| Records |
| Author |
Shahar, T.; Rozovski, U.; Hess, K.R.; Hossain, A.; Gumin, J.; Gao, F.; Fuller, G.N.; Goodman, L.; Sulman, E.P.; Lang, F.F. |
| Title |
Percentage of mesenchymal stem cells in high-grade glioma tumor samples correlates with patient survival |
Type |
Journal Article |
| Year |
2017 |
Publication |
Neuro-Oncology |
Abbreviated Journal |
Neuro Oncol |
| Volume |
19 |
Issue |
5 |
Pages |
660-668 |
| Keywords |
*glioblastoma; *mesenchymal stem cells; *microenvironment; *prognosis |
| Abstract |
Background: Human mesenchymal stem cells (hMSCs) have been shown to reside as stromal cells in human gliomas as glioma-associated hMSCs (GA-hMSCs), but their biological role remains unclear. Because recent evidence indicates that GA-hMSCs drive tumor cell proliferation and stemness, we hypothesized that a higher percentage of GA-hMSCs in tumors predicts poor patient prognosis. Method: We determined the percentage of cells coexpressing GA-hMSC markers CD105+/CD73+/CD90+ from patients with newly diagnosed high-grade glioma and analyzed the association between this percentage and overall survival (OS) in 3 independent cohorts: fresh surgical glioblastoma specimens (cohort 1, N = 9), cultured tumor specimens at passage 3 (cohort 2, N = 28), and The Cancer Genome Atlas (TCGA) database. Results: In all cohorts, patient OS correlated with the percentages of GA-hMSCs in tumors. For cohort 1, the median OS of patients with tumors with a low percentage of triple-positive cells was 46 months, and for tumors with a high percentage of triple-positive cells, it was 12 months (hazard ratio [HR] = 0.24; 95% CI: 0.02-0.5, P = .02). For cohort 2, the median OS of patients with tumors with a low percentage of GA-hMSCs was 66 months, and for tumors with a high percentage, it was 11 months (HR = 0.38; 95% CI: 0.13-0.9, P = .04). In the database of TCGA, the median OS times in patients with high and low coexpression levels of CD105/CD73/CD90 were 8.4 months and 13.1 months (HR = 0.4; 95% CI: 0.1-0.88; P = .04), respectively. Conclusions: The percentage of GA-MSCs inversely correlates with OS, suggesting a role for GA-MSCs in promoting aggressive behavior of gliomas. |
| Address |
Brain Tumor Center, Unit 442, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA |
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English |
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1522-8517 |
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| Notes |
PMID:28453745 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96589 |
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| Author |
Roy, A.; Attarha, S.; Weishaupt, H.; Edqvist, P.-H.; Swartling, F.J.; Bergqvist, M.; Siebzehnrubl, F.A.; Smits, A.; Ponten, F.; Tchougounova, E. |
| Title |
Serglycin as a potential biomarker for glioma: association of serglycin expression, extent of mast cell recruitment and glioblastoma progression |
Type |
Journal Article |
| Year |
2017 |
Publication |
Oncotarget |
Abbreviated Journal |
Oncotarget |
| Volume |
8 |
Issue |
15 |
Pages |
24815-24827 |
| Keywords |
Cd44; Zeb1; glioma; mast cell; serglycin |
| Abstract |
Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients. Analysis of serglycin expression in a large cohort of low- and high-grade human glioma samples reveals that its expression is grade dependent and is positively correlated with mast cell (MC) infiltration. Moreover, serglycin expression in patient-derived glioma cells is significantly increased upon MC co-culture. This is also accompanied by increased expression of CXCL12, CXCL10, as well as markers of cancer progression, including CD44, ZEB1 and vimentin.In conclusion, these findings indicate the importance of infiltrating MCs in glioma by modulating signaling cascades involving serglycin, CD44 and ZEB1. The present investigation reveals serglycin as a potential prognostic marker for glioma and demonstrates an association with the extent of MC recruitment and glioma progression, uncovering potential future therapeutic opportunities for patients. |
| Address |
Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden |
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English |
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1949-2553 |
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| Notes |
PMID:28445977 |
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no |
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ref @ user @ |
Serial |
96590 |
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Emery, I.F.; Gopalan, A.; Wood, S.; Chow, K.-H.; Battelli, C.; George, J.; Blaszyk, H.; Florman, J.; Yun, K. |
| Title |
Expression and function of ABCG2 and XIAP in glioblastomas |
Type |
Journal Article |
| Year |
2017 |
Publication |
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 |
