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Pharmacological Research Nov 2023Circular RNA (circRNA) is one of non-coding RNA with specific circular structure, which has been found to be involved in regulating a series of malignant biological...
Circular RNA (circRNA) is one of non-coding RNA with specific circular structure, which has been found to be involved in regulating a series of malignant biological behaviors in many malignant tumors. In this study, based on the IDH1 molecular typing of gliomas, we identified a significant downregulation of circRNA (circIQGAP1) expression in IDH1 mutant gliomas by high-throughput sequencing. In 79 tissue samples, we confirmed that circIQGAP1 expression was significantly downregulated in IDH1 mutant gliomas, and that low circIQGAP1 expression was positively associated with better prognosis. Knockdown of circIQGAP1 in glioma cell lines inhibited glioma cell malignancy and conversely overexpression of circIQGAP1 promoted glioma malignancy. circIQGAP1 regulated glioma cell migration, proliferation, invasion and apoptosis through miR-1256/RCAN1/Bax/Bcl-2/Caspase3 and miR-622/RCAN2/Bax/Bcl-2/Caspase3 axes. These results suggest that circIQGAP1 plays an important role in glioma development, promotes tumor growth, and is a potential therapeutic target for glioma.
Topics: Humans; RNA, Circular; bcl-2-Associated X Protein; Glioma; Proto-Oncogene Proteins c-bcl-2; Transcription Factors; MicroRNAs; DNA-Binding Proteins; Muscle Proteins
PubMed: 37918583
DOI: 10.1016/j.phrs.2023.106979 -
Molecular Therapy : the Journal of the... Jun 2020Malignant gliomas, the most lethal type of primary brain tumor, continue to be a major therapeutic challenge. Here, we found that enterovirus A71 (EV-A71) can be...
Malignant gliomas, the most lethal type of primary brain tumor, continue to be a major therapeutic challenge. Here, we found that enterovirus A71 (EV-A71) can be developed as a novel oncolytic agent against malignant gliomas. EV-A71 preferentially infected and killed malignant glioma cells relative to normal glial cells. The virus receptor human scavenger receptor class B, member 2 (SCARB2), and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)-mediated cell death were involved in EV-A71-induced oncolysis. In mice with implanted subcutaneous gliomas, intraneoplastic inoculation of EV-A71 caused significant tumor growth inhibition. Furthermore, in mice bearing intracranial orthotopic gliomas, intraneoplastic inoculation of EV-A71 substantially prolonged survival. By insertion of brain-specific microRNA-124 (miR124) response elements into the viral genome, we improved the tumor specificity of EV-A71 oncolytic therapy by reducing its neurotoxicity while maintaining its replication potential and oncolytic capacity in gliomas. Our study reveals that EV-A71 is a potent oncolytic agent against malignant gliomas and may have a role in treating this tumor in the clinical setting.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cells, Cultured; Cytopathogenic Effect, Viral; Disease Models, Animal; Enterovirus A, Human; Gene Expression; Genes, Reporter; Genetic Therapy; Genetic Vectors; Glioma; Humans; Lysosomal Membrane Proteins; Mice; Oncolytic Virotherapy; Oncolytic Viruses; Receptors, Scavenger; Transgenes; Treatment Outcome; Virus Replication; Xenograft Model Antitumor Assays
PubMed: 32304669
DOI: 10.1016/j.ymthe.2020.04.005 -
Neurosurgery Jun 2021Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied... (Review)
Review
Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions. Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function. Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients. A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.
Topics: Adult; Brain Neoplasms; Cognition; Cognitive Dysfunction; Glioma; Humans; Neuropsychological Tests; Neurosurgeons; Quality of Life
PubMed: 33289504
DOI: 10.1093/neuros/nyaa400 -
Frontiers in Immunology 2021Exosomes, the small extracellular vesicles, are released by multiple cell types, including tumor cells, and represent a novel avenue for intercellular communication... (Review)
Review
Exosomes, the small extracellular vesicles, are released by multiple cell types, including tumor cells, and represent a novel avenue for intercellular communication transferring diverse biomolecules. Recently, microRNAs (miRNAs) were demonstrated to be enclosed in exosomes and therefore was protected from degradation. Such exosomal miRNAs can be transmitted to recipient cells where they could regulate multiple cancer-associated biological processes. Accumulative evidence suggests that exosomal miRNAs serve essential roles in modifying the glioma immune microenvironment and potentially affecting the malignant behaviors and therapeutic responses. As exosomal miRNAs are detectable in almost all kinds of biofluids and correlated with clinicopathological characteristics of glioma, they might be served as promising biomarkers for gliomas. We reviewed the novel findings regarding the biological functions of exosomal miRNAs during glioma pathogenesis and immune regulation. Furthermore, we elaborated on their potential clinical applications as biomarkers in glioma diagnosis, prognosis and treatment response prediction. Finally, we summarized the accessible databases that can be employed for exosome-associated miRNAs identification and functional exploration of cancers, including glioma.
