Emerging treatment strategies for glioblastoma multiforme

Carlsson, Steven K.; Wahlestedt, Claes

doi:10.15252/emmm.201302627

Cited by 312 publications

(312 citation statements)

References 90 publications

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“…Despite advances in surgical resection, radiotherapy, chemotherapy and other therapeutic approaches, including immune and gene therapy, the prognosis for patients with glioblastoma remains poor (3)(4)(5)(6)(7). A previous study demonstrated that the median survival time of patients with glioblastoma was 4.9 months following diagnosis (8).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-590-3p enhances the radioresistance in glioblastoma cells by targeting LRIG1

Chen

Wang

Zhu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. microRNA (miR)-590 has been found to serve potential roles in cancer development; however, the expression and function of miR-590 in human gliomas remains to be elucidated. The present study aimed to investigate the expression of miR-590 in human glioma tissues and radioresistant human glioblastoma cells (U251R), and to determine the effect and related molecular mechanism of miR-590-3p on the radiosensitivity of U251R cells in vitro. The results from reverse transcription-quantitative polymerase chain reaction indicated that miR-590-3p was upregulated in human glioma tissues and radioresistant human glioblastoma cells, and that miR-590-3p expression was higher in high grade than in low grade gliomas. In vitro experiments revealed that the miR-590-3p inhibitor enhanced the radiosensitivity of U251R cells by suppressing cell viability, decreasing colony formation capacity and increasing cell apoptosis rate, as demonstrated by MTT, colony formation and flow cytometry analyses. A luciferase reporter assay demonstrated that leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) was a direct target of miR-590-3p. Furthermore, it was demonstrated that the effect of miR-590-3p suppression on cell viability, colony formation capacity and cell apoptosis rate was attenuated by the knockdown of LRIG1 in the U251R cells. In conclusion, the present study revealed that miR-590-3p was upregulated in human glioma tissues and radioresistant human glioblastoma cells, and miR-590-3p contributes to the radioresistance of human glioblastoma cells by directly targeting LRIG1. These findings may provide potential therapeutic strategies to prevent radioresistance in human gliomas.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-590-3p enhances the radioresistance in glioblastoma cells by targeting LRIG1

Chen

Wang

Zhu

et al. 2017

Experimental and Therapeutic Medicine

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“…All the above-cited mechanisms are becoming of utmost importance in understanding and treatment of the disease, (reviewed in Ref. 16). As all current therapeutic approaches provide poor success in prolonging patients' survival, a challenge is given for novel techniques, such glioblastoma-targeting by aptamers.…”

Section: Aptamers In Gliomamentioning

confidence: 99%

“…In brain tumours magnetic resonance imaging (MRI) represents a standard method for defining lesion boundaries (16) observed as spatially localized signal intensities, by which areas of relative darkness and brightness could be distinguished (31). For a more exact differentiation of GBM from the surrounding brain tissue, a positron emission tomography (PET) is used as a complementary technology (16). PET allows for acquiring images of the tumour boundaries by high-energy gamma-rays that are emitted from isotopelabeled natural biological molecules residing and being concentrated in the cancer cells (32), due to their altered metabolism.…”

Section: Clinical Applications Of Aptamers Imagingmentioning

confidence: 99%

“…PET allows for acquiring images of the tumour boundaries by high-energy gamma-rays that are emitted from isotopelabeled natural biological molecules residing and being concentrated in the cancer cells (32), due to their altered metabolism. Still, more refined and non-invasive diagnostic measures for identification of GBM borders are needed for improved surgical removal, possibly resulting in better patient survival (16). In this respect, aptamers with the ability to couple with some diagnostic agents, such as fluorescent or radionuclide labels, bioconjugates and nanoparticles, represent advanced imaging tools for in vivo tumour visualization, as show on Figure 1.…”

Section: Clinical Applications Of Aptamers Imagingmentioning

confidence: 99%

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Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

