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Professor Parry Guilford: Director

Understanding and utilising cancer gene expression

Professor Guilford’s work with both a fatal form of inherited stomach cancer, and bladder cancer, has seen the development of diagnostic tools that have profound effects on saving lives.

In 2017 his work has been recognised as recipient of the Distinguished Research Medal, the University of Otago's highest research honour. Previously his work has also been recognised by the award of the top Health Research Council of New Zealand medal; the Beaven Medal, for his contribution to translational research, and the Royal Society of New Zealand's Sir Charles Hercus Medal for biomedical sciences.

This work also has implications for diagnostic tools for prostate, ovarian, cervical and uterine cancer.

"By understanding the exact differences between any given patient's cancer and normal tissue, we have a powerful starting point for designing drugs that will kill cancer cells but not healthy cells. This will lead to better treatments and fewer side effects."

Professor Guilford is a Principal Investigator in the Cancer Genetics Laboratory, and co-founder and Chief Scientific Officer of Pacific Edge Ltd.

Pacific Edge specialises in the discovery and commercialisation of diagnostic and prognostic technology for the early detection and monitoring of cancer. Professor Guilford is also senior inventor on Pacific Edge patents including its flagship bladder cancer diagnostic test Cxbladder®.

Bladder cancer diagnostics breakthrough

Professor Guilford's work has been integral in the development of Cxbladder®. This is a clinically validated urine test that measures the gene expression levels of five biomarkers in order to diagnose bladder cancer. This product has recently won the NZ Innovation Awards and has secured significant contracts with healthcare providers in NZ and the USA.

Inherited stomach cancer

Professor Guilford's work in understanding the role of mutations in the CDH1 gene in familial gastric cancer and the subsequent development of a genetic test, has dramatically decreased the mortality from this form of inherited cancer.

Tumours develop by acquiring mutations in genes that control cell proliferation, survival and migration. Although these mutations help the development of the cancer cells, they can also create weaknesses. Professor Guilford and his team are working to find those weaknesses and develop drugs that exploit them.

Multiple vulnerabilities have been identified in cancers with mutations in the tumour suppressor gene CDH1. Drugs that exploit some of these vulnerabilities have already been identified and are being rapidly progressed towards the treatment of common forms of breast and stomach cancer. This successful strategy is now being applied to common mutations in colorectal cancer.

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Publications

Godwin, T. D., Kelly, S. T., Brew, T. P., Bougen-Zhukov, N. M., Single, A. B., Chen, A., Stylianou, C. E., … Currie, S. K., … Beetham, H. G., … Black, M. A., & Guilford, P. J. (2018). E-cadherin-deficient cells have synthetic lethal vulnerabilities in plasma membrane organisation, dynamics and function. Gastric Cancer. Advance online publication. doi: 10.1007/s10120-018-0859-1

Hakkaart, C., Ellison-Loschmann, L., Day, R., Sporle, A., Koea, J., Harawira, P., … Guilford, P. (2018). Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori. Familial Cancer. Advance online publication. doi: 10.1007/s10689-018-0080-8

Figueiredo, J., Melo, S., Gamet, K., Godwin, T., Seixas, S., Sanches, J. M., Guilford, P., & Seruca, R. (2018). E-cadherin signal sequence disruption: A novel mechanism underlying hereditary cancer. Molecular Cancer, 17, 112. doi: 10.1186/s12943-018-0859-0

Sika-Paotonu, D., Viali, S., Naseri, L. T. T. K., So'o, F. L. T. I. A., Lameko, T. V., Punivalu, M., … Guilford, P. (2018). The application of ctDNA technology for early Cancer diagnostics in Samoa. Journal of Immunology, 200(1, Suppl.), 120.40. [Abstract]

Sika-Paotonu, D., & Guilford, P. (2018). Exploring the applicability of ctDNA technology as a diagnostic tool for improved Cancer care and management within the Pacific. Journal of Immunology, 200(1, Suppl.), 120.20. [Abstract]

Chapter in Book - Research

Dunbier, A. K., & Guilford, P. J. (2002). Gastric cancer: Inherited predisposition. In S. R. Hamilton & L. A. Aaltonen (Eds.), Encyclopedia of Cancer, Volume 2. (2nd ed.) (pp. 253-258). USA: Elsevier Science.

