Inhibitory effect of a cholecystokinin antagonist on pancreatic carcinogenesis after pancreatobiliary diversion

ABSTRACT The role of cholecystokinin (CCK) has been explored in pancreatic carcinogenesis following pancreatobiliary diversion (PBD), using the specific CCK receptor antagonist CR-1409. Male

Wistar rats (n = 80) weighing 70-100 g were given weekly i.p. injections of azaserine (30 mg kg-1 week-1) for 3 consecutive weeks. One week later animals were randomised to receive either

PBD or sham PBD and thereafter to receive s.c. injections of either saline or CR-1409 (10 mg kg-1 day-1, 5 days a week). Six months after operation surviving rats were killed as follows:

sham + saline 20, PBD + saline 19, sham + CR-1409 14, PBD + CR-1409 11. Cardiac blood was taken for CCK assay and the pancreas was excised for wet weight measurement and quantitative

estimation of atypical acinar cell foci (AACF), the precursor of carcinoma. PBD reduced median body weight (3-20% less than shams) but trebled the absolute and relative pancreatic weights (P

< 0.001). CR-1409 blunted this adaptive response to PBD, reducing absolute pancreatic weight by 35% (P < 0.005). PBD quadrupled circulating CCK concentrations, regardless of the

antagonist treatment. Acidophilic AACF occurred only in rats with PBD. CR-1409 markedly reduced the number of observed acidophilic AACF by 90% (P < 0.001) and the number of foci per

pancreas by 93% (P < 0.001). Moreover, CR-1409 reduced the mean focal diameter of each lesion by 18% (P < 0.005), the mean focal volume by 58% (P < 0.05) and the percentage of

pancreas occupied by acidophilic foci by 95% (P < 0.001). PBD enhances pancreatic carcinogenesis by causing hypercholecystokininaemia, and CR-1409 largely inhibits this enhancement.

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TRANSIT BIPARTITION USING AN OBESE RODENT MODEL Article Open access 01 December 2023 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Surgery, Royal Postgraduate Medical School,

Hammersmith Hospital, London, UK P Watanapa Authors * P Watanapa View author publications You can also search for this author inPubMed Google Scholar * B Flaks View author publications You

can also search for this author inPubMed Google Scholar * H Oztas View author publications You can also search for this author inPubMed Google Scholar * PH Deprez View author publications

You can also search for this author inPubMed Google Scholar * J Calam View author publications You can also search for this author inPubMed Google Scholar * RCN Williamson View author

publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Watanapa, P., Flaks, B., Oztas,

H. _et al._ Inhibitory effect of a cholecystokinin antagonist on pancreatic carcinogenesis after pancreatobiliary diversion. _Br J Cancer_ 67, 663–667 (1993).

https://doi.org/10.1038/bjc.1993.123 Download citation * Issue Date: 01 April 1993 * DOI: https://doi.org/10.1038/bjc.1993.123 SHARE THIS ARTICLE Anyone you share the following link with

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