P-cadherin overexpression Is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation

Purpose: P-cadherin overexpressionhas been reported in breast carcinomas,where itwas associated with proliferative high-grade histological tumors. This study aimed to analyze P-cadherin expression in invasive breast cancer and to correlate it with tumor markers, pathologic features, and patient survival. Another purpose was to evaluate the P-cadherin promoter methylation pattern as the molecularmechanismunderlying this gene regulation. Experimental Design: Using a series of invasive breast carcinomas, P-cadherin expressionwas evaluated and correlated with histologic grade, estrogen receptor, MIB-1, and p53 and c-erbB-2 expression. In order to assess whether P-cadherin expression was associated with changes in CDH3 promoter methylation, we studied the methylation status of a gene 5V-flanking region in these same carcinomas.This analysis was also done for normal tissue and for a breast cancer cell line treatedwith a demethylating agent. Results: P-cadherinexpression showeda strong correlationwithhighhistologic grade, increased proliferation, c-erbB-2 and p53 expression, lack of estrogen receptor, and poor patient survival. This overexpressioncanbe regulatedby gene promotermethylationbecause the 5-Aza-2V-deoxycytidine treatment ofMCF-7/AZ cells increased P-cadherinmRNA and proteinlevels. Additionally, we found that 71% of P- adherin-negative cases showed promoter methylation,whereas 65% of positive ones were unmethylated (P = 0.005). The normal P-cadherin-negative breast epithelial cells showed consistent CDH3 promotermethylation. Conclusions: P-cadherin expressionwas strongly associatedwith tumor aggressiveness, being a good indicator of clinical outcome. Moreover, the aberrant expression of P-cadherin in breast cancermight be regulated by gene promoter hypomethylation

P-cadherin expression in glandular lesions of the uterine cervix detected by liquid-based cytology

Objective: To study P-cadherin aberrant expression as a possible marker for cervical adenocarcinomas in cytological samples. Methods: We studied P-cadherin immunoexpression in liquid-based cervical cytology samples of biopsy-proven cervical lesions. Results: We found a statistically significant correlation between P-cadherin expression and a cytological diagnosis of malignancy, either glandular or squamous (P < 0.0001). Twenty-two of 33 malignant cases showed P-cadherin membrane staining. None of the 30 benign cases tested showed membrane staining, but three of them displayed an aberrant nuclear P-cadherin expression. Conclusions: We concluded that P-cadherin can be used to discriminate between malignant and benign cervical cytological specimens, but not to discriminate glandular from squamous lesions

Molecular analysis of c-Kit and PDGFRA in GISTs diagnosed by EUS

Gastrointestinal stromal tumors (GISTs) are characterized by overexpression and mutations of c-Kit. Approximately 80% of c-Kit mutations occur in exon H, being a response factor to imatinib (Gleevec) therapy. Mutations of platelet-derived growth factor receptor-a (PDGFRA) are observed in a subset of GISTs lacking c-Kit mutations. We aimed to assess whether c-Kit and PDGFRA mutation analysis of GISTs obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) could be routinely performed. Mutation analysis of c-Kit hotspot exons (9, 11, 13, and 17) and PDGFRA hotspot exons (12 and 18) was performed in aspirates of 33 GISTs and 18 non-GIST mesenchymal tumors. Of the GIST cases, 19 (58%) of 33 contained a mutation in exon 11, 1 (3%) in exon 9, and none in exons 13 and 17. No activating c-Kit mutations were identified in non-GIST cases. No PDGFRA mutation was detected. Mutation analysis is possible in these FNA cell blocks and can assist in the diagnosis and therapeutic decisions in GIST cases.Supported in part by NOVARTIS Oncologyinfo:eu-repo/semantics/publishedVersio