Fenoglio-Preiser, C., Carneiro, F., Correa, P., Guilford, P., & et al (2000). Gastric carcinoma. In S. R. Hamilton & L. A. Aaltonen (Eds.), World Health Organization classification of tumours: Pathology and genetics of tumours of the digestive system. (pp. 39-52). Lyon, France: IARC Press.

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Journal - Research Article

Godwin, T. D., Kelly, S. T., Brew, T. P., Bougen-Zhukov, N. M., Single, A. B., Chen, A., Stylianou, C. E., … Currie, S. K., … Beetham, H. G., … Black, M. A., & Guilford, P. J. (2018). E-cadherin-deficient cells have synthetic lethal vulnerabilities in plasma membrane organisation, dynamics and function. Gastric Cancer. Advance online publication. doi: 10.1007/s10120-018-0859-1

Hakkaart, C., Ellison-Loschmann, L., Day, R., Sporle, A., Koea, J., Harawira, P., … Guilford, P. (2018). Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori. Familial Cancer. Advance online publication. doi: 10.1007/s10689-018-0080-8

Ellison-Loschmann, L., Sporle, A., Corbin, M., Cheng, S., Harawira, P., Gray, M., … Guilford, P., … Pearce, N. (2017). Risk of stomach cancer in Aotearoa/New Zealand: A Māori population based case-control study. PLoS ONE, 12(7), e0181581. doi: 10.1371/journal.pone.0181581

Lotan, Y., OʼSullivan, P., Raman, J. D., Shariat, S. F., Kavalieris, L., Frampton, C., Guilford, P., … Darling, D. (2017). Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma. Urologic Oncology, 35(8), 513.e15-513.e22. doi: 10.1016/j.urolonc.2017.03.008

McInnes, T., Zou, D., Rao, D. S., Munro, F. M., Phillips, V. L., McCall, J. L., Black, M. A., Reeve, A. E., & Guilford, P. J. (2017). Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer. BMC Cancer, 17, 228. doi: 10.1186/s12885-017-3226-4

Kavalieris, L., O'Sullivan, P., Frampton, C., Guilford, P., Darling, D., Jacobson, E., … Lotan, Y. (2017). Performance characteristics of a multigene urine biomarker test for monitoring for recurrent urothelial carcinoma in a multicenter study. Journal of Urology, 197(6), 1419-1426. doi: 10.1016/j.juro.2016.12.010

Hoeksema, K., Wee, R., Macdonald, A., Guilford, P., Wall, J., & Cornwall, J. (2017). Where to from here? Posthumous healthcare data, digital e(lectronic)-mortality and New Zealand’s healthcare future. New Zealand Medical Journal, 130(1459), 64-70. Retrieved from http://www.nzma.org.nz/journal

van der Post, R. S., Vogelaar, I. P., Carneiro, F., Guilford, P., Huntsman, D., Hoogerbrugge, N., … Fitzgerald, R. C. (2015). Hereditary diffuse gastric cancer: Updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. Journal of Medical Genetics, 52, 361-374. doi: 10.1136/jmedgenet-2015-103094

Hansford, S., Kaurah, P., Li-Chang, H., Woo, M., Senz, J., Pinheiro, H., … Guilford, P., … Huntsman, D. G. (2015). Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncology, 1(1), 23-32. doi: 10.1001/jamaoncol.2014.168

Single, A., Beetham, H., Telford, B. J., Guilford, P., & Chen, A. (2015). A comparison of real-time and endpoint cell viability assays for improved synthetic lethal drug validation. Journal of Biomolecular Screening, 20(10), 1286-1293. doi: 10.1177/1087057115605765

