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Anti-gastrin antibodies raised by gastrimmune inhibit growth of the human colorectal tumour AP5

โœ Scribed by Susan A. Watson; Dov Michaeli; Steven Grimes; Teresa M. Morris; David Crosbee; Mark Wilkinson; Graham Robinson; John F. R. Robertson; Robert J. C. Steele; Jack D. Hardcastle


Book ID
102870044
Publisher
John Wiley and Sons
Year
1995
Tongue
French
Weight
823 KB
Volume
61
Category
Article
ISSN
0020-7136

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โœฆ Synopsis


The neutralising ability of rabbit anti-gastrin-I 7 (G 17) antiserum raised by Gastrimmune, an immunogen constructed of the N-terminal portion of human G I 7 conjugated to diptheria toxoid (DT), was evaluated. The anti-serum (denoted anti-G I 7 DT) was shown to displace '25[1] G I 7 from the gastrin receptors on AR42j cells. The therapeutic effect of the rabbit anti-G 17:DT anti-serum was evaluated on a freshly derived human colorectal cancer cell line, AP5, which was shown to express both gastrin receptors and gastrin immunoreactivity as assessed by immunocytochemistry. Rabbit anti-G I7:DT anti-serum was shown to block basal in vitro growth of AP5 cells when used at an antigen binding capacity of 3.75 X M. The same dilution of anti-serum completely reversed growth stimulated by human GI7 at concentrations of I X 10-10 and I x M but did not inhibit growth at I X M 617. When AP5 was grown as a xenograft in nude imice, the sensitivity to the proliferative effect of human G I 7 was; maintained. In addition, the basal growth of AP5 xenografts was significantly reduced by i.v. infusion of rabbit anti-G I7:DT anti-serum when compared to treatment with rabbit anti:DT control anti-serum. Thus anti-G I7:DT antibodies raised by Gastrimmune may be of clinical value in gastrin-sensitive tumours.


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