Carcinoma da mama de tipo basal

Breast cancer presents as a heterogeneous disease, not only for the clinic and histology, but also in genetic expression profile. Studies using cDNA microarrays have recently led to the re-classification of invasive breast carcinomas, based on their molecular signature, into three main groups: luminal; HER2 (Human Epidermal Receptor 2) overexpressing, and basal-like. Although the latter group is the least prevalent it is the most agressive one, lacking a target based therapy, since their main characteristic is being negative for hormonal receptors or HER2. So, it is of paramount importance to try to unravel their histogenic origin and characterize their molecular and immunohistochemical profiles. EGFR (Epidermal Growth Factor Receptor), which is overexpressed in a high proportion of these carcinomas, is a potential therapeutic target, and clinical trials with inhibitors of its activity may represent important advances in basal-like breast carcinomas therapy.O cancro da mama apresenta-se como uma doença heterogénea, não só clínica e histologicamente, como também no seu perfil de expressão genética. A avaliação por cDNA microarrays permitiu re-classificar recentemente os carcinomas da mama invasivos, de acordo com uma assinatura molecular, em três grandes grupos: luminal; com sobre- expressão de HER2 (Human Epidermal Receptor 2 – receptor epidérmico humano 2) e o de tipo basal. Este último é dos três o menos prevalente mas o mais agressivo e aquele que não possui tratamento dirigido, uma vez que não expressa receptores hormonais ou HER2, que são actuais alvos terapêuticos no cancro da mama. Os carcinomas da mama de tipo basal têm sido tema de vários trabalhos de investigação que visam conhecer a sua origem histogenética, bem como a sua caracterização do ponto de vista molecular e imunohistoquímico. O EGFR (Epidermal Growth Factor Receptor – receptor do factor de crescimento epidérmico), que se encontra sobre-expresso numa elevada percentagem destes carcinomas, é um potencial alvo terapêutico, e ensaios clínicos utilizando fármacos inibidores da sua actividade podem representar importantes avanços na terapia dirigida dos carcinomas da mama de tipo basal.info:eu-repo/semantics/publishedVersio

Comparison of strength and proprioception parameters between subjects with and without functional ankle instability

Después del esguince de tobillo, el 40% de los sujetos siguen informando que hay una sensación de inestabilidad articular que se relaciona con la disfunción del musculo-esquelética llamada inestabilidad funcional del tobillo (IFT). Sin embargo, todavía no se conoce el mecanismo que es responsable por esta disfunción musculo-esquelética. En este sentido, el conocimiento de las alteraciones musculo-esqueléticas que ocurren en personas con IFT puede ser un factor importante para planear intervenciones preventivas más eficaces. De esta manera, esta investigación tiene como objetivo comparar el momento de torque (PT) de inversión concéntrica (INV) y eversión (EVE), la razón convencional (EVE/INV) y el reposicionamiento pasivo de las articulaciones en personas con y sin IFT en atletas recreacionales del género femenino. La muestra está compuesta por 22 voluntarios en la franja etaria entre 18 y 25 años, los cuales se dividieron en un grupo control y un grupo con IFT. La evaluación del torque se realizó en un dinamómetro isocinético con cinco contracciones máximas concéntricas con velocidades de 60 y 120 grados.s-1 en un movimiento de INV y EVE y reposicionamiento pasivo de la articulación con ángulo objetivo de 10° y 20° de inversión. Se analizó los datos del PT, de la razón convencional y la media del error absoluta del ángulo objetivo. Para el análisis, se utilizó la prueba t-Student para muestras independientes. Si comparados con las personas control se observó que las personas con IFT presentaron una disminución de la fuerza eversora y también un desequilibrio de la razón muscular, lo que puede aumentar la susceptibilidad de éstos a los esguinces de tobillos.After an ankle sprain 40% of individuals continue to report a sensation of joint instability that is related to musculoskeletal dysfunction called functional ankle instability (FAI). However, a mechanism like this musculoskeletal dysfunction occurs remains unknown. In this sense, the knowledge of musculoskeletal changes that occur in individuals with FAI may be an important factor to plot more effective preventive interventions. Thus, the aim of this study was to compare peak torque (PT) concentric inversion (INV) and eversion (EVE), conventional ratio (EVE/ INV) and passive joint repositioning in individuals with and without FAI in recreational athletes females. The sample consisted of 22 volunteers aged 18-25 years who were divided into control group and the group with FAI. The torque rating was performed on an isokinetic dynamometer with five maximal concentric contractions at speeds of 60 and 120 graus.s-1 in INV and EVE movement and passive joint repositioning to target angle of 10° and 20° of inversion. PT data, conventional ratio and average absolute error of the target angle were analyzed. Statistical analysis was performed using the Student t-test for independent samples. Found that individuals with LFS showed decreased evertor strength compared to control subjects, as well as unbalanced muscle ratio, which may increase the susceptibility of this group to ankle sprains.Após a entorse de tornozelo, 40% dos indivíduos continuam a relatar uma sensação de instabilidade articular que está relacionada à disfunção músculo-esquelética denominada instabilidade funcional do tornozelo (IFT). Contudo, o mecanismo como ocorre esta disfunção músculo-esquelética ainda permanece desconhecido. Nesse sentido, o conhecimento das alterações músculo-esqueléticas que ocorrem em indivíduos com IFT pode ser um fator importante para traçar intervenções preventivas mais efetivas. Dessa forma, o objetivo deste estudo foi comparar o pico de torque (PT) concêntrico de inversão (INV) e eversão (EVE), a razão convencional (EVE/INV) e o reposicionamento articular passivo em indivíduos com e sem IFT em atletas recreacionais do gênero feminino. A amostra foi composta por 22 voluntárias na faixa etária entre 18 e 25 anos que foram divididas em grupo controle e grupo com IFT. A avaliação do torque foi realizada em um dinamômetro isocinético com cinco contrações máximas concêntricas a velocidades de 60 e 120 graus.s-1 no movimento de INV e EVE e reposicionamento articular passivo com ângulo-alvo de 10° e 20° de inversão. Foram analisados os dados de PT, razão convencional e média do erro absoluto do ângulo-alvo. A análise estatística foi feita com o teste t-Student para amostras independentes. Foi encontrado que indivíduos com IFT apresentaram diminuição da força eversora comparados aos indivíduos controle, bem como desequilíbrio da razão muscular, que podem aumentar a predisposição deste grupo a entorses de tornozelos

