Dr. Graham Pidgeon

• Owusu Akuffo K, Nolan J, Stack J,Moran R, Feeney J,Kenny RA, Peto T, Dooley C, O'Halloran AM, Cronin C, and Beatty S. , Prevalence of age-related macular degeneration in the Republic of Ireland. , British Journal of Ophthalmology, 99, 2015, p1037-1044Journal Article, 2015, DOI , TARA - Full Text
• Lynam-Lennon N, Connaughton R, Carr E, Mongan AM, O'Farrell NJ, Porter RK, Brennan L, Pidgeon GP, Lysaght J, Reynolds JV, O'Sullivan J., Excess visceral adiposity induces alterations in mitochondrial function and energy metabolism in esophageal adenocarcinoma., BMC Cancer, 3, (14), 2014, p907-Journal Article, 2014, TARA - Full Text
• Cathcart MC, Lysaght J, Pidgeon GP, Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention., Cancer metastasis reviews, 30, (3-4), 2011, p363-85Journal Article, 2011, DOI
• Lynam-Lennon N, Connaughton R, Carr E, Mongan AM, O'Farrell NJ, Porter RK, Brennan L, Pidgeon GP, Lysaght J, Reynolds JV, O'Sullivan J, Excess visceral adiposity induces alterations in mitochondrial function and energy metabolism in esophageal adenocarcinoma., BMC cancer, 14, 2014, p907Journal Article, 2014, DOI , TARA - Full Text
• Cathcart MC, Gately K, Cummins R, Drakeford C, Kay EW, O'Byrne KJ, Pidgeon GP, Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer., Biochimica et biophysica acta, 1842, (5), 2014, p747-55Journal Article, 2014, DOI
• Barr, M.P., Gray, S.G., Gately, K., (...), Pidgeon, G.P., O'Byrne, K.J., Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer, Molecular Cancer, 14, (1), 2015, p45-Journal Article, 2015, DOI , TARA - Full Text
• Mongan AM, Lynam-Lennon N, Casey R, Maher S, Pidgeon G, Reynolds JV, O'Sullivan J, Visceral obesity stimulates anaphase bridge formation and spindle assembly checkpoint dysregulation in radioresistant oesophageal adenocarcinoma., Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2015Journal Article, 2015
• Malley CO, Pidgeon GP, The mTOR pathway in obesity driven gastrointestinal cancers: Potential targets and clinical trials., BBA clinical, 5, 2016, p29-40Journal Article, 2016, DOI , TARA - Full Text
• Mongan A.M, Lynam-Lennon N, Casey R, Maher S, Pidgeon G, Reynolds J.V, O†Sullivan J, Erratum to: Visceral obesity stimulates anaphase bridge formation and spindle assembly checkpoint dysregulation in radioresistant oesophageal adenocarcinoma (Clin Transl Oncol, 10.1007/s12094-015-1411-y), Clinical and Translational Oncology, 18, (6), 2016, p651-Journal Article, 2016, DOI , URL
• Moore G.Y, Pidgeon G.P, Cross-talk between cancer cells and the tumour microenvironment: The role of the 5-lipoxygenase pathway, International Journal of Molecular Sciences, 18, (2), 2017Journal Article, 2017, DOI , URL
• Cathcart M.-C, Useckaite Z, Drakeford C, Semik V, Lysaght J, Gately K, O'Byrne K.J, Pidgeon G.P, Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo, BMC Cancer, 16, (1), 2016, p707-Journal Article, 2016, DOI , URL , TARA - Full Text
• Doyle SL, Mongan AM, Donohoe CL, Pidgeon GP, Sherlock M, Reynolds JV, Lysaght J., Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma., Diseases of the Esophagus, 30, (6), 2017, p1 - 11Journal Article, 2017, DOI
• Kenna, M.M. and McGarrigle, S. and Pidgeon, G.P., The next generation of PI3K-Akt-mTOR pathway inhibitors in breast cancer cohorts, Biochimica et Biophysica Acta - Reviews on Cancer, 1870, (2), 2018, p185-197Journal Article, 2018, DOI , URL
• Charmsaz, S. and Prencipe, M. and Kiely, M. and Pidgeon, G.P. and Collins, D.M., Innovative technologies changing cancer treatment, Cancers, 10, (6), 2018, p208-Journal Article, 2018, DOI , URL , TARA - Full Text
• Mongan AM, Lynam-Lennon N, Doyle SL, Casey R, Carr E, Cannon A, Conroy MJ, Pidgeon GP, Brennan L, Lysaght J, Reynolds JV, O'Sullivan J., Visceral Adipose Tissue Modulates Radiosensitivity in Oesophageal Adenocarcinoma., International journal of medical sciences, 16, (4), 2019, p519-528Journal Article, 2019, DOI , TARA - Full Text
• G.P. Pidgeon, M.P. Barr, J.H. Harmey, D.A. Foley, D.J. Bouchier-Hayes, Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells, British Journal of Cancer, 85, (2), 2001, p273 - 278Journal Article, 2001, DOI , TARA - Full Text
• G. P. Pidgeon, J. H. Harmey, E. Kay, M. Da Costa, H. P. Redmond and D. J. Bouchier-Hayes, The role of endotoxin/lipopolysaccharide in surgically induced tumour growth in a murine model of metastatic disease, British journal of cancer, 81, (8), 1999, p1311-7Journal Article, 1999, DOI , TARA - Full Text
• G.P. Pidgeon, M. Kandouz, A. Meram, K.V. Honn., Mechanisms controlling cell cycle arrest and induction of apoptosis after 12-lipoxygenase inhibition in prostate cancer cells., Cancer Research, 62, (9), 2002, p2721 - 2727Journal Article, 2002, URL , TARA - Full Text
• G.P. Pidgeon, K. Tang, R.L. Rice, A. Zacharek, L. Li, J. D. Taylor, K.V. Honn., Overexpression of leukocyte-type 12-lipoxygenase promotes W256 tumor cell survival by enhancing alphavbeta5 expression., International Journal of Cancer, 105, (4), 2003, p459 - 471Journal Article, 2003, URL
• G.P. Pidgeon, K. Tang, Y.L. Cai, E. Piasentin, K.V. Honn., Overexpression of platelet-type 12-lipoxygenase promotes tumor cell survival by enhancing alpha(v)beta(3) and alpha(v)beta(5) integrin expression., Cancer Research, 63, (14), 2003, p4258 - 4267Journal Article, 2003, DOI , TARA - Full Text
• M. Kandouz, D. Nie, G.P. Pidgeon, S. Krishnamoorthy, K.R. Maddipati, K.V. Honn., Platelet-type 12-lipoxygenase activates NF-kappaB in prostate cancer cells., Prostaglandins and Other Lipid Mediators, 71, (3-4), 2003, p189 - 204Journal Article, 2003, URL
• G.P. Pidgeon, R. Tamosiuniene, G. Chen, I. Leonard, O. Belton, A. Bradford, D.J. Fitzgerald, Intravascular thrombosis after hypoxia-induced pulmonary hypertension: regulation by cyclooxygenase-2., Circulation, 110, (17), 2004, p2701 - 2707Journal Article, 2004, URL
• Barr M.P., Gray S.G., Gately K., Hams E., Fallon P.G., Davies A.M., Richard D.J., Pidgeon G.P., O'Byrne K.J., Erratum: Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer (Molecular Cancer (2015) DOI: 10.1186/s12943-015-0310-8), Molecular Cancer, 19, (1), 2020Journal Article, 2020, DOI
