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Journal of Cellular and Molecular... Aug 2019Despite aggressive multimodality treatment, the prognosis of glioma, especially malignant glioma, remains very poor. After decades of effort, anti-angiogenic therapy has... (Review)
Review
Despite aggressive multimodality treatment, the prognosis of glioma, especially malignant glioma, remains very poor. After decades of effort, anti-angiogenic therapy has become an important method of cancer treatment in addition to surgery, radiotherapy and chemotherapy. Although the performance of anti-angiogenic therapy in colorectal cancer is good, its performance in malignant glioma remains unsatisfactory. Several phase III clinical trials showed no overall survival benefits. To solve this problem, the division of patients into groups based on their molecular biomarkers is an important step. This paper provides current insights into anti-angiogenic drugs undergoing clinical trials and discusses the potential of molecular biomarkers to guide glioma diagnosis.
Topics: Angiogenesis Inhibitors; Bevacizumab; Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Indoles; Molecular Targeted Therapy; Prognosis; Snake Venoms
PubMed: 31210419
DOI: 10.1111/jcmm.14417 -
International Journal of Molecular... May 2021Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct... (Review)
Review
Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct tumor zones of this heterogeneous neoplasm develop their own microenvironment, in which subpopulations of cancer cells communicate. Adaptation to hypoxia in the center of the expanding tumor mass leads to the glycolytic and angiogenic switch, accompanied by upregulation of different glycolytic enzymes, transporters, and other metabolites. These processes render the tumor microenvironment more acidic, remodel the extracellular matrix, and create energy gradients for the metabolic communication between different cancer cells in distinct tumor zones. Escape mechanisms from hypoxia-induced cell death and energy deprivation are the result. The functional consequences are more aggressive and malignant behavior with enhanced proliferation and survival, migration and invasiveness, and the induction of angiogenesis. In this review, we go from the biochemical principles of aerobic and anaerobic glycolysis over the glycolytic switch, regulated by the key transcription factor hypoxia-inducible factor (HIF)-1α, to other important metabolic players like the monocarboxylate transporters (MCTs)1 and 4. We discuss the metabolic symbiosis model via lactate shuttling in the acidic tumor microenvironment and highlight the functional consequences of the glycolytic switch on glioma malignancy. Furthermore, we illustrate regulation by micro ribonucleic acids (miRNAs) and the connection between mutation status and glycolytic metabolism. Finally, we give an outlook about the diagnostic and therapeutic implications of the glycolytic switch and the relation to tumor immunity in malignant glioma.
Topics: Animals; Brain; Brain Chemistry; Brain Neoplasms; Carbonic Anhydrases; Glioma; Glycolysis; Humans; Hydrogen-Ion Concentration; Lactic Acid; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 34073734
DOI: 10.3390/ijms22115518 -
Ultrasonics Sonochemistry Jul 2017Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include... (Review)
Review
Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include surgery, radiation therapy, and chemotherapy, although these approaches often failed to control tumor progression or improve patient survival. Sonodynamic therapy is a developing cancer treatment that uses ultrasound combined with a sonosensitizer to synergistically kill tumor cells, and has provided impressive results in both in vitro and in vivo studies. The ultrasound waves can penetrate deep tissues and reversibly open the blood-brain barrier to enhance drug delivery to the brain. Thus, sonodynamic therapy has a promising potential in glioma treatment. In this review, we summarize the studies that have confirmed the pre-clinical efficacy of sonodynamic therapy for glioma treatment, and discuss the future directions for this emerging treatment.
Topics: Animals; Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Glioma; Humans; Ultrasonic Waves
PubMed: 28427672
DOI: 10.1016/j.ultsonch.2017.02.020 -
Cell Research Jun 2021Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis....
Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM. Integrating time-series analyses of whole-exome sequencing, bulk and single-cell RNA-seq, we reconstructed gliomagenic trajectories, and identified a persistent NSC-like population at all stages of tumorigenesis. Through trajectory analyses and lineage tracing, we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells, which sequentially generate malignant heterogeneity and induce tumor phenotype transitions. We further uncovered stage-specific oncogenic cascades, and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor. Importantly, the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations, during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis. Together, our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs, and provide a blueprint for potential early-stage treatment/diagnosis for GBM.
Topics: Carcinogenesis; Glioblastoma; Glioma; Humans; Neoplastic Stem Cells; Neural Stem Cells
PubMed: 33390587
DOI: 10.1038/s41422-020-00451-z -
Journal of Neuro-oncology Jun 2017Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided... (Review)
Review
Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided only modest improvements in overall survival and remain limited by inevitable local recurrence, necessitating exploration of novel therapies. Among approaches being investigated, one of the leading contenders is immunotherapy, which aims to modulate immune pathways to stimulate the selective destruction of malignant cells. Dendritic cells (DCs) are potent initiators of adaptive immune responses and therefore crucial players in the development and success of immunotherapy. Clinical trials of various DC-based vaccinations have demonstrated the induction of anti-tumor immune responses and prolonged survival in the setting of many cancers. In this review, we summarize current literature regarding DCs and their role in the tumor microenvironment, their application and current clinical use in immunotherapy, current challenges limiting their efficacy in anti-cancer therapy, and future avenues for developing successful anti-tumor DC-based vaccines.
Topics: Animals; Brain Neoplasms; Cancer Vaccines; Dendritic Cells; Glioma; Humans
PubMed: 28434112
DOI: 10.1007/s11060-017-2446-4 -
Molecular and Cellular Biochemistry Feb 2022Autophagy is the process of recycling and utilization of degraded organelles and macromolecules in the cell compartments formed during the fusion of autophagosomes with... (Review)
Review
Autophagy is the process of recycling and utilization of degraded organelles and macromolecules in the cell compartments formed during the fusion of autophagosomes with lysosomes. During autophagy induction the healthy and tumor cells adapt themselves to harsh conditions such as cellular stress or insufficient supply of nutrients in the cell environment to maintain their homeostasis. Autophagy is currently seen as a form of programmed cell death along with apoptosis and necroptosis. In recent years multiple studies have considered the autophagy as a potential mechanism of anticancer therapy in malignant glioma. Although, subsequent steps in autophagy development are known and well-described, on molecular level the mechanism of autophagosome initiation and maturation using autophagy-related proteins is under investigation. This article reviews current state about the mechanism of autophagy, its molecular pathways and the most recent studies on roles of autophagy-related proteins and their isoforms in glioma progression and its treatment.
Topics: Apoptosis; Autophagosomes; Autophagy; Autophagy-Related Proteins; Glioma; Humans; Neoplasm Proteins
PubMed: 34854022
DOI: 10.1007/s11010-021-04308-w -
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 -
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