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Effects of new bisphosphonic acids on tumor-induced bone destruction in the rat

  • Original Papers
  • Experimental Oncology
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Summary

This report is concerned with therapeutic studies utilizing new bisphosphonic acids on tumor-induced osteolytic metastases. The bone metastases on SD rats were induced by intraarterial and intraosseous transplantation of Walker carcinosarcoma 256B ascites cells. The treatment was carried out using disodium-3-amino-1-hydroxypropylidene-1,1-bisphophonate (APD), diglycidyl-[3-(3,3-bisphosphono-3-hydroxy-propylamino)-2-hydroxypropyl-]urazol-Na2 (DDU) and 1,2,4-triglycidylurazol (TGU). The extent of bone metastases was determined by X-ray on the 5th and 10th days following tumor inoculation, as well as both microradiographically and histologically upon termination of the experiment.

High dose DDU produced a clear reduction of the tumor osteolysis, but these positive results were surpassed using APD. The best results were achieved by pretreatment with APD 24 h prior to tumor inoculation.

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References

  1. Abrams HL (1950) Skeletal metastases in carcinoma. Radiology 55:534

    Google Scholar 

  2. Atassi G, Dumont P, Fisher U, Zeidler M, Budnowski M (1984) Preclinical evaluation of the anti tumor activity of new epoxyde derivatives. Cancer Treat Rev, 11:99–110

    Google Scholar 

  3. van Breukelen FJM, Bijvoet OLM, Oosterom AT (1979) Inhibition of osteolytic bone lesions by 3-amino-1-hydroxy-propylidene-1,1-bisphosponate (APD). Lancet I (8120):803–805

    Google Scholar 

  4. Douglas DL, Cundy T, Hanis JA, Preston FE, Rusel RGG, Woodhead S (1980) Inhibitory action of dichloromethylene diphosphonate on bone resorption in man. In: Donath A, Courvoisier B (eds) Bone and tumors. Edition Medicine and Hygiene, Geneve, pp 161–165

    Google Scholar 

  5. Elomaa I, Blomquist C, Gröhn P (1983) Long-term controlled trial with diphosphonate in patients with osteolytic bone metastases. Lancet I (8317):146–149

    Google Scholar 

  6. Felix R, Fleisch H (1982) Chemie und Wirkung der Bisphosphonate. In: Ziegler R (ed) EHDP. Ein neues therapeutisches Prinzip bei Osteopathien und Calciumstoffwechselstörungen. Urban & Schwarzenberg, München Wien Baltimore

    Google Scholar 

  7. Fleisch H, Russel RGG, Francis MD (1969) Diphosphonates inhibit hydroxylapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 165:1262–1264

    Google Scholar 

  8. Frijlink WB, Bijvoet OLM, te Velde J, Heynen G (1979) Treatment of Paget's disease with (3-amino-1-hydroxypropylidene)-1,1-biphosphonate (APD). The Lancet I (8120):799–803

    Google Scholar 

  9. Galasko CSB (1981) Bone metastases studied by experimental models. Schweiz Med Wochenschr 111:1862–1868

    Google Scholar 

  10. Guatani A, Polentarutti N, Filippeschi S, Marmonti L, Corti F, Italia C, Coccioli G, Donelle MG, Montovani A, Garattini S (1984) Effects of disodium etidronate in murine tumor models. Eur J Cancer Clin Oncol 20 (5):685–693

    Google Scholar 

  11. Johnson KF, Wesseler MA, Martodam RR, Olson HM, Poser JW (1982) The effects of diphosphonates on tumor-induced hypercalcemia and osteolysis in Walker carcinosarcoma 256 (WLSG) in rats. Proc Am Assoc Cancer Res 23:896

    Google Scholar 

  12. Jung A, Fleisch H (1981) Les diphosphonated dans le traitement des metastases osseuses. Schweiz Med Wochenschr 111, 49:1878–1882

    Google Scholar 

  13. Jung A, Barres C, Mermillod B, Courvoisier B (1979) Effet de deux diphosphonates sur la lyse osseuse induite par des extraits tumoraux. Schweiz Med Wochenschr 109:1888–1890

    Google Scholar 

  14. Jung A, Bornand I, Mermillod B, Evuard C, Meunier PI (1984) Inhibition by diphosphonates of bone resorption induced by the Walker tumor of the rat. Cancer Res 44:3007–3011

    Google Scholar 

  15. Krempien B, Pfeilschifter I, Minne H (1982) Influence of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) on bone remodelling. In: Silbermann M, Slavkin HC (eds) Current advances in skeletogenesis. Proc 5th int workshop on calcified tissues. Diryat-Anarim, Israel, 117–122

