scholarly journals The Molecular Basis of Resistance to the Antiproliferative Effect of EGFR Inhibition in Human Glioblastoma Multiforme Cell Lines

10.5772/24053 ◽  
2011 ◽  
Author(s):  
Georg Karpel-Massler ◽  
Marc-Eric Halatsch
Keyword(s):  
Glioblastoma Multiforme ◽  
Cell Lines ◽  
Molecular Basis ◽  
Antiproliferative Effect ◽  
Human Glioblastoma ◽  
Egfr Inhibition ◽  
Human Glioblastoma Multiforme

scholarly journals Lomeguatrib Increases the Radiosensitivity of MGMT Unmethylated Human Glioblastoma Multiforme Cell Lines

2021 ◽  
Vol 22 (13) ◽  
pp. 6781
Author(s):  
Anna Kirstein ◽  
Daniela Schilling ◽  
Stephanie E. Combs ◽  
Thomas E. Schmid
Keyword(s):  
Glioblastoma Multiforme ◽  
Cell Lines ◽  
Dna Methyltransferase ◽  
Treatment Options ◽  
Treatment Resistance ◽  
Cell Cycle Distribution ◽  
Human Glioblastoma ◽  
Human Glioblastoma Multiforme ◽  
Mgmt Protein

Background: Treatment resistance of glioblastoma multiforme to chemo- and radiotherapy remains a challenge yet to overcome. In particular, the O6-methylguanine-DNA-methyltransferase (MGMT) promoter unmethylated patients have only little benefit from chemotherapy treatment using temozolomide since MGMT counteracts its therapeutic efficacy. Therefore, new treatment options in radiotherapy need to be developed to inhibit MGMT and increase radiotherapy response. Methods: Lomeguatrib, a highly specific MGMT inhibitor, was used to inactivate MGMT protein in vitro. Radiosensitivity of established human glioblastoma multiforme cell lines in combination with lomeguatrib was investigated using the clonogenic survival assay. Inhibition of MGMT was analyzed using Western Blot. Cell cycle distribution and apoptosis were investigated to determine the effects of lomeguatrib alone as well as in combination with ionizing radiation. Results: Lomeguatrib significantly decreased MGMT protein and reduced radiation-induced G2/M arrest. A radiosensitizing effect of lomeguatrib was observed when administered at 1 µM and increased radioresistance at 20 µM. Conclusion: Low concentrations of lomeguatrib elicit radiosensitization, while high concentrations mediate a radioprotective effect.

scholarly journals Molecular and functional MDR1-Pgp and MRPs expression in human glioblastoma multiforme cell lines

2002 ◽  
Vol 98 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Xavier Declèves ◽  
Anne Fajac ◽  
Jacqueline Lehmann-Che ◽  
Marcienne Tardy ◽  
Claire Mercier ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Cell Lines ◽  
Human Glioblastoma ◽  
Human Glioblastoma Multiforme

Role of galectin-1 in migration and invasion of human glioblastoma multiforme cell lines

2008 ◽  
Vol 109 (2) ◽  
pp. 273-284 ◽  
Author(s):  
Tae-Young Jung ◽  
Shin Jung ◽  
Hyang-Hwa Ryu ◽  
Young-Il Jeong ◽  
Yong-Hao Jin ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Western Blot ◽  
Cell Lines ◽  
Blot Analysis ◽  
Migration And Invasion ◽  
Genetic Changes ◽  
Human Glioblastoma ◽  
Human Glioblastoma Multiforme ◽  
Human Gbm

Object Galectin-1 is highly expressed in motile cell lines. The authors investigated whether galectin-1 actually modulates the migration and invasion of human glioblastoma multiforme (GBM) cell lines, and whether its expression with respect to invasion and prognosis is attributable to certain glioma subgroups. Methods In the human GBM cell lines U343MG-A, U87MG, and U87MG-10′, the RNA differential display was evaluated using Genefishing technology. The results were validated by reverse transcription polymerase chain reaction and Northern blot analysis to detect possible genetic changes as the determining factors for the motility of the malignant glioma. The migration and invasion abilities were investigated in human GBM cell lines and galectin-1 transfectant using an in vitro brain slice invasion model and a simple scratch technique. The morphological and cytoskeletal (such as the development of actin and vimentin) changes were examined under light and confocal microscopy. Galectin-1 expression was assessed on immunohistochemical tests and Western blot analysis. Results Endogenous galectin-1 expression in the human GBM cell lines was statistically correlated with migratory abilities and invasiveness. The U87-G-AS cells became more round than the U87MG cells and lacked lamellipodia. On immunohistochemical staining, galectin-1 expression was increased in higher-grade glioma subgroups (p = 0.027). Conclusions Diffuse gliomas demonstrated higher expression levels than pilocytic astrocytoma in the Western blot. Galectin-1 appears to modulate migration and invasion in human glioma cell lines and may play a role in tumor progression and invasiveness in human gliomas.

