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Tumori Aug 2023The purpose of this editorial is to consider some of the aspects of the diagnosis and treatment of adult gliomas. These are rare diseases with all their limitations....
The purpose of this editorial is to consider some of the aspects of the diagnosis and treatment of adult gliomas. These are rare diseases with all their limitations. Innovations in diagnosis and therapy and their constraints are analyzed and compared with the current treatment reality. Aspects affecting these patients' quality of life are highlighted.
Topics: Humans; Adult; Brain Neoplasms; Quality of Life; Glioma
PubMed: 36964665
DOI: 10.1177/03008916231159716 -
Genes & Development Aug 2023The different cell types in the brain have highly specialized roles with unique metabolic requirements. Normal brain function requires the coordinated partitioning of... (Review)
Review
The different cell types in the brain have highly specialized roles with unique metabolic requirements. Normal brain function requires the coordinated partitioning of metabolic pathways between these cells, such as in the neuron-astrocyte glutamate-glutamine cycle. An emerging theme in glioblastoma (GBM) biology is that malignant cells integrate into or "hijack" brain metabolism, co-opting neurons and glia for the supply of nutrients and recycling of waste products. Moreover, GBM cells communicate via signaling metabolites in the tumor microenvironment to promote tumor growth and induce immune suppression. Recent findings in this field point toward new therapeutic strategies to target the metabolic exchange processes that fuel tumorigenesis and suppress the anticancer immune response in GBM. Here, we provide an overview of the intercellular division of metabolic labor that occurs in both the normal brain and the GBM tumor microenvironment and then discuss the implications of these interactions for GBM therapy.
Topics: Humans; Glioblastoma; Brain; Neuroglia; Astrocytes; Neurons; Tumor Microenvironment
PubMed: 37648371
DOI: 10.1101/gad.350693.123 -
Nature Communications Jan 2024Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are...
Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are associated with cancer progression, yet their formation mechanism and role in oncolytic virotherapy remain elusive. In this study, we demonstrate that, in glioma, upregulation of IGF2BP3 enhances the expression of E3 ubiquitin protein ligase MIB1, promoting FTO degradation via the ubiquitin-proteasome pathway. This results in increased m6A-mediated CSF3 release and NET formation. Oncolytic herpes simplex virus (oHSV) stimulates IGF2BP3-induced NET formation in malignant glioma. In glioma models in female mice, a BET inhibitor enhances the oncolytic activity of oHSV by impeding IGF2BP3-induced NETosis, reinforcing virus replication through BRD4 recruitment with the CDK9/RPB-1 complex to HSV gene promoters. Our findings unveil the regulation of m6A-mediated NET formation, highlight oncolytic virus-induced NETosis as a critical checkpoint hindering oncolytic potential, and propose targeting NETosis as a strategy to overcome resistance in oncolytic virotherapy.
Topics: Female; Mice; Animals; Oncolytic Virotherapy; Drug Resistance, Neoplasm; Nuclear Proteins; Transcription Factors; Glioma; Simplexvirus; Oncolytic Viruses
PubMed: 38167409
DOI: 10.1038/s41467-023-44576-2 -
Aging Oct 2023The expression of long non-coding RNA (lncRNA) can function as diagnostic and therapeutic biomarker for tumors. This research explores the role of PD-L1-related lncRNAs...
BACKGROUND
The expression of long non-coding RNA (lncRNA) can function as diagnostic and therapeutic biomarker for tumors. This research explores the role of PD-L1-related lncRNAs in affecting malignant characteristics and the immune microenvironment of glioma.
METHODS
Downloading gene expression profiles and clinicopathological information of glioma from TCGA and CGGA databases, 6 PD-L1-related lncRNAs were identified through correlation analysis, Cox and LASSO regression analysis, establishing the risk score model based on them. Bioinformatics analysis and cell experiments were adopted to verify the effects of LINC01271 on glioma.
RESULTS
Risk scores based on 6 PD-L1-related lncRNAs (AL355974.3, LINC01271, AC011899.3, MIR4500HG, LINC02594, AL357055.3) can reflect malignant characteristics and immunotherapy response of glioma. Patients with high LINC01271 expression had a worse prognosis, a higher abundance of M1 subtype macrophages in the immune microenvironment, and a higher degree of tumor malignancy. Experiments confirmed its positive regulatory effect on the proliferation and migration of glioma cells.
CONCLUSIONS
The risk score model based on 6 PD-L1-related lncRNAs can reflect the malignant characteristics and prognosis of glioma. LINC01271 can independently be used as a new target for prognosis evaluation and therapy.
