Skip to main content
Log in

Local microwave hyperthermia (43° C) and stimulation of the macrophage and T-lymphocyte systems in treatment of Guerin epithelioma in rats

  • Original Papers
  • Published:
Zeitschrift für Krebsforschung und Klinische Onkologie Aims and scope Submit manuscript

Summary

Rats bearing Guerin epithelioma were exposed to 3 or 6 sessions of local microwave hyperthermia (LMwH) (2450 MHz, tumor temperature 43° C, time of exposition 45 min) on the 3rd or 5th week after implantation of tumor cells. In some of the animals LMwH was combined with the administration of immunopotentiating (IP) substances—purified Streptolysin S (SLS) (1 mg/kg b.w.) or Corynebacterium parvum (CP) (1 mg/kg b.w., intratumorally)-injected 3 times weekly on the 4th and 6th weeks after implantation of tumor cells. All the animals were immunized with bovine serum albumine (BSA) 2 and 3 weeks after tumor implantation. Size of tumors was measured each 4 days and the growth curves were analysed. Eight weeks after implantation all the animals were killed and the following tests were performed: weight of tumors, BSA antibodies titre (passive hemagglutination test using BSA-glutaraldehyde coupled sheep red blood cells), 3H-leucine and 3H-uridine incorporation to phytohemagglutinin (PHA)-stimulated spleen lymphocytes and to mixed tumor cell-lymphocyte cultures, cytotoxicity of isolated spleen lymphocytes and peritoneal macrophages to 51Cr-labeled primary cultures of Guerin tumor cells, lysozyme (muramidase) activity in blood serum.

LMwH inhibited growth of Guerin tumors and the effect was enhanced by combined treatment with IP substances. Combined application of LMwH and CP resulted in complete disappearance of 9 of 12 tumors, while LMwH and IP applied separately led to eradication of 2–5 tumors of 12.

LMwH stimulated reactivity of the T-lymphocyte and macrophage systems enhancing both non-specific (increased production of BSA antibodies, high reactivity of spleen lymphocytes to PHA, increased serum lysozyme levels) and specific (increased cytotoxicity of lymphocytes and macrophages to cultured tumor cells and higher reactivity of lymphocytes to mitomycin-inhibited tumor cells) immune responses.

The role of immunostimulation by LMwH is stressed as an important factor in tumor-inhibiting effect of hyperthermia in addition to the well known selective heat killing of neoplastic cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alexander, R.: The role of macrophages in the host defence against cancer. In: Mizuno, D. (Ed.): Host defence against cancer and its potentiation, pp. 113–130. Baltimore, London, Tokyo: University Park Press 1975

    Google Scholar 

  • Aurameas, S., Taudou, B., Chuilon, S.: Glutaraldehyde, cyanuric chloride, and tetrazolized-O-dianizidine as coupling reagents in the passive hemagglutination test. Immunochemistry 6, 67–76 (1969)

    Google Scholar 

  • Baum, M, Breese, M.: Antitumour effect of Corynebacterium parvum. Brit. J. Cancer 33, 468–473 (1976)

    Google Scholar 

  • Bennett, T.P.: Membrane filtration for determining protein in the presence of interfering substances. Nature 213, 1131 (1967)

    Google Scholar 

  • Bernheimer, A.W.: Formation of a bacterial toxin (streptolysin S) by resting cells. J. exp. Med. 90, 373–392 (1949)

    Google Scholar 

  • Bomford, R., Christie, G.H.: Mechanism of macrophage activation by Corynebacterium parvum. II. In vivo experiments. Cell Immunol. 17, 150–159 (1975)

    Google Scholar 

  • Bronk, B.V.: Thermal potentiation of mammalian cell killing: clues for understanding and potential for tumor therapy. Adv. Radiation Biol. 6, 267–324 (1976)

    Google Scholar 

  • Currie, G.A.: Serum lysozyme as a marker of host resistance. II. Patient with malignant melanoma, hypernephroma or breast carcinoma. Brit. J. Cancer 33, 593–599 (1976)

    Google Scholar 

  • Currie, G.A., Eccles, S.A.: Serum lysozyme as a marker of host resistance. I. Production by macrophages resident in rat sacromata. Brit. J. Cancer 33, 51–59 (1976)

    Google Scholar 

  • Dickson, J.A.: Hazards and potentiators of hyperthermia. In: Wizenberg, M.J., Robinson, J.E. (Eds.): Proceedings of the International Symposium on Cancer Therapy by Hyperthermia and Radiation. Amer. Coll. of Radiology, Chavy Chase, Md., pp. 134–150 1976

    Google Scholar 

  • Dickson, J.A., Calderwood, S.K.: In vivo hyperthermia of Yoshida tumor induces entry of non-proliferating cells into cycle. Nature 263, 772–774 (1976)

    Google Scholar 

  • Dickson, J.A., Muckle, D.S.: Total body hyperthermia versus primary tumor hyperthermia in the treatment of the rabbit VX2 carcinoma. Cancer Res. 32, 1916–1923 (1972)

