Why do we use the term ‘resilience’ and what are the implications of this use for urban space? The reflection in this article is based on this question. The purpose of this text is to illustrate – in ...dialectic form – the way in which resilience has been used in neoliberal strategies of urban transformation, given that it has been instrumentalized to normalize distinct spaces in cities. To respond to the question, document analysis has been used as a research methodology. Among the main conclusions of the study on which this article is based, two aspects regarding urban resilience that had not been studied to-date stand out. First, the use of the term reflects typical characteristics of performative concepts, with the power that that type of notion has for reducing its object to a hegemonic and repetitive narrative – in this case, the urban and its construction. Second, in concordance with critical urban theory and through a genealogical analysis of Foucauldian inspiration applied to the instrumental use of resilience, it is shown how this concept has been converted into a notion that facilitates the neoliberal project, which has dominated processes of change in urban Latin America in the 21st century.
Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic ...characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.
Non-coding RNAs are important regulators of differentiation during embryogenesis as well as key players in the fine-tuning of transcription and furthermore, they control the post-transcriptional ...regulation of mRNAs under physiological conditions. Deregulated expression of non-coding RNAs is often identified as one major contribution in a number of pathological conditions. Non-coding RNAs are a heterogenous group of RNAs and they represent the majority of nuclear transcripts in eukaryotes. An evolutionary highly conserved sub-group of non-coding RNAs is represented by vault RNAs, named since firstly discovered as component of the largest known ribonucleoprotein complexes called “vault”. Although they have been initially described 30 years ago, vault RNAs are largely unknown and their molecular role is still under investigation. In this review we will summarize the known functions of vault RNAs and their involvement in cellular mechanisms.
Non-coding RNAs represent a significant proportion of the human genome. After having been considered as ‘junk’ for a long time, non-coding RNAs are now well established as playing important roles in ...maintaining cellular homeostasis and functions. Some non-coding RNAs show cell- and tissue-specific expression patterns and are specifically deregulated under pathological conditions (e.g
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cancer). Therefore, non-coding RNAs have been extensively studied as potential biomarkers in the context of different diseases with a focus on microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) for several years. Since their discovery, miRNAs have attracted more attention than lncRNAs in research studies; however, both families of non-coding RNAs have been established to play an important role in gene expression control, either as transcriptional or post-transcriptional regulators. Both miRNAs and lncRNAs can regulate key genes involved in the development of cancer, thus influencing tumour growth, invasion, and metastasis by increasing the activation of oncogenic pathways and limiting the expression of tumour suppressors. Furthermore, miRNAs and lncRNAs are also emerging as important mediators in drug-sensitivity and drug-resistance mechanisms. In the light of these premises, a number of pre-clinical and early clinical studies are exploring the potential of non-coding RNAs as new therapeutics. The aim of this review is to summarise the latest knowledge of the use of miRNAs and lncRNAs as therapeutic tools for cancer treatment.
Sequential profiling of plasma cell-free DNA (cfDNA) holds immense promise for early detection of patient progression. However, how to exploit the predictive power of cfDNA as a liquid biopsy in the ...clinic remains unclear. RAS pathway aberrations can be tracked in cfDNA to monitor resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer. In this prospective phase II clinical trial of single-agent cetuximab in
wild-type patients, we combine genomic profiling of serial cfDNA and matched sequential tissue biopsies with imaging and mathematical modeling of cancer evolution. We show that a significant proportion of patients defined as
wild-type based on diagnostic tissue analysis harbor aberrations in the RAS pathway in pretreatment cfDNA and, in fact, do not benefit from EGFR inhibition. We demonstrate that primary and acquired resistance to cetuximab are often of polyclonal nature, and these dynamics can be observed in tissue and plasma. Furthermore, evolutionary modeling combined with frequent serial sampling of cfDNA allows prediction of the expected time to treatment failure in individual patients. This study demonstrates how integrating frequently sampled longitudinal liquid biopsies with a mathematical framework of tumor evolution allows individualized quantitative forecasting of progression, providing novel opportunities for adaptive personalized therapies.
Liquid biopsies capture spatial and temporal heterogeneity underpinning resistance to anti-EGFR monoclonal antibodies in colorectal cancer. Dense serial sampling is needed to predict the time to treatment failure and generate a window of opportunity for intervention.
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MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that ...miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment.
•miR-135b is overexpressed in mouse and human colorectal cancer•miR-135b overexpression is associated with poor clinical outcome•miR-135b activation is triggered by oncogenic pathways in colorectal cancer•miR-135b represents a therapeutic target for colorectal cancer
Valeri et al. identify miR-135b as a key oncogenic pathway effector involved in transformation and colorectal cancer (CRC) progression. Upregulation of miR-135b in human CRCs correlates with poor clinical outcome. miR-135b targets several tumor suppressor genes and is a potential target for CRC therapy.
Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of ...microRNA 21 (MIR21 or miRNA21) are increased in CCAs. We investigated whether miRNA21 mediates resistance of CCA cells and organoids to HSP90 inhibitors.
We performed a high-throughput screen of 484 small-molecule compounds to identify those that reduced viability of 6 human CCA cell lines. We tested the effects of HSP90 inhibitors on cells with disruption of the MIR21 gene, cells incubated with MIR21 inhibitors, and stable cell lines with inducible expression of MIR21. We obtained CCA biopsies from patients, cultured them as organoids (patient-derived organoids). We assessed their architecture, mutation and gene expression patterns, response to compounds in culture, and when grown as subcutaneous xenograft tumors in mice.
