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Author Paldino, M.J.; Hedges, K.; Rodrigues, K.M.; Barboriak, D.P.
Title Repeatability of quantitative metrics derived from MR diffusion tractography in paediatric patients with epilepsy Type Journal Article
Year 2014 Publication The British Journal of Radiology Abbreviated Journal Br J Radiol
Volume 87 Issue 1037 Pages (down) 20140095
Keywords Anisotropy; Child; Diffusion Tensor Imaging/*methods; Epilepsy/*pathology; Female; Humans; Image Interpretation, Computer-Assisted; Male; Reproducibility of Results; Retrospective Studies
Abstract OBJECTIVE: To quantify the test-retest repeatability of mean diffusivity (MD) and fractional anisotropy (FA) derived from diffusion tensor imaging (DTI) tractography in a cohort of paediatric patients with localization-related epilepsy. METHODS: 30 patients underwent 2 DTI acquisitions [repetition time/echo time (ms), 7000/90; flip, 90 degrees ; b-value, 1000 s mm(-2); voxel (mm), 2 x 2 x 2]. Two observers used Diffusion Toolkit and TrackVis ( www.trackvis.org ) to segment and analyse the following tracts: corpus callosum, corticospinal tracts, arcuate fasciculi, inferior longitudinal fasciculi and inferior fronto-occipital fasciculi. Mean MD and mean FA were calculated for each tract. Each observer independently analysed one of the DTI data sets for every patient. RESULTS: Segmentation identified all tracts in all subjects, except the arcuate fasciculus. There was a highly consistent relationship between repeated observations of MD (r = 0.993; p < 0.0001) and FA (r = 0.990; p < 0.0001). For each tract, coefficients of variation ranged from 0.9% to 2.1% for MD and from 1.5% to 2.8% for FA. The 95% confidence limits (CLs) for change ranged from 2.8% to 6% for MD and from 4.3% to 8.6% for FA. For the arcuate fasciculus, Cohen's kappa for agreement between the observers (identifiable vs not identifiable) was 1.0. CONCLUSION: We quantified the repeatability of two commonly utilized scalar metrics derived from DTI tractography. For an individual patient, changes greater than the repeatability coefficient or 95% CLs for change are unlikely to be related to variability in their measurement. ADVANCES IN KNOWLEDGE: Reproducibility of these metrics will aid in the design of future studies and might one day be used to guide management in patients with epilepsy.
Address Department of Radiology, Children's Hospital Boston and Harvard Medical School, Boston, MA, 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 0007-1285 ISBN Medium
Area Expedition Conference
Notes PMID:24720623 Approved no
Call Number ref @ user @ Serial 90641
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Author Gravina, G.L.; Mancini, A.; Colapietro, A.; Vitale, F.; Vetuschi, A.; Pompili, S.; Rossi, G.; Marampon, F.; Richardson, P.J.; Patient, L.; Patient, L.; Burbidge, S.; Festuccia, C.
Title The novel CXCR4 antagonist, PRX177561, reduces tumor cell proliferation and accelerates cancer stem cell differentiation in glioblastoma preclinical models Type Journal Article
Year 2017 Publication Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine Abbreviated Journal Tumour Biol
Volume 39 Issue 6 Pages (down) 1010428317695528
Keywords Adult; Animals; Cell Differentiation/drug effects; Cell Line, Tumor; Cell Movement/drug effects; Cell Proliferation/drug effects; Chemokine CXCL12/*genetics; Disease-Free Survival; Glioblastoma/*drug therapy/genetics; Humans; Mice; Neoplasm Recurrence, Local/*drug therapy/genetics/pathology; Neoplastic Stem Cells/drug effects/pathology; Neovascularization, Pathologic/*drug therapy/genetics/pathology; Receptors, CXCR4/antagonists & inhibitors/*genetics; Signal Transduction/drug effects; Tumor Microenvironment/drug effects; Cxcr4; Glioblastoma; angiogenesis; monocyte infiltration
Abstract Glioblastoma is the most frequent and the most lethal primary brain tumor among adults. Standard of care is the association of radiotherapy with concomitant or adjuvant temozolomide. However, to date, recurrence is inevitable. The CXCL12/CXCR4 pathway is upregulated in the glioblastoma tumor microenvironment regulating tumor cell proliferation, local invasion, angiogenesis, and the efficacy of radio-chemotherapy. In this study, we evaluated the effects of the novel CXCR4 antagonist, PRX177561, in preclinical models of glioblastoma. CXCR4 expression and PRX177561 effects were assessed on a panel of 12 human glioblastoma cells lines and 5 patient-derived glioblastoma stem cell cultures. Next, the effect of PRX177561 was tested in vivo, using subcutaneous injection of U87MG, U251, and T98G cells as well as orthotopic intrabrain inoculation of luciferase-transfected U87MG cells. Here we found that PRX177561 impairs the proliferation of human glioblastoma cell lines, increases apoptosis, and reduces CXCR4 expression and cell migration in response to stromal cell-derived factor 1alpha in vitro. PRX177561 reduced the expression of stem cell markers and increased that of E-cadherin and glial fibrillary acidic protein in U87MG cells consistent with a reduction in cancer stem cells. In vivo, PRX177561 reduced the weight and increased the time to progression of glioblastoma subcutaneous tumors while increasing disease-free survival and overall survival of mice bearing orthotopic tumors. Our findings suggest that targeting stromal cell-derived factor 1 alpha/CXCR4 axis by PRX177561 might represent a novel therapeutic approach against glioblastoma and support further investigation of this compound in more complex preclinical settings in order to determine its therapeutic potential.
