The predominance of M2-polarized macrophages in the stroma of low-hypoxic bladder tumors is associated with BCG immunotherapy failure

OBJECTIVE: Bacillus Calmette-Guérin (BCG) immunotherapy is the gold standard treatment for superficial bladder tumors with intermediate/high risk of recurrence or progression. However, approximately 30% of patients fail to respond to the treatment. Effective BCG therapy needs precise activation of the type 1 helper cells immune pathway. Tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phenotype and may directly interfere with the BCG-induced antitumor immune response. Thus, we aim to clarify the influence of TAMs, in particular of the M2 phenotype in stroma and tumor areas, in BCG treatment outcome. PATIENTS AND METHODS: The study included 99 patients with bladder cancer treated with BCG. Tumors resected before treatment were evaluated using immunohistochemistry for CD68 and CD163 antigens, which identify a lineage macrophage marker and a M2-polarized specific cell surface receptor, respectively. CD68+ and CD163+ macrophages were evaluated within the stroma and tumor areas, and high density of infiltrating cells spots were selected for counting. Hypoxia, an event known to modulate macrophage phenotype, was also assessed through hypoxia induced factor (HIF)-1α expression. RESULTS: Patients in whom BCG failed had high stroma-predominant CD163+ macrophage counts (high stroma but low tumor CD163+ macrophages counts) when compared with the ones with a successful treatment (71% vs. 47%, P = 0.017). Furthermore, patients presenting this phenotype showed decreased recurrence-free survival (log rank, P = 0.008) and a clear 2-fold increased risk of BCG treatment failure was observed in univariate analysis (hazard ratio = 2.343; 95% CI: 1.197-4.587; P = 0.013). Even when adjusted for potential confounders, such as age and therapeutic scheme, multivariate analysis revealed 2.6-fold increased risk of recurrence (hazard ratio = 2.627; 95% CI: 1.340-5.150; P = 0.005). High stroma-predominant CD163+ macrophage counts were also associated with low expression of HIF-1α in tumor areas, whereas high counts of CD163+ in the tumor presented high expression of HIF-1α in tumor nests. CONCLUSIONS: TAMs evaluation using CD163 is a good indicator of BCG treatment failure. Moreover, elevated infiltration of CD163+ macrophages, predominantly in stroma areas but not in the tumor, may be a useful indicator of BCG treatment outcome, possibly owing to its immunosuppressive phenotype.

Volunteers and management factors in nonprofit organisations: a brief literature review

The objective of this paper is to review and discuss the literature about the management factors that can influence volunteer work. First we present the different management factors. This discussion is followed by the identification of the key management factors in volunteering: recruitment, training and rewarding. Finally, we present two main gaps in the literature that justify the scope for further research: (i) how management factors (recruitment, training and rewarding) influence volunteers’ satisfaction and retention; and (ii) predominance of the investigations in the North American context, followed by English and Australian context.

When Corporate Governance crosses the firm borders: family firms in local productive systems

The family involvement in firms is observable is most economies around the world, although there are significant differences among these countries, not only regarding its predominance in these economies, but also in what refers to the levels of involvement of the family in business. This research aims at understanding the family-based firms’ management when compared to non family based, with particular regards to the forms of corporate governance. This analysis is based on case studies and on secondary data found in the literature to support the findings from the empirical research. The data was collected via face to face in-depth interviews with entrepreneurs from the furniture and the events organisation industries (where the family is predominantly present in the furniture but not on the events organisation industry) and with industry and regional business associations. The case studies used in this research allowed the comparison between the Portuguese firms when the family plays an important role in business and those in which the family is absent. It has been found that there are important differences in businesses in countries/industries/local productive systems in which the family is seen as a dominant institution in the society (where businesses are based on strong ties; there is a harmonious relationship between the family members; and the family is accepted locally and dominates the firm organization) and on situations in which the family plays a more marginal role in the society. In fact, the family brings special characteristics to the business, in terms of management, corporate governance, inter and intra firm relationships and succession. Our findings confirm other empirical studies’ results found in the literature. Thus, this article provides a discussion on the factors that play a role in the form of corporate governance structure in family firms highlighting the pros and cons of organising the firm around the family.