    Google Scholar 

  • Dietzel, F.: Tumor und Temperatur. München: Urban & Schwarzenberg 1975

    Google Scholar 

  • Dukort, P., Vasella, S., Schlafli, E., Perren, B.: Immunopotentiating agents: activity profiles and possible mode of action. In: Minuzo, D. (Ed.): Host defence against cancer and its potentiation, pp. 97–112. Baltimore, London, Tokyo: Univ. Park Press 1975

    Google Scholar 

  • Eccles, S.A., Alexander, P.: Macrophage content of tumor in relation to metastatic spread and host immune reaction. Nature 250, 667 (1974)

    Google Scholar 

  • Embleton, M.J.: Effect of BCG on cell-mediated cytotoxicity and serum blocking factor during growth of rat hepatoma. Brit. J. Cancer 33, 584–592 (1976)

    Google Scholar 

  • Evans, R.: Macrophages and the tumor bearing host. Brit. J. Cancer 28, 19–25 (1973)

    Google Scholar 

  • Evans, R., Alexander, P.: Mechanism of immunologically specific killing of tumor cells by macrophages. Nature 236, 168 (1972)

    Google Scholar 

  • Fischer, J.C., Grace, W.R., Mannick, J.A.: The effect of non-specific immune stimulation with Corynebacterium parvum on patterns of tumor growth. Cancer 26, 1379–1382 (1970)

    Google Scholar 

  • Ghaffar, A., Cullen, R.T., Dunbar, N., Woodruff, F.A.: Anti-tumor effect in vitro of lymphocytes and macrophages from mice treated with Corynebacterium parvum. Brit. J. Cancer 29, 199–208 (1974)

    Google Scholar 

  • Guy, A.W.: Physical aspects of the electromagnetic heating of tissue volume. In: Wizenberg, M.J., Robinson, J.E. (Eds.): Proceedings of the International Symposium on Cancer Therapy by Hyperthermia and Radiation. Amer. Coll. Radiology, Chavy Chase, Md., pp. 179–192, 1976

    Google Scholar 

  • Guy, A.W., Lehmann, J.F., Stonebridge, J.B.: Therapeutic application of electromagnetic power. Proc. IEEE 1, 55–75 (1974)

    Google Scholar 

  • Halpern, B. (Ed.): Corynebacterium parvum: its application in experimental and clinical oncology. New York: Plenum Press 1975

    Google Scholar 

  • Halpern, B., Biozzi, G., Stiffel, C., Mouton, D.: Inhibition of tumor growth by administration of killed Corynebacterium parvum. Nature 212, 853–859 (1966)

    Google Scholar 

  • Halpern, B., Fray, A., Crepin, Y.: Corynebacterium parvum, a potent immunostimulant in experimental infection and in malignancies. In: Wolstenholme, G.E.W., Knight, J. (Eds.): CIBA found. Symp. No. 18. Immunopotentiation, pp. 217–236. Amsterdam, Elsevier, North Holland 1973

    Google Scholar 

  • Hansen, N.E., Andersen, V.: Lysozyme activity in human neutrophilic granulocytes. Brit. J. Haematol. 24, 613–623 (1973)

    Google Scholar 

  • Har-Kedar, I., Bleehen, N.N.: Experimental and clinical aspects of hyperthermia applied to the treatment of cancer with special reference to the role of ultrasonic and microwave heating. Adv. Radiation Biol. 6, 229–266 (1976)

    Google Scholar 

  • Harris, J.W.: Effect of tumor-like assay conditions, ionizing radiation and hyperthermia on immune lysis of tumor cells by cytotoxic T-lymphocytes. Cancer Res. 36, 2733–2739 (1976)

    Google Scholar 

  • Hellström, K., Hellström, I.: The role of cell-mediated immunity in control and growth of tumors. In: Bach, F.H., Good, R.A. (Eds.): Clinical immunobiology, Vol.2, pp. 233–264. New York: Academy Press 1974

    Google Scholar 

  • Henle, K.J., Leeper, D.B.: Interaction of hyperthermia and radiation in CHO cells: recovery kinetics. Radiation Res. 66, 505–518 (1976)

    Google Scholar 

  • Herberman, R.B.: Cell-mediated immunity to tumor cells. Adv. Cancer Res. 19, 207–248 (1947)

    Google Scholar 

  • Herberman, R.B., Aoki, T., Nunn, M.: Specifity of 51Cr-release cytotoxicity of lymphocytes immunize to murine sarcoma virus. J. Nat. Cancer Inst. 53, 1103–1111 (1974)

    Google Scholar 

  • Herberman, R.B., Nunn, M., Holden, H.T., Laurin, D.H.: Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells. Int. J. Cancer 16, 230–239 (1975)

