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Author Emery, I.F.; Gopalan, A.; Wood, S.; Chow, K.-H.; Battelli, C.; George, J.; Blaszyk, H.; Florman, J.; Yun, K. url  doi
openurl 
  Title Expression and function of ABCG2 and XIAP in glioblastomas Type Journal Article
  Year 2017 Publication (up) Journal of Neuro-Oncology Abbreviated Journal J Neurooncol  
  Volume 133 Issue 1 Pages 47-57  
  Keywords Abcg2; Glioblastoma; Glioma stem cells; Ko143; Xiap  
  Abstract Despite multimodal treatment that includes surgery, radiation and chemotherapy, virtually all glioblastomas (GBM) recur, indicating that these interventions are insufficient to eradicate all malignant cells. To identify potential new therapeutic targets in GBMs, we examined the expression and function of proteins that are associated with therapy resistance and cancer cell survival. We measured the expression of eight such proteins in 50 GBM samples by immunohistochemistry and analyzed patient survival. We report that GBM patients with high expression of ABCG2 (also called BCRP) or XIAP at the protein level had worse survival than those with low expression. The adjusted hazard ratio for ABCG2 was 2.35 and for XIAP was 2.65. Since glioma stem cells (GSCs) have been shown to be more resistant than bulk tumor cells to anti-cancer therapies and to express high levels of these proteins, we also sought to determine if ABCG2 and XIAP have functional roles in GSCs. We used small molecule inhibitors to treat patient-derived GBM tumorspheres in vitro and observed that inhibitors of ABCG2, Ko143 and fumitremorgin, significantly reduced self-renewal. These results suggest that ABCG2 and XIAP proteins may be useful indicators of patient survival and that inhibition of ABCG2 may be a promising therapeutic strategy in GBMs.  
  Address Peak Center for Brain and Pituitary Tumors, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA. kyun@houstonmethodist.org  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 0167-594X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28432589 Approved no  
  Call Number ref @ user @ Serial 96591  
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Author Azoulay, M.; Santos, F.; Shenouda, G.; Petrecca, K.; Oweida, A.; Guiot, M.C.; Owen, S.; Panet-Raymond, V.; Souhami, L.; Abdulkarim, B.S. url  doi
openurl 
  Title Benefit of re-operation and salvage therapies for recurrent glioblastoma multiforme: results from a single institution Type Journal Article
  Year 2017 Publication (up) Journal of Neuro-Oncology Abbreviated Journal J Neurooncol  
  Volume 132 Issue 3 Pages 419-426  
  Keywords Bevacizumab; Glioblastoma; Radiation; Recurrence; Surgery; Temozolomide  
  Abstract The optimal management of recurrent glioblastoma (GBM) has yet to be determined. We aim to assess the benefits of re-operation and salvage therapies (chemotherapy and/or re-irradiation) for recurrent GBM and to identify prognostic factors associated with better survival. All patients who underwent surgery for GBM between January 2005 and December 2012 followed by adjuvant radiotherapy, and who developed GBM recurrence on imaging were included in this retrospective study. Univariate and multivariate analysis was performed using Cox models in order to identify factors associated with overall survival (OS). One hundred and eighty patients treated to a dose of 60 Gy were diagnosed with recurrent GBM. At a median follow-up time of 6.2 months, the median survival (MS) from time of recurrence was 6.6 months. Sixty-nine patients underwent repeat surgery for recurrence based on imaging. To establish the benefits of repeat surgery and salvage therapies, 68 patients who underwent repeat surgery were matched to patients who did not based on extent of initial resection and presence of subventricular zone involvement at recurrence. MS for patients who underwent re-operation was 9.6 months, compared to 5.3 months for patients who did not have repeat surgery (p < 0.0001). Multivariate analysis in the matched pairs confirmed that repeat surgery with the addition of other salvage treatment can significantly affect patient outcome (HR 0.53). Re-operation with additional salvage therapies for recurrent GBM provides survival prolongation at the time of progression.  
  Address Department of Oncology, Division of Radiation Oncology, Cedars Cancer Centre, McGill University Health Centre, 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Canada. bassam.abdulkarim@mcgill.ca  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0167-594X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28374095 Approved no  
  Call Number ref @ user @ Serial 96599  
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Author Ludwig, K.; Kornblum, H.I. url  doi
openurl 
  Title Molecular markers in glioma Type Journal Article
  Year 2017 Publication (up) Journal of Neuro-Oncology Abbreviated Journal J Neurooncol  
  Volume Issue Pages  
  Keywords Glioblastoma; Glioma stem cell; Molecular markers; Mutations; Pathways  
  Abstract Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.  
