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Professor Nigel Bundred

Professor Nigel Bundred


Professor (MB BS, MD, FRCS)

Websites

Research Interests

My current research programme is concentrated on two main areas, breast cancer,  and Parathyroid Hormone related protein/hypercalcaemia of malignancy.  I currently have a team of 2 research registrars, 2 postdoctoral assistants and 2 technicians working on various current laboratory research areas. In addition 3 ½  research nurses and 1 graduate research worker are working on various clinical trials on studies for which I have obtained funding.  In total nine MD theses and 1 PhD have been awarded under my supervision.

Active research areas encompass breast cancer prevention, mechanisms of bone metastasis, angiogenesis, stem cell (non-adherent) culture of DCIS and invasive breast cancer.

Ductal Carcinoma in Situ (DCIS)

DCIS constitutes 30% of all screen detected breast cancer.  I have developed an athymic nude mouse model in which human DCIS is implanted as xenografts and survives up to two months, in collaboration with Professor Chris Potten in the Paterson Institute for Cancer Research

In xenografts removed sequentially at 14, 28 and 56 days proliferation and steroid receptor expression were measured.  Oestrogen Receptor Negative Comedo DCIS was not stimulated by oestrogen nor inhibited by the pure antioestrogens (ICI 182780).  In contrast, papillary or cribriform (steroid receptor positive) DCIS was stimulated to proliferate by oestrogen implants (paper published in J Natl Cancer Inst). We have since followed up these studies by examining whether monoclonal antibodies to the CerbB2 oncogene or Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition prevent DCIS growth.  Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition with Iressa prevented epithelial proliferation and induced apoptosis both in normal breast and DCIS xenografts implanted into nude mice whereas monoclonal antibody to CerbB2 oncoprotein had no such effects.  In addition, Iressa inhibited downstream signalling pathways including MAPkinase and phosphorylation of the EGFR.  Other studies using breast cancer cell lines expressing EGFR and CerbB2 have demonstrated that blocking the EGFR also inhibits phosphorylation of the CerbB2 oncoprotein and downstream signalling.

RAS Farnesyl Transferase Inhibition research has won national and international recognition with the award of the Patey Prize to Mr Kai Chan, Research Registrar at the Surgical Research Society in December 1999 and with publication in prestigious American Journals (J National Cancer Institute and Cancer Research).   A follow-up paper on the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor work has been published in Cancer Research.  The major thrust of the research is currently in the area of pre-invasive malignancy in breast cancer and the factors that promote conversion of DCIS to an invasive malignancy.

More recently we have identified stem cells from DCIS lesions and demonstrated growth inhibition of non-adherent stem like cells by NOTCH and epidermal growth factor receptor inhibition.

We have pioneered the developed of IAP kinase development of preoperative studies in ductal carcinoma in situ and a recent study has shown that an aromatase inhibitor (Exemestane) significantly inhibits proliferation in oestrogen receptor positive DCIS.  We have currently received Ethical Approval and have initiated the trial of a HER1/2 small molecule inhibitor, Lapatinib, in DCIS preoperatively.  This trial will investigate the mechanism of action of Lapatinib and look for potential markers of response. 

Control of Apoptosis in the Normal Breast in Breast Cancer

We have developed studies on apoptosis in both normal breast, DCIS and invasive cancer (in collaboration with Professor Charles Streuli) where we investigated mechanisms of inducing or preventing apoptosis in the breast.   We initially developed new measures of apoptosis (activated caspase3 immunohistochemistry) and more latterly we have investigated the role of inhibitors of apoptosis intracellular proteins which block apoptosis and are elevated in breast cancer. 

More recently we have obtained a grant from Breast Cancer Campaign to study inhibitors of apoptosis proteins (IAPs).  These proteins prevent the final execution of the cell and we are analysing which of the 8 proteins are over expressed in breast cancer and whether inhibiting individual IAPs will induce tumour response and an increase in apoptosis.  It is likely that by increasing apoptosis through inhibiting IAPs, conventional therapy with either endocrine agents or chemotherapy will be enhanced.

Teaching

Modules

• Thyroid disease (RS989T9009)

I have an undergraduate surgical firm (3rd year) and run Speciality Study Modules (SSM) for final year students and have been involved in teaching undergraduates and postgraduates since 1980.