Cells with IDH1 and PBRM1 mutations had the highest level of sensitivity to histone deacetylase inhibitors. HSP90 inhibitors were effective in all cell lines, irrespective of mutations. Sensitivity of cells to HSP90 inhibitors correlated inversely with baseline level of MIR21. Disruption of MIR21 increased cell sensitivity to HSP90 inhibitors. CCA cells that expressed transgenic MIR21 were more resistant to HSP90 inhibitors than cells transfected with control vectors; inactivation of MIR21 in these cells restored sensitivity to these agents. MIR21 was shown to target the DnaJ heat shock protein family (Hsp40) member B5 (DNAJB5). Transgenic expression of DNAJB5 in CCA cells that overexpressed MIR21 re-sensitized them to HSP90 inhibitors. Sensitivity of patient-derived organoids to HSP90 inhibitors, in culture and when grown as xenograft tumors in mice, depended on expression of miRNA21.
miRNA21 appears to mediate resistance of CCA cells to HSP90 inhibitors by reducing levels of DNAJB5. HSP90 inhibitors might be developed for the treatment of CCA and miRNA21 might be a marker of sensitivity to these agents.
Abstract Based on the policy document analysis method and a conceptual framework derived from Science and Technology Studies, this paper analyses the construction of institutionally legitimated forms ...of discursive limitation of energy governance in Brazil. The paper analyzes a subset of selected vital policy documents produced by regulatory bodies such as the National Energy Agency (ANEEL) and the Energy Research Office (EPE). As an insight for further research on the governance of energy policy, the paper’s contribution to the debate is to bring to the fore the relevance of recasting the whole process of regulation of distributed energy in terms of an attempt to build a narrative of control over socio-technical innovation with the potential to democratize access to and use of energy services. This policy narrative’s unspoken goal is to retain control of the Brazilian energy transition at the central level.
Resumo Com base no método de análise de documentos de política e a abordagem da teoria dos Estudos da Ciência e a Tecnologia, analisamos neste artigo a construção de formas institucionalmente legitimadas de limitação discursiva da energia distribuída no Brasil. No artigo analisa-se um subconjunto de documentos centrais para a definição da política energética da energia distribuída, entre aqueles produzidos por órgãos reguladores, como a Agência Nacional de Energia Elétrica (ANEEL) e a Agência de Pesquisa Energética (EPE). Como contribuição para pesquisas futuras sobre a governança da política energética trazemos à tona a relevância de reformular todo o processo de regulação da energia distribuída em termos de uma tentativa de construir uma narrativa de controle sobre as inovações técnicas com potencial para democratizar o acesso e uso dos serviços de energia. O objetivo tácito dessa narrativa política é manter o controle e a centralização
Resumen Con base en el método de análisis de documentos de política y el enfoque teórico de los Estudios Sociales de la Ciencia y la Tecnología (STS por el acrónimo en inglés), este artículo analiza la construcción de formas institucionalmente legítimas de normalización discursiva de la energía distribuida en Brasil. El artículo analiza un subconjunto de documentos que se destacan como fundamentales para la definición de la política energética para de energía distribuida, incluidos aquellos elaborados por organismos reguladores como la Agencia Nacional de Energía Eléctrica (ANEEL) y la Agencia de Investigación Energética (EPE). Como contribución a la investigación futura sobre la gobernanza de la política energética, el artículo destaca la relevancia de reformular todo el proceso de regulación de la energía distribuida en términos de un intento de construir una narrativa de control sobre las innovaciones técnicas y su potencial de democratizar el acceso y el uso de los servicios energéticos. El objetivo tácito de esta narrativa política es mantener el control centralizado de la transición energética brasileña.
Nota del editor Lampis, Andrea
Revista colombiana de sociología,
01/2017, Volume:
40, Issue:
1
Journal Article
Peer reviewed
Open access
En el documental La sal de la Tierra, Wim Wenders presenta a Sebastião Salgado con las palabras del epígrafe. Las personas con sus dignidades, diversidades, vidas, aspiraciones, sueños, identidades e ...historias son el centro de lo que vale la pena fotografiar. Cada paisaje, sujeto, horizonte —nos comenta Salgado en el documental— producirá una fotografía diferente, según quien tome la foto, pues la relación entre lo observado, lo vivido y lo rememorado tiene una especificidad y una poética jamás idénticas, que depende del que actúa el dispositivo de remembrar, capturar, reconstruir o reimaginar la memoria. La idea de la resignificación es central en este número 40(1) de la Revista Colombiana de Sociología (rcs)1, así como lo han planteado la editora y los editores invitados de la sección temática (st), al sugerir como eje central para la convocatoria, el título Memorias del presente y del futuro: ¿cómo, para quién, para qué?
Nota del editor Lampis, Andrea
Revista colombiana de sociología,
07/2016, Volume:
39, Issue:
2
Journal Article
Peer reviewed
Open access
Con el número 39.2 del 2016, la RCS incursiona en el campo de los Estudios Sociales de la Ciencia y la Tecnología (ESCT), presentando una sección temática (ST) amplia y orgánica, la cual, por la ...amplitud de los temas abarcados y el éxito de la convocatoria, tiene prácticamente el carácter de un libro de investigación publicado bajo forma de artículos indexados. Mucho del éxito de la convocatoria acerca de "qué ciencia y qué tecnología para cuál sociedad" se debe a nuestra editora invitada, la profesora Olga Restrepo, y a nuestro editor invitado, el profesor Yuri Jack Gómez, quienes han sabido tejer y ensamblar a lo largo de años el posicionamiento de este eje fundamental en el marco de los estudios sociológicos contemporáneos
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