• Cryan LM, Pidgeon GP, Fitzgerald DJ, O'Brien CJ., COX-2 protects against thrombosis of the retinal vasculature in a mouse model of proliferative retinopathy., Molecular Vision, 12, (Apr 20), 2006, p405 - 414Journal Article, 2006, URL , TARA - Full Text
• Pidgeon GP, Lysaght J, Krishnamoorthy S, Reynolds JV, O'Byrne K, Nie D, Honn KV., Lipoxygenase metabolism: roles in tumor progression and survival., Cancer Metastasis Reviews, 3-4, 2007, p503 - 524Journal Article, 2007
• Cathcart MC, Tamosiuniene R, Chen G, Neilan TG, Bradford A, O' Byrne KJ, Fitzgerald DJ, Pidgeon GP., COX-2-Linked Attenuation of Hypoxia-Induced Pulmonary Hypertension and Intravascular Thrombosis., Journal of Pharmacology and Expreimental Therapeutics, 2008Journal Article, 2008
• Mary-Clare Cathcart, John V. Reynolds, Kenneth J. O'Byrne, Graham P. Pidgeon, The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer , Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1805, (2), 2010, p153-166Journal Article, 2010, DOI , URL , TARA - Full Text
• Lynam-Lennon N, Reynolds JV, Pidgeon GP, Lysaght J, Marignol L, Maher SG, Alterations in DNA repair efficiency are involved in the radioresistance of esophageal adenocarcinoma., Radiation research, 174, (6), 2010, p703 - 711Journal Article, 2010, DOI
• J. Lysaght, E.P. van der Stok, E.H. Allott, R. Casey, C.L. Donohoe, J.M. Howard, S.A. McGarrigle, N. Ravi, J.V. Reynolds, G.P. Pidgeon, Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue, Cancer Letters, 312, (1), 2011, p62-72Journal Article, 2011, DOI , URL , TARA - Full Text
• Lysaght J, Allott EH, Donohoe CL, Howard JM, Pidgeon GP, Reynolds JV., T lymphocyte activation in visceral adipose tissue of patients with oesophageal adenocarcinoma., British Journal of Surgery, 98, (7), 2011, p964 - 974Journal Article, 2011, DOI
• Carroll PA, Healy L, Lysaght J, Boyle T, Reynolds JV, Kennedy MJ, Pidgeon G, Connolly EM., Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer., Molecular Carcinogenesis, 50, (8), 2011, p643 - 651Journal Article, 2011, DOI
• SL Doyle, C Donohoe, S Finn, J Howard, FE Lithander, JV Reynolds, G Pidgeon, J Lysaght , IGF-1 and its Receptor in Esophageal Cancer: Association with Adenocarcinoma and Visceral Obesity, American Journal of Gastroenterology, 107, 2012, p196 - 204Journal Article, 2012, DOI , URL
• Mary-Clare Cathcart, Kenneth J. O'Byrne, John V. Reynolds, Jacintha O' Sullivan, Graham P. Pidgeon, COX-Derived prostanoid pathways in gastrointestinal cancer development and progression: Novel targets for prevention and intervention, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1825, (1), 2012, p49-63Journal Article, 2012, DOI , URL , TARA - Full Text
• Byrne M, Reynolds JV, O'Donnell JS, Keogan M, White B, Byrne M, Murphy S, Maher SG, Pidgeon GP, Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery., British Journal of Cancer, 102, (1), 2010, p73-9Journal Article, 2010, DOI , URL , TARA - Full Text
• Donohoe CL, Doyle SL, McGarrigle S, Cathcart MC, Daly E, O'Grady A, Lysaght J, Pidgeon GP, Reynolds JV., Role of the insulin-like growth factor 1 axis and visceral adiposity in oesophageal adenocarcinoma, British Journal of Surgery, 99, (3), 2012, p387-96Journal Article, 2012, DOI , URL
• Allott EH, Lysaght J, Cathcart MC, Donohoe CL, Cummins R, McGarrigle SA, Kay E, Reynolds JV, Pidgeon GP, MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation, Molecular Carcinogenesis, 2012Journal Article, 2012, DOI , URL
• Howard JM, Beddy P, Ennis D, Keogan M, Pidgeon GP, Reynolds JV, Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma., The British journal of surgery, 97, (7), 2010, p1020-7Journal Article, 2010
• Howard JM, Pidgeon GP, Reynolds JV, Leptin and gastrointestinal malignancies , Obesity Reviews, 11, (12), 2010, p863-874Journal Article, 2010, DOI , URL
• Lynam-Lennon N, Reynolds JV, Marignol L, Sheils OM, Pidgeon GP, Maher SG, MicroRNA-31 modulates tumour sensitivity to radiation in oesophageal adenocarcinoma., Journal of molecular medicine (Berlin, Germany), 2012Journal Article, 2012, DOI
• Allott EH, Morine MJ, Lysaght J, McGarrigle SA, Donohoe CL, Reynolds JV, Roche HM, Pidgeon GP, Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis., Clinical and translational gastroenterology, 3, 2012, pe12Journal Article, 2012, DOI , TARA - Full Text
• Allott EH, Oliver E, Lysaght J, Gray SG, Reynolds JV, Roche HM, Pidgeon GP, The SGBS cell strain as a model for the in vitro study of obesity and cancer., Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 14, (10), 2012, p774-82Journal Article, 2012, DOI
• Howard JM, Cathcart MC, Healy L, Beddy P, Muldoon C, Pidgeon GP, Reynolds JV, Leptin and adiponectin receptor expression in oesophageal cancer., The British journal of surgery, 101, (6), 2014, p643-52Journal Article, 2014, DOI , TARA - Full Text
• Lahiff C, Schilling C, Cathcart MC, Mulligan N, Doran P, Muldoon C, Murray D, Pidgeon GP, Reynolds JV, Macmathuna P, Prognostic significance of neuroepithelial transforming gene 1 in adenocarcinoma of the oesophagogastric junction., The British journal of surgery, 101, (2), 2014, p55-62Journal Article, 2014, DOI , TARA - Full Text
• Doyle SL, Bennett AM, Donohoe CL, Mongan AM, Howard JM, Lithander FE, Pidgeon GP, Reynolds JV, Lysaght J, Establishing computed tomography-defined visceral fat area thresholds for use in obesity-related cancer research., Nutrition research (New York, N.Y.), 33, (3), 2013, p171-9Journal Article, 2013, DOI
• Allott EH, Lysaght J, Cathcart MC, Donohoe CL, Cummins R, McGarrigle SA, Kay E, Reynolds JV, Pidgeon GP, MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation., Molecular carcinogenesis, 52, (2), 2013, p144-54Journal Article, 2013, DOI
• Lahiff C, Cotter E, Casey R, Doran P, Pidgeon G, Reynolds J, Macmathuna P, Murray D, Expression of neuroepithelial transforming gene 1 is enhanced in oesophageal cancer and mediates an invasive tumour cell phenotype., Journal of experimental & clinical cancer research : CR, 32, (1), 2013, p55Journal Article, 2013, DOI , TARA - Full Text

My research interests focus on the regulation of vascular function and angiogenesis by bioactive lipids/prostanoids. Biologically active products derived from cyclooxygenase (COX) and lipoxygenase (LOX) mediated metabolism of arachidonic acid are involved in a range of clinical conditions, including arthritis, cancer and heart disease. One area of my research is in the examination of the role of the different COX isoforms, and their downstream products in pulmonary disease. There are reports that drugs which selectively inhibit COX-2 have detrimental effects on cardiac function, to date our results confirm that selective inhibition of COX-2 in models of hypoxia-induced pulmonary hypertension aggravates the problem. We are currently examining the mechanisms whereby cyclooxygenase isozymes regulate pulmonary hypertension and lung cancer, with an emphasis on COX-mediated angiogenesis and thrombosis in these diseases. A second area of research involves examining the role of bioactive lipids as survival factors in cancer. We are currently examining the role of 12-lipoxygenase, COX-2 and thromboxane synthase as survival factors in lung cancer and mesothelioma. The goal of this research is to identify the mechanisms whereby these enzymes facilitate tumour survival under conditions found within the tumour microenvironment, including hypoxia and serum deprivation. My third area of research interest is in the Vascular Endothelial Growth Factor receptors and their expression in lung cancer and mesothelioma. I am particularly interested in the Neuropilin family of receptors, their role in cell survival and regulation by bioactive lipids. We are currently examining the expression profile of VEGF receptors in cell lines and retrospective human lung cancers, to correlate their expression with tumour grade and stage.

