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International Journal of Molecular... May 2020Among heterogeneous primary tumors of the central nervous system (CNS), gliomas are the most frequent type, with glioblastoma multiforme (GBM) characterized with the... (Review)
Review
Among heterogeneous primary tumors of the central nervous system (CNS), gliomas are the most frequent type, with glioblastoma multiforme (GBM) characterized with the worst prognosis. In their development, certain chemokine/receptor axes play important roles and promote proliferation, survival, metastasis, and neoangiogenesis. However, little is known about the significance of atypical receptors for chemokines (ACKRs) in these tumors. The objective of the study was to present the role of chemokines and their conventional and atypical receptors in CNS tumors. Therefore, we performed a thorough search for literature concerning our investigation via the PubMed database. We describe biological functions of chemokines/chemokine receptors from various groups and their significance in carcinogenesis, cancer-related inflammation, neo-angiogenesis, tumor growth, and metastasis. Furthermore, we discuss the role of chemokines in glioma development, with particular regard to their function in the transition from low-grade to high-grade tumors and angiogenic switch. We also depict various chemokine/receptor axes, such as CXCL8-CXCR1/2, CXCL12-CXCR4, CXCL16-CXCR6, CX3CL1-CX3CR1, CCL2-CCR2, and CCL5-CCR5 of special importance in gliomas, as well as atypical chemokine receptors ACKR1-4, CCRL2, and PITPMN3. Additionally, the diagnostic significance and usefulness of the measurement of some chemokines and their receptors in the blood and cerebrospinal fluid (CSF) of glioma patients is also presented.
Topics: Animals; Chemokines; Glioma; Humans; Receptors, Chemokine
PubMed: 32456359
DOI: 10.3390/ijms21103704 -
Journal of Molecular Neuroscience : MN Aug 2023Inflammatory response plays a crucial role in the development and progression of gliomas. Whereas the prognostic esteem of inflammatory response-related genes has never...
Inflammatory response plays a crucial role in the development and progression of gliomas. Whereas the prognostic esteem of inflammatory response-related genes has never been comprehensively explored in glioma, the RNA-seq information and clinical data of patients with glioma were extracted from TCGA, CGGA, and Rembrandt databases. The differentially expressed genes (DEGs) were picked out between glioma tissue and non-tumor brain tissue (NBT). Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to construct the prognostic signature in the TCGA cohort and verified in other cohorts. Kaplan-Meier survival analyses were conducted to compare the overall survival (OS) between the high and low-risk groups. Univariate and multivariate Cox analyses were subsequently used to confirm the independent prognostic factors of OS, and then, the nomogram was established based them. Furthermore, immune infiltration, immune checkpoints, and immunotherapy were also probed and compared between high and low-risk groups. The four genes were also analyzed by qRT-PCR, immunohistochemistry, and western blot trials between glioma tissue and NBT. The 39 DEGs were identified between glioma tissue and NBT, of which 31 genes are associated to the prognosis of glioma. The 8 optimal inflammatory response-related genes were selected to construct the prognostic inflammatory response-related signature (IRRS) through the LASSO regression. The effectiveness of the IRRS was verified in the TCGA, CGGA, and Rembrandt cohorts. Meanwhile, a nomogram with better accuracy was established to predict OS based on the independent prognostic factors. The IRRS was highly correlated with clinicopathological features, immune infiltration, and genomic alterations in glioma patients. In addition, four selective genes also verified the difference between glioma tissue and NBT. A novel prognostic signature was associated with the prognosis, immune infiltration, and immunotherapy effect in patients with gliomas. Thus, this study could provide a perspective for glioma prognosis and treatment.
Topics: Humans; Glioma; Immunotherapy; Brain; Blotting, Western; Databases, Factual
PubMed: 37488455
DOI: 10.1007/s12031-023-02142-x -
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 developedĀ 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 -
Brain Pathology (Zurich, Switzerland) Nov 2015This review is focused on describing the use of magnetic resonance (MR) spectroscopy for metabolic imaging of brain tumors. We will first review the MR metabolic imaging... (Review)
Review
This review is focused on describing the use of magnetic resonance (MR) spectroscopy for metabolic imaging of brain tumors. We will first review the MR metabolic imaging findings generated from preclinical models, focusing primarily on in vivo studies, and will then describe the use of metabolic imaging in the clinical setting. We will address relatively well-established (1) H MRS approaches, as well as (31) P MRS, (13) C MRS and emerging hyperpolarized (13) C MRS methodologies, and will describe the use of metabolic imaging for understanding the basic biology of glioma as well as for improving the characterization and monitoring of brain tumors in the clinic.
Topics: Animals; Brain Neoplasms; Glioma; Humans; Magnetic Resonance Spectroscopy
PubMed: 26526945
DOI: 10.1111/bpa.12310 -
Frontiers in Endocrinology 2023Gliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic...
