| Records |
| Author |
Nourallah, B.; Digpal, R.; Jena, R.; Watts, C. |
| Title |
Irradiating the Subventricular Zone in Glioblastoma Patients: Is there a Case for a Clinical Trial? |
Type |
Journal Article |
| Year |
2017 |
Publication |
Clinical Oncology (Royal College of Radiologists (Great Britain)) |
Abbreviated Journal |
Clin Oncol (R Coll Radiol) |
| Volume |
29 |
Issue |
1 |
Pages |
26-33 |
| Keywords |
Adult; Brain Neoplasms/*radiotherapy; Glioblastoma/*radiotherapy; Humans; Lateral Ventricles/*radiation effects; Male; Neoplastic Stem Cells/radiation effects; Stem Cell Niche/radiation effects; Cancer stem cells; glioblastoma; neural stem cells; radiotherapy; subventricular zone |
Abstract  |
Glioblastoma is the most common and aggressive adult brain tumour. Over the last 10 years it has emerged that the subventricular zone (SVZ), the largest adult neural stem cell niche, has an important role in the disease. Converging evidence has implicated transformation of adult neural stems in gliomagenesis and the permissive stem cell niche in disease recurrence. Concurrently, clinical studies have suggested that SVZ involvement is a negative prognostic marker. It would follow that irradiating the SVZ may improve outcomes in glioblastoma by directly targeting this putative sanctuary site. To investigate this potential strategy, 11 retrospective studies and 1 prospective study examined the relationship between dose to the SVZ and survival outcomes in glioblastoma patients. This review summarises the theoretical underpinning of this strategy, provides a critical evaluation of the existing evidence and discusses the rationale for a clinical trial. |
| Address |
John van Geest Centre for Repair, Cambridge, UK; Department of Clinical Neurosciences, Division of Neurosurgery, Addenbrookes Hospital, Cambridge, UK. Electronic address: cw209@cam.ac.uk |
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English |
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| ISSN |
0936-6555 |
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| Notes |
PMID:27729188 |
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no |
| Call Number |
ref @ user @ |
Serial |
96633 |
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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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| ISSN |
1010-4283 |
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| Notes |
PMID:28639900 |
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no |
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ref @ user @ |
Serial |
96581 |
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| Author |
Magrath, J.W.; Kim, Y. |
| Title |
Salinomycin's potential to eliminate glioblastoma stem cells and treat glioblastoma multiforme (Review) |
Type |
Journal Article |
| Year |
2017 |
Publication |
International Journal of Oncology |
Abbreviated Journal |
Int J Oncol |
| Volume |
51 |
Issue |
3 |
Pages |
753-759 |
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| Abstract |
Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain tumor. Despite treatment with surgery, radiotherapy, and chemotherapy with the drug temozolomide, the expected survival after diagnosis remains low. The median survival is only 14.6 months and the two-year survival is a mere 30%. One reason for this is the heterogeneity of GBM including the presence of glioblastoma cancer stem cells (GSCs). GSCs are a subset of cells with the unique ability to proliferate, differentiate, and create tumors. GSCs are resistant to chemotherapy and radiation and thought to play an important role in recurrence. In order to effectively treat GBM, a drug must be identified that can kill GSCs. The ionophore salinomycin has been shown to kill cancer stem cells and is therefore a promising future treatment for GBM. This study focuses on salinomycin's potential to treat GBM including its ability to reduce the CSC population, its toxicity to normal brain cells, its mechanism of action, and its potential for combination treatment. |
| Address |
Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL 35487-0203, USA |
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English |
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Series Issue |
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Edition |
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1019-6439 |
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| Notes |
PMID:28766685 |
Approved |
no |
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ref @ user @ |
Serial |
96573 |
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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 |
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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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Edition |
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1937-6448 |
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| Notes |
PMID:28729027 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96577 |
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| Author |
Miranda, A.; Blanco-Prieto, M.; Sousa, J.; Pais, A.; Vitorino, C. |
| Title |
Breaching barriers in glioblastoma. Part I: Molecular pathways and novel treatment approaches |
Type |
Journal Article |
| Year |
2017 |
Publication |
International Journal of Pharmaceutics |
Abbreviated Journal |
Int J Pharm |
| Volume |
531 |
Issue |
1 |
Pages |
372-388 |
| Keywords |
Glioblastoma; Molecular mechanisms; Temozolomide; Therapeutic advances; Therapeutic resistance |
| Abstract |
Glioblastoma multiforme (GBM) is the most common primary brain tumour, and the most aggressive in nature. The prognosis for patients with GBM remains poor, with a median survival time of only 1-2 years. The treatment failure relies on the development of resistance by tumour cells and the difficulty of ensuring that drugs effectively cross the dual blood brain barrier/blood brain tumour barrier. The advanced molecular and genetic knowledge has allowed to identify the mechanisms responsible for temozolomide resistance, which represents the standard of care in GBM, along with surgical resection and radiotherapy. Such resistance has motivated the researchers to investigate new avenues for GBM treatment intended to improve patient survival. In this review, we provide an overview of major obstacles to effective treatment of GBM, encompassing biological barriers, cancer stem cells, DNA repair mechanisms, deregulated signalling pathways and autophagy. New insights and potential therapy approaches for GBM are also discussed, emphasizing localized chemotherapy delivered directly to the brain, immunotherapy, gene therapy and nanoparticle-mediated brain drug delivery. |
| Address |
Faculty of Pharmacy, University of Coimbra, Portugal; Pharmacometrics Group of the Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, Portugal. Electronic address: csvitorino@ff.uc.pt |
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English |
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0378-5173 |
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| Notes |
PMID:28755993 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96574 |
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