Records |
Author |
Behling, F.; Kaltenstadler, M.; Noell, S.; Schittenhelm, J.; Bender, B.; Eckert, F.; Tabatabai, G.; Tatagiba, M.; Skardelly, M. |
Title  |
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 |
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English |
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ISSN |
1878-8750 |
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Notes |
PMID:28729143 |
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no |
Call Number |
ref @ user @ |
Serial |
96576 |
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Author |
Brodie, S.; Lee, H.K.; Jiang, W.; Cazacu, S.; Xiang, C.; Poisson, L.M.; Datta, I.; Kalkanis, S.; Ginsberg, D.; Brodie, C. |
Title  |
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 |
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English |
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ISSN |
1949-2553 |
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Notes |
PMID:28423669 |
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no |
Call Number |
ref @ user @ |
Serial |
96594 |
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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 |
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 |
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ISSN |
1010-4283 |
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Notes |
PMID:28639900 |
Approved |
no |
Call Number |
ref @ user @ |
Serial |
96581 |
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Author |
Radbel, J.; Boutsikaris, D. |
Title  |
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 |
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Series Editor |
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0733-8627 |
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Notes |
PMID:27908328 |
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no |
Call Number |
ref @ user @ |
Serial |
99263 |
Permanent link to this record |
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Author |
Radbel, J.; Boutsikaris, D. |
Title  |
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 |
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English |
Summary Language |
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Abbreviated Series Title |
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0733-8627 |
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Notes |
PMID:27908328 |
Approved |
no |
Call Number |
ref @ user @ |
Serial |
100293 |
Permanent link to this record |