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

Malignant glioma continues to be a major target for gene therapy and virotherapy due to its aggressive growth and the current lack of effective treatment. However, these approaches have been hampered by inefficient infection of glioma cells by viral vectors,particularly vectors derived from serotype 5 adenoviruses (Ad5). This results from limited cell surface expression of the primary adenovirus receptor, coxsackie-adenovirus-receptor (CAR), on tumor cells. To circumvent this problem, Ad fiber pseudotyping,the genetic replacement of either the entire fiber or fiber knob domain with its structural counterpart from another human Ad serotype that recognizes a cellular receptor other than CAR, has been shown to enhance Ad infectivity in a variety of tumor types,including human glioma. Here, we have extended the paradigm of genetic pseudotyping to include fiber domains from non-human or"xenotype" Ads for infectivity enhancement of human glioma cell populations. In this study, we evaluated the gene transfer efficiency of a panel of Ad vectors which express one of five different "xenotype"fiber knob domains, including those derived from murine,ovine, porcine and canine species, in both human glioma cell lines as well as primary glioma tumor cells from patients. Adenovirus vectors displaying either canine Ad or porcine Ad fiber elements had the highest gene transfer to both glioma cell lines and primary tumor cells. The correlation between the viral infectivity of modified adenovirus vectors and expression of human CAR and CD46(an adenovirus type B receptor) on the surfaces of tumor cells was also analyzed. Taken together, human adenovirus vectors modified with "xenotype" fiber elements could be excellent candidates to target human glioma.
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PMID:Characterization of infectivity of knob-modified adenoviral vectors in glioma. 1875 25

A key step in angiogenesis is the upregulation of growth factor receptors on endothelial cells. Here, we demonstrate that a small regulatory microRNA, miR-296, has a major role in this process. Glioma cells and angiogenic growth factors elevate the level of miR-296 in primary human brain microvascular endothelial cells in culture. The miR-296 level is also elevated in primary tumor endothelial cells isolated from human brain tumors compared to normal brain endothelial cells. Growth factor-induced miR-296 contributes significantly to angiogenesis by directly targeting the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) mRNA, leading to decreased levels of HGS and thereby reducing HGS-mediated degradation of the growth factor receptors VEGFR2 and PDGFRbeta. Furthermore, inhibition of miR-296 with antagomirs reduces angiogenesis in tumor xenografts in vivo.
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PMID:miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. 1897 27

We sought to establish a new orthotopic glioma model of nude mice by transfer of DsRed2, a red fluorescent protein gene, to malignant glioma cells and to perfuse the tissue with fluorescein isothiocyanate (FITC) dextran in vivo, which would permit the concurrent detection of brain tumor invasion and angiogenesis in vivo by florescence microscopy. 9L or U87 malignant glioma cells with DsRed2 expression were intracerebrally injected into the nude mice. FITC-dextran was administered intravenously to the mice bearing DsRed2-9L or DsRed2-U87 cells immediately before they were sacrificed at 10 days or 15 days after the implantation, respectively. Coronal vibratome sections were examined using 2D and 3D fluorescence microscopy and the results were compared with those examined by routine hematoxylin and eosin (H & E) staining. Angiogenesis induced by glioma was confirmed by two-dimensional and three-dimensional imaging analysis. DsRed2 fluorescence clearly demarcated the primary tumor margins and readily allowed for the visualization of local invasion at the single-cell level in the brain adjacent to tumor. We found that a few tumor cells migrated from the tumor mass along the aberrant microvasculature, but did not extend out of the angiogenic areas. However, locally invasive foci were very difficult to detect by H & E staining. We demonstrated, for the first time, that abnormal vascular structure and glioma cells can be visualized concurrently by fluorescence microscopy. This method is superior to H & E staining for the detection and study of physiologically relevant patterns of brain tumor invasion and angiogenesis in vivo.
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PMID:Dual-color fluorescence imaging in a nude mouse orthotopic glioma model. 1944 36

