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Journal of Photochemistry and... Jul 2015Fluorescent agents, e.g. 5-aminolevulinic acid (5-ALA), fluorescein and indocyanine green (ICG) are in common use in neurosurgery for tumor resection and neurovascular... (Review)
Review
Fluorescent agents, e.g. 5-aminolevulinic acid (5-ALA), fluorescein and indocyanine green (ICG) are in common use in neurosurgery for tumor resection and neurovascular surgery. Protoporphyrine IX (PPIX) as major metabolite of 5-ALA is a strong fluorescent substance accumulated within malignant glioma tissue and a very sensitive and specific tool for visualizing high grade glioma tissue during surgery. Furthermore, 5-ALA or rather PPIX also offers an intratumoral therapeutic option stimulated by laser light in specific wavelength. Fluorescein was demonstrated to show similar fluorescent reactions in neurosurgery, but is controversial in its use, especially in high grade tumor surgery. Intraoperative angiography during resection of arterio-venous malformations, extracranial-intracranial-bypass or aneurysm surgery is supported by ICG fluorescence. Generally ICG will provide beneficial information for both, exposure of the pathology and illustration of healthy structures. This manuscript shows an overview of the literature focussing fluorescence in neurosurgery.
Topics: Aminolevulinic Acid; Brain Neoplasms; Glioma; Humans; Indocyanine Green; Optical Imaging; Photochemotherapy; Photosensitizing Agents; Protoporphyrins
PubMed: 26000742
DOI: 10.1016/j.jphotobiol.2015.05.002 -
Journal of Lipid Research Jan 2015Advances in our understanding of glioma biology has led to an increase in targeted therapies in preclinical and clinical trials; however, cellular heterogeneity often... (Review)
Review
Advances in our understanding of glioma biology has led to an increase in targeted therapies in preclinical and clinical trials; however, cellular heterogeneity often precludes the targeted molecules from being found on all glioma cells, thus reducing the efficacy of these treatments. In contrast, one trait shared by virtually all tumor cells is altered (dysregulated) metabolism. Tumor cells have an increased reliance on glucose, suggesting that treatments affecting cellular metabolism may be an effective method to improve current therapies. Indeed, metabolism has been a focus of cancer research in the last few years, as many pathways long associated with tumor growth have been found to intersect metabolic pathways in the cell. The ketogenic diet (high fat, low carbohydrate and protein), caloric restriction, and fasting all cause a metabolic change, specifically, a reduction in blood glucose and an increase in blood ketones. We, and others, have demonstrated that these metabolic changes improve survival in animal models of malignant gliomas and can potentiate the anti-tumor effect of chemotherapies and radiation treatment. In this review we discuss the use of metabolic alteration for the treatment of malignant brain tumors.
Topics: Animals; Brain Neoplasms; Caloric Restriction; Diet, Ketogenic; Glioma; Humans
PubMed: 24503133
DOI: 10.1194/jlr.R046797 -
No Shinkei Geka. Neurological Surgery May 2021Malignant gliomas have a poor prognosis despite advances in surgical procedures, radiotherapy, and the emergence of new treatments have improved outcomes. One of these...
Malignant gliomas have a poor prognosis despite advances in surgical procedures, radiotherapy, and the emergence of new treatments have improved outcomes. One of these new treatments is gene therapy, which has been developed as a new therapeutic strategy. Recently, new methods and approaches have been developed. Gene therapy involves the introduction of genes or cells into a glioma, or the human body, to treat gliomas; various genes such as cancer-suppressing genes, immunomodulation cytokine-related genes, and suicide genes are used in this treatment. Viral therapy is a treatment that oncolytic viral replicates in tumor cells to destroy tumors. Various viral genes can also be used as therapeutic genes. Currently, the most well-studied and accumulated viruses are adenoviruses and HSV-1. Various clinical trials have been conducted using gene therapy and viral therapy, some of which are scheduled to be approved in the near future. Gene therapy and viral therapy have dramatically improved and have developed progressively since their first clinical use.
