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Journal of Cellular and Molecular... Jul 2023The expression changes of baculovirus inhibitor of apoptosis repeat-containing protein5 in brain glioma after administration of Scutellarin was detected. To explore the...
The expression changes of baculovirus inhibitor of apoptosis repeat-containing protein5 in brain glioma after administration of Scutellarin was detected. To explore the effort of scutellarin on anti-glioma by downregulating BIRC5.The effect of scutellarin on tumour growth and animal survival was detected by administering scutellarin to nude mice subcutaneous tumour formation and SD rats in situ tumour formation models. A significantly different gene BIRC5 was found by using the combination of TCGA databases and network pharmacology. And then qPCR was performed to detect the expression of BIRC5 in glioma tissues, cells and normal brain tissues and glial cells. CCK-8 was used to detect the IC50 of scutellarin on glioma cells. The wound healing assay, flow cytometry and MTT test were used to detect the effect of scutellarin on the apoptosis and proliferation of glioma cells. The expression of BIRC5 in glioma tissues was significantly higher than that in normal brain tissues. Scutellarin can significantly reduce tumour growth and improve animal's survival. After scutellarin was administered, the expression of BIRC5 in U251 cells was significantly reduced. And after same time, apoptosis increased and cell proliferation was inhibited. This original research showed that scutellarin can promote the apoptosis of glioma cells and inhibit the proliferation by downregulating the expression of BIRC5.
Topics: Mice; Rats; Animals; Mice, Nude; Rats, Sprague-Dawley; Apoptosis; Cell Proliferation; Glioma; Cell Line, Tumor; Brain Neoplasms; Gene Expression Regulation, Neoplastic
PubMed: 37340587
DOI: 10.1111/jcmm.17788 -
International Journal of Molecular... Jun 2023Exosomes constitute small extracellular vesicles that contain lipids, proteins, nucleic acids, and glycoconjugates from the secreted cells and are capable of... (Review)
Review
Exosomes constitute small extracellular vesicles that contain lipids, proteins, nucleic acids, and glycoconjugates from the secreted cells and are capable of transmitting signals between cells and coordinating cellular communication. By this means, they are ultimately involved in physiology and disease, including development, homeostasis, and immune system regulation, as well as contributing to tumor progression and neurodegenerative diseases pathology. Recent studies have shown that gliomas secrete a panel of exosomes which have been associated with cell invasion and migration, tumor immune tolerance, potential for malignant transformation, neovascularization, and resistance to treatment. Exosomes have therefore emerged as intercellular communicators, which mediate the tumor-microenvironment interactions and exosome-regulated glioma cell stemness and angiogenesis. They may induce tumor proliferation and malignancy in normal cells by carrying pro-migratory modulators from cancer cells as well as many different molecular cancer modifiers, such as oncogenic transcripts, miRNAs, mutant oncoproteins, etc., which promote the communication of cancer cells with the surrounding stromal cells and provide valuable information on the molecular profile of the existing tumor. Moreover, engineered exosomes can provide an alternative system for drug delivery and enable efficient treatment. In the present review, we discuss the latest findings regarding the role of exosomes in glioma pathogenesis, their utility in non-invasive diagnosis, and potential applications to treatment.
Topics: Humans; Exosomes; Glioma; Neoplasms; Extracellular Vesicles; Cell Communication; Biomarkers; Tumor Microenvironment
PubMed: 37373314
DOI: 10.3390/ijms241210162 -
Frontiers in Immunology 2020Glioma is the most malignant primary tumor of the central nervous system and is characterized by an extremely low overall survival. Recent breakthroughs in cancer... (Review)
Review
Glioma is the most malignant primary tumor of the central nervous system and is characterized by an extremely low overall survival. Recent breakthroughs in cancer therapy using immune checkpoint blockade have attracted significant attention. However, despite representing the most promising (immunotherapy) treatment for cancer, the clinical application of immune checkpoint blockade in glioma patients remains challenging due to the "cold phenotype" of glioma and multiple factors inducing resistance, both intrinsic and acquired. Therefore, comprehensive understanding of the tumor microenvironment and the unique immunological status of the brain will be critical for the application of glioma immunotherapy. More sensitive biomarkers to monitor the immune response, as well as combining multiple immunotherapy strategies, may accelerate clinical progress and enable development of effective and safe treatments for glioma patients.
