| Records |
| Author |
Azoulay, M.; Santos, F.; Shenouda, G.; Petrecca, K.; Oweida, A.; Guiot, M.C.; Owen, S.; Panet-Raymond, V.; Souhami, L.; Abdulkarim, B.S. |
| Title |
Benefit of re-operation and salvage therapies for recurrent glioblastoma multiforme: results from a single institution |
Type |
Journal Article |
| Year |
2017 |
Publication |
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 |
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English |
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0167-594X |
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| Notes |
PMID:28374095 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96599 |
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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 |
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 |
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English |
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1010-4283 |
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| Notes |
PMID:28347245 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96600 |
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Momeny, M.; Moghaddaskho, F.; Gortany, N.K.; Yousefi, H.; Sabourinejad, Z.; Zarrinrad, G.; Mirshahvaladi, S.; Eyvani, H.; Barghi, F.; Ahmadinia, L.; Ghazi-Khansari, M.; Dehpour, A.R.; Amanpour, S.; Tavangar, S.M.; Dardaei, L.; Emami, A.H.; Alimoghaddam, K.; Ghavamzadeh, A.; Ghaffari, S.H. |
| Title |
Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells |
Type |
Journal Article |
| Year |
2017 |
Publication |
Scientific Reports |
Abbreviated Journal |
Sci Rep |
| Volume |
7 |
Issue |
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Pages |
44075 |
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| Abstract |
Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Tivozanib diminished GBM cell invasion through impairing the proteolytic cascade of cathepsin B/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase-2 (MMP-2). Combination of tivozanib with EGFR small molecule inhibitor gefitinib synergistically increased sensitivity to gefitinib. Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro. Further in vivo studies are warranted to explore the anti-tumour activity of tivozanib in combinatorial approaches in GBM. |
| Address |
Haematology/Oncology and Stem Cell Transplantation Research Centre, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran |
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English |
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Edition |
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2045-2322 |
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| Notes |
PMID:28287096 |
Approved |
no |
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ref @ user @ |
Serial |
96601 |
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Celiku, O.; Tandle, A.; Chung, J.-Y.; Hewitt, S.M.; Camphausen, K.; Shankavaram, U. |
| Title |
Computational analysis of the mesenchymal signature landscape in gliomas |
Type |
Journal Article |
| Year |
2017 |
Publication |
BMC Medical Genomics |
Abbreviated Journal |
BMC Med Genomics |
| Volume |
10 |
Issue |
1 |
Pages |
13 |
| Keywords |
Cd44; Computational modeling; Epithelial to mesenchymal transition; Glioma |
| Abstract |
BACKGROUND: Epithelial to mesenchymal transition, and mimicking processes, contribute to cancer invasion and metastasis, and are known to be responsible for resistance to various therapeutic agents in many cancers. While a number of studies have proposed molecular signatures that characterize the spectrum of such transition, more work is needed to understand how the mesenchymal signature (MS) is regulated in non-epithelial cancers like gliomas, to identify markers with the most prognostic significance, and potential for therapeutic targeting. RESULTS: Computational analysis of 275 glioma samples from “The Cancer Genome Atlas” was used to identify the regulatory changes between low grade gliomas with little expression of MS, and high grade glioblastomas with high expression of MS. TF (transcription factor)-gene regulatory networks were constructed for each of the cohorts, and 5 major pathways and 118 transcription factors were identified as involved in the differential regulation of the networks. The most significant pathway – Extracellular matrix organization – was further analyzed for prognostic relevance. A 20-gene signature was identified as having prognostic significance (HR (hazard ratio) 3.2, 95% CI (confidence interval) = 1.53-8.33), after controlling for known prognostic factors (age, and glioma grade). The signature's significance was validated in an independent data set. The putative stem cell marker CD44 was biologically validated in glioma cell lines and brain tissue samples. CONCLUSIONS: Our results suggest that the differences between low grade gliomas and high grade glioblastoma are associated with differential expression of the signature genes, raising the possibility that targeting these genes might prolong survival in glioma patients. |
| Address |
Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 10 Center Drive, Bldg. 10, Rm. B3B70, Bethesda, MD, 20892, USA. uma@mail.nih.gov |
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English |
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1755-8794 |
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| Notes |
PMID:28279210 |
Approved |
no |
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ref @ user @ |
Serial |
96602 |
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Jensen, S.S.; Petterson, S.A.; Halle, B.; Aaberg-Jessen, C.; Kristensen, B.W. |
| Title |
Effects of the lysosomal destabilizing drug siramesine on glioblastoma in vitro and in vivo |
Type |
Journal Article |
| Year |
2017 |
Publication |
BMC Cancer |
Abbreviated Journal |
BMC Cancer |
| Volume |
17 |
Issue |
1 |
Pages |
178 |
| Keywords |
Brain slice cultures; Cancer stem cell; Glioblastoma; Lysosomes; Siramesine; Spheroids |
| Abstract |
BACKGROUND: Glioblastoma is the most frequent and most malignant brain tumor with the patients having a median survival of only 14.6 months. Although glioblastoma patients are treated with surgery, radiation and chemotherapy recurrence is inevitable. A stem-like population of radio- and chemoresistant brain tumor-initiating cells combined with the invasive properties of the tumors is believed to be critical for treatment resistance. In the present study, the aim was to investigate the effect of a novel therapeutic strategy using the lysosomotropic detergent siramesine on glioblastomas. METHODS: Standard glioma cell lines and patient-derived spheroids cultures with tumor-initiating stem-like cells were used to investigate effects of siramesine on proliferation and cell death. Responsible mechanisms were investigated by inhibitors of caspases and cathepsins. Effects of siramesine on migrating tumor cells were investigated by a flat surface migration assay and by implanting spheroids into organotypic rat brain slice cultures followed by confocal time-lapse imaging. Finally the effect of siramesine was investigated in an orthotopic mouse glioblastoma model. Results obtained in vitro and in vivo were confirmed by immunohistochemical staining of histological sections of spheroids, spheroids in brain slice cultures and tumors in mice brains. RESULTS: The results showed that siramesine killed standard glioma cell lines in vitro, and loss of acridine orange staining suggested a compromised lysosomal membrane. Co-treatment of the cell lines with inhibitors of caspases and cathepsins suggested differential involvement in cell death. Siramesine caused tumor cell death and reduced secondary spheroid formation of patient-derived spheroid cultures. In the flat surface migration model siramesine caused tumor cell death and inhibited tumor cell migration. This could not be reproduced in the organotypic three dimensional spheroid-brain slice culture model or in the mice xenograft model. CONCLUSIONS: In conclusion the in vitro results obtained with tumor cells and spheroids suggest a potential of lysosomal destabilizing drugs in killing glioblastoma cells, but siramesine was without effect in the organotypic spheroid-brain slice culture model and the in vivo xenograft model. |
| Address |
Institute of Clinical Research, University of Southern Denmark, Winslowparken 19.3, 5000, Odense C, Denmark. bjarne.winther.kristensen@rsyd.dk |
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English |
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1471-2407 |
ISBN |
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| Notes |
PMID:28270132 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96603 |
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