Address 1 Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, L'Aquila, Italy
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 1010-4283 ISBN Medium
Area Expedition Conference
Notes PMID:28639900 Approved no
Call Number ref @ user @ Serial 96581
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Author de Sousa, J.F.; Torrieri, R.; Serafim, R.B.; Di Cristofaro, L.F.M.; Escanfella, F.D.; Ribeiro, R.; Zanette, D.L.; Paco-Larson, M.L.; da Silva, W.A.J.; Tirapelli, D.P. da C.; Neder, L.; Carlotti, C.G.J.; Valente, V.
Title Expression signatures of DNA repair genes correlate with survival prognosis of astrocytoma patients Type Journal Article
Year 2017 Publication Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine Abbreviated Journal Tumour Biol
Volume 39 Issue 4 Pages (down) 1010428317694552
Keywords Apoptosis; Astrocytoma/genetics/metabolism/*mortality; Brain Neoplasms/genetics/metabolism/*mortality; Cell Cycle; Cell Line, Tumor; *DNA Repair; DNA Repair Enzymes/genetics/metabolism; Exodeoxyribonucleases/genetics/metabolism; Gene Expression; Humans; Kaplan-Meier Estimate; N-Glycosyl Hydrolases/genetics/metabolism; Prognosis; DNA repair; astrocytoma; genomic instability; glioblastoma; tumor progression
Abstract Astrocytomas are the most common primary brain tumors. They are very resistant to therapies and usually progress rapidly to high-grade lesions. Here, we investigated the potential role of DNA repair genes in astrocytoma progression and resistance. To this aim, we performed a polymerase chain reaction array-based analysis focused on DNA repair genes and searched for correlations between expression patters and survival prognoses. We found 19 genes significantly altered. Combining these genes in all possible arrangements, we found 421 expression signatures strongly associated with poor survival. Importantly, five genes (DDB2, EXO1, NEIL3, BRCA2, and BRIP1) were independently correlated with worse prognoses, revealing single-gene signatures. Moreover, silencing of EXO1, which is remarkably overexpressed, promoted faster restoration of double-strand breaks, while NEIL3 knockdown, also highly overexpressed, caused an increment in DNA damage and cell death after irradiation of glioblastoma cells. These results disclose the importance of DNA repair pathways for the maintenance of genomic stability of high-grade astrocytomas and suggest that EXO1 and NEIL3 overexpression confers more efficiency for double-strand break repair and resistance to reactive oxygen species, respectively. Thereby, we highlight these two genes as potentially related with tumor aggressiveness and promising candidates as novel therapeutic targets.
Address 7 Center for Integrative Systems Biology (CISBi), NAP/USP, Ribeirao Preto, Brazil
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 1010-4283 ISBN Medium
Area Expedition Conference
Notes PMID:28378638 Approved no
Call Number ref @ user @ Serial 96598
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Author Bischof, J.; Westhoff, M.-A.; Wagner, J.E.; Halatsch, M.-E.; Trentmann, S.; Knippschild, U.; Wirtz, C.R.; Burster, T.
Title Cancer stem cells: The potential role of autophagy, proteolysis, and cathepsins in glioblastoma stem cells Type Journal Article
Year 2017 Publication Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine Abbreviated Journal Tumour Biol
Volume 39 Issue 3 Pages (down) 1010428317692227
Keywords Animals; Autophagy; Brain Neoplasms/*metabolism/*pathology; Cathepsins/*metabolism; Glioblastoma/*metabolism/*pathology; Humans; Neoplastic Stem Cells/*metabolism/*pathology; Proteolysis; *Major histocompatibility complex class I; *autophagy; *cathepsin; *glioblastoma
Abstract One major obstacle in cancer therapy is chemoresistance leading to tumor recurrence and metastasis. Cancer stem cells, in particular glioblastoma stem cells, are highly resistant to chemotherapy, radiation, and immune recognition. In case of immune recognition, several survival mechanisms including, regulation of autophagy, proteases, and cell surface major histocompatibility complex class I molecules, are found in glioblastoma stem cells. In different pathways, cathepsins play a crucial role in processing functional proteins that are necessary for several processes and proper cell function. Consequently, strategies targeting these pathways in glioblastoma stem cells are promising approaches to interfere with tumor cell survival and will be discussed in this review.
Address 3 Department of Neurosurgery, Surgery Center, Ulm University Medical Center, Ulm University, Ulm, Germany
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 1010-4283 ISBN Medium
Area Expedition Conference
Notes PMID:28347245 Approved no
Call Number ref @ user @ Serial 96600
Permanent link to this record
 

 
Author Miller, L.M.; Clark, E.; Dipchand, C.; Hiremath, S.; Kappel, J.; Kiaii, M.; Lok, C.; Luscombe, R.; Moist, L.; Oliver, M.; MacRae, J.
Title Hemodialysis Tunneled Catheter-Related Infections Type Journal Article
Year 2016 Publication Canadian Journal of Kidney Health and Disease Abbreviated Journal Can J Kidney Health Dis
Volume 3 Issue Pages (down) 2054358116669129
Keywords antimicrobial locks; catheter-related bacteremia; catheter-related infection complications; central venous catheter; hemodialysis; tunneled catheter
Abstract Catheter-related bloodstream infections, exit-site infections, and tunnel infections are common complications related to hemodialysis central venous catheter use. The various definitions of catheter-related infections are reviewed, and various preventive strategies are discussed. Treatment options, for both empiric and definitive infections, including antibiotic locks and systemic antibiotics, are reviewed.
Address Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Alberta, Canada
Corporate Author Canadian Society of Nephrology Vascular Access Work Group 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 2054-3581 ISBN Medium
Area Expedition Conference
Notes PMID:28270921 Approved no
Call Number ref @ user @ Serial 99134
Permanent link to this record