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. 1989 Nov;60(5):785–788. doi: 10.1038/bjc.1989.360

Urinary excretion of prostacyclin and thromboxane degradation products in patients with ovarian malignancy: effect of cytostatic treatment.

A Aitokallio-Tallberg 1, L Viinikka 1, O Ylikorkala 1
PMCID: PMC2247297  PMID: 2803956

Abstract

We studied the effect of ovarian cancer and its chemotherapy on the urinary excretion of prostacyclin (PGI2) and thromboxane A2 (TxA2) hydration and metabolic products. In six patients we measured 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha (PGI2 products) and thromboxane B2 (TxB2) and 2,3-dinor-TxB2 (TxA2 products) by HPLC followed by radioimmunoassay before, during and after the combined infusion of cisplatin, 4'epi-adriamycin and cyclophosphamide. Before the first cytostatic infusion, the urinary excretion of prostanoids was on average 4.4-5.8 times higher than in patients with ovarian endometriosis (n = 19). The infusion of cytostatics led to a 50-120% rise in the excretion of prostanoids during the first post-infusion 9 hours, but in the subsequent 10 hours their output was 25-45% below the initial value and remained low for at least 2 weeks. Following repetitive courses of cytostatics (2-4 per patient), prostanoid excretion tended to normalise. These data suggest that ovarian cancer is associated with increased production of PGI2 and TxA2, and that cytostatics suppress this production. This may be of biological significance in tumour behaviour and in the effect of cytostatics.

