Project description:Glioblastoma multiforme (GBM) is a highly malignant brain cancer, and microglial cells play a critical role in its progression. Activation of microglia can either promote or inhibit GBM growth depending on the stage of tumour development and on the microenvironment. As current treatments for GBM have limited efficacy, there is an urgent need to develop novel strategies based on nanoplatforms for drug delivery and efficient targeting. This study investigated the microglial response and the therapeutic efficacy of dual cell membrane-coated and doxorubicin-loaded hexagonal boron nitride nanoplatelets, tested on human microglia and GBM cells. The results showed promising therapeutic effects on glioma cells and an M2 microglia polarization, highlighted through proteomic analysis.
Project description:The purpose of this study is to determine whether the combination of two agents, INC280 and bevacizumab, is safe and effective when administered to patients with Glioblastoma Multiforme (GBM) who have progressed after receiving prior therapy or who have unresectable GBM.
Project description:glioblastoma multiforme genomic profiling by single nucleotide polymorphism microarray<br><br>Human GBM (glioblastoma multiforme)cell lines (U87, U118, U138, U343, U373, T98G) were maintained in Dulbecco's modified Eagle's medium with 10 % fetal calf serum, 10 U/ml penicillin-G, and 10 mg/ml streptomycin. All cells were incubated at 37 oC in 5% CO2.<br><br>Four primary GBM explants were established from patients with glioblastoma multiforme undergoing surgery as following described: Tumor specimens were immediately transported to the laboratory, finely minced to single cell suspension and cultured in complete medium [Ham's F-12/DME High Glucose medium containing 10% fetal calf serum, 10 U/ml penicillin-G, and 10 mg/ml streptomycin and 2 mM glutamax-1 into 100 cm2 tissue culture plastic dishes the second passage. All cells were incubated at 37 oC in 5% CO2.<br><br>GBM (glioblastoma multiforme) tissue samples were quick frozen. <br><br>Standard proteinase K-phenol-chloroform extraction method was used to extract DNA from GBM samples, cell lines and explants.<br><br>The matched peripheral blood data can be used as normalized data for their matched tumor tissue data. <br><br>The cell lines samples and two explants without normalized data, but they can be normalized by one of the peripheral blood DNA data.
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net ) 25 glioblastoma multiforme tumors hybridized on Illumina SNP and Affymetrix gene expression arrays. Project leader : François DUCRAY (francois.ducray@chu-lyon.fr). CIT Analysis : Julien LAFFAIRE (laffairej@ligue-cancer.net). Note: PFS : progression-free survival, OS: Overall Survival,BCNU : Carmustine (chemotherapy agent). RESPONDER: if the patient has shown or not shown a response to the treatment (Bevacizumab (Avastin) plus Irinotecan). Progression during : If the disease has progressed (cancer relapse or patient's death); otherwise (patient is alive without relapse).
Project description:Ten pairs frozen Glioblastoma Multiforme (GBM) from initial and recurrent surgery after radio-chemotherapy were screened by CGH Array.
Project description:We used microarrays to investigate the whole genome gene expression level changes of LncRNAs in human Glioblastoma multiforme (GBM) and normal brain tissues, and try to find out some LncRNA associated with the tumorigenesis of GBM.
Project description:Human Glioblastoma Multiforme tumors taken before dendritic cell vaccination, the recurrent tumors taken after vaccination and control GBM tumors from non vaccinated patients. Experiment Overall Design: Six Glioblastoma Multiforme patients underwent surgery. Their brain tumors were removed and analyzed via microarray. The lysate from the tumors were cultured with the patients' dendritic cells and the DCs were injected back into the patients. The patients GBMs returned and they underwent surgery a second time and those tumors were also analyzed via microarray. Tumors from the first and second GBM surgeries of 5 patients who did not receive DC vaccines are included as controls.
Project description:Overexpression of the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM) (1). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A (DZNep), or its specific down-regulation by shRNA, strongly impairs GBM cancer stem cell self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM cancer stem cells, we found the expression of c-myc, recently reported to be essential for GBM cancer stem cells, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated down-regulation of EZH2 in combination with chromatin immunoprecipitation (ChIP) experiments revealed that c-myc is a direct target of EZH2 in GBM cancer stem cells. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM cancer stem cell maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management. Experiment Overall Design: Three samples of cancer stem-cell enriched gliospheres from primary glioblastoma multiforme cell cultures were treated with DZNep. Untreated gliospheres from the same cultures were used as controls.