Bevacizumab treatment for ovarian cancer alter the expression of micro RNAs (miRNAs), leading to activate VEGF-independent angiogenesis pathway.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE176165 | GEO | 2021/06/05
REPOSITORIES: GEO
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Project description:Bevacizumab treatment for ovarian cancer alter the expression of micro RNAs (miRNAs), leading to activate VEGF-independent angiogenesis pathway.
| PRJNA735203 | ENA
Project description:We asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct (N1D), which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle. Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability. Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone. 6 neuroblastoma tumors were transfected with Notch1 decoy, 6 with Notch1 decoy and treated with bevacizumab, 6 tumors treated with bevacizumab, and 6 control tumors were profiled by human 133A 2.0 arrays
2013-12-01 | E-GEOD-48880 | biostudies-arrayexpress
Project description:Purpose: To study the potential priming benefit of bevacizumab from subsequent immunotherapy (durvalumab) in advanced breast cancer patients Methods: We tested this hypothesis by adding durvalumab after progression to maintenance single-agent bevacizumab treatment in advanced HER2-negative patients (average 3 treatment lines). In order to study the potential priming benefit, patients had to experience disease progression while on bevacizumab maintenance prior to entering the trial. In addition, we sought to find traits in peripheral-blood mononuclear cells (PBMCs) and tumor biopsies that informed about this immuno-priming, in an attempt to search for novel biomarkers of efficacy of the combo and obtain a better understanding of the biology of this clinical scenario. Results: Patients that experienced clinical benefit, compared with the remaining patients, displayed a lymphocyte pattern in PBMCs consisting on increased T-effector subpopulations (CD4- and CD8- effector and effector-memory) and decreased immunosuppressive T-regulatory cells. Gene-expression studies in tumor samples showed a congruent pattern, with increased T-effector and memory T cell signatures in responders, and increased T-regulatory and decreased active dendritic cells in non-responders. These events were observed in patients that displayed vascular normalization features as a result of previous bevacizumab, supporting the immuno-priming effects of this strategy.
2020-10-15 | GSE139050 | GEO
Project description:Immuno-priming with bevacizumab: durvalumab plus bevacizumab after prolonged exposition to bevacizumab in breast cancer
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Project description:TMT proteomics was used to detect the difference in protein expression of bevacizumab-resistant xenograft tumor tissue in nude mice.
2022-10-13 | PXD030202 | Pride
Project description:The VEGF targeted antiangiogenic drug bevacizumab has shown varying results in clinical trials of breast cancer. Identifying robust biomarkers for selecting patients that may benefit from bevacizumab treatment and for monitoring of response is important for the future use of this drug. Two established xenograft models representing basal-like and luminal-like breast cancer were used to study bevacizumab treatment response on the metabolic and gene expression levels. Mice given no treatment or treated with bevacizumab, doxorubicin or the combination of these two drugs were sacrificed at day 3 or 10. High resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) and gene expression microarray analysis was performed on all tumor samples. Combination treatment with bevacizumab had the strongest growth inhibiting effect in the basal-like tumors, and this was reflected in a significant response in the metabolomic and transcriptomic profiles. In the luminal-like xenografts, addition of bevacizumab did not improve the effect of doxorubicin. On the global transcriptomic level, the largest changes in gene expression were observed for the most efficient treatment in each of the two xenograft models. The metabolite glycerophosphocholine (GPC) showed opposite response in the treated xenografts compared with untreated controls: lower in basal-like tumors and higher in luminal-like tumors. Lower levels of creatine, taurine and glycine were observed in the basal-like xenografts given bevacizumab as monotherapy compared with untreated xenografts. Comparing combination therapy with doxorubicin monotherapy in basal-like xenografts, 14 genes showed significant differential expression, including higher expression of very low density lipoprotein receptor (VLDLR), and lower expression of hemoglobin, theta 1 (HBQ1). Using published gene expression signatures, bevacizumab treated tumors were associated with a more hypoxic phenotype, while no evidence was found for associations between bevacizumab treatment and vascular invasion or increasing tumor grade. This study underlines the importance of characterizing biological differences between subtypes of breast cancer to identify personalized biomarkers for selecting patients for bevacizumab treatment and evaluating response to therapy. 60 samples are analyzed. For each of the two xenograft models, tumors were collected from animals that were untreated or treated with bevacizumab (5 mg/kg), doxorubicin (8 mg/kg) or a combination of the two therapies (n = 6 tumors for each group). Bevacizumab treatment was repeated at day 4 and day 7. Animals were sacrificed and tissue harvested at either day 3 or 10 after treatment, in triplicates within each treatment group. This resulted in 24 tumor samples from each of the models. In addition, untreated and bevacizumab treated luminal-like xenografts not fed with estradiol were included for comparison (n = 12). Note that the untreated controls are overlapping with the samples in the GEO series with accession number: GSE25915.
2013-06-01 | E-GEOD-37543 | biostudies-arrayexpress
Project description:Objective: Insights about differences in tumor vasculature and how it reacts to VEGF inhibition is limited, but nevertheless of major relevance to anti-angiogenic therapy. In this study we therefore characterize the effect of bevacizumab combined with chemoradiotherapy (CRT), and explore molecular and genetic markers for response prediction to this combination treatment. Material and Methods: In an academic multicentric randomized phase II study, patients with advanced rectal cancer have been treated with bevacizumab (5mg/kg) in combination with capecitabine (1650mg/m2/day) and radiotherapy (45Gy; 1.8Gy/day) with (50mg/m2) or without oxaliplatin prior to surgery. Of 59 patients, tumor tissue and blood samples were collected before treatment and after the first loading dose of bevacizumab but before CRT (week 3). First, cDNA micro-arrays were performed on the biopsies to investigate differences in gene expression of tumors from patients with and without a pathological complete response (pCR) before start of treatment and to identify biological processes affected by bevacizumab delivery. The paraffin embedded tissue was stained for blood vessels (CD31/CD34) combined with α-SMA (pericytes) and CA-IX (hypoxia). To explore candidate blood-based biomarkers ELISA’s were performed for PDGF-AA, PDGF-BB, THBS-1, IL-8, CYR61 and Ang-2. The expression of all markers was correlated with the pathological response of the patients. Results: Differences in tumoral gene expression are observed between patients with and without a pCR, with the first response group presenting a more angiogenic phenotype before start of treatment and changes in angiogenic processes after bevacizumab delivery. One dose of bevacizumab leads to a decrease in the number of pericyte covered blood vessels, a decrease in circulating PDGF-AA, PDGF-BB and Thrombospondin-1. Patients showing a pCR having less pericyte covered blood vessels, more hypoxia, and less circulating PDGF-BB compared to patients who did not have a pCR after bevacizumab treatment with chemoradiation and bevacizumab. Conclusions: The translational data demonstrate that tumors with an angiogenic expression profile respond better to bevacizumab combined with CRT and points towards a possible role for PDGF, CA-IX and pericyte covered blood vessels for the early response prediction to this treatment. Our findings suggest a role for mural cell recruitment and vessel maturation for the susceptibility of the tumor vasculature to bevacizumab treatment. Further validation of our biological observations and hypothesis generating data in randomized trials is needed.
2016-08-02 | GSE60331 | GEO
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:To investigate the possible mechanism of bevacizumab resistance in ovarian cancer ,we examined the changes in gene expression of SKOV3 before and after bevacizumab intervention. Results provide insight into molecular mechanisms of acquired resistance to bevacizumab in ovarian cancer.
2023-12-31 | GSE165419 | 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