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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Solid tumors contain a subset of stem-like cells that are resistant to the cytotoxic effects of chemotherapy/radiotherapy, but their susceptibility to cytolytic T lymphocyte (CTL) effector mechanisms has not been well characterized. Using a panel of early-passage human brain tumor stem/initiating cell (BTSC) lines derived from high-grade gliomas, we show that BTSCs are subject to immunologic recognition and elimination by CD8(+) CTLs. Compared with serum-differentiated CD133(low) tumor cells and established glioma cell lines, BTSCs are equivalent with respect to expression levels of HLA class I and ICAM-1, similar in their ability to trigger degranulation and cytokine synthesis by antigen-specific CTLs, and equally susceptible to perforin-dependent CTL-mediated cytolysis. BTSCs are also competent in the processing and presentation of antigens as evidenced by the killing of these cells by CTL when antigen is endogenously expressed. Moreover, we show that CTLs can eliminate all BTSCs with tumor-initiating activity in an antigen-specific manner in vivo. Current models predict that curative therapies for many cancers will require the elimination of the stem/initiating population, and these studies lay the foundation for developing immunotherapeutic approaches to eradicate this tumor population.
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PMID:Recognition and killing of brain tumor stem-like initiating cells by CD8+ cytolytic T cells. 1990 40

Glioma, especially high-grade glioblastoma multiforme (GBM), is the most common and aggressive type of brain tumor, accounting for about half of all the primary brain tumors. Despite continued advances in surgery, chemotherapy, and radiotherapy, the clinical outcomes remain dismal. The 2-year survival rate of GBM is less than 30%. Better understanding of GBM biology is needed to develop novel therapies. Recent studies have demonstrated the existence of a small subpopulation of cells with stemlike features called cancer stem cells (CSCs). These GBM CSCs are self renewable and highly tumorigenic. They not only are chemo-radio resistant but also often contain multidrug resistance genes and drug transporter genes. These characteristics enable GBM CSCs to survive standard cytotoxic therapies. Among GBM CSCs, CD133(+) cells are a well-defined population and are prospectively isolated by their cell-surface marker. Increasing data show that the presence of CD133(+) CSCs highly correlates with patient survival, making these cells an ideal immunotherapy target population. The authors have reviewed recent studies related with GBM CSCs (particularly CD133(+) CSCs) and the novel therapeutic strategies targeting these cells.
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PMID:Glioma stem cell research for the development of immunotherapy. 1994 74

In recent years, a small number of cells that have stem cell properties were identified in human gliomas called brain tumor stem cells (BTSCs), which were thought to mainly contribute to the initiation and development of gliomas and could be identified by the surface marker CD133. However, recent studies indicated that the expression of CD133 might be regulated by environmental conditions such as hypoxia and that there might be CD133(-) BTSCs. Genetic mouse models demonstrated that some gliomas originated from transformed neural stem cells (NSCs). Therefore, we investigated the expression of CD15, a surface marker for NSCs, in tumor spheres derived from astrocytoma and ependymoma. CD15(+) cells isolated from these tumor spheres had properties of BTSCs including self-renewal, multidifferentiation, and the ability to recapitulate the phenocopy of primary tumors. CD15 exhibited stable expression in long-term cultured tumor spheres, which sustained BTSCs properties, whereas CD133 expression decreased significantly in late passages. Furthermore, CD15(+)CD133(-) cells isolated from early or late passages of tumor spheres showed similar characteristics of BTSCs. Examination of glioma samples by immunohistochemistry showed that CD15 was expressed in a subset of human brain tumors. Therefore, CD15 can be used as a marker of stem-like cells derived from brain tumors that might contain CD133(-) BTSCs.
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PMID:Brain Tumor Stem-Like Cells Identified by Neural Stem Cell Marker CD15. 1995 86