Topics: Animals; Brain Neoplasms; Glioma; Humans; Immune Checkpoint Inhibitors; Molecular Targeted Therapy; Signal Transduction; Treatment Outcome; Tumor Microenvironment
PubMed: 33329549
DOI: 10.3389/fimmu.2020.578877 -
Frontiers in Immunology 2023Glioblastoma is the most common primary malignant tumor of the central nervous system, which has the characteristics of strong invasion, frequent recurrence, and rapid... (Review)
Review
Glioblastoma is the most common primary malignant tumor of the central nervous system, which has the characteristics of strong invasion, frequent recurrence, and rapid progression. These characteristics are inseparable from the evasion of glioma cells from immune killing, which makes immune escape a great obstacle to the treatment of glioma, and studies have confirmed that glioma patients with immune escape tend to have poor prognosis. The lysosomal peptidase lysosome family plays an important role in the immune escape process of glioma, which mainly includes aspartic acid cathepsin, serine cathepsin, asparagine endopeptidases, and cysteine cathepsins. Among them, the cysteine cathepsin family plays a prominent role in the immune escape of glioma. Numerous studies have confirmed that glioma immune escape mediated by lysosomal peptidases has something to do with autophagy, cell signaling pathways, immune cells, cytokines, and other mechanisms, especially lysosome organization. The relationship between protease and autophagy is more complicated, and the current research is neither complete nor in-depth. Therefore, this article reviews how lysosomal peptidases mediate the immune escape of glioma through the above mechanisms and explores the possibility of lysosomal peptidases as a target of glioma immunotherapy.
Topics: Humans; Peptide Hydrolases; Cysteine; Cathepsins; Glioma; Lysosomes
PubMed: 37398678
DOI: 10.3389/fimmu.2023.1154146 -
Tomography (Ann Arbor, Mich.) May 2024Despite their relatively low incidence globally, central nervous system (CNS) tumors remain amongst the most lethal cancers, with only a few other malignancies... (Review)
Review
Despite their relatively low incidence globally, central nervous system (CNS) tumors remain amongst the most lethal cancers, with only a few other malignancies surpassing them in 5-year mortality rates. Treatment decisions for brain tumors heavily rely on histopathological analysis, particularly intraoperatively, to guide surgical interventions and optimize patient outcomes. Frozen sectioning has emerged as a vital intraoperative technique, allowing for highly accurate, rapid analysis of tissue samples, although it poses challenges regarding interpretive errors and tissue distortion. Raman histology, based on Raman spectroscopy, has shown great promise in providing label-free, molecular information for accurate intraoperative diagnosis, aiding in tumor resection and the identification of neurodegenerative disease. Techniques including Stimulated Raman Scattering (SRS), Coherent Anti-Stokes Raman Scattering (CARS), Surface-Enhanced Raman Scattering (SERS), and Tip-Enhanced Raman Scattering (TERS) have profoundly enhanced the speed and resolution of Raman imaging. Similarly, Confocal Laser Endomicroscopy (CLE) allows for real-time imaging and the rapid intraoperative histologic evaluation of specimens. While CLE is primarily utilized in gastrointestinal procedures, its application in neurosurgery is promising, particularly in the context of gliomas and meningiomas. This review focuses on discussing the immense progress in intraoperative histology within neurosurgery and provides insight into the impact of these advancements on enhancing patient outcomes.
Topics: Humans; Spectrum Analysis, Raman; Neurosurgical Procedures; Brain Neoplasms; Glioma; Microscopy, Confocal
PubMed: 38787014
DOI: 10.3390/tomography10050054 -
Journal of Veterinary Diagnostic... Sep 2022Ependymoma, one of the most common gliomas in cats, occurs most often in the lateral and third ventricles and has variable histologic patterns that often form rosettes...