Glioblastoma multiforme is a grade IV astrocytic tumor with a very high mortality rate. Although current treatment often includes surgical resection, this rarely removes all primary tumor cells, so is usually followed by radiation and/or chemotherapy. Remaining migratory tumor cells invade surrounding healthy tissue and contribute to secondary and tertiary tumor recurrence; therefore, despite significant research into glioma removal and treatment, prognosis remains poor. A variety of treatment modalities have been investigated to deliver drug to these cells, including systemic, diffusive and convection-enhanced delivery (CED). As systemic delivery is limited by molecules larger than approximately 500 Da being unable to cross the blood-brain barrier (BBB), therapeutic concentrations are difficult to attain; thus, localized delivery options relying on diffusion and CED have been used to circumvent the BBB. Although CED enables delivery to a greater volume of tissue than diffusive delivery alone, limitations still exist, requiring that these delivery strategies be improved. This review enumerates the strengths and weaknesses of these currently used strategies and details how predictive mathematical modeling can be used to aid investigators in optimizing these delivery modalities for clinical application.
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PMID:Targeted drug delivery for treatment and imaging of glioblastoma multiforme. 1953 36

Nearly 10% of human gliomas are oligodendrogliomas. Deletion of chromosome arm 19q, often in conjunction with deletion of 1p, has been observed in 65-80% of these tumors. This has suggested the presence of a tumor suppressor gene located on the 19q arm. Chromosome 19 deletion is also of interest due to the better prognosis of patients with deletion, including longer survival and better response to chemotherapy, compared with patients without deletion. Two glioma cell lines with deletion of 19q were used for chromosome 19 microcell-mediated transfer, to assess the effect of replacing the deleted segment. Complementation with chromosome 19 significantly reduced the growth rate of the hybrid cells compared with the parental cell lines. Affymetrix U133 Plus 2.0 Gene Chip analysis was performed to measure and compare the expression of the chromosome 19 genes in the chromosome 19 hybrid cell lines to the parental cell line. Probes were considered significantly different when a P value <0.01 was seen in all of the cell line comparisons. Of 345 probes within the commonly deleted 19q region, seven genes (APOE, RCN3, FLJ10781, SAE1, STRN4, CCDC8, and BCL2L12) were identified as potential candidate genes. RT-PCR analysis of primary tumor specimens showed that several genes had significant differences when stratified by tumor morphology or deletion status. This suggests that one or more of these candidates may play a role in glioma formation or progression.
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PMID:Characterization and gene expression profiling in glioma cell lines with deletion of chromosome 19 before and after microcell-mediated restoration of normal human chromosome 19. 1954 81

Glioblastoma multiforme (GB) is the most aggressive, and the most frequent primary tumor of the brain in adults. Presence of less-differentiated areas which exhibit a small cell morphology and neural immunophenotype is quite uncommon in GBs. Tumor tissue which had been determined in the frontotemporal region of a 61-year-old female patient and evaluated to be consistent with GB radiologically was subjected to total excision. Histopathological examination revealed two different components making up the tumor tissue. Using a morphological and immunophenotypic approach, the predominant component of the tumor was found to bear the properties of classic GB. The other component was composed of undifferentiated areas exhibiting small cell morphology and diffuse neuronal immunophenotype. The case was diagnosed as 'Glioblastoma with primitive neuroectodermal tumor-like component'. The patient who had been subjected to postoperative radiotherapy, showed no sign of recurrence during the follow-up examination performed on the 9th month. The histogenesis and prognostic significance of neuronal differentiation observed in glial tumors are not known yet. Inclusion of this component in pathological reports is important regarding formation of a database for future studies.
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PMID:Glioblastoma with primitive neuroectodermal tumor-like features: case report. 1962 Dec 91

The malignant glioma is the most common primary human brain tumor. Its tendency to invade away from the primary tumor mass is considered a leading cause of tumor recurrence and treatment failure. Accordingly, the molecular pathogenesis of glioma invasion is currently under investigation. Previously, we examined a gene expression array database comparing human gliomas to nonneoplastic controls and identified several Rac guanine nucleotide exchange factors with differential expression. Here, we report that the guanine nucleotide exchange factor SWAP-70 has increased expression in malignant gliomas and strongly correlates with lowered patient survival. SWAP-70 is a multifunctional signaling protein involved in membrane ruffling that works cooperatively with activated Rac. Using a glioma tissue microarray, we validated that SWAP-70 demonstrates higher expression in malignant gliomas compared with low-grade gliomas or nonneoplastic brain tissue. Through immunofluorescence, SWAP-70 localizes to membrane ruffles in response to the growth factor, epidermal growth factor. To assess the role of SWAP-70 in glioma migration and invasion, we inhibited its expression withsmall interfering RNAs and observed decreased glioma cell migration and invasion. SWAP-70 overexpression led to increased levels of active Rac even in low-serum conditions. In addition, when SWAP-70 was overexpressed in glioma cells, we observed enhanced membrane ruffle formation followed by increased cellmigration and invasiveness. Taken together, our findings suggest that the guanine nucleotide exchange factor SWAP-70 plays an important role in the migration and invasion of human gliomas into the surrounding tissue.
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PMID:The Guanine Nucleotide Exchange Factor SWAP-70 Modulates the Migration and Invasiveness of Human Malignant Glioma Cells. 1995 92

