The therapeutic potential of recombinant BCG expressing the antigen S1PT in the intravesical treatment of bladder cancer

Purpose: Bacillus Calmette-Guerin (BCG) continues to be employed as the most effective immunotherapy against superficial bladder cancer. We have developed an rBCG-S1PT strain that induces a stronger cellular immune response than BCG. This preclinical study was designed to test the potential of rBCG-S1PT as an immunotherapeutic agent for intravesical bladder cancer therapy. Materials and methods: A tumor was induced in C57BL/6 mice after chemical cauterization of the bladder and inoculation of the tumor cell line MB49. Next, mice were treated by intravesical instillation with BCG, rBCG-S1PT, or PBS once a week for 4 weeks. After 35 days, the bladders were removed and weighed, Th1 (IL-2, IL-12, INOS, INF-gamma, TNF-alpha), and Th2 (IL-5, IL-6, IL-10, TGF-beta) cytokine mRNA responses in individual mice bladders were measured by quantitative real time PCR, and the viability of MB49 cells in 18-hour coculture with splenocytes from treated mice was assessed. In an equivalent experiment, animals were observed for 60 days to quantify their survival. Results: Both BCG and rBCG-S1PT immunotherapy resulted in bladder weight reduction, and rBCG-S1PT increased survival time compared with the control group. There were increases in TNF-alpha in the BCG treated group, as well as increases in TNF-alpha and IL-10 mRNA in the rBCG-S1PT group. The viability of MB49 cells cocultured with splenocytes from rBCG-S1PT-treated mice was lower than in both the BCG and control groups. Conclusions: rBCG-S1PT therapy improved outcomes and lengthened survival times. These results indicate that rBCG could serve as a useful substitute for wild-type BCG. (C) 2010 Elsevier Inc. All rights reserved.

Peritoneal Dialysis in Acute Kidney Injury: Lessons Learned and Applied

Peritoneal dialysis (PD) is a simple, safe, gentle, and efficient renal replacement therapy (RRT) method. It is able to correct acute kidney injury (AKI)-induced metabolic, electrolytic, and acid-base disorders and volume overload both in and out the intensive care unit setting. Some PD modalities, such as high-volume PD and continuous flow PD, can provide RRT doses and efficiency comparable to extracorporeal blood purification methods. PD is particularly suitable for children, patients with refractory heart failure or hemodynamically instable, conditions where systemic anticoagulation should be avoided, patients with difficulty for vascular access and hypo- and hyperthermia conditions. In the following manuscript, PD technical aspects and the possible advantages and limitations of this RRT method will be discussed, and the more recent literature on clinical experience with PD for treatment of AKI will be reviewed.

miRNA analysis of prostate cancer by quantitative real time PCR: Comparison between formalin-fixed paraffin embedded and fresh-frozen tissue

Objective: Micro RNA (miRNA) is a class of small noncoding RNA that plays a major role in the regulation of gene expression, which has been related to cancer behavior. The possibility of analyzing miRNA from the archives of pathology laboratories is exciting, as it allows for large retrospective studies. Formalin is the most common fixative used in the surgical pathology routine, and its promotion of nucleic acid degradation is well known. Our aim is to compare miRNA profiles from formalin-fixed paraffin embedded (FFPE) tissues with fresh-frozen prostate cancer tissues. Methods: The expression of 14 miRNAs was determined by quantitative real time polymerase chain reaction (qRT-PCR) in 5 paired fresh-frozen and FFPE tissues, which were representative of prostate carcinoma. Results: There was a very good correlation of the miRNA expression of miR-let7c and miR-32 between the fresh-frozen and FFPE tissues, with Pearson`s correlation coefficients of 0.927 (P = 0.023) and 0.960 (P = 0.010), respectively. For the remaining miRNAs, the correlation was good with Spearman correlation coefficient of 0.638 (P < 0.001). Conclusion: Analysis of miRNAs from routinely processed and stored FFPE prostate tissue is feasible for some miRNAs using qRT-PCR. Further studies should be conducted to confirm the reliability of using stock tissues for miRNA expression determination. (C) 2011 Elsevier Inc. All rights reserved.