Topics: Brain Neoplasms; Genetic Therapy; Glioma; Humans; Oncolytic Virotherapy
PubMed: 34092566
DOI: 10.11477/mf.1436204434 -
Journal of Immunology Research 2017Macrophages are major cell types of the immune system, and they comprise both tissue-resident populations and circulating monocyte-derived subsets. Here, we discuss... (Review)
Review
Macrophages are major cell types of the immune system, and they comprise both tissue-resident populations and circulating monocyte-derived subsets. Here, we discuss microglia, the resident macrophage within the central nervous system (CNS), and CNS-infiltrating macrophages. Under steady state, microglia play important roles in the regulation of CNS homeostasis through the removal of damaged or unnecessary neurons and synapses. In the face of inflammatory or pathological insults, microglia and CNS-infiltrating macrophages not only constitute the first line of defense against pathogens by regulating components of innate immunity, but they also regulate the adaptive arms of immune responses. Dysregulation of these responses contributes to many CNS disorders. In this overview, we summarize the current knowledge regarding the highly diverse and complex function of microglia and macrophages during CNS autoimmunity-multiple sclerosis and cancer-malignant glioma. We emphasize how the crosstalk between natural killer (NK) cells or glioma cells or glioma stem cells and CNS macrophages impacts on the pathological processes. Given the essential role of CNS microglia and macrophages in the regulation of all types of CNS disorders, agents targeting these subsets are currently applied in preclinical and clinical trials. We believe that a better understanding of the biology of these macrophage subsets offers new exciting paths for therapeutic intervention.
Topics: Adaptive Immunity; Animals; Autoimmunity; Cell Communication; Cell- and Tissue-Based Therapy; Central Nervous System; Glioma; Homeostasis; Humans; Immunity, Innate; Killer Cells, Natural; Macrophages; Microglia; Multiple Sclerosis
PubMed: 29410971
DOI: 10.1155/2017/5150678 -
Cold Spring Harbor Perspectives in... Jan 2015Malignant glioma remains incurable despite tremendous advancement in basic research and clinical practice. The identification of the cell(s) of origin should provide... (Review)
Review
Malignant glioma remains incurable despite tremendous advancement in basic research and clinical practice. The identification of the cell(s) of origin should provide deep insights into leverage points for one to halt disease progression. Here we summarize recent studies that support the notion that neural stem cell (NSC), astrocyte, and oligodendrocyte precursor cell (OPC) can all serve as the cell of origin. We also lay out important considerations on technical rigor for further exploring this subject. Finally, we share perspectives on how one could apply the knowledge of cell of origin to develop effective treatment methods. Although it will be a difficult battle, victory should be within reach as along as we continue to assimilate new information and facilitate the collaboration among basic scientists, translational researchers, and clinicians.
Topics: Astrocytes; Brain Neoplasms; Glioma; Humans; Neural Stem Cells; Oligodendroglia
PubMed: 25635044
DOI: 10.1101/cshperspect.a020610 -
Scientific Reports Dec 2019We conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and...
We conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and T2-weighted magnetic resonance images (T2WIs). We proposed a framework and applied it to CE-T1WIs and T2WIs (with tumor region data) acquired preoperatively from 157 patients with malignant glioma (grade III: 55, grade IV: 102) as the primary dataset and 67 patients with malignant glioma (grade III: 22, grade IV: 45) as the validation dataset. Radiomic features such as size/shape, intensity, histogram, and texture features were extracted from the tumor regions on the CE-T1WIs and T2WIs. The Wilcoxon-Mann-Whitney (WMW) test and least absolute shrinkage and selection operator logistic regression (LASSO-LR) were employed to select the radiomic features. Various machine learning (ML) algorithms were used to construct prediction models for the malignant glioma grades using the selected radiomic features. Leave-one-out cross-validation (LOOCV) was implemented to evaluate the performance of the prediction models in the primary dataset. The selected radiomic features for all folds in the LOOCV of the primary dataset were used to perform an independent validation. As evaluation indices, accuracies, sensitivities, specificities, and values for the area under receiver operating characteristic curve (or simply the area under the curve (AUC)) for all prediction models were calculated. The mean AUC value for all prediction models constructed by the ML algorithms in the LOOCV of the primary dataset was 0.902 ± 0.024 (95% CI (confidence interval), 0.873-0.932). In the independent validation, the mean AUC value for all prediction models was 0.747 ± 0.034 (95% CI, 0.705-0.790). The results of this study suggest that the malignant glioma grades could be sufficiently and easily predicted by preparing the CE-T1WIs, T2WIs, and tumor delineations for each patient. Our proposed framework may be an effective tool for preoperatively grading malignant gliomas.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Area Under Curve; Brain Neoplasms; Child; Contrast Media; Databases as Topic; Female; Glioma; Humans; Machine Learning; Magnetic Resonance Imaging; Male; Middle Aged; ROC Curve; Reproducibility of Results; Young Adult
PubMed: 31857632
DOI: 10.1038/s41598-019-55922-0 -
Journal of Molecular Neuroscience : MN Aug 2021Glioma is one of the most common neurological malignancies worldwide. Delta-like ligand 3 (DLL3), an inhibitory ligand-driven activation of the Notch pathway, has been...
