Enhancement of Nonspecific Resistance to Tumor by Endotoxin

  • R. Christopher Butler


Since the late 1800s, bacterial products have been used as antitumor agents for the treatment of cancer patients. In spite of the fact that most patients treated with these products have been in advanced stages of the disease, the clinical results obtained have been generally encouraging and occasionally remarkable. Endotoxin has been shown to be one of the most potent antitumor components in these bacterial preparations. Therefore, endotoxin has been extensively studied in animal tumor models to determine the conditions under which it may be used most effectively against tumors.


Migration Inhibition Factor Serratia Marcescens Tumor Challenge Ascites Tumor Tumor Hemorrhage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander, P., and Evans, R., 1971, Endotoxin and double-stranded RNA render macrophages cytotoxic, Nature New Biol. 232:76.PubMedGoogle Scholar
  2. Arai, M., Nakahara, M., Hamano, K., and Okazaki, H., 1975, Isolation and characterization of antitumor lipopolysaccharide from Proteus mirabilis, Agnc. Biol. Chem. 39:1813.CrossRefGoogle Scholar
  3. Beebe, S. P., and Tracy, M., 1907, The treatment of experimental tumors with bacterial toxins,J. Am. Med. Assoc. 49:1493.CrossRefGoogle Scholar
  4. Behling, U. H., and Nowotny, A., 1977, Immune adjuvancy of lipopolysaccharide and a nontoxic hydrolytic product demonstrating oscillating effects with time, J. Immunol. 118:1905.PubMedGoogle Scholar
  5. Bober, L. A., Kranepool, M. J., and Hollander, V. P., 1976, Inhibitory effect of endotoxin on the growth of plasma cell tumor, Cancer Res. 36:927.PubMedGoogle Scholar
  6. Braun, V., 1973, Immunologic and antineoplastic effects of endotoxin: Role of membranes and mediation by cyclic adenosine-3′, 5′-monophosphate, J. Infect. Dis. 128 (Suppl.):118.Google Scholar
  7. Butler, R. C., and Friedman, H., 1980a, Leukemia virus-induced immunosuppression: Reversal by subcellular factors, Ann. N. Y. Acad. Sci. 332:446.CrossRefGoogle Scholar
  8. Butler, R. C., and Friedman, H., 1980b, Restoration of leukemia cell immune responses by bacterial products, in: Current Chemotherapy and Infectious Disease (J. D. Nelson and C. Grassi, eds.), American Society for Microbiology, Washington, D. C.Google Scholar
  9. Butler, R. C., and Nowotny, A., 1976, Colony stimulating factor (CSF)-containing serum has anti-tumor effects, IRCS Med. Sci. 4:206.Google Scholar
  10. Butler, R. C., and Nowotny, A., 1979, Enhancement of nonspecific resistance to tumor by combinations of immunostimulatory bacterial products, Cancer Immunol. Immunother. 6:255.CrossRefGoogle Scholar
  11. Butler, R. C., Nowotny, A., and Friedman, H., 1977, Stimulation of an in vitro antibody response by endotoxin-induced soluble factors, J. Reticuloendothelial Soc. 22:28.Google Scholar
  12. Butler, R. C., Abdelnoor, A. M., and Nowotny, A., 1978, Interrelationship between bone marrow colony-stimulating (CSF) and antitumor resistance (TUR) enhancing activities of post-endotoxin sera, Proc. Nat. Acad. Sci. USA 75:2893.PubMedCrossRefGoogle Scholar
  13. Butler, R. C., Nowotny, A., and Friedman, H., 1980a, Macrophage factors that enhance the antibody response, Ann. N.Y. Acad. Sci. 332:564.CrossRefGoogle Scholar
  14. Butler, R. C., Friedman, H., and Nowotny, A., 1980b, Restoration of depressed antibody responses of leukemic splenocytes treated with LPS-induced factors, Adv. Exp. Med. Biol. 121A:315.Google Scholar
  15. Cameron, D. J., and Churchill, W. H., 1980, Cytotoxicity of human macrophages for tumor cells: Enhancement by bacterial lipopolysaccharides (LPS),J. Immunol. 124:408.Google Scholar
