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. 1984 Sep;81(18):5845–5848. doi: 10.1073/pnas.81.18.5845

Long-acting delivery systems for peptides: inhibition of rat prostate tumors by controlled release of [D-Trp6]luteinizing hormone-releasing hormone from injectable microcapsules.

T W Redding, A V Schally, T R Tice, W E Meyers
PMCID: PMC391808  PMID: 6237365

Abstract

Intramuscular injection of [6-D-tryptophan]-luteinizing hormone-releasing hormone [( D-Trp6]LH-RH) in microcapsules of poly(DL-lactide-co-glycolide), designed to release a controlled dose of the peptide over a 30-day period, decreased the weights of androgen-dependent Dunning prostate tumors in rats and suppressed serum testosterone levels more effectively than daily subcutaneous administration of equivalent or double doses of unencapsulated [D-Trp6]LH-RH. The microcapsules or daily injections of [D-Trp6]LH-RH also significantly decreased tumor volumes. Microcapsules of [D-Trp6]LH-RH or related analogs that can be injected once a month should make the treatment of patients with prostate carcinoma and other neoplasms or disorders more convenient and efficacious.

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Selected References

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

  1. Ahmed S. R., Brooman P. J., Shalet S. M., Howell A., Blacklock N. J., Rickards D. Treatment of advanced prostatic cancer with LHRH analogue ICI 118630: clinical response and hormonal mechanisms. Lancet. 1983 Aug 20;2(8347):415–419. doi: 10.1016/s0140-6736(83)90387-2. [DOI] [PubMed] [Google Scholar]
  2. Allen J. M., O'Shea J. P., Mashiter K., Williams G., Bloom S. R. Advanced carcinoma of the prostate: treatment with a gonadotrophin releasing hormone agonist. Br Med J (Clin Res Ed) 1983 May 21;286(6378):1607–1609. doi: 10.1136/bmj.286.6378.1607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Auclair C., Kelly P. A., Coy D. H., Schally A. V., Labrie F. Potent inhibitory activity of [D-Leu6, Des-Gly-NH2(10)]LHRH ethylamide on LH/hCG and PRL testicular receptor levels in the rat. Endocrinology. 1977 Dec;101(6):1890–1893. doi: 10.1210/endo-101-6-1890. [DOI] [PubMed] [Google Scholar]
  4. Beck L. R., Cowsar D. R., Lewis D. H., Gibson J. W., Flowers C. E., Jr New long-acting injectable microcapsule contraceptive system. Am J Obstet Gynecol. 1979 Oct 1;135(3):419–426. doi: 10.1016/0002-9378(79)90717-8. [DOI] [PubMed] [Google Scholar]
  5. Borgmann V., Nagel R., Al-Abadi H., Schmidt-Gollwitzer M. Treatment of prostatic cancer with LH-RH analogues. Prostate. 1983;4(6):553–568. doi: 10.1002/pros.2990040603. [DOI] [PubMed] [Google Scholar]
  6. Clayton R. N. Hypothalamic-releasing hormones: therapeutic potential of gonadotrophin-releasing hormone: a review. Q J Med. 1984 Winter;53(209):17–27. [PubMed] [Google Scholar]
  7. Corbin A., Beattie C. W., Tracy J., Jones R., Foell T. J., Yardley J., Rees R. W. The anti-reproductive pharmacology of LH-RH and agonistic analogues. Int J Fertil. 1978;23(2):81–92. [PubMed] [Google Scholar]
  8. Corbin A. From contraception to cancer: a review of the therapeutic applications of LHRH analogues as antitumor agents. Yale J Biol Med. 1982 Jan-Feb;55(1):27–47. [PMC free article] [PubMed] [Google Scholar]
  9. Coy D. H., Vilchez-Martinez J. A., Coy E. J., Schally A. V. Analogs of luteinizing hormone-releasing hormone with increased biological activity produced by D-amino acid substitutions in position 6. J Med Chem. 1976 Mar;19(3):423–425. doi: 10.1021/jm00225a018. [DOI] [PubMed] [Google Scholar]
  10. Heston W. D., Menon M., Tananis C., Walsh P. C. Androgen, estrogen and progesterone receptors of the R3327H Copenhagen rat prostatic tumor. Cancer Lett. 1979 Jan;6(1):45–50. doi: 10.1016/s0304-3835(79)80019-1. [DOI] [PubMed] [Google Scholar]
  11. Johnson E. S., Gendrich R. L., White W. F. Delay of puberty and inhibition of reproductive processes in the rat by a gonadotropin-releasing hormone agonist analog. Fertil Steril. 1976 Jul;27(7):853–860. doi: 10.1016/s0015-0282(16)41963-1. [DOI] [PubMed] [Google Scholar]