Ependymoma, one of the most common gliomas in cats, occurs most often in the lateral and third ventricles and has variable histologic patterns that often form rosettes and pseudorosettes. Oligodendrocyte transcription factor (OLIG2) is expressed in oligodendrocyte precursor cells and mature oligodendrocytes. Although widely used as a diagnostic marker for most gliomas, OLIG2 is reported to have minimal immunolabeling in ependymomas. Here we characterize the OLIG2 immunolabeling pattern in 19 cases of feline ependymoma, which occurred predominantly in the lateral and third ventricles. Immunohistochemistry for GFAP was variable in 14 cases and was typically localized in the cytoplasmic processes of the neoplastic ependymal cells, especially in the rosettes and pseudorosettes. Nuclear OLIG2 immunolabeling was present in 17 cases and varied in intensity from weak (4 cases) to strong (13 cases). The distribution of OLIG2 immunolabeling within the neoplasms included none (2 cases), <25% (7 cases), 25-50% (6 cases), 51-75% (2 cases), and >75% (3 cases). OLIG2 immunolabeling intensity and distribution is widespread in feline ependymoma, in contrast to ependymomas in other species, and should not be relied upon as a specific marker for feline oligodendroglioma.
Topics: Animals; Brain Neoplasms; Cat Diseases; Cats; Ependymoma; Glioma; Immunohistochemistry; Oligodendroglioma
PubMed: 35762120
DOI: 10.1177/10406387221107898 -
Aging Sep 2023Glioma is the most frequent primary tumor of the central nervous system. The high heterogeneity of glioma tumors enables them to adapt to challenging environments,...
BACKGROUND
Glioma is the most frequent primary tumor of the central nervous system. The high heterogeneity of glioma tumors enables them to adapt to challenging environments, leading to resistance to treatment. Therefore, to detect the driving factors and improve the prognosis of glioma, it is essential to have a comprehensive understanding of the genomic heterogeneity, stemness, and immune microenvironment of glioma.
METHODS
We classified gliomas into various subtypes based on stemness, genomic heterogeneity, and immune microenvironment consensus clustering analysis. We identified risk hub genes linked to heterogeneous characteristics using WGCNA, LASSO, and multivariate Cox regression analysis and utilized them to create an effective risk model.
RESULTS
We thoroughly investigated the genomic heterogeneity, stemness, and immune microenvironment of glioma and identified the risk hub genes RAB42, SH2D4A, and GDF15 based on the TCGA dataset. We developed a risk model utilizing these genes that can reliably predict the prognosis of glioma patients. The risk signature showed a positive correlation with T cell exhaustion and increased infiltration of immunosuppressive cells, and a negative correlation with the response to immunotherapy. Moreover, we discovered that SH2D4A, one of the risk hub genes, could stimulate the migration and proliferation of glioma cells.
CONCLUSIONS
This study identified risk hub genes and established a risk model by analyzing the genomic heterogeneity, stemness, and immune microenvironment of glioma. Our findings will facilitate the diagnosis and prediction of glioma prognosis and may lead to potential treatment strategies for glioma.
