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Author Goffart, N.; Lombard, A.; Lallemand, F.; Kroonen, J.; Nassen, J.; Di Valentin, E.; Berendsen, S.; Dedobbeleer, M.; Willems, E.; Robe, P.; Bours, V.; Martin, D.; Martinive, P.; Maquet, P.; Rogister, B.
Title CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone Type Journal Article
Year 2017 Publication Neuro-Oncology Abbreviated Journal Neuro Oncol
Volume 19 Issue 1 Pages 66-77
Keywords Animals; Brain Neoplasms/metabolism/*pathology/radiotherapy; Chemokine CXCL12/*metabolism; Cranial Irradiation/*adverse effects; Gamma Rays/adverse effects; Glioblastoma/metabolism/*pathology/radiotherapy; Humans; Lateral Ventricles/metabolism/*pathology/radiation effects; Mice; Mice, Nude; Neoplastic Stem Cells/metabolism/*pathology/radiation effects; *Radiation Tolerance; Signal Transduction/radiation effects; Tumor Cells, Cultured; Cxcl12; glioblastoma; mesenchymal activation; radioresistance; subventricular zone
Abstract BACKGROUND: Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line, it has recently been demonstrated that GSCs are able to escape the tumor mass and preferentially colonize the adult subventricular zone (SVZ). At a distance from the initial tumor site, these GSCs might therefore represent a high-quality model of clinical resilience to therapy and cancer relapses as they specifically retain tumor-initiating abilities. METHOD: While relying on recent findings that have validated the existence of GSCs in the human SVZ, we questioned the role of the SVZ niche as a potential GSC reservoir involved in therapeutic failure. RESULTS: Our results demonstrate that (i) GSCs located in the SVZ are specifically resistant to radiation in vivo, (ii) these cells display enhanced mesenchymal roots that are known to be associated with cancer radioresistance, (iii) these mesenchymal traits are specifically upregulated by CXCL12 (stromal cell-derived factor-1) both in vitro and in the SVZ environment, (iv) the amount of SVZ-released CXCL12 mediates GBM resistance to radiation in vitro, and (v) interferes with the CXCL12/CXCR4 signalling system, allowing weakening of the tumor mesenchymal roots and radiosensitizing SVZ-nested GBM cells. CONCLUSION: Together, these data provide evidence on how the adult SVZ environment, through the release of CXCL12, supports GBM therapeutic failure and potential tumor relapse.
Address (down) Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liege, Liege, Belgium (N.G., A.L., J.N., M.D., E.W., B.R.); Department of Neurosurgery, CHU and University of Liege, Liege, Belgium (A.L., D.M.); Department of Radiotherapy and Oncology, CHU and University of Liege, Liege, Belgium (F.L., P.M.); Laboratory of Tumor and Development Biology, GIGA-Cancer Research Center, University of Liege, Liege, Belgium (F.L.); Cyclotron Research Centre, University of Liege, Liege, Belgium (F.L.); Human Genetics, CHU and University of Liege, Liege, Belgium (N.G., J.K., V.B.); Department of Neurosurgery, Brain Center Rudolf Magnus Institute of Neurosciences and the T&P Bohnenn Laboratory for Neuro-Oncology University Medical Center, Utrecht, The Netherlands (N.G., J.K., S.B., P.R.); GIGA-Viral Vector Plateform, University of Liege, Liege, Belgium (E.D.V.); Department of Neurology, CHU and University of Liege, Liege, Belgium (P.M., B.R.)
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1522-8517 ISBN Medium
Area Expedition Conference
Notes PMID:27370398 Approved no
Call Number ref @ user @ Serial 96647
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Author Fogel, O.; Richard-Miceli, C.; Tost, J.
Title Epigenetic Changes in Chronic Inflammatory Diseases Type Journal Article
Year 2017 Publication Advances in Protein Chemistry and Structural Biology Abbreviated Journal Adv Protein Chem Struct Biol
Volume 106 Issue Pages 139-189
Keywords Behcet's disease; Crohn's disease; DNA methylation; Ewas; Epigenetics; Histone modifications; Inflammatory bowel disease; Psoriasis; Spondyloarthritis; Ulcerative colitis
Abstract The number of people diagnosed with chronic inflammatory diseases has increased noteworthy in the last 40 years. Spondyloarthritis (SpA), inflammatory bowel diseases (IBD), and psoriasis are the most frequent chronic inflammatory diseases, resulting from a combination of genetic predisposition and environmental factors. Epigenetic modifications include DNA methylation, histone modifications, and small and long noncoding RNAs. They are influenced by environmental exposure, life-style, and aging and have recently been shown to be altered in many complex diseases including inflammatory diseases. While epigenetic modifications have been well characterized in other diseases such as cancer and autoimmune diseases, knowledge on changes in inflammatory diseases is lagging behind with some disease-specific differences. While the DNA methylation profile of different cell types in patients with IBD has been relatively well described, less is known on changes implicated in psoriasis, and no systematic genome-wide studies have so far been performed in SpA. In this chapter, we review in detail the reported changes in patterns of DNA methylation and posttranslational histone modifications in chronic inflammatory diseases highlighting potential connections between disease-associated pathophysiological changes such as the dysbiosis of the microbiome or genetic variations associated with disease susceptibility and the epigenome. We also discuss important parameters of meaningful epigenetic studies such as the use of well defined, disease-relevant cell populations, and elude on the potential future of engineering of the epigenome in inflammatory diseases.
