Gene expression signatures for anti-glioma therapy with Ad-SGE-REIC and bevacizumab
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PROVIDER: PRJNA848377 | ENA |
REPOSITORIES: ENA
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Project description:We investigated the gene expression profile of tumor-bearing mouse brain treated with PBS(control), Ad-SGE-REIC(SGE), or combination of Ad-SGE-REIC and bevacizumab (SGE+BEV).
2022-08-09 | GSE205928 | GEO
Project description:Bevacizumab represents anti-angiogenic effect in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the resistance to the initial response. Such resistance could be regulated by various cell types and soluble factors, although the underlying mechanisms, especially cell-based mechanisms, remain incompletely understood. Here, we identified bone marrow-derived fibrocytes as a novel contributor for the acquired resistance to bevacizumab, defined as alpha-1 type I collagen-positive and CXCR4-positive cells. In mouse models of lung cancer and malignant pleural mesothelioma, fibrocytes mediated the resistance to bevacizumab as a main producer of fibroblast growth factor 2. Using clinical specimens of lung cancer that were surgically resected after bevacizumab treatment, we demonstrated that the number of fibrocytes was significantly increased in bevacizumab-treated tumor, and was correlated with the number of treatment cycles as well as CD31-positive vessels. Our results identify fibrocytes as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy.
2015-12-03 | GSE59476 | GEO
Project description:Bevacizumab induces glioblastoma resistance in two in vivo xenograft models. Two cell lines were developed with acquired resistance to bevacizumab. Gene expression difference were analyzed between treated and untreated tumors. Purpose: Antiangiogenic therapy reduces vascular permeability and delays progression but may ultimately promote an aggressive treatment-resistant phenotype. The aim of the present study was to identify mechanisms responsible for glioblastoma resistance to antiangiogenic therapy. Experimental Design: Glioma stem cell (GSC) NSC11 and U87 cell lines with acquired resistance to bevacizumab were developed from orthotopic xenografts in nude mice treated with bevacizumab. Genome-wide analyses were used to identify changes in tumor subtype and specific factors associated with resistance. Results: Mice with established parental NSC11 and U87 cells responded to bevacizumab, whereas glioma cell lines derived at the time of acquired resistance to anti-VEGF therapy were resistant to bevacizumab and did not have prolongation of survival compared to untreated controls. Gene expression profiling comparing anti-VEGF therapy-resistant cell lines to untreated controls demonstrated an increase in genes associated with a mesenchymal origin, cellular migration/invasion, and inflammation. Gene Set Enrichment Analysis (GSEA) demonstrated that bevacizumab-treated tumors showed a highly significant correlation to published mesenchymal gene signatures. Mice bearing resistant tumors showed significantly greater infiltration of myeloid cells in NSC11 and U87 resistant tumors. Invasion-related genes were also upregulated in both NSC11 and U87 resistant cells, which had higher invasion rates in vitro compared with their respective parental cell lines. Conclusions: Our studies identify multiple pro-inflammatory factors associated with resistance and identify a proneural-to-mesenchymal transition (PMT) in tumors resistant to antiangiogenic therapy. Glioma cell lines were injected into the caudate of nude mice and were allowed to grow untreated (samples labeled control) or were treated with 10 mg/kg IP twice weekly with bevacizumab (samples labeled Avastin). At the time of animal death, tumor tissue from the mouse was removed, and RNA was isolated and analyzed using gene expression. U87R and NSC11R represent cells resistant to bevacizumab (Avastin).
2013-07-01 | E-GEOD-45161 | biostudies-arrayexpress
Project description:The combination of bevacizumab with temozolomide and radiotherapy was shown to prolong progression-free survival in newly diagnosed glioblastoma patients, and this emphasizes the potential of bevacizumab as a glioma treatment. However, while bevacizumab effectively inhibits angiogenesis, it has also been reported to induce invasive proliferation. This study examined gene expression in glioma cells to investigate the mechanisms of bevacizumab-induced invasion. We made a human glioma U87ΔEGFR cell xenograft model by stereotactically injecting glioma cells into the brain of animals. We administered bevacizumab intraperitoneally three times per week. At 18 days after tumor implantation, the brains were removed for histopathology and mRNA was extracted. In vivo, bevacizumab treatment increased glioma cell invasion. qRT-PCR array analysis were perfomed.