Matrix metalloproteinase-2 polymorphism is associated with prognosis in prostate cancer

Objective: Prostate cancer (PCa) is the most frequent tumor in males in Brazil. Single nucleotide polymorphisms (SNP) have been demonstrated in the promoter region of matrix metalloproteinases (MMPs) genes and have been associated with development and progression of some cancers. In this study, our aim was to investigate a possible relation between polymorphism of the promoter region of the MMP2 gene and classical prognostic parameters in prostate cancer. Materials and methods: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by real-time polymerase chain reaction, using fluorescent probes (TaqMan). Results: In patients with tumors of a higher stage (pT3), a polymorphic allele in the MMP2 gene was more frequent (P = 0.026) than in patients with lower tumor stage. A polymorphic allele in the MMP2 gene was more frequent in Gleason >= 7 than in Gleason <= 6 (P = 0.042). Conclusions: We conclude that MMP2 polymorphism can be used together with pathological stage and Gleason score to identify patients with worse prognosis. Our results illustrate the potential use of MMP2 SNP as a molecular marker for prostate cancer. (C) 2010 Elsevier Inc. All rights reserved.

Nonoperative Approaches to Rectal Cancer: A Critical Evaluation

A neoadjuvant multimodality approach with chemoradiation therapy (CRT) is the preferred treatment strategy for most distal rectal cancers. Significant downstaging and complete pathologic response may develop after this strategy, and there is still controversy regarding the management of these patients. In this setting, a nonoperative approach has been suggested in select patients with complete clinical response after thorough clinical, endoscopic, and radiologic assessment. However, the assessment of these patients is not straightforward and remains complex. Available data regarding this approach are limited to a single institution`s experience from retrospective analyses. Standardization of the assessment of tumor response and the development of radiological/molecular tools may clarify the role of no immediate surgery in patients with complete clinical response after neoadjuvant CRT. Advances in radiation and medical oncology could potentially lead to significant improvements in complete tumor regression rates, leading to an increase in importance of a minimally invasive approach in patients with rectal cancer. Semin Radiat Oncol 21:234-239 (C) 2011 Elsevier Inc. All rights reserved.

Isoforms of hyaluronidases can be a predictor of a prostate cancer of good prognosis

Introduction: Hyaluronidases (HAases) are enzymes related to cancer progression. Isoforms of HAases have been described as products of alternative splicing responsible for differences in enzyme activity. The heterogeneity of HAase expression has been identified in tumors and could be related to the differences in their biological behavior. Methods: Thirty-seven patients subjected to radical prostatectomy for prostate cancer were divided into 2 groups for the analyses: Low (<= 6-18) and high (>= 7-19) Gleason score and tumor behavior; recurrence 15 and nonrecurrence 22, mean follow-up 52.6 months. Conclusion: A profile of HAase related to low Gleason score and non-tumor recurrence was characterized by expression of HYAL3-v1, HYAL1-v3, and HYAL3-v2. More studies should be made in order to confirm with larger series. (C) 2009 Elsevier Inc. All rights reserved.

Current management practices for acromegaly: an international survey

To determine whether peer-reviewed consensus statements have changed clinical practice, we surveyed acromegaly care in specialist centers across the globe, and determined the degree of adherence to published consensus guidelines on acromegaly management. Sixty-five acromegaly experts who participated in the 7th Acromegaly Consensus Workshop in March 2009 responded. Results indicated that the most common referring sources for acromegaly patients were other endocrinologists (in 26% of centers), neurosurgeons (25%) and primary care physicians (21%). In sixty-nine percent of patients, biochemical diagnoses were made by evaluating results of a combination of growth hormone (GH) nadir/basal GH and elevated insulin like growth factor-I (IGF-I) levels. In both Europe and the USA, neurosurgery was the treatment of choice for GH-secreting microadenomas and for macroadenomas with compromised visual function. The most widely used criteria for neurosurgical outcome assessment were combined measurements of IGF-I and GH levels after oral glucose tolerance test (OGTT) 3 months after surgery. Ninety-eight percent of respondents stated that primary treatment with somatostatin receptor ligands (SRLs) was indicated at least sometime during the management of acromegaly patients. In nearly all centers (96%), the use of pegvisomant monotherapy was restricted to patients who had failed to achieve biochemical control with SRL therapy. The observation that most centers followed consensus statement recommendations encourages the future utility of these workshops aimed to create uniform management standards for acromegaly.

Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis

Objective: MicroRNAs (miRNAs) are small noncoding regulatory RNAs (19-25 nucleotides) that play a major role in regulation of gene expression. They are responsible for the control of fundamental cellular processes that has been reported to be involved in human tumorigenesis. The characterization of miRNA profiles in human tumors is crucial for the understanding of carcinogenesis processes, finding of new tumor markers, and discovering of specific targets for the development of innovative therapies. The aim of this study is to find miRNAs involved in prostate cancer progression comparing the profile of miRNA expressed by localized high grade carcinoma and bone metastasis. Material and methods: Two groups of tumors where submitted to analyses. The first is characterized by 18 patients who underwent radical prostatectomy for treatment of localized high grade prostate carcinoma (PC) with mean Gleason score 8.6, all staged pT3. The second group is composed of 4 patients with metastatic, androgen-independent prostate carcinoma, and 2 PC cell lines. LNCaP derived from a metastatic PC to a lymph node, and another derived from an obstructive, androgen-independent PC (PcBRA1). Expression analysis of 14 miRNAs was carried out using quantitative RT-PCR. Results: miR-let7c, miR-100, and miR-218 were significantly overexpressed by all localized high GS, pT3 PC in comparison with metastatic carcinoma. (35.065 vs. 0.996 P < 0.001), (55.550 vs. 8.314, P = 0.010), and (33.549 vs. 2.748, P = 0.001), respectively. Conclusion: We hypothesize that miR-let7c, miR-100, and miR-218 may be involved in the process of metastasization of PC, and their role as controllers of the expression of RAS, c-myc, Laminin 5 beta 3, THAP2, SMARCA5, and BAZ2A should be matter of additional studies. (C) 2011 Elsevier Inc. All rights reserved.

Role of Microparticles in the Hemostatic Dysfunction in Acute Promyelocytic Leukemia

Serious bleeding and thrombotic complications are frequent in acute promyelocytic leukemia (APL) and are major causes of morbidity and mortality. Microparticles (MP) have been used to study the risk and pathogenesis of thrombosis in many malignant disorders. To date, from published articles, this approach had not been applied to APL. In this article, the hemostatic dysfunction in this disorder is briefly reviewed. A study design to address this problem using MP is described. MP bearing tissue factor, profibrinolytic factors (tissue plasminogen activator and annexin A2), and the antifibrinolytic factor plasminogen activator inhibitor type 1 were measured using flow cytometry. The cellular origin of the MP was identified by specific cell surface markers. Comparison of the various populations of MP was made between samples collected at the time of diagnosis with those collected at molecular remission. Preliminary data suggest that this approach is feasible.

Cultural Specific Training in Corruption Reporting for Pacific Island Journalists

Notes that very few journalists have formal training in corruption reporting. Discusses workshops held in 2000 and 2001 on the subject of corruption reporting for Pacific Island journalists. Explains the role of the media as an anti-corruption mechanism and the difficulty journalists face in identifying and sometimes stamping out corruption. Looks at the programs adopted and explains the responses of journalists.

Biostatistics in Australia: Directions in the new millennium

The Biostatistics Collaboration of Australia (BCA) was formed in response to a shortage of statisticians seeking careers in the medical and health professions. The Collaboration has been successful in developing postgraduate courses (Graduate Certificate, Graduate Diploma and Masters) offered by a consortium of seven Australian Universities. These courses are available through a distance learning medium. The BCA was successful in securing funding from the Federal government to launch these courses, which commenced in March 2001. Two traineeships by the NSW Department of Health have also been awarded and a third is currently advertised. There has been close collaboration with governments, the pharmaceutical industry and research organisations to ensure that course content reflects practical problems and addresses industry needs. A second objective of the BCA is to provide ongoing workshops for practising biostatisticians to enhance professional development. These workshops serve to ring together biostatisticians from both within Australia and the Asia-Pacific region, providing a forum for discussion of current statistical thinking. (author abstract)

Engaging with theories of dialogue and voice: Using Bakhtin as a framework to understand teaching and learning Indigenous Australian women's performance