I taught anatomy in Newcastle to medical, dental and physiotherapy students and in all the academic centres in which I have worked I have been involved in bedside and formal teaching of medical students.

I undertake regular ward and outpatient clinic teaching and act as an internal examiner for the University of Manchester. I am a Lecturer on the third year medical students Basic Integrated Science Course for Breast Disease and I also lecture on the introductory course teaching medical students basic clinical skills.

Biography

I am a Professor of Surgical Oncology and Consultant Surgeon at the University Hospital of South Manchester and Christie Hospital. I received his medical degree from Newcastle University Medical School, Newcastle-upon-Tyne, United Kingdom, and have studied in Edinburgh, Leicester, Cardiff and Birmingham, United Kingdom.

My research interests are in preinvasive cancer (ductal carcinoma in situ), breast cancer chemoprevention and bone metastases and I was awarded a Hunterian Professorship in 1995 for my work on parathyroid hormone related peptide and its role in bone metastases by the Royal College of Surgeons of England.

I have a large clinical commitment in the Manchester Breast Centre, the largest breast unit in the United Kingdom and I am also a member of numerous medical societies and has been the recipient of numerous honours and awards, including the Patey Prize from the Surgical Research Society and the Ronald Raven Prize from the British Association of Surgical Oncology. In 2007 I was appointed as Clinical Lead for Research for the Greater Manchester and Cheshire Cancer Research Network.

I have authored/co-authored more than 160 peer-reviewed articles and my work has appeared in many journals, including the Journal of the National Cancer Institute, The Lancet, Cancer Research and Cancer.

Additional Information

I perform immediate breast reconstruction in Manchester and also operate on patients referred from other centres for reconstruction.  I use the same techniques in rescue mastectomies and palliative surgery of advanced localised cancers of the breast and other sites.

I provide surgical management of parathyroid disease (primary and tertiary hyperparathyroidism) and thyroid cancer for the Christie and Withington Hospitals.  In particular I am experienced in re-exploring the neck for missed parathyroid glands and re-operative surgery for thyroid cancer.

Recent Publications

2007
Lavelle K, Moran A, Howell A, Bundred N, Campbell M, Todd C (2007) Older women with operable breast cancer are less likely to have surgery. Br J Surg (in press).

Farnie G, Clarke RB, Spence K, Pinnock N, Brennan K, Anderson NG, Bundred NJ (2007) Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways. J Natl Cancer Inst. 99:616-27.

Lavelle K, Todd C, Moran A, Howell A, Bundred N, Campbell M (2007) Non-standard management of breast cancer increases with age in the UK: a population based cohort of women > or =65 years. Br J Cancer. 96:1197-203

Patiar S, Kirwan CC, McDowell G, Bundred NJ, McCollum CN, Byrne GJ (2007) Prevention of venous thromboembolism in surgical patients with breast cancer. Br J Surg. 94:412-20

Howell A, Clarke RB, Evans G, Bundred N, Cuzick J, Santen R, Allred C (2007) Estrogen deprivation for breast cancer prevention. Recent Results Cancer Res. 174:151-67

Barnes NL, Warnberg F, Farnie G, White D, Jiang W, Anderson E, Bundred NJ (2007) Cyclooxygenase-2 inhibition: effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer. Br J Cancer. 96:575-82.

2006
Wilson GR, Cramer A, Welman A, Knox F, Swindell R, Kawakatsu H, Clarke RB, Dive C, Bundred NJ (2006) Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity. Br J Cancer. 95:1410-4.

Kirwan CC, McCollum CN, Bundred NJ, Byrne GJ (2006) Current UK practice of thromboprophylaxis for breast surgery. Br J Surg. 93:1224-5

Maurice A, Evans DG, Shenton A, Ashcroft L, Baildam A, Barr L, Byrne G, Bundred N, Boggis C, Wilson M, Duffy SW, Howell A (2006) Screening younger women with a family history of breast cancer--does early detection improve outcome? Eur J Cancer. 42:1385-90.

Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, Yiangou C, Horgan K, Bundred N, Monypenny I, England D, Sibbering M, Abdullah TI, Barr L, Chetty U, Sinnett DH, Fleissig A, Clarke D, Ell PJ (2006) Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 98:599-609.

Warnberg F, White D, Anderson E, Knox F, Clarke RB, Morris J, Bundred NJ (2006) Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo. Breast Cancer Res. 8:R21

Barnes N, Haywood P, Flint P, Knox WF, Bundred NJ (2006) Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence. Br J Cancer. 94:253-8.