Address (down) Laboratory for Epigenetics and Environment, Centre National de Genotypage, CEA-Institut de Genomique, Evry, France. Electronic address: tost@cng.fr
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1876-1623 ISBN Medium
Area Expedition Conference
Notes PMID:28057210 Approved no
Call Number ref @ user @ Serial 96374
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Author Villagra, P.; Quintana, C.
Title Disaster Governance for Community Resilience in Coastal Towns: Chilean Case Studies Type Journal Article
Year 2017 Publication International Journal of Environmental Research and Public Health Abbreviated Journal Int J Environ Res Public Health
Volume 14 Issue 9 Pages
Keywords community resilience; disaster governance; tsunami
Abstract This study aimed to further our understanding of a characteristic of Community Resilience known as Disaster Governance. Three attributes of Disaster Governance-redundancy, diversity, and overlap-were studied in four coastal towns in southern Chile that are at risk of tsunamis. Overall, we explored how different spatial structures of human settlements influence Disaster Governance. Using the Projective Mapping Technique, the distribution of emergency institutions (N = 32) and uses given to specific sites (e.g., for refuge, sanitary purposes and medical attention) were mapped. Content and GIS analyses (Directional Distribution and Kernel Density Index) were used to explore the dispersion and concentration of institutions and uses in each town. Disaster Governance was found to be highly influenced by decisions taken during regional, urban, and emergency planning. Governance is better in towns of higher order in the communal hierarchical structure. Most of the emergency institutions were found to be located in central and urban areas, which, in turn, assures more redundancy, overlap, and diversity in governance in the event of a tsunami. Lack of flexibility of emergency plans also limits governance in rural and indigenous areas. While the spatial relationships found in this study indicate that urban sectors have better Disaster Governance than rural and indigenous sectors, the influence of resource availability after tsunamis, the role and responsibility of different levels of governments, and the politics of disaster also play an important role in Disaster Governance for determining Community Resilience. These findings shed light on emergency planning and aspects of the Disaster Management cycle.
Address (down) Laboratorio de Paisaje y Resiliencia Urbana, Universidad Austral de Chile, Valdivia 509000, Chile. contacto@pru-lab.cl
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1660-4601 ISBN Medium
Area Expedition Conference
Notes PMID:28906480 Approved no
Call Number ref @ user @ Serial 97628
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Author Nourallah, B.; Digpal, R.; Jena, R.; Watts, C.
Title Irradiating the Subventricular Zone in Glioblastoma Patients: Is there a Case for a Clinical Trial? Type Journal Article
Year 2017 Publication Clinical Oncology (Royal College of Radiologists (Great Britain)) Abbreviated Journal Clin Oncol (R Coll Radiol)
Volume 29 Issue 1 Pages 26-33
Keywords Adult; Brain Neoplasms/*radiotherapy; Glioblastoma/*radiotherapy; Humans; Lateral Ventricles/*radiation effects; Male; Neoplastic Stem Cells/radiation effects; Stem Cell Niche/radiation effects; Cancer stem cells; glioblastoma; neural stem cells; radiotherapy; subventricular zone
Abstract Glioblastoma is the most common and aggressive adult brain tumour. Over the last 10 years it has emerged that the subventricular zone (SVZ), the largest adult neural stem cell niche, has an important role in the disease. Converging evidence has implicated transformation of adult neural stems in gliomagenesis and the permissive stem cell niche in disease recurrence. Concurrently, clinical studies have suggested that SVZ involvement is a negative prognostic marker. It would follow that irradiating the SVZ may improve outcomes in glioblastoma by directly targeting this putative sanctuary site. To investigate this potential strategy, 11 retrospective studies and 1 prospective study examined the relationship between dose to the SVZ and survival outcomes in glioblastoma patients. This review summarises the theoretical underpinning of this strategy, provides a critical evaluation of the existing evidence and discusses the rationale for a clinical trial.
