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Author Canario Guzman, J.A.; Espinal, R.; Baez, J.; Melgen, R.E.; Rosario, P.A.P.; Mendoza, E.R.
Title (up) Ethical challenges for international collaborative research partnerships in the context of the Zika outbreak in the Dominican Republic: a qualitative case study Type Journal Article
Year 2017 Publication Health Research Policy and Systems Abbreviated Journal Health Res Policy Syst
Volume 15 Issue 1 Pages 82
Keywords Capacity-building; Caribbean region; Developing countries; Disease outbreaks; Dominican Republic; Health equity; Health research systems; Research ethics; Research networks; Zika virus
Abstract BACKGROUND: The establishment of international collaborative research partnerships in times of infectious disease outbreaks of international importance has been considered an ethical imperative. Frail health research systems in low- and middle-income countries can be an obstacle to achieve the goal of knowledge generation and the search for health equity before, during and after infectious disease outbreaks. METHODS: A qualitative case study was conducted to identify the challenges and opportunities facing the Dominican Republic with regards to developing international collaborative research partnerships in the context of the Zika outbreak and its ethical implications. Researchers conducted 34 interviews (n = 30 individual; n = 4 group) with 39 participants (n = 23 males; n = 16 females) representing the government, universities, international donor agencies, non-governmental organisations, community-based organisations and medical societies, in two metropolitan cities. RESULTS: Five international collaborative research projects related to the Zika virus were identified. Major ethical challenges were linked to the governance of health research, training of human resources, the institutionalisation of scientific activity, access to research funds and cultural aspects. Capacity-building was not necessarily a component of some partnership agreements. With few exceptions, local researchers were merely participating in data collection and less on defining the problem. Opportunities for collaborative work included the possibility of participation in international research consortiums through calls for proposals. CONCLUSIONS: The Dominican government and research stakeholders can contribute to the international response to the Zika virus through active participation in international collaborative research partnerships; however, public recognition of the need to embrace health research as part of public policy efforts is warranted. A working group led by the government and formed by national and international research stakeholders will be key to identify ways in which the country could respond to the ethical demand of generating new knowledge in times of outbreaks.
Address Centro Nacional de Investigaciones en Salud Materno Infantil Dr. Hugo Mendoza (CENISMI), Centro Los Heroes, Santo Domingo, Republica Dominicana
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 1478-4505 ISBN Medium
Area Expedition Conference
Notes PMID:28946911 Approved no
Call Number ref @ user @ Serial 97627
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Author Emery, I.F.; Gopalan, A.; Wood, S.; Chow, K.-H.; Battelli, C.; George, J.; Blaszyk, H.; Florman, J.; Yun, K.
Title (up) Expression and function of ABCG2 and XIAP in glioblastomas Type Journal Article
Year 2017 Publication Journal of Neuro-Oncology Abbreviated Journal J Neurooncol
Volume 133 Issue 1 Pages 47-57
Keywords Abcg2; Glioblastoma; Glioma stem cells; Ko143; Xiap
Abstract Despite multimodal treatment that includes surgery, radiation and chemotherapy, virtually all glioblastomas (GBM) recur, indicating that these interventions are insufficient to eradicate all malignant cells. To identify potential new therapeutic targets in GBMs, we examined the expression and function of proteins that are associated with therapy resistance and cancer cell survival. We measured the expression of eight such proteins in 50 GBM samples by immunohistochemistry and analyzed patient survival. We report that GBM patients with high expression of ABCG2 (also called BCRP) or XIAP at the protein level had worse survival than those with low expression. The adjusted hazard ratio for ABCG2 was 2.35 and for XIAP was 2.65. Since glioma stem cells (GSCs) have been shown to be more resistant than bulk tumor cells to anti-cancer therapies and to express high levels of these proteins, we also sought to determine if ABCG2 and XIAP have functional roles in GSCs. We used small molecule inhibitors to treat patient-derived GBM tumorspheres in vitro and observed that inhibitors of ABCG2, Ko143 and fumitremorgin, significantly reduced self-renewal. These results suggest that ABCG2 and XIAP proteins may be useful indicators of patient survival and that inhibition of ABCG2 may be a promising therapeutic strategy in GBMs.
Address Peak Center for Brain and Pituitary Tumors, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA. kyun@houstonmethodist.org
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 0167-594X ISBN Medium
Area Expedition Conference
Notes PMID:28432589 Approved no
Call Number ref @ user @ Serial 96591
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Author Rosager, A.M.; Sorensen, M.D.; Dahlrot, R.H.; Boldt, H.B.; Hansen, S.; Lathia, J.D.; Kristensen, B.W.