Analysis of EGFR Overexpression, EGFR gene amplification and the EGFRvIII Mutation in portuguese high-grade gliomas

Background: Patients with malignant gliomas do not respond to any current therapy. Epidermal growth factor receptor (EGFR) controls several oncogenic processes, being frequently up-regulated in gliomas due to overexpression, gene amplification and gene mutation. EGFR inhibitors are being tried in gliomas, yet the molecular determinants of therapeutic response are unclear. Materials and Methods: EGFR overexpression, EGFRvIII mutation and EGFR amplification were determined by immunohistochemistry and chromogenic in situ hybridization (CISH) in 27 primary glioblastomas (GBM), 24 anaplastic oligodendrogliomas (AO) and four anaplastic oligoastrocytomas (AOA). Results: EGFR overexpression was associated with EGFR amplification, being found in 48% and 53% GBM, 33% and 40% AO and 75% and 67% AOA, respectively. EGFRvIII was found in 22% GBM, 8% AO and was absent in AOA. No association was observed between EGFR alterations and patient survival. Conclusion: We characterized, for the first time, EGFR molecular alterations in Portuguese patients with malignant glioma and identified a subpopulation of patients presenting putative biomarkers for EGFR-based therapies

Significance of osteopontin expression in human invasive breast tumour stroma

Osteopontin has been reported to stimulate cell adhesion, migration and specific signalling functions. Its overexpression has been found in melanoma, breast, lung, colorectal, stomach and ovarian cancer. However, its overexpression and role in human breast cancer remains to be elucidated. In this study, invasive breast tumours from 129 patients were examined by immunohistochemistry in order to assess osteopontin association with several molecular tumour markers. Additionally, its relationship with proliferation and angiogenesis was determined. Ultimately, other tumour variables such as histological grade, tumour size and nodal status were also assessed. Results achieved showed that no statistical significant association exists between osteopontin expression and major clinicopathological parameters or angiogenesis, except for the number of lymph nodes involved. However, a correlation with some molecular markers was observed, namely with P-Cadherin, EGFR, cytokeratin 14 and vimentin. Additionally, higher proliferation rates were found for the tumours expressing osteopontin. Although several studies refer osteopontin as a potential breast cancer biomarker, it is still not clear if it can provide important diagnosis information, evaluate treatment effects or assess the potential for metastatic disease in patients.Fundação para a Ciência e a Tecnologia (FCT

