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Author Vershkov, D.; Benvenisty, N.
Title Human pluripotent stem cells in modeling human disorders: the case of fragile X syndrome Type Journal Article
Year 2017 Publication Regenerative Medicine Abbreviated Journal Regen Med
Volume 12 Issue 1 Pages 53-68
Keywords disease modeling; drug discovery; embryonic stem cells; fragile X syndrome; human pluripotent stem cells; neural differentiation
Abstract Human pluripotent stem cells (PSCs) generated from affected blastocysts or from patient-derived somatic cells are an emerging platform for disease modeling and drug discovery. Fragile X syndrome (FXS), the leading cause of inherited intellectual disability, was one of the first disorders modeled in both embryonic stem cells and induced PCSs and can serve as an exemplary case for the utilization of human PSCs in the study of human diseases. Over the past decade, FXS-PSCs have been used to address the fundamental questions regarding the pathophysiology of FXS. In this review we summarize the methodologies for generation of FXS-PSCs, discuss their advantages and disadvantages compared with existing modeling systems and describe their utilization in the study of FXS pathogenesis and in the development of targeted treatment.
Address The Azrieli Center for Stem Cells & Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel
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ISSN (down) 1746-0751 ISBN Medium
Area Expedition Conference
Notes PMID:27900874 Approved no
Call Number ref @ user @ Serial 95909
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Author Goncalves, D.P.N.; Rodriguez, R.D.; Kurth, T.; Bray, L.J.; Binner, M.; Jungnickel, C.; Gur, F.N.; Poser, S.W.; Schmidt, T.L.; Zahn, D.R.T.; Androutsellis-Theotokis, A.; Schlierf, M.; Werner, C.
Title Enhanced targeting of invasive glioblastoma cells by peptide-functionalized gold nanorods in hydrogel-based 3D cultures Type Journal Article
Year 2017 Publication Acta Biomaterialia Abbreviated Journal Acta Biomater
Volume 58 Issue Pages 12-25
Keywords 3D culture; Cancer stem cells; Glioblastoma Multiforme; Gold nanorods; Photothermolysis
Abstract Cancer stem cells (CSCs) are responsible for drug resistance, tumor recurrence, and metastasis in several cancer types, making their eradication a primary objective in cancer therapy. Glioblastoma Multiforme (GBM) tumors are usually composed of a highly infiltrating CSC subpopulation, which has Nestin as a putative marker. Since the majority of these infiltrating cells are able to elude conventional therapies, we have developed gold nanorods (AuNRs) functionalized with an engineered peptide capable of specific recognition and selective eradication of Nestin positive infiltrating GBM-CSCs. These AuNRs generate heat when irradiated by a near-infrared laser, and cause localized cell damage. Nanoparticle internalization assays performed with GBM-CSCs or Nestin negative cells cultured as two-dimensional (2D) monolayers or embedded in three-dimensional (3D) biodegradable-hydrogels of tunable mechanical properties, revealed that the AuNRs were mainly internalized by GBM-CSCs, and not by Nestin negative cells. The AuNRs were taken up via energy-dependent and caveolae-mediated endocytic mechanisms, and were localized inside endosomes. Photothermal treatments resulted in the selective elimination of GBM-CSCs through cell apoptosis, while Nestin negative cells remained viable. Results also indicated that GBM-CSCs embedded in hydrogels were more resistant to AuNR photothermal treatments than when cultured as 2D monolayers. In summary, the combination of our engineered AuNRs with our tunable hydrogel system has shown the potential to provide an in vitro platform for the evaluation and screening of AuNR-based cancer therapeutics, leading to a substantial advancement in the application of AuNRs for targeted GBM-CSC therapy. STATEMENT OF SIGNIFICANCE: There is an urgent need for reliable and efficient therapies for the treatment of Glioblastoma Multiforme (GBM), which is currently an untreatable brain tumor form with a very poor patient survival rate. GBM tumors are mostly comprised of cancer stem cells (CSCs), which are responsible for tumor reoccurrence and therapy resistance. We have developed gold nanorods functionalized with an engineered peptide capable of selective recognition and eradication of GBM-CSCs via heat generation by nanorods upon NIR irradiation. An in vitro evaluation of nanorod therapeutic activities was performed in 3D synthetic-biodegradable hydrogel models with distinct biomechanical cues, and compared to 2D cultures. Results indicated that cells cultured in 3D were more resistant to photothermolysis than in 2D systems.
Address Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Strasse 6, 01069 Dresden, Germany
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ISSN (down) 1742-7061 ISBN Medium
Area Expedition Conference
Notes PMID:28576716 Approved no
Call Number ref @ user @ Serial 96583
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Author Safon, C.; Keene, D.; Guevara, W.J.U.; Kiani, S.; Herkert, D.; Munoz, E.E.; Perez-Escamilla, R.
Title Determinants of perceived insufficient milk among new mothers in Leon, Nicaragua Type Journal Article
Year 2017 Publication Maternal & Child Nutrition Abbreviated Journal Matern Child Nutr
Volume 13 Issue 3 Pages
Keywords Baby-friendly hospital initiative; breastfeeding; breastfeeding promotion; breastfeeding support; perceived insufficient milk; qualitative methods
Abstract Breastfeeding has been shown to improve maternal and child health. In Nicaragua, the primary risk of death and disability-adjusted life years among children under 5 years of age is suboptimal breastfeeding. Although the Nicaraguan Ministry of Health promotes exclusive breastfeeding from within the first half hour through the first 6 months of life, less than a third of children in the country under 6 months of age are exclusively breastfed. As part of a larger, mixed-methods study, 21 semi-structured, in-depth interviews were conducted with new mothers recruited from three primary health centers between June and August 2015 in order to identify the social, cultural, and structural factors that contribute to infant feeding practices and the discrepancy between recommendations and practices among mothers who delivered at an urban public hospital in Leon, Nicaragua. Audio recordings were transcribed verbatim, and interview transcripts were coded and analyzed by a three-member team using a grounded theory approach. Findings highlight a widespread perception of insufficient milk among mothers that influenced early cessation of exclusive breastfeeding and other infant feeding practices. This perception stemmed from anxiety about meeting infant nutritional needs and infant satiety, anxiety about maternal nutrition, advice from and role modeling of family members about mixed feeding, and perceived infant feeding norms. Results suggest that support modeled after the 10 steps of the Baby-friendly Hospital Initiative as well as strengthened policy-level support are needed. Community interventions that address cultural and structural barriers to improve breastfeeding practices may also help to increase breastfeeding rates.