In this paper I explore the Indigenous Australian women's performance classroom (hereafter ANTH2120) as a dialectic and discursive space where the location of possibility is opened for female Indigenous performers to enter into a dialogue from and between both non-Indigenous and Indigenous voices. The work of Bakhtin on dialogue serves as a useful standpoint for understanding the multiple speaking positions and texts in the ANTH2120 context. Bakhtin emphasizes performance, history, actuality and the openness of dialogue to provide an important framework for analysing multiple speaking positions and ways of making meaning through dialogue between shifting and differing subjectivities. I begin by briefly critiquing Bakhtin's "dialogic imagination" and consider the application and usefulness of concepts such as dialogism, heteroglossia and the utterance to understanding the ANTH2120 classroom as a polyphonic and discursive space. I then turn to an analysis of dialogue in the ANTH2120 classroom and primarily situate my gaze on an examination of the interactions that took place between the voices of myself as family/teacher/student and senior Yanyuwa women from the r e m o t e N o r t h e r n T e r r i t o r y A b o r i g i n a l c o m m u n i t y o f B o r r o l o o l a as family/performers/teachers. The 2000 and 2001 Yanyuwa women's performance workshops will be used as examples of the way power is constantly shifting in this dialogue to allow particular voices to speak with authority, and for others to remain silent as roles and relationships between myself and the Yanyuwa women change. Conclusions will be drawn regarding how my subject positions and white race privilege affect who speaks, who listens and on whose terms, and further, the efficacy of this pedagogical platform for opening up the location of possibility for Indigenous Australian women to play a powerful part in the construction of knowledges about women's performance traditions.

A Educação Ambiental nos encontros do Congo com os cotidianos escolares de uma Escola Municipal da Barra do Jucu, Vila Velha, ES

A pesquisa “A Educação Ambiental nos encontros do Congo com os cotidianos escolares de uma Escola Municipal da Barra do Jucu, Vila Velha, ES” se apoia na produção narrativa em Educação Ambiental com os cotidianos, com a intenção de problematizar os saberes e fazeres socioambientais produzidos nos encontros entre a produção cultural do congo com as práticas escolares cotidianas. Com as conversas e narrativas dos sujeitos da pesquisa, alunos(as), professores(as), congueiros(as), pais de alunos e outros representantes da comunidade escolar, problematizamos e mapeamos esses saberesfazeres socioambientais, bem como compreendemos suas diferentes traduções. Os cotidianos escolares são considerados espaços de burla às hierarquizações culturais, ambientais, sociais e curriculares, por serem espaços privilegiados de práticas curriculares que vão além das propostas instituídas, e enfatizamos como o entorno da escola com suas especificidades locais se constituem potências para a produção de saberes e a criação de currículos cotidianamente. As oficinas de congo que acontecem na Escola Municipal da Barra do Jucu foram acompanhadas e mostraram-se potentes para o desenvolvimento da Educação Ambiental numa perspectiva pós-colonial, que acredita na possibilidade de um pensamento que vá além da relação dicotômica cultura/natureza e da não homogeneização cultural. As produções culturais desenvolvidas nas oficinas possibilitaram “outras” alternativas para a produção de subjetividades e para trocas de saberes socioambientais e culturais, baseados na solidariedade que potencializa práticas sociais sustentáveis.

Pensando o currículo com as crianças: ou sobre aprendizagens inventivas na educação infantil

