Skip to main content
Annals of Surgery logoLink to Annals of Surgery
. 1996 Jan;223(1):4–11. doi: 10.1097/00000658-199601000-00002

Progress toward hormonal therapy of gastrointestinal cancer.

R J Bold 1, J Ishizuka 1, C M Townsend Jr 1
PMCID: PMC1235057  PMID: 8554417

Abstract

OBJECTIVE: The authors discuss ongoing research to determine the mechanisms by which peptide hormones regulate growth of gastrointestinal cancer and ways in which this information might be used to develop noncytotoxic therapy. SUMMARY BACKGROUND: Approximately 100,000 people die of cancer of the gastrointestinal (GI) tract each year. Surgery is curative only when the tumor is localized. Chemotherapy and radiotherapy have limited efficacy for locally advanced or widespread disease. Various peptide hormones regulate the growth of these tumors. As for breast and prostate cancer, the growth regulatory effect of these hormones is being studied as a potential mechanism of hormonal therapy. CONCLUSION: Gut peptide hormones regulate the growth of GI malignancies through all-specific receptors and signal transduction pathways. Interruption or modification of these growth regulatory mechanisms may lead to specific noncytotoxic therapy. In combination with surgical extirpation, such hormonally based treatment may be curative of advanced GI cancer.

Full text

PDF
4

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anisowicz A., Bardwell L., Sager R. Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7188–7192. doi: 10.1073/pnas.84.20.7188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beauchamp R. D., Townsend C. M., Jr, Singh P., Glass E. J., Thompson J. C. Proglumide, a gastrin receptor antagonist, inhibits growth of colon cancer and enhances survival in mice. Ann Surg. 1985 Sep;202(3):303–309. doi: 10.1097/00000658-198509000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bold R. J., Ishizuka J., Townsend C. M., Jr, Thompson J. C. Biomolecular advances in gastrointestinal hormones. Arch Surg. 1993 Nov;128(11):1268–1273. doi: 10.1001/archsurg.1993.01420230096015. [DOI] [PubMed] [Google Scholar]
  4. Bold R. J., Lowry P. S., Ishizuka J., Battey J. F., Townsend C. M., Jr, Thompson J. C. Bombesin stimulates the in vitro growth of a human gastric cancer cell line. J Cell Physiol. 1994 Dec;161(3):519–525. doi: 10.1002/jcp.1041610315. [DOI] [PubMed] [Google Scholar]
  5. Bold R. J., Warren R. E., Ishizuka J., Cho-Chung Y. S., Townsend C. M., Jr, Thompson J. C. Experimental gene therapy of human colon cancer. Surgery. 1994 Aug;116(2):189–196. [PubMed] [Google Scholar]
  6. Cho-Chung Y. S., Clair T., Tortora G., Yokozaki H., Pepe S. Suppression of malignancy targeting the intracellular signal transducing proteins of cAMP: the use of site-selective cAMP analogs, antisense strategy, and gene transfer. Life Sci. 1991;48(12):1123–1132. doi: 10.1016/0024-3205(91)90449-l. [DOI] [PubMed] [Google Scholar]
  7. Cummings B. J. Radiation therapy for colorectal cancer. Surg Clin North Am. 1993 Feb;73(1):167–181. doi: 10.1016/s0039-6109(16)45935-9. [DOI] [PubMed] [Google Scholar]
  8. Evers B. M., Hurlbut S. C., Tyring S. K., Townsend C. M., Jr, Uchida T., Thompson J. C. Novel therapy for the treatment of human carcinoid. Ann Surg. 1991 May;213(5):411–416. doi: 10.1097/00000658-199105000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GREGORY R. A., TRACY H. J. THE CONSTITUTION AND PROPERTIES OF TWO GASTRINS EXTRACTED FROM HOG ANTRAL MUCOSA. Gut. 1964 Apr;5:103–114. [PMC free article] [PubMed] [Google Scholar]
  10. Hirai M., Ishizuka J., Hirai A., Bold R. J., Townsend C. M., Jr, Thompson J. C. Bombesin stimulates intracellular Ca2+ mobilization but not proliferation on human colon cancer cells. Life Sci. 1993;53(24):1859–1865. doi: 10.1016/0024-3205(93)90493-m. [DOI] [PubMed] [Google Scholar]
