The Centre initiated its grant funding from the Digestive Cancer Campaign in April 2004 to coincide with the move of Nick Lemoine's Molecular Oncology Unit and Ajay Kakkar's Surgical Sciences Unit to the new Clinical Centre at Barts & The London. This has given the opportunity to reorganise both the clinical and laboratory elements of the London component of the Centre for Pancreatic Cancer Research, which complements the existing strengths - genetics, proteomics and clinical trials - of the Liverpool group.

The first appointment funded by the DCC grant is a postdoctoral research fellowship for Dr Celina Costas to join the group where her skills in molecular virology will be crucial to the development of the new class of oncolytic viruses with which the principal investigators in the Centre plan clinical trials in patients with pancreatic cancer. Dr Costas did her PhD in Spain and had several years of research experience in the US before moving to the UK this year. She will be constructing new generations of adenovirus that replicate and destroy pancreatic cancer cells by targeting the key genetic events that drive their malignant behaviour. Her first priority will be to test the effectiveness of the new versions of the virus in combination with chemotherapy, as the international ESPAC-1 trial (see publications below) led by Professor John Neoptolemos showed convincingly that use of a chemotherapeutic agent such as 5-fluorouracil is of major clinical benefit - and should therefore become standard of care in this disease.

The pancreatic gene therapy group now comprises Dr Costas as the lead virologist, Dr Gunnel Hallden who is a molecular cell biologist with crucial biotechnology experience, Dr Pompa Bhattacharyya who is a clinical research fellow with an interest in gastrointestinal cancer, and two technicians. There is considerable synergy with the molecular genetics group at Barts & The London, and with the molecular oncology group led by Drs Mark Boyd and Eithne Costello in Liverpool. Between them, the genetic events associated with the various stages of the disease are being dissected using a combination of leading edge technologies including laser capture microdissection, genomics and proteomic approaches.

Centre publications of 2003/4:

Halloran CM, Ghaneh P, Shore S, Greenhalf W, Zumstein L, Wilson D, Neoptolemos JP, Costello E. 5-Fluorouracil or gemcitabine combined with adenoviral-mediated reintroduction of p16INK4A greatly enhanced cytotoxicity in Panc-1 pancreatic adenocarcinoma cells. J Gene Med. 2004 May; 6(5):514-25.

Jones LE, Humphreys MJ, Campbell F, Neoptolemos JP, Boyd MT. Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: increased expression of matrix metalloproteinase-7 predicts poor survival. Clin Cancer Res. 2004 Apr 15;10(8):2832-45.

Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Buchler MW; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18;350(12):1200-10.

Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P, Truninger K, Ammann R, Cavallini G, Charnley RM, Uomo G, Delhaye M, Spicak J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP; European Registry of Hereditary Pancreatitis and Pancreatic Cancer (EUROPAC). Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol. 2004 Mar;2(3):252-61.

Alexakis N, Campbell F, Eardley N, Smart HL, Garvey C, Neoptolemos JP. T cell lymphoplasmacellular and eosinophilic infiltration of the pancreas with involvement of the gallbladder and duodenum in non-alcoholic duct-destructive chronic pancreatitis. Langenbecks Arch Surg. 2004 Feb 10 [Epub ahead of print]

Vimalachandran D, Ghaneh P, Costello E, Neoptolemos JP. Genetics and prevention of pancreatic cancer. Cancer Control. 2004 Jan-Feb;11(1):6-14.

Kakkar AK, Levine MN, Kadziola Z, Lemoine NR, Low V, Patel HK, Rustin G, Thomas M, Quigley M, Williamson RC. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol. 2004 May 15;22(10):1944-8.

Critchley RJ, Jezzard S, Radford KJ, Goussard S, Lemoine NR, Grillot-Courvalin C, Vassaux G. Potential therapeutic applications of recombinant, invasive E. coli. Gene Ther. 2004 May 13 [Epub ahead of print]

Madhusudan S, Tamir A, Bates N, Flanagan E, Gore ME, Barton DP, Harper P, Seckl M, Thomas H, Lemoine NR, Charnock M, Habib NA, Lechler R, Nicholls J, Pignatelli M, Ganesan TS. A multicenter Phase I gene therapy clinical trial involving intraperitoneal administration of E1A-lipid complex in patients with recurrent epithelial ovarian cancer overexpressing HER-2/neu oncogene. Clin Cancer Res. 2004 May 1;10(9):2986-96.

Lemoine NR, McNeish IA. Gene transfer: Bax to the future for cancer therapy. Gut. 2004 Apr;53(4):478-9.

Groot-Wassink T, Aboagye EO, Wang Y, Lemoine NR, Reader AJ, Vassaux G. Quantitative imaging of Na/I symporter transgene expression using positron emission tomography in the living animal. Mol Ther. 2004 Mar;9(3):436-42.

McNeish IA, Bell SJ, Lemoine NR. Gene therapy progress and prospects: cancer gene therapy using tumour suppressor genes. Gene Ther. 2004 Mar;11(6):497-503.

Capurso G, Delle Fave G, Lemoine NR. Etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity. J Natl Cancer Inst. 2004 Jan 7;96(1):75

Marani M, Hancock D, Lopes R, Tenev T, Downward J, Lemoine NR. Role of Bim in the survival pathway induced by Raf in epithelial cells. Oncogene. 2004 Apr 1;23(14):2431-41.

Brown NL, Lemoine NR. Clinical trials with GDEPT: cytosine deaminase and 5-fluorocytosine. Methods Mol Med. 2004;90:451-7.

