Project description:RhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We used microarrays to link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to RhoB/VEZF1-mediated gene regulation in primary human blood versus lymphatic endothelial cells. Pure populations of human primary BVECs and LVECs silenced for RhoB or VEZF1 were used for RNA extraction and hybridization on Affymetrix microarrays. We extracted these cells from human male foreskins from at least four individuals and purified them using Dynabeads associated with vascular markers (CD31 and Podoplanin).
Project description:RhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We used microarrays to link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to RhoB/VEZF1-mediated gene regulation in primary human blood versus lymphatic endothelial cells.
Project description:In this study we used in vitro approaches to investigate whether it has any inhibitory properties on OSCC cells. We also tried to understand the possible mechanisms of Sal B on this type of malignancy with respect to angiogenesis. 2 OSCC cell lines were treated with 100ug/ml Sal B for 48hours. cDNAmicroarray was used to evaluated the expressions of 96 genes known to be involving in modulating the biological process of angiogenesis.
Project description:A Microarray Search for Effects of Thyrotropin and Iodide on Angiogenesis Factors Objective: Excess iodide has been administered to hyperthyroid patients before thyroid surgery to reduce intraoperative bleeding and oozing. The purpose of this study was to elucidate the mechanism by which iodide reduces blood flow in the hypervascular thyroid gland. Design: Human thyroid follicles were cultured in the presence or absence of thyrotropin (TSH), or in medium containing various concentrations of iodide, and TSH- or iodide-regulated gene expression was analyzed by cDNA microarray. Main outcome: TSH stimulated the expression of thyroglobulin, peroxidase, sodium-iodide symporter, vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PGF) but decreased that of VEGF-C by half. When thyroid follicles were cultured in high-iodide (10-5M) medium, TSH-induced expression of VEGF-A, VEGF-B and PGF was decreased, accompanied by a reduction of VEGF-A release into the medium. Furthermore, expression of putative angiogenesis inhibitors such as urokinase-type plasminogen activator (PLAU) was increased. These findings were confirmed by real-time polymerase chain reaction (PCR) and Northern blot hybridization. Conclusions: We have demonstrated for the first time that iodide at high concentration decreases the expression of the angiogenic factors VEGF-A, VEGF-B, and PGF, accompanied by an increase in the expression of possible anti-angiogenic factors such as PLAU. These proangiogenic and antiangiogenic factors may at least partly account for the iodide-induced decrease in thyroid blood flow.
Project description:In this study we used in vitro approaches to investigate whether it has any inhibitory properties on OSCC cells. We also tried to understand the possible mechanisms of Sal B on this type of malignancy with respect to angiogenesis.
Project description:To further investigate the molecular functions of CXCR4 in angiogenesis, we knocked out CXCR4 in HCE-T-cell lines, which were further undergo hypoxic treatment, using the CRISPR‒Cas9 system.
Project description:This is a clinical trial investigating the effectiveness and safety of the combination of the study drugs bevacizumab and AMG386 in patients with advanced (metastatic) chemotherapy-naive bowel (colorectal) cancer. Chemotherapy has a significant impact in metastatic bowel cancer in terms of maintenance of quality of life and extension of survival. However, ultimately tumours will develop resistance to these agents and further treatment options are urgently required.
Angiogenesis is a process that results in the formation of new blood vessels. Similar to normal tissues, solid tumours require new blood vessels for growth and survival. Hence, drugs targeting angiogenesis may be useful treatment options for patients with bowel cancer.
AMG386 and bevacizumab act on 2 different pathways relevant to angiogenesis. There is evidence from laboratory and animal studies to suggest that such a combination could be useful as a cancer treatment. Previous studies in humans have shown that AMG386 and bevacizumab can be combined safely.. This study aims to evaluate the effectiveness and safety of the combination of AMG386 and bevacizumab in patients with advanced bowel cancer.
40 patients from approximately four hospitals in Australia will participate in this trial, with approximately 20 patients being enrolled at Austin Health. All participants will receive the same treatment.