  11. Ishizuka J., Beauchamp R. D., Sato K., Townsend C. M., Jr, Thompson J. C. Novel action of transforming growth factor beta 1 in functioning human pancreatic carcinoid cells. J Cell Physiol. 1993 Jul;156(1):112–118. doi: 10.1002/jcp.1041560116. [DOI] [PubMed] [Google Scholar]
  12. Ishizuka J., Beauchamp R. D., Townsend C. M., Jr, Greeley G. H., Jr, Thompson J. C. Receptor-mediated autocrine growth-stimulatory effect of 5-hydroxytryptamine on cultured human pancreatic carcinoid cells. J Cell Physiol. 1992 Jan;150(1):1–7. doi: 10.1002/jcp.1041500102. [DOI] [PubMed] [Google Scholar]
  13. Ishizuka J., Martinez J., Townsend C. M., Jr, Thompson J. C. The effect of gastrin on growth of human stomach cancer cells. Ann Surg. 1992 May;215(5):528–534. doi: 10.1097/00000658-199205000-00016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ishizuka J., Townsend C. M., Jr, Bold R. J., Martinez J., Rodriguez M., Thompson J. C. Effects of gastrin on 3',5'-cyclic adenosine monophosphate, intracellular calcium, and phosphatidylinositol hydrolysis in human colon cancer cells. Cancer Res. 1994 Apr 15;54(8):2129–2135. [PubMed] [Google Scholar]
  15. Ishizuka J., Townsend C. M., Jr, Thompson J. C. Neurotensin regulates growth of human pancreatic cancer. Ann Surg. 1993 May;217(5):439–446. doi: 10.1097/00000658-199305010-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jensen E. V., Block G. E., Smith S., Kyser K., DeSombre E. R. Estrogen receptors and breast cancer response to adrenalectomy. Natl Cancer Inst Monogr. 1971 Dec;34:55–70. [PubMed] [Google Scholar]
  17. Johnson L. R. New aspects of the trophic action of gastrointestinal hormones. Gastroenterology. 1977 Apr;72(4 PT2):788–792. [PubMed] [Google Scholar]
  18. Levitan N. Chemotherapy in colorectal carcinoma. Surg Clin North Am. 1993 Feb;73(1):183–198. doi: 10.1016/s0039-6109(16)45936-0. [DOI] [PubMed] [Google Scholar]
  19. Marcus-Sekura C. J. Techniques for using antisense oligodeoxyribonucleotides to study gene expression. Anal Biochem. 1988 Aug 1;172(2):289–295. doi: 10.1016/0003-2697(88)90447-2. [DOI] [PubMed] [Google Scholar]
  20. Pawson T. Signal transduction--a conserved pathway from the membrane to the nucleus. Dev Genet. 1993;14(5):333–338. doi: 10.1002/dvg.1020140502. [DOI] [PubMed] [Google Scholar]
  21. Rozengurt E. Neuropeptides as cellular growth factors: role of multiple signalling pathways. Eur J Clin Invest. 1991 Apr;21(2):123–134. doi: 10.1111/j.1365-2362.1991.tb01801.x. [DOI] [PubMed] [Google Scholar]
  22. Spindel E. R., Giladi E., Segerson T. P., Nagalla S. Bombesin-like peptides: of ligands and receptors. Recent Prog Horm Res. 1993;48:365–391. doi: 10.1016/b978-0-12-571148-7.50017-8. [DOI] [PubMed] [Google Scholar]
  23. Thompson J. C. Humoral control of gut function. Am J Surg. 1991 Jan;161(1):6–18. doi: 10.1016/0002-9610(91)90354-g. [DOI] [PubMed] [Google Scholar]
  24. Townsend C. M., Jr, Singh P., Thompson J. C. Effects of gastrointestinal peptides on gastrointestinal cancer growth. Gastroenterol Clin North Am. 1989 Dec;18(4):777–791. [PubMed] [Google Scholar]
  25. Townsend C. M., Jr, Singh P., Thompson J. C. Gastrointestinal hormones and gastrointestinal and pancreatic carcinomas. Gastroenterology. 1986 Oct;91(4):1002–1006. doi: 10.1016/0016-5085(86)90707-9. [DOI] [PubMed] [Google Scholar]
  26. Wank S. A., Pisegna J. R., de Weerth A. Brain and gastrointestinal cholecystokinin receptor family: structure and functional expression. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8691–8695. doi: 10.1073/pnas.89.18.8691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. ZOLLINGER R. M., ELLISON E. H. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg. 1955 Oct;142(4):709-23; discussion, 724-8. [PMC free article] [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES