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Laboratory Investigation; a Journal of... Jul 2022Comprehensive molecular profiling has dramatically transformed the diagnostic neuropathology of brain tumors. Diffuse gliomas, the most common and deadly brain tumor... (Review)
Review
Comprehensive molecular profiling has dramatically transformed the diagnostic neuropathology of brain tumors. Diffuse gliomas, the most common and deadly brain tumor variants, are now classified by highly recurrent biomarkers instead of histomorphological characteristics. Several of the key molecular alterations driving glioma classification involve epigenetic dysregulation at a fundamental level, implicating fields of biology not previously thought to play major roles glioma pathogenesis. This article will review the major epigenetic alterations underlying malignant gliomas, their likely mechanisms of action, and potential strategies for their therapeutic targeting.
Topics: Biomarkers; Biomarkers, Tumor; Brain Neoplasms; Epigenesis, Genetic; Glioma; Humans
PubMed: 35152274
DOI: 10.1038/s41374-022-00741-7 -
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 -
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 -
Chinese Medical Journal May 2015This overview seeked to bring together the microRNA (miRNA) researches on biogenesis and bio-function in these areas of clinical diagnosis and therapy for malignant... (Review)
Review
OBJECTIVE
This overview seeked to bring together the microRNA (miRNA) researches on biogenesis and bio-function in these areas of clinical diagnosis and therapy for malignant glioma.
DATA SOURCES
Using the keyword terms "glioma" and "miRNA," we performed the literature search in PubMed, Ovid, and web.metstr.com databases from their inception to October 2014.
STUDY SELECTION
In screening out the quality of the articles, factors such as clinical setting of the study, the size of clinical samples were taken into consideration. Animal studied for verification and reviews article were also included in our data collection.
RESULTS
Despite many advance in miRNA for malignant glioma, further studies were still required to focus on the following aspects: (i) Improving the understanding about biogenesis of miRNA and up-down regulation; (ii) utilizing high-throughput miRNA expression analysis to screen out the core miRNA for glioma; (iii) Focusing related miRNAs on the signal transduction pathways that regulate the proliferation and growth of glioma.
CONCLUSIONS
We discussed the most promising miRNA, correlative signaling pathway and their relation with gliomas in the way of prompting miRNA target into being a clinical therapeutic strategy.
Topics: Brain Neoplasms; Gene Expression Regulation, Neoplastic; Glioma; Humans; MicroRNAs
PubMed: 25947409
DOI: 10.4103/0366-6999.156141 -
Current Neurology and Neuroscience... Jan 2015Glioblastoma is a grade IV astrocytoma that is widely accepted in clinical neurosurgery as being an extremely lethal diagnosis. Long-term survival rates remain dismal,... (Review)
Review
Glioblastoma is a grade IV astrocytoma that is widely accepted in clinical neurosurgery as being an extremely lethal diagnosis. Long-term survival rates remain dismal, and even when tumors undergo gross resection with confirmation of total removal on neuroimaging, they invariably recur with even greater virulence. Standard therapeutic modalities as well as more contemporary treatments have largely resulted in disappointing improvements. However, the therapeutic potential of vaccine immunotherapy for malignant glioma should not be underestimated. In contrast to many of the available treatments, vaccine immunotherapy is unique because it offers the means of delivering treatment that is highly specific to both the patient and the tumor. Peptide, heat-shock proteins, and dendritic cell vaccines collectively encapsulate the majority of research efforts involving vaccine-based treatment modalities. In this review, important recent findings for these vaccine types are discussed in the context of ongoing clinical trials. Broad challenges to immunotherapy are also considered.
Topics: Animals; Brain Neoplasms; Cancer Vaccines; Dendritic Cells; Glioma; Heat-Shock Proteins; Humans; Peptides
PubMed: 25431096
DOI: 10.1007/s11910-014-0508-y -
Expert Review of Molecular Diagnostics May 2012Glioma remains incurable despite great advancements in medicine. Targeting the cell of origin for gliomas could bring great hope for patients. However, as a collection... (Review)
Review
Glioma remains incurable despite great advancements in medicine. Targeting the cell of origin for gliomas could bring great hope for patients. However, as a collection of diverse diseases, each subtype of glioma could derive from a distinct cell of origin. To resolve such a complex problem, one must use multiple research approaches to gain deep insights. Here we review current evidence regarding the cell of origin from clinical observations, whole-genome molecular pathology and glioma animal models. We conclude that neural stem cells, glial progenitors (including oligodendrocyte progenitor cells) and astrocytes could all serve as cells of origin for gliomas, and that cells incurring initial mutations (cells of mutation) might not transform, while their progeny cells could instead transform and act as cells of origin. Further studies with multidisciplinary approaches are needed to link each subtype to a particular cell of origin, and to develop effective therapies that target the signaling network within these cells.
