Abstract |
The effect of gastrin neutralization was evaluated on the in vivo growth of the rat colon line, DHDK12, which expressed cholecystokinin B/ gastrin receptors and secreted glycine-extended gastrin-17 (G17). Gastrin neutralization was achieved by administration of the immunogen, Gastrimmune, which is composed of the amino terminal portion of G17 linked to a diphtheria toxoid. A rat-specific version of Gastrimmune was used to preimmunize rats, with control animals receiving diphtheria toxoid only. The antibodies raised neutralized both carboxy-amidated and glycine-extended G17. The tumor was implanted into the muscle layer of the abdominal wall, and rats immunized with Gastrimmune had significantly reduced median cross-sectional tumor areas (70.2% reduction; P = 0.005) and weights (56.5% reduction; P = 0.0078)) when compared to control rats. Histological analysis revealed that the tumors had an enhanced degree of necrosis, with the area of viable tumor in the Gastrimmune-immunized rat reduced to 40.3% compared to 58.6% in the control rats (P = 0.003). Immunization with Gastrimmune raised antibodies that inhibited the growth of a rat colon tumor. This could have been mediated by neutralization of both serum G17 and cell-associated precursor gastrin molecules.
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Authors | S A Watson, D Michaeli, S Grimes, T M Morris, G Robinson, A Varro, T A Justin, J D Hardcastle |
Journal | Cancer research
(Cancer Res)
Vol. 56
Issue 4
Pg. 880-5
(Feb 15 1996)
ISSN: 0008-5472 [Print] United States |
PMID | 8631028
(Publication Type: Journal Article)
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Chemical References |
- Cancer Vaccines
- Diphtheria Toxoid
- Gastrins
- Immunoglobulin Isotypes
- Immunotoxins
- Receptor, Cholecystokinin B
- Receptors, Cholecystokinin
- gastrin immunogen
- glycine-extended gastrin 17
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Topics |
- Amino Acid Sequence
- Animals
- Antibody Formation
- Antigen-Antibody Reactions
- Cancer Vaccines
- Cell Division
- Colonic Neoplasms
(pathology, therapy)
- Diphtheria Toxoid
(immunology, therapeutic use)
- Drug Design
- Gastrins
(biosynthesis, immunology, therapeutic use)
- Humans
- Immunoglobulin Isotypes
(biosynthesis)
- Immunotoxins
(therapeutic use)
- Male
- Molecular Sequence Data
- Rabbits
- Rats
- Rats, Inbred Strains
- Receptor, Cholecystokinin B
- Receptors, Cholecystokinin
(biosynthesis)
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