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Anti-angiogenic alternatives to VEGF blockade

, School of Cardiovascular Research, College of Medical and Dental Sciences, University of Birmingham , Birmingham , UK 1 Roy Bicknell 2 & Kabir A. Khan Angiogenesis is a major requirement for tumour ... Conflict of interest Roy Bicknell is a named inventor of a patent filed by Cancer Research UK in the United States Patent and trademark Office on 3 September 2009 under No. 61/239,584, bearing Attorney

In Vivo Evidence for Platelet-Induced Physiological Angiogenesis by a COX Driven Mechanism

We sought to determine a role for platelets in in vivo angiogenesis, quantified by changes in the capillary to fibre ratio (C∶F) of mouse skeletal muscle, utilising two distinct forms of capillary growth to identify differential effects. Capillary sprouting was induced by muscle overload, and longitudinal splitting by chronic hyperaemia. Platelet depletion was achieved by anti...

Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer

Gliomas are a highly heterogeneous group of brain tumours that are refractory to treatment, highly invasive and pro-angiogenic. Glioblastoma patients have an average survival time of less than 15 months. Understanding the molecular basis of different grades of glioma, from well differentiated, low-grade tumours to high-grade tumours, is a key step in defining new therapeutic...

RhoJ interacts with the GIT–PIX complex and regulates focal adhesion disassembly

RhoJ is a Rho GTPase expressed in endothelial cells and tumour cells, which regulates cell motility, invasion, endothelial tube formation and focal adhesion numbers. This study aimed to further delineate the molecular function of RhoJ. Using timelapse microscopy RhoJ was found to regulate focal adhesion disassembly; small interfering RNA (siRNA)-mediated knockdown of RhoJ...

Electroporation and Microinjection Successfully Deliver Single-Stranded and Duplex DNA into Live Cells as Detected by FRET Measurements

Förster resonance energy transfer (FRET) technology relies on the close proximity of two compatible fluorophores for energy transfer. Tagged (Cy3 and Cy5) complementary DNA strands forming a stable duplex and a doubly-tagged single strand were shown to demonstrate FRET outside of a cellular environment. FRET was also observed after transfecting these DNA strands into fixed and...

A computational framework for gene regulatory network inference that combines multiple methods and datasets

Background Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the...

Gene Expression Analysis in Human Breast Cancer Associated Blood Vessels

Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours...

Gene signatures in wound tissue as evidenced by molecular profiling in the chick embryo model

Background Modern functional genomic approaches may help to better understand the molecular events involved in tissue morphogenesis and to identify molecular signatures and pathways. We have recently applied transcriptomic profiling to evidence molecular signatures in the development of the normal chicken chorioallantoic membrane (CAM) and in tumor engrafted on the CAM. We have...

A new procedure for determining the genetic basis of a physiological process in a non-model species, illustrated by cold induced angiogenesis in the carp

Background Physiological processes occur in many species for which there is yet no sequenced genome and for which we would like to identify the genetic basis. For example, some species increase their vascular network to minimise the effects of reduced oxygen diffusion and increased blood viscosity associated with low temperatures. Since many angiogenic and endothelial genes have...

Hypoxia and oxidative stress in breast cancer: Oxidative stress - its effects on the growth, metastatic potential and response to therapy of breast cancer

Reactive oxygen species (ROS) damage DNA, but the role of ROS in breast carcinoma may not be limited to the mutagenic activity that drives carcinoma initiation and progression. Carcinoma cells in vitro and in vivo are frequently under persistent oxidative stress. In the present review, we outline potential causes of oxygen radical generation within carcinoma cells and explore the...

A novel method of differential gene expression analysis using multiple cDNA libraries applied to the identification of tumour endothelial genes

Background In this study, differential gene expression analysis using complementary DNA (cDNA) libraries has been improved. Firstly by the introduction of an accurate method of assigning Expressed Sequence Tags (ESTs) to genes and secondly, by using a novel likelihood ratio statistical scoring of differential gene expression between two pools of cDNA libraries. These methods were...

Antibody Targeting of Cathepsin S Inhibits Angiogenesis and Synergistically Enhances Anti-VEGF

. Olwill are (or were) employees of Fusion Antibodies Ltd. Roy Bicknell, Christopher J. Scott and James Johnston are consultants for Fusion Antibodies Ltd. This does not alter the authors adherence to all ... plated in the presence of 10 ng/ml VEGF (Sigma, UK) and 250 ng/ml anti-VEGF antibody (Roy Bicknell) or 200 nM Fsn0503 or a combination of both. 4 fields of view were imaged (Nikon eclipse TS100 microscope

Correlating Global Gene Regulation to Angiogenesis in the Developing Chick Extra-Embryonic Vascular System

Background Formation of blood vessels requires the concerted regulation of an unknown number of genes in a spatial-, time- and dosage-dependent manner. Determining genes, which drive vascular maturation is crucial for the identification of new therapeutic targets against pathological angiogenesis. Methology/Principal Findings We accessed global gene regulation throughout...