Topics: Humans; B7-H1 Antigen; RNA, Long Noncoding; Glioma; Computational Biology; Databases, Factual; Tumor Microenvironment; Prognosis
PubMed: 37837543
DOI: 10.18632/aging.205120 -
CNS Neuroscience & Therapeutics Aug 2023Gliomas are the most common primary malignant tumors in the central nervous system. However, conventional treatments, such as surgical resection and postoperative... (Review)
Review
Gliomas are the most common primary malignant tumors in the central nervous system. However, conventional treatments, such as surgical resection and postoperative combined chemo- and radio-therapy, are ineffective in improving patients' long-term survival. The tumor microenvironment (TME) consists of stromal cells, tumor components, and innate and acquired immune cells, and these cells, along with the extracellular matrix, regulate and communicate intercellularly to promote TME formation. The immune microenvironment plays a vital role in the development of glioma. Exosomes, which are extracellular vesicles (EVs), facilitate intercellular communication and regulation within the TME. Tumor cells can release exosomes to transmit messages, induce macrophage polarization, and inhibit immune cell activity, ultimately promoting metastasis and immune evasion. Moreover, immune cells can regulate tumorigenesis and progression through exosomes. This review summarized the biological properties of exosomes and their effects on the tumor microenvironment and provides an overview of the interactions between glioma cells and immune cells.
Topics: Humans; Exosomes; Tumor Microenvironment; Glioma; Extracellular Vesicles; Cell Communication; Neoplasms
PubMed: 37170647
DOI: 10.1111/cns.14239 -
Cancer Letters Nov 2023SEM1, a 26 S proteasome complex subunit, is an essential regulator of tumor growth. However, the underlying mechanism of SEM1 mediated glioma progression remains to be...
INTRODUCTION
SEM1, a 26 S proteasome complex subunit, is an essential regulator of tumor growth. However, the underlying mechanism of SEM1 mediated glioma progression remains to be elucidated.
METHODS
Data from bulk-tumor, single-cell, and spatial sequencing were analyzed to reveal correlations between SEM1 and clinical traits, cell types, and functional enrichment in gliomas. Immunohistochemistry was used to assess SEM1 expression. MTT, flow cytometry, apoptosis signature, epithelial-mesenchymal transition signature, Transwell, and organoid assays were used to study SEM1's effect on the malignant behavior of glioma (U251 and LN229) cells. Weighted gene co-expression network analysis (WGCNA) was conducted to construct an SEM1-mediated malignant regulatory network. Accordingly, survival analysis, therapeutic response, drug prediction, and molecular docking analyses were performed.
RESULTS
High SEM1 expression was observed in gliomas and correlated with worse clinical features and prognosis. Moreover, SEM1 is mainly localized in malignant cells (glioma cells). SEM1 knockout inhibited the proliferation, invasion, and migration of glioma cells and promoted their apoptosis. We also constructed an SEM1 malignant regulatory network that was bridged by the PI3K-Akt pathway. The network had a high prognostic value. Finally, drugs potentially targeting SEM1 were screened and docked to SEM1.
CONCLUSIONS
SEM1 is critically involved in the proliferation, apoptosis, invasion, and migration of glioma cells. The SEM1 malignant regulatory network shows high significance for the prognosis and treatment of gliomas.
Topics: Humans; Glioblastoma; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Molecular Docking Simulation; Cell Proliferation; Cell Line, Tumor; Signal Transduction; Glioma; Apoptosis; Cell Movement
PubMed: 37652287
DOI: 10.1016/j.canlet.2023.216368 -
Oncogene Jul 2023Gliomas are highly malignant tumors accounting for the majority of brain neoplasms. They are characterized by nuclear atypia, high mitotic rate and cellular polymorphism... (Review)
Review
Gliomas are highly malignant tumors accounting for the majority of brain neoplasms. They are characterized by nuclear atypia, high mitotic rate and cellular polymorphism that often contributes to aggressiveness and resistance to standard therapy. They often associate with challenging treatment approaches and poor outcomes. New treatment strategies or regimens to improve the efficacy of glioma treatment require a deeper understanding of glioma occurrence and development as well as elucidation of their molecular biological characteristics. Recent studies have revealed RNA modifications as a key regulatory mechanism involved in tumorigenesis, tumor progression, immune regulation, and response to therapy. The present review discusses research advances on several RNA modifications involved in glioma progression and tumor microenvironment (TME) immunoregulation as well as in the development of adaptive drug resistance, summarizing current progress on major RNA modification targeting strategies.