    Google Scholar 

  16. Krempien B, Diel I, Jockle-Kretz B, Büchele R, Andre L (1984) Das Walker Carcino-Sarkom 256 als Modell für die Entwicklung von Knochenmetastasen. Untersuchungen zum Einfluß des Knochenstoffwechsels auf die Entwicklung von Knochenmetastasen. Verh Dtsch Ges Pathol 68:211–216

    Google Scholar 

  17. Manegold C, Krempien B (1984) Beckenkammnadelbiopsie in der Diagnostik von Knochen- und Knochenmarkserkrankungen. Dtsch Med Wochenschr 24:954–956

    Google Scholar 

  18. Martodam RR, Johnson KY, Jung A (1981) The effects of diphosphonates (bone seeking agents) on hypercalcemia and increased bone resorption in the rat Walker 256 tumor and in humans. 4th Annual San Antonio breast cancer symposium, Texas cancer therapy and research center of South Texas, USA

  19. Minne HW, Rane F, Klär H, Ziegler R, Bijvoet OLM (1980) Treatment of paraneoplastic hypercalcemia with a new diphosphonate (APD) in the animal experiment. In: Donath A, Convoisier B (eds) Bone and tumors, Medicine and Hygiene, Geneve, pp 166–169

    Google Scholar 

  20. Peto R, Pike MC, Armitage P, Brelow NE, Cox PR, Howard SV, Mantel N, McPherson U, Peto J, Smith PG (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. Br J Cancer 35:1–39

    Google Scholar 

  21. Rade J, Croese JW, Zurcher C, Enden-Vieveen MHM, van den Brondigh RJ, Hazil M, Haaijman JJ, Reitsma PH, Bijvoet OLM (1985) Influence of treatment with APD-bisphosphonate on the bone lesions in the mouse 5T2 multiple myeloma. Cancer 55:1030–1040

    Google Scholar 

  22. Reitsma PH, Bijvoet OLM, Verlinden-Ooms H, Wee-Pals van der LIA (1980) Kinetic studies of bone and mineral metabolism during treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in rats. Calcif Tissue Int 32:145–157

    Google Scholar 

  23. Reitsma PH, Teitelbaum SL, Bijvoet OLM, Hahn AJ (1982) Differential action of the bisphosphonates (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and disodium dichlormethylidene bisphosponate (Cl2MDP) on rat macrophage mediated bone resorption in vitro. 2. Clin Invest 70:927–933

    Google Scholar 

  24. Samuel AW, Rushton S, Galasko CS (1979) Effects of prostaglandin inhibitors and diphosphonates on tumor-mediated osteolysis. Br J Surg 66:901

    Google Scholar 

  25. Schürer CC, Peters U, Tischer JT (1981) Therapeutische Möglichkeiten bei paraneoplastischer Hypercalcämie. Med Welt 32:1219

    Google Scholar 

  26. Sleebohm HP, Bijvoet OLM, van Oosterom AT, Gleed JH, O'Riordan JL (1983) Comparison of intravenous (3-amino-1-hydroxypropylidene)-1,1-bisphosponate and volume repletion in tumor-induced hypercalcemia. Lancet II (8344):239–243

    Google Scholar 

  27. Wingen F, Schmähl D (1985) Distribution of 3-amino-1-hydroxypropane-1,1-diphosphonic acid (APD) in rats and effects on rat osteosarcoma. Arzneimittelforsch 35 (II) 10, 1565–1571 (1985)

    Google Scholar 

  28. Wingen F, Schmähl D (in preparation) Effects of new bisphosphonic acids in subcutaneously growing Walker carcinomas in rats

  29. Wingen F, Schmähl D, Berger MR, Spring H (1984) Intraosseosly transplantable osteosarcoma with regularly disseminating pulmonary metastases in rats. Cancer Lett 23:201–211

    Google Scholar 

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Authors and Affiliations

  1. Institute of Toxicology and Chemotherapy, German Cancer Research Center, Im Neuenheimer Feld 280, D-6900, Heidelberg, Germany

    Franz Wingen

  2. Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, D-6900, Heidelberg, Germany

    Thomas Eichmann & Burkhard Krempien

  3. Department of Internal Medicine I, University of Heidelberg, Bergheimer Straße, D-6900, Heidelberg, Germany

    Christian Manegold

Authors
  1. Franz Wingen
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  2. Thomas Eichmann
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  3. Christian Manegold
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  4. Burkhard Krempien
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Dedicated to Professor Dietrich Schmähl on the occasion of his 60th birthday

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Wingen, F., Eichmann, T., Manegold, C. et al. Effects of new bisphosphonic acids on tumor-induced bone destruction in the rat. J Cancer Res Clin Oncol 111, 35–41 (1986). https://doi.org/10.1007/BF00402773

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  • DOI: https://doi.org/10.1007/BF00402773

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