Address Yale School of Public Health, New Haven, Connecticut, USA
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ISSN (down) 1740-8695 ISBN Medium
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Notes PMID:27650889 Approved no
Call Number ref @ user @ Serial 97340
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Author Foro Arnalot, P.; Pera, O.; Rodriguez, N.; Sanz, X.; Reig, A.; Membrive, I.; Ortiz, A.; Granados, R.; Algara, M.
Title Influence of incidental radiation dose in the subventricular zone on survival in patients with glioblastoma multiforme treated with surgery, radiotherapy, and temozolomide Type Journal Article
Year 2017 Publication Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico Abbreviated Journal Clin Transl Oncol
Volume Issue Pages
Keywords Glioblastoma; Radiotherapy; Subventricular zone
Abstract PURPOSE: To determine if there is an association between the incidental radiation dose to the subventricular zone and survival in patients with glioblastoma multiforme treated with surgery, radiotherapy and temozolomide. METHODS AND MATERIALS: Sixty-five patients, treated between 2006 and 2015, were included in this retrospective study. The doses (75th percentile; p75) administered to the ipsilateral, contralateral and bilateral subventricular zone were compared to overall survival and progression-free survival using Cox proportional hazards models. Covariates included: age, sex, surgery, tumor location, and concomitant and adjuvant temozolomide. RESULTS: Median progression-free survival and overall survival were 11.5 +/- 9.96 and 18.8 +/- 18.5 months, respectively. The p75 doses to the ipsilateral, contralateral and bilateral subventrivular zone were, respectively, 57.30, 48.8, and 52.7 Gy. Patients who received a dose >/=48.8 Gy in the contralateral subventricular zone had better progression-free survival than those who received lower doses (HR 0.46; 95% CI 0.23-0.91 P = 0.028). This association was not found for overall survival (HR 0.60; 95% CI 0.30-1.22 P = 0.16). Administration of adjuvant temozolomide was significantly associated with improved progression-free survival (HR 0.19; 95% CI 0.09-0.41 P < 0.0001) and overall survival (HR 0.11; 95% CI 0.05-0.24 P = 0.001). In the subgroup of 46 patients whose O6-methylguanine-DNA methyltransferase gene promoter status was known, the methylation had no effect on either progression-free survival (P = 0.491) or overall survival (P = 0.203). CONCLUSION: High-dose radiation in the contralateral subventricular zone was associated with a significant improvement in progression-free survival but not overall survival in patients treated for glioblastoma multiforme.
Address Universitat Pompeu Fabra, Barcelona, Spain
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ISSN (down) 1699-048X ISBN Medium
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Notes PMID:28389881 Approved no
Call Number ref @ user @ Serial 96597
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Author Glaser, T.; Han, I.; Wu, L.; Zeng, X.
Title Targeted Nanotechnology in Glioblastoma Multiforme Type Journal Article
Year 2017 Publication Frontiers in Pharmacology Abbreviated Journal Front Pharmacol
Volume 8 Issue Pages 166
Keywords blood-brain barrier; cancer stem cell; glioma; nanomedicine; nanotechnology; targeted therapy
Abstract Gliomas, and in particular glioblastoma multiforme, are aggressive brain tumors characterized by a poor prognosis and high rates of recurrence. Current treatment strategies are based on open surgery, chemotherapy (temozolomide) and radiotherapy. However, none of these treatments, alone or in combination, are considered effective in managing this devastating disease, resulting in a median survival time of less than 15 months. The efficiency of chemotherapy is mainly compromised by the blood-brain barrier (BBB) that selectively inhibits drugs from infiltrating into the tumor mass. Cancer stem cells (CSCs), with their unique biology and their resistance to both radio- and chemotherapy, compound tumor aggressiveness and increase the chances of treatment failure. Therefore, more effective targeted therapeutic regimens are urgently required. In this article, some well-recognized biological features and biomarkers of this specific subgroup of tumor cells are profiled and new strategies and technologies in nanomedicine that explicitly target CSCs, after circumventing the BBB, are detailed. Major achievements in the development of nanotherapies, such as organic poly(propylene glycol) and poly(ethylene glycol) or inorganic (iron and gold) nanoparticles that can be conjugated to metal ions, liposomes, dendrimers and polymeric micelles, form the main scope of this summary. Moreover, novel biological strategies focused on manipulating gene expression (small interfering RNA and clustered regularly interspaced short palindromic repeats [CRISPR]/CRISPR associated protein 9 [Cas 9] technologies) for cancer therapy are also analyzed. The aim of this review is to analyze the gap between CSC biology and the development of targeted therapies. A better understanding of CSC properties could result in the development of precise nanotherapies to fulfill unmet clinical needs.
Address Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen UniversityGuangzhou, China
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) 1663-9812 ISBN Medium
Area Expedition Conference
Notes PMID:28408882 Approved no
Call Number ref @ user @ Serial 96596
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