Dixon JM, Bundred N (2006) Aromatase inhibitors for early breast cancer therapy: a choice of effective treatment strategies. Eur J Surg Oncol. 32:123-5

2005
McDowell G, Temple I, Li C, Kirwan CC, Bundred NJ, McCollum CN, Burton IE, Kumar S, Byrne GJ (2005) Alteration in platelet function in patients with early breast cancer. Anticancer Res. 25:3963-6.

Bundred NJ (2005) The effects of aromatase inhibitors on lipids and thrombosis. Br J Cancer. 2005 93:S23-7.

Bundred NJ, Barnes NL (2005) Potential use of COX-2-aromatase inhibitor combinations in breast cancer. Br J Cancer. 93:S10-5

Bundred N (2005) Preclinical and clinical experience with fulvestrant (Faslodex) in postmenopausal women with hormone receptor-positive advanced breast cancer. Cancer Invest. 23:173-81.

Barnes NL, Khavari S, Boland GP, Cramer A, Knox WF, Bundred NJ (2005) Absence of HER4 expression predicts recurrence of ductal carcinoma in situ of the breast. Clin Cancer Res. 11:2163-8.

Barnes NL, Boland GP, Davenport A, Knox WF, Bundred NJ (2005) Relationship between hormone receptor status and tumour size, grade and comedo necrosis in ductal carcinoma in situ. Br J Surg. 92:429-34.

Kroiss R, Fentiman IS, Helmond FA, Rymer J, Foidart JM, Bundred N, Mol-Arts M, Kubista E (2005) The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial. BJOG. 112:228-33.
Clarke RB, Bundred NJ (2005) Do early premalignant changes in normal breast epithelial cells predict cancer development? Breast Cancer Res. 7:18-20

2004
Boland GP, Butt IS, Prasad R, Knox WF, Bundred NJ (2004) COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ. Br J Cancer. 90:423-9.

Ahmad T, Farnie G, Bundred NJ, Anderson NG (2004) The mitogenic action of insulin-like growth factor I in normal human mammary epithelial cells requires the epidermal growth factor receptor tyrosine kinase. J Biol Chem. 279:1713-9

2003
Down S, Barr L, Baildam AD, Bundred N (2003) Management of accessory breast tissue in the axilla. Br J Surg. 90:1213-4.

Prasad R, Boland GP, Cramer A, Anderson E, Knox WF, Bundred NJ (2003) Short-term biologic response to withdrawal of hormone replacement therapy in patients with invasive breast carcinoma. Cancer. 98:2539-46.

Bundred NJ, Morris J (2003) Breast cancer and hormone-replacement therapy: the Million Women Study. Lancet. 36:1329

Boland GP, McKeown A, Chan KC, Prasad R, Knox WF, Bundred NJ (2003) Biological response to hormonal manipulation in oestrogen receptor positive ductal carcinoma in situ of the breast. Br J Cancer. 89:277-83

Boland GP, Chan KC, Knox WF, Roberts SA, Bundred NJ (2003) Value of the Van Nuys Prognostic Index in prediction of recurrence of ductal carcinoma in situ after breast-conserving surgery. Br J Surg. 90:426-32

Freeman SR, Washington SJ, Pritchard T, Barr L, Baildam AD, Bundred NJ (2003) Long term results of a randomised prospective study of preservation of the intercostobrachial nerve. Eur J Surg Oncol. 29:213-5.

Hoey RP, Sanderson C, Iddon J, Brady G, Bundred NJ, Anderson NG (2003) The parathyroid hormone-related protein receptor is expressed in breast cancer bone metastases and promotes autocrine proliferation in breast carcinoma cells. Br J Cancer. 88:567-73.

2002
Linforth R, Anderson N, Hoey R, Nolan T, Downey S, Brady G, Ashcroft L, Bundred N (2002) Co-expression of parathyroid hormone related protein and its receptor in early breast cancer predicts poor patient survival. Clin Cancer Res. 8:3172-7.

