ADAPTIVE AND INNATE IMMUNE RESPONSES
TRIGGERED TO NEUTRALIZE GASTRIN HORMONES
AS A THERAPY FOR GI CANCERS



CLINICAL

Pancreatic Cancer

1.  Gilliam AD, Topuzov EG et al., Randomised, double blind, placebo-controlled, multi-centre, group-sequential trial of G17DT for patients  with advanced pancreatic cancer unsuitable or unwilling to take chemotherapy.  Abstract no 2511, ASCO 2004 meeting publication.  Full paper:  An International Multicenter Randomized Controlled Trial of G17DT in Patients With Pancreatic Cancer.  Gilliam AD, Broome P, TopuzovEG, Garin A, et al.,  Pancreas 41 (3) 374-379      http://journals.lww.com/pancreasjournal/Abstract/2012/0400/An_International_Multicenter_Randomized_Controlled.4.aspx
2.  AD Gilliam, SA Watson.  Emerging biological therapies for pancreatic carcinoma.  Eur J Surg Oncol, 28(4): 370-8, 2002.
3.  SA Watson, AD Gilliam. G17DT - A New Weapon in the Therapeutic Armoury for Gastrointestinal Malignancy.  Exp Op Biol Ther, 1(2): 309-317, 2001.
4.   Shapiro J, Marshall J et al.  G17DT + gemcitabine (Gem) vs placebo + Gem in untreated subjects with advanced, recurrent or metastatic adenocarcinoma of the pancreas.  Results of a randomized, double-blind multinational, multicenter study.  Abstract no 4012, ASCO 2005 meeting publication.
5.  A multicenter phase II study of irinotecan in combination with G17DT immunogen in subjects with metastatic colorectal adenocarcinoma (CRC) refractory to previous irinotecan-based chemotherapy.  C Rocha Lima, R Buck, K Meyer, W Perkins, D Michaeli.  ASCO 2004 annual meeting poster publication.
6.  Phase II study of anti-gastrin-17 antibodies raised to G17DT in advanced pancreatic cancer.  Brett BT, Smith SC, Bouvier CV, Michaeli  D et al.,  J Clin Oncol 20 (20) 2002, 4225-31
7.  The Effect of Jaundice on the Generation of Anti-gastrin Antibodies in G17-DT Immunized Patients with Advanced Pancreatic Cancer.   A.S. Takhar, A.D. Gilliam, S.A. Watson, M. Henwood,B.J. Rowlands, D. Michaeli, P. Broome, I.J. Beckingham.  EJSO 32, 2006, 197-200
8. Gut. 2000 Apr; 46(4):582-3.  Towards immunotherapy for pancreatic cancer.  Brett BT, Caplin ME


Gastric Cancer

1. Ajani JA, Hecht JR, Ho L, et al An Open-Label, Multinational, Multicenter Study of G17DT Vaccination Combined with Cisplatin and 5-Fluorouracil in Patients with Untreated, Advanced Gastric or Gastroesophageal Cancer: The GC4 Study.   Cancer May 1, 2006 Vol 106 9, 1908-16
2. M Henwood, PA Clarke, AM Smith, SA Watson.Expression of gastrin in developing gastric adenocarcinoma.  Br J Surg,88(4): 564-568, 2001.


Colorectal Cancer

1.  AM Smith, T Justin, D Michaeli, SA Watson. Phase I/II study of G17:DT, an anti-gastrin immunogen, in advanced colorectal cancer.  Clin. Can. Res. 6: 4719-4724, 2001.
2.  A multicenter phase II study of irinotecan in combination with G17DT immunogen in subjects with metastatic colorectal adenocarcinoma (CRC) refractory to previous irinotecan-based chemotherapy.  C Rocha Lima, R Buck, K Meyer, W Perkins, D Michaeli.  ASCO 2004 annual meeting poster publication.
3.  SA Watson, TM Morris, DF McWilliams, JC Harris, A Smith, PA Clarke.  Potential role of endocrine gastrin in the colonic adenoma-carcinoma sequence.  Br J Cancer, 87:567-573, 2002.
4.  Pluzanska A.    ASCO: Aphton sponsored symposium May 2001.
5.  SA Watson, AD Gilliam, AM Smith.  Anti-Gastrin Hormone Therapy in the Treatment of Colorectal Cancer.  Drugs of the Future, 26(9): 865-872, 2001.
6.  AM Smith, SA Watson.  Review Article: gastrin and colorectal cancer.  Aliment.Pharmacol.Ther, 14(10):1231-1247, 2000.