• Title

  An investigation of the thromboxane and prostacyclin synthase pathways in non-small cell lung cancer.
  Summary

  This research project will provide significant insights into the potential mechanisms whereby the balance between the expression of thromboxane synthase and prostacyclin synthase in lung cancer may confer a survival advantage on tumour cells directly. The series of experiments will examine the potential correlation between tumour expression of these PGH2 metabolising enzymes and clinical parameters, including thrombotic events, tumour angiogenesis and overall survival. These pathways have been implicated in various forms of malignancies and a number of specific inhibitors of TXS have shown promise in clinical trials, suggesting the translation of the research proposed here into future clinical applications in lung cancer should be rapid. The in vitro experiments are carefully designed to explore the potential survival mechanisms at the cellular protein level, by generating NSCLC clones with overexpression or silenced expression of these targets using molecular strategies. These clones will be thoroughly characterised both invitro and invivo for their effect on tumour cells. Direct clinical relevance will be highlighted by retrospectively examining the expression of TXS and PGIS expression in a series of resected lung tumours with varying stage and type of disease and also in frozen normal / tumour samples taken from the EU biobank at St. James Hospital. By furthering our knowledge of these critical regulatory mechanisms controlling tumour cell survival, it is anticipated that new interventional therapies may be designed to target lung cancer, either alone or in combination with conventional radiotherapy and chemotherapy.
  Funding Agency

  Cancer Research Ireland
  Date From

  2008
  Date To

  2011
• Title

  Neuropilin-1 expression and regulation by 12-Lipoxygenase in lung cancer.
  Summary

