Municipal de Educação Infantil Marise Paiva, ambas ubicadas en la Zona Este en la ciudad de Natal. De la análisis del contenido de los datos, emergió la temática Saberes Docentes para la Alfabetización de Niños de seis años en la Enseñanza Fundamental que, a la vez, cubre dos categorías de saberes, con suyas respectivas subcategorías: Saberes Docentes Transversales a las Práctica Pedagógica de Alfabetización y Saberes Docentes Específicos a la Práctica Pedagógica de Alfabetización. Entre tantos aprendizaje proporcionadas por el estudio, comprendemos que, sea en la Educação Infantil, sea en la Enseñanza Fundamental, el trabajo con el niño no debe constituirse en la negación de su infancia. Sin embargo, en se tratando de el EF, el esfuerzo para no desvirtuar la voluntad política de proporcionar al niño oportunidades de alfabetización debe ser redoblado, una vez que ésa etapa de la educación podrá ser la marca de un rico y agradable proceso de alfabetización, como puede ser motivo para que el niño se torne desinteresado y acobardado para aprender a leer y a escribir, si no fueren respetadas las necesidades y especificidades propias de ése momento de su desarollo. El estudio también ratificó nuestra comprensión de que la Alfabetización es un proceso peculiar, no constituyéndose, por lo tanto, en tarea simple para el docente, ni tampoco para el niño, visto que la lengua escrita, por si misma, ya es un objeto de estudio bastante complejo. Comprendemos, sin embargo, que esa complejidad no puede tornarse obstáculo para que, también en la escuela pública, ya a los seis años, se permita al niño un trabajo de calidad que tiene por meta su alfabetización, hasta porque, mientras participantes de una sociedad letrada, antes de ingresar a la escuela, los niños ya construyeran concepciones previas sobre la lectura y la escrita, a las cuales el profesor debe estar muy atento

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