PRECLINICAL

1.  SA Watson, AM Smith. Hypergastrinaemia promotes adenoma progression in the APCMin-/+ mouse model of familial adenomatous polyposis.  Cancer Res. 61: 625-631, 2001.
2.  SA Watson. Oncogenic targets of b-catenin-mediated transcription involved in the molecular pathogenesis of intestinal polyposis.  Lancet, 357(9256): 572-573, 2001
3.   AM Smith, T Morris, T Justin, D Michaeli, SA Watson. Gastrimmune induced anti-gastrin-17 antibodies inhibit acid secretion in a rat fistula model. Aliment Pharmacol Ther, 15(12): 1981-8, 2001.
4.  SA Watson, KE Robinson, D McWilliams, D Michaeli, AM Smith, G Robinson.  Transforming growth factor-a-mediated growth pathways in human gastro-intestinal cell lines in relation to the gastrin autocrine pathway.  Int. J.Cancer, 87:20-28, 2000.
5.  SA Watson, PA Clarke, TM Morris, ME Caplin. Antiserum raised against an epitope of the CCKB/gastrin receptor inhibits hepatic invasion of a human colon tumor.  Cancer Res. 60(20): 5902-5907, 2000.
6.   AM Smith, SA Watson. Gastrin And Gastrin Receptor Activation - An Early Event In The Adenoma-Carcinoma Sequence.  Gut.47: 820-824, 2000.
7. AM Smith, T Justin, D Michaeli, SA Watson. Phase I/II study of G17-DT, an anti-gastrin immunogen, in advanced colorectal cancer.  Clin Cancer Res. 6(12): 4719-24, 2000.
8.  ME Caplin, P Clarke, S Grimes, AP Dhillon, K Khan, K Savage, J Lewin, D Michaeli, RE Pounder, SA Watson.  Demonstration of new sites of expression of the CCK-B/gastrin receptor in pancreatic acinar AR42J cells using immunoelectron microscopy.  Regulatory Peptides, 84(1-3):81-89, 1999.
9.      SA Watson, D Michaeli, T Morris, P Clarke, A Varro, N Griffin, A Smith, T Justin and JD Hardcastle.  Antibodies raised by Gastrimmune inhibit the spontaneous metastases of a human colorectal tumour cell line, AP5LV.  Eur. J. Cancer, 35(8): 1286-1291, 1999.
10.  SA Watson, D Michaeli, S Grimes, T Morris, A Varro, P Clarke, AM Smith, TA Justin and JD Hardcastle.  A comparison of an anti-gastrin antibody and cytotoxic drugs in the therapy of human gastric ascites in scid mice.  Int. J. Cancer, 81(2): 248-254, 1999.
11.  SA Watson, TM Morris, A Varro, D Michaeli and AM Smith.  A comparison of the therapeutic effectiveness of gastrin neutralisation in two human gastric cancer models: relation to endocrine and autocrine/paracrine gastrin mediated growth.  Gut, 45(6): 812-817, 1999.
12.  A Smith, S Watson and JD Hardcastle.  Gastric carcinoid expresses the gastrin autocrine pathway. Br. J. Surg.85: 1285-1289, 1998.
13. SA Watson, D Michaeli, T Justin, S Grimes, TM Morris, G Robinson, PA Clarke and JD Hardcastle.  Pre-clinical evaluation of the gastrimmune immunogen alone and in combination with 5-Fluorouracil/leucovorin in a rat colorectal cancer model.  Int. J. Cancer75: 873-877, 1998.
14. SA Watson, PA Clarke, AM Smith, A Varro, D Michaeli, S Grimes, M Caplin and JD Hardcastle.  Expression of CCKB/gastrin receptor isoforms in gastrointestinal tumour cells.  Int. J. Cancer77: 572-577, 1998.
15. DF McWilliams, SA Watson, DM Crosbee, D Michaeli, R Seth.  Coexpression of gastrin and gastrin receptors (CCK-B and DCCK-B in gastrointestinal tumour cell lines.  Gut42 (6): 795-798, 1998.
16.  SA Watson and A Smith.  Gastrin in pancreatic tumours transfected with CCK-B receptors Gastroenterology,114: 419, 1997.
17. SA Watson, D Michaeli, S Grimes, TM Morris, G Robinson, A Varro, TA Justin, and JD Hardcastle.  Gastrimmune raises antibodies that neutralise amidated and glycine extended gastrin-17 and inhibit the growth of colon cancer.  Cancer Res.56: 880-885, 1996.
18.  SA Watson, D Michaeli, S Grimes, TM Morris, D Crosbee, M Wilkinson, JFR Robertson, RJC Steel and JD Hardcastle.  Anti-gastrin antibodies raised by  Gastrimmune inhibit the growth of human colorectal tumour cells.  Int. J. Cancer, 61: 233-240, 1995.
19.  SA Watson, T Clifford, T Sykes, E Robinson and RJC Steele.  Gastrin sensitivity of primary human colorectal cancer: the effect of gastrin receptor antagonism.  Eur. J. Cancer, 31A (12): 2086-2092, 1995.
20.  SA Watson.  Gastrin antagonist and gastrointestinal tumours.  Expert Opinion on Investigational Drugs.  4: 1253-1266, 1995.