Telford, B. J., Chen, A., Beetham, H., Frick, J., Brew, T. P., Gould, C. M., Single, A., Godwin, T., … Guilford, P. (2015). Synthetic lethal screens identify vulnerabilities in GPCR signalling and cytoskeletal organization in E-cadherin-deficient cells. Molecular Cancer Therapeutics, 14(5), 1213-1223. doi: 10.1158/1535-7163.mct-14-1092

Chen, A., Beetham, H., Black, M. A., Priya, R., Telford, B. J., Guest, J., Wiggins, G. A. R., Godwin, T. D., … Guilford, P. J. (2014). E-cadherin loss alters cytoskeletal organization and adhesion in non-malignant breast cells but is insufficient to induce an epithelial-mesenchymal transition. BMC Cancer, 14, 552. doi: 10.1186/1471-2407-14-552

Willson, J. S. B., Godwin, T. D., Wiggins, G. A. R., Guilford, P. J., & McCall, J. L. (2013). Primary hepatocellular neoplasms in a MODY3 family with a novel HNF1A germline mutation. Journal of Hepatology, 59(4), 904-907. doi: 10.1016/j.jhep.2013.05.024

Huang, R. Y.-J., Guilford, P., & Thiery, J. P. (2012). Early events in cell adhesion and polarity during epithelial-mesenchymal transition. Journal of Cell Science, 125(19), 4417-4422. doi: 10.1242/jcs.099697

Evans, J. J., Chitcholtan, K., Dann, J. M., Guilford, P., Harris, G., Lewis, L. K., Nagase, J., … Sykes, P. H. (2012). Adrenomedullin interacts with VEGF in endometrial cancer and has varied modulation in tumours of different grades. Gynecologic Oncology, 125(1), 214-219. doi: 10.1016/j.ygyno.2011.12.429

O'Sullivan, P., Sharples, K., Dalphin, M., Davidson, P., Gilling, P., Cambridge, L., … Luxmanan, C., … Yoon, H.-S., … Guilford, P. J. (2012). A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria. Journal of Urology, 188(3), 741-747. doi: 10.1016/j.juro.2012.05.003

Nasri, S., Anjomshoaa, A., Song, S., Guilford, P., McNoe, L., Black, M., Phillips, V., Reeve, A., & Humar, B. (2010). Oligonucleotide array outperforms SNP array on formalin-fixed paraffin-embedded clinical samples. Cancer Genetics & Cytogenetics, 198(1), 1-6. doi: 10.1016/j.cancergencyto.2009.12.002

Guilford, P., Humar, B., & Blair, V. (2010). Hereditary diffuse gastric cancer: Translation of CDH1 germline mutations into clinical practice. Gastric Cancer, 13(1), 1-10. doi: 10.1007/s10120-009-0531-x

Guise, C. P., Abbattista, M. R., Singleton, R. S., Holford, S. D., Connolly, J., Dachs, G. U., Fox, S. B., Pollock, R., Harvey, J., Guilford, P., … Patterson, A. V. (2010). The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Research, 70(4), 1573-1584. doi: 10.1158/0008-5472.CAN-09-3237

Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., … on behalf of the International Gastric Cancer Linkage Consortium. (2010). Hereditary diffuse gastric cancer: Updated consensus guidelines for clinical management and directions for future research. Journal of Medical Genetics, 47(7), 436-444. doi: 10.1136/jmg.2009.074237

Mai, P. L., Friedlander, M., Tucker, K., Phillips, K.-A., Hogg, D., Jewett, M. A. S., … Guilford, P., … Greene, M. H. (2010). The International Testicular Cancer Linkage Consortium: A clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred. Urologic Oncology, 28(5), 492-499. doi: 10.1016/j.urolonc.2008.10.004

Humar, B., Blair, V., Charlton, A., More, H., Martin, I., & Guilford, P. (2009). E-cadherin deficiency initiates gastric signet-ring cell carcinoma in mice and man. Cancer Research, 69(5), 2050-2056.

Zou, D., Yoon, H.-S., Perez, D., Weeks, R. J., Guilford, P., & Humar, B. (2009). Epigenetic silencing in non-neoplastic epithelia identifies E-cadherin (CDH1) as a target for chemoprevention of lobular neoplasia. Journal of Pathology, 218(2), 265-272. doi: 10.1002/path.2541

Zou, D., Yoon, H.-S., Anjomshoaa, A., Perez, D., Fukuzawa, R., Guilford, P., & Humar, B. (2009). Increased levels of active c-Src distinguish invasive from in situ lobular lesions. Breast Cancer Research, 11(4), R45. doi: 10.1186/bcr2332

Nasri, S., More, H., Graziano, F., Ruzzo, A., Wilson, E., Dunbier, A., McKinney, C., Merriman, T., Guilford, P., … Humar, B. (2008). A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: A case control study in an Italian population. BMC Cancer, 8, 138. doi: 10.1186/1471-2407-8-138

John, T., Black, M. A., Toro, T. T., Leader, D., Gedye, C. A., Davis, I. D., Guilford, P. J., & Cebon, J. S. (2008). Predicting clinical outcome through molecular profiling in stage III melanoma. Clinical Cancer Research, 14(16), 5173-5180.

Holyoake, A., O'Sullivan, P., Pollock, R., Best, T., Watanabe, J., Kajita, Y., … da Silva Tatley, F., Cambridge, L., Toro, T., … Guilford, P. (2008). Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder. Clinical Cancer Research, 14(3), 742-749. doi: 10.1158/1078-0432.CCR-07-1672

Linger, R., Dudakia, D., Huddart, R., Tucker, K., Friedlander, M., Phillips, K.-A., … Guilford, P., … Rapley, E. A. (2008). Analysis of the DND I gene in men with sporadic and familial testicular germ cell tumors. Genes Chromosomes & Cancer, 47(3), 247-252. doi: 10.1002/gcc.20526

Humar, B., & Guilford, P. (2008). Hereditary diffuse gastric cancer and lost cell polarity: A short path to cancer. Future Oncology, 4(2), 229-239.

Kawanishi, H., Matsui, Y., Ito, M., Watanabe, J., Takahashi, T., Nishizawa, K., … Guilford, P., Reeve, A., … Ogawa, O. (2008). Secreted CXCL1 is a potential mediator and marker of the tumor invasion of bladder cancer. Clinical Cancer Research, 14(9), 2579-2587. doi: 10.1158/1078-0432.CCR-07-1922

Kwak, M. K., Lee, H.-J., Hur, K., Park, D. J., Lee, H. S., Kim, W. H., … Guilford, P., & Yang, H.-K. (2008). Expression of Krüppel-like factor 5 in human gastric carcinomas. Journal of Cancer Research & Clinical Oncology, 134(2), 163-167. doi: 10.1007/s00432-007-0265-2

Guilford, P., Blair, V., More, H., & Humar, B. (2007). A short guide to hereditary diffuse gastric cancer. Hereditary Cancer in Clinical Practice, 5(4), 183-194.

Matsui, S., Ito, M., Nishiyama, H., Uno, H., Kotani, H., Watanabe, J., Guilford, P., Reeve, A., … Ogawa, O. (2007). Genomic characterization of multiple clinical phenotypes of cancer using multivariate linear regression models. Bioinformatics, 23(6), 732-738.

Ito, M., Nishiyama, H., Kawanishi, H., Matsui, S., Guilford, P., Reeve, A., & Ogawa, O. (2007). P21-activated kinase 1: A new molecular marker for intravesical recurrence after transurethral resection of bladder cancer. Journal of Urology, 178, 1073-1079.

