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Glioblastomas contain stem‐like cells that can be maintained in vitro using specific serum‐free conditions. We investigated whether glioblastoma stem‐like (GS) cell lines preserve the expression phenotype of human glioblastomas more closely than conventional glioma cell lines. Expression profiling revealed that a distinct subset of GS lines, which displayed a full stem‐like phenotype (GSf), mirrored...
Malignant glioma is among of the most devastating, and least curable, types of cancer. Since the re‐emergence of the cancer stem cell hypothesis, much progress has been made towards elucidating the cellular origin of these tumors. The hypothesis that tumors are hierarchically organized, with a cancer stem cell at the top that shares defining features with somatic stem cells and provides therapeutic...
Diffuse gliomas such as astrocytomas and oligodendrogliomas are the most common form of intrinsic brain tumor in adults. Even within a single pathologic class, these tumors are both histologically and molecularly diverse, although not randomly so. Recent large‐scale genomic analyses have revealed patterns of molecular changes within tumor subclasses that harbor distinct underlying biology, clinical...
Isocitrate dehydrogenases (IDHs) convert isocitrate to α‐ketoglutarate by oxidative decarboxylation and are thereby involved in multiple metabolic processes. Mutations in the genes encoding IDH1 and IDH2 were first reported in human gliomas in 2008 and later on also identified in a minority of patients with acute myeloid leukemia. The mutations universally affect codons 132 in IDH1 and 172 in IDH2...
Glioblastomas (GBM), the most common primary brain tumors, infiltrate the brain, grow rapidly, and are refractory to current therapies. Signature genetic lesions in glioblastomas include mutation of the epidermal growth factor receptor tyrosine kinase (EGFR) receptor tyrosine kinase and activating mutations in components of the PI‐3 kinase (PI3K) pathway. Despite years of study, how these pathways...
The biological significance of CD133 in glioblastoma is controversial. Above all, there is disagreement concerning the proper approach, the appropriate (cell) model and the suitable microenvironment to study this molecule, often leading to inconsistent experimental results among studies. In consideration of a primary need to dissect and to understand the CD133 phenotype in glioblastoma we performed...
Glioblastoma multiform (GBM) are devastating brain tumors containing a fraction of multipotent stem‐like cells which are highly tumorigenic. These cells are resistant to treatments and are likely to be responsible for tumor recurrence. One approach to eliminate GBM stem‐like cells would be to force their terminal differentiation. During development, neurons formation is controlled by neurogenic transcription...
Glioblastoma is the most prevalent primary brain tumor and is essentially universally fatal within 2 years of diagnosis. Glioblastomas contain cellular hierarchies with self‐renewing glioblastoma stem cells (GSCs) that are often resistant to chemotherapy and radiation therapy. GSCs express high amounts of repressor element 1 silencing transcription factor (REST), which may contribute to their resistance...
Glioblastomas, the most aggressive form of primary brain tumors with a tendency to invade surrounding healthy brain tissues, remains an incurable disease. Intersectin (ITSN) is a multidomain adapter protein implicated in endocytosis, exocytosis, and multiple signaling pathways. Prior research of ours has shown intersectin1‐S (ITSN1‐S) is critical for the migration and invasion of glioma cells by regulating...
Brain tumors represent the most common solid tumor of childhood, with gliomas comprising the largest fraction of these cancers. Several features distinguish them from their adult counterparts, including their natural history, causative genetic mutations, and brain locations. These unique properties suggest that the cellular and molecular etiologies that underlie their development and maintenance might...
Glioblastoma (GBM) is the most aggressive brain tumor in adults. It is strongly infiltrated by microglia and peripheral monocytes that support tumor growth. In the present study we used RNA sequencing to compare the expression profile of CD11b+ human glioblastoma‐associated microglia/monocytes (hGAMs) to CD11b+ microglia isolated from non‐tumor samples. Hierarchical clustering and principal component...
Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells that comprise ~50% of all brain cells and are therefore likely to establish direct...
Glioblastoma is a malignant brain tumor that portends a poor prognosis. Its resilience, in part, is related to a remarkable capacity for manipulating the microenvironment to promote its growth and survival. Microglia/macrophages are prime targets, being drawn into the tumor and stimulated to produce factors that support tumor growth and evasion from the immune system. Here we show that the RNA regulator,...
Glioblastoma (GBM) is a deadly disease with a need for deeper understanding and new therapeutic approaches. The microenvironment of glioblastoma has previously been shown to guide glioblastoma progression. In this study, astrocytes were investigated with regard to their effect on glioblastoma proliferation through correlative analyses of clinical samples and experimental in vitro and in vivo studies...
The microenvironment and architecture of peritumoral tissue have been suggested to affect permissiveness for infiltration of malignant cells. Astrocytes constitute a heterogeneous population of cells and have been linked to proliferation, migration, and drug sensitivity of glioblastoma (GBM) cells. Through double‐immunohistochemical staining for platelet‐derived growth factor receptor α (PDGFRα)...
Glioblastoma (GBM) is the most aggressive primary brain tumor. In addition to being genetically heterogeneous, GBMs are also immunologically heterogeneous. However, whether the differences in immune microenvironment are driven by genetic driver mutation is unexplored. By leveraging the versatile RCAS/tv‐a somatic gene transfer system, we establish a mouse model for Classical GBM by introducing EGFRvIII...
Gliomas are the most common primary intrinsic brain tumors occurring in adults. Of all malignant gliomas, glioblastoma (GBM) is considered the deadliest tumor type due to diffuse brain invasion, immune evasion, cellular, and molecular heterogeneity, and resistance to treatments resulting in high rates of recurrence. An extensive understanding of the genomic and microenvironmental landscape of gliomas...
High‐grade gliomas (HGGs) are aggressive, treatment‐resistant, and often fatal human brain cancers. The TNF‐like weak inducer of apoptosis (TWEAK)/fibroblast growth factor‐inducible 14 (Fn14) signaling axis is involved in tissue repair after injury and constitutive signaling has been implicated in the pathogenesis of numerous solid cancers. The Fn14 gene is expressed at low levels in the normal,...
Microglia actively promotes the growth of high‐grade gliomas. Within the glioma microenvironment an amoeboid microglial morphology has been observed, however the underlying causes and the related impact on microglia functions and their tumor promoting activities is unclear. Using the advantages of the larval zebrafish model, we identified the underlying mechanism and show that microglial morphology...
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