Urological Research

, Volume 7, Issue 2, pp 71–78 | Cite as

Effect of intralesional and systemic BCG-application or a combined cyclophosphamide/BCG treatment on experimental bladder cancer

  • H. -D. Adolphs
  • J. Thiele
  • H. Kiel


Infiltrating transitional cell carcinomas of the urinary bladder were induced by ingestion of 0.188% N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) in 145 female Wistar rats. After 8 months of carcinogen exposure, the animals were divided into different treatment groups. They received cyclophosphamide intraperitoneally as a single injection or BCG either once intralesionally or weekly subcutaneously or a combination of cyclophosphamide followed by subcutaneous BCG. The treatment effect was determined by body weight measurements and bladder tumour weight after 12 months. Compared with a control group statistically significant differences of bladder tumour weights were found after treatment with BCG alone or in combination with cyclophosphamide. Intralesional BCG resulted in an insignificant increase of tumour weights.

Key words

Experimental bladder carcinoma Cyclophosphamide Tumour weight 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adolphs, H.-D., Thiele, J., Kiel, H., Steffens, L.: Induction of transitional cell carcinoma of the urinary bladder in rats by feeding N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. Histological and ultrastructural findings. Urological Research 6, 19 (1978)Google Scholar
  2. 2.
    Amiel, J. L., Berardet, M.: Factor time for active immunotherapy after cytoreductive chemotherapy. European Journal of Cancer 10, 89 (1974)Google Scholar
  3. 3.
    Baldwin, R. W., Price, M. R., Robins, R. A.: Blocking of lymphocyte-mediated cytotoxicity for rat hepatoma cells by tumourspecific antigen-antibody complexes. Nature (New Biol.) 238, 185 (1972)Google Scholar
  4. 4.
    Baldwin R. W., Pimm, M. V.: BCG immunotherapy of pulmonary growths from intravenously t transferred rat tumour cells. British Journal of Cancer 27, 48 (1973)Google Scholar
  5. 5.
    Bansal, S. C., Sjögren, H. O.: Effects of BCG on various facets of the immune response against polyoma tumors in rats. International Journal of Cancer 11, 162 (1973)Google Scholar
  6. 6.
    Bast, R. C., Zbar, B., Borsos, T., Rapp, H. J.: BCG and cancer (1). New England Journal of Medicine 290, 1413 (1974)Google Scholar
  7. 7.
    Bast, R. C., Zbar, B., Borsos, T., Rapp, H. J.: BCG and cancer (1). New England Journal of Medicine 290, 1458 (1974)Google Scholar
  8. 8.
    Bekierkunst, A.: Immunotherapy of cancer with nonliving mycobacteria and cord factor (trehalose-6,6′-dimycolate) in aqueous medium. Journal of the National Cancer Institute 57, 963 (1976)Google Scholar
  9. 9.
    Bogden, A. E., Esber, H. J., Taylor, D. J., Gray, J. H.: Comparative study on the effects of surgery, chemotherapy, and immunotherapy, alone and in combination, on metastases of the 13762 mammary adenocarcinoma. Cancer Research 34, 1627 (1974)Google Scholar
  10. 10.
    Buskirk, H. H., Crim, J. A., Petering, H. G., Merritt, K., Johnson, A. G.: Effect of uracil mustard and several antitumor drugs on the primary antibody response in rats and mice. Journal of the National Cancer Institute 34, 747 (1965)Google Scholar
  11. 11.
    Chaussoux, D., Salomon, J.-C.: Therapeutic effect of intratumoral injection of BCG and other substances in rats and mice. International Journal of Cancer 16, 515 (1975)Google Scholar
  12. 12.
    Currie G. A., Bagshawe, K. D.: Active immunotherapy with corynebacterium parvum and chemotherapy in murine fibrosarcomas. British Medical Journal 1, 541 (1970)Google Scholar
  13. 13.
    Daly, J. J., Prout Jr., G. R., Ahl, C. A.: Demonstration of specific antigen in N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide induced rat bladder tumor. Journal of Urology 109, 253 (1973)Google Scholar
  14. 14.
    DeKernion, J. B., Soloway, M. S., Persky, L.: Chemotherapy of experimental transitional-cell carcinoma. Urology 4, 63 (1974)Google Scholar
  15. 15.
    Ertürk, E., Price, J. M., Morris, J. E., Cohen, S. M., Leith, R. S., von Esch, A. M., Crovetti, A. J.: The production of carcinoma of the urinary bladder in rats by feeding N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. Cancer Research 27, 1998 (1967)Google Scholar