Macrophages as biomarkers in BCG treatment response in bladder cancer

Bladder cancer is a common urologic cancer and the majority has origin in the urothelium. Patients with intermediate and high risk of recurrence/progression bladder cancer are treated with intravesical instillation with Bacillus Calmette-Guérin, however, approximately 30% of patients do not respond to treatment. At the moment, there are no accepted biomarkers do predict treatment outcome and an early identification of patients better served by alternative therapeutics. The treatment initiates a cascade of cytokines responsible by recruiting macrophages to the tumor site that have been shown to influence treatment outcome. Effective BCG therapy needs precise activation of the Th1 immune pathway associated with M1 polarized macrophages. However, tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phenotype, either immunosuppressive or angiogenic, that interfere in different ways with the BCG induced antitumor immune response. The M2 macrophage is influenced by different microenvironments in the stroma and the tumor. In particular, the degree of hypoxia in the tumors is responsible by the recruitment and differentiation of macrophages into the M2 angiogenic phenotype, suggested to be associated with the response to treatment. Nevertheless, neither the macrophage phenotypes present nor the influence of localization and hypoxia have been addressed in previous studies. Therefore, this work devoted to study the influence of TAMs, in particular of the M2 phenotype taking into account their localization (stroma or tumor) and the degree of hypoxia in the tumor (low or high) in BCG treatment outcome. The study included 99 bladder cancer patients treated with BCG. Tumors resected prior to treatment were evaluated using immunohistochemistry for CD68 and CD163 antigens, which identify a lineage macrophage marker and a M2-polarized specific cell surface receptor, respectively. Tumor hypoxia was evaluated based on HIF-1α expression. As a main finding it was observed that a high predominance of CD163+ macrophage counts in the stroma of tumors under low hypoxia was associated with BCG immunotherapy failure, possibly due to its immunosuppressive phenotype. This study further reinforces the importance the tumor microenvironment in the modulation of BCG responses.

Estudo da influência de parâmetros ambientais (Fe e N) na produtividade lipídica da microalga Chlamydomonas sp.

Mestrado em Engenharia Química - Ramo Tecnologias de Protecção Ambiental

Seasonal patterns of polycyclic aromatic hydrocarbons in digestive gland and arm of octopus (Octopus vulgaris) from the Northwest Atlantic

Among organic pollutants existing in coastal areas, polycyclic aromatic hydrocarbons (PAHs) are of great concern due to their ubiquity and carcinogenic potential. The aim of this study was to evaluate the seasonal patterns of PAHs in the digestive gland and arm of the common octopus (Octopus vulgaris) from the Northwest Atlantic Portuguese coast. In the different seasons, 18 PAHs were determined and the detoxification capacity of the species was evaluated. Ethoxyresorufin O-deethylase (EROD) and ethoxycoumarin O-deethylase (ECOD) activities were measured to assess phase I biotransformation capacity. Individual PAH ratios were used for major source (pyrolytic/petrogenic) analysis. Risks for human consumption were determined by the total toxicity equivalence approach. Generally, low levels of PAHs were detected in the digestive gland and in the arm of octopus, with a predominance of low molecular over high molecular weight compounds. PAHs exhibited seasonality in the concentrations detected and in their main emission sources. In the digestive gland, the highest total PAH levels were observed in autumn possibly related to fat availability in the ecosystem and food intake. The lack of PAH elimination observed in the digestive gland after captivity could be possibly associated to a low biotransformation capacity, consistent with the negligible/undetected levels of EROD and ECOD activity in the different seasons. The emission sources of PAHs found in the digestive gland varied from a petrogenic profile observed in winter to a pyrolytic pattern in spring. In the arm, the highest PAH contents were observed in June; nevertheless, levels were always below the regulatory limits established for food consumption. The carcinogenic potential calculated for all the sampling periods in the arm were markedly lower than the ones found in various aquatic species from different marine environments. The results presented in this study give relevant baseline data for environmental monitoring of organic pollution in coastal areas.

Otimização da extração sólido-líquido de antioxidantes de subprodutos florestais pelo método de superfície de resposta

