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Journal of B.U.ON. : Official Journal... 2016Cancer research has revealed the existence of cancer stem cells (CSCs). However, the influence of the surrounding stromal cells present in the microenvironment on CSCs... (Review)
Review
Cancer research has revealed the existence of cancer stem cells (CSCs). However, the influence of the surrounding stromal cells present in the microenvironment on CSCs is still poorly understood. The latest studies on gliomas suggested that the microenvironment of human gliomas contains both glioma stem cells (GSCs) and glioma associated (GA)-mesenchymal stem cells (MSCs; (GA-MSCs). Also, studies have suggested that nano- sized vesicles, termed exosomes, have been recently observed to contribute towards intercellular communication within the tumor niche. The present review article will highlight the current view of exosomal communication in gliomas.
Topics: Animals; Brain Neoplasms; Exosomes; Glioma; Humans; Mesenchymal Stem Cells; Neoplastic Stem Cells; Signal Transduction; Stem Cell Niche; Tumor Microenvironment
PubMed: 28039693
DOI: No ID Found -
Brain : a Journal of Neurology Oct 2021Over the past decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumours. It has become evident... (Review)
Review
Over the past decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumours. It has become evident that paediatric high-grade gliomas differ from those in adults with respect to multiple defining aspects including: DNA copy number, gene expression profiles, tumour locations within the CNS and genetic alterations such as somatic histone mutations. Despite these advances, clinical trials for children with gliomas have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences between the two. Additionally, although our knowledge of the intrinsic cellular mechanisms driving tumour progression has considerably expanded, little is known about the dynamic tumour immune microenvironment in paediatric high-grade gliomas. In this review, we explore the genetic and epigenetic landscape of these gliomas and how this drives the creation of specific tumour subgroups with meaningful survival outcomes. Further, we provide a comprehensive analysis of the paediatric high-grade glioma tumour immune microenvironment and discuss emerging therapeutic efforts aimed at exploiting the immune functions of these tumours.
Topics: Brain Neoplasms; Cell- and Tissue-Based Therapy; Child; Epigenesis, Genetic; Glioma; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasm Grading; Tumor Microenvironment
PubMed: 33856022
DOI: 10.1093/brain/awab155 -
Journal of Neuro-oncology Jul 2008We investigated the protein expression of three glioma-associated antigens (GAAs) in pediatric brain stem glioma (BSG) and non-brain stem glioma (NBSG) cases with a view...
We investigated the protein expression of three glioma-associated antigens (GAAs) in pediatric brain stem glioma (BSG) and non-brain stem glioma (NBSG) cases with a view to their possible use in immunotherapy. Expression of EphA2, IL-13Ralpha2 and Survivin were studied by immunohistochemistry on paraffin-embedded tissues using a series of 15 BSG cases and 12 NBSG cases. Thirteen of 15 BSGs and all 12 NBSGs expressed at least one of GAAs; and 7 BSGs and 9 NBSGs expressed at least two of these GAAs at higher levels than non-neoplastic brain. There was no association between the tumor grade and levels of GAA expression. Although many cases demonstrated diffuse expression of GAAs throughout specimens, partial or patchy expression was noted in a small number of cases, suggesting a need for targeting multiple GAAs in immunotherapy. These results suggest that EphA2, IL-13Ralpha2 and Survivin are suitable targets for developing vaccine strategies for pediatric glioma.
Topics: Adult; Biomarkers, Tumor; Brain Neoplasms; Brain Stem Neoplasms; Child; Child, Preschool; Gene Expression; Glioma; Humans; Immunohistochemistry; Infant; Inhibitor of Apoptosis Proteins; Interleukin-13 Receptor alpha2 Subunit; Microtubule-Associated Proteins; Neoplasm Proteins; Receptor, EphA2; Survivin
PubMed: 18324354
DOI: 10.1007/s11060-008-9566-9 -
Drug Resistance Updates : Reviews and... May 2019Diffuse midline gliomas (DMG) are rapidly fatal tumors of the midbrain in children, characterized by a diffuse growing pattern and high levels of intrinsic resistance to... (Review)
Review
Diffuse midline gliomas (DMG) are rapidly fatal tumors of the midbrain in children, characterized by a diffuse growing pattern and high levels of intrinsic resistance to therapy. The location of these tumors, residing behind the blood-brain barrier (BBB), and the limited knowledge about the biology of these tumors, has hindered the development of effective treatment strategies. However, the introduction of diagnostic biopsies and the implementation of autopsy protocols in several large centers world-wide has allowed for a detailed characterization of these rare tumors. This has resulted in the identification of novel therapeutic targets, as well as major advances in understanding the biology of DMG in relation to therapy resistance. We here provide an overview of the cellular pathways and tumor-specific aberrations that have been targeted in preclinical DMG research, and discuss the advantages and limitations of these therapeutic strategies in relation to therapy resistance and BBB-penetration. Therewith, we aim to provide researchers with a framework for successful preclinical therapy development.
