| Records |
| 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 |
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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 |
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English |
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| ISSN |
1937-6448 |
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| 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 |
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English |
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0025-7974 |
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| 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 |
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Issue |
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Pages |
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| 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 |
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English |
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0167-594X |
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| Notes |
PMID:28677106 |
Approved |
no |
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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 |
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| 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 |
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English |
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2045-2322 |
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| Notes |
PMID:28655889 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96580 |
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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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English |
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Edition |
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1010-4283 |
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| Notes |
PMID:28639900 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96581 |
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