The imprinted gene PEG3 confers parenting and sexual behaviors, alters growth and development, and regulates apoptosis. However, a molecular mechanism that can account for the diverse functions of Peg3/Pw1 is not known. To elucidate Peg3-regulated pathways, we performed a functional screen in zebrafish. Enforced overexpression of PEG3 mRNA during zebrafish embryogenesis decreased beta-catenin protein expression and inhibited Wnt-dependent tail development. Peg3/Pw1 also inhibited Wnt signaling in human cells by binding to beta-catenin and promoting its degradation via a p53/Siah1-dependent, GSK3beta-independent proteasomal pathway. The inhibition of the Wnt pathway by Peg3/Pw1 suggested a role in tumor suppression. Hypermethylation of the PEG3 promoter in primary human gliomas led to a loss of imprinting and decreased PEG3 mRNA expression that correlated with tumor grade. The decrease in Peg3/Pw1 protein expression increased beta-catenin, promoted proliferation, and inhibited p53-dependent apoptosis in human CD133(+) glioma stem cells. Thus, mammalian imprinting utilizes Peg3/Pw1 to co-opt the Wnt pathway, thereby regulating development and glioma growth.
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PMID:The imprinted gene PEG3 inhibits Wnt signaling and regulates glioma growth. 2006 27

Only a subset of patients with newly diagnosed glioblastoma (GBM) exhibit a response to standard therapy. To date, a biomarker panel with predictive power to distinguish treatment sensitive from treatment refractory GBM tumors does not exist. An analysis was performed using GBM microarray data from 4 independent data sets. An examination of the genes consistently associated with patient outcome, revealed a consensus 38-gene survival set. Worse outcome was associated with increased expression of genes associated with mesenchymal differentiation and angiogenesis. Application to formalin fixed-paraffin embedded (FFPE) samples using real-time reverse-transcriptase polymerase chain reaction assays resulted in a 9-gene subset which appeared robust in these samples. This 9-gene set was then validated in an additional independent sample set. Multivariate analysis confirmed that the 9-gene set was an independent predictor of outcome after adjusting for clinical factors and methylation of the methyl-guanine methyltransferase promoter. The 9-gene profile was also positively associated with markers of glioma stem-like cells, including CD133 and nestin. In sum, a multigene predictor of outcome in glioblastoma was identified which appears applicable to routinely processed FFPE samples. The profile has potential clinical application both for optimization of therapy in GBM and for the identification of novel therapies targeting tumors refractory to standard therapy.
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PMID:A multigene predictor of outcome in glioblastoma. 2015 Mar 67

Tumor-initiating cells with stem cell properties are believed to sustain the growth of gliomas, but proposed markers such as CD133 cannot be used to identify these cells with sufficient specificity. We report an alternative isolation method purely based on phenotypic qualities of glioma-initiating cells (GICs), avoiding the use of molecular markers. We exploited intrinsic autofluorescence properties and a distinctive morphology to isolate a subpopulation of cells (FL1(+)) from human glioma or glioma cultures. FL1(+) cells are capable of self-renewal in vitro, tumorigenesis in vivo and preferentially express stem cell genes. The FL1(+) phenotype did not correlate with the expression of proposed GIC markers. Our data propose an alternative approach to investigate tumor-initiating potential in gliomas and to advance the development of new therapies and diagnostics.
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PMID:Marker-independent identification of glioma-initiating cells. 2416 86

A glioblastoma stem cell (GSC) line, GSC11, grows as neurospheres in serum-free media supplemented with EGF (epidermal growth factor) and bFGF (basic fibroblast growth factor), and, if implanted in nude mice brains, will recapitulate high-grade glial tumors. Treatment with a STAT3 (signal transducer and activator of transcription 3) phosphorylation inhibitor (WP1193) or 10% FBS (fetal bovine serum) both led to a decrease in expression of the stem cell marker CD133 in GSC11 cells, but differed in phenotype changes. Altered glycolipid profiles were associated with some differentially expressed glycogenes. In serum treated cells, an overall increase in glycosphingolipids may be due to increased expression of ST6GALNAC2, a sialyltransferase. Serum treated cells express more phosphatidylcholine (PC), short chain sphingomyelin (SM) and unsaturated long chain phosphatidylinositol (PI). Decrease of a few glycosphingolipids in the STAT3 phosphorylation inhibited cells may be linked to decreased transcripts of ST6GALNAC2 and UGCGL2, a glucosylceramide synthase. A rare 3-sulfoglucuronylparagloboside carrying HNK1 (human natural killer-1) epitope was found expressed in the GSC11 and the phenotypically differentiated cells. Its up-regulation correlates with increased transcripts of a HNK1 biosynthesis gene, B3GAT2 after serum treatment. Taken together with a quantitative phosphoproteomic study of the same GSC line (C. L. Nilsson, et al. J. Proteome Res. 2010, 9, 430-443), this report represents the most complete systems biology study of cancer stem cell (CSC) differentiation to date. The synergies derived by the combination of glycomic, transcriptomic and phosphoproteomic data may aid our understanding of intracellular and cell-surface events associated with CSC differentiation.
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PMID:Glycomic and transcriptomic response of GSC11 glioblastoma stem cells to STAT3 phosphorylation inhibition and serum-induced differentiation. 2019 6