  12. Koutsilieris M., Tolis G. Gonadotropin-releasing hormone agonistic analogues in the treatment of advanced prostatic carcinoma. Prostate. 1983;4(6):569–577. doi: 10.1002/pros.2990040604. [DOI] [PubMed] [Google Scholar]
  13. Labrie F., Dupont A., Belanger A., Lacoursiere Y., Raynaud J. P., Husson J. M., Gareau J., Fazekas A. T., Sandow J., Monfette G. New approach in the treatment of prostate cancer: complete instead of partial withdrawal of androgens. Prostate. 1983;4(6):579–594. doi: 10.1002/pros.2990040605. [DOI] [PubMed] [Google Scholar]
  14. Laron Z., Kauli R., Zeev Z. B., Comaru-Schally A. M., Schally A. V. D-TRP5-analogue of luteinising hormone releasing hormone in combination with cyproterone acetate to treat precocious puberty. Lancet. 1981 Oct 31;2(8253):955–956. doi: 10.1016/s0140-6736(81)91155-7. [DOI] [PubMed] [Google Scholar]
  15. Markland F. S., Jr, Lee L. Characterization and comparison of the estrogen and androgen receptors from the R-3327 rat prostatic adenocarcinoma. J Steroid Biochem. 1979 Jan;10(1):13–20. doi: 10.1016/0022-4731(79)90135-3. [DOI] [PubMed] [Google Scholar]
  16. Pelletier G., Cusan L., Auclair C., Kelly P. A., Désy L., Labrie F. Inhibition of spermatogenesis in the rat by treatment with [D-Ala6, Des-Gly-NH210] LHRH ethylamide. Endocrinology. 1978 Aug;103(2):641–643. doi: 10.1210/endo-103-2-641. [DOI] [PubMed] [Google Scholar]
  17. Redding T. W., Schally A. V. Inhibition of prostate tumor growth in two rat models by chronic administration of D-Trp6 analogue of luteinizing hormone-releasing hormone. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6509–6512. doi: 10.1073/pnas.78.10.6509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sandow J., Von Rechenberg W., Jerzabek G., Stoll W. Pituitary gonadotropin inhibition by a highly active analog of luteinizing hormone-releasing hormone. Fertil Steril. 1978 Aug;30(2):205–209. doi: 10.1016/s0015-0282(16)43461-8. [DOI] [PubMed] [Google Scholar]
  19. Schally A. V., Comaru-Schally A. M., Redding T. W. Antitumor effects of analogs of hypothalamic hormones in endocrine-dependent cancers. Proc Soc Exp Biol Med. 1984 Mar;175(3):259–281. doi: 10.3181/00379727-175-41797. [DOI] [PubMed] [Google Scholar]
  20. Schally A. V., Coy D. H., Arimura A. LH-RH agonists and antagonists. Int J Gynaecol Obstet. 1980;18(5):318–324. doi: 10.1002/j.1879-3479.1980.tb00507.x. [DOI] [PubMed] [Google Scholar]
  21. Schally A. V., Redding T. W., Comaru-Schally A. M. Inhibition of prostate tumors by agonistic and antagonistic analogs of LH-RH. Prostate. 1983;4(6):545–552. doi: 10.1002/pros.2990040602. [DOI] [PubMed] [Google Scholar]
  22. Schally A. V., Redding T. W., Comaru-Schally A. M. Potential use of analogs of luteinizing hormone-releasing hormones in the treatment of hormone-sensitive neoplasms. Cancer Treat Rep. 1984 Jan;68(1):281–289. [PubMed] [Google Scholar]
  23. Shessel F. S., Block N. L., Stover B., Claflin A., Malinin T. I., Politano V. A. Endocrine manipulation of the Dunning prostatic adenocarcinoma. Invest Urol. 1980 May;17(6):529–533. [PubMed] [Google Scholar]
  24. Tolis G., Ackman D., Stellos A., Mehta A., Labrie F., Fazekas A. T., Comaru-Schally A. M., Schally A. V. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1658–1662. doi: 10.1073/pnas.79.5.1658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Walker K. J., Nicholson R. I., Turkes A. O., Turkes A., Griffiths K., Robinson M., Crispin Z., Dris S. Therapeutic potential of the LHRH agonist, ICI 118630, in the treatment of advanced prostatic carcinoma. Lancet. 1983 Aug 20;2(8347):413–415. doi: 10.1016/s0140-6736(83)90386-0. [DOI] [PubMed] [Google Scholar]
  26. Waxman J. H., Wass J. A., Hendry W. F., Whitfield H. N., Besser G. M., Malpas J. S., Oliver R. T. Treatment with gonadotrophin releasing hormone analogue in advanced prostatic cancer. Br Med J (Clin Res Ed) 1983 Apr 23;286(6374):1309–1312. doi: 10.1136/bmj.286.6374.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]

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