Title (up) Expression and prognostic value of JAM-A in gliomas Type Journal Article
Year 2017 Publication Journal of Neuro-Oncology Abbreviated Journal J Neurooncol
Volume Issue Pages
Keywords Astrocytic brain tumors; Glioma; Junctional adhesion molecule-A; Prognosis; Tumor stem cell
Abstract Gliomas are among the most lethal cancers, being highly resistant to both chemo- and radiotherapy. The expression of junctional adhesion molecule-A (JAM-A) was recently identified on the surface of stem cell-like brain tumor-initiating cells and suggested to function as a unique glioblastoma niche adhesion factor influencing the tumorigenic potential of brain tumor-initiating cells. We have recently identified high JAM-A expression to be associated with poor outcome in glioblastomas, and our aim was to further investigate the expression of JAM-A in gliomas focusing especially on the prognostic value in WHO grade II and III gliomas. JAM-A protein expression was evaluated by immunohistochemistry and advanced quantitative image analysis with continuous estimates of staining intensity. The JAM-A antibody stained tumor cell membranes and cytoplasm to various extent in different glioma subtypes, and the intensity was higher in glioblastomas than low-grade gliomas. We could not detect an association with overall survival in patients with grade II and III tumors. Double-immunofluorescence stainings in glioblastomas revealed co-expression of JAM-A with CD133, SOX2, nestin, and GFAP in tumor cells as well as some co-expression with the microglial/macrophage marker IBA-1. In conclusion, JAM-A expression was higher in glioblastomas compared to low-grade gliomas and co-localized with recognized stem cell markers suggesting an association of JAM-A with glioma aggressiveness. No significant association between JAM-A expression and overall survival was found in grade II and III gliomas. Further research is needed to determine the function and clinical impact of JAM-A in gliomas.
Address Department of Clinical Research, University of Southern Denmark, Winslowparken 19, 3rd floor, 5000, Odense, Denmark
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 0167-594X ISBN Medium
Area Expedition Conference
Notes PMID:28677106 Approved no
Call Number ref @ user @ Serial 96579
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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.
Title (up) 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 1932-6203 ISBN Medium
Area Expedition Conference
Notes PMID:28241049 Approved no
Call Number ref @ user @ Serial 96604
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Author de Sousa, J.F.; Torrieri, R.; Serafim, R.B.; Di Cristofaro, L.F.M.; Escanfella, F.D.; Ribeiro, R.; Zanette, D.L.; Paco-Larson, M.L.; da Silva, W.A.J.; Tirapelli, D.P. da C.; Neder, L.; Carlotti, C.G.J.; Valente, V.
Title (up) Expression signatures of DNA repair genes correlate with survival prognosis of astrocytoma patients Type Journal Article
Year 2017 Publication Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine Abbreviated Journal Tumour Biol
Volume 39 Issue 4 Pages 1010428317694552
Keywords Apoptosis; Astrocytoma/genetics/metabolism/*mortality; Brain Neoplasms/genetics/metabolism/*mortality; Cell Cycle; Cell Line, Tumor; *DNA Repair; DNA Repair Enzymes/genetics/metabolism; Exodeoxyribonucleases/genetics/metabolism; Gene Expression; Humans; Kaplan-Meier Estimate; N-Glycosyl Hydrolases/genetics/metabolism; Prognosis; DNA repair; astrocytoma; genomic instability; glioblastoma; tumor progression
Abstract Astrocytomas are the most common primary brain tumors. They are very resistant to therapies and usually progress rapidly to high-grade lesions. Here, we investigated the potential role of DNA repair genes in astrocytoma progression and resistance. To this aim, we performed a polymerase chain reaction array-based analysis focused on DNA repair genes and searched for correlations between expression patters and survival prognoses. We found 19 genes significantly altered. Combining these genes in all possible arrangements, we found 421 expression signatures strongly associated with poor survival. Importantly, five genes (DDB2, EXO1, NEIL3, BRCA2, and BRIP1) were independently correlated with worse prognoses, revealing single-gene signatures. Moreover, silencing of EXO1, which is remarkably overexpressed, promoted faster restoration of double-strand breaks, while NEIL3 knockdown, also highly overexpressed, caused an increment in DNA damage and cell death after irradiation of glioblastoma cells. These results disclose the importance of DNA repair pathways for the maintenance of genomic stability of high-grade astrocytomas and suggest that EXO1 and NEIL3 overexpression confers more efficiency for double-strand break repair and resistance to reactive oxygen species, respectively. Thereby, we highlight these two genes as potentially related with tumor aggressiveness and promising candidates as novel therapeutic targets.
Address 7 Center for Integrative Systems Biology (CISBi), NAP/USP, Ribeirao Preto, Brazil
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 1010-4283 ISBN Medium
Area Expedition Conference
Notes PMID:28378638 Approved no
Call Number ref @ user @ Serial 96598
Permanent link to this record