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Aging May 2020Immune response mediated by macrophages is critical in tumor progression and implicates new targets in potential efficient immunotherapies. Tumor associated macrophages...
Immune response mediated by macrophages is critical in tumor progression and implicates new targets in potential efficient immunotherapies. Tumor associated macrophages (TAM) are divided into either polarized M1 or M2 phenotype depending on different regulators of polarization and pro- or anti-oncogenic roles they play. Glioma-infiltrated TAMs have been newly reported contrary to the current polarization dogma. Instead, macrophages in glioma exhibit a continuum phenotype between the M1- and M2-like TAM that resembling M0 macrophage. Here we proposed an OS (overall survival)-correlated gene () via screening with transcriptional expression levels and methylation data in two glioma databases. was found highly expressed in glioma of higher WHO grade and Mesenchymal subtype glioma, and its transcriptional level could predict OS efficiently in validation datasets. EFEMP2 exhibited a remarkable preference of intercellular expression. In vitro assay showed that EFEMP2's level in medium was closely related to glioma cells' growth. Moreover, expression level was remarkably correlated with immunological responses. M0-like macrophage as a feature of malignancy of glioblastoma revealed distinct assembly in glioma with high level of . These results revealed 's role as a potential characteristic marker of malignant glioma, which are enriched of M0 macrophage.
Topics: Brain Neoplasms; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Extracellular Matrix Proteins; Glioma; Humans; Macrophages; Phenotype; Tumor Cells, Cultured
PubMed: 32396873
DOI: 10.18632/aging.103147 -
Current Neurology and Neuroscience... Feb 2016Malignant gliomas are intractable and among the most lethal human malignancies. Like other cancers, metabolic reprogramming is a key feature of glioma and is thought to... (Review)
Review
Malignant gliomas are intractable and among the most lethal human malignancies. Like other cancers, metabolic reprogramming is a key feature of glioma and is thought to accommodate the heightened nutrient requirements for tumor cell proliferation, growth, and survival. This metabolic rewiring, driven by oncogenic signaling and molded by the unique environment of the brain, may impose vulnerabilities that could be exploited therapeutically for increased tumor control. In this review, we discuss the prominent metabolic features of malignant glioma, the key pathways regulating glioma metabolism, and the potential therapeutic opportunities for targeting metabolic processes.
Topics: Brain; Glioma; Humans; Signal Transduction
PubMed: 26759318
DOI: 10.1007/s11910-015-0613-6 -
Cancer Gene Therapy Jun 2022Glioma is a common type of malignant and aggressive tumor in the brain. Despite progress on mechanistic studies, current understanding of the initiation and progression...
Glioma is a common type of malignant and aggressive tumor in the brain. Despite progress on mechanistic studies, current understanding of the initiation and progression of glioma remains incomplete. GIGYF2 is a critical regulator in neural development and degeneration, however, its contribution in glioma is not yet elucidated. In this study, using an integrative approach spanning bioinformatic analysis and functional approaches, we explored the potential contribution of GIGYF2 in glioma. Bioinformatic data from public database and our cohort showed that GIGYF2 expression was closely associated with low glioma malignancy and better patient survival. Elevation of GIGYF2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. We further establish its molecular mechanism by demonstrating that GIGYF2 inhibits MMP-9 mediated cell migration pathway and pro-survival AKT/Bax/Caspase-3 signaling. Our work identifies the suppressive role of GIGYF2 in gliomas, and clarifies the relationship between GIGYF2 expression and glioma malignancy, which may provide a potential target for future interventions.
Topics: Brain Neoplasms; Carrier Proteins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Glioma; Humans; Signal Transduction; Temozolomide
PubMed: 34059782
DOI: 10.1038/s41417-021-00353-1 -
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 -
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 -
Seminars in Oncology Nursing Dec 2018To provide an overview of the symptoms commonly experienced by patients with malignant glioma, and discuss the pathophysiology and interventions associated with those. (Review)
Review
OBJECTIVES
To provide an overview of the symptoms commonly experienced by patients with malignant glioma, and discuss the pathophysiology and interventions associated with those.
DATA SOURCES
A review of published scientific literature and clinical literature, and online information from National Comprehensive Cancer Network, Oncology Nursing Society, Epilepsy Foundation of America, and the American Brain Tumor Association.
CONCLUSION
The unique symptom burden associated with a malignant glioma diagnosis often disrupts the lives of patients and their caregivers. Clinical support and interventions addressing malignant glioma-related focal deficits, seizures, headaches, venous thromboembolism, mood disturbances, fatigue, and sleep-wake disturbance can positively impact patient and caregiver experiences while living with malignant glioma.
IMPLICATIONS FOR NURSING PRACTICE
Understanding the pathophysiology of these symptoms and reviewing nursing-led and supported interventions will empower the nurse in providing comprehensive care to patients with malignant glioma and their caregivers.
