Heparan sulfate glycosaminoglycans: (un)expected allies in cancer clinical management

In an era when cancer glycobiology research is exponentially growing, we are witnessing a progressive translation of the major scientific findings to the clinical practice with the overarching aim of improving cancer patients’ management. Many mechanistic cell biology studies have demonstrated that heparan sulfate (HS) glycosaminoglycans are key molecules responsible for several molecular and biochemical processes, impacting extracellular matrix properties and cellular functions. HS can interact with a myriad of different ligands, and therefore, hold a pleiotropic role in regulating the activity of important cellular receptors and downstream signalling pathways. The aberrant expression of HS glycan chains in tumours determines main malignant features, such as cancer cell proliferation, angiogenesis, invasion and metastasis. In this review, we devote particular attention to HS biological activities, its expression profile and modulation in cancer. Moreover, we highlight HS clinical potential to improve both diagnosis and prognosis of cancer, either as HS-based biomarkers or as therapeutic targets.This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and by the grant POCI-01-0145-FEDER-028489 (to A.M.). J.P. and C.M. are funded by FCT PhD scholarships SFRH/BD/137319/2018 and 2020.06412.BD, respectively. The APC was funded by FCT grant POCI-01-0145-FEDER-028489. The authors acknowledge the support of the COST Action CA18103 INNOGLY

Antonio Gramsci’s impact on critical pedagogy

This paper provides an account of Antonio Gramsci’s impact on the area of critical pedagogy. It indicates the Gramscian influence on the thinking of major exponents of the field. It foregrounds Gramsci's ideas and then indicates how they have been taken up by a selection of critical pedagogy exponents who were chosen on the strength of their identification and engagement with Gramsci's ideas, some of them even having written entire essays on Gramsci. The essay concludes with a discussion concerning an aspect of Gramsci's concerns, the question of powerful knowledge, which, in the present author's view, provides a formidable challenge to critical pedagogues.peer-reviewe

Citizenship Education and the Role of Immigrant Students in the Nordic Countries

This chapter addresses the issue of citizenship education and the role of immigrant students in the Nordic countries from the perspective of liberal theories of citizenship education. Liberal approaches to citizenship education have recently encountered rigorous critique: the critics argue that the supposedly democratic, rational, and neutral principles and ideals associated with liberal theories are in reality rooted in a particular way of life and national identity. Accordingly, inculcating these principles and ideals in citizenship education excludes and marginalizes students belonging to minorities, immigrant students in particular. This chapter aims to respond to this critique by separating between two branches of liberal theories of citizenship education, ‘patriotic’ and ‘political’. The chapter argues that while the ‘patriotic’ approach is vulnerable to the aforementioned critique, it does not apply to the ‘political’ line of thought. Rather, the ‘political’ approach, rooted in John Rawls’ political liberalism and the notion of reasonableness, provides a foundation for criticizing policies and practices that marginalize students with immigrant backgrounds. Finally, utilizing Rawlsian theory of citizenship education as a starting point, the chapter makes some suggestions on how the status of immigrant students could be improved in the Nordic countries.Peer reviewe

Can universal insecticide-treated net campaigns achieve equity in coverage and use? the case of northern Nigeria

<p>Abstract</p> <p>Background</p> <p>Insecticide-treated nets (ITNs) are effective tools for malaria prevention and can significantly reduce severe disease and mortality due to malaria, especially among children under five in endemic areas. However, ITN coverage and use remain low and inequitable among different socio-economic groups in sub-Saharan Africa, particularly in Nigeria. Several strategies have been proposed to increase coverage and use and reduce inequity in Nigeria, including free distribution campaigns recently conducted by the Nigerian federal government. Using data from the first post-campaign survey, the authors investigated the effect of the mass free distribution campaigns in achieving equity in household ownership and use of ITNs.</p> <p>Methods</p> <p>A post-campaign survey was undertaken in November 2009 in northern Nigeria to assess the effect of the campaigns in addressing equity across different socio-economic groups. The survey included 987 households randomly selected from 60 clusters in Kano state. Using logistic regression and the Lorenz concentration curve and index, the authors assessed equity in ITN coverage and use.</p> <p>Results</p> <p>ITN ownership coverage increased from 10% before the campaigns to 70%-a more than fivefold increase. The campaigns reduced the ownership coverage gap by 75%, effectively reaching parity among wealth quintiles (Concentration index 0.02, 95% CI (-0.02 ; 0.05) versus 0.21 95%CI (0.08 ; 0.34) before the campaigns). ITN use (individuals reporting having slept under an ITN the night before the survey visit) among individuals from households owning at least one ITN, was 53.1% with no statistically significant difference between the lowest, second, third and fourth wealth quintiles and the highest wealth quintile (lowest: odds ratio (OR) 0.87, 95% confidence interval (CI) (0.67 ; 1.13); second: OR 0.85, 95% CI (0.66 ; 1.24); third: OR 1.10 95% CI (0.86 ; 1.4) and fourth OR 0.91 95% CI (0.72 ; 1.15).</p> <p>Conclusion</p> <p>The campaign had a significant impact by increasing ITN coverage and reducing inequity in ownership and use. Free ITN distribution campaigns should be sustained to increase equitable coverage. These campaigns should be supplemented with other ITN distribution strategies to cover newborns and replace aging nets.</p

Androgenic suppression combined with radiotherapy for the treatment of prostate adenocarcinoma: a systematic review

<p>Abstract</p> <p>Background</p> <p>Locally advanced prostate cancer is often associated with elevated recurrence rates. Despite the modest response observed, external-beam radiotherapy has been the preferred treatment for this condition. More recent evidence from randomised trials has demonstrated clinical benefit with the combined use of androgen suppression in such cases. The aim of this meta-analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival, disease-free survival and toxicity.</p> <p>Methods</p> <p>Databases (MEDLINE, EMBASE, LILACS, Cochrane databases and ClinicalTrials.gov) were scanned for randomised clinical trials involving radiotherapy with or without androgen suppression in local prostate cancer. The search strategy included articles published until October 2011. The studies were examined and the data of interest were plotted for meta-analysis. Survival outcomes were reported as a hazard ratio with corresponding 95% confidence intervals.</p> <p>Results</p> <p>Data from ten trials published from 1988 to 2011 were included, comprising 6555 patients. There was a statistically significant advantage to the use of androgen suppression, in terms of both overall survival and disease free survival, when compared to radiotherapy alone. The use of long-term goserelin (up to three years) was the strategy providing the higher magnitude of clinical benefit. In contrast to goserelin, there were no trials evaluating the use of other luteinizing hormone-releasing hormone (LHRH) analogues as monotherapy. Complete hormonal blockade was not shown to be superior to goserelin monotherapy.</p> <p>Conclusions</p> <p>Based on the findings of this systematic review, the evidence supports the use of androgen suppression with goserelin monotherapy as the standard treatment for patients with prostate cancer treated with radiotherapy, which are at high risk of recurrence or metastases.</p

Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection

The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. The screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. The 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. In addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy