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Author Miranda, A.; Blanco-Prieto, M.; Sousa, J.; Pais, A.; Vitorino, C.
Title Breaching barriers in glioblastoma. Part I: Molecular pathways and novel treatment approaches Type Journal Article
Year 2017 Publication International Journal of Pharmaceutics Abbreviated Journal Int J Pharm
Volume 531 Issue 1 Pages (down) 372-388
Keywords Glioblastoma; Molecular mechanisms; Temozolomide; Therapeutic advances; Therapeutic resistance
Abstract Glioblastoma multiforme (GBM) is the most common primary brain tumour, and the most aggressive in nature. The prognosis for patients with GBM remains poor, with a median survival time of only 1-2 years. The treatment failure relies on the development of resistance by tumour cells and the difficulty of ensuring that drugs effectively cross the dual blood brain barrier/blood brain tumour barrier. The advanced molecular and genetic knowledge has allowed to identify the mechanisms responsible for temozolomide resistance, which represents the standard of care in GBM, along with surgical resection and radiotherapy. Such resistance has motivated the researchers to investigate new avenues for GBM treatment intended to improve patient survival. In this review, we provide an overview of major obstacles to effective treatment of GBM, encompassing biological barriers, cancer stem cells, DNA repair mechanisms, deregulated signalling pathways and autophagy. New insights and potential therapy approaches for GBM are also discussed, emphasizing localized chemotherapy delivered directly to the brain, immunotherapy, gene therapy and nanoparticle-mediated brain drug delivery.
Address Faculty of Pharmacy, University of Coimbra, Portugal; Pharmacometrics Group of the Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, Portugal. Electronic address: csvitorino@ff.uc.pt
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Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0378-5173 ISBN Medium
Area Expedition Conference
Notes PMID:28755993 Approved no
Call Number ref @ user @ Serial 96574
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Author Alshehri, M.M.; Robbins, S.M.; Senger, D.L.
Title The Role of Neurotrophin Signaling in Gliomagenesis: A Focus on the p75 Neurotrophin Receptor (p75NTR/CD271) Type Journal Article
Year 2017 Publication Vitamins and Hormones Abbreviated Journal Vitam Horm
Volume 104 Issue Pages (down) 367-404
Keywords Brain tumor; Cd271; Cancer stem cells; Glioblastoma; Glioma invasion; Nerve growth factor; Neurotrophin; p75(NTR)
Abstract The p75 neurotrophin receptor (p75NTR, a.k.a. CD271), a transmembrane glycoprotein and a member of the tumor necrosis family (TNF) of receptors, was originally identified as a nerve growth factor receptor in the mid-1980s. While p75NTR is recognized to have important roles during neural development, its presence in both neural and nonneural tissues clearly supports the potential to mediate a broad range of functions depending on cellular context. Using an unbiased in vivo selection paradigm for genes underlying the invasive behavior of glioma, a critical characteristic that contributes to poor clinical outcome for glioma patients, we identified p75NTR as a central regulator of glioma invasion. Herein we review the expanding role that p75NTR plays in glioma progression with an emphasis on how p75NTR may contribute to the treatment refractory nature of glioma. Based on the observation that p75NTR is expressed and functional in two critical glioma disease reservoirs, namely, the highly infiltrative cells that evade surgical resection, and the radiation- and chemotherapy-resistant brain tumor-initiating cells (also referred to as brain tumor stem cells), we propose that p75NTR and its myriad of downstream signaling effectors represent rationale therapeutic targets for this devastating disease. Lastly, we provide the provocative hypothesis that, in addition to the well-documented cell autonomous signaling functions, the neurotrophins, and their respective receptors, contribute in a cell nonautonomous manner to drive the complex cellular and molecular composition of the brain tumor microenvironment, an environment that fuels tumorigenesis.
Address Arnie Charbonneau Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address: senger@ucalgary.ca
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Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0083-6729 ISBN Medium
Area Expedition Conference
Notes PMID:28215302 Approved no
Call Number ref @ user @ Serial 96606
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Author Gragnani, A.; de Oliveira, A.F.; Boro, D.; Pham, T.N.; Ferreira, L.M.