Topics: Animals; Biomarkers, Tumor; Cell Communication; Cell Proliferation; Databases, Genetic; Disease Management; Disease Susceptibility; Exosomes; Glioma; Humans; Immunomodulation; MicroRNAs; Molecular Targeted Therapy; Neovascularization, Pathologic; RNA Transport; Signal Transduction
PubMed: 35095909
DOI: 10.3389/fimmu.2021.813747 -
Advanced Science (Weinheim,... May 2022Immunotherapy with toll like receptor 9 (TLR9) agonist CpG ODN offers an emergent strategy to treat life-threatening malignant glioma. CpG is typically applied...
Immunotherapy with toll like receptor 9 (TLR9) agonist CpG ODN offers an emergent strategy to treat life-threatening malignant glioma. CpG is typically applied invasively by intracranial and intrathecal administration which induces not only poor compliance and lessened potency but also possibly strong adverse effects and immunotoxicity. Here, it is reported that immunotherapy of murine LCPN glioma is greatly boosted by polymersome-steered intravenous and intranasal brain delivery of CpG. CpG is efficiently loaded in apolipoprotein E peptide-directed polymersomes to give blood-brain barrier permeable and glioma and cervical lymph node-homing CpG nano-immunoadjuvant (t-NanoCpG) which strongly stimulates the maturation of dendritic cells, antigen cross-presentation, and production of proinflammatory cytokines in vivo. Intriguingly, both intravenous and intranasal administration of t-NanoCpG brings about significant survival benefits in murine LCPN glioma-bearing mice while free CpG and nontargeted CpG nano-immunoadjuvant (NanoCpG) afford modest therapeutic effects. Moreover, combination of t-NanoCpG with radiotherapy further boosts the immunotherapeutic effects leading to more improved survival rate of mice. This intelligent brain-permeable nano-immunoadjuvant provides a new, minimally invasive and highly potent strategy for immunotherapy of glioma.
Topics: Adjuvants, Immunologic; Animals; Glioma; Immunologic Factors; Immunotherapy; Mice; Toll-Like Receptor 9
PubMed: 35253404
DOI: 10.1002/advs.202103689 -
Pathology Oncology Research : POR Oct 2014Malignant gliomas are among the deadliest primary brain tumors. Despite multimodal therapy and advances in chemotherapy, imaging, surgical and radiation techniques,... (Review)
Review
Malignant gliomas are among the deadliest primary brain tumors. Despite multimodal therapy and advances in chemotherapy, imaging, surgical and radiation techniques, these tumors remain virtually incurable. Glioma stem cells may be responsible for resistance to traditional therapies and tumor recurrence. Therefore, elimination of glioma stem cells may be crucial for achieving therapeutic efficacy. Metformin, a small molecule drug widely used in the therapy of type 2 diabetes, has shown significant anti-tumor effects in patients with breast cancer and prostate cancer. Recent preclinical data suggest that metformin also has therapeutic effects against glioma. Here we review the markers and hallmarks of glioma stem cells, and the molecular mechanisms involved in therapeutic targeting of glioma stem cells by metformin.
Topics: Biomarkers, Tumor; Glioma; Humans; Hypoglycemic Agents; Metformin; Neoplastic Stem Cells; Prognosis
PubMed: 25168767
DOI: 10.1007/s12253-014-9837-z -
International Journal of Molecular... Nov 2017Gliomas are devastating brain cancers that have poor prognostic outcomes for their patients. Short overall patient survival is due to a lack of durable, efficacious... (Review)
Review
Gliomas are devastating brain cancers that have poor prognostic outcomes for their patients. Short overall patient survival is due to a lack of durable, efficacious treatment options. Such therapeutic difficulties exist, in part, due to several glioma survival adaptations and mechanisms, which allow glioma cells to repurpose paracrine signalling pathways and ion channels within discreet microenvironments. These Darwinian adaptations facilitate invasion into brain parenchyma and perivascular space or promote evasion from anti-cancer defence mechanisms. Ultimately, this culminates in glioma repopulation and migration at distances beyond the original tumour site, which is a considerable obstacle for effective treatment. After an era of failed phase II trials targeting individual signalling pathways, coupled to our increasing knowledge of glioma sub-clonal divergence, combinatorial therapeutic approaches which target multiple molecular pathways and mechanisms will be necessary for better treatment outcomes in treating malignant gliomas. Furthermore, next-generation therapy which focuses on infiltrative tumour phenotypes and disruption of the vascular and perivascular microenvironments harbouring residual disease cells offers optimism for the localised control of malignant gliomas.
