The University of Sheffield
Department of Oncology

Uveal Melanoma Research

Dr K Sisley, Non-Clinical Lecturer
Ms C Nicholls, Scientific Officer
Dr JK Woodward, Postdoctoral Research Assistant

Research Interests

Certain forms of ocular melanomas can be aggressive and spread to other parts of the body. Other eye melanomas are relatively benign. The reasons behind these differences are unclear and our studies are designed to determine why variations in behaviour exist and how we can potentially exploit this information to improve patient treatment and survival.

Genetics of Ocular Melanoma

Image

Specific chromosome abnormalities are more frequently found in these melanomas, particular of chromosomes 1,3,6,8 and 11, and we are studying the relevance of these changes. Cytogenetic analysis is undertaken on all tumours available for research, to identify gross alterations. Further study to identify the genes important in the development of these tumours is currently being undertaken, and our work is supported by the use of fluorescence in situ hybridisation (FISH), and microsatelite analysis.




Uveal melanoma Invasion and Interaction with Endothelium

Image

These tumours can spread specifically to the liver. The spread of ocular melanomas (or metastasis) is a complex procedure involving many cellular interactions including those with the endothelium. The process can be highly inefficient, but some melanomas are much more effective at overcoming the barriers to their spread. We are studying the factors that can both positively and negatively regulate uveal melanoma spread, and are specifically investigating the interactions between tumour and endothelial cells.




Recent Publications (2000-2002)

1 Sisley K, Parsons MA, Garnham J, Potter AM, Curtis DI, Rees RC, Rennie IG (2000). Association of specific chromosome alterations with tumour phenotype in posterior uveal melanoma. British Journal Cancer 82: 330-338.



2 Hedley SJ, Murray AK, Sisley K, Ghanem G, Moradini R, Gawkrodger DJ, MacNeil S (2000). A-Melanocyte stimulating hormone can reduce T-cell interaction with melanoma cells in vitro. Melanoma Res 10: 323-330

3 Muthana M, McIntyre C, Sisley K, Rennie IG, Murray AK (2000). Dead or alive: Immunogenicity of human melanoma cells when presented by dendritic cells. Cancer Res 60:6441-6447

4 Cresswell AC, Sisley K, Laws D, Parsons MA, Rennie IG, Murray AK (2001). Reduced expression of TAP-1 and TAP-2 in posterior uveal melanoma associates with progression to metastatic disease. Melanoma Res 11: 275-281

5 Baker JKL, Elshaw SR, Mathewman GEL, Nichols CE, Murray AK, Parsons MA, Rennie IG, Sisley K (2001). Expression of Integrins, Degradative enzymes and their inhibitors in uveal melanoma, differences between their in vitro and in vivo expression. Melanoma Res 11: 265-273.

6 Elshaw SR, Sisley K, Cross N, Murray AK, MacNeil SM, Wagner M, Nichols CE, Rennie IG (2001). A comparison of ocular melanocyte and uveal melanoma cell invasion and the implication of a1b1, a4b1 and a6b1 integrins. Brit J Ophthamol 85: 732-738.

7 Prasad S, Puri P, Sisley K, Parsons MA, Rennie IG (2001). Cytogenetic analysis in ocular lymphoma. Br J Ophthalmol 85: 1388-1389

8 Patel KA, Edmondson ND, Talbot F, Parsons MA, Rennie IG Sisley K (2001). Prediction of prognosis in patients with uveal melanoma using fluorescence in situ hybridization. Br J Ophthalmol 85: 1440-1444

9 Mulcahy KA, Alexander S, Platts KE, Wardle C, Sisley K, Rennie IG, Murray AK (2002). CD80-mediated induction of immunostimulation in two ocular melanoma cell lines is augmented by interferon-g. Melanoma Res 12: 129-138.

10 Woodward JKL, Nichols CE, Rennie IG, Parsons MA, Murray AK, Sisley K (2002). An in vitro assay to assess uveal melanoma invasion across endothelial and basement membrane barriers. Invest Ophthalmol Vis Sci 43:1708-1714.

11 Woodward JKL, Elshaw SR, Murray AK, Nichols CE, Cross N, Laws D, Rennie IG, Sisley K (2002). Stimulation and inhibition of uveal melanoma invasion by HGF, GRO, IL-1alpha and TGF-beta. Invest Ophthalmol Vis Sci 43:3144-3152.