Ninguém consegue sair ileso de um encontro com o currículo e com a escola, principalmente diante de relações tão assimétricas de poder que não valorizam o que as crianças têm a dizer. Quantas narrativas curriculares sobre as crianças? Quantas narrativas curriculares com as crianças? As narrativas e as fotografias se seguirão nesta pesquisa, porque com elas nos colocamos a pensar nos processos de criação curricular, explorando novas sensibilidades, novas maneiras de ver e falar, a partir das redes de sentidos, forjadas nos contextos vividos, imaginados ou pensados, dentrofora da escola. Também incluímos a forma como as crianças se relacionam com as práticas pedagógicas dos professores e do modo como se relacionam com a escola. Nessa perspectiva, interessa-nos pensar em como os usos (CERTEAU, 1994) da imagem fotográfica são capazes de afetar (e até transformar) as práticas curriculares, traçando algo da potência da/na imagem fotográfica em sua função fabuladora por meio das oficinas de fotografias realizadas com as crianças em virtude da pesquisa. A fotografia se torna potente como um recurso para provocar a invenção tessitura de outros sentidos em currículo não porque em sua materialidade ela está repleta de sentidos de currículo à priori, mas porque pode ou não, ao ser usada (CERTEAU, 1994), ao ser vista pelas crianças, agenciar outros possíveis para o currículo. Assim, o foco da discussão não é a fotografia em si nem a criança em si, ou seja, não há protagonismo nem da criança nem da fotografia. O foco está nas relações, naquilo que nos passa, isto é, na experiência estética (LARROSA, 2004b) que ocorre ao entrarmos em contato, ao vermos, ao compormos com as fotografias! Nesse sentido, pensamos as oficinas de fotografias como um dispositivo de criação e produção de acontecimentos em currículo, considerando-as máquinas de fazer “ver e falar”, o que as justifica como uma estratégia narrativa capaz de produzir acontecimentos na imagem e no mundo. Que sentidos de currículo são produzidos em multiplicidades? Pelas minoridades pretendemos movimentar nosso pensamento: que quer pensar um currículo como fabulação sem dizer o que ele é, mas no que ele vai se transformando com a chegada das crianças. No encontro das imagens com as palavras, em que o currículo vai se transformando? Sob a mesma superfície chamada currículo em extensão com as crianças, co-habitantes, encontrar os modos de olhar esse currículo e de dizê-lo por meio das fotografias, das narrativas, dos cartazes, dos desenhos, das poesias... As conversas com as crianças provocam o real, colocam em desequilíbrio algumas ideias feitas em educação, exigindo reordenações e invenções de outros pensamentos para a educação. É dessa criação de efeitos impensáveis que surge a invenção de currículos possíveis. Aprender a olhar mais (até cansar!) aquilo que não percebemos no dia a dia tem uma dimensão política muito importante; por meio desse gesto (que aprendemos com as crianças) podemos criar um novo pensamento político em educação. A partir daquilo que nos dá a ver, as crianças vão inaugurar sentidos impertinentes, desestabilizadores daquilo que chamamos de currículo e escola. O desafio consiste em falar da força contida na imagem fotográfica sem vontade de interpretá-la ou descrevê-la, mas escrever e pensar pelas fotografias num movimento de criação de sentidos e acontecer por elas.

Tramas e urdiduras: o protagonismo como exercício na atividade docente de professores de educação física

Trata-se de uma pesquisa-intervenção com o objetivo principal de analisar como os professores fazem exercício protagonista na atividade. Embasa-se principalmente no aporte conceitual da perspectiva ergológica de Yves Schwartz para realizar a análise da atividade no cotidiano escolar. O estudo foi desenvolvido em uma Escola Municipal de Ensino Fundamental de Serra/ES com duas professoras e um professor de Educação Física. As estratégias metodológicas utilizadas foram constituídas de acompanhamento da atividade desenvolvida pelos professores nas aulas, no Curso de Formação Permanente de Área de Educação Física, promovido pela Secretaria Municipal de Educação, participação no cotidiano escolar e a construção coletiva de um processo de formação na escola por meio de oficinas de práticas corporais. As técnicas de produção e registro dos dados foram compostas por diário de campo, fotos, conversas gravadas em áudio, entrevistas, questionário e documentos elaborados pela escola, como o Projeto Político-Pedagógico. A confrontação dos dados realizada com os docentes nas conversas produziu importantes deslocamentos nas análises e convocou autores e conceitos que não estavam previstos para o debate sobre o exercício protagonista. A produção dos dados gerou mudança na atividade docente e colocou em questão modos de gestão e organização do trabalho na Rede Serra de Educação, provocando transformações nos modelos de formação permanente dos professores de Educação Física do município. Os exercícios protagonistas empreendidos na atividade docente colocaram competências em circulação e tornaram visíveis os efeitos de trama e urdidura que atravessam e compõem a atividade docente dos professores de Educação Física no cotidiano escolar.