  16. Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N., and Williamson, B., 1975, An endotoxin-induced serum factor that causes necrosis of tumors, Proc. Nat. Acad. Sci. USA 72:3666.PubMedCrossRefGoogle Scholar
  17. Chang, H., Thompson, J. J., and Nowotny, A., 1974, Release of colony stimulating factor (CSF) by non-endotoxic breakdown products of bacterial lipopolysaccharides, Immunol. Commun. 3:402.Google Scholar
  18. Chedid, L., Parent, M., Parent, F., Gustafson, R. H., and Berger, F. M., 1972, Biological study of a nontoxic, water-soluble immunoadjuvant from mycobacterial cell walls, Proc. Nat. Acad. Sci. USA 69:855.PubMedCrossRefGoogle Scholar
  19. Coley, W. B., 1893, The treatment of malignant tumors by repeated inoculations of erysipelas, with a report of original cases, Am. J. Med. Sci. 105:487.CrossRefGoogle Scholar
  20. Copeland, M. M., 1967, Primary malignant tumors of bone: Evaluation of current diagnosis and treatment, Cancer 20:738.PubMedCrossRefGoogle Scholar
  21. Coutinho, A., 1976, Genetic control of B-cell responses. II. Identification of the spleen B-cell defect in C3H JHeJ mice, Scand. J. Immunol. 123:61.Google Scholar
  22. Duran-Reynals, F., 1935, Reaction of spontaneous mouse carcinomas to blood-carried bacterial toxins, Proc. Soc. Exp. Biol. Med. 32:1517.Google Scholar
  23. Evans, R., and Alexander, P., 1972, Mechanism of immunologically specific killing of tumor cells by macrophages, Nature (London) 236:168.CrossRefGoogle Scholar
  24. Felton, L. D., Kauffman, C., and Stahl, H. T., 1935, The precipitation of bacterial polysaccharides with calcium phosphate,J. Bacterwl. 29:149.Google Scholar
  25. Fogg, L. C., 1936, Effect of certain bacterial products upon the growth of mouse tumor, Public Health Rep. 51:56.CrossRefGoogle Scholar
  26. Fowler, G. A., 1969a, Enhancement of Natural Resistance to Malignant Melanoma with Special Reference to the Beneficial Effects of Concurrent Infections and Bacterial Toxin Therapy, Monograph No. 9, New York Cancer Research Institute, New York.Google Scholar
  27. Fowler, G. A., 1969b, Beneficiai Effects of Acute Bacterial Infections or Bacterial Toxin Therapy of Cancer of the Colon or Rectum, Monograph No. 10, New York Cancer Research Institute, New York.Google Scholar
  28. Friedman, H., and Butler, R. C., 1979, Immunomodulatory effects of endotoxin-induced factors, in: Microbiology 1979 (D. Schlessinger, ed.), American Society for Microbiology, Washington, D.C.Google Scholar
  29. Gardner, R. E., Bailey, G. H., and Hyde, R. R., 1939, Hemorrhagic activity of toxic carbohydrate complexes from bacteria on a transplantable rat tumor, Am. J. Hyg. 29:1.Google Scholar
  30. Glaser, M., Djeu, J. Y., Kirchner, H., and Herberman, R. B., 1976, Augmentation of cell-mediated cytotoxicity against syngeneic Gross virus-induced lymphoma in rats by phytohemagglutinin and endotoxin,J. Immunol. 116:1542.Google Scholar
  31. Gratia, A., and Linz, R., 1931, Le phénomène de Shwartzman dans la sarcome du cobaye, C. R. Soc. Bwl. 108:427.Google Scholar
  32. Grohsman, J., and Nowotny, A., 1972, The immune recognition of TA3 tumors, its facilitation by endotoxin, and abrogation by ascites fluid,J. Immunol. 109:1090.PubMedGoogle Scholar
  33. Hartwell, J. L., Shear, M. J., and Adams, J. R., 1943, Chemical treatment of tumors. VII. Nature of the hemorrhage-producing fraction from Serratia marcescens (Bacillus prodigwsus) culture filtrate,J.Nat. Cancer Inst. 4:107.Google Scholar
  34. Henderson, J. S., Migliore, R. D., and Berbrayer, D., 1976, Interference by cortisone with endotoxin’s adjuvator action on transplantation of a mouse tumour, J. Cancer Res. 33: 203.Google Scholar
