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150 THE POTENTIAL ROLE OF GASTRIN IN PANCREATIC CANCER PROGRESSION-RAISED SERUM AMIDATED GASTRIN AND PROGASTRIN LEVELS IN PATIENTS WITH ADVANCED PANCREATIC CANCER
A.D. Gilliam, P.A. Clarke, B.J. Rowlands, I.J. Beckingham, S.A. Watson. Academic Unit of Cancer Studies, Academic Department of Surgery, University Hospital, Nottingham NG7 2UH, UK
Aim: To assess the endocrine role of gastrin in pancreatic carcinoma progression.
Method: A prospective study was established in which patients with resectable (n=17) and advanced (n=68) pancreatic carcinoma had their serum assayed for amidated and progastrin. Hormone levels were compared to positive controls (patients undergoing liver resection for colonic metastases, n=24). Gastrin and CCK 2 receptor expression was measured in 17 resected pancreatic tumours and four pancreatic tumour cell lines by RT-PCR, using the SYBR green dye, and immunohistochemical staining or western blotting using antibodies directed against gastrin and CCK2.
Results: There was a significantly greater serum amidated gastrin and progastrin levels in patients with advanced pancreatic cancer when compared to patients with resectable disease (p=0.008* and 0.046*). Patients with advanced pancreatic cancer also had significantly greater amidated gastrin and progastrin levels than patients undergoing liver resection for colonic metastases (p=0.023*). There was, however, no significant difference in amidated gastrin levels in patients with resectable pancreatic carcinoma and patients with metastatic colonic carcinoma (p=0.09*). Gastrin and CCK 2 expression was confirmed at the gene level in 13 pancreatic adenocarcinomas by RT-PCR, and immunocytochemistry in 17 pancreatic tumours. Gastrin and CCK-2 expression was also demonstrated in all four pancreatic tumour cell lines at the gene and protein levels by RT-PCR and western blotting. (*Independent samples T-test.)
Conclusion: This study confirms the autocrine, paracrine and endocrine role of gastrin in pancreatic carcinoma progression. Increased plasma levels of amidated gastrin may be a future biomarker for advanced pancreatic cancer. Anti-gastrin therapy may represent a novel therapeutic strategy for the management of pancreatic cancer.
151 GEMCITABINE DOES NOT INHIBIT THE BIOLOGICAL ACTIVITY OF A HUMAN PANCREATIC TUMOUR GROWING IN THE PANCREAS OF IMMUNODEFICIENT MICE.
A.D. Gilliam, W.J. Speake, R.A. Dean, D. McWilliams, P.A. Clarke, T. Morris, S.A. Watson. …