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Author Behling, F.; Kaltenstadler, M.; Noell, S.; Schittenhelm, J.; Bender, B.; Eckert, F.; Tabatabai, G.; Tatagiba, M.; Skardelly, M. url  doi
openurl 
  Title (down) The Prognostic Impact of Ventricular Opening in Glioblastoma Surgery: A Retrospective Single Center Analysis Type Journal Article
  Year 2017 Publication World Neurosurgery Abbreviated Journal World Neurosurg  
  Volume 106 Issue Pages 615-624  
  Keywords Extent of resection; Glioblastoma; Hydrocephalus; Overall survival; Prognosis; Tumor volume; Ventricle opening  
  Abstract OBJECTIVE: Ventricular opening during glioblastoma (GBM) resection is controversial. Sufficient evidence regarding its prognostic role is missing. We investigated the impact of ventricular opening on overall survival (OS), hydrocephalus development, and postoperative morbidity in patients with GBM. METHODS: Patients who underwent primary GBM resection between 2006 and 2013 were assessed retrospectively. Established predictors for overall survival (age, Karnofsky Performance Status, extent of resection, O-6-methylguanine-DNA methyltransferase promoter methylation status, isocitrate dehydrogenase mutation status) and further clinical data (postoperative status, further treatment, preoperative tumor volume, proximity to the ventricle) were included in univariate and multivariate analyses. RESULTS: Thirteen (5.7%) of 229 patients developed a hydrocephalus. Multivariate logistic regression showed that neither ventricular opening, tumor size, proximity to the ventricle, nor extent of resection were significant risk factors for hydrocephalus. Ventricular opening did not delay postoperative therapy and was not associated with neurological morbidity. Kaplan-Meier analysis demonstrated that patients who underwent ventricular opening (n = 114) exhibited a median OS of 14.3 months (12.9-16.5), whereas patients who did not undergo ventricular opening (n = 115) exhibited a median OS of 18.6 months (16.1-20.8). However, multivariate Cox regression (n = 134) did not confirm ventricular opening as an independent negative predictor of OS (risk ratio 1.09, P = 0.77). Instead, it showed that a greater preoperative tumor volume >22.8 cm3 was a negative predictor of OS (risk ratio 1.76, P = 0.02). CONCLUSIONS: Because extent of resection is a strong independent predictor of OS and ventricular opening is safe, neurosurgeons should consider ventricular opening to achieve maximal tumor resection.  
  Address Department of Neurosurgery, University Hospital Tuebingen, Eberhard Karls University, Tuebingen, Germany; Center for CNS Tumors, Comprehensive Cancer Center Tuebingen Stuttgart, University Hospital Tuebingen, Eberhard Karls University, Tuebingen, 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 1878-8750 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28729143 Approved no  
  Call Number ref @ user @ Serial 96576  
Permanent link to this record
 

 
Author Brodie, S.; Lee, H.K.; Jiang, W.; Cazacu, S.; Xiang, C.; Poisson, L.M.; Datta, I.; Kalkanis, S.; Ginsberg, D.; Brodie, C. url  doi
openurl 
  Title (down) The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells Type Journal Article
  Year 2017 Publication Oncotarget Abbreviated Journal Oncotarget  
  Volume 8 Issue 19 Pages 31785-31801  
  Keywords Talnec2; glioblastoma; glioma stem cells; long non-cording RNAs; mesenchymal transformation  
  Abstract Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), the median survival of 12-14 months has not changed significantly. Therefore, there is an imperative need to identify molecular mechanisms that play a role in patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM with poor prognosis, in GBM specimens derived from short-term survivors and in glioma cells and glioma stem cells (GSCs). Silencing of TALNEC2 inhibited cell proliferation and arrested the cells in the G1\S phase of the cell cycle in various cancer cell lines. In addition, silencing of TALNEC2 decreased the self-renewal and mesenchymal transformation of GSCs, increased sensitivity of these cells to radiation and prolonged survival of mice bearing GSC-derived xenografts. Using miRNA array analysis, we identified specific miRNAs that were altered in the silenced cells that were associated with cell-cycle progression, proliferation and mesenchymal transformation. Two of the downregulated miRNAs, miR-21 and miR-191, mediated some of TALNEC2 effects on the stemness and mesenchymal transformation of GSCs. In conclusion, we identified a novel E2F1-regulated lncRNA that is highly expressed in GBM and in tumors from patients of short-term survival. The expression of TALNEC2 is associated with the increased tumorigenic potential of GSCs and their resistance to radiation. We conclude that TALNEC2 is an attractive therapeutic target for the treatment of GBM.  
  Address Davidson Laboratory of Cell Signaling and Tumorigenesis, Hermelin Brain Tumor Center, Department of Neurosurgery, Detroit, MI, 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 PMID:28423669 Approved no  
  Call Number ref @ user @ Serial 96594  
Permanent link to this record
 

