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Author Glaser, T.; Han, I.; Wu, L.; Zeng, X. url  doi
openurl 
  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 (up) 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 1663-9812 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28408882 Approved no  
  Call Number ref @ user @ Serial 96596  
Permanent link to this record
 

 
Author Zapotoczna, M.; Forde, E.; Hogan, S.; Humphreys, H.; O'Gara, J.P.; Fitzgerald-Hughes, D.; Devocelle, M.; O'Neill, E. url  doi
openurl 
  Title Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides Type Journal Article
  Year 2017 Publication The Journal of Infectious Diseases Abbreviated Journal J Infect Dis  
  Volume 215 Issue 6 Pages 975-983  
  Keywords Animals; Anti-Bacterial Agents/*pharmacology; Biofilms/*drug effects; Catheter-Related Infections/*drug therapy; Cytokines/blood; Disease Models, Animal; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects; Microbial Sensitivity Tests; Peptides/*pharmacology; Peptides, Cyclic/pharmacology; Rats; Rats, Sprague-Dawley; Staphylococcal Infections/*drug therapy; Vancomycin/administration & dosage; *Staphylococcus aureus; *antimicrobial peptides (AMPs); *biofilm; *catheter lock solution (CLS)  
  Abstract (up) Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections.  
  Address Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland  
  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 0022-1899 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28453851 Approved no  
  Call Number ref @ user @ Serial 99511  
Permanent link to this record
 

 
Author Zapotoczna, M.; Forde, E.; Hogan, S.; Humphreys, H.; O'Gara, J.P.; Fitzgerald-Hughes, D.; Devocelle, M.; O'Neill, E. url  doi
openurl 
  Title Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides Type Journal Article
  Year 2017 Publication The Journal of Infectious Diseases Abbreviated Journal J Infect Dis  
  Volume 215 Issue 6 Pages 975-983  
  Keywords Animals; Anti-Bacterial Agents/*pharmacology; Biofilms/*drug effects; Catheter-Related Infections/*drug therapy; Cytokines/blood; Disease Models, Animal; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects; Microbial Sensitivity Tests; Peptides/*pharmacology; Peptides, Cyclic/pharmacology; Rats; Rats, Sprague-Dawley; Staphylococcal Infections/*drug therapy; Vancomycin/administration & dosage; *Staphylococcus aureus; *antimicrobial peptides (AMPs); *biofilm; *catheter lock solution (CLS)  
  Abstract (up) Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections.  
  Address Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland  
  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 0022-1899 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28453851 Approved no  
  Call Number ref @ user @ Serial 100541  
Permanent link to this record
 

 
Author Li, M.; Zhao, H.; Ananiev, G.E.; Musser, M.T.; Ness, K.H.; Maglaque, D.L.; Saha, K.; Bhattacharyya, A.; Zhao, X. url  doi
openurl 
  Title Establishment of Reporter Lines for Detecting Fragile X Mental Retardation (FMR1) Gene Reactivation in Human Neural Cells Type Journal Article
  Year 2017 Publication Stem Cells (Dayton, Ohio) Abbreviated Journal Stem Cells  
  Volume 35 Issue 1 Pages 158-169  
  Keywords Drug discovery; Fmr1; Fmrp; Fragile X syndrome; High throughput; Induced pluripotent stem cells; Luciferase  
  Abstract (up) Human patient-derived induced pluripotent stem cells (hiPSCs) provide unique opportunities for disease modeling and drug development. However, adapting hiPSCs or their differentiated progenies to high throughput assays for phenotyping or drug screening has been challenging. Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and a major genetic cause of autism. FXS is caused by mutational trinucleotide expansion in the FMR1 gene leading to hypermethylation and gene silencing. One potential therapeutic strategy is to reactivate the silenced FMR1 gene, which has been attempted using both candidate chemicals and cell-based screening. However, molecules that effectively reactivate the silenced FMR1 gene are yet to be identified; therefore, a high throughput unbiased screen is needed. Here we demonstrate the creation of a robust FMR1-Nluc reporter hiPSC line by knocking in a Nano luciferase (Nluc) gene into the endogenous human FMR1 gene using the CRISPR/Cas9 genome editing method. We confirmed that luciferase activities faithfully report FMR1 gene expression levels and showed that neural progenitor cells derived from this line could be optimized for high throughput screening. The FMR1-Nluc reporter line is a good resource for drug screening as well as for testing potential genetic reactivation strategies. In addition, our data provide valuable information for the generation of knockin human iPSC reporter lines for disease modeling, drug screening, and mechanistic studies. Stem Cells 2017;35:158-169.  
  Address Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, 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 1066-5099 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27422057 Approved no  
  Call Number ref @ user @ Serial 95937  
Permanent link to this record
 

 
Author Vershkov, D.; Benvenisty, N. url  doi
openurl 
  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 (up) 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  
  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 1746-0751 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27900874 Approved no  
  Call Number ref @ user @ Serial 95909  
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