Project description:Ovarian cancer is a highly aggressive female tract cancer. Anti-VEGF therapy is widely used for the treatment of ovarian cancer, however it has shown moderate impact on patient prognosis. The elucidation of mechanism of drug resistance is highly beneficial for the advances in ovarian cancer treatment. Here, we investigated gene expression profile of HM-1 tumor which were treated with or without anti-VEGF antibody (B20-4.1.1) using transcriptome array to identify special molecular features of ovarian tumor after anti-VEGF treatment.
Project description:Recent randomized clinical trial revealed the additional effect of bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF)-A, to conventional chemotherapy on survival of patients with metastatic colorectal cancer. However, a number of preclinical reports indicate resistant mechanisms to anti-angiogenic therapy in several tumor models. We investigated the phenotypic alterations of colorectal cancer xenograft during antiangiogenic therapy. TK-4, a solid tumor strain derived from human colon cancer, was orthotopically implanted into cecal walls of nude mice and treated with anti-VEGF antibody or control IgG for 35 days. Gene expression was analyzed using microarrays (Human Gene 1.0ST Array, Affymetrix).
Project description:This microarray experiment was designed to identify genes and pathways modulated in ovarian cancer xenografts treated with anti-human VEGF mAb (Bevacizumab). Tumors were established in NOD/SCID mice by s.c. injection of human ovarian cancer cells (IGROV-1 and SKOV3). Mice were treated with the anti-VEGF monoclonal antibody Bevacizumab or with PBS (control). Total RNA was extracted from tumor samples and hybridized on Affymetrix GeneChip™ PrimeView™ Human Gene Expression Arrays. Each sample was derived from a different mouse (n=5 mice/group). In order to evaluate the effects of the anti-human VEGF mAb in the two models, expression data of IGROV-1 and SKOV3 derived tumors were normalized and analyzed separately. Raw microarray data, preprocessed data matrix and results of differential expression analysis are available together with the applied protocols.
Project description:Recent randomized clinical trial revealed the additional effect of bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF)-A, to conventional chemotherapy on survival of patients with metastatic colorectal cancer. However, a number of preclinical reports indicate resistant mechanisms to anti-angiogenic therapy in several tumor models. We investigated the phenotypic alterations of colorectal cancer xenograft during antiangiogenic therapy.
Project description:The vascular endothelial growth factor (VEGF) /VEGF receptor (VEGFR) axis is an essential regulator of angiogenesis and important therapeutic target in cancer. However, the efficacy of combination treatment with an anti-VEGFR2 antibody and anti-VEGFR-A antibody on tumor progression is not clear. In this study, we examined the anti-tumor effect of the combination treatment using BALB/c-nu/nu mouse xenograft model subcutaneously injected with human gastric cancer MKN45 cells. In this model, we evaluated intra-tumor molecular changes after the combination treatment by cDNA microarray analysis.
Project description:The purpose of this study is evaluate the pharmacokinetics, pharmacodynamics, immunogenicity and anti-tumor effect of of fully human anti - VEGF monoclonal antibody LY00101 and explore the potential prognostic and predictive biomarkers.
This study will not take into account the results of molecular-genetic tests of patients enrolled in the study
Project description:MicroRNA expression profiling of human microvascular endothelial cells (HMVECs) treated with either vascular endothelial growth factor (VEGF) only or in combination with the natural angiogenesis inhibitor pigment epithelial-derived factor (PEDF). Originally we were interested in the microRNA-mediated regulation of angiogenesis by the endogenous anti-angiogenic PEDF. To identify the microRNAs involved in PEDF signaling in activated endothelial cells, we compared the levels of microRNAs in non-treated microvascular endothelial cells, cells treated with VEGF, and cells treated with a combination of VEGF and PEDF. After treatment, total RNA content was isolated and sent for analysis to LC Sciences, LLC. They performed expression profiling and completed statistical analysis, based on which we confirmed the regulation of one of the microRNAs, mir-27b. In the following experiments, we identified the targets of mir-27b relevant for angiogenesis and confirmed our findings in zebrafish and mouse models. The manuscript describes the key role of mir-27b in determination of the endothelial tip cell fate and venous differentiation by regulating Notch ligand Delta-like ligand 4 (Dll4) and Sprouty homologue 2 (Spry2). Three-condition experiment: untreated (control) HMVECs vs. VEGF-treated HMVECs vs. PEDF/VEGF-treated HMVECs.
Project description:MicroRNA expression profiling of human microvascular endothelial cells (HMVECs) treated with either vascular endothelial growth factor (VEGF) only or in combination with the natural angiogenesis inhibitor pigment epithelial-derived factor (PEDF). Originally we were interested in the microRNA-mediated regulation of angiogenesis by the endogenous anti-angiogenic PEDF. To identify the microRNAs involved in PEDF signaling in activated endothelial cells, we compared the levels of microRNAs in non-treated microvascular endothelial cells, cells treated with VEGF, and cells treated with a combination of VEGF and PEDF. After treatment, total RNA content was isolated and sent for analysis to LC Sciences, LLC. They performed expression profiling and completed statistical analysis, based on which we confirmed the regulation of one of the microRNAs, mir-27b. In the following experiments, we identified the targets of mir-27b relevant for angiogenesis and confirmed our findings in zebrafish and mouse models. The manuscript describes the key role of mir-27b in determination of the endothelial tip cell fate and venous differentiation by regulating Notch ligand Delta-like ligand 4 (Dll4) and Sprouty homologue 2 (Spry2).
Project description:To examine potential mechanisms underlying resistance to anti-VEGF antibody (AVA) therapy, we used mouse models to identify tumors that demonstrated growth subsequent to a period of initial response. Specifically, we established orthotopic mouse models of ovarian cancer designed to develop adaptive resistance after treatment with an AVA. To examine potential mechanisms underlying resistance to anti-VEGF antibody (AVA) therapy, we used mouse models to identify tumors that demonstrated growth subsequent to a period of initial response. Specifically, we established orthotopic mouse models of ovarian cancer designed to develop adaptive resistance after treatment with an AVA.