Glioma is one of the most common neurological malignancies worldwide. Delta-like ligand 3 (DLL3), an inhibitory ligand-driven activation of the Notch pathway, has been shown to be significantly associated with overall survival in patients with glioma. Therefore, the purpose of this study was to determine whether DLL3 as a biomarker in glioma is associated with patients' clinicopathological features and prognosis. We identified differences in transcriptome and promoter methylation in the Chinese Glioma Genome Atlas (CGGA) in patients with malignant glioma with shorter (less than 1 year) and longer (greater than 3 years) survival time. Further analysis of The Cancer Genome Atlas (TCGA) revealed that four genes (DLL3, TSPAN15, RTN1, PAK7) are highly associated with patient prognosis and play an indispensable role in evolution. We chose the expression level of DLL3 in glioma patients for our study. Patients were divided into groups with low and high expression of DLL3 according to the cutoff values obtained, and Kaplan-Meier and Cox analysis were used to examine the correlation between DLL3 gene expression and patient survival. We then performed a gene set enrichment analysis (GSEA) to identify significantly enriched signaling pathways. Our results confirmed that the overall survival of patients with low DLL3 expression was significantly shorter than that of patients with high DLL3 expression. GSEA showed that the signaling pathways of the immune process and immune response, among others, were enhanced with the DLL3 low-expression phenotype. Collectively, our findings signify that DLL3 is a potent prognostic factor for glioma, which can provide a viable approach for glioma prognostic assessment and valuable insights for anti-tumor immune-targeted therapies.
Topics: Adult; Biomarkers, Tumor; Brain Neoplasms; Computational Biology; DNA Methylation; Databases, Genetic; Female; Glioma; Humans; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins
PubMed: 33713320
DOI: 10.1007/s12031-021-01817-7 -
Expert Review of Neurotherapeutics 2015Glioma stem cells (GSCs) constitute a slow-dividing, small population within a heterogeneous glioblastoma. They are able to self-renew, recapitulate a whole tumor, and... (Review)
Review
Glioma stem cells (GSCs) constitute a slow-dividing, small population within a heterogeneous glioblastoma. They are able to self-renew, recapitulate a whole tumor, and differentiate into other specific glioblastoma multiforme (GBM) subpopulations. Therefore, they have been held responsible for malignant relapse after primary standard therapy and the poor prognosis of recurrent GBM. The failure of current therapies to eliminate specific GSC subpopulations has been considered a major factor contributing to the inevitable recurrence in GBM patients after treatment. Here, we discuss the molecular mechanisms of chemoresistance of GSCs and the reasons why complete eradication of GSCs is so difficult to achieve. We will also describe the targeted therapies currently available for GSCs and possible mechanisms to overcome such chemoresistance and avoid therapeutic relapse.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Glioblastoma; Glioma; Humans; Neoplasm Recurrence, Local; Neoplastic Stem Cells
PubMed: 26027432
DOI: 10.1586/14737175.2015.1051968 -
Journal of Cancer Research and Clinical... Apr 2015Malignant gliomas invariably recur after irradiation, showing radioresistance. Meanwhile, cranial irradiation can bring some risk for developing cognitive dysfunction.... (Review)
Review
Malignant gliomas invariably recur after irradiation, showing radioresistance. Meanwhile, cranial irradiation can bring some risk for developing cognitive dysfunction. There is increasing evidence that cytokines play their peculiar roles in these processes. On the one hand, cytokines directly influence the progression of malignant glioma, promoting or suppressing tumor progression. On the other hand, cytokines indirectly contribute to the immunologic response against gliomas, exhibiting pro-inflammatory or immunosuppressive activities. We propose that cytokines are not simply unregulated products from tumor cells or immune cells, but mediators finely adjust the balance between glioma cells and tumor microenvironment after irradiation. The paper, therefore, focuses on the changes of cytokines after irradiation, analyzing how these mediate the response of tumor cells and normal cells to irradiation. In addition, cytokine-based immunotherapeutic strategies, accompanied with irradiation, for the treatment of gliomas are also discussed.
Topics: Brain; Brain Neoplasms; Cranial Irradiation; Cytokines; Glioma; Humans; Treatment Outcome; Tumor Microenvironment
PubMed: 25005789
DOI: 10.1007/s00432-014-1772-6 -
Neurosurgery Jun 2021
Topics: Adult; Brain Neoplasms; Cognitive Dysfunction; Glioma; Humans; Neurosurgeons
PubMed: 33289515
DOI: 10.1093/neuros/nyaa408