Boland GP, Knox WF, Bundred NJ (2002) Molecular markers and therapeutic targets in ductal carcinoma in situ. Microsc Res Tech. 59:3-11

Warnberg F, Bundred N (2002) Will early detection of non-axillary sentinel nodes affect treatment decisions? Br J Cancer. 87:691-3

Bundred NJ, Anderson E, Nicholson RI, Dowsett M, Dixon M, Robertson JF (2002) Fulvestrant, an estrogen receptor downregulator, reduces cell turnover index more effectively than tamoxifen. Anticancer Res. 22:2317-9.

Bundred N, Howell A (2002) Fulvestrant (Faslodex): current status in the therapy of breast cancer.
Expert Rev Anticancer Ther. 2:151-60.

Gilmore AP, Valentijn AJ, Wang P, Ranger AM, Bundred N, O'Hare MJ, Wakeling A, Korsmeyer SJ, Streuli CH (2002) Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor. J Biol Chem. 277:27643-50.

Dey P, Bundred N, Gibbs A, Hopwood P, Baildam A, Boggis C, James M, Knox F, Leidecker V, Woodman C (2002) Costs and benefits of a one stop clinic compared with a dedicated breast clinic: randomised controlled trial. BMJ. 324:507.

Chan KC, Knox WF, Gee JM, Morris J, Nicholson RI, Potten CS, Bundred NJ (2002) Effect of epidermal growth factor receptor tyrosine kinase inhibition on epithelial proliferation in normal and premalignant breast. Cancer Res. 62:122-8.

2001
Anderson NG, Ahmad T, Chan K, Dobson R, Bundred NJ (2001) ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR-positive cancer cell lines with or without erbB2 overexpression. Int J Cancer. 94:774-82.

Hadjiloucas I, Gilmore AP, Bundred NJ, Streuli CH. Assessment of apoptosis in human breast tissue using an antibody against the active form of caspase 3: relation to tumour histopathological characteristics. Br J Cancer. 2001 85:1522-6.

Bundred NJ, Chan K, Anderson NG (2001) Studies of epidermal growth factor receptor inhibition in breast cancer. Endocr Relat Cancer. 8:183-9.

Robertson JF, Nicholson RI, Bundred NJ, Anderson E, Rayter Z, Dowsett M, Fox JN, Gee JM, Webster A, Wakeling AE, Morris C, Dixon M (2001) Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer. Cancer Res. 61:6739-46.

Dowsett M, Bundred NJ, Decensi A, Sainsbury RC, Lu Y, Hills MJ, Cohen FJ, Veronesi P, O'Brien ME, Scott T, Muchmore DB (2001) Effect of raloxifene on breast cancer cell Ki67 and apoptosis: a double-blind, placebo-controlled, randomized clinical trial in postmenopausal patients. Cancer Epidemiol Biomarkers Prev. 10:961-6.

Bundred NJ (2001) Prognostic and predictive factors in breast cancer. Cancer Treat Rev. 27:137-42.

Chan KC, Knox WF, Gandhi A, Slamon DJ, Potten CS, Bundred NJ (2001) Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation. Br J Surg. 88:412-8.

Chan KC, Knox WF, Sinha G, Gandhi A, Barr L, Baildam AD, Bundred NJ (2001) Extent of excision margin width required in breast conserving surgery for ductal carcinoma in situ. Cancer. 91:9-16.

2000
Ghellal A, Li C, Hayes M, Byrne G, Bundred N, Kumar S (2000) Prognostic significance of TGF beta 1 and TGF beta 3 in human breast carcinoma. Anticancer Res. 20:4413-8.

Byrne GJ, Bundred NJ (2000) Surrogate markers of tumoral angiogenesis. Int J Biol Markers. 15:334-9.

Li C, Guo B, Wilson PB, Stewart A, Byrne G, Bundred N, Kumar S (2000) Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer. Int J Cancer. 89:122-6.

Gandhi A, Holland PA, Knox WF, Potten CS, Bundred NJ (2000) Effects of a pure antiestrogen on apoptosis and proliferation within human breast ductal carcinoma in situ. Cancer Res. 60:4284-8.

Byrne GJ, Ghellal A, Iddon J, Blann AD, Venizelos V, Kumar S, Howell A, Bundred NJ (2000) Serum soluble vascular cell adhesion molecule-1: role as a surrogate marker of angiogenesis. J Natl Cancer Inst. 92:1329-36.

Mantell DJ, Owens PE, Bundred NJ, Mawer EB, Canfield AE (2000) 1 alpha,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo. Circ Res. 2000 87:214-20.