Connor S, Ghaneh P, Raraty M, Rosso E, Hartley MN, Garvey C, Hughes M, McWilliams R, Evans J, Rowlands P, Sutton R, Neoptolemos JP. Increasing age and APACHE II scores are the main determinants of outcome from pancreatic necrosectomy. Br J Surg. 2003 Dec;90(12):1542-8.

Shekouh AR, Thompson CC, Prime W, Campbell F, Hamlett J, Herrington CS, Lemoine NR, Crnogorac-Jurcevic T, Buechler MW, Friess H, Neoptolemos JP, Pennington SR, Costello E. Application of laser capture microdissection combined with two-dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma. Proteomics. 2003 Oct;3(10):1988-2001.

Alexakis N, Ghaneh P, Connor S, Raraty M, Sutton R, Neoptolemos JP. Duodenum- and spleen-preserving total pancreatectomy for end-stage chronic pancreatitis. Br J Surg. 2003 Nov;90(11):1401-8.

Crnogorac-Jurcevic T, Missiaglia E, Blaveri E, Gangeswaran R, Jones M, Terris B, Costello E, Neoptolemos JP, Lemoine NR. Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent. J Pathol. 2003 Sep;201(1):63-74.

Alexakis N, Bosonnet L, Connor S, Ellis I, Sutton R, Campbell F, Hughes M, Garvey C, Neoptolemos JP. Double resection for patients with pancreatic cancer and a second primary renal cell cancer. Dig Surg. 2003;20(5):428-32.

Rosso E, Alexakis N, Ghaneh P, Lombard M, Smart HL, Evans J, Neoptolemos JP. Pancreatic pseudocyst in chronic pancreatitis: endoscopic and surgical treatment. Dig Surg. 2003;20(5):397-406

Raraty MG, Neoptolemos JP. Compartments that cause the real damage in severe acute pancreatitis. Am J Respir Crit Care Med. 2003 Jul 15;168(2):141-2.

Bhatia M, Proudfoot AE, Wells TN, Christmas S, Neoptolemos JP, Slavin J. Treatment with Met-RANTES reduces lung injury in caerulein-induced pancreatitis. Br J Surg. 2003 Jun;90(6):698-704.

Connor S, Ghaneh P, Raraty M, Sutton R, Rosso E, Garvey CJ, Hughes ML, Evans JC, Rowlands P, Neoptolemos JP. Minimally invasive retroperitoneal pancreatic necrosectomy. Dig Surg. 2003;20(4):270-7.

Neoptolemos JP, Cunningham D, Friess H, Bassi C, Stocken DD, Tait DM, Dunn JA, Dervenis C, Lacaine F, Hickey H, Raraty MG, Ghaneh P, Buchler MW. Adjuvant therapy in pancreatic cancer: historical and current perspectives. Ann Oncol. 2003 May;14(5):675-92.

Bhatia M, Slavin J, Cao Y, Basbaum AI, Neoptolemos JP. Related Articles, Links

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury. Am J Physiol Gastrointest Liver Physiol. 2003 May;284(5):G830-6.

Evans JD, Cornford PA, Dodson A, Neoptolemos JP, Foster CS. Expression patterns of protein kinase C isoenzymes are characteristically modulated in chronic pancreatitis and pancreatic cancer. Am J Clin Pathol. 2003 Mar;119(3):392-402.

Hahn SA, Greenhalf B, Ellis I, Sina-Frey M, Rieder H, Korte B, Gerdes B, Kress R, Ziegler A, Raeburn JA, Campra D, Grutzmann R, Rehder H, Rothmund M, Schmiegel W, Neoptolemos JP, Bartsch DK. BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst. 2003 Feb 5;95(3):214-21.

Roche CJ, Hughes ML, Garvey CJ, Campbell F, White DA, Jones L, Neoptolemos JP. CT and pathologic assessment of prospective nodal staging in patients with ductal adenocarcinoma of the head of the pancreas. Am J Roentgenol. 2003 Feb;180(2):475-80.

Pardo OE, Lesay A, Arcaro A, Lopes R, Ng BL, Warne PH, McNeish IA, Tetley TD, Lemoine NR, Mehmet H, Seckl MJ, Downward J. Fibroblast growth factor 2-mediated translational control of IAPs blocks mitochondrial release of Smac/DIABLO and apoptosis in small cell lung cancer cells. Mol Cell Biol. 2003 Nov;23(21):7600-10.

Wang Y, Hallden G, Hill R, Anand A, Liu TC, Francis J, Brooks G, Lemoine N, Kirn D. E3 gene manipulations affect oncolytic adenovirus activity in immunocompetent tumor models. Nat Biotechnol. 2003 Nov;21(11):1328-35.

Crnogorac-Jurcevic T, Missiaglia E, Blaveri E, Gangeswaran R, Jones M, Terris B, Costello E, Neoptolemos JP, Lemoine NR. Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent. J Pathol. 2003 Sep;201(1):63-74.

Hallden G, Hill R, Wang Y, Anand A, Liu TC, Lemoine NR, Francis J, Hawkins L, Kirn D. Novel immunocompetent murine tumor models for the assessment of replication-competent oncolytic adenovirus efficacy. Mol Ther. 2003 Sep;8(3):412-24.

Wang Y, Groot-Wassink T, Lemoine NR, Vassaux G. Cellular characterization of the tropism of recombinant adenovirus for the adrenal glands. Eur J Clin Invest. 2003 Sep;33(9):794-8.

Radford KJ, Jackson AM, Wang JH, Vassaux G, Lemoine NR. Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: presentation of MART1 to CD8+ T cells. Int J Cancer. 2003 Jul 20;105(6):811-9.