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Neuro-oncology Mar 2016The shared goal of all parties developing therapeutics against malignant gliomas is to positively impact the lives of people affected by these cancers. Clinical outcome... (Review)
Review
The shared goal of all parties developing therapeutics against malignant gliomas is to positively impact the lives of people affected by these cancers. Clinical outcome assessment (COA) tools, including measures of patient-reported outcome, performance outcome, clinician-reported outcome, and observer-reported outcome, allow patient-focused assessments to complement traditional efficacy measures such as overall survival and radiographic endpoints. This review examines the properties of various COA measures used in malignant glioma clinical trials to date and cross references their content to the priority signs, symptoms, and functional limitations defined through a community survey conducted by the National Brain Tumor Society. The overarching goal of this initiative is to identify COA measures that are feasible and have appropriate psychometric properties for use in this patient population as well as highlight where further development is needed.
Topics: Animals; Brain Neoplasms; Clinical Trials as Topic; Glioma; Humans; Outcome Assessment, Health Care; Quality of Life; Surveys and Questionnaires
PubMed: 26989128
DOI: 10.1093/neuonc/nov291 -
Neuro-oncology Feb 2022
Topics: Brain Neoplasms; Glioma; Humans; Incidence
PubMed: 34695207
DOI: 10.1093/neuonc/noab250 -
Cancer Biology & Medicine Nov 2022Understanding the racial specificities of diseases-such as adult diffuse glioma, the most common primary malignant tumor of the central nervous system-is a critical step... (Review)
Review
Understanding the racial specificities of diseases-such as adult diffuse glioma, the most common primary malignant tumor of the central nervous system-is a critical step toward precision medicine. Here, we comprehensively review studies of gliomas in East Asian populations and other ancestry groups to clarify the racial differences in terms of epidemiology and genomic characteristics. Overall, we observed a lower glioma incidence in East Asians than in Whites; notably, patients with glioblastoma had significantly younger ages of onset and longer overall survival than the Whites. Multiple genome-wide association studies of various cohorts have revealed single nucleotide polymorphisms associated with overall and subtype-specific glioma susceptibility. Notably, only 3 risk loci-5p15.33, 11q23.3, and 20q13.33-were shared between patients with East Asian and White ancestry, whereas other loci predominated only in particular populations. For instance, risk loci 12p11.23, 15q15-21.1, and 19p13.12 were reported in East Asians, whereas risk loci 8q24.21, 1p31.3, and 1q32.1 were reported in studies in White patients. Although the somatic mutational profiles of gliomas between East Asians and non-East Asians were broadly consistent, a lower incidence of amplification in glioblastoma and a higher incidence of 1p19q-- triple-negative low-grade glioma were observed in East Asian cohorts. By summarizing large-scale disease surveillance, germline, and somatic genomic studies, this review reveals the unique characteristics of adult diffuse glioma among East Asians, to guide clinical management and policy design focused on patients with East Asian ancestry.
Topics: Adult; Humans; Glioblastoma; Genome-Wide Association Study; Glioma; Asian People; Mutation
PubMed: 36350002
DOI: 10.20892/j.issn.2095-3941.2022.0418 -
Cell Death & Disease Feb 2021High-grade glioma is the most common and aggressive primary brain tumor in adults with poor therapeutic efficiency and survival prognosis. Cell division cycle associated...
High-grade glioma is the most common and aggressive primary brain tumor in adults with poor therapeutic efficiency and survival prognosis. Cell division cycle associated 8 (CDCA8) has been well known as a cell cycle regulator and tumor promotor in various malignant tumors. However, its biological role in glioma still remains unclear. Our results showed that high level of CDCA8 was significantly correlated with advanced WHO grade and poor overall survival and disease-free survival prognosis. In vitro and in vivo investigations demonstrated that CDCA8 promoted the glioma malignancy by promoting cell proliferation, cell migration, and inhibiting cell apoptosis. Moreover, we found its synergetic biological protein-E2F1 by the gene microarray chip. In this study, we revealed that CDCA8 synergized with E2F1 facilitated the proliferation and migration of glioma. In conclusion, our study provides a novel promising therapeutic targets and prognostic biomarkers for malignant glioma treatment.
Topics: Animals; Brain Neoplasms; Cell Cycle Proteins; Cell Movement; E2F1 Transcription Factor; Female; Gene Expression Regulation, Neoplastic; Glioma; Humans; Mice; Mice, Nude; Prognosis; Transfection
PubMed: 33542211
DOI: 10.1038/s41419-021-03405-4 -
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 -
Molecular Cancer Feb 2018Glioma is one of the most prevalent types of primary intracranial carcinoma with varying malignancy grades I-IV and histological subtypes, including astrocytomas,... (Review)
Review
Glioma is one of the most prevalent types of primary intracranial carcinoma with varying malignancy grades I-IV and histological subtypes, including astrocytomas, glioblastoma multiform (GBM), oligodendrogliomas and mixed tumors. Glioma is characterized by rapid cell proliferation and angiogenesis, and the WHO grade IV glioblastoma, which is highly malignant with poor prognosis because GBM stem-like cells (GSCs) are resistant to conventional therapy and easily recrudescent, accounts for the majority of gliomas. Consequently, investigations exploring the accurate molecular mechanisms and reliable therapeutic targets for gliomas have drawn extensive attention.Based on the increasing amount of functional lncRNAs aberrantly expressed in glioma tissues and cell lines, lncRNAs might be critical for glioma initiation, progression and other malignant phenotypes. This review summarizes the latest insights into the lncRNA field and their functional roles in glioma, therefore evaluating the potential clinical applications of lncRNAs as prospective novel biomarkers and therapeutic targets.
Topics: Animals; Biomarkers; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Genetic Therapy; Glioma; Humans; Molecular Targeted Therapy; Phenotype; Prognosis; RNA Transport; RNA, Long Noncoding; Structure-Activity Relationship
PubMed: 29458374
DOI: 10.1186/s12943-018-0812-2 -
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