Understanding multiple endocrine neoplasia type 1.

Mode of access: Internet.

Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX (TM) adjuvant in women with cervical intraepithelial neoplasia

Purpose: Persistent infection of cervical epithelium with high risk human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV 16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX(TM) adjuvant (HPV16 Immunotherapeutic) for patients with CIN. Experimental design: Patients with CIN (n = 3 1) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy. Results: Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients. Conclusions : The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX(TM) adjuvant is safe and induces vaccine antigen specific cell mediated immunity. (C) 2004 Elsevier Ltd. All rights reserved.

Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia

Purpose: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. Experimental Design: RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. Results: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARa, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and Pan IN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early Pan IN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. Conclusions: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.

Characterization of tumour-infiltrating lymphocytes and apoptosis in colitis-associated neoplasia: comparison with sporadic colorectal cancer

The development of colorectal cancer is a major complication for patients with chronic idiopathic colitis. Colitis-associated tumours tend to occur at a younger age and be more aggressive than sporadic colorectal cancers. While we have previously associated the presence of tumour-infiltrating lymphocytes (TILs) and increased apoptosis in sporadic colorectal cancer with high-level microsatellite instability and improved prognosis, little is known of the relationship between these variables in colitis-associated colorectal cancer. The aim of this study was to correlate TILs and tumour cell apoptosis in colitis-associated neoplasms stratified according to microsatellite instability. Twenty tumour and 11 dysplastic samples resected from 21 patients with long-standing colitis were analysed for microsatellite instability at 10 microsatellite markers. TIL distribution (CD3, CD8) and function (granzyme B) were quantified by immunohistochemistry. Neoplastic cell apoptosis was assessed using the M30 CytoDEATH antibody. These findings were compared with 40 microsatellite stable (MSS) sporadic colorectal cancers previously evaluated for TILs and neoplastic apoptosis. Low-level microsatellite instability was found in 1/20 colitis-associated tumours. All other colitis-associated lesions were designated MSS. CD3(+) and CD8(+) TIL counts were significantly higher in colitis-associated lesions compared with NISS sporadic colorectal cancer (p < 0.0001, p = 0.001 respectively). Despite their higher TIL density, colitis-associated tumours were more likely to present late (Dukes' stage C or D) (P = 0.02). Functionally, colitis-associated TILs demonstrated significantly less granzyme B expression compared to sporadic cancers (p = 0.002). The level of tumour cell apoptosis was similar between the two groups (sporadic, 1.53%; colitis cancers, 1.45%). In conclusion, NISS colitis-associated tumours have a higher prevalence of CD3(+)/CD8(+) TILs but no associated increase in tumour cell killing by apoptosis. Unlike cytotoxic T cells in sporadic colorectal cancer, TILs do not appear to enhance the prognosis of colitis-associated colorectal cancer. This may be related to an impairment of granzyme B expression within these lesions. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia

center dot PURPOSE: To evaluate topical interferon alfa-2b (IFN-alpha 2b) for the treatment of recalcitrant ocular surface squamous neoplasia (OSSN). center dot DESIGN: Prospective, noncomparative, interventional consecutive case series. center dot METHODS: Ten patients with recalcitrant OSSN were treated with topical IFN-alpha 2b (1 million IU/ml) four times a day until clinical resolution of the lesion or until the lesion appeared nonresponsive-that is, treatment failure. Progress was assessed by clinical examination and photographic records, with a minimum follow,up of six months. center dot RESULTS: Eight of 10 patients achieved clinical resolution from topical IFN-alpha 2b treatment. One patient developed invasive squamous cell carcinoma and underwent exenteration. The other patient required further mitomycin C therapy to achieve clinical resolution. The mean duration to clinical resolution for the eight patients treated with IFN-alpha 2b was 21.9 weeks (range six to 59 weeks). There have been no recurrences for any of the nine patients during follow-up (mean 55.0 weeks; range 26 to 84 weeks). center dot CONCLUSIONS: Topical IFN-alpha 2b is an important treatment modality for recalcitrant OSSN; it avoids the risks of further limbal stem cell destruction from other agents and surgical excision. If invasive disease is diagnosed at any stage, topical therapy is contraindicated, necessitating surgical excision. (Am J Ophthalmol 2006; 142:568-571. (c) 2006 by Elsevier Inc. All rights reserved.)

Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16-associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus-like particles was assessed in patients with CIN 2 (n = 169) and CIN 3 (n = 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA-positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P = 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16-associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16-associated CIN 3 in patient population studied.

Characterisation of the signalment, clinical and survival characteristics of 41 cats with mast cell neoplasia

Mast cell tumours (MCTs) are relatively common tumours of cats, and are the second most common cutaneous tumours in cats in the USA. While the primary splenic form of the disease is far less common, it is usually associated with more severe clinical signs. Signalment, clinical and survival characteristics of mast cell neoplasia were characterised in 41 cats. The most common tumour location was cutaneous/ subcutaneous head and trunk. Stage la was the most common tumour stage at first diagnosis (n = 20), followed by stage 4 (both stage 4a and stage 4b; n = 10). Of 22 cats that underwent excisional biopsy, mast cell neoplasia recurred in four cats during the study period. Three of the 41 cats presented with simultaneous cutaneous and either splenic or lymph node tumours. A comparison between cats with only cutaneous tumours (n = 30) and those with tumours involving the spleen or lymph nodes (n = 11) showed longer survival times for the cutaneous-only group (P = 0.031). Twelve of the 41 cats died of mast cell neoplasia during the study period. When a subgroup of cats with only cutaneous tumours (no lymph node or visceral involvement) were divided according to whether there were multiple (five or more) tumours (n = 6) or a single tumour (n = 19), cats with single tumours survived longer than those with multiple tumours (P = 0.001). Solitary cutaneous feline MCTs without spread to the lymph nodes usually manifest as benign disease with a relatively protracted course. However, multiple cutaneous tumours, recurrent tumours and primary splenic disease should receive a guarded prognosis due to the relatively short median survival times associated with these forms of the disease. (C) 2006 ESFM and AAFR Published by Elsevier Ltd. All rights reserved.

New era: Prophylactic surgery for patients with multiple endocrine neoplasia-2A

Background: The surgical management of patients with multiple endocrine neoplasia-2A (MEN-2A) continues to evolve with specific genotype-phenotype correlations allowing for a more tailored approach. In this study, we report the surgical management of one of the largest MEN-2A families with a rearranged during transfection (RET) codon 804 mutation. Method: This is a cohort study comprising all at-risk kindred within a single known MEN-2A family. Prophylactic total thyroidectomy with lymph node dissection was recommended to all mutation carriers aged 5 years and older. Results: There were a total of 48 at-risk individuals in the MEN-2A kindred, with 22 patients undergoing thyroidectomy after appropriate preoperative evaluation. A total of 9 patients had medullary thyroid cancer including 5 with a normal preoperative calcitonin level. A total of 11 patients had C-cell hyperplasia and 7 showed histological evidence of parathyroid disease. Only the index case had a phaeochromocytoma. Conclusion: Genetic testing for germline mutations in the RET proto-oncogene has allowed precise identification of affected RET carriers and provided the opportunity for prophylactic or 'preclinical' surgery to treat and in fact to prevent medullary thyroid cancer. This concept of prophylactic surgery based on a genetic test is likely to be applied more widely as the tools of molecular biology advance.