Topics: Adult; Aged; Aged, 80 and over; Epilepsy; Fatigue; Female; Glioma; Humans; Male; Middle Aged; Oncology Nursing; Practice Guidelines as Topic; Sleep Wake Disorders; Thromboembolism
PubMed: 30424920
DOI: 10.1016/j.soncn.2018.10.014 -
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 -
Journal of UOEH 20205-Aminolevulinic acid (ALA) has been widely used as an intravital fluorescence marker in the fluorescence-guided resection of malignant gliomas. Although not a... (Review)
Review
5-Aminolevulinic acid (ALA) has been widely used as an intravital fluorescence marker in the fluorescence-guided resection of malignant gliomas. Although not a photosensitizer itself, 5-ALA is a prodrug that accumulates protoporphyrin IX (PpIX) in the mitochondria of glioma cells; PpIX acts as a photosensitizer. Fluorescence-guided resection for malignant gliomas has some pitfalls. Moreover, 5-ALA is not merely a fluorescence marker but has potential as a mitochondria-targeting drug for malignant glioma therapy. In this article, we review the literature related to 5-ALA, discuss the pitfalls of fluorescence-guided resection using 5-ALA for malignant gliomas, and describe the application of 5-ALA for malignant glioma therapy with personal opinions.
Topics: Aminolevulinic Acid; Brain Neoplasms; Fluorescence; Glioma; Humans; Mitochondria; Photosensitizing Agents; Protoporphyrins; Reactive Oxygen Species; Surgery, Computer-Assisted
PubMed: 32213740
DOI: 10.7888/juoeh.42.27 -
International Journal of Molecular... Nov 2022Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant tumor of the central nervous system. GBM has a very low 5-year survival rate and...
Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant tumor of the central nervous system. GBM has a very low 5-year survival rate and reaching merely a median of ~15 months even with aggressive treatments. PPARγ (Peroxisome proliferator- activated receptor gamma) agonists (ciglitazone), while being widely used on patients of type 2 diabetes mellitus, also have approved anticancer effects. Their action mechanisms on malignant glioma are not fully understood. The aim of this study is to investigate the potential therapeutic effect of PPARγ agonists on maligant glioma. Glioma cell line and in-vivo/ex-vivo animal model intervened by ciglitazone were used to assess the associated mechanism and therapeutic effect. Our results from in vivo and ex vivo experiments showed that ciglitazone not only inhibited tumor growth and its associated angiogenesis, but it also reduced colony formation and migration of tumors. Ciglitazone inhibited the phosphorylation of STAT3 (signal transducer and activator of transcription 3) (at the point of tyrosine 705 by increasing both the amount and activity of SHP-2 (Src homology region 2-containing protein tyrosine phosphatase 2) proteins, based on evidence obtained from immunoprecipitation and immunohistochemistry. Furthermore, ciglitazone activated proteasomes and lysosomes to degrade cell-cycle-related proteins like Cyclin D1, Cyclin E, CDK2 (Cyclin-dependent kinase 2), and CDK4 (Cyclin-dependent kinase 4). Ciglitazone triggered expressions of LC3 (Microtubule-associated protein 1A/1B-light chain 3) and formation of acidic vesicular organelles (AVOs), both of which were implicated in the autophagy pathway. In conclusion, ciglitazone showed the multiple actions to regulate the growth of glioma, which appeared to be a potential candidate for treating malignant glioma.
Topics: Animals; PPAR gamma; Diabetes Mellitus, Type 2; Thiazolidinediones; Glioma; Hypoglycemic Agents; Cell Cycle Proteins; Glioblastoma; Microtubule-Associated Proteins; Cell Line, Tumor
PubMed: 36362294
DOI: 10.3390/ijms232113510 -
Critical Reviews in Oncology/hematology Apr 2017Coined as the "Warburg effect" and a recognized hallmark of cancer, energy metabolism is aberrantly geared towards aerobic glycolysis in most human cancers, including... (Review)
Review
BACKGROUND
Coined as the "Warburg effect" and a recognized hallmark of cancer, energy metabolism is aberrantly geared towards aerobic glycolysis in most human cancers, including malignant glioma. Ketogenic metabolic therapy (KMT), i.e. nutritional intervention with ketogenic or low-glycemic diets, has been proposed as an anti-neoplastic strategy in glioma patients.
MATERIALS AND METHODS
We here review the rationale and existing data investigating KMT in management of patients with malignant glioma and discuss the promise and potential challenges of this novel strategy. Results from published clinical studies and ongoing clinical trials on the topic are systematically reviewed, including 6 published original articles and 10 ongoing clinical trials. Search criteria for this review entailed the databases MEDLINE, EMBASE, Cochrane CENTRAL, and Google Scholar, as well as ICTRP (WHO) and ClinicalTrials.gov (NIH) registries.
RESULTS
A substantial amount of preclinical literature demonstrates KMT efficacy and safety in model systems of malignant glioma. Clinical literature indicates KMT safety and feasibility; 2 clinical studies suggest KMT-associated anti-neoplastic efficacy and clinical benefit. Ongoing clinical trials address KMT safety and metabolic impact, patient compliance, and patient clinical/survival benefit.
CONCLUSIONS
While clinical evidence is still limited in this evolving field, increasing numbers of ongoing clinical trials suggest that KMT is emerging as a potential therapeutic option and might be combinable with existing anti-neoplastic treatments for malignant glioma. Emerging clinical data will help answer questions concerning safety and efficacy of KMT, and are aiming to identify the most promising KMT regimen, compatibility with other anti-cancer treatments, ethical aspects, and impact on quality of life of cancer patients.
Topics: Animals; Diet, Ketogenic; Glioma; Humans
PubMed: 28325264
DOI: 10.1016/j.critrevonc.2017.02.016