  35. Hoshi, A., Kanzawa, F., Kuretani, K., Homma, J. Y., and Abe, C., 1972, Anti-tumor activity of protein moiety of the Pseudomonas aeruginosa endotoxin, Gann 63:503.PubMedGoogle Scholar
  36. Hoshi, A., Kanzawa, F., Kuretani, K., Homma, J. Y., Abe, C., 1973, Anti-tumor activity of constituents of Pseudomonas aeruginosa, Gann 64:423.Google Scholar
  37. Männel, D. N., Farrar, J. J., and Mergenhagen, S. E., 1980, Separation of a serum-derived tumoricidal factor from a helper factor for plaque-forming cells, J. Immunol. 124: 1106.PubMedGoogle Scholar
  38. Miller, T. R., and Nicholson, J. T., 1971, End results in reticulum cell sarcoma of bone treated by bacterial toxin therapy alone or combined with surgery and Jor radiotherapy (47 cases) or with concurrent infection (5 cases), Cancer 27:524.PubMedCrossRefGoogle Scholar
  39. Mita, A., 1972, Immunological evidences for proliferation and migration of lymphocytes induced by administration of potent antitumor phosphomucolipid in tumor-bearing mice, Rev. Eur. Etud. Clin. Biol. 17:860.PubMedGoogle Scholar
  40. Mizuno, D., Yoshioka, O., Akamatu, M., and Kataoka, T., 1968, Antitumor effect of intracutaneous injection of bacterial lipopolysaccharide, Cancer Res. 28:1531.PubMedGoogle Scholar
  41. Nakahara, M., Kitahara, N., Hamano, K., Arai, M., and Okazaki, H., 1975, Antitumor lipopolysaccharide from heptoseless mutant of Proteus mirabilis, Agnc. Biol. Chem. 39: 1821.CrossRefGoogle Scholar
  42. Nauts, H. C., Fowler, G. A., and Bogatko, F. H., 1953, A review of the influence of bacterial infection and of bacterial products (Coley’s toxins) on malignant tumors in man, Acta Med. Scand. 145(Suppl. 276): 103.Google Scholar
  43. Ng, A. K., Butler, R. C., Chen, C.-L., and Nowotny, A., 1976, Relationship of structure to function in bacterial endotoxins. IX. Differences in the lipid moiety of endotoxic gly-colipids,J. Bacteriol. 126:511.PubMedGoogle Scholar
  44. Nigam, V. N., 1975, Effect of core lipopolysaccharides from Salmonella minnesota R mutants on the survival times of mice bearing Ehrlich tumor, Cancer Res. 35:628.PubMedGoogle Scholar
  45. Nowotny, A., and Butler, R. C., 1980, Studies on the endotoxin induced tumor resistance, Adv. Exp. Med. Biol. 121B:455.Google Scholar
  46. Nowotny, A., Golub, S., and Key, B., 1971, Fate and effect of endotoxin derivatives in tumor-bearing mice, Proc. Soc. Exp. Biol. Med. 136:66.PubMedGoogle Scholar
  47. Nowotny, A., Behling, U. H., and Chang, H. L., 1975, Relation of structure to function in bacterial endotoxins. VIII. Biological activities in a polysaccharide-rich fraction, J. Immunol. 115:199.PubMedGoogle Scholar
  48. O’Malley, W. E., Achinstcin, B., and Shear, M. J., 1962, Action of bacterial polysaccharide on tumors. II. Damage of sarcoma 37 by serum of mice treated with Serratia marcescens polysaccharide, and induced tolerance,J. Nat. Cancer Inst. 29:1169.Google Scholar
  49. Parr, I., Wheeler, E., and Alexander, P., 1973, Similarities of the anti-tumour actions of endotoxin, lipid A and double-stranded RNA, Br. J. Cancer 27:370.PubMedCrossRefGoogle Scholar
  50. Pimm, M. V., and Baldwin, R. W., 1974, BCG immunotherapy of rat tumours in athymic nude mice, Nature (London) 254:77.CrossRefGoogle Scholar
  51. Prigal, S. J., 1968, A new application of mineral oil emulsions: The induction in mice of prolonged resistance to a variety of lethal challenges, Ann. Allergy 26:374.PubMedGoogle Scholar
  52. Ribi, E., Meyer, T. J., Azuma, I., and Abar, B., 1972, Mycobacterial cell wall components in tumor suppression and regression, Nat. Cancer Inst. Monogr. 39:115.Google Scholar
  53. Ribi, E., Granger, D. L., Milner, K. C., and Strain, S. M., 1975, Brief communication: Tumor regression caused by endotoxins and mycobacterial fractions, J. Nat. Cancer Inst. 55:1253.PubMedGoogle Scholar
