Head and Neck Cancer

Head and Neck Cancer Basic Research group

Group Leader:
Associate Professor Barbara Rose

Members:
Dr Guy Lyons
Dr Nham Tran
Dr Angela Hong
Professor C Soon Lee h

 
Research Overview:
There are three main streams to our research programme. The first relates to the role of wart virus (papillomavirus) in head and neck cancer. Although tobacco and alcohol are the major causes of head and neck cancer it is now accepted that certain types of wart virus (human papillomavirus) induce a proportion of these tumours. We are carrying out a multicentre study of oropharyngeal cancers from 900 patients from 10 Australian centres. Our aims are to determine whether patients  whose cancers are caused by the virus have a better prognosis than those caused by smoking or alcohol. Our particular interest is in whether the virus influences the response to radiotherapy which is frequently used in the treatment of these cancers. If the virus is linked with a better clinical outcome and this is treatment related, testing of head and neck tumours for the virus may become part of routine management and treatment of individual patients may depend on whether their tumour is virus-related.  Collectively these advances would be expected to substantially reduce morbidity and mortality from one of the most debilitating forms of cancer. Our second project involves investigations of the role of a newly discovered class of small molecules called microRNAs in the development and behaviour of head and neck cancer. The discovery of miRNAs has generated much excitement in the scientific and medical communities. However, this study is still in its infancy. The third project is investigating the cell factors involved in the transition of from a benign tumour to a malignant squamous cell carcinoma. We are focussing on a transcription factor called “Snail” and have shown that it has the ability to block the normal differentiation of keratinocytes and cause them to invade the tissues that surrounds tumours.

Highlights 2006/2007
Competitive funding for 2007 from the Sydney Cancer Centre Foundation for project investigating the role of small non-coding molecules (miRNAs) in head and neck carcinogenesis.

Competitive funding for 2006-2007 from Sydney Cancer Centre Foundation for project investigating the regulation of keratinocyte differentiation by Snail.

Competitive funding for 2007-2009 from Cancer Council NSW for project investigating the regulation of keratinocyte differentiation by Snail.

Competitive funding NHMRC Equipment grant: Total internal reflectance fluorescence microscope $75,000   

Dr Rose presented a summary of the clinical, basic and translational research being carried out within the Sydney Head and Neck Institute, Sydney Cancer Centre Royal Prince Alfred Hospital at the inaugural Cancer Research Network meeting held on September 12 2006

Dr Lyons was selected for an oral presentation of his work at the Australian Health and Medical Research Congress in Melbourne, Nov 2006, and the Australasian Society for Dermatological Research in Adelaide, May 2007

Associate Professor Rose and Dr Tran presented reults of their work in the 8th Annual Australian and New Zealand Head and Neck Society Meeting in Wellington , New Zealand in October 2006

Dr Nham Tran presented the results of miRNA research in an oral presentation at the 9th Annual Australian and New Zealand Head and Neck Society Meeting held in Brisbane in July 2007

New collaboration established with Professor Richard Christopherson at Dept Molecular and Microbial Biosciences University of Sydney to use sophisticated new techniques to explore alterations in cell proteins that might affect the response of head and neck cancers to radiation therapy.

Invitations received for collaborations on our HPV work from the Peter MacCallum Institute Melbourne and the Dana Farber Institute Boston USA

Publications 2006/2007
(1) Li W, Tran N, Lee CS, O’Brien CJ, Tse GM, Scolyer R, Hong A, Milross C, Hung Yu K, Rose B New evidence for geographic variation in the role of human papillomavirus in tonsillar carcinogenesis. Pathology, 39:217-222 2007.

(2) Brian Morris, Barbara Rose. Cervical Screening for the 21st century - Likely trend toprimary HPV testing of self-collected specimens Clinical Chemistry and Laboratory Medicine 2007 45 577-91.

(3) Tran N, O’Brien C, and Rose B MicroRNA expression profiles in head and neck cancer cell lines. Biochemical and Biophysical Research Communications 2007; 358:12-17.

(4) Patel RS, Hughes C, Dom M, Fredericks S, Lee CS , Rose B, Gao K, Smith G , Hong A, Wong M, CJ O’Brien. Cyclin A expression in pleomorphic adenomas and carcinomas in ex-pleomorphic adenoma of the parotid salivary gland. Histopathology 2007 (51) 21-25.

(5) Kandasamy J, Smith A, Diaz S, Rose B, and O’Brien C. Heterogeneity of PLAG1 gene rearrangements in pleomorphic adenoma. Cancer Genetics and Cytogenetics  177 2007 1-5

(6) RS Patel, B Rose, H Bawdon, A Hong, CS Lee, S Fredericks, K Gao, CJ O’Brien Cyclin D1 and p16 expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid gland. Histopathology In Press, June 15 2007.

(7) Min, D., Lyons, J.G., Jia, J., Lo, L., and McLennan, S.V. (2006) "Reverse MDPF-labeled gelatin zymography: a rapid real-time method for absolute quantitation of tissue inhibitors of metalloproteinases." Electrophoresis 27:357-364.

(8) Failes, T.W., Cullinane, C., Diakos, C.I., Yamamoto, N., Lyons, J.G., and Hambley, T.W. Studies of a cobalt(III) complex of the MMP inhibitor Marimastat: a potential hypoxia-activated prodrug. Chemistry 13:2974-82 2007.

(9) Halliday, G.M. and Lyons, J.G. Inflammatory doses of UV may not be necessary for skin carcinogenesis. Photochem. Photobiol. (in press).

(10) Lyons, J.G., Lobo, E., Martorana, A.M., and Myerscough, M.R. Clonal diversity in carcinomas: its implications for tumour progression and the contribution made to it by epithelial-mesenchymal transitions. Clin. Exp. Metastasis (accepted for publication)