scholarly journals Dp71 Expression in Human Glioblastoma

2019 ◽  
Vol 20 (21) ◽  
pp. 5429 ◽  
Author(s):  
Simona Ruggieri ◽  
Michelina De Giorgis ◽  
Tiziana Annese ◽  
Roberto Tamma ◽  
Angelo Notarangelo ◽  
...  
Keyword(s):  
Nervous System ◽  
Glioblastoma Multiforme ◽  
Cell Lines ◽  
Glioblastoma Cell ◽  
Coding Region ◽  
Double Labeling ◽  
Human Glioblastoma ◽  
Lamin B ◽  
Human Glioblastoma Multiforme ◽  
Glioblastoma Cell Lines

Background: Dp71 is the most abundant dystrophin (DMD) gene product in the nervous system. Mutation in the Dp71 coding region is associated with cognitive disturbances in Duchenne muscular dystrophy (DMD) patients, but the function of dystrophin Dp71 in tumor progression remains to be established. This study investigated Dp71 expression in glioblastoma, the most common and aggressive primary tumor of the central nervous system (CNS). Methods: Dp71 expression was analyzed by immunofluorescence, immunohistochemistry, RT-PCR, and immunoblotting in glioblastoma cell lines and cells isolated from human glioblastoma multiforme (GBM) bioptic specimens. Results: Dp71 isoform was expressed in normal human astrocytes (NHA) cell lines and decreased in glioblastoma cell lines and cells isolated from human glioblastoma multiforme bioptic specimens. Moreover, Dp71 was localized in the nucleus in normal cells, while it was localized into the cytoplasm of glioblastoma cells organized in clusters. We have shown, by double labeling, that Dp71 colocalizes with lamin B in normal astrocytes cells, confirming the roles of Dp71 and lamin B in maintaining nuclear architecture. Finally, we demonstrated that decreased Dp71 protein in cells isolated from human bioptic specimens was inversely correlated with the Ki-67 tumor proliferative index. Conclusion: A decreased Dp71 expression is associated with cancer proliferation and poor prognosis in glioblastoma.

Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib

2009 ◽  
Vol 111 (2) ◽  
pp. 211-218 ◽  
Author(s):  
Marc-Eric Halatsch ◽  
Sarah Löw ◽  
Kay Mursch ◽  
Thomas Hielscher ◽  
Ursula Schmidt ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Candidate Genes ◽  
Cell Lines ◽  
Cellular Response ◽  
Kinase Inhibitor ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expressions ◽  
Human Glioblastoma ◽  
Human Glioblastoma Multiforme

Object The authors have previously reported that erlotinib, an EGFR tyrosine kinase inhibitor, exerts widely variable antiproliferative effects on 9 human glioblastoma multiforme (GBM) cell lines in vitro and in vivo. These effects were independent of EGFR baseline expression levels, raising the possibility that more complex genetic properties form the molecular basis of the erlotinib-sensitive and erlotinib-resistant GBM phenotypes. The aim of the present study was to determine candidate genes for mediating the cellular response of human GBMs to erlotinib. Methods Complementary RNA obtained in cell lines selected to represent the sensitive, somewhat responsive, and resistant phenotypes were hybridized to CodeLink Human Whole Genome Bioarrays. Results Expression analysis of 814 prospectively selected genes involved in major proliferation and apoptosis signaling pathways identified 19 genes whose expression significantly correlated with phenotype. Functional annotation analysis revealed that 2 genes (DUSP4 and STAT1) were significantly associated with sensitivity to erlotinib, and 10 genes (CACNG4, FGFR4, HSPA1B, HSPB1, NFATC1, NTRK1, RAC1, SMO, TCF7L1, and TGFB3) were associated with resistance to erlotinib. Moreover, 5 genes (BDNF, CARD6, FOSL1, HSPA9B, and MYC) involved in antiapoptotic pathways were unexpectedly found to be associated with sensitivity. Gene expressions were confirmed by quantitative polymerase chain reaction. Conclusions Based on an analysis of gene expressions in cell lines with sensitive, somewhat responsive, and resistant phenotypes, the authors propose candidate genes for GBM response to erlotinib. The 10 gene candidates for conferring GBM resistance to erlotinib may represent therapeutic targets for enhancing the efficacy of erlotinib against GBMs. Five additional genes warrant further investigation into their role as putative cotargets of erlotinib.

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