Evaluation of the surface of root canal walls after utilization of endodontic rotary systems: SEM study

The objective of the present study was to determine, by scanning electron microscopy, the aspect of root canal walls after utilization of different rotary instrumentation systems for root canal preparation. Forty-two single-rooted and straight teeth were divided into six groups, whose root canals were prepared using the following rotary systems: groups 1 and 2 - Quantec; groups 3 and 4 - Pow-R; groups 5 and 6 - Profile. Irrigation was performed with 2.5% sodium hypochlorite solution in all groups, while only groups 2, 4 and 6 received a final flush with EDTA. Data were analyzed by non-parametric Kruskal-Wallis and Miller tests. Removal of the smear layer and other debris was more effective in the groups receiving EDTA as final irrigant. The Profile system showed the best cleaning, generating only a minimum smear layer, with a significant difference being observed compared to the Pow-R system (pO objetivo do presente estudo foi avaliar por meio de microscopia eletrônica de varredura, o aspecto superficial de paredes de canais radiculares apos uso de sistemas rotatórios de instrumentação endodôntica. Quarenta e dois dentes unirradiculados e com canais retilíneos foram divididos em seis grupos experimentais. Foram preparados utilizando-se os seguintes sistemas: Grupos 1 e 2 - Sistema Quantec; grupos 3 e 4 - Sistema Pow-R; grupos 5 e 6 - Sistema Profile. A irrigação foi realizada com solução de hipoclorito de sódio a 2.5% em todos os grupos durante a instrumentação. Apenas nos grupos 2, 4 e 6 foi realizada toalete final dos canais com solução de EDTA. O dados foram analisados pelos testes não paramétricos de Kruskal-Wallis e Miller. Foi observada maior remoção de smear layer e outros resíduos nos grupos onde foi realizada a toalete final com solução de EDTA. O sistema Profile mostrou melhor resultado, gerando menor quantidade de resíduos, com diferença significante quando comparado com o sistema Pow-R(

Novel and classic myoepithelial/stem cell markers in metaplastic carcinomas of the breast

Metaplastic carcinomas of the breast (MCBs) are unusual neoplasms characterized by an admixture of glandular epithelial components, which frequently exhibit features of squamous differentiation, and mesenchymal malignant components. Regardless of the presence of myoepithelial features in MCB, no consensus concerning their putative histogenesis has yet been achieved. Recently, novel putative myoepithelial markers have been developed, including p63, maspin, and P-cadherin. We assessed the expression of these myoepithelial markers in MCBs and compared their expression with classic myoepithelial markers. Immunohistochemistry using the streptavidin– biotin–peroxidase complex technique with antibodies raised against p63, maspin, P-cadherin, actin (clones CGA7, 1A4 and HHF35), cytokeratin 14 (Ck14), and vimentin was performed on 16 MCBs (7 matrix-producing MCBs, 6 adenosquamous MCBs, and 3 MCBs with heterologous elements). In healthy breast lobules and ducts adjacent to the tumors, myoepithelial cells showed distinctive and consistent immunoreactivity for p63, maspin, P-cadherin, actin, S-100 protein, and Ck14. Matrix- producing MCBs were positive for maspin in all cases, for p63 in 4 of 7 cases, and for P-cadherin in 4 of 7 cases. Adenosquamous MCB showed immunoreactivity for p63, maspin, and P-cadherin in 5 of 6 cases. All novel myoepithelial markers and Ck14 decorated squamous cell islands. MCBs with heterologous elements were positive for p63 in 1 case, for maspin in all 3 cases, and for P-cadherin in 2 cases. All cases showed at least one of the novel myoepithelial markers. Eleven of 16 cases were positive for actin. Eleven of 14 cases reacted with Ck14, and all cases that stained for S-100 protein (9 of 9) and vimentin (13 of 13) were also positive. Based on our findings, the balance of probabilities favors that MCBs may have a basal or myoepithelial cell histogenesis and differentiation.Fundacão para a Ciência e a Tecnologia (FCT), Ministério da Ciência e Tecnologia (MCT) - SFRH/BD/5386/2001