  This research project will provide significant insights into the potential mechanisms whereby neuropilin-1 expression in lung cancer may confer a survival advantage on tumour cells directly. The series of experiments will examine the potential correlation between tumour expression of the arachidonic acid metabolising enzyme 12-LOX and neuropilin-1 receptor expression in lung cancer. Each of these pathways have been implicated in various forms of malignancies and a number of specific inhibitors of LOX pathways have shown promise in clinical trials, suggesting the translation of the research proposed here into future clinical applications in lung cancer should be rapid. These experiments are carefully designed to explore the potential survival mechanisms at the cellular protein level, by overexpression of 12-LOX while targeting NRP-1 pathways by a neutralising or RNA silencing approach. Direct clinical relevance will be highlighted by retrospectively examining the expression of 12-LOX and NRP-1 expression in a series of resected lung tumours with varying stage and type of disease. By furthering our knowledge of these critical regulatory mechanisms controlling tumour cell survival, it is anticipated that new interventional therapies may be designed to target lung cancer, either alone or in combination with conventional radiotherapy and chemotherapy.
  Funding Agency

  Cancer Research Ireland
  Date From

  2005
  Date To

  2008
• Title

  COX-isoforms and prostaglandins in an hypoxia-induced model of pulmonary hypertension.
  Summary

  Altered regulation of the cyclooxygenase (COX) signalling pathway underlies the development and progression of many diseases. The PGI2/TXA2 ratio is of particular importance in-vivo, with the corresponding synthases being shown to be differentially regulated. COX-derived prostanoids have been implicated in the development of PH, and an imbalance between the generation of thromboxane A2 (TXA2) and prostacyclin (PGI2) has been reported in both primary and secondary forms of the disease. These prostanoids have directly opposing effects; PGI2 is a potent vasodilator, is anti-proliferative, and inhibits platelet activation and aggregation, while TXA2 is a vasoconstrictor, is mitogenic and activates platelets and their aggregation. COX-2 is the main isoform responsible for the generation of PGI2, while TXA2 is mainly derived from platelets, where COX-1 is the main isoform. Exogenous PGI2 is effective in reducing pulmonary vascular resistance in some forms of human pulmonary hypertension (PH). To examine whether endogenous prostanoids played a similar role in PH, we examined the effect of deleting COX-gene isoforms in a chronic hypoxia model of the disease. An experimental model of pulmonary hypertension (PH) was generated using COX-gene disrupted mice. PH was induced by 3 weeks of hypobaric hypoxia, and was confirmed by direct measurement of right ventricular end systolic pressure (RVESP), right ventricular hypertrophy (RVH) and increased haematocrit. RVESP was increased in wild-type (WT) hypoxic mice compared to normoxic controls, while COX-2 knock-out (KO) mice showed a further increase in RVESP following hypoxia. Urinary TXB2 excretion increased following hypoxia, an effect that was exacerbated following COX-2 gene disruption. In contrast, the increase in 6-keto-PGF1á excretion following hypoxia was reduced by COX-2 gene disruption. Tail-cut bleed times were reduced following hypoxia, and there was (immunohistochemical) evidence of intravascular thrombosis in lung vessels that was exacerbated by disruption of COX-2 and reduced by deletion of COX-1. The thromboxane receptor antagonist, ifetroban (50mg/kg/day) offset the effect of COX-2 gene deletion, by attenuating the hypoxia-induced rise in RVESP and intravascular thrombosis. In addition to pulmonary vascular thrombosis, a second characteristic feature of pulmonary hypertension is the development of pulmonary vascular remodelling an angiogenesis. Real-time PCR analysis of vascular remodelling in the disease implicated a number of genes to be altered in the disease including VEGFC, EphB2, TNFá, TNFaip2, and CCl2. Genes of particular interest included VEGFC, EphB2, TNFá and TNFaip2, which are all pro-angiogenic factors that were down-regulated following COX-2 gene disruption. Further work is required to determine whether these changes in gene expression profile represent a beneficial or detrimental adaptation to chronic hypoxia exposure. In conclusion, the findings of this research demonstrate that COX-2 gene deletion exacerbates the pathogenesis of pulmonary hypertension, enhances sensitivity to TXA2 and induces intravascular thrombosis in response to hypoxia. COX-2 gene deletion also down-regulated the expression of a number of angiogenic genes in response to hypoxia, suggesting that expression of these genes may have a beneficial effect in the pathogenesis of the disease. Our data provides evidence that endogenous prostanoids modulate the pulmonary response to hypoxia.
  Funding Agency

  Health Research Board
  Date From

  2004
  Date To

  2007

• Health Research Board PostDoctoral Fellowship 2004
• Cancer Research Foundation of America Research Fellowship 2001

• Member of the American Association of Cancer Research Current
• Member of the Irish Association of Cancer Research Current
• Honarary Fellow of the IBS (Institute of Biomedical Sciences), RCSI. Current