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Author Mercatelli, N.; Galardi, S.; Ciafre, S.A. url  doi
openurl 
  Title MicroRNAs as Multifaceted Players in Glioblastoma Multiforme Type Journal Article
  Year 2017 Publication International Review of Cell and Molecular Biology Abbreviated Journal Int Rev Cell Mol Biol  
  Volume 333 Issue Pages 269-323  
  Keywords Biomarker; Cancer stem cells; Glioblastoma; MicroRNAs; Microenvironment; OncomomiRs; Therapy; Tumor suppressors  
  Abstract Glioblastoma multiforme (GBM) is the most common and inevitably lethal primary brain tumor, with a median survival rate of only 15 months from diagnosis. The current standard treatment involves maximal surgical resection flanked by radiotherapy and chemotherapy with the alkylating agent temozolomide. However, even such aggressive treatment is never curative, and recurrent tumors always arise, commonly in more aggressive, chemo- and radio-resistant forms, leading to untreatable and deadly tumors. MicroRNAs, recognized major players in cancer, are deeply involved in GBM, as shown by more than a decade of studies. In this review, we revise the main milestones of MicroRNA studies in GBM, and the latest relevant discoveries in this field. Examples are given of MicroRNAs working as “oncomiRs” or tumor suppressors, with specific connections with GBM clinical subtypes, patients' survival, and resistance to therapies. As the interaction of GBM cells with the microenvironment was proven as a key determinant of tumor growth, the role of MicroRNAs in GBM microenvironment, tumor angiogenesis, and tumor-secreted microvesicles is also reviewed. Finally, we discuss the latest findings presenting MicroRNAs as possible therapeutic targets for GBM, or their use as circulating biomarkers in diagnosis and prognosis.  
  Address Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy  
  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 (down) 1937-6448 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28729027 Approved no  
  Call Number ref @ user @ Serial 96577  
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Author Pinsky, I.; Noto, A.R.; Botequio de Moraes, M.C.; Lucas Dos Santos, E.; Sparks, R.; O'Brien, K. url  openurl
  Title Alcohol Industry Sponsorship of University Student Sports Clubs in Brazil Type Journal Article
  Year 2017 Publication Journal of Studies on Alcohol and Drugs Abbreviated Journal J Stud Alcohol Drugs  
  Volume 78 Issue 2 Pages 306-312  
  Keywords Alcohol Drinking/*economics; Brazil; Commerce; Humans; Marketing/*economics; Perception; *Sports; Students; *Universities  
  Abstract OBJECTIVE: The university sport environment represents an important target for alcohol industry marketing. This study investigated the nature of relationships between the alcohol industry and university student sports clubs (USSCs). METHOD: Semi-structured interviews were conducted with board members from 60 active USSCs in the city of Sao Paulo, Brazil. Interviews were transcribed and subjected to content analysis using NVivo10. RESULTS: All invited USSCs participated in the study. Most (n = 53; 88%) reported having signed contracts with the alcohol industry (breweries, in every case) to have their sports events and parties sponsored. The most common sponsorship arrangement involved the supply of discounted beer for sport and student events. T-shirts, beer freezers, and stereo systems were also frequently provided by the alcohol industry to support alcohol-related sports events. In addition, the alcohol industry event promoters helped market the events and products. In return, the USSCs agreed to exclusively sell the sponsors' brand of beer and/or order and sell a quota of beer at their events. Forty-nine interviewees (81%) reported agreements with alcohol companies whereby open bars (free alcohol events) would also be provided. Despite reporting a range of alcohol harms, participants did not perceive there to be a high risk of harm from the alcohol sponsorship arrangements. CONCLUSIONS: Most USSCs in Sao Paulo, Brazil, have formalized contracts with the alcohol industry that promote the marketing, sale, and consumption of alcohol at parties and university games. A critical review of the impacts of these practices and university policies on alcohol industry sponsorship that can take account of the role of such arrangements in student drinking is warranted.  
  Address School of Social Sciences, Monash University, Melbourne, Australia  
  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 (down) 1937-1888 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28317512 Approved no  
  Call Number ref @ user @ Serial 97333  
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Author Patino, A.; Alcalde, V.; Gutierrez, C.; Romero, M.G.; Carrillo, A.M.; Vargas, L.E.; Vallejo, C.E.; Zarama, V.; Mora Rodriguez, J.L.; Bustos, Y.; Granada, J.; Aguiar, L.G.; Menendez, S.; Cohen, J.I.; Saavedra, M.A.; Rodriguez, J.M.; Roldan, T.; Arbelaez, C. url  doi
openurl 
  Title Characteristics of Emergency Medicine Residency Programs in Colombia Type Journal Article
  Year 2017 Publication The Western Journal of Emergency Medicine Abbreviated Journal West J Emerg Med  
  Volume 18 Issue 6 Pages 1120-1127  
  Keywords  
  Abstract INTRODUCTION: Emergency medicine (EM) is in different stages of development around the world. Colombia has made significant strides in EM development in the last two decades and recognized it as a medical specialty in 2005. The country now has seven EM residency programs: three in the capital city of Bogota, two in Medellin, one in Manizales, and one in Cali. The seven residency programs are in different stages of maturity, with the oldest founded 20 years ago and two founded in the last two years. The objective of this study was to characterize these seven residency programs. METHODS: We conducted semi-structured interviews with faculty and residents from all the existing programs in 2013-2016. Topics included program characteristics and curricula. RESULTS: Colombian EM residencies are three-year programs, with the exception of one four-year program. Programs accept 3-10 applicants yearly. Only one program has free tuition and the rest charge tuition. The number of EM faculty ranges from 2-15. EM rotation requirements range from 11-33% of total clinical time. One program does not have a pediatric rotation. The other programs require 1-2 months of pediatrics or pediatric EM. Critical care requirements range from 4-7 months. Other common rotations include anesthesia, general surgery, internal medicine, obstetrics, gynecology, orthopedics, ophthalmology, radiology, toxicology, psychiatry, neurology, cardiology, pulmonology, and trauma. All programs offer 4-6 hours of protected didactic time each week. Some programs require Advanced Cardiac Life Support, Pediatric Advanced Life Support and Advanced Trauma Life Support, with some programs providing these trainings in-house or subsidizing the cost. Most programs require one research project for graduation. Resident evaluations consist of written tests and oral exams several times per year. Point-of-care ultrasound training is provided in four of the seven programs. CONCLUSION: As emergency medicine continues to develop in Colombia, more residency programs are expected to emerge. Faculty development and sustainability of academic pursuits will be critically important. In the long term, the specialty will need to move toward certifying board exams and professional development through a national EM organization to promote standardization across programs.  
  Address Harvard Affiliated Emergency Medicine Residency, Massachusetts General Hospital / Brigham and Women's Hospital, Boston, Massachusetts  
  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 (down) 1936-900X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29085546 Approved no  
  Call Number ref @ user @ Serial 97625  
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Author Howard, C.M.; Valluri, J.; Alberico, A.; Julien, T.; Mazagri, R.; Marsh, R.; Alastair, H.; Cortese, A.; Griswold, M.; Wang, W.; Denning, K.; Brown, L.; Claudio, P.P. url  doi
openurl 
  Title Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients Type Journal Article
  Year 2017 Publication Translational Oncology Abbreviated Journal Transl Oncol  
  Volume 10 Issue 2 Pages 241-254  
  Keywords  
  Abstract INTRODUCTION: The prognosis of glioblastoma (GBM) treated with standard-of-care maximal surgical resection and concurrent adjuvant temozolomide (TMZ)/radiotherapy remains very poor (less than 15 months). GBMs have been found to contain a small population of cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. The highly invasive nature of high-grade gliomas and their inherent resistance to therapy lead to very high rates of recurrence. For these reasons, not all patients with similar diagnoses respond to the same chemotherapy, schedule, or dose. Administration of ineffective anticancer therapy is not only costly but more importantly burdens the patient with unnecessary toxicity and selects for the development of resistant cancer cell clones. We have developed a drug response assay (ChemoID) that identifies the most effective chemotherapy against CSCs and bulk of tumor cells from of a panel of potential treatments, offering great promise for individualized cancer management. Providing the treating physician with drug response information on a panel of approved drugs will aid in personalized therapy selections of the most effective chemotherapy for individual patients, thereby improving outcomes. A prospective study was conducted evaluating the use