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English |
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0167-594X |
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| Notes |
PMID:28432589 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96591 |
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| Author |
Batista, K.M.P.; Eulate-Beramendi, S.A. de; Pina, K.Y.A.R. de; Figueira, P.R.; Canal, A.F.; Chasin, J.M.A.; Meilan, A.; Ugalde, R.; Vega, I.F. |
| Title |
Mesenchymal/proangiogenic factor YKL-40 related to glioblastomas and its relationship with the subventricular zone |
Type |
Journal Article |
| Year |
2017 |
Publication |
Folia Neuropathologica |
Abbreviated Journal |
Folia Neuropathol |
| Volume |
55 |
Issue |
1 |
Pages |
14-22 |
| Keywords |
Ykl-40; glioblastoma; glioblastoma stem cells; subventricular zone |
| Abstract |
<i>Glioblastoma is the most common primary brain tumor. Despite multimodality therapy with aggressive microsurgical resection and adjuvant chemotherapy and radiotherapy, the median survival is below 15 months. Glioblastomas are heterogeneous tumors with high resistance to most chemotherapeutic drugs. According to reliable evidence, YKL-40, one of the best investigated chitinase-like protein, may facilitate invasion, migration and angiogenesis, and could be also responsible for temozolomide resistance in glioblastoma, thus conferring a dismal prognosis. Previous studies have demonstrated that glioblastoma stem cells give rise to endothelial cells through an YKL-40 influence. Such factor is closely related to the subventricular zone. This review focuses on the most recent theories involving the possible relationship between topographic gliomagenesis related to the subventricular zone and YKL-40.</i>. |
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English |
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1509-572X |
ISBN |
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| Notes |
PMID:28430288 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96592 |
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| Author |
Khalifa, J.; Tensaouti, F.; Lusque, A.; Plas, B.; Lotterie, J.-A.; Benouaich-Amiel, A.; Uro-Coste, E.; Lubrano, V.; Cohen-Jonathan Moyal, E. |
| Title |
Subventricular zones: new key targets for glioblastoma treatment |
Type |
Journal Article |
| Year |
2017 |
Publication |
Radiation Oncology (London, England) |
Abbreviated Journal |
Radiat Oncol |
| Volume |
12 |
Issue |
1 |
Pages |
67 |
| Keywords |
Glioblastoma; Prognostic factors; Radiotherapy; Stem-cell niche; Subventricular Zone |
| Abstract |
BACKGROUND: We aimed to identify subventricular zone (SVZ)-related prognostic factors of survival and patterns of recurrence among patients with glioblastoma. METHODS: Forty-three patients with primary diagnosed glioblastoma treated in our Cancer Center between 2006 and 2010 were identified. All patients received surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral (iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively segmented and radiation dose-volume histograms were generated. Multivariate analysis using the Cox proportional hazards model was assessed to examine the relationship between prognostic factors and time to progression (TTP) or overall survival (OS). RESULTS: Median age was 59 years (range: 25-85). Median follow-up, OS and TTP were 22.7 months (range 7.5-69.7 months), 22.7 months (95% CI 14.5-26.2 months) and 6.4 months (95% CI 4.4-9.3 months), respectively. On univariate analysis, initial contact to SVZ was a poor prognostic factor for OS (18.7 vs 41.7 months, p = 0.014) and TTP (4.6 vs 12.9 months, p = 0.002). Patients whose bSVZ volume receiving at least 20 Gy (V20Gy) was greater than 84% had a significantly improved TTP (17.7 months vs 5.2 months, p = 0.017). This radiation dose coverage was compatible with an hippocampal sparing. On multivariate analysis, initial contact to SVZ and V20 Gy to bSVZ lesser than 84% remained poor prognostic factors for TTP (HR = 3.07, p = 0.012 and HR = 2.67, p = 0.047, respectively). CONCLUSION: Our results suggest that contact to SVZ, as well as insufficient bSVZ radiation dose coverage (V20Gy <84%), might be independent poor prognostic factors for TTP. Therefore, targeting SVZ could be of crucial interest for optimizing glioblastoma treatment. |
| Address |
INSERM U1037, Centre de Recherche contre le Cancer de Toulouse, 1 avenue Irene Joliot-Curie, Toulouse Cedex, 31059, France |
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English |
Summary Language |
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Edition |
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1748-717X |
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| Notes |
PMID:28424082 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96593 |
| Permanent link to this record |