 
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. url  doi
openurl 
  Title (down) 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 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  
Permanent link to this record
 

 
Author Radbel, J.; Boutsikaris, D. url  doi
openurl 
  Title (down) The New Usual Care Type Journal Article
  Year 2017 Publication Emergency Medicine Clinics of North America Abbreviated Journal Emerg Med Clin North Am  
  Volume 35 Issue 1 Pages 11-23  
  Keywords Anti-Bacterial Agents/therapeutic use; Catheterization, Central Venous; Clinical Protocols/standards; Evidence-Based Medicine; Fluid Therapy; Humans; Sepsis/diagnosis/*therapy; ARISE trial; Early goal-directed therapy (EGDT); ProCESS trial; ProMISe trial; Sepsis; Usual care  
  Abstract Recent literature continues to refine which components of the early goal-directed therapy (EGDT) algorithm are necessary. Given it utilizes central venous pressure, continuous central venous oxygen saturation, routine blood transfusions, and inotropic medications, this algorithm can be timely, invasive, costly, and potentially harmful. New trials highlight early recognition, early fluid resuscitation, appropriate antibiotic treatment, source control, and the application of a multidisciplinary evidence-based approach as essential components of current sepsis management. This article discusses the landmark sepsis trials that have been published over the past several decades and offers recommendations on what should currently be considered 'usual care'.  
  Address Department of Emergency Medicine, Saint Peters University Hospital, 254 Easton Ave, New Brunswick, NJ 08901, USA; Division of Pulmonary and Critical Care, Department of Medicine, Rutgers Robert Wood Johnson Medical School, One Robert Johnson Place, New Brunswick, NJ 08903, USA. Electronic address: boutsida@rwjms.rutgers.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 0733-8627 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27908328 Approved no  
  Call Number ref @ user @ Serial 99263  
Permanent link to this record
 

 
Author Radbel, J.; Boutsikaris, D. url  doi
openurl 
  Title (down) The New Usual Care Type Journal Article
  Year 2017 Publication Emergency Medicine Clinics of North America Abbreviated Journal Emerg Med Clin North Am  
  Volume 35 Issue 1 Pages 11-23  
  Keywords Anti-Bacterial Agents/therapeutic use; Catheterization, Central Venous; Clinical Protocols/standards; Evidence-Based Medicine; Fluid Therapy; Humans; Sepsis/diagnosis/*therapy; ARISE trial; Early goal-directed therapy (EGDT); ProCESS trial; ProMISe trial; Sepsis; Usual care  
  Abstract Recent literature continues to refine which components of the early goal-directed therapy (EGDT) algorithm are necessary. Given it utilizes central venous pressure, continuous central venous oxygen saturation, routine blood transfusions, and inotropic medications, this algorithm can be timely, invasive, costly, and potentially harmful. New trials highlight early recognition, early fluid resuscitation, appropriate antibiotic treatment, source control, and the application of a multidisciplinary evidence-based approach as essential components of current sepsis management. This article discusses the landmark sepsis trials that have been published over the past several decades and offers recommendations on what should currently be considered 'usual care'.  
  Address Department of Emergency Medicine, Saint Peters University Hospital, 254 Easton Ave, New Brunswick, NJ 08901, USA; Division of Pulmonary and Critical Care, Department of Medicine, Rutgers Robert Wood Johnson Medical School, One Robert Johnson Place, New Brunswick, NJ 08903, USA. Electronic address: boutsida@rwjms.rutgers.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 0733-8627 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27908328 Approved no  
  Call Number ref @ user @ Serial 100293  
Permanent link to this record
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