Topics: Humans; Tumor Microenvironment; Genomics; Prognosis; Immunotherapy; Cluster Analysis; Glioma
PubMed: 37698534
DOI: 10.18632/aging.205018 -
Molecular Medicine Reports Aug 2021With the rapid development of sequencing technologies, the characteristics and functions of circular RNAs (circRNAs) in different tissues, and their underlying... (Review)
Review
With the rapid development of sequencing technologies, the characteristics and functions of circular RNAs (circRNAs) in different tissues, and their underlying pathophysiological mechanisms, have been identified. circRNAs are significantly enriched in the brain and are continually expressed from the embryonic stage to the adult stage in rats. Previous studies have reported that certain circRNAs are differentially expressed in glioma and regulate a number of biological processes, such as cell proliferation, metastasis and oncogenesis of glioma. Furthermore, certain circRNAs have been associated with tumor size, World Health Organization tumor grade and poor prognosis in patients with glioma. It has been hypothesized that circRNAs may be involved in the onset and progression of glioma through transcriptional regulation, protein translation and binding to microRNAs. These properties and functions suggest the potential of circRNAs as prognostic biomarkers and therapeutic targets for glioma. For the present review, published studies were examined from PubMed, Embase, Cochrane Central and the reference lists of the retrieved articles. The aim of the present review was to summarize the progress of circRNA research in glioma, discuss the potential diagnostic and prognostic values, and the roles of circRNAs in glioma, and provide a novel theoretical basis and research concepts for the prediction, diagnosis and treatment of glioma.
Topics: Animals; Biomarkers, Tumor; Brain; Cell Proliferation; Databases, Factual; Gene Expression Regulation, Neoplastic; Glioma; Humans; RNA, Circular; Rats
PubMed: 34165178
DOI: 10.3892/mmr.2021.12240 -
Theranostics 2023The CRISPR/Cas13a system offers the advantages of rapidity, precision, high sensitivity, and programmability as a molecular diagnostic tool for critical illnesses. One...
The CRISPR/Cas13a system offers the advantages of rapidity, precision, high sensitivity, and programmability as a molecular diagnostic tool for critical illnesses. One of the salient features of CRISPR/Cas13a-based bioassays is its ability to recognize and cleave the target RNA specifically. Simple and efficient approaches for RNA manipulation would enrich our knowledge of disease-linked gene expression patterns and provide insights into their involvement in the underlying pathomechanism. However, only a few studies reported the Cas13a-based reporter system for molecular diagnoses. A tiled crRNA pool targeting a particular RNA transcript was generated, and the optimally potential crRNA candidates were selected using bioinformatics modeling and biological validation methods. For imaging assessment of the anti-GBM effectiveness, we exploited a human GBM patient-derived xenograft model in nude mice. The most efficient crRNA sequence with a substantial cleavage impact on the target RNA as well as a potent collateral cleavage effect, was selected. In the xenografted GBM rodent model, the Cas13a-based reporter system enabled us imaging of the tumor growth. Furthermore, systemic treatments using this approach slowed tumor progression and increased the overall survival time in mice. Our work demonstrated the clinical potential of a Cas13a-based imaging method for the targeted degradation of specific RNAs in glioma cells, and suggested the feasibility of a tailored approach like Cas13a for the modulation of diagnosis and treatment options in glioma.
Topics: Humans; Animals; Mice; Clustered Regularly Interspaced Short Palindromic Repeats; Mice, Nude; Precision Medicine; CRISPR-Cas Systems; RNA; Glioma
PubMed: 37908718
DOI: 10.7150/thno.84429 -
Cell Communication and Signaling : CCS Oct 2020Glioma is the most common primary brain tumor, and is a major health problem throughout the world. Today, researchers have discovered many risk factors that are... (Review)
Review
Glioma is the most common primary brain tumor, and is a major health problem throughout the world. Today, researchers have discovered many risk factors that are associated with the initiation and progression of gliomas. Studies have shown that PIWI-interacting RNAs (piRNAs) and PIWI proteins are involved in tumorigenesis by epigenetic mechanisms. Hence, it seems that piRNAs and PIWI proteins may be potential prognostic, diagnostic or therapeutic biomarkers in the treatment of glioma. Previous studies have demonstrated a relationship between piRNAs and PIWI proteins and some of the molecular and cellular pathways in glioma. Here, we summarize recent evidence and evaluate the molecular mechanisms by which piRNAs and PIWI proteins are involved in glioma. Video abstract.
Topics: Animals; Argonaute Proteins; Biomarkers, Tumor; Epigenesis, Genetic; Glioma; Humans; Models, Biological; RNA, Small Interfering
PubMed: 33109195
DOI: 10.1186/s12964-020-00657-z