We report a case of intramedullary cervical metastasis from cerebellar anaplastic oligodendroglioma without any MR appearance for CSF dissemination or recurrence in the primary tumor site. The case was a 73-year-old female who underwent tumor resection for cerebellar anaplastic oligodendroglioma following irradiation and TMZ chemotherapy. One year and a half later, a small nodular lesion developed at the temporal lobe. While treatment with TMZ was restarted during the course, another intramedullary cervical lesion produced additionally without any CSF dissemination or recurrence at the primary site. The histological examination obtained in spinal surgery revealed evidence of similar features consistent with a previous cerebellar tumor with anaplastic oligodendroglioma. Although CSF dissemination by malignant glioma with leptomeningeal enhancement is relatively well recognized at their terminal stage, cases with intramedullary cervical metastasis without any leptomeningeal enhancement have only been rarely described. We discussed the mechanisms of intramedullary cervical metastasis from intracranial malignant glioma.
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PMID:[A case of intramedullary cervical metastasis from cerebellar anaplastic oligodendroglioma without typical MR appearance for CSF dissemination]. 2022 74

To identify a novel amplified cancer gene a systematic screen of 975 human cancer DNA samples, 750 cell lines and 225 primary tumors, using the Affymetrix 10K SNP microarray was undertaken. The screen identified 193 amplicons. A previously uncharacterized amplicon located on 6p21.2 whose 1 Mb minimal common amplified region contained eight genes (GLO1, DNAH8, GLP1R, C6orf64, KCNK5, KCNK17, KCNK16, and C6orf102) was further investigated to determine which gene(s) are the biological targets of this amplicon. Real time quantitative PCR (qPCR) analysis of all amplicon 6p21.2 genes in 618 human cancer cell lines identified GLO1, encoding glyoxalase 1, to be the most frequently amplified gene [twofold or greater amplification in 8.4% (49/536) of cancers]. Also the association between amplification and overexpression was greatest for GLO1. RNAi knockdown of GLO1 had the greatest and most consistent impact on cell accumulation and apoptosis. Cell lines with GLO1 amplification were more sensitive to inhibition of GLO1 by bromobenzylglutathione cyclopentyl diester (BBGC). Subsequent qPCR of 520 primary tumor samples identified twofold and greater amplification of GLO1 in 8/37 (22%) of breast, 12/71 (17%) of sarcomas, 6/53 (11.3%) of nonsmall cell lung, 2/23 (8.7%) of bladder, 6/93 (6.5%) of renal and 5/83 (6%) of gastric cancers. Amplification of GLO1 was rare in colon cancer (1/35) and glioma (1/94). Collectively the results indicate that GLO1 is at least one of the targets of gene amplification on 6p21.2 and may represent a useful target for therapy in cancers with GLO1 amplification.
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PMID:GLO1-A novel amplified gene in human cancer. 2054 45

Differentiation of gliomas and reactive gliosis may be challenging both at primary tumor occurrence and at posttherapy biopsy. The most frequent IDH1 mutation found in the majority of WHO grade II and III gliomas can be visualized with an antibody specifically detecting mutant IDH1 protein. In this study, mIDH1R132H immunoreactivity in 120 reactive gliosis specimens of various etiologies is compared with Wilms Tumor 1 (WT1) and p53 expression, both markers applied for the differentiation of reactive gliosis and glioma. Although WT1 and p53 positive glial cells were found in 17% and 63% of cases respectively, all samples were negative for mIDH1R132H. Furthermore, we investigated 19 posttherapy gliomas (6 WHO II, 13 WHO III) with extensive reactive changes and detected mIDH1R132H positive cells in 13 specimens. In 5 of these cases, tumor cells were missed by conventional staining, showing the improved sensitivity of mIDH1R132H. Thus, mIDH1R132H is a tumor-specific marker that is superior to other established markers to differentiate reactive from neoplastic cells in grade II and III gliomas and allows identifying tumor cells in posttherapy specimens with extensive reactive changes. As IDH mutations are not characteristic of grade IV primary glioblastomas, this antibody cannot differentiate primary glioblastoma from reactive gliosis. Thus, caution has to be taken and a combined panel with other markers is needed.
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PMID:Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. 2066 Oct 18


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