    Google Scholar 

  • Herberman, R.B., Nunn, M., Laurin, D.H.: Natural cytotoxic reactivity of mouse lymphoid cells against syngeneis and allogeneic tumors. I. Distribution of reactivity and specifity. Int. J. Cancer 16, 216–229 (1975)

    Google Scholar 

  • Howell, S.B., Dean, J.H., Law, L.W.: Defects in cell-mediated immunity during growth of a syngeneic Simian virus-induced tumor. Int. J. Cancer 15, 152–169 (1975)

    Google Scholar 

  • Hryniewicz,W., Gray,E.D., Wannamaker,L.W., Kanclerski,K.: Purification and some properties of Streptolysin S. Infection and Immunity (in press) (1977)

  • Kiessling, R., Petranyi, G., Karre, K., Jondal, M., Tracey, P., Wigzell, H.: Killer cells: a functional comparison between natural, immune T-cells and antibody-dependent in vitro systems. J. exp. Med. 143, 772–780 (1976)

    Google Scholar 

  • Kirchner, H.H., Glaser, M., Herberman, R.B.: Suppression of cell-mediated tumor immunity by Corynebacterium parvum. Nature 257, 396–398 (1975)

    Google Scholar 

  • Kovacs, C.J., Hopkins, H.A., Evans, M.J., Looney, W.B.: Changes in cellularity induced by radiation in a solid tumor. Int. J. Radiat. Biol. 30, 101–113 (1976)

    Google Scholar 

  • Kramer,S. (Ed.): Hyperthermia in the treatment of the cancer patient. Cancer 37 (Suppl.4), 2075–2083 (1976)

  • Leith, J.T., Miller, R.C., Gerner, E.W., Boone, M.L.: Hyperthermic potentiation. Biological aspects and applications to radiation therapy. Cancer 39, 766–779 (1977)

    Google Scholar 

  • Marmor, J.B., Hahn, N., Hahn, G.M.: Tumor cure and cell survival after localized radiofrequency heating. Cancer Res. 37, 879–883 (1977)

    Google Scholar 

  • Mathe, G.: Cancer active immunotherapy. Rec. Res. Cancer Res. 55, 1–402 (1976)

    Google Scholar 

  • Mendecki, J., Friedenthal, E., Botstein, C.: Effects of microwave-induced local hyperthermia on mammary adenocarcinoma in C3H mice. Cancer Res. 36, 2112–2114 (1976)

    Google Scholar 

  • Miller, G.A., Feldman, J.D.: Genetic role of rat macrophage cytotoxicity against tumor. Int. J. Cancer 18, 168–175 (1976)

    Google Scholar 

  • Mondovi, B., Santoro, A.S., Strom, R., Faiola, R., Fanelli, A.R.: Increased immunogenicity of Ehrlich ascites cells after heat treatment. Cancer 30, 885–888 (1972)

    Google Scholar 

  • Osserman, E.F., LawIor, D.P.: Serum and urinary lysozyme (muramidase) in monocytic and monomyelocytic leukaemia. J. exp. Med. 124, 921–934 (1966)

    Google Scholar 

  • Overgaard, J.: Combined adriamycin and hyperthermia treatment of a murine mammary carcinoma in vivo. Cancer Res. 36, 3077–3081 (1976)

    Google Scholar 

  • Overgaard, K., Overgaard, J.: Pathology of heat damage studies on the histopathology in tumor tissue exposed in vivo to hyperthermia and combined hyperthermia and Roentgen irridiation. In: Wizenberg, M.J., Robinson, J.E. (Eds.): Proceedings of the International Symposium on Cancer Therapy by Hyperthermia and Radiation. Amer. Coll. Radiol., Chavy Chase, Md., pp. 115–127 1976

    Google Scholar 

  • Popovic, V., Popovic, P.: Hyperthermiain biology and in medicine. New York: Grune & Stratton, pp. 230–245 (1974)

    Google Scholar 

  • Popovic, P., Sybers, H.A., Popovic, V.: Regression of spontaneous mammary tumors in C3H mice after 5-fluorouracil and differential hypothermia. Panminerva Med. 13, 523–526 (1971)

    Google Scholar 

  • Robinson, J.E., McCulloch, D., Edelsack, E.A.: Microwave heating of malignant mouse tumors and tissue equivalent phantom systems. J. Microwave Power 11, 87–98 (1976)

    Google Scholar 

  • Scott, M.T.: Biological effects of the adjuvant Corynebacterium parvum. I. Inhibition of PHA, mixed lymphocyte, and GVH reactivity. Cell. Immunol. 5, 459–468 (1972)

    Google Scholar 

  • Scott, M.T.: Corynebacterium parvum as a therapeutic anti-tumor agent in mice. I. Systemic effects from intravenous injection. J. Nat. Cancer Inst. 53, 855–860 (1974)

    Google Scholar 

  • Scott, M.T.: Corynebacterium parvum as a therapeutic anit-tumor agent in mice. II. Local injection. J. Nat. Cancer Inst. 53, 861–865 