Delač

Motaln

Ulrich³

et al. 2015

Cytometry Pt A

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Aptamers are short single-stranded nucleic acids (RNA or ssDNA), identified by an in vitro selection process, denominated SELEX, from a partially random oligonucleotide library. They bind to a molecular target, a protein or other complex macromolecular structures of interest with high affinity and specificity, comparable to those of antibodies. Recently, aptamer selection protocols were developed for targeting living cells, including tumors. Chemical modifications of the aptamers and modalities of their detection and delivery systems are already available with high selectivity and targeting ability for the desired cancer cell type, making them promising for diagnosis and therapy. Glioblastoma multiformae represents the most malignant and fatal stage of glioma, and is also the most frequent brain tumor. Glioblastoma-specific aptamers were developed by either targeting the whole cell surface or known glioma biomarkers. These aptamers may gain importance for imaging, tumor cell isolation from biopsies and drug delivery. In biomedical imaging techniques, aptamers coupled with radionuclide or fluorescent labels, bioconjugates and nanoparticles offer an advanced, noninvasive manner for defining the glioblastoma tissue border. Though single modality aptamer imaging probes have some limitations, these are overcome by the use of multimodal probes. Due to selectivity and chemical characteristics, aptamers can be coupled to functionalized nanoparticles and loaded with a drug, appeared promising for in vivo targeting of glioblastoma. Finally, aptamers are effective mediators for gene silencing when coupled to small interfering RNA and a viral vector, thus providing a novel tool with enhanced targeting capability in drug delivery, designed for tailored treatment of glioblastoma patients. V C 2015 International Society for Advancement of Cytometry Key terms aptamer; SELEX; cancer biomarkers; cell and target protein; imaging; drug delivery; glioblastoma; nanoparticles APTAMERS AND THE SELEX TECHNOLOGY IN CANCER APTAMERS, first introduced by Tuerk and Gold (1) and Ellington and Szostak (2), are short chains of DNA or RNA oligonucleotides that bind to small molecules, peptides, and macromolecules, such as proteins of various sizes and conformations. These are identified by an in vitro selection method in a stepwise evolutionary process from a combinatorial library of partial randomized oligonucleotides, consisting of up to 10 15 different sequences and secondary and tertiary structures by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). It begins with a pool of variable oligonucleotide sequences with multiple rounds of target exposure of the combinatorial RNA or DNA library, followed by elution of target binders and enrichment of those by RT-PCR or PCR procedures are performed. These results in exponential increase of oligonucleotides with improved ligand to target binding in the previously combinatorial library, which finally is narrowed down to a homogeneous population of high-affinity...

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“…It binds to VEGF-A ligand and therefore affects angiogenesis by inhibiting VEGF-endothelial cell interaction. Bevacizumab is active and approved for use in many tumor types [2].…”

Section: Introductionmentioning

confidence: 99%

Bevacizumab in high grade glioma: Is there a subgroup that benefits?

Rigakos¹,

Kyriazoglou²,

Vernadou³

et al. 2017

Hematol Med Oncol

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Background: Prognosis for patients with original glioblastoma diagnosis remains poor. Antiangiogenic therapy with Bevacizumab in first line treatment did not lead to improvement in overall survival, while progression-free survival was prolonged by 3 to 4 months, in recent phase III studies. Bevacizumab therapy in glioblastomas is not successfully associated with any prognostic biological markers. Our study investigates the correlation between the use of bevacizumab and several clinical and molecular markers measured in gliomas everyday clinical practice.

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Emerging treatment strategies for glioblastoma multiforme

Cited by 312 publications

References 90 publications

MicroRNA-590-3p enhances the radioresistance in glioblastoma cells by targeting LRIG1

MicroRNA-590-3p enhances the radioresistance in glioblastoma cells by targeting LRIG1

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

Bevacizumab in high grade glioma: Is there a subgroup that benefits?

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