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Author (down) Yan, H.; Romero-Lopez, M.; Benitez, L.I.; Di, K.; Frieboes, H.B.; Hughes, C.C.W.; Bota, D.A.; Lowengrub, J.S.
Title 3D Mathematical Modeling of Glioblastoma Suggests That Transdifferentiated Vascular Endothelial Cells Mediate Resistance to Current Standard-of-Care Therapy Type Journal Article
Year 2017 Publication Cancer Research Abbreviated Journal Cancer Res
Volume 77 Issue 15 Pages 4171-4184
Keywords Brain Neoplasms/*pathology; Cell Transdifferentiation/physiology; Endothelial Cells/*pathology; Glioblastoma/*pathology; Humans; *Models, Theoretical; Neoplastic Stem Cells/*pathology
Abstract Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, cross-talk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Furthermore, GSC also transdifferentiate into bona fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional antiangiogenic therapies. Here we use three-dimensional mathematical modeling to investigate GBM progression and response to therapy. The model predicted that GSCs drive invasive fingering and that GEC spontaneously form a network within the hypoxic core, consistent with published experimental findings. Standard-of-care treatments using DNA-targeted therapy (radiation/chemo) together with antiangiogenic therapies reduced GBM tumor size but increased invasiveness. Anti-GEC treatments blocked the GEC support of GSCs and reduced tumor size but led to increased invasiveness. Anti-GSC therapies that promote differentiation or disturb the stem cell niche effectively reduced tumor invasiveness and size, but were ultimately limited in reducing tumor size because GECs maintain GSCs. Our study suggests that a combinatorial regimen targeting the vasculature, GSCs, and GECs, using drugs already approved by the FDA, can reduce both tumor size and invasiveness and could lead to tumor eradication. Cancer Res; 77(15); 4171-84. (c)2017 AACR.
Address Center for Complex Biological Systems, University of California, Irvine, California
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 0008-5472 ISBN Medium
Area Expedition Conference
Notes PMID:28536277 Approved no
Call Number ref @ user @ Serial 96585
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Author (down) Voss, D.M.; Spina, R.; Carter, D.L.; Lim, K.S.; Jeffery, C.J.; Bar, E.E.
Title Disruption of the monocarboxylate transporter-4-basigin interaction inhibits the hypoxic response, proliferation, and tumor progression Type Journal Article
Year 2017 Publication Scientific Reports Abbreviated Journal Sci Rep
Volume 7 Issue 1 Pages 4292
Keywords
Abstract We have previously shown that glioblastoma stem cells (GSCs) are enriched in the hypoxic tumor microenvironment, and that monocarboxylate transporter-4 (MCT4) is critical for mediating GSC signaling in hypoxia. Basigin is involved in many physiological functions during early stages of development and in cancer and is required for functional plasma membrane expression of MCT4. We sought to determine if disruption of the MCT-Basigin interaction may be achieved with a small molecule. Using a cell-based drug-screening assay, we identified Acriflavine (ACF), a small molecule that inhibits the binding between Basigin and MCT4. Surface plasmon resonance and cellular thermal-shift-assays confirmed ACF binding to basigin in vitro and in live glioblastoma cells, respectively. ACF significantly inhibited growth and self-renewal potential of several glioblastoma neurosphere lines in vitro, and this activity was further augmented by hypoxia. Finally, treatment of mice bearing GSC-derived xenografts resulted in significant inhibition of tumor progression in early and late-stage disease. ACF treatment inhibited intratumoral expression of VEGF and tumor vascularization. Our work serves as a proof-of-concept as it shows, for the first time, that disruption of MCT binding to their chaperon, Basigin, may be an effective approach to target GSC and to inhibit angiogenesis and tumor progression.
Address Department of Neurological Surgery, Case Western Reserve University School of Medicine and The Case Comprehensive Cancer Center, Cleveland, OH, USA. eli.bar@case.edu
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 2045-2322 ISBN Medium
Area Expedition Conference
Notes PMID:28655889 Approved no
Call Number ref @ user @ Serial 96580
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Author (down) Villalobos, A.M.; Barraza, F.; Jorquera, H.; Schauer, J.J.
