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Author Labriola, L.; Pochet, J.-M. url  doi
openurl 
  Title Any use for alternative lock solutions in the prevention of catheter-related blood stream infections? Type Journal Article
  Year 2017 Publication The Journal of Vascular Access Abbreviated Journal J Vasc Access  
  Volume (down) 18 Issue Suppl. 1 Pages 34-38  
  Keywords Anti-Infective Agents/adverse effects/*therapeutic use; Anticoagulants/therapeutic use; Bacteremia/diagnosis/microbiology/*prevention & control; Biofilms; Catheter-Related Infections/diagnosis/microbiology/*prevention & control; Catheterization, Central Venous/adverse effects/*instrumentation; *Catheters, Indwelling/adverse effects/microbiology; *Central Venous Catheters/adverse effects/microbiology; Equipment Design; Humans; *Renal Dialysis; Risk Factors; Treatment Outcome  
  Abstract The prevention of catheter-related blood stream infections (CRBSI) in hemodialysis (HD) patients remains a challenge because of high morbidity and mortality associated to CRBSI. Alternative locking solutions (ALS) containing an antithrombotic substance with additional antimicrobial or antibiofilm properties (citrate, ethylenediaminetetraacetic acid [EDTA], 70% ethanol, thrombolytics) with or without the addition of molecules with specific antimicrobial activity (antibiotics, taurolidine, paraben-methylene-blue) has been proposed with the aim to prevent or eradicate intraluminal biofilm colonization and subsequent CRBSI. In this review, we examine the available evidence concerning their efficacy and potential side effects, in order to determine whether ALS should be implemented widely or only in selected cases.  
  Address Department of Nephrology, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels – Belgium  
  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 1129-7298 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28297055 Approved no  
  Call Number ref @ user @ Serial 99036  
Permanent link to this record
 

 
Author Labriola, L.; Pochet, J.-M. url  doi
openurl 
  Title Any use for alternative lock solutions in the prevention of catheter-related blood stream infections? Type Journal Article
  Year 2017 Publication The Journal of Vascular Access Abbreviated Journal J Vasc Access  
  Volume (down) 18 Issue Suppl. 1 Pages 34-38  
  Keywords Anti-Infective Agents/adverse effects/*therapeutic use; Anticoagulants/therapeutic use; Bacteremia/diagnosis/microbiology/*prevention & control; Biofilms; Catheter-Related Infections/diagnosis/microbiology/*prevention & control; Catheterization, Central Venous/adverse effects/*instrumentation; *Catheters, Indwelling/adverse effects/microbiology; *Central Venous Catheters/adverse effects/microbiology; Equipment Design; Humans; *Renal Dialysis; Risk Factors; Treatment Outcome  
  Abstract The prevention of catheter-related blood stream infections (CRBSI) in hemodialysis (HD) patients remains a challenge because of high morbidity and mortality associated to CRBSI. Alternative locking solutions (ALS) containing an antithrombotic substance with additional antimicrobial or antibiofilm properties (citrate, ethylenediaminetetraacetic acid [EDTA], 70% ethanol, thrombolytics) with or without the addition of molecules with specific antimicrobial activity (antibiotics, taurolidine, paraben-methylene-blue) has been proposed with the aim to prevent or eradicate intraluminal biofilm colonization and subsequent CRBSI. In this review, we examine the available evidence concerning their efficacy and potential side effects, in order to determine whether ALS should be implemented widely or only in selected cases.  