Topics: Glioma; Humans; Neoplasm Invasiveness; Parenchymal Tissue; Prognosis; Signal Transduction; Tumor Microenvironment
PubMed: 29113105
DOI: 10.3390/ijms18112342 -
Postepy Biochemii Oct 2018Growing evidence supports a critical role of the tumor-reprogrammed stromal cells in tumor growth and progression. Several extracellular communication networks are... (Review)
Review
Growing evidence supports a critical role of the tumor-reprogrammed stromal cells in tumor growth and progression. Several extracellular communication networks are hijacked by the tumors to influence the surrounding tumor microenvironment. In malignant gliomas, tumor derived factors attract brain resident microglia and peripheral macrophages. These cells, instead of initiating antitumor responses, are re-educated by tumor cells and participate in matrix remodeling, support invasion and angiogenesis, and induce immunosuppression. Molecular underlining of these mutual and complex interactions in malignant gliomas is the main scope of this review.
Topics: Brain Neoplasms; Glioma; Humans; Macrophages; Microglia; Tumor Microenvironment
PubMed: 30656895
DOI: 10.18388/pb.2018_123 -
Neuro-oncology Apr 2016The recent discovery of distinct, ultra-long, and highly functional membrane protrusions in gliomas, particularly in astrocytomas, extends our understanding of how these... (Review)
Review
The recent discovery of distinct, ultra-long, and highly functional membrane protrusions in gliomas, particularly in astrocytomas, extends our understanding of how these tumors progress in the brain and how they resist therapies. In this article, we will focus on ideas on how to target these membrane protrusions, for which we have suggested the term "tumor microtubes" (TMs), and the malignant multicellular network they form. First, we discuss TM-specific features and their differential biological functions known so far. Second, the connection between 1p/19q codeletion and the inability to form functional TMs via certain neurodevelopmental pathways is presented; this could provide an explanation for the distinct clinical features of oligodendrogliomas. Third, the role of TMs for primary and potentially also adaptive resistance to cytotoxic therapies is highlighted. Fourth, avenues for therapeutic approaches to inhibit TM formation and/or function are discussed, with a focus on disruption (or exploitation) of network functionality. Finally, we propose ideas on how to use TMs as a biomarker in glioma patients. An increasing understanding of TMs in clinical and preclinical settings will show us whether they really are a long-sought-after Achilles' heel of treatment-resistant gliomas.
Topics: Brain Neoplasms; Cell Physiological Phenomena; Glioma; Humans; Neural Pathways; Signal Transduction
PubMed: 26995789
DOI: 10.1093/neuonc/now014 -
Journal of Neuro-oncology Jan 2024Malignant gliomas are a therapeutic challenge and remain nearly uniformly fatal. While new targeted chemotherapeutic agentsagainst malignant glioma have been... (Review)
Review
BACKGROUND
Malignant gliomas are a therapeutic challenge and remain nearly uniformly fatal. While new targeted chemotherapeutic agentsagainst malignant glioma have been developed in vitro, these putative therapeutics have not been translated into successful clinical treatments. The lack of clinical effectiveness can be the result of ineffective biologic strategies, heterogeneous tumor targets and/or the result of poortherapeutic distribution to malignant glioma cells using conventional nervous system delivery modalities (intravascular, cerebrospinal fluid and/orpolymer implantation), and/or ineffective biologic strategies.
METHODS
The authors performed a review of the literature for the terms "convection enhanced delivery", "glioblastoma", and "glioma". Selectclinical trials were summarized based on their various biological mechanisms and technological innovation, focusing on more recently publisheddata when possible.
RESULTS
We describe the properties, features and landmark clinical trials associated with convection-enhanced delivery for malignant gliomas.We also discuss future trends that will be vital to CED innovation and improvement.
CONCLUSION
Efficacy of CED for malignant glioma to date has been mixed, but improvements in technology and therapeutic agents arepromising.
Topics: Humans; Convection; Drug Delivery Systems; Brain Neoplasms; Glioma; Biological Products; Antineoplastic Agents
PubMed: 38261143
DOI: 10.1007/s11060-023-04552-8