  16. 16.
    Ertürk, E., Cohen, S. M., Price, J. M., Bryan, G. T.: Pathogenesis, histology, and transplantability of urinary bladder carcinomas induced in albino rats by oral administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. Cancer Research 29, 228 (1969)Google Scholar
  17. 17.
    Gheorghiu, M., Chambon, L.: Preservation of fresh BCG-scarification vaccine at 4,-25, and-70°C. Cancer Immunology and Immunotherapy 1, 11 (1976)Google Scholar
  18. 18.
    Gray, G. R., Ribi, E., Granger, D., Parker, R., Azuma, I., Yamamoto, K.: Brief communication: Immunotherapy of cancer: tumor suppression and regression by cell walls of mycobacterium phlei attached to oil problets. Journal of the National Cancer Institute 55, 727 (1975)Google Scholar
  19. 19.
    Gutterman, J., Mavlight, G., McBride, C. E., Frei III, E., Hersh E. M.: BCG stimulation of immune responsiveness in patients with malignant melanoma. Cancer 32, 321 (1973)Google Scholar
  20. 20.
    Haines, R. F., Johnson, A. E., Petering, H. G.: Variable influences of antitumor drugs and progestational agents on immune responses in rodents. Federation Proceedings 26, 934 (1967)Google Scholar
  21. 21.
    Halle-Pannenko, O., Bouret, C., Kamel, M.: Comparison of various BCG preparations in the EORTC-ICIG experimental screening for systemic immunity adjuvants applicable to cancer immunotherapy. Cancer Immunology and Immunotherapy 1, 17 (1976)Google Scholar
  22. 22.
    Hanna Jr., M. G., Peters, L. C., Gutterman, J. U., Hersh, E. M.: Evaluation of BCG administered by scarification for immunotherapy of metastatic hepatocarcinoma in the guinea pig. Journal of the National Cancer Institute 56, 1013 (1976)Google Scholar
  23. 23.
    Harmel Jr., P. R., Zbar, B., Rapp, H. J.: Brief communication: Suppression and regression of a transplanted tumor in the guinea pig colon mediated by mycobacterium bovis, strain BCG. Journal of the National Cancer Institute 54, 515 (1975)Google Scholar
  24. 24.
    Jacobs, J. B., Arai, M., Cohen, S. M., Friedell, G. H.: A long-term study of reversible and progressive urinary bladder cancer lesions in rats fed N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. Cancer Research 37, 2817 (1977)Google Scholar
  25. 25.
    Khalil, A., Bourut, C., Halle-Pannenko, O., Mathé, G., Rappaport, H.: Histologic reactions of the thymus, spleen, liver and lymph nodes to intravenous and subcutaneous BCG injections. Biomedicine 22, 122 (1975)Google Scholar
  26. 26.
    Kiel, H., Adolphs, H.-D., Thiele, J., Steffens, L.: Biological behavior or N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide induced carcinoma of the transitional epithelium in the rat. Zeitschrift für Krebsforschung 91, 267 (1978)Google Scholar
  27. 27.
    Koss, L. G.: Tumors of the urinary bladder. Atlas of tumor pathology, Fasc. 11. Washing D. C.: Armed Forces Institute of Pathology, 1975Google Scholar
  28. 28.
    MacKanness, G. B., Auclair, D. J., Lagrange, P. H.: Immunopotentiation with BCG. I. Immune response to different strains and preparations. Journal of the National Cancer Institute 51, 1655 (1973)Google Scholar
  29. 29.
    Mathé, G., Amiel, J. L., Schwarzenberg, L., Schneider, M., Cattan, A., Schlumberger, J. R., Hayat, M., de Vassal, F.: Active immunotherapy for acute lymphoblastic leukaemia. Lancet 1, 697 (1969)CrossRefPubMedGoogle Scholar
  30. 30.
    Mathé, G., Halle-Pannenko, O., Bouret, C.: Immune manipulation by BCG administered before or after cyclophosphamide for chemoimmunotherapy of L 12 10 leukaemia. European Journal of Cancer 10, 661 (1974)Google Scholar
  31. 31.
    Moertel, C. G., Ritts, jr., R. E., Schutt, A. J., Hahn, R. G.: Clinical studies of methanol extraction residue fraction of bacillus Calmette-Guérin as an immunostimulant in patients with advanced cancer. Cancer Research 35, 3075 (1975)Google Scholar
  32. 32.
    Mostofi, F. K., Sobin, L. H., Torloni, H.: Histological typing of urinary bladder tumors. In: International histological classification of tumors. 10, WHO, Geneva (1973)Google Scholar
  33. 33.