Title Response and legislative changes after the Kiss nightclub tragedy in Santa Maria/RS/Brazil: Learning from a large-scale burn disaster Type Journal Article
Year 2017 Publication Burns : Journal of the International Society for Burn Injuries Abbreviated Journal Burns
Volume 43 Issue 2 Pages (down) 343-349
Keywords Brazil/epidemiology; Burns/epidemiology/*prevention & control; Carbon Monoxide Poisoning/epidemiology; Crowding; Disasters/*prevention & control; Fires/legislation & jurisprudence/*prevention & control; Humans; Hydrolases/poisoning; Mass Casualty Incidents/*prevention & control/statistics & numerical data; *Public Policy; Retrospective Studies; Safety/*legislation & jurisprudence; Smoke Inhalation Injury/epidemiology; Burn disaster; Fire prevention and protection; Kiss nightclub; Legislation; Mass casualty incident; Santa Maria
Abstract PURPOSE: A major fire occurred on January 27, 2013, at 02:30 at Kiss nightclub in the city of Santa Maria, State of Rio Grande do Sul, in Southern Brazil. In this retrospective report, we aimed to describe the nightclub fire event, its immediate consequences, and evaluated its impact on legislation. Our objective was to disseminate the lessons we learned from this large-scale nightclub fire disaster. METHODS: We conducted a literature review in PubMed and Lilacs database from 2013 to 2015 related to the nightclub Kiss, Santa Maria, fire, burns, and similar events worldwide over the past 15 years. We searched in the general press and online media information sites, and seeking legislation about this topic at the federal level in Brazil. We reported on the legislation changes that resulted from this nightclub fire. RESULTS: Current federal legislation on fire prevention and the scope of public safety, including night clubs and discos, states is the duty of the state and everyone's responsibility, pursuant to Article 144 of the Federal Constitution of Brazil. Thus, the federal union, individual states and municipalities have the power to legislate on fire prevention, and especially to ensure the security of the population. A state law called “Law Kiss”, was passed in 2014, establishing standards on safety, prevention and protection against fire in buildings and areas of fire risk in the state of Rio Grande do Sul. On a national level, a law of prevention and fire fighting in Brazil was also drafted after the Santa Maria disaster (Law project no. 4923, 2013). Currently, this bill is still awaiting sanction before it can take effect. CONCLUSION: As we push for enactment of the national law of prevention and fire fighting in Brazil, we will continue emphasizing fire prevention, fire protection, fire fighting, means of escape and proper management. All similar events in this and other countries remind us that similar tragedies may occur anywhere, and that the analysis of facts, previous mistakes, during and after the incident are crucial to our understanding, and will help us lessen the chance of future occurrences.
Address Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Brazil
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Language English Summary Language Original Title
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Series Volume Series Issue Edition
ISSN 0305-4179 ISBN Medium
Area Expedition Conference
Notes PMID:27663506 Approved no
Call Number ref @ user @ Serial 97661
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Author Mistry, A.M.; Dewan, M.C.; White-Dzuro, G.A.; Brinson, P.R.; Weaver, K.D.; Thompson, R.C.; Ihrie, R.A.; Chambless, L.B.
Title Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum Type Journal Article
Year 2017 Publication Journal of Neuro-Oncology Abbreviated Journal J Neurooncol
Volume 132 Issue 2 Pages (down) 341-349
Keywords Glioblastoma; Stem cells; Subgranular zone; Subventricular zone; Survival; Ventricular-subventricular zone
Abstract The clinical effect of radiographic contact of glioblastoma (GBM) with neurogenic zones (NZ)-the ventricular-subventricular (VSVZ) and subgranular (SGZ) zones-and the corpus callosum (CC) remains unclear and, in the case of the SGZ, unexplored. We investigated (1) if GBM contact with a NZ correlates with decreased survival; (2) if so, whether this effect is associated with a specific NZ; and (3) if radiographic contact with or invasion of the CC by GBM is associated with decreased survival. We retrospectively identified 207 adult patients who underwent cytoreductive surgery for GBM followed by chemotherapy and/or radiation. Age, preoperative Karnofsky performance status score (KPS), and extent of resection were recorded. Preoperative MRIs were blindly analyzed to calculate tumor volume and assess its contact with VSVZ, SGZ, CC, and cortex. Overall (OS) and progression free (PFS) survivals were calculated and analyzed with multivariate Cox analyses. Among the 207 patients, 111 had GBM contacting VSVZ (VSVZ+GBMs), 23 had SGZ+GBMs, 52 had CC+GBMs, and 164 had cortex+GBMs. VSVZ+, SGZ+, and CC+ GBMs were significantly larger in size relative to their respective non-contacting controls. Multivariate Cox survival analyses revealed GBM contact with the VSVZ, but not SGZ, CC, or cortex, as an independent predictor of lower OS, PFS, and early recurrence. We hypothesize that the VSVZ niche has unique properties that contribute to GBM pathobiology in adults.