The newly proposed glioma stem cell (GSC) hypothesis may re-model the way we diagnose and treat the tumor, which highlights the need for a complete knowledge on the genetic and epigenetic "blueprints" of GSCs. To identify the true "stemness" signatures, pure GSC populations are primarily needed. Reliable in vitro methods enriching for GSCs and thereby identifying the key stem-like characteristics constitute the preliminary step forward. We discuss in this review the current widely used methods for enriching and isolating GSCs, namely neurosphere assay, CD133 Immunophenotyping and side population assay, and detail their limitations and potential pitfalls that could complicate interpretation of corresponding results.
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PMID:The utility and limitations of neurosphere assay, CD133 immunophenotyping and side population assay in glioma stem cell research. 2033 19

We have previously demonstrated the multipotent nature of human umbilical cord blood stem cells (hUCB). In this study, we have attempted to show the use of hUCB in glioma therapy. We used hUCB enriched in CD44 and CD133 cells for our studies and observed that glioma cells co-cultured with hUCB undergo apoptosis. To prove the role of cell-to-cell contact in the induction of apoptotic events, we used a modified 0.22 microm Boyden's chamber where the upper surface was used to culture glioma cells (SNB19 or U87) or xenografts (4910 or 5310) and the lower surface to culture hUCB. TUNEL assay was carried out to determine the degree of apoptotic induction and we observed that glioma or xenograft cells co-cultured with hUCB had a higher number of TUNEL-positive characteristics (63+/-6%) compared to the controls. Further, we co-cultured glioma cells labeled with lipophilic green fluorescent dye and hUCB labeled with lipophilic red fluorescent dye. FACS analysis of cells collected from the upper and lower surfaces revealed that glioma cells had taken up red fluorescent dye from the stem cells (70+/-3%) when compared to glioma cells co-cultured with fibroblast cells (15+/-4%). The apoptotic events in the glioma and xenograft cells co-cultured with hUCB were also confirmed by Western blot analysis for the cleavage of PARP and activation of caspase 8. In addition, elevated levels of CHK-2 levels and downregulation of MAP2K1 were observed in glioma cells co-cultured with hUCB indicating the DNA damage and decrease in cell survival. Nude mice, intracranially implanted with luciferase-expressing U87 cells followed by implantation of hUCB or human fibroblast cells showed retardation of intracranial tumors in hUCB-implanted mice. Taken together, these results demonstrate that hUCB have therapeutic potential with possible clinical implications.
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PMID:Induction of apoptosis in glioma cells requires cell-to-cell contact with human umbilical cord blood stem cells. 2037 90

Glioma results from unregulated expansion of a self-renewing glioma-initiating cell population. The regulatory pathways which are essential for sustaining the self-renewal of glioma-initiating cells remain largely unknown. Cell surface N-linked oligosaccharides play functional roles in determining cell fate and are associated with glioma malignancy. Previously, we have reported that beta1,4-galactosyltransferase V (beta1,4GalT V) effectively galactosylates the GlcNAcbeta1-->6Man arm of the highly branched N-glycans and positively regulates glioma cell growth. Here, we show that decreasing the expression of beta1,4GalT V by RNA interference in glioma cells attenuated the formation of polylactosamine and inhibited the ability of tumor formation in vivo. Down-regulation of beta1,4GalT V depleted CD133-positive cells in glioma xenograft, and inhibited the self-renewal capacity and the tumorigenic potential of glioma-initiating cells. These data reveal a critical role of beta1,4GalT V in the self-renewal and tumorigenicity of glioma-initiating cells, and indicate that manipulating beta1,4GalT V expression may have therapeutic potential for the treatment of malignant glioma.
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PMID:Beta1,4-galactosyltransferase V regulates self-renewal of glioma-initiating cell. 2041 17


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