    Pai, S. H., Amaral, L., Werthamer, S., Zak, F. G.: Ultrastructure and reversibility of bladder carcinoma of rats produced by feeding of N-[4-(5-nitro-2-furyl)-2-thiazozyl] formamide. Investigative Urology 11, 125 (1973)Google Scholar
  34. 34.
    Pearson, J. W., Perk, K., Chirigos, M. A., Pryor, J. W., Fuhrman, F. S.: Histological and combined chemoimmunostimulation therapy studies against a murine leukemia. International Journal of Cancer 16, 142 (1975)Google Scholar
  35. 35.
    Purnell, D. M., Bartlett, G. L., Kreider, J. W., Biro, T. G.: Corynebacterium parvum and cyclophosphamide as combination treatment for a murine mammary adenocarcinoma. Cancer Research 37, 1137 (1977)Google Scholar
  36. 36.
    Santos, G. W.: Immunosuppressive drugs I. Federation Proceedings 26, 907 (1967)Google Scholar
  37. 37.
    Sher, N. A., Pearson, J. W., Chaparas, S. D., Chirigos, M. A.: Effect of three strains of BCG against a murine leukemia after drug therapy. Journal of the National Cancer Institute 51, 2001 (1973)Google Scholar
  38. 38.
    Sher, N. A., Chaparas, S. D., Pearson, J. W., Chirigos, M. A.: Virulence of six strains of mycobacterium bovis (BCG) in mice. Infection and Immunity 8, 736 (1973)Google Scholar
  39. 39.
    Sjögren, H. O., Hellström, I., Bansal, S. C., Hellström, K. E.: Suggestive evidence that the “blocking antibodies” of tumor-bearing individuals may be antigen-antibody complexes. Proceedings of the National Academy of Science 68, 1372 (1971)Google Scholar
  40. 40.
    Smith, H. G., Bast jr., R. C., Zbar, B., Rapp, H. J.: Eradication of microscopic lymph node metastases after injection of living BCG adjacent ot the primary tumor. Journal of the National Cancer Institute 55, 1345 (1975)Google Scholar
  41. 41.
    Soloway, M. S.: Single and combination chemotherapy for primary murine bladder cancer. Cancer 36, 333 (1975)Google Scholar
  42. 42.
    Sparks, F. C., Breeding, J. H.: Tumor regression and enhancement resulting from immunotherapy with bacillus Calmette-Guérin and neuraminidase. Cancer Research 34, 3262 (1974)Google Scholar
  43. 43.
    Sparks, F. C., Albert, N. E., Breeding, J. H.: Effect of isonicotinic acid hydrazide on the intratumor injection of BCG. Journal of the National Cancer Institute 58, 367 (1977)Google Scholar
  44. 44.
    Tanaka, T., Sasaki, N.: Effect of immunotherapy, chemotherapy, and surgery on tumor immunity in mice. Gann 65, 395 (1974)Google Scholar
  45. 45.
    Tiltman, A. J., Friedell, G. H.: The histogenesis of experimental bladder cancer. Investigative Urology 9, 218 (1971)Google Scholar
  46. 46.
    Tokunaga, T., Yamamoto, S., Nakamura, R. M., Kataoka, T.: Immunotherapeutic and immunoprophylatic effects of BCG on 3-methylcholanthrene-induced autochthonous tumors in swiss mice. Journal of the National Cancer Institute 53, 459 (1974)Google Scholar
  47. 47.
    Wang, C. Y., Hayashida, S., Pamukcu, A. M., Bryan, G. T.: Enhancing effect of allopurinol on the induction of bladder cancer in rats by N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. Cancer Research 36, 1551 (1976)Google Scholar
  48. 48.
    Yalciner, S., Friedell, G. H.: Cilia in the epithelium of the urinary bladder during experimental carcinogenesis. Journal of the National Cancer Institute 51, 501 (1973)Google Scholar
  49. 49.
    Youn, J. K., le Francois, D., Santillana, M., Hue, G., Barski, G.: Effect of BCG treatment on the evaluation of cell-mediated immunity in mice bearing transplantable syngeneic tumors. European Journal of Cancer 13, 177 (1977)Google Scholar
  50. 50.
    Zbar, B., Ribi, E., Meyer, T., Azuma, I., Rapp, H. J.: Immunotherapy of cancer: regression of established intradermal tumors after intralesional injection of mycobacterial cell walls attached to oil droplets. Journal of the National Cancer Institute 52, 1571 (1974)Google Scholar
  51. 51.
    Zbar, B., Rapp, H. J.: Immunotherapy of guinea pig cancer with BCG. Cancer 54, 1532 (1974)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • H. -D. Adolphs
    • 1
  • J. Thiele
    • 2
    • 3
  • H. Kiel
    • 2
    • 3
  1. 1.Department of UrologyUniversity of BonnBonnGermany
  2. 2.Institute of PathologyMedical SchoolHannoverGermany
  3. 3.Department of Laboratory AnimalsChemie Grünenthal GmbHStolbergGermany

Personalised recommendations