Topics: Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Cell Cycle Checkpoints; Child; Drug Resistance, Neoplasm; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Glioma; Histone Deacetylases; Histones; Humans; Mesencephalon; Molecular Targeted Therapy; Neoplasm Proteins; Signal Transduction
PubMed: 31202081
DOI: 10.1016/j.drup.2019.06.001 -
Neuro-oncology May 2024H3 K27M-mutant diffuse glioma is a recently identified brain tumor associated with poor prognosis. As of 2016, it is classified by the World Health Organization as a...
H3 K27M-mutant diffuse glioma is a recently identified brain tumor associated with poor prognosis. As of 2016, it is classified by the World Health Organization as a distinct form of grade IV glioma. Despite recognition as an important prognostic and diagnostic feature in diffuse glioma, radiation remains the sole standard of care and no effective systemic therapies are available for H3K27M mutant tumors. This review will detail treatment interventions applied to diffuse midline glioma and diffuse intrinsic pontine glioma (DIPG) prior to the identification of the H3 K27M mutation, the current standard-of-care for H3 K27M-mutant diffuse glioma treatment, and ongoing clinical trials listed on www.clinicaltrials.gov evaluating novel therapeutics in this population. Current clinical trials were identified using clinicaltrials.gov, and studies qualifying for this analysis were active or ongoing interventional trials that evaluated a therapy in at least 1 treatment arm or cohort comprised exclusively of patients with DIPG and H3 K27M-mutant glioma. Forty-one studies met these criteria, including trials evaluating H3 K27M vaccination, chimeric antigen receptor T-cell therapy, and small molecule inhibitors. Ongoing evaluation of novel therapeutics is necessary to identify safe and effective interventions in this underserved patient population.
Topics: Humans; Brain Stem Neoplasms; Diffuse Intrinsic Pontine Glioma; Glioma; Mutation; Histones; Prognosis; Brain Neoplasms
PubMed: 38102230
DOI: 10.1093/neuonc/noad220 -
Cancer Cell Apr 2006Stem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we...
Stem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we demonstrate that SCF directly activates brain microvascular endothelial cells (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human gliomas express SCF in a grade-dependent manner and induce normal neurons to express SCF in brain regions infiltrated by glioma cells, areas that colocalize with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated angiogenesis and glioma growth in vivo, whereas overexpression of SCF is associated with shorter survival in patients with malignant gliomas. Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain.
Topics: Animals; Brain; Cells, Cultured; Down-Regulation; Endothelial Cells; Fibroblast Growth Factors; Gene Expression Regulation, Neoplastic; Glioma; Humans; Mice; Neurons; Protein Binding; Proto-Oncogene Proteins c-kit; RNA, Small Interfering; Signal Transduction; Stem Cell Factor; Survival Rate
PubMed: 16616334
DOI: 10.1016/j.ccr.2006.03.003 -
International Journal of Molecular... Dec 2021Recent studies have begun to reveal surprising levels of cell diversity in the human brain, both in adults and during development. Distinctive cellular phenotypes point... (Review)
Review
Recent studies have begun to reveal surprising levels of cell diversity in the human brain, both in adults and during development. Distinctive cellular phenotypes point to complex molecular profiles, cellular hierarchies and signaling pathways in neural stem cells, progenitor cells, neuronal and glial cells. Several recent reports have suggested that neural stem and progenitor cell types found in the developing and adult brain share several properties and phenotypes with cells from brain primary tumors, such as gliomas. This transcriptomic crosstalk may help us to better understand the cell hierarchies and signaling pathways in both gliomas and the normal brain, and, by clarifying the phenotypes of cells at the origin of the tumor, to therapeutically address their most relevant signaling pathways.
Topics: Brain Neoplasms; Cell Communication; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Glioma; Humans; Neoplastic Stem Cells; Neural Stem Cells; Phenotype; Signal Transduction; Telencephalon
PubMed: 34948008
DOI: 10.3390/ijms222413211 -
The Oncologist 2012Brainstem gliomas are uncommon in adults and account for only 1%-2% of intracranial gliomas. They represent a heterogeneous group of tumors that differ from those found... (Review)
Review
Brainstem gliomas are uncommon in adults and account for only 1%-2% of intracranial gliomas. They represent a heterogeneous group of tumors that differ from those found in their pediatric counterparts. In adults, a low-grade phenotype predominates, which is a feature that likely explains their better prognosis compared to that in children. Because biopsies are rarely performed, classifications based on the radiological aspect of magnetic resonance imaging results have been proposed to establish treatment strategies and to determine outcomes: (a) diffuse intrinsic low-grade, (b) enhancing malignant glioma, (c) focal tectal gliomas, and (d) exophytic gliomas. Despite significant advances in neuroradiology techniques, a purely radiological classification remains imperfect in the absence of a histological diagnosis. Whereas a biopsy may often be reasonably avoided in the diffuse nonenhancing forms, obtaining histological proof seems necessary in many contrast-enhanced brainstem lesions because of the wide variety of differential diagnoses in adults. Conventional radiotherapy is the standard treatment for diffuse intrinsic low-grade brainstem gliomas in adults (the median survival is 5 years). In malignant brainstem gliomas, radiotherapy is the standard treatment. However, the possible benefit of combined radiotherapy and chemotherapy (temozolomide or other agents) has not been thoroughly evaluated in adults. The role of anti-angiogenic therapies in brainstem gliomas remains to be defined. A better understanding of the biology of these tumors is of primary importance for identifying homogeneous subgroups and for improving therapy options and outcomes.
Topics: Adult; Age of Onset; Brain Stem Neoplasms; Follow-Up Studies; Glioma; Humans; Magnetic Resonance Imaging; Neoplasm Staging; Prognosis
PubMed: 22382458
DOI: 10.1634/theoncologist.2011-0335 -
Molecules and Cells Jul 2009Gliomas, much like other cancers, are composed of a heterogeneous mix of neoplastic and non-neoplastic cells that include both native and recruited cells. There is... (Review)
Review
Gliomas, much like other cancers, are composed of a heterogeneous mix of neoplastic and non-neoplastic cells that include both native and recruited cells. There is extensive diversity among the tumor cells, with differing capacity for in vitro and in vivo growth, a property intimately linked to the cell's differentiation status. Those cells that are undifferentiated, self-renewing, with the capacity for developing tumors (tumorigenic) cells are designated by some as cancer stem cells, because of the stem-like properties. These cells may be a critical therapeutic target. However the exact identity and cell(s) of origin of the so-called glioma cancer stem cell remain elusive. Here we review the current understanding of glioma cancer stem cell biology.
Topics: AC133 Antigen; Animals; Antigens, CD; Biomarkers, Tumor; Brain Neoplasms; Cell Differentiation; Cell Proliferation; Cell Survival; Glioma; Glycoproteins; Humans; Neoplastic Stem Cells; Peptides
PubMed: 19655094
DOI: 10.1007/s10059-009-0111-2 -
Neoplasia (New York, N.Y.) Mar 2015Malignant gliomas are the most common malignant primary brain tumors and one of the most challenging forms of cancers to treat. Despite advances in conventional... (Review)
Review
Malignant gliomas are the most common malignant primary brain tumors and one of the most challenging forms of cancers to treat. Despite advances in conventional treatment, the outcome for patients remains almost universally fatal. This poor prognosis is due to therapeutic resistance and tumor recurrence after surgical removal. However, over the past decade, molecular targeted therapy has held the promise of transforming the care of malignant glioma patients. Significant progress in understanding the molecular pathology of gliomagenesis and maintenance of the malignant phenotypes will open opportunities to rationally develop new molecular targeted therapy options. Recently, therapeutic strategies have focused on targeting pro-growth signaling mediated by receptor tyrosine kinase/RAS/phosphatidylinositol 3-kinase pathway, proangiogenic pathways, and several other vital intracellular signaling networks, such as proteasome and histone deacetylase. However, several factors such as cross-talk between the altered pathways, intratumoral molecular heterogeneity, and therapeutic resistance of glioma stem cells (GSCs) have limited the activity of single agents. Efforts are ongoing to study in depth the complex molecular biology of glioma, develop novel regimens targeting GSCs, and identify biomarkers to stratify patients with the individualized molecular targeted therapy. Here, we review the molecular alterations relevant to the pathology of malignant glioma, review current advances in clinical targeted trials, and discuss the challenges, controversies, and future directions of molecular targeted therapy.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Combined Modality Therapy; Glioma; Humans; Molecular Targeted Therapy; Signal Transduction
PubMed: 25810009
DOI: 10.1016/j.neo.2015.02.002