Portugal continental apresenta uma vasta área florestal, que representa cerca de 35,4% da ocupação total do solo, com predominância de espécies como o eucalipto (Eucalyptus globulus) e o pinheiro-bravo (Pinus pinaster). Estas espécies apresentam uma elevada importância a nível económico, designadamente devido à sua ampla utilização, nomeadamente na indústria de celulose e papel, gerando elevadas quantidades de resíduos. Este resíduo de biomassa florestal é utilizado, na sua totalidade, para a geração de energia, na forma de eletricidade ou aquecimento. No entanto, existem outras opções viáveis, a nível económico, tais como a valorização destes subprodutos como fonte de compostos polifenólicos tornando-os, assim, um produto de valor acrescentado. A extração de compostos fenólicos de subprodutos florestais, como folhas de eucalipto e agulhas de pinheiros tem vindo a aumentar devido, principalmente, à substituição de antioxidantes sintéticos, contribuindo para a valorização de subprodutos florestais. Contudo, apesar de todas as potenciais aplicações e vantagens, apenas algumas centenas de espécies aromáticas identificadas são utilizadas à escala comercial. Neste trabalho foi avaliada a capacidade antioxidante de subprodutos da floresta, otimizando as condições de extração através do estudo dos fatores: tempo de extração, temperatura e composição de solvente através do método de superfície de resposta. O planeamento experimental utilizado teve como base um planeamento de compósito central e a avaliação do perfil de antioxidantes das matrizes analisadas foi realizada através de métodos de quantificação total, como o teor fenólico total, a atividade anti-radicalar – método do DPPH (radical 2,2-difenil-1-picrilhidrazilo) e o método de FRAP. Estes métodos analíticos convencionais foram modificados e, devidamente validados, para a análise em leitor de microplacas. Verificou-se que os extratos de pinheiro e de eucalipto, tanto as amostras verdes com as amostras, apresentam uma promissora capacidade antioxidante. O planeamento fatorial aplicado permitiu otimizar as condições de extração em relação às matrizes verdes. Contudo, o mesmo não se verificou em relação às matrizes secas. A composição (% de água) é sem dúvida o fator com mais efeito em todas as amostras (coeficientes de primeira e segunda ordem no modelo). Também a temperatura foi identificada como um fator com efeito significativo sobre os sistemas em análise.

An organizational culture approach to performance in information technology micro-firms

This study aims to analyze and compare micro-firms’ organizational culture related to organizational performance. A case study methodology was used based on four firms, competitors among themselves in the Information Technology business, focusing on the years between 2008-2013. Findings pointed out many similarities to larger firms, but some specificities of micro-firms were found and propositions were defined: clan culture predominance is related to best performing micro-firms; the configuration of several culture types seemed to be the most suitable for obtaining good organizational results, provided that they do not focus only on hierarchy and market types of culture; the market culture predominance perception by employees is associated with low job satisfaction; and, after a certain time in business, micro-firms, as do larger companies, seek to standardize and control processes. Recognizing that organizational culture is considered important to firms’ results, this study sheds some light on that important factor for micro-firms.

Tendências de recompensas em empresas portuguesas

Esta dissertação tem como objetivo central conhecer os sistemas de recompensas em empresas portuguesas. Primeiramente é realizada uma abordagem aos conceitos subjacentes ao sistema de recompensas e, simultaneamente é exposta teoria sobre o tipo de recompensas mais utilizadas e como estas diferem consoante o cargo/função. Foi aplicado um inquérito por questionário a uma amostra de 144 empresas localizadas por todo o país. Foram testadas hipóteses de estudo capazes de permitir caraterizar o sistema de recompensas desenvolvido nas empresas em estudo. Os resultados do estudo permitem concluir que: 1) os sistemas de recompensas baseados na antiguidade estão atualmente em desuso, ao contrário dos sistemas de recompensas baseados na função/cargo, no desempenho e nas competências; 2) o principal objetivo do sistema de recompensas das empresas do estudo é a motivação dos colaboradores; 3) a conjugação das recompensas monetárias e não monetárias são as mais valorizadas pelas empresas; 4) predomina a compensação variável nos sistemas de recompensas das empresas bem como os incentivos mistos (individuais e de grupo); 5) predominam os incentivos de curto-prazo no sistema de recompensas; 6) o bónus anual é o incentivo mais utilizado; 7) os benefícios e alguns dos incentivos tendem a ser maiores à medida que se sobe na hierarquia funcional da empresa; 8) o benefício predominante é a atribuição de telemóvel e o seguro de saúde; 9) as formas de reconhecimento mais comuns são os prémios de desempenho, o feedback contínuo, as promoções e as placas comemorativas; 10) a maioria dos inquiridos acredita que as oportunidades de desenvolvimento de carreira é uma importante medida para a retenção dos colaboradores; 11) as oportunidades de desenvolvimento são mais utilizadas pelas empresas de maior dimensão e; 12) os benefícios sociais são considerados a componente mais importante para garantir a retenção dos colaboradores. Com base nestes resultados, na parte final da dissertação são apresentadas algumas implicações teóricas e práticas, algumas limitações do estudo, bem como pistas para investigações futuras.