Topics: Humans; Glioma; Brain Neoplasms; RNA; Carcinogenesis; Tumor Microenvironment
PubMed: 37322070
DOI: 10.1038/s41388-023-02746-y -
Frontiers in Immunology 2023Gliomas are one of the most common primary malignant tumours of the central nervous system (CNS), of which glioblastomas (GBMs) are the most common and destructive type.... (Review)
Review
Gliomas are one of the most common primary malignant tumours of the central nervous system (CNS), of which glioblastomas (GBMs) are the most common and destructive type. The glioma tumour microenvironment (TME) has unique characteristics, such as hypoxia, the blood-brain barrier (BBB), reactive oxygen species (ROS) and tumour neovascularization. Therefore, the traditional treatment effect is limited. As cellular oxidative metabolites, ROS not only promote the occurrence and development of gliomas but also affect immune cells in the immune microenvironment. In contrast, either too high or too low ROS levels are detrimental to the survival of glioma cells, which indicates the threshold of ROS. Therefore, an in-depth understanding of the mechanisms of ROS production and scavenging, the threshold of ROS, and the role of ROS in the glioma TME can provide new methods and strategies for glioma treatment. Current methods to increase ROS include photodynamic therapy (PDT), sonodynamic therapy (SDT), and chemodynamic therapy (CDT), etc., and methods to eliminate ROS include the ingestion of antioxidants. Increasing/scavenging ROS is potentially applicable treatment, and further studies will help to provide more effective strategies for glioma treatment.
Topics: Humans; Reactive Oxygen Species; Glioma; Photochemotherapy; Antioxidants; Tumor Microenvironment
PubMed: 38130720
DOI: 10.3389/fimmu.2023.1259797 -
International Journal of Molecular... Jan 2024Currently, there is a lack of effective therapies for the majority of glioblastomas (GBMs), the most common and malignant primary brain tumor. While immunotherapies have... (Review)
Review
Currently, there is a lack of effective therapies for the majority of glioblastomas (GBMs), the most common and malignant primary brain tumor. While immunotherapies have shown promise in treating various types of cancers, they have had limited success in improving the overall survival of GBM patients. Therefore, advancing GBM treatment requires a deeper understanding of the molecular and cellular mechanisms that cause resistance to immunotherapy. Further insights into the innate immune response are crucial for developing more potent treatments for brain tumors. Our review provides a brief overview of innate immunity. In addition, we provide a discussion of current therapies aimed at boosting the innate immunity in gliomas. These approaches encompass strategies to activate Toll-like receptors, induce stress responses, enhance the innate immune response, leverage interferon type-I therapy, therapeutic antibodies, immune checkpoint antibodies, natural killer (NK) cells, and oncolytic virotherapy, and manipulate the microbiome. Both preclinical and clinical studies indicate that a better understanding of the mechanisms governing the innate immune response in GBM could enhance immunotherapy and reinforce the effects of chemotherapy and radiotherapy. Consequently, a more comprehensive understanding of the innate immune response against cancer should lead to better prognoses and increased overall survival for GBM patients.
Topics: Humans; Glioma; Immunotherapy; Brain Neoplasms; Glioblastoma; Immunity, Innate
PubMed: 38256021
DOI: 10.3390/ijms25020947 -
British Journal of Pharmacology Oct 2023Glioblastoma (GBM) is the most aggressive brain tumour in the central nervous system, but the current treatment is very limited and unsatisfactory. PGE -initiated cAMP...
BACKGROUND AND PURPOSE
Glioblastoma (GBM) is the most aggressive brain tumour in the central nervous system, but the current treatment is very limited and unsatisfactory. PGE -initiated cAMP signalling via EP and EP receptors is involved in the tumourigenesis of multiple cancer types. However, whether or how EP and EP receptors contribute to GBM growth largely remains elusive.
EXPERIMENTAL APPROACH
We performed comprehensive data analysis of gene expression in human GBM samples and determined their expression correlations through multiple bioinformatics approaches. A time-resolved fluorescence energy transfer (TR-FRET) assay was utilized to characterize PGE -mediated cAMP signalling via EP and EP receptors in human glioblastoma cells. Using recently reported potent and selective small-molecule antagonists, we determined the effects of inhibition of EP and EP receptors on GBM growth in subcutaneous and intracranial tumour models.
KEY RESULTS
The expression of both EP and EP receptors was upregulated and highly correlated with a variety of tumour-promoting cytokines, chemokines, and growth factors in human gliomas. Further, they were heterogeneously expressed in human GBM cells, where they compensated for each other to mediate PGE -initiated cAMP signalling and to promote colony formation, cell invasion and migration. Inhibition of EP and EP receptors revealed that these receptors might mediate GBM growth, angiogenesis, and immune evasion in a compensatory manner.
CONCLUSION AND IMPLICATIONS
The compensatory roles of EP and EP receptors in GBM development and growth suggest that concurrently targeting these two PGE receptors might represent a more effective strategy than inhibiting either alone for GBM treatment.
Topics: Humans; Dinoprostone; Glioblastoma; Glioma; Receptors, Prostaglandin E, EP2 Subtype; Receptors, Prostaglandin E, EP4 Subtype
PubMed: 37232020
DOI: 10.1111/bph.16148