  Address Department of Nephrology, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels – Belgium  
  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 1129-7298 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28297055 Approved no  
  Call Number ref @ user @ Serial 100066  
Permanent link to this record
 

 
Author Jensen, S.S.; Petterson, S.A.; Halle, B.; Aaberg-Jessen, C.; Kristensen, B.W. url  doi
openurl 
  Title Effects of the lysosomal destabilizing drug siramesine on glioblastoma in vitro and in vivo Type Journal Article
  Year 2017 Publication BMC Cancer Abbreviated Journal BMC Cancer  
  Volume (down) 17 Issue 1 Pages 178  
  Keywords Brain slice cultures; Cancer stem cell; Glioblastoma; Lysosomes; Siramesine; Spheroids  
  Abstract BACKGROUND: Glioblastoma is the most frequent and most malignant brain tumor with the patients having a median survival of only 14.6 months. Although glioblastoma patients are treated with surgery, radiation and chemotherapy recurrence is inevitable. A stem-like population of radio- and chemoresistant brain tumor-initiating cells combined with the invasive properties of the tumors is believed to be critical for treatment resistance. In the present study, the aim was to investigate the effect of a novel therapeutic strategy using the lysosomotropic detergent siramesine on glioblastomas. METHODS: Standard glioma cell lines and patient-derived spheroids cultures with tumor-initiating stem-like cells were used to investigate effects of siramesine on proliferation and cell death. Responsible mechanisms were investigated by inhibitors of caspases and cathepsins. Effects of siramesine on migrating tumor cells were investigated by a flat surface migration assay and by implanting spheroids into organotypic rat brain slice cultures followed by confocal time-lapse imaging. Finally the effect of siramesine was investigated in an orthotopic mouse glioblastoma model. Results obtained in vitro and in vivo were confirmed by immunohistochemical staining of histological sections of spheroids, spheroids in brain slice cultures and tumors in mice brains. RESULTS: The results showed that siramesine killed standard glioma cell lines in vitro, and loss of acridine orange staining suggested a compromised lysosomal membrane. Co-treatment of the cell lines with inhibitors of caspases and cathepsins suggested differential involvement in cell death. Siramesine caused tumor cell death and reduced secondary spheroid formation of patient-derived spheroid cultures. In the flat surface migration model siramesine caused tumor cell death and inhibited tumor cell migration. This could not be reproduced in the organotypic three dimensional spheroid-brain slice culture model or in the mice xenograft model. CONCLUSIONS: In conclusion the in vitro results obtained with tumor cells and spheroids suggest a potential of lysosomal destabilizing drugs in killing glioblastoma cells, but siramesine was without effect in the organotypic spheroid-brain slice culture model and the in vivo xenograft model.  
  Address Institute of Clinical Research, University of Southern Denmark, Winslowparken 19.3, 5000, Odense C, Denmark. bjarne.winther.kristensen@rsyd.dk  
  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 1471-2407 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28270132 Approved no  
  Call Number ref @ user @ Serial 96603  
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Author Gersey, Z.C.; Rodriguez, G.A.; Barbarite, E.; Sanchez, A.; Walters, W.M.; Ohaeto, K.C.; Komotar, R.J.; Graham, R.M. url  doi
openurl 
  Title Curcumin decreases malignant characteristics of glioblastoma stem cells via induction of reactive oxygen species Type Journal Article
  Year 2017 Publication BMC Cancer Abbreviated Journal BMC Cancer  
  Volume (down) 17 Issue 1 Pages 99  
  Keywords Acetylcysteine/pharmacology; Adult; Antineoplastic Agents/*pharmacology; Cell Proliferation/drug effects; Cell Survival/drug effects; Curcumin/*pharmacology; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Free Radical Scavengers; Glioblastoma/drug therapy/pathology; Humans; Inhibitor of Apoptosis Proteins/metabolism; Inhibitory Concentration 50; Mitogen-Activated Protein Kinases/metabolism; Neoplastic Stem Cells/*drug effects; Oxidative Stress; Reactive Oxygen Species/*metabolism; STAT3 Transcription Factor/metabolism; Tumor Cells, Cultured; Brain tumor; Curcumin; Glioblastoma; Natural product; Reactive oxygen species; Stat3; Stem cell  