O BANCO MUNDIAL E A EDUCAÇÃO NO BRASIL: ESTUDO REALIZADO A PARTIR DAS TESES DEFENDIDAS NA UNIVERSIDADE ESTADUAL DE CAMPINAS (UNICAMP), NO PERÍODO DE 1995 A 2007

Este estudo visa analisar as interferencias do Banco Mundial na Educacao Brasileira a partir do estudo de seis teses (aqui identificadas pelas iniciais A,B,C, D, E e F) de doutorado relativas ao tema, defendidas na Universidade Estadual de Campinas (Unicamp), sendo quatro delas (A, B, C, e D) voltadas a area de educacao e duas (E e F) a area de Ciencias Sociais e Economia. O estudo das teses parte dos objetivos de cada uma, que podem ser resumidos da seguinte forma: a Tese A - ¡ªA Mundializacao da Educacao: o Projeto Neoliberal de Sociedade e de Educacao no Brasil e na Venezuela. (MELO, 2003) -, sob a orientacao do Prof. Dr. Nilson Joseph Demange, teve como objetivo investigar o processo de mundializacao da educacao como elemento de uma nova fase de internacionalizacao e acumulacao capitalista, conduzida hegemonicamente pelos sujeitos politicos coletivos que assumem o projeto neoliberal de sociabilidade, especialmente o Fundo Monetario Internacional e o Banco Mundial, que buscam ser condutores das reformas estruturais para a America Latina e Caribe; a Tese B . ¡ªO Capital Financeiro e a Educacao no Brasil. (DEITOS, 2005) -, sob a orientacao da Profa. Dra. Maria Elizabete Sampaio Prado Xavier, teve como objetivo definir quais as consequencias da consolidacao do projeto, para a redefinicao das politicas educacionais na America Latina e Caribe; a Tese C . ¡ªGlobalizacao e Descentralizacao: o Processo de Desconstrucao do Sistema Educacional Brasileiro pela Via da Municipalizacao. (ROSAR, 1995) -, sob a orientacao do Prof. Dr. Demerval Saviani, teve como objetivo analisar as reformas educacionais empreendidas no Brasil, no periodo de 1995-2002, particularmente a politica educacional nacional para o ensino medio e profissional, com financiamento externo do Banco Internacional para Reforma e Desenvolvimento (BIRD); a Tese D . ¡ªAs Politicas Educacionais para o Desenvolvimento e o Trabalho Docente. (SOUZA, 1999) ., sob a orientacao da Profa. Dra. Liliana Rolisen Petrilli Segnini, trata da politica educacional para o ensino de 1¨¬ grau, tracada segundo a visao de seu autor no ambito de projetos federais, com o objetivo de induzir a municipalizacao do ensino, transferindo encargos para o municipio, sem a realizacao de investimentos financeiros satisfatorios nessa instancia; a Tese E . ¡ªEconomia, poder e influencias externa: O Grupo Banco Mundial e as Politicas de Ajustes Estruturais na America Latina, nas Decadas de Oitenta e Noventa. (COELHO, 2002) ., sob a orientacao do Prof. Dr. Sebastiao Carlos Velasco e Cruz, teve como objetivo analisar as relacoes entre o projeto educacional implementado pelo governo estadual, no periodo entre 1995 e 1998 e suas concepcoes de politicas educacionais; a Tese F - ¡ªA Questao Social e os Limites do Projeto Liberal no Brasil. (GIMENES, 2007) ., sob a orientacao do Prof. Dr. Carlos Alonso Barbosa de Oliveira, teve como objetivo analisar a relacao entre a economia, o poder politico e a influencia externa, focalizando o Grupo Banco Mundial e os programas de ajustamento estrutural na America Latina. Por fim este estudo mescla teses brasileiras advindas da area da Educacao e da Economia; foca o banco mundial e sua influencia no Brasil, oferecendo uma visao das conexoes logicas existentes entre elas. Como conclusao deste trabalho, apresentaremos as consideracoes finais de cada uma das teses, bem como as limitacoes e sugestoes para

Cenário da produção acadêmica em história da matemática no ensino de matemática: uma análise reflexiva das teses e dissertações (1990-2010)