BACKGROUND
Gliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic reprogramming of tumour cells, the prognosis of which cannot be accurately predicted by current histopathology. Therefore, Identify a mitochondrial gene with immune-related features that could be used to predict the prognosis of glioma patients.
METHODS
Gliomas data were downloaded from the TCGA database and mitochondrial-associated genes were obtained from the MITOCARTA 3.0 dataset. The CGGA, kamoun and gravendeel databases were used as external datasets. LASSO(Least absolute shrinkage and selection operator) regression was applied to identify prognostic features, and area and nomograms under the ROC(Receiver Operating Characteristic) curve were used to assess the robustness of the model. Single sample genomic enrichment analysis (ssGSEA) was employed to explore the relationship between model genes and immune infiltration, and drug sensitivity was used to identify targeting drugs. Cellular studies were then performed to demonstrate drug killing against tumours.
RESULTS
COX assembly mitochondrial protein homolog (), Cytochrome c oxidase protein 20 homolog () and Cytochrome b-c1 complex subunit 7 () were identified as prognostic key genes in glioma, with , progressively increasing and progressively decreasing with decreasing risk scores. ROC curve analysis of the TCGA training set model yielded AUC (Area Under The Curve) values >0.8 for 1-, 2- and 3-year survival, and the model was associated with both CD8+ T cells and immune checkpoints. Finally, using cellMiner database and molecular docking, it was confirmed that binds covalently to Amonafide lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion.
CONCLUSION
Our three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets.
Topics: Humans; Prognosis; Molecular Docking Simulation; Precision Medicine; DNA, Mitochondrial; Glioma; Mitochondria
PubMed: 37091853
DOI: 10.3389/fendo.2023.1172182 -
CNS Oncology 2015Anaplastic oligodendrogliomas (AOs) are rare brain tumors responsive to chemotherapy with procarbazine, lomustine (CCNU) and vincristine (PCV), especially when harboring... (Review)
Review
Anaplastic oligodendrogliomas (AOs) are rare brain tumors responsive to chemotherapy with procarbazine, lomustine (CCNU) and vincristine (PCV), especially when harboring 1p19q codeletion. However, with the emergence of temozolomide as an easier to administer and less toxic alternative regimen, PCV fell out of favor. Now, long-term results of two Phase III studies conceived in the 1990s, Radiation Therapy Oncology Group (RTOG) 9402 and European Organisation for Research and Treatment of Cancer (EORTC) 26951, resurrected debate about the potential role of PCV. No adequately powered prospective trial has compared chemotherapy alone with PCV versus temozolomide for newly diagnosed 1p19q codeleted AOs. Available data suggest responses may be both more frequent and more durable with PCV, and survival may be longer. Which regimen is 'better', therefore, depends on the importance of different metrics (i.e., toxicity, complexity, efficacy), and await definitive results from the important ongoing and recently redesigned CODEL international Phase III trial.
Topics: Antineoplastic Agents; Brain Neoplasms; Clinical Trials as Topic; Dacarbazine; Humans; Lomustine; Oligodendroglioma; Procarbazine; Temozolomide; Treatment Outcome; Vincristine
PubMed: 26544062
DOI: 10.2217/cns.15.36 -
Journal of Neuro-oncology Jul 2013Malignant gliomas remain incurable and present unique challenges to clinicians, radiologists and clinical and translational investigators. One of the major problems in... (Review)
Review
Malignant gliomas remain incurable and present unique challenges to clinicians, radiologists and clinical and translational investigators. One of the major problems in treatment of these tumors is our limited ability to reliably assess tumor response or progression. The most frequently used neuro-imaging studies (contrast-enhanced MRI and CT) rely on changes of blood-brain barrier (BBB) integrity, providing only an indirect assessment of tumor burden. In addition, the BBB can be altered by commonly used interventions including radiation, glucocorticoids and vascular endothelial growth factor inhibitors, further complicating the interpretation of scans. Newer radiologic techniques including PET and magnetic resonance spectroscopy are theoretically promising but thus far have not meaningfully changed the assessment of patients with malignant gliomas. A tumor-specific, blood-based biomarker would be of immediate use to clinicians and investigators if sufficiently sensitive and specific. This review discusses the potential utility of such a biomarker, the general classes of tumor-derived blood-based biomarkers and it summarizes the currently available data on circulating tumor cells, circulating nucleic acids and circulating proteins in patients with malignant gliomas. It is unclear which marker or marker class appears to be the most promising for these tumors. This article provides thoughts on how novel candidate blood-based markers could be discovered and tested in a more comprehensive way and why these efforts should be among the top priorities in neuro-oncologic research in the coming years.