  54. Ribi, E., Takayama, K., Milner, K., Gray, G., Goren, M., Parker, R., McLaughlin, C., and Kelly, M., 1976, Regression of tumors by an endotoxin combined with trehalose mycolates of differing structure, Cancer Immunol. 1:265.Google Scholar
  55. Ribi, E., Cantrell, J. L., Nowotny, A., Parker, R., Schwartzman, S. C., Von Eschen, K. B., and Wheat, R. W., 1979, Tumor regression caused by endotoxins combined with trehalose dimycolate, Toxicon 17:150.CrossRefGoogle Scholar
  56. Ruff, M. R., and Gifford, G. E., 1980, Purification and physico-chemical characterization of rabbit tumor necrosis factor,J. Immunol. 125:1671.PubMedGoogle Scholar
  57. Shapiro, C. J., 1940, The effect of a toxic carbohydrate complex from S. ententidis on transplantable rat tumors in tissue cultures, Am. J. Hyg. 31:114.Google Scholar
  58. Shear, M. J., and Andervont, H. B., 1936, Chemical treatment of tumors. III. Separation of hemorrhage-producing fraction of E. coll filtrate, Proc. Soc. Exp. Biol. Med. 34:323.Google Scholar
  59. Shwartzman, G., 1936, Reactivity of malignant neoplasms to bacterial filtrates. II. Relation of mortality to hemorrhagic necrosis and regression elicited by certain bacterial filtrates, Arch. Pathol. 21:509.Google Scholar
  60. Shwartzman, G., and Michailovsky, N., 1932, Phenomenon of local skin reactivity to bacterial filtrates in the treatment of mouse sarcoma 180, Proc. Soc. Exp. Biol. Med. 29: 737.Google Scholar
  61. Stanley, E. R., Hansen, G., Woodcock, J., and Metcalf, D., 1975, Colony stimulating factor and the regulation of granulopoiesis and macrophage production, Fed. Proc. 34: 2272.PubMedGoogle Scholar
  62. Strausser, H. R., and Bober, L. A., 1972, Inhibition of tumor growth and survival of aged mice inoculated with Moloney tumor transplants and treated with endotoxin, Cancer Res. 32:2156.PubMedGoogle Scholar
  63. Tripodi, D., Hollenbeck, L., and Pollack, W., 1970, The effect of endotoxin on the implantation of a mouse sarcoma, Int. Arch. Allergy 37:575.PubMedCrossRefGoogle Scholar
  64. Wahl, S. M., 1974, Role of macrophages in inducing monocyte (MNL) chemotactic factor (CTF) production by guinea pig T and B lymphocytes, Fed. Proc. 33:744.Google Scholar
  65. Wilton, J. L., Rosenstreich, D. L., and Oppenheim, J. J., 1975, Activation of guinea pig macrophages by bacterial lipopolysaccharide requires bone marrow derived lymphocytes,J. Immunol. 114:388.PubMedGoogle Scholar
  66. Yang, C., and Nowotny, A., 1974, Effect of endotoxin on tumor resistance in mice, Infect. Immun. 9:95.PubMedGoogle Scholar
  67. Yang-Ko, C., Grohsman, J., Rote, N., Jr., Nowotny, A., 1974, Non-specific resistance induced in allogeneic mice to the transplantable TA3-Ha tumor by endotoxin and its derivatives, 8th International Congress on Chemotherapy, Athens, pp. 193–197.Google Scholar
  68. Yoshida, T., Sonozaki, H., and Cohen, S., 1973, The production of migration inhibition factor by B and T cells of the guinea pig, J. Exp. Med. 138:784PubMedCrossRefGoogle Scholar
  69. Zahl, P. A., Hutner, S. H., Spitz, S., Sugiura, K., and Cooper, F. S., 1942, Action of bacterial toxins on tumors. I. Relationship of tumor-hemorrhagic agent to endotoxin antigens of gram-negative bacteria, Am. J. Hyg. 36:224.Google Scholar
  70. Zbar, B., Bernstein, I. D., and Rapp, H. J., 1972, Suppression of tumor growth at the site of infection with living Bacillus Calmette & Guerin,J. Natl. Cancer Inst. 46:831–839.Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • R. Christopher Butler
    • 1
  1. 1.Departments of Microbiology and ImmunologyThe Arlington HospitalArlingtonUSA

Personalised recommendations