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Author Shahar, T.; Rozovski, U.; Hess, K.R.; Hossain, A.; Gumin, J.; Gao, F.; Fuller, G.N.; Goodman, L.; Sulman, E.P.; Lang, F.F.
Title Percentage of mesenchymal stem cells in high-grade glioma tumor samples correlates with patient survival Type Journal Article
Year 2017 Publication Neuro-Oncology Abbreviated Journal Neuro Oncol
Volume 19 Issue 5 Pages 660-668
Keywords *glioblastoma; *mesenchymal stem cells; *microenvironment; *prognosis
Abstract Background: Human mesenchymal stem cells (hMSCs) have been shown to reside as stromal cells in human gliomas as glioma-associated hMSCs (GA-hMSCs), but their biological role remains unclear. Because recent evidence indicates that GA-hMSCs drive tumor cell proliferation and stemness, we hypothesized that a higher percentage of GA-hMSCs in tumors predicts poor patient prognosis. Method: We determined the percentage of cells coexpressing GA-hMSC markers CD105+/CD73+/CD90+ from patients with newly diagnosed high-grade glioma and analyzed the association between this percentage and overall survival (OS) in 3 independent cohorts: fresh surgical glioblastoma specimens (cohort 1, N = 9), cultured tumor specimens at passage 3 (cohort 2, N = 28), and The Cancer Genome Atlas (TCGA) database. Results: In all cohorts, patient OS correlated with the percentages of GA-hMSCs in tumors. For cohort 1, the median OS of patients with tumors with a low percentage of triple-positive cells was 46 months, and for tumors with a high percentage of triple-positive cells, it was 12 months (hazard ratio [HR] = 0.24; 95% CI: 0.02-0.5, P = .02). For cohort 2, the median OS of patients with tumors with a low percentage of GA-hMSCs was 66 months, and for tumors with a high percentage, it was 11 months (HR = 0.38; 95% CI: 0.13-0.9, P = .04). In the database of TCGA, the median OS times in patients with high and low coexpression levels of CD105/CD73/CD90 were 8.4 months and 13.1 months (HR = 0.4; 95% CI: 0.1-0.88; P = .04), respectively. Conclusions: The percentage of GA-MSCs inversely correlates with OS, suggesting a role for GA-MSCs in promoting aggressive behavior of gliomas.
Address Brain Tumor Center, Unit 442, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 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 1522-8517 ISBN Medium
Area Expedition Conference
Notes (up) PMID:28453745 Approved no
Call Number ref @ user @ Serial 96589
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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 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 (up) 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 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 (up) PMID:28453851 Approved no
Call Number ref @ user @ Serial 100541
Permanent link to this record
 

 
Author Kim, M.Y.; Park, S.-J.; Shim, J.W.; Song, Y.J.; Yang, K.; Park, S.-J.; Heo, K.
Title Accumulation of low-dose BIX01294 promotes metastatic potential of U251 glioblastoma cells Type Journal Article
Year 2017 Publication Oncology Letters Abbreviated Journal Oncol Lett
Volume 13 Issue 3 Pages 1767-1774
Keywords Bix01294; epithelial-mesenchymal transition; glioblastoma stem cells; metastasis
Abstract BIX01294 (Bix) is known to be a euchromatic histone-lysine N-methyltransferase 2 inhibitor and treatment with Bix suppresses cancer cell survival and proliferation. In the present study, it was observed that sequential treatment with low-dose Bix notably increases glioblastoma cell migration and metastasis. It was demonstrated that U251 cells sequentially treated with low-dose Bix exhibited induced characteristic changes in critical epithelial-mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, beta-catenin and zinc finger protein SNAI2. Notably, sequential treatment with Bix also increased the expression of cancer stem cell-associated markers, including sex determining region Y-box 2, octamer-binding transcription factor 4 and cluster of differentiation 133. Neurosphere formation was significantly enhanced in cells sequentially treated with Bix, compared with control cells (control: P=0.011; single treatment of Bix, P=0.045). The results of the present study suggest that accumulation of low-dose Bix enhanced the migration and metastatic potential of glioblastoma cells by regulating EMT-associated gene expression, which may be the cause of the altered properties of glioblastoma stem cells.
Address Research Center, Dongnam Institute of Radiological and Medical Science (DIRAMS), Busan 619-953, Republic of Korea
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 1792-1074 ISBN Medium
Area Expedition Conference
Notes (up) PMID:28454322 Approved no
Call Number ref @ user @ Serial 96588
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Author Oliva, C.R.; Zhang, W.; Langford, C.; Suto, M.J.; Griguer, C.E.
Title Repositioning chlorpromazine for treating chemoresistant glioma through the inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit Type Journal Article
Year 2017 Publication Oncotarget Abbreviated Journal Oncotarget
Volume 8 Issue 23 Pages 37568-37583
Keywords chlorpromazine; cytochrome c oxidase; glioblastoma; inhibitor; stem cells
Abstract Patients with glioblastoma have one of the lowest overall survival rates among patients with cancer. Standard of care for patients with glioblastoma includes temozolomide and radiation therapy, yet 30% of patients do not respond to these treatments and nearly all glioblastoma tumors become resistant. Chlorpromazine is a United States Food and Drug Administration-approved phenothiazine widely used as a psychotropic in clinical practice. Recently, experimental evidence revealed the anti-proliferative activity of chlorpromazine against colon and brain tumors. Here, we used chemoresistant patient-derived glioma stem cells and chemoresistant human glioma cell lines to investigate the effects of chlorpromazine against chemoresistant glioma. Chlorpromazine selectively and significantly inhibited proliferation in chemoresistant glioma cells and glioma stem cells. Mechanistically, chlorpromazine inhibited cytochrome c oxidase (CcO, complex IV) activity from chemoresistant but not chemosensitive cells, without affecting other mitochondrial complexes. Notably, our previous studies revealed that the switch to chemoresistance in glioma cells is accompanied by a switch from the expression of CcO subunit 4 isoform 2 (COX4-2) to COX4-1. In this study, chlorpromazine induced cell cycle arrest selectively in glioma cells expressing COX4-1, and computer-simulated docking studies indicated that chlorpromazine binds more tightly to CcO expressing COX4-1 than to CcO expressing COX4-2. In orthotopic mouse brain tumor models, chlorpromazine treatment significantly increased the median overall survival of mice harboring chemoresistant tumors. These data indicate that chlorpromazine selectively inhibits the growth and proliferation of chemoresistant glioma cells expressing COX4-1. The feasibility of repositioning chlorpromazine for selectively treating chemoresistant glioma tumors should be further explored.
Address Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, 35294 Alabama, 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 1949-2553 ISBN Medium
Area Expedition Conference
Notes (up) PMID:28455961 Approved no
Call Number ref @ user @ Serial 96587
Permanent link to this record