Address Department of Neurological Surgery, Vanderbilt University Medical Center, T-4224 Medical Center North, 1161 21st Avenue South, Nashville, TN, 37232-2380, USA
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Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0167-594X ISBN Medium
Area Expedition Conference
Notes PMID:28074322 Approved no
Call Number ref @ user @ Serial 96612
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Author Souza, R.L.; Mugabe, V.A.; Paploski, I.A.D.; Rodrigues, M.S.; Moreira, P.S.D.S.; Nascimento, L.C.J.; Roundy, C.M.; Weaver, S.C.; Reis, M.G.; Kitron, U.; Ribeiro, G.S.
Title Effect of an intervention in storm drains to prevent Aedes aegypti reproduction in Salvador, Brazil Type Journal Article
Year 2017 Publication Parasites & Vectors Abbreviated Journal Parasit Vectors
Volume 10 Issue 1 Pages (down) 328
Keywords Aedes aegypti; Arboviruses; Catch basin; Disease vectors; Entomology; Epidemiology; Insect vectors; Mosquitoes; Storm drain
Abstract BACKGROUND: Aedes aegypti, the principal vector for dengue, chikungunya and Zika viruses, is a synanthropic species that uses stagnant water to complete its reproductive cycle. In urban settings, rainfall water draining structures, such as storm drains, may retain water and serve as a larval development site for Aedes spp. reproduction. Herein, we describe the effect of a community-based intervention on preventing standing water accumulation in storm drains and their consequent infestation by adult and immature Ae. aegypti and other mosquitoes. METHODS: Between April and May of 2016, local residents association of Salvador, Brazil, after being informed of water accumulation and Ae. aegypti infestation in the storm drains in their area, performed an intervention on 52 storm drains. The intervention consisted of placing concrete at the bottom of the storm drains to elevate their base to the level of the outflow tube, avoiding water accumulation, and placement of a metal mesh covering the outflow tube to avoid its clogging with debris. To determine the impact of the intervention, we compared the frequency at which the 52 storm drains contained water, as well as adult and immature mosquitoes using data from two surveys performed before and two surveys performed after the intervention. RESULTS: During the pre-intervention period, water accumulated in 48 (92.3%) of the storm drains, and immature Ae. aegypti were found in 11 (21.2%) and adults in 10 (19.2%). After the intervention, water accumulated in 5 (9.6%) of the storm drains (P < 0.001), none (0.0%) had immatures (P < 0.001), and 3 (5.8%) contained adults (P = 0.039). The total number of Ae. aegypti immatures collected decreased from 109 to 0 (P < 0.001) and adults decreased from 37 to 8 (P = 0.011) after the intervention. Collection of immature and adult non-Aedes mosquitoes (mainly Culex spp.) in the storm drains also decreased after the intervention. CONCLUSION: This study exemplifies how a simple intervention targeting storm drains can result in a major reduction of water retention, and, consequently, impact Ae. aegypti larval populations. Larger and multi-center evaluations are needed to confirm the potential of citywide structural modifications of storm drains to reduce Aedes spp. infestation level.
Address Instituto de Saude Coletiva, Universidade Federal da Bahia, Salvador, Bahia, Brazil. guilherme.ribeiro@bahia.fiocruz.br
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 1756-3305 ISBN Medium
Area Expedition Conference
Notes PMID:28697811 Approved no
Call Number ref @ user @ Serial 97633
Permanent link to this record