| Records |
| 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 |
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Thesis |
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Place of Publication |
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Editor |
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| Language |
English |
Summary Language |
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Original Title |
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| Series Editor |
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Series Title |
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Abbreviated Series Title |
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| Series Volume |
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Series Issue |
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Edition |
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| ISSN |
1663-9812 |
ISBN |
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Medium |
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| Area |
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Expedition |
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Conference |
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| Notes |
PMID:28408882 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96596 |
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| Author |
Zapotoczna, M.; Forde, E.; Hogan, S.; Humphreys, H.; O'Gara, J.P.; Fitzgerald-Hughes, D.; Devocelle, M.; O'Neill, E. |
| 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 |
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 |
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Thesis |
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Place of Publication |
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Editor |
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| Language |
English |
Summary Language |
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Original Title |
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Series Title |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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| ISSN |
0022-1899 |
ISBN |
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Medium |
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Expedition |
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Conference |
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| Notes |
PMID:28453851 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
99511 |
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| Author |
Zapotoczna, M.; Forde, E.; Hogan, S.; Humphreys, H.; O'Gara, J.P.; Fitzgerald-Hughes, D.; Devocelle, M.; O'Neill, E. |
| 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 |
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 |
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Thesis |
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| Publisher |
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Place of Publication |
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Editor |
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| Language |
English |
Summary Language |
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Original Title |
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| Series Editor |
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Series Title |
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Abbreviated Series Title |
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| Series Volume |
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Series Issue |
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Edition |
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| ISSN |
0022-1899 |
ISBN |
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Medium |
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Expedition |
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Conference |
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| Notes |
PMID:28453851 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
100541 |
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| Author |
Li, M.; Zhao, H.; Ananiev, G.E.; Musser, M.T.; Ness, K.H.; Maglaque, D.L.; Saha, K.; Bhattacharyya, A.; Zhao, X. |
| 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 |
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 |
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Thesis |
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Place of Publication |
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Editor |
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| Language |
English |
Summary Language |
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Original Title |
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Series Title |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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| ISSN |
1066-5099 |
ISBN |
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Medium |
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Expedition |
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Conference |
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| Notes |
PMID:27422057 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
95937 |
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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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Thesis |
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Place of Publication |
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Editor |
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| Language |
English |
Summary Language |
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Original Title |
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Series Title |
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Abbreviated Series Title |
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| Series Volume |
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Series Issue |
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Edition |
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| ISSN |
1746-0751 |
ISBN |
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Medium |
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| Area |
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Expedition |
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Conference |
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| Notes |
PMID:27900874 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
95909 |
| Permanent link to this record |