This research aims to make a reflective analysis about the academic production originated in the stricto sensu post graduation programs in the country, produced in the period of 1990 to 2010, in the field of History of Mathematics, especifically on works about the History of Mathematics in Mathematics education and that present pedagogical proposals that make use of the History of Mathematics in order to teach Mathematics. Defending the thesis that the researches on mathematics education with goals turned to the use of didactic proposals related to the history of mathematic that take in consideration the coherency between epistemological aspects inherent to mathematics history and anthological elements materialized on the conceptions of mathematics and mathematics history and of apprenticeship (implicitly or explicitly exposed) may originate significant contribution to the field of history of mathematics on education. Among these, nine were Master’s Degree dissertations and five PHD’s theses. The reflective analysis was accomplished from two matrixes; one from theoretical nature and the other, ontologic nature, elaborated from the pretexts of Sanches Gamboa, about the epistemological analysis from academic production in the field of Mathematics Education and the following theoretical perspectives in the field of History of Mathematics Education, that are: linear evolutionary theory, structural construtivist operative, evolutionary discontinuous, historical and socialcultural investigation and the use of activities estimulating the usage of verbal and nonverbal expressions. These perspectives were based on the works of Miguel and Miorim, Mendes and Radford. As results, we have detected some established dissonances between the categories related to theoretical and ontologic levels and the pedagogical proposal presented in these researches. On the other hand, we have discovered works that are able to establish consonances between the theoretical and ontological elements and the presented pedagogical proposal. These works carry significative contributions to the field of History of Mathematics applied to Mathematics pedagogical practice, inclusively presenting significative theoretical elements to the production of knowledge recognized as scientific in the Mathematics field

Resumo de dissertações e teses: a estrutura composicional à luz da Análise Textual dos Discursos

This doctoral dissertationproposes the description, interpretation and analysis of the compositional structure of thesis and dissertation abstracts, with regard to the linguistic mechanisms that evidence text zones of different typological sequences, such as those of the text plan. Along these lines, the research problem was developed from the notion of compositional structure (sequences and text plans), as one of the levels or plans of text analysis, according to the theoretical framework proposed by Jean-Michel Adam (2011a). The main objective of this study was to recognize how the compositional structure, of thesis and dissertation abstracts, is achieved, with respect to text units and the global organization of this text category. The hypothesis posed in this research posits that specific informational text composition categories of abstracts are necessary to process the representation of the original text and the way in which it makes its meaning. Subsequently, this study is based on the theoretical and methodological framework of Text Linguistics (TL) and, above all, Textual Discourse Analysis (TDA), as we endeavor to understand the organizational structure of abstracts from both a linguistic and textual perspective. This structure involves the text plan of abstracts, with respect to their communicative purpose, i.e, the sharing of scientific information in its standard textual form. Thus, the development of this study, from a theoretical and methodological perspective, is based on the theoretical and descriptive premises from TDA (ADAM, 2011a, 2012; PASSEGGI et al., 2010), and also from TL (BEAUGRANDE; DRESSLER, (2012 [1981]); COSERIU; LAMAS (2010); MARCUSCHI, 2009 [1983]; FÁVERO; KOCH, 1994;KOCH, 2006; BENTES, 2004; BENTES; LEITE, 2010), within the field of text studies. The methodology of this study relies on empirical, documental research, which is qualitative, and adopts a descriptive and interpretive approach. From the empirical perspective, our objective is to understand the problems pertaining to the textual composition of abstracts, aiming to elucidate them in light of the theoretical and methodological framework previously mentioned. The corpus of the analysis is comprised of seven abstracts designated for systematic data collection. These texts, written between 2004 and 2011,were selected from Master’s theses and Doctoral dissertations in their electronic version, from the graduate program at the Federal University of Rio Grande do Norte. A thorough review of the literature reveals a clear fluctuation in the terminology of the concept, ‘abstract’. The results of the analysis revealed that the abstracts, which comprise the corpus of analysis in this study, in general, present typological heterogeneity, while the text plan remains fixed. Finally, the new knowledge gained in this research contributes both to the understanding of the compositional structure of abstracts as well as their production.

