Nigel Acheson

Clinical Relevance of Increased Endothelial and Mesothelial Expression of Proangiogenic Proteases and VEGFA in the Omentum of Patients with Metastatic Ovarian High-Grade Serous Carcinoma

Epithelial ovarian cancer (EOC) metastasis to the omentum requires implantation and angiogenesis. We propose that prometastatic changes in the omental endothelium (for angiogenesis) and mesothelium (for implantation) are critical. We investigated the expression of angiogenic proteases [cathepsin D (CD), cathepsin L (CL), and matrix metalloproteinase 2 (MMP2) and MMP9] and vascular endothelial growth factor A (VEGFA) in the mesothelium and endothelium of omentum from patients with EOC with omental metastases and control patients with benign ovarian tumors. Endothelial expression of CL, VEGFA, and MMP9 and mesothelial expression of VEGFA, MMP9, and CD were significantly increased in patients with metastasized EOC. High expression of MMP9 and VEGFA in endothelium and mesothelium and CD in mesothelium was positively associated with poor disease-specific survival (DSS). High MMP9 expression in either endothelium or mesothelium and presence of ascites prospectively showed the greatest risk of shorter DSS [hazard ratio (HR)= 6.16, 95% confidence interval (CI) = 1.76-21.6, P = .0045; HR = 11.42, 95% CI = 2.59-50.35, P = .0013; and HR = 6.35, 95% CI = 2.01-20.1, P = .002, respectively]. High endothelial MMP9 expression and ascites were independent predictors of reduced DSS and overall survival, together resulting in worst patient prognosis. Our data show that omental metastasis of EOC is associated with increased proangiogenic protein expression in the omental endothelium and mesothelium.

An improved and reliable method for isolation of microvascular endothelial cells from human omentum.

Please cite this paper as: Winiarski, Acheson, Gutowski, McHarg and Whatmore (2011). An Improved and Reliable Method for Isolation of Microvascular Endothelial Cells from Human Omentum. Microcirculation18(8), 635–645.

Radiotherapy: principles and applications

The therapeutic use of radiation in gynaecological cancer quickly followed the discovery of X-rays by Roentgen in 1895 and radium by the Curies in 1898. The aim of radiotherapy is to destroy the cancer if possible without damaging the surrounding normal tissues. The application of a cancericidal dose of radiation to the cancer must be balanced against the inevitable collateral damage caused to local normal organs at risk. Radiotherapy treatment can involve a combination of external beam radiotherapy and brachytherapy. External radiotherapy (teletherapy) employs the use of a high-energy photon (X-ray) beam generated from a linear accelerator. Brachytherapy (Greek brachy, short) involves the use of sealed radiotherapy sources placed close to the treated tissue. The sources may be placed in the natural cavities of the vagina or uterus (intracavitary treatment) or needles or tubes inserted into the tissues (interstitial brachytherapy). The two modalities of external beam radiotherapy and brachytherapy can be combined or used individually.