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A comparison of the therapeutic effectiveness of gastrin neutralisation in two human gastric cancer models: relation to endocrine and autocrine/paracrine gastrin mediated growth

Abstract

BACKGROUND Gastrin is a growth factor for established tumours.

AIMS To 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.

METHODS MGLVA1 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.

RESULTS In 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.

CONCLUSIONS Gastrimmune may have potential therapeutic benefit on gastrin sensitive gastric tumours and may interact with both endocrine and autocrine mediated growth pathways.

  • gastrin
  • gastric cancer
  • Gastrimmune
  • autocrine/paracrine growth
  • Abbreviations used in this paper

    ABC
    antigen binding capacity
    CCK
    cholecystokinin
    CCKBR
    CCKB/gastrin receptors
    DEPC
    diethyl pyrocarbonate
    G17
    gastrin 17
    GI
    gastrointestinal
    GlyG17
    glycine extended gastrin 17
    SCID
    severe combined immunodeficient
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