Análise da expressão dos receptores HER-2 e sua correlação clínica em pacientes com neoplasia gástrica do setor de Oncologia do Hospital de Clínicas da Universidade Federal de Uberlândia-UFU

Introduction: Gastric cancer is currently the fourth higher cancer mortality rate among men in the world and the fifth among women, despite the progressive advances in oncology. The identification of tumor receptors and the development of target-drugs to block them has contributed to increased survival and quality of life of patients, but it becomes important to know the tumor profile of the population being treated, avoiding burdening treatment with examinations and treatments that are not cost-effective. Objective: To evaluate the profile of the population with gastric cancer treated in five years at the Clinical Hospital of the Federal University of Uberlândia and verify the correlation between overexpression of HER-2 receptor with an unfavorable prognosis. Methods: 203 records with gastric cancer were selected through the system database, attending a five-year period, of which 117 paraffin blocks were available for immunohistochemical assessment of HER2 receptor. Results: 2.6% of tumors showed overexpression of HER2, considering for this study two crosses as positive. There was no statistically significant difference in correlation between expression of the HER2 receptor with age, gender, tumor grade, local involvement, Lauren classification, Borrmann classification or staging. Conclusion: For this studied population, we can conclude that there is no need to employ HER2 blockers with high cost as a target-therapy in patients with gastric cancer, since no clinical benefit probably will be obtained due to a low percentage of these patients that demonstrated superexpression of this receptor or even there is no patients with gastric cancer with superexpression of HER2 with more than three crosses of positivity in immunochemistry

A PESQUISA ACADÊMICA SOBRE COMUNICAÇÃO POPULAR, ALTERNATIVA E COMUNITÁRIA NO BRASIL: análise de dissertações e teses produzidas em Programas de Pós-Graduação em Comunicação entre 1972 - 2012

Mapeamento das dissertações e teses referentes à subárea da comunicação popular, alternativa e comunitária (CPAC) desenvolvidas nos Programas de Pós-Graduação em Comunicação stricto sensu no Brasil, de 1972 a 2012. Dentre os objetivos estão localizar as pesquisas; os autores; sua distribuição no tempo e espaço; identificar as instituições e orientadores que impulsionam a subárea; definir as abordagens teórico-metodológicas; e apontar autores/conceitos referência. Por meio de pesquisa exploratória e aplicação de quatro filtros, chegou-se a uma amostra final de 102 pesquisas, 87 dissertações e 15 teses, submetidas à análise quantitativa, por meio de Análise de Conteúdo a partir de partes pré-definidas (Resumo, Palavras chave, Introdução, Sumário, Considerações Finais e capítulo metodológico, quando presente), e a uma análise qualitativa do conteúdo completo das 15 teses. O método que orienta esta pesquisa é o histórico dialético, na perspectiva da busca de uma análise de conjunto e atenta às contradições e mudanças que o objeto está implicado; e a pesquisa bibliográfica que a fundamenta se ancora em autores como Jorge González, Cicilia Peruzzo, Regina Festa, Pedro Gilberto Gomes, Gilberto Giménez e Augusto Triviños e foi realizada com o apoio do software NVivo. Resultados quantitativos indicam: a) predominância de pesquisas sobre comunicação comunitária (68%) b) predominância de estudos empíricos (79%); c) a variedade de denominações atribuídas às experiências pelos pesquisadores; d) a constante luta das classes populares por democratização da comunicação e por direitos sociais ao longo dos anos; e) a influência e importância dos intelectuais orgânicos nas experiências estudadas, f) problemas metodológicos; g) UMESP, USP e UFRJ como instituições protagonistas, e, h) Cicilia Peruzzo e Raquel Paiva como as que mais orientam teses e dissertações sobre a temática. Quanto à análise qualitativa verificaram-se alguns critérios que permeiam a CPAC: 1) a definição de classes subalternas; 2) a importância da participação ativa das comunidades nos processos de comunicação; e 3) formas, conteúdos e objetivos que se complementam e dão identidade às experiências