of the ChemoID drug response assay in GBM patients treated with standard of care. METHODS: Forty-one GBM patients (mean age 54 years, 59% male), all eligible for a surgical biopsy, were enrolled in an Institutional Review Board-approved protocol, and fresh tissue samples were collected for drug sensitivity testing. Patients were all treated with standard-of-care TMZ plus radiation with or without maximal surgery, depending on the status of the disease. Patients were prospectively monitored for tumor response, time to recurrence, progression-free survival (PFS), and overall survival (OS). Odds ratio (OR) associations of 12-month recurrence, PFS, and OS outcomes were estimated for CSC, bulk tumor, and combined assay responses for the standard-of-care TMZ treatment; sensitivities/specificities, areas under the curve (AUCs), and risk reclassification components were examined. RESULTS: Median follow-up was 8 months (range 3-49 months). For every 5% increase in in vitro CSC cell kill by TMZ, 12-month patient response (nonrecurrence of cancer) increased two-fold, OR=2.2 (P=.016). Similar but somewhat less supported associations with the bulk tumor test were seen, OR=2.75 (P=.07) for each 5% bulk tumor cell kill by TMZ. Combining CSC and bulk tumor assay results in a single model yielded a statistically supported CSC association, OR=2.36 (P=.036), but a much attenuated remaining bulk tumor association, OR=1.46 (P=.472). AUCs and [sensitivity/specificity] at optimal outpoints (>40% CSC cell kill and >55% bulk tumor cell kill) were AUC=0.989 [sensitivity=100/specificity=97], 0.972 [100/89], and 0.989 [100/97] for the CSC only, bulk tumor only, and combined models, respectively. Risk categorization of patients was improved by 11% when using the CSC test in conjunction with the bulk test (risk reclassification nonevent net reclassification improvement [NRI] and overall NRI=0.111, P=.030). Median recurrence time was 20 months for patients with a positive (>40% cell kill) CSC test versus only 3 months for those with a negative CSC test, whereas median recurrence time was 13 months versus 4 months for patients with a positive (>55% cell kill) bulk test versus negative. Similar favorable results for the CSC test were observed for PFS and OS outcomes. Panel results across 14 potential other treatments indicated that 34/41 (83%) potentially more optimal alternative therapies may have been chosen using CSC results, whereas 27/41 (66%) alternative therapies may have been chosen using bulk tumor results. CONCLUSIONS: The ChemoID CSC drug response assay has the potential to increase the accuracy of bulk tumor assays to help guide individualized chemotherapy choices. GBM cancer recurrence may occur quickly if the CSC test has a low in vitro cell kill rate even if the bulk tumor test cell kill rate is high.  
  Address Department of BioMolecular Sciences, National Center for Natural Products Research, University of Mississippi, University, MS; Department of Radiation Oncology, University of Mississippi Medical Center Cancer Institute, Jackson, MS 39216. Electronic address: pclaudio@olemiss.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 (down) 1936-5233 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28199863 Approved no  
  Call Number ref @ user @ Serial 96608  
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Author Brown, D.V.; Filiz, G.; Daniel, P.M.; Hollande, F.; Dworkin, S.; Amiridis, S.; Kountouri, N.; Ng, W.; Morokoff, A.P.; Mantamadiotis, T. url  doi
openurl 
  Title Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume 12 Issue 2 Pages e0172791  
  Keywords AC133 Antigen/*metabolism; Animals; Antigens, CD44/*metabolism; Basic Helix-Loop-Helix Transcription Factors/metabolism; Biomarkers, Tumor/metabolism; Brain Neoplasms/*metabolism/pathology; Cell Proliferation; Female; Glioblastoma/*metabolism/pathology; Humans; Hypoxia; Mice; Mice, Inbred BALB C; Neoplasm Recurrence, Local; Neoplastic Stem Cells/*metabolism/pathology; Nerve Tissue Proteins/metabolism; Phenotype  
  Abstract Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC). CD133 expression has been used as a marker of GSCs, however recent evidence suggests the relationship between CD133 expression, GSCs and molecular subtype is more complex than initially proposed. The expression of CD133, Olig2 and CD44 was investigated using patient derived glioma stem-like cells (PDGCs) in vitro and in vivo. Different PDGCs exhibited a characteristic equilibrium of distinct CD133+ and CD44+ subpopulations and the influence of environmental factors on the intra-tumor equilibrium of CD133+ and CD44+ cells in PDGCs was also investigated, with hypoxia inducing a CD44+ to CD133+ shift and chemo-radiotherapy inducing a CD133+ to CD44+ shift. These data suggest that surveillance and modulation of intra-tumor heterogeneity using molecular markers at initial surgery and surgery for recurrent GBM may be important for more effective management of GBM.  
  Address Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia  
  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 (down) 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28241049 Approved no  
  Call Number ref @ user @ Serial 96604  
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