Title Wood burning pollution in southern Chile: PM2.5 source apportionment using CMB and molecular markers Type Journal Article
Year 2017 Publication Environmental Pollution (Barking, Essex : 1987) Abbreviated Journal Environ Pollut
Volume 225 Issue Pages 514-523
Keywords Aerosols/analysis; Air Pollutants/*analysis; Chile; Cities; Coal; Dust; *Environmental Monitoring; Fires; Heating; Nitrates/analysis; Particulate Matter/*analysis; Seasons; Smoke; Sulfates/analysis; Wood/chemistry; Cmb-Mm; Fuel poverty; Source apportionment; Southern Chile; Sustainable urban development; Wood burning
Abstract Temuco is a mid-size city representative of severe wood smoke pollution in southern Chile; i.e., ambient 24-h PM2.5 concentrations have exceeded 150 mug/m3 in the winter season and the top concentration reached 372 mug/m3 in 2010. Annual mean concentrations have decreased but are still above 30 mug/m3. For the very first time, a molecular marker source apportionment of ambient organic carbon (OC) and PM2.5 was conducted in Temuco. Primary resolved sources for PM2.5 were wood smoke (37.5%), coal combustion (4.4%), diesel vehicles (3.3%), dust (2.2%) and vegetative detritus (0.7%). Secondary inorganic PM2.5 (sulfates, nitrates and ammonium) contributed 4.8% and unresolved organic aerosols (generated from volatile emissions from incomplete wood combustion), including secondary organic aerosols, contributed 47.1%. Adding the contributions of unresolved organic aerosols to those from primary wood smoke implies that wood burning is responsible for 84.6% of the ambient PM2.5 in Temuco. This predominance of wood smoke is ultimately due to widespread poverty and a lack of efficient household heating methods. The government has been implementing emission abatement policies but achieving compliance with ambient air quality standards for PM2.5 in southern Chile remains a challenge.
Address Environmental Chemistry and Technology Program, University of Wisconsin-Madison, 660 North Park Street, Madison, WI 53706, USA
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 0269-7491 ISBN Medium
Area Expedition Conference
Notes PMID:28318790 Approved no
Call Number ref @ user @ Serial 97509
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Author (down) 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 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 (down) Vidaurre, T.; Santos, C.; Gomez, H.; Sarria, G.; Amorin, E.; Lopez, M.; Regalado, R.; Manrique, J.; Tarco, D.; Ayestas, C.; Calderon, M.; Mas, L.; Neciosup, S.; Salazar, M.; Chavez, J.C.; Ubillus, M.; Limache, A.; Ubillus, J.C.; Navarro, J.; Sarwal, K.; Sutcliffe, S.; Gutierrez-Aguado, A.; Silva, M.; Mena, A.; Guillen, M.E.; Castaneda, C.; Abugattas, J.
Title The implementation of the Plan Esperanza and response to the imPACT Review Type Journal Article
Year 2017 Publication The Lancet. Oncology Abbreviated Journal Lancet Oncol
Volume 18 Issue 10 Pages e595-e606
Keywords Delivery of Health Care/organization & administration; Developing Countries; Early Detection of Cancer/*economics; Female; Health Care Costs; *Health Expenditures; Health Planning/*organization & administration; Humans; Male; Needs Assessment; Peru; Poverty; Preventive Medicine/*organization & administration; Risk Assessment
Abstract Following the implementation of the National Cancer Prevention and Control Results-based Budget Programme (PpR Cancer-024) in 2011, the Peruvian Government approved the Plan Esperanza-a population-based national cancer control plan-in 2012. Legislation that ensured full government-supported funding for people who were otherwise unable to access or afford care and treatment accompanied the Plan. In 2013, the Ministry of Health requested an integrated mission of the Programme of Action for Cancer Therapy (imPACT) report to strengthen cancer control in Peru. The imPACT Review, which was executed in 2014, assessed Peru's achievements in cancer control, and areas for improvement, including cancer control planning, further development of population-based cancer registration, increased prevention, early diagnosis, treatment and palliative care, and the engagement and participation of civil society in the health-care system. This Series paper gives a brief history of the development of the Plan Esperanza, describes the innovative funding model that supports it, and summarises how funds are disseminated on the basis of disease, geography, and demographics. An overview of the imPACT Review, and the government's response in the context of the Plan Esperanza, is provided. The development and execution of the Plan Esperanza and the execution of and response to the imPACT Review demonstrates the Peruvian Government's commitment to fighting cancer across the country, including in remote and urban areas.
Address National Institute of Neoplastic Diseases, Lima, Peru
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 1470-2045 ISBN Medium
Area Expedition Conference
Notes PMID:28971826 Approved no
Call Number ref @ user @ Serial 97626
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