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Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth.
The gastrin receptor antagonist, CR2093, competed with 125I-gastrin-17 (5 x 10(-10) M) for binding to gastrin receptors on the rat pancreatic adenocarcinoma, AR42J (CR2093 concentration inducing 50% of 125I-gastrin-17 binding (IC50) was 8 x 10(-5) M), on the human gastric adenocarcinoma, MKN45 (IC50...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1992
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977787/ https://www.ncbi.nlm.nih.gov/pubmed/1616859 |
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author | Watson, S. A. Crosbee, D. M. Morris, D. L. Robertson, J. F. Makovec, F. Rovati, L. C. Hardcastle, J. D. |
author_facet | Watson, S. A. Crosbee, D. M. Morris, D. L. Robertson, J. F. Makovec, F. Rovati, L. C. Hardcastle, J. D. |
author_sort | Watson, S. A. |
collection | PubMed |
description | The gastrin receptor antagonist, CR2093, competed with 125I-gastrin-17 (5 x 10(-10) M) for binding to gastrin receptors on the rat pancreatic adenocarcinoma, AR42J (CR2093 concentration inducing 50% of 125I-gastrin-17 binding (IC50) was 8 x 10(-5) M), on the human gastric adenocarcinoma, MKN45 (IC50 5.5 x 10(-5) M) and the human colo-rectal adenocarcinoma C523 (IC50 greater than 10(-4) M). Intravenous administration of CR2093 (40 mg kg-1 day-1) reduced the gastrin-17 stimulated growth of AR42J xenografts in nude mice to below that of the original basal growth (P = 0.0166 from basal and P = 0.0109 from gastrin stimulated growth). CR2093 administration also reduced the gastrin-stimulated growth of MKN45 xenografts (P = 0.045) but failed to inhibit the gastrin enhanced proliferation of C523 xenografts. This may be related to the affinity (Kd) of the gastrin receptors present on the xenograft lines as the Kds of the two xenografts inhibited by CR2093 were 4.6 x 10(-10) M (AR42J) and 1.2 x 10(-9) M (MKN45) respectively whereas the Kd of C523 was of higher affinity (2.2 x 10(-10) M). GR antagonists may be a viable therapeutic option for gastrin receptor positive, gastro-intestinal tumours. |
format | Text |
id | pubmed-1977787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1992 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-19777872009-09-10 Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth. Watson, S. A. Crosbee, D. M. Morris, D. L. Robertson, J. F. Makovec, F. Rovati, L. C. Hardcastle, J. D. Br J Cancer Research Article The gastrin receptor antagonist, CR2093, competed with 125I-gastrin-17 (5 x 10(-10) M) for binding to gastrin receptors on the rat pancreatic adenocarcinoma, AR42J (CR2093 concentration inducing 50% of 125I-gastrin-17 binding (IC50) was 8 x 10(-5) M), on the human gastric adenocarcinoma, MKN45 (IC50 5.5 x 10(-5) M) and the human colo-rectal adenocarcinoma C523 (IC50 greater than 10(-4) M). Intravenous administration of CR2093 (40 mg kg-1 day-1) reduced the gastrin-17 stimulated growth of AR42J xenografts in nude mice to below that of the original basal growth (P = 0.0166 from basal and P = 0.0109 from gastrin stimulated growth). CR2093 administration also reduced the gastrin-stimulated growth of MKN45 xenografts (P = 0.045) but failed to inhibit the gastrin enhanced proliferation of C523 xenografts. This may be related to the affinity (Kd) of the gastrin receptors present on the xenograft lines as the Kds of the two xenografts inhibited by CR2093 were 4.6 x 10(-10) M (AR42J) and 1.2 x 10(-9) M (MKN45) respectively whereas the Kd of C523 was of higher affinity (2.2 x 10(-10) M). GR antagonists may be a viable therapeutic option for gastrin receptor positive, gastro-intestinal tumours. Nature Publishing Group 1992-06 /pmc/articles/PMC1977787/ /pubmed/1616859 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Watson, S. A. Crosbee, D. M. Morris, D. L. Robertson, J. F. Makovec, F. Rovati, L. C. Hardcastle, J. D. Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth. |
title | Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth. |
title_full | Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth. |
title_fullStr | Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth. |
title_full_unstemmed | Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth. |
title_short | Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth. |
title_sort | therapeutic effect of the gastrin receptor antagonist, cr2093 on gastrointestinal tumour cell growth. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977787/ https://www.ncbi.nlm.nih.gov/pubmed/1616859 |
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