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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
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title (down)
Series Volume Series Issue Edition
ISSN 1878-8750 ISBN Medium
Area Expedition Conference
Notes PMID:28729143 Approved no
Call Number ref @ user @ Serial 96576
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Author Mercatelli, N.; Galardi, S.; Ciafre, S.A.
Title MicroRNAs as Multifaceted Players in Glioblastoma Multiforme Type Journal Article
Year 2017 Publication International Review of Cell and Molecular Biology Abbreviated Journal Int Rev Cell Mol Biol
Volume 333 Issue Pages 269-323
Keywords Biomarker; Cancer stem cells; Glioblastoma; MicroRNAs; Microenvironment; OncomomiRs; Therapy; Tumor suppressors
Abstract Glioblastoma multiforme (GBM) is the most common and inevitably lethal primary brain tumor, with a median survival rate of only 15 months from diagnosis. The current standard treatment involves maximal surgical resection flanked by radiotherapy and chemotherapy with the alkylating agent temozolomide. However, even such aggressive treatment is never curative, and recurrent tumors always arise, commonly in more aggressive, chemo- and radio-resistant forms, leading to untreatable and deadly tumors. MicroRNAs, recognized major players in cancer, are deeply involved in GBM, as shown by more than a decade of studies. In this review, we revise the main milestones of MicroRNA studies in GBM, and the latest relevant discoveries in this field. Examples are given of MicroRNAs working as “oncomiRs” or tumor suppressors, with specific connections with GBM clinical subtypes, patients' survival, and resistance to therapies. As the interaction of GBM cells with the microenvironment was proven as a key determinant of tumor growth, the role of MicroRNAs in GBM microenvironment, tumor angiogenesis, and tumor-secreted microvesicles is also reviewed. Finally, we discuss the latest findings presenting MicroRNAs as possible therapeutic targets for GBM, or their use as circulating biomarkers in diagnosis and prognosis.
Address Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title (down)
Series Volume Series Issue Edition
ISSN 1937-6448 ISBN Medium
Area Expedition Conference
Notes PMID:28729027 Approved no
Call Number ref @ user @ Serial 96577
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Author Roh, T.H.; Park, H.H.; Kang, S.-G.; Moon, J.H.; Kim, E.H.; Hong, C.-K.; Ahn, S.S.; Choi, H.J.; Cho, J.; Kim, S.H.; Lee, S.K.; Kim, D.S.; Kim, S.H.; Suh, C.-O.; Lee, K.S.; Chang, J.H.
Title Long-term outcomes of concomitant chemoradiotherapy with temozolomide for newly diagnosed glioblastoma patients: A single-center analysis Type Journal Article
Year 2017 Publication Medicine Abbreviated Journal Medicine (Baltimore)
Volume 96 Issue 27 Pages e7422
Keywords Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating/*therapeutic use; Brain Neoplasms/diagnosis/genetics/metabolism/*therapy; *Chemoradiotherapy; DNA Methylation; DNA Modification Methylases/genetics/metabolism; DNA Repair Enzymes/genetics/metabolism; Dacarbazine/*analogs & derivatives/therapeutic use; Disease-Free Survival; Female; Follow-Up Studies; Glioblastoma/diagnosis/genetics/metabolism/*therapy; Humans; Male; Middle Aged; Prognosis; Promoter Regions, Genetic; Retrospective Studies; Treatment Outcome; Tumor Suppressor Proteins/genetics/metabolism; Young Adult
Abstract The present study analyzed outcomes of surgery followed by concomitant chemoradiotherapy (CCRT) with temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM) at a single institution. Outcomes were retrospectively reviewed in 252 consecutive patients with newly diagnosed GBM who underwent surgery followed by CCRT with TMZ at the authors' institution between 2005 and 2013. At initial operation, 126 (50.0%), 55 (21.8%), 45 (17.9%), and 26 (10.3%) patients underwent gross total resection (GTR), subtotal resection, partial resection (PR), and biopsy, respectively. Their median overall survival (OS) was 20.8 months (95% confidence interval [CI] 17.7-23.9 months) and their median progression-free survival was 12.7 months (95% CI 11.2-14.2 months). The O-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 78 (34.1%) of the 229 patients assayed, and an isocitrate dehydrogenase 1 mutation was detected in 7 (6.6%) of the 106 patients analyzed. Univariate analyses showed that patient age, involvement of eloquent areas, involvement of the subventricular zone, presence of leptomeningeal seeding, Karnofsky Performance Status, extent of resection (EOR), MGMT promoter methylation, and presence of an oligodendroglioma component were prognostic of OS. Multivariate analysis showed that age, involvement of eloquent areas, presence of leptomeningeal seeding, EOR, and MGMT promoter methylation were significantly predictive of survival. OS in patients with GBM who undergo surgery followed by CCRT with TMZ is enhanced by complete resection. Other factors significantly prognostic of OS include that age, involvement of eloquent areas, presence of leptomeningeal seeding, and MGMT promoter methylation.