  Address Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. Hkornblum@mednet.ucla.edu  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  ISSN 0167-594X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28233083 Approved no  
  Call Number ref @ user @ Serial 96605  
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Author Munthe, S.; Halle, B.; Boldt, H.B.; Christiansen, H.; Schmidt, S.; Kaimal, V.; Xu, J.; Zabludoff, S.; Mollenhauer, J.; Poulsen, F.R.; Kristensen, B.W. url  doi
openurl 
  Title Shift of microRNA profile upon glioma cell migration using patient-derived spheroids and serum-free conditions Type Journal Article
  Year 2017 Publication (up) Journal of Neuro-Oncology Abbreviated Journal J Neurooncol  
  Volume 132 Issue 1 Pages 45-54  
  Keywords Glioblastoma; MicroRNA; Migration; Serum-free; Target  
  Abstract Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM cells using serum-free stem cell conditions. We used patient-derived GBM spheroid cultures for a novel serum-free migration assay. MiRNA expression of migrating tumor cells isolated at maximum migration speed was compared with corresponding spheroids using an OpenArray Real-Time PCR System. The miRNA profiling revealed 30 miRNAs to be differentially expressed. In total 13 miRNAs were upregulated and 17 downregulated in migrating cells compared to corresponding spheroids. The three most deregulated miRNAs, miR-1227 (up-regulated), miR-32 (down-regulated) and miR-222 (down-regulated), were experimentally overexpressed. A non-significantly increased migration rate was observed after miR-1227 overexpression. A significantly reduced migration rate was observed after miR-32 and miR-222 overexpression. In conclusion a shift in microRNA profile upon glioma cell migration was identified using an assay avoiding serum-induced migration. Both the miRNA profiling and the functional validation suggested that miR-1227 may be associated with increased migration and miR-32 and miR-222 with decreased migration. These miRNAs may represent potential novel targets in migrating glioma cells.  
  Address Institute of Clinical Research, University of Southern Denmark, Winslowparken 19, 5000, Odense C, Denmark. bjarne.winther.kristensen@rsyd.dk  
  Corporate Author Thesis  
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  ISSN 0167-594X ISBN Medium  
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  Notes PMID:28091986 Approved no  
  Call Number ref @ user @ Serial 96611  
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Author Mistry, A.M.; Dewan, M.C.; White-Dzuro, G.A.; Brinson, P.R.; Weaver, K.D.; Thompson, R.C.; Ihrie, R.A.; Chambless, L.B. url  doi
openurl 
  Title Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum Type Journal Article
  Year 2017 Publication (up) Journal of Neuro-Oncology Abbreviated Journal J Neurooncol  
  Volume 132 Issue 2 Pages 341-349  
  Keywords Glioblastoma; Stem cells; Subgranular zone; Subventricular zone; Survival; Ventricular-subventricular zone  
  Abstract The clinical effect of radiographic contact of glioblastoma (GBM) with neurogenic zones (NZ)-the ventricular-subventricular (VSVZ) and subgranular (SGZ) zones-and the corpus callosum (CC) remains unclear and, in the case of the SGZ, unexplored. We investigated (1) if GBM contact with a NZ correlates with decreased survival; (2) if so, whether this effect is associated with a specific NZ; and (3) if radiographic contact with or invasion of the CC by GBM is associated with decreased survival. We retrospectively identified 207 adult patients who underwent cytoreductive surgery for GBM followed by chemotherapy and/or radiation. Age, preoperative Karnofsky performance status score (KPS), and extent of resection were recorded. Preoperative MRIs were blindly analyzed to calculate tumor volume and assess its contact with VSVZ, SGZ, CC, and cortex. Overall (OS) and progression free (PFS) survivals were calculated and analyzed with multivariate Cox analyses. Among the 207 patients, 111 had GBM contacting VSVZ (VSVZ+GBMs), 23 had SGZ+GBMs, 52 had CC+GBMs, and 164 had cortex+GBMs. VSVZ+, SGZ+, and CC+ GBMs were significantly larger in size relative to their respective non-contacting controls. Multivariate Cox survival analyses revealed GBM contact with the VSVZ, but not SGZ, CC, or cortex, as an independent predictor of lower OS, PFS, and early recurrence. We hypothesize that the VSVZ niche has unique properties that contribute to GBM pathobiology in adults.  
  Address Department of Neurological Surgery, Vanderbilt University Medical Center, T-4224 Medical Center North, 1161 21st Avenue South, Nashville, TN, 37232-2380, 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 0167-594X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28074322 Approved no  
  Call Number ref @ user @ Serial 96612  
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