  Abstract BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and lethal form of primary brain tumor in adults. Following standard treatment of surgery, radiation and chemotherapy, patients are expected to survive 12-14 months. Theorized cause of disease recurrence in these patients is tumor cell repopulation through the proliferation of treatment-resistant cancer stem cells. Current research has revealed curcumin, the principal ingredient in turmeric, can modulate multiple signaling pathways important for cancer stem cell self-renewal and survival. METHODS: Following resection, tumor specimens were dissociated and glioblastoma stem cells (GSCs) were propagated in neurosphere media and characterized via immunocytochemistry. Cell viability was determined with MTS assay. GSC proliferation, sphere forming and colony forming assays were conducted through standard counting methods. Reactive oxygen species (ROS) production was examined using the fluorescent molecular probe CM-H2DCFA. Effects on cell signaling pathways were elucidated by western blot. RESULTS: We evaluate the effects of curcumin on patient-derived GSC lines. We demonstrate a curcumin-induced dose-dependent decrease in GSC viability with an approximate IC50 of 25 muM. Treatment with sub-toxic levels (2.5 muM) of curcumin significantly decreased GSC proliferation, sphere forming ability and colony forming potential. Curcumin induced ROS, promoted MAPK pathway activation, downregulated STAT3 activity and IAP family members. Inhibition of ROS with the antioxidant N-acetylcysteine reversed these effects indicating a ROS dependent mechanism. CONCLUSIONS: Discoveries made in this investigation may lead to a non-toxic intervention designed to prevent recurrence in glioblastoma by targeting glioblastoma stem cells.  
  Address Department of Neurological Surgery, University of Miami Brain Tumor Initiative (UMBTI) Research Laboratory, Lois Pope LIFE Center, 2nd Floor, 1095 NW 14th Terrace, Miami, Florida, 33136, USA. rgraham@med.miami.edu  
  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 1471-2407 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28160777 Approved no  
  Call Number ref @ user @ Serial 96610  
Permanent link to this record
 

 
Author Spencer, D.A.; Auffinger, B.M.; Murphy, J.P.; Muroski, M.E.; Qiao, J.; Gorind, Y.; Lesniak, M.S. url  doi
openurl 
  Title Hitting a Moving Target: Glioma Stem Cells Demand New Approaches in Glioblastoma Therapy Type Journal Article
  Year 2017 Publication Current Cancer Drug Targets Abbreviated Journal Curr Cancer Drug Targets  
  Volume (down) 17 Issue 3 Pages 236-254  
  Keywords Brain Neoplasms/drug therapy/pathology; Drug Resistance, Neoplasm/drug effects; Glioblastoma/*drug therapy/pathology; Glioma/drug therapy/*pathology; Humans; Molecular Targeted Therapy/*methods; Neoplastic Stem Cells/drug effects/*pathology/radiation effects; Chemotherapy; drug targets; glioblastoma multiforme; glioma stem cells; niches; recurrence; resistance  
  Abstract BACKGROUND: Glioblastoma multiforme (GBM) continues to devastate patients and outfox investigators and clinicians despite the preponderance of research directed at its biology, pathogenesis and therapeutic advances. GBM routinely outlasts multidisciplinary treatment protocols, almost inevitably recurring in a yet more aggressive and resistant form with distinct genetic differences from the original tumor. Attempts to glean further insight into GBM point increasingly toward a subpopulation of cells with a stem-like phenotype. These cancer stem cells, similar to those now described in a variety of malignancies, are capable of tumorigenesis from a population of susceptible cells. CONCLUSIONS: Glioma stem cells have thus become a prevalent focus in GBM research for their presumed role in development, maintenance and recurrence of tumors. Glioma stem cells infiltrate the white matter surrounding tumors and often evade resection. They are uniquely suited both biochemically and environmentally to resist the best therapy currently available, intrinsically and efficiently resistant to standard chemo- and radiotherapy. These stem cells create an extremely heterogenous tumor that to date has had an answer for every therapeutic question, with continued dismal patient survival. Targeting this population of glioma stem cells may hold the long-awaited key to durable therapeutic efficacy in GBM.  
  Address Neuro-Oncology Laboratory, Department of Neurosurgery, Northwestern University, 676 N. St. Clair Street, Suite 2210, Chicago, IL60611, United States  
  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 1568-0096 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27993114 Approved no  
  Call Number ref @ user @ Serial 96616  
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