Address aYonsei University Graduate School, Seoul bDepartment of Neurosurgery, Ajou University Hospital, Ajou University School of Medicine, Suwon cDepartment of Neurosurgery dDepartment of Radiology eDepartment of Medical Oncology fDepartment of Radiation Oncology gDepartment of Pathology, Yonsei University College of Medicine hBrain Tumor Center, Severance Hospital, Yonsei University Health System iBrain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title (down)
Series Volume Series Issue Edition
ISSN 0025-7974 ISBN Medium
Area Expedition Conference
Notes PMID:28682902 Approved no
Call Number ref @ user @ Serial 96578
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Author Rosager, A.M.; Sorensen, M.D.; Dahlrot, R.H.; Boldt, H.B.; Hansen, S.; Lathia, J.D.; Kristensen, B.W.
Title Expression and prognostic value of JAM-A in gliomas Type Journal Article
Year 2017 Publication Journal of Neuro-Oncology Abbreviated Journal J Neurooncol
Volume Issue Pages
Keywords Astrocytic brain tumors; Glioma; Junctional adhesion molecule-A; Prognosis; Tumor stem cell
Abstract Gliomas are among the most lethal cancers, being highly resistant to both chemo- and radiotherapy. The expression of junctional adhesion molecule-A (JAM-A) was recently identified on the surface of stem cell-like brain tumor-initiating cells and suggested to function as a unique glioblastoma niche adhesion factor influencing the tumorigenic potential of brain tumor-initiating cells. We have recently identified high JAM-A expression to be associated with poor outcome in glioblastomas, and our aim was to further investigate the expression of JAM-A in gliomas focusing especially on the prognostic value in WHO grade II and III gliomas. JAM-A protein expression was evaluated by immunohistochemistry and advanced quantitative image analysis with continuous estimates of staining intensity. The JAM-A antibody stained tumor cell membranes and cytoplasm to various extent in different glioma subtypes, and the intensity was higher in glioblastomas than low-grade gliomas. We could not detect an association with overall survival in patients with grade II and III tumors. Double-immunofluorescence stainings in glioblastomas revealed co-expression of JAM-A with CD133, SOX2, nestin, and GFAP in tumor cells as well as some co-expression with the microglial/macrophage marker IBA-1. In conclusion, JAM-A expression was higher in glioblastomas compared to low-grade gliomas and co-localized with recognized stem cell markers suggesting an association of JAM-A with glioma aggressiveness. No significant association between JAM-A expression and overall survival was found in grade II and III gliomas. Further research is needed to determine the function and clinical impact of JAM-A in gliomas.
Address Department of Clinical Research, University of Southern Denmark, Winslowparken 19, 3rd floor, 5000, Odense, Denmark
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title (down)
Series Volume Series Issue Edition
ISSN 0167-594X ISBN Medium
Area Expedition Conference
Notes PMID:28677106 Approved no
Call Number ref @ user @ Serial 96579
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Author Voss, D.M.; Spina, R.; Carter, D.L.; Lim, K.S.; Jeffery, C.J.; Bar, E.E.
Title Disruption of the monocarboxylate transporter-4-basigin interaction inhibits the hypoxic response, proliferation, and tumor progression Type Journal Article
Year 2017 Publication Scientific Reports Abbreviated Journal Sci Rep
Volume 7 Issue 1 Pages 4292
Keywords
Abstract We have previously shown that glioblastoma stem cells (GSCs) are enriched in the hypoxic tumor microenvironment, and that monocarboxylate transporter-4 (MCT4) is critical for mediating GSC signaling in hypoxia. Basigin is involved in many physiological functions during early stages of development and in cancer and is required for functional plasma membrane expression of MCT4. We sought to determine if disruption of the MCT-Basigin interaction may be achieved with a small molecule. Using a cell-based drug-screening assay, we identified Acriflavine (ACF), a small molecule that inhibits the binding between Basigin and MCT4. Surface plasmon resonance and cellular thermal-shift-assays confirmed ACF binding to basigin in vitro and in live glioblastoma cells, respectively. ACF significantly inhibited growth and self-renewal potential of several glioblastoma neurosphere lines in vitro, and this activity was further augmented by hypoxia. Finally, treatment of mice bearing GSC-derived xenografts resulted in significant inhibition of tumor progression in early and late-stage disease. ACF treatment inhibited intratumoral expression of VEGF and tumor vascularization. Our work serves as a proof-of-concept as it shows, for the first time, that disruption of MCT binding to their chaperon, Basigin, may be an effective approach to target GSC and to inhibit angiogenesis and tumor progression.
Address Department of Neurological Surgery, Case Western Reserve University School of Medicine and The Case Comprehensive Cancer Center, Cleveland, OH, USA. eli.bar@case.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title (down)
Series Volume Series Issue Edition
ISSN 2045-2322 ISBN Medium
Area Expedition Conference
Notes PMID:28655889 Approved no
Call Number ref @ user @ Serial 96580
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