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

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

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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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 24 print issues and online access $259.00 per year only $10.79 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS HYPOGLYCEMIC MECHANISM OF INTESTINAL BYPASS SURGERY IN TYPE 2 DIABETIC RATS Article Open access 03 November 2021 CHEMICAL PANCREATECTOMY IN NON-HUMAN PRIMATES ABLATES THE ACINI AND DUCTS AND ENHANCES BETA-CELL FUNCTION Article Open access 05 June 2023 COMPARISON OF THREE DIFFERENT ANASTOMOTIC METHODS OF SLEEVE GASTRECTOMY WITH 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 will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

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.


Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this


journal Receive 24 print issues and online access $259.00 per year only $10.79 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now


Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer


support SIMILAR CONTENT BEING VIEWED BY OTHERS HYPOGLYCEMIC MECHANISM OF INTESTINAL BYPASS SURGERY IN TYPE 2 DIABETIC RATS Article Open access 03 November 2021 CHEMICAL PANCREATECTOMY IN


NON-HUMAN PRIMATES ABLATES THE ACINI AND DUCTS AND ENHANCES BETA-CELL FUNCTION Article Open access 05 June 2023 COMPARISON OF THREE DIFFERENT ANASTOMOTIC METHODS OF SLEEVE GASTRECTOMY WITH


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


will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt


content-sharing initiative