Article
A comparison of the therapeutic effectiveness of gastrin
neutralisation in two human gastric cancer models: relation to
endocrine and autocrine/paracrine gastrin mediated
growth
S A Watsona, T M Morrisa, A Varrob, D Michaelic, A M Smitha
a Academic Unit of
Cancer Studies, Department of Surgery, University of Nottingham, UK, b Department of Physiology, University of
Liverpool, UK, c Aphton
Corporation, California, USA
Correspondence to: Dr S A Watson, Academic Unit of Cancer Studies, Department of Surgery, University of Nottingham, UK.
Accepted for publication 6 July 1999
BACKGROUND
Gastrin is a growth
factor for established tumours.
AIMSTo investigate the therapeutic
effect of antibodies, raised against the Gastrimmune immunogen, which
neutralise the glycine extended and carboxy amidated forms of gastrin
17 in two human gastric cancer models.
METHODSMGLVA1 cells (which have a
gastrin autocrine/paracrine phenotype) and ST16 cells (which have an
endocrine phenotype) were injected into the peritoneal cavity of SCID
mice. Peritoneal tumours, ascites, and cachexia formation occurred,
with the monitored endpoint being morbidity.
RESULTSIn MGLVA1 cells,
intravenous administration of antibodies raised against Gastrimmune
increased the 50% median survived by 25% at three different initial
cell seeding concentrations (1 × 106-5 × 105 per mouse). In ST16 cells, the effect of Gastrimmune
induced antibodies on time to morbidity was greatest at the lowest cell seeding concentration (5 × 105 cells/mouse) with the 50%
median survival increased by 74% and overall survival achieved in 38%
of the mice.
CONCLUSIONSGastrimmune may have
potential therapeutic benefit on gastrin sensitive gastric tumours and
may interact with both endocrine and autocrine mediated growth pathways.
Keywords: gastrin; gastric cancer; Gastrimmune; autocrine/paracrine growth
© 1999 by Gut
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