Address (down) John van Geest Centre for Repair, Cambridge, UK; Department of Clinical Neurosciences, Division of Neurosurgery, Addenbrookes Hospital, Cambridge, UK. Electronic address: cw209@cam.ac.uk
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0936-6555 ISBN Medium
Area Expedition Conference
Notes PMID:27729188 Approved no
Call Number ref @ user @ Serial 96633
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Author Herrero, M.; Thornton, P.K.; Power, B.; Bogard, J.R.; Remans, R.; Fritz, S.; Gerber, J.S.; Nelson, G.; See, L.; Waha, K.; Watson, R.A.; West, P.C.; Samberg, L.H.; van de Steeg, J.; Stephenson, E.; van Wijk, M.; Havlik, P.
Title Farming and the geography of nutrient production for human use: a transdisciplinary analysis Type Journal Article
Year 2017 Publication The Lancet. Planetary Health Abbreviated Journal Lancet Planet Health
Volume 1 Issue 1 Pages e33-e42
Keywords
Abstract BACKGROUND: Information about the global structure of agriculture and nutrient production and its diversity is essential to improve present understanding of national food production patterns, agricultural livelihoods, and food chains, and their linkages to land use and their associated ecosystems services. Here we provide a plausible breakdown of global agricultural and nutrient production by farm size, and also study the associations between farm size, agricultural diversity, and nutrient production. This analysis is crucial to design interventions that might be appropriately targeted to promote healthy diets and ecosystems in the face of population growth, urbanisation, and climate change. METHODS: We used existing spatially-explicit global datasets to estimate the production levels of 41 major crops, seven livestock, and 14 aquaculture and fish products. From overall production estimates, we estimated the production of vitamin A, vitamin B12, folate, iron, zinc, calcium, calories, and protein. We also estimated the relative contribution of farms of different sizes to the production of different agricultural commodities and associated nutrients, as well as how the diversity of food production based on the number of different products grown per geographic pixel and distribution of products within this pixel (Shannon diversity index [H]) changes with different farm sizes. FINDINGS: Globally, small and medium farms (</=50 ha) produce 51-77% of nearly all commodities and nutrients examined here. However, important regional differences exist. Large farms (>50 ha) dominate production in North America, South America, and Australia and New Zealand. In these regions, large farms contribute between 75% and 100% of all cereal, livestock, and fruit production, and the pattern is similar for other commodity groups. By contrast, small farms (</=20 ha) produce more than 75% of most food commodities in sub-Saharan Africa, southeast Asia, south Asia, and China. In Europe, west Asia and north Africa, and central America, medium-size farms (20-50 ha) also contribute substantially to the production of most food commodities. Very small farms (</=2 ha) are important and have local significance in sub-Saharan Africa, southeast Asia, and south Asia, where they contribute to about 30% of most food commodities. The majority of vegetables (81%), roots and tubers (72%), pulses (67%), fruits (66%), fish and livestock products (60%), and cereals (56%) are produced in diverse landscapes (H>1.5). Similarly, the majority of global micronutrients (53-81%) and protein (57%) are also produced in more diverse agricultural landscapes (H>1.5). By contrast, the majority of sugar (73%) and oil crops (57%) are produced in less diverse ones (H</=1.5), which also account for the majority of global calorie production (56%). The diversity of agricultural and nutrient production diminishes as farm size increases. However, areas of the world with higher agricultural diversity produce more nutrients, irrespective of farm size. INTERPRETATION: Our results show that farm size and diversity of agricultural production vary substantially across regions and are key structural determinants of food and nutrient production that need to be considered in plans to meet social, economic, and environmental targets. At the global level, both small and large farms have key roles in food and nutrition security. Efforts to maintain production diversity as farm sizes increase seem to be necessary to maintain the production of diverse nutrients and viable, multifunctional, sustainable landscapes. FUNDING: Commonwealth Scientific and Industrial Research Organisation, Bill & Melinda Gates Foundation, CGIAR Research Programs on Climate Change, Agriculture and Food Security and on Agriculture for Nutrition and Health funded by the CGIAR Fund Council, Daniel and Nina Carasso Foundation, European Union, International Fund for Agricultural Development, Australian Research Council, National Science Foundation, Gordon and Betty Moore Foundation, and Joint Programming Initiative on Agriculture, Food Security and Climate Change-Belmont Forum.
Address (down) International Institute for Applied Systems Analysis, Laxenburg, Austria
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2542-5196 ISBN Medium
Area Expedition Conference
Notes PMID:28670647 Approved no
Call Number ref @ user @ Serial 97264
Permanent link to this record