Topics: Animals; Brain Neoplasms; Disease Models, Animal; Glioma; Humans; Mutation
PubMed: 22616703
DOI: 10.1586/erm.12.30 -
Journal of Neuro-oncology Sep 2014Malignant glioma (MG) is a devastating neurological disease with a uniformly poor prognosis and a clinical course characterized by progressive functional and cognitive... (Review)
Review
Malignant glioma (MG) is a devastating neurological disease with a uniformly poor prognosis and a clinical course characterized by progressive functional and cognitive impairment. A small body of literature addresses patients' and caregivers' prognostic awareness (PA), or understanding of prognosis in patients with cancer. Studies that examine PA and desire for prognostic information among patients with MG are limited. We sought to review the existing literature on PA and communication of prognostic information to patients with MG. Fourteen studies examining PA or experience and preferences regarding communication of prognostic information were included. The definition and measurement of PA across studies varied, and the prevalence of accurate PA ranged from 25 to 100 % of participants. There is likely a subset of patients who do not desire accurate prognostic information, although the patient and disease characteristics that predict this preference are currently unknown. This review suggests that patients with MG desire prognostic information communicated in a manner that preserves hope. Systematic investigation to define communication needs for prognostic information in the unique clinical setting of MG is needed.
Topics: Attitude to Health; Awareness; Brain Neoplasms; Communication; Glioma; Humans; Physician-Patient Relations; Prognosis
PubMed: 24874468
DOI: 10.1007/s11060-014-1487-1 -
Swiss Medical Weekly 2011Glioblastomas (World Health Organisation (WHO) grade IV) and anaplastic gliomas (astrocytomas, oligoastrocytomas, oligodendrogliomas) (WHO grade III) are collectively... (Review)
Review
Glioblastomas (World Health Organisation (WHO) grade IV) and anaplastic gliomas (astrocytomas, oligoastrocytomas, oligodendrogliomas) (WHO grade III) are collectively referred to as malignant gliomas. The diagnosis of malignant glioma may be suspected based on clinical history and neuroimaging findings, but histological confirmation remains the diagnostic "gold standard". Molecular markers such as 1p/19q codeletion and isocitrate dehydrogenase (IDH) mutation provide important diagnostic and prognostic information. O-methylguanylmethyltransferase (MGMT) promoter methylation is another favourable prognostic marker and predicts benefit from alkylating agent chemotherapy in glioblastoma. Additionally, the extent of neurosurgical resection is a prognostic factor. Radiotherapy of the involved brain region or chemotherapy using the alkylating agent, temozolomide, are common therapeutic options for patients with anaplastic glioma. In contrast, temozolomide plus radiotherapy is the standard of care for most patients with glioblastoma. The increasing population of elderly patients with glioblastoma represents a particular challenge, with surgery followed by radiotherapy as the standard of care. Contemporary clinical studies focus on the role of angiogenesis. Specifically, pivotal phase III studies exploring the antibody to vascular endothelial growth factor (VEGF), bevacizumab, and the αvβ3/5 antagonist, cilengitide, in the management of newly diagnosed glioblastoma have completed enrolment. Moreover, a broad spectrum of other experimental treatment approaches, including immunotherapy with vaccines against glioma-associated antigens, are currently being explored in phase I/II clinical trials.
Topics: Biomarkers, Tumor; Central Nervous System Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Oligodendroglioma
PubMed: 21607882
DOI: 10.4414/smw.2011.13210 -
International Journal of Molecular... Nov 2021Despite extensive preclinical research on immunotherapeutic approaches, malignant glioma remains a devastating disease of the central nervous system for which standard... (Review)
Review
Despite extensive preclinical research on immunotherapeutic approaches, malignant glioma remains a devastating disease of the central nervous system for which standard of care treatment is still confined to resection and radiochemotherapy. For peripheral solid tumors, immune checkpoint inhibition has shown substantial clinical benefit, while promising preclinical results have yet failed to translate into clinical efficacy for brain tumor patients. With the advent of high-throughput sequencing technologies, tumor antigens and corresponding T cell receptors (TCR) and antibodies have been identified, leading to the development of chimeric antigen receptors (CAR), which are comprised of an extracellular antibody part and an intracellular T cell receptor signaling part, to genetically engineer T cells for antigen recognition. Due to efficacy in other tumor entities, a plethora of CARs has been designed and tested for glioma, with promising signs of biological activity. In this review, we describe glioma antigens that have been targeted using CAR T cells preclinically and clinically, review their drawbacks and benefits, and illustrate how the emerging field of transgenic TCR therapy can be used as a potent alternative for cell therapy of glioma overcoming antigenic limitations.
Topics: Animals; Brain Neoplasms; Glioma; Humans; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen
PubMed: 34884607
DOI: 10.3390/ijms222312810