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Selected References

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  1. Aitokallio-Tallberg A. M., Viinikka L. U., Ylikorkala R. O. Increased synthesis of prostacyclin and thromboxane in human ovarian malignancy. Cancer Res. 1988 May 1;48(9):2396–2398. [PubMed] [Google Scholar]
  2. Aitokallio-Tallberg A., Viinikka L., Ylikorkala O. Urinary 6-keto-prostaglandin F1a in patients with gynaecological tumours. Cancer Lett. 1987 Feb;34(2):201–206. doi: 10.1016/0304-3835(87)90011-5. [DOI] [PubMed] [Google Scholar]
  3. Alam M., Jogee M., MacGregor W. G., Dowdell J. W., Elder M. G., Myatt L. Peripheral plasma immunoreactive 6-oxo-prostaglandin F1 alpha and gynaecological tumours. Br J Cancer. 1982 Mar;45(3):384–389. doi: 10.1038/bjc.1982.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bennett A., Berstock D. A., Carroll M. A. Increased survival of cancer-bearing mice treated with inhibitors of prostaglandin synthesis alone or with chemotherapy. Br J Cancer. 1982 May;45(5):762–768. doi: 10.1038/bjc.1982.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bennett A. Prostanoids and cancer. Ann Clin Res. 1984;16(5-6):314–317. [PubMed] [Google Scholar]
  6. Brash A. R., Jackson E. K., Saggese C. A., Lawson J. A., Oates J. A., FitzGerald G. A. Metabolic disposition of prostacyclin in humans. J Pharmacol Exp Ther. 1983 Jul;226(1):78–87. [PubMed] [Google Scholar]
  7. Dawood M. Y., Khan-Dawood F. S., Wilson L., Jr Peritoneal fluid prostaglandins and prostanoids in women with endometriosis, chronic pelvic inflammatory disease, and pelvic pain. Am J Obstet Gynecol. 1984 Feb 15;148(4):391–395. doi: 10.1016/0002-9378(84)90713-0. [DOI] [PubMed] [Google Scholar]
  8. Deliconstantinos G. Physiological aspects of membrane lipid fluidity in malignancy. Anticancer Res. 1987 Sep-Oct;7(5B):1011–1021. [PubMed] [Google Scholar]
  9. Fischer S., Bernutz C., Meier H., Weber P. C. Formation of prostacyclin and thromboxane in man as measured by the main urinary metabolites. Biochim Biophys Acta. 1986 Apr 15;876(2):194–199. doi: 10.1016/0005-2760(86)90274-2. [DOI] [PubMed] [Google Scholar]
  10. FitzGerald G. A., Pedersen A. K., Patrono C. Analysis of prostacyclin and thromboxane biosynthesis in cardiovascular disease. Circulation. 1983 Jun;67(6):1174–1177. doi: 10.1161/01.cir.67.6.1174. [DOI] [PubMed] [Google Scholar]
  11. Gorman R. R., Bunting S., Miller O. V. Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins. 1977 Mar;13(3):377–388. doi: 10.1016/0090-6980(77)90018-1. [DOI] [PubMed] [Google Scholar]
  12. Hainsworth J. D., Grosh W. W., Burnett L. S., Jones H. W., 3rd, Wolff S. N., Greco F. A. Advanced ovarian cancer: long-term results of treatment with intensive cisplatin-based chemotherapy of brief duration. Ann Intern Med. 1988 Feb;108(2):165–170. doi: 10.7326/0003-4819-108-2-165. [DOI] [PubMed] [Google Scholar]
  13. Honn K. V., Bockman R. S., Marnett L. J. Prostaglandins and cancer: a review of tumor initiation through tumor metastasis. Prostaglandins. 1981 May;21(5):833–864. doi: 10.1016/0090-6980(81)90240-9. [DOI] [PubMed] [Google Scholar]
  14. Honn K. V., Busse W. D., Sloane B. F. Prostacyclin and thromboxanes. Implications for their role in tumor cell metastasis. Biochem Pharmacol. 1983 Jan 1;32(1):1–11. doi: 10.1016/0006-2952(83)90644-5. [DOI] [PubMed] [Google Scholar]
  15. Honn K. V., Cicone B., Skoff A. Prostacyclin: a potent antimetastatic agent. Science. 1981 Jun 12;212(4500):1270–1272. doi: 10.1126/science.7015512. [DOI] [PubMed] [Google Scholar]
  16. Honn K. V., Meyer J. Thromboxanes and prostacyclin: positive and negative modulators of tumor growth. Biochem Biophys Res Commun. 1981 Oct 30;102(4):1122–1129. doi: 10.1016/s0006-291x(81)80128-3. [DOI] [PubMed] [Google Scholar]
  17. Karmali R. A. Eicosanoids in neoplasia. Prev Med. 1987 Jul;16(4):493–502. doi: 10.1016/0091-7435(87)90063-6. [DOI] [PubMed] [Google Scholar]
  18. Mackay I. G., Muir A. L., Watson M. L. Contribution of prostaglandins to the systemic and renal vascular response to frusemide in normal man. Br J Clin Pharmacol. 1984 May;17(5):513–519. doi: 10.1111/j.1365-2125.1984.tb02383.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Patrono C., Ciabattoni G., Patrignani P., Filabozzi P., Pinca E., Satta M. A., van Dorne D., Cinotti G. A., Pugliese F., Pierucci A. Evidence for a renal origin of urinary thromboxane B2 in health and disease. Adv Prostaglandin Thromboxane Leukot Res. 1983;11:493–498. [PubMed] [Google Scholar]
  20. Patrono C., Pugliese F., Ciabattoni G., Patrignani P., Maseri A., Chierchia S., Peskar B. A., Cinotti G. A., Simonetti B. M., Pierucci A. Evidence for a direct stimulatory effect of prostacyclin on renin release in man. J Clin Invest. 1982 Jan;69(1):231–239. doi: 10.1172/JCI110435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Roberts L. J., 2nd, Sweetman B. J., Oates J. A. Metabolism of thromboxane B2 in man. Identification of twenty urinary metabolites. J Biol Chem. 1981 Aug 25;256(16):8384–8393. [PubMed] [Google Scholar]
  22. Rosenkranz B., Fischer C., Weimer K. E., Frölich J. C. Metabolism of prostacyclin and 6-keto-prostaglandin F1 alpha in man. J Biol Chem. 1980 Nov 10;255(21):10194–10198. [PubMed] [Google Scholar]
  23. Stamford I. F., Melhuish P. B., Carroll M. A., Corrigan C. J., Patel S., Bennett A. Survival of mice with NC carcinoma is unchanged by drugs that are thought to inhibit thromboxane synthesis or increase prostacyclin formation. Br J Cancer. 1986 Aug;54(2):257–263. doi: 10.1038/bjc.1986.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sundström H., Ylikorkala O., Kauppila A. Serum selenium and thromboxane in patients with gynaecological cancer. Carcinogenesis. 1986 Jul;7(7):1051–1052. doi: 10.1093/carcin/7.7.1051. [DOI] [PubMed] [Google Scholar]
  25. Viinikka L., Ylikorkala O. Measurement of thromboxane B2 in human plasma or serum by radioimmunoassay. Prostaglandins. 1980 Oct;20(4):759–766. doi: 10.1016/0090-6980(80)90114-8. [DOI] [PubMed] [Google Scholar]
  26. Von Hoff D. D., Rozencweig M. cis-Diamminedichloroplatinum(II): a metal complex with significant anticancer activity. Adv Pharmacol Chemother. 1979;16:273–298. doi: 10.1016/s1054-3589(08)60247-1. [DOI] [PubMed] [Google Scholar]
  27. Wilson T. W. Responses to furosemide in normotensive and hypertensive subjects. Clin Pharmacol Ther. 1983 Nov;34(5):590–595. doi: 10.1038/clpt.1983.220. [DOI] [PubMed] [Google Scholar]
  28. Ylikorkala D., Viinikka L. Measurement of 6-keto-prostaglandin E1 alpha in human plasma with radioimmunoassay: effect of prostacyclin infusion. Prostaglandins Med. 1981 Apr;6(4):427–436. doi: 10.1016/0161-4630(81)90075-6. [DOI] [PubMed] [Google Scholar]
  29. Ylikorkala O., Kauppila A., Viinikka L. Effect of cytostatics on prostaglandin F2 alpha prostacyclin, and thromboxane in patients with gynecologic malignancies. Obstet Gynecol. 1981 Oct;58(4):483–486. [PubMed] [Google Scholar]
  30. Ylikorkala O., Koskimies A., Laatkainen T., Tenhunen A., Viinikka L. Peritoneal fluid prostaglandins in endometriosis, tubal disorders, and unexplained infertility. Obstet Gynecol. 1984 May;63(5):616–620. [PubMed] [Google Scholar]
  31. Ylikorkala O., Kuusi T., Tikkanen M. J., Viinikka L. Desogestrel- and levonorgestrel-containing oral contraceptives have different effects on urinary excretion of prostacyclin metabolites and serum high density lipoproteins. J Clin Endocrinol Metab. 1987 Dec;65(6):1238–1242. doi: 10.1210/jcem-65-6-1238. [DOI] [PubMed] [Google Scholar]
  32. Ylikorkala O., Pekonen F., Viinikka L. Renal prostacyclin and thromboxane in normotensive and preeclamptic pregnant women and their infants. J Clin Endocrinol Metab. 1986 Dec;63(6):1307–1312. doi: 10.1210/jcem-63-6-1307. [DOI] [PubMed] [Google Scholar]

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