2019-02-07 | GSE126168 | GEO
Project description:Bevacizumab induces glioblastoma resistance in two in vivo xenograft models. Two cell lines were developed with acquired resistance to bevacizumab. Gene expression difference were analyzed between treated and untreated tumors. Purpose: Antiangiogenic therapy reduces vascular permeability and delays progression but may ultimately promote an aggressive treatment-resistant phenotype. The aim of the present study was to identify mechanisms responsible for glioblastoma resistance to antiangiogenic therapy. Experimental Design: Glioma stem cell (GSC) NSC11 and U87 cell lines with acquired resistance to bevacizumab were developed from orthotopic xenografts in nude mice treated with bevacizumab. Genome-wide analyses were used to identify changes in tumor subtype and specific factors associated with resistance. Results: Mice with established parental NSC11 and U87 cells responded to bevacizumab, whereas glioma cell lines derived at the time of acquired resistance to anti-VEGF therapy were resistant to bevacizumab and did not have prolongation of survival compared to untreated controls. Gene expression profiling comparing anti-VEGF therapy-resistant cell lines to untreated controls demonstrated an increase in genes associated with a mesenchymal origin, cellular migration/invasion, and inflammation. Gene Set Enrichment Analysis (GSEA) demonstrated that bevacizumab-treated tumors showed a highly significant correlation to published mesenchymal gene signatures. Mice bearing resistant tumors showed significantly greater infiltration of myeloid cells in NSC11 and U87 resistant tumors. Invasion-related genes were also upregulated in both NSC11 and U87 resistant cells, which had higher invasion rates in vitro compared with their respective parental cell lines. Conclusions: Our studies identify multiple pro-inflammatory factors associated with resistance and identify a proneural-to-mesenchymal transition (PMT) in tumors resistant to antiangiogenic therapy.
2013-07-01 | GSE45161 | GEO
Project description:The patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received bevacizumab therapy as first line or second line treatment. Responders and nonresponders were determined based on RECIST and confirmed by CT or MRI. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. Colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. To identify molecular signatures to predict response to bevacizumab, gene expression profiles were compared between Reponder and Non-responder.
2013-01-03 | E-GEOD-19862 | biostudies-arrayexpress
Project description:Purpose: To identify transcriptional changes by RNA-seq in tumor samples, before bevacizumab combination treatment and after bevacizumab combination treatment in both responding and non-responding recurrent glioblastoma patients
2017-04-20 | GSE79671 | GEO
Project description:Modern therapy approaches fail to prevent high grade glioma recurrence. So, alternative ways need to be developed. Changing glioma cells’ fate is an alternative way to prevent tumor growth. Two-step protocol based on an antiproliferative G-quadruplex and small molecules triggering neural differentiation showed to be effective on glioblastoma cell cultures. This approach was named a differential therapy. In this paper, we broaden the spectrum of cell cultures to gliomas of II, III and IV grades, showing the universality of suggested protocol on a variety of cancer cells. We checked the reasonability of consistent addition of factors to the glioma cells. Moreover, we demonstrated a significant inhibition of tumor growth after injection of GQIcombi into 101/8 tumor in glioma rat model. Thus, the proposed strategy of influencing on cancer cell growth is applicable to be further translated for therapy use.
2024-01-09 | GSE250617 | GEO
Project description:The patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received bevacizumab therapy as first line or second line treatment. Responders and nonresponders were determined based on RECIST and confirmed by CT or MRI. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133.
2013-01-03 | GSE19862 | GEO
Project description:Gliomas are the most frequent type of primary tumor of the central nervous system in adults with significant morbidity and mortality. Despite the development of novel, complex, multidisciplinary, and targeted therapies, glioma therapy has not progressed much over the last decades. Therefore, there is an urgent need to develop novel patient-adjusted immunotherapies that actively stimulate antitumor T cells generating long-term memory and thus resulting in significant clinical benefits. This work aimed to investigate the efficacy and molecular mechanism of dendritic cell (DC) vaccines loaded with glioma cells undergoing immunogenic cell death (ICD) induced by photosens based photodynamic therapy (PS-PDT) and to identify reliable prognostic genes’ signatures for predicting patients’ overall survival (OS). The analysis of the transcriptional program of the ICD-based DC vaccine led to the identification of robust induction of Th17 signature when used as a vaccine, these DCs demonstrate retinoic acid receptor-related orphan receptor-γt dependent efficacy in orthotopic mouse model. Moreover, by comparative analysis of transcriptome program of the ICD-based DC vaccine with transcriptome data from the TCGA-low grade glioma (LGG) dataset the four-gene signature (CFH, GALNT3, SMC4, VAV3) associated with OS of glioma patients have been identified. This model has been validated on OS of CGGA-LGG, TCGA-glioblastoma multiforme (GBM) and CGGA-GBM datasets to determine whether it has a similar prognostic value. For this the sensitivity and specificity of the prognostic model for predicting the OS were evaluated by calculating the area under curve (AUC) of the time-dependent receiver operating characteristic (ROC) curve. The values of AUC for TCGA-LGG, CGGA-LGG, TCGA-GBM and CGGA-GBM were, respectively, 0.75, 0.73, 0.9 and 0.69 for predicting 5-year survival rates. These data open attractive prospects for improving glioma therapy by employing ICD and PS-PDT-based DC vaccines to induce Th17 immunity and to use this prognostic model to predict the OS of glioma patients.
2022-12-21 | GSE218081 | GEO