Topics: Biomarkers; Biomarkers, Tumor; Glioma; Humans; Prognosis
PubMed: 23670054
DOI: 10.1007/s11060-013-1144-0 -
Neoplasia (New York, N.Y.) Jan 2023Diffuse Midline Glioma (DMG) which includes Diffuse Intrinsic Pontine Glioma (DIPG) is an infiltrative tumor of the midline structures of the central nervous system that... (Review)
Review
Diffuse Midline Glioma (DMG) which includes Diffuse Intrinsic Pontine Glioma (DIPG) is an infiltrative tumor of the midline structures of the central nervous system that demonstrates an aggressive pattern of growth and has no known curative treatment. As these tumors progress, children experience ongoing neurological decline including inability to ambulate, swallow and communicate effectively. We propose that optimal care for patients with DMG should involve a specialized team experienced in caring for the multifaceted needs of these patients and their families. Herein we review the roles and evidence to support early involvement of a specialized interdisciplinary team and outline our views on best practices for these challenging tumors.
Topics: Humans; Child; Brain Stem Neoplasms; Glioma
PubMed: 36410226
DOI: 10.1016/j.neo.2022.100851 -
Journal of B.U.ON. : Official Journal... 2021The role of RNA methylation in human cancers has emerged. Its biological function in glioma development is explored in the present study.
PURPOSE
The role of RNA methylation in human cancers has emerged. Its biological function in glioma development is explored in the present study.
METHODS
Differential levels and prognostic potentials of COL4A1 and METTL3 in glioma were analyzed by bioinformatic method. The regulatory effect of METTL3 on COL4A1 was assessed through qRT-PCR, MeRIP and dual-luciferase reporter assay. Their biological functions in influencing proliferative and metastatic capacities of glioma cells were examined by EdU, colony formation and Transwell assay, respectively.
RESULTS
COL4A1 was upregulated in glioma tissues, and METTL3 was downregulated. Knockdown of METTL3 in U87 and U251 cells could reduce the methylation level of COL4A1 and upregulate its expression level. Intervention of COL4A1 suppressed proliferative and metastatic capacities of glioma cells, while intervention of METTL3 yielded the opposite results.
CONCLUSION
METTL3 reduces the methylation level of COL4A1 and upregulates its expression level, which further stimulates the malignant development of glioma. METTL3/COL4A1 can be potential therapeutic targets of glioma.
Topics: Collagen Type IV; Glioma; Humans; Methylation; Methyltransferases; Prognosis; Tumor Cells, Cultured
PubMed: 34565019
DOI: No ID Found -
Frontiers in Immunology 2024TGFB-induced factor homeobox 2 (TGIF2), a member of the Three-Amino-acid-Loop-Extension (TALE) superfamily, has been implicated in various malignant tumors. However, its...
BACKGROUND
TGFB-induced factor homeobox 2 (TGIF2), a member of the Three-Amino-acid-Loop-Extension (TALE) superfamily, has been implicated in various malignant tumors. However, its prognostic significance in glioma, impact on tumor immune infiltration, and underlying mechanisms in glioma development remain elusive.
METHODS
The expression of TGIF2 in various human normal tissues, normal brain tissues, and gliomas was investigated using HPA, TCGA, GTEx, and GEO databases. The study employed several approaches, including Kaplan-Meier analysis, ROC analysis, logistic regression, Cox regression, GO analysis, KEGG analysis, and GSEA, to explore the relationship between TGIF2 expression and clinicopathologic features, prognostic value, and potential biological functions in glioma patients. The impact of TGIF2 on tumor immune infiltration was assessed through Estimate, ssGSEA, and Spearman analysis. Genes coexpressed with TGIF2 were identified, and the protein-protein interaction (PPI) network of these coexpressed genes were constructed using the STRING database and Cytoscape software. Hub genes were identified using CytoHubba plugin, and their clinical predictive value was explored. Furthermore, experiments were performed by knocking down and knocking out TGIF2 using siRNA and CRISPR/Cas9 gene editing, and the role of TGIF2 in glioma cell invasion and migration was analyzed using transwell assay, scratch wound-healing assay, RT-qPCR, and Western blot.
RESULTS
TGIF2 mRNA was found to be upregulated in 21 cancers, including glioma. High expression of TGIF2 was associated with malignant phenotypes and poor prognosis in glioma patients, indicating its potential as an independent prognostic factor. Furthermore, elevated TGIF2 expression positively correlated with cell cycle regulation, DNA synthesis and repair, extracellular matrix (ECM) components, immune response, and several signaling pathways that promote tumor progression. TGIF2 showed correlations with Th2 cells, macrophages, and various immunoregulatory genes. The hub genes coexpressed with TGIF2 demonstrated significant predictive value. Additionally, experiments revealed that knockdown and knockout of TGIF2 inhibited glioma cell invasion, migration and suppressed the epithelial-mesenchymal transition (EMT) phenotype.
CONCLUSION
TGIF2 emerges as a potential biomarker for glioma, possibly linked to tumor immune infiltration and EMT.
Topics: Humans; Prognosis; Biomarkers; Glioma; Phenotype; Amino Acids; Repressor Proteins; Homeodomain Proteins
PubMed: 38629068
DOI: 10.3389/fimmu.2024.1356833