More, H., Humar, B., Weber, W., Ward, R., Christian, A., Lintott, C., … Guilford, P. (2007). Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene. Human Mutation, 28(2). doi: 10.1002/humu.9473

Lin, Y.-H., Friederichs, J., Black, M. A., Mages, J., Rosenberg, R., Guilford, P. J., Phillips, V., Thompson-Fawcett, M., … van Rij, A., Yoon, H.-S., McCall, J. L., … Reeve, A. E. (2007). Multiple gene expression classifiers from different array platforms predict poor prognosis of colorectal cancer. Clinical Cancer Research, 13(2), 498-507. doi: 10.1158/1078-0432.CCR-05-2734

Humar, B., Fukuzawa, R., Blair, V., Dunbier, A., More, H., Charlton, A., … Reeve, A. E., … Guilford, P. (2007). Destabilized adhesion in the gastric proliferative zone and c-Src kinase activation mark the development of early diffuse gastric cancer. Cancer Research, 67(6), 2480-2489. doi: 10.1158/0008-5472.CAN-06-3021

Crockford, G. P., Linger, R., Hockley, S., Dudakia, D., Johnson, L., Huddart, R., … Guilford, P., … Rapley, E. A. (2006). Genome-wide linkage screen for testicular germ cell tumour susceptibility loci. Human Molecular Genetics, 15(3), 443-451. doi: 10.1093/hmg/ddi459

Ramos-de la Medina, A., More, H., Medina-Franco, H., Humar, B., Gamboa, A., Ortiz, L. J., … Guilford, P. (2006). Single nucleotide polymorphisms (SNPs) at CDH1 promoter region in familial gastric cancer. Revista Española de Enfermedades Digestivas, 98(1), 36-41.

Blair, V., Martin, I., Shaw, D., Winship, I., Kerr, D., Arnold, J., … Cox, B., Humar, B., More, H., & Guilford, P. (2006). Hereditary diffuse gastric cancer: Diagnosis and management. Clinical Gastroenterology & Hepatology, 4, 262-275. doi: 10.1016/j.cgh.2005.12.003

Nathanson, K. L., Kanetsky, P. A., . . ., Guilford, P., & et al (2005). The Y deletion gr/gr and susceptibility to testicular germ cell tumor. American Journal of Human Genetics, 77, 1034-1043.

Shaw, D., Blair, V., Framp, A., Harawira, P., McLeod, M., & Guilford, P. (2005). Chromoendoscopic surveillance in hereditary diffuse gastric cancer: An alternative to prophylactic gastrectomy? Gut, 54, 461-468.

Charlton, A., Blair, V., Shaw, D., Parry, S., Guilford, P., & Martin, I. G. (2004). Hereditary diffuse gastric cancer: Predominance of multiple foci of signet ring cell carcinoma in distal stomach and transitional zone. Gut, 53, 814-820.

Rapley, E. A., Hockley, S., Warren, W., Johnson, L., Huddart, R., Crockford, G., … Guilford, P., … Stratton, M. R. (2004). Somatic mutations of KIT in familial testicular germ cell tumours. British Journal of Cancer, 90, 2397-2401. doi: 10.1038/sj.bjc.6601880

Graziano, F., Arduini, F., Ruzzo, A., Bearzi, I., Humar, B., More, H., … Guilford, P., … Cascinu, S. (2004). Prognostic analysis of E-cadherin gene promoter hypermethylation in patients with surgically resected, node-positive, diffuse gastric cancer. Clinical Cancer Research, 10, 2784-2789.

da Silva Tatley, F. M., Aldwell, F., Dunbier, A. K., & Guilford, P. J. (2003). N-terminal E-cadherin peptides act as decoy receptors for Listeria monocytogenes. Infection & Immunity, 71(3), 1580-1583.

Humar, B., Graziano, F., Cascinu, S., Catalano, V., Ruzzo, A. M., Magnani, M., Toro, T. T., Burchill, T., Futschik, M., Merriman, T. R., & Guilford, P. J. (2002). Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer. Oncogene, 21, 8192-8195.

Humar, B., Toro, T. T., Graziano, F., Muller, H., Dobbie, Z., Kwang-Yang, H., … Merriman, T. R., & Guilford, P. J. (2002). Novel Germline CDH1 mutations in hereditary diffuse gastric cancer families. Human Mutation, 19, 518-525.

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