21.  SA Watson, TL Clifford and RJC Steele.  Inhibitory effect of the gastrin receptor antagonist, CR2093 on the basal, gastrin stimulated and growth factor stimulated growth of the pancreatic cell line, AR42J.  Anti-Cancer Drugs,5: 591-594, 1994.
22.  SA Watson and RJC Steele.  Gastrin antagonists in the treatment of gastric cancer. Anti-Cancer Drugs, 4: 599-604, 1993.
23.   SA Watson, DL Morris, LG Durrant, JF Robertson and JD Hardcastle.  Inhibition of gastrin stimulated growth of gastrointestinal tumour cells by Octreotide and the gastrin/cholecystokinin receptor antagonists, Proglumide and Lorglumide.  Eur. J. Cancer,28A: 1462-1467, 1992.
24. SA Watson, DL Morris, FJ Robertson and JD Hardcastle.  Therapeutic effects of the gastrin receptor antagonist, CR2093 on  gastrointestinal tumour cell growth.  Br. J. Cancer,65: 879-883, 1992.
25.  Bold RJ, Ishizuka J et al. Gastrin stimulates growth of human colon cancer cells via a receptor other than CCK-A or CCK-B. Biochemical and Biophysical Research Communications. 1994; 202 (3): 1222-1226
26. Caplin ME, Millson C et al.. Serum gastrin levels and identification of CCK-B/gastrin receptor following partial hepatectomy for liver tumours in man. Gastroenterology 1996; 110 (4): A1162
27. Ciccotosto GD, McLeish A et al. Expression, processing and secretion of Gastrin in patients with colorectal carcinoma. Gastroenterology 1995; 109: 1142-1153
28.  DeWeerth A, Von Schrenck T et al. Human pancreatic cancer cell lines express the CCKB/gastrin receptor. Gastroenterology, 1994 A289
29.  Gilliam AD,  Morris TM, Watson SA.  G17DT Antibodies Inhibit Growth of a Human Pancreatic tumour growing in the pancreas of immunodeficient mice.  Poster of Distinction, American Gastroenterology Association Annual General Meeting, Atlanta, May 2001
30.  Iwase K, Evers MB et al. Regulation of growth of human gastric cancer by gastrin and glycine-extended pro-gastrin. Gastroenterology, 1997; 113: 782-790
31.  Justin T, Watson S, Michaeli D, Hardcastle J, Steele R.  Gastric acid suppression using anti-gastrin 17  antibodies produced by a gastrin immunogen, Gastrimmune, in an in vivo pig model.  Gastroenterology 1995.  108(4): 125.
32.  Koh TJ, Nicholls PJ et al, Glycine-extended gastrin promotes growth of a human hepatoma cell line.    Gastroenterology. 1996; 110(4): A1089
33.  Makishima R, Larkin P, Michaeli D, and Gaginella TS.  Active immunization against gastrin-17 with an   N-terminal derived immunogen inhibits gastric and duodenal lesions in rats. Gastroenterology 1994.  106: A824.
34.  Negre F, Fagot-Revurat P et al, Autocrine stimulation of AR4-2J rat pancreatic tumour cell growth by glycine- extended gastrin. Int J Cancer 1996; 66(5): 653-658
35. Seva C, Dickinson CJ, Yamada T.  Growth-promoting effects of glycine-extended progastrin. Science 1994; 265: 410-412
36. Smith AM, Watson SA et al. Gastrin may have an autocrine/paracrine role in Barrett’s oesophagus and oesophageal adenocarcinoma. Br. J. Surgery., 1996;84: 706
37.  Smith AM, Morris T, Michaeli D, Watson SA.  Gastrimmune induced anti-gastrin antibodies inhibit stimulated acid output in a rat gastric fistula model.  Gut 1999.   44: 379.
38. Smith AM, Watson SA. Review article: gastrin and colorectal cancer. Aliment Pharmacol Therap 2000; 14: 1231-1247
39.  Smith JP, Fantaskey AP, Liu G and Zagon IS. Ifentification of gastrin as a growth peptide in human pancreatic cancer. Am J Physiol 1995; 268: R135-R141
40.  Stepan V, Sawada M et al Glycine-extended gastrin exerts growth-promoting effects on colon cancer cell lines. Gastroenterology. 1996; 100(4): A1122
41.  Watson SA, Durrant LG et al. Growth-promoting action of gastrin on human colonic and gastric tumour cells cultured in vitro. Br. J. Surg., 1988; 75: 342-345
42.  Watson SA, Durrant LG, Crosbie JD, Morris DL. The in vitro growth response of primary human colorectal and gastric cancer cells to gastrin. Int J Cancer 1989; 43:692-696.
43.  Yao CZ, Bold RJ, Ishizuka J, Townsend Jr CM, Thompson JC. Growth of mouse hepatocytes is stimulated by gastrin. J Cell Physiol 1995; 163:532-537.


MISCELLANEOUS

1.  Stubbs M, Khan K, Watson SA, Savage K, Dhillon AP, Caplin ME.  Endocytosis of anti-CCK-B gastrin receptor antibody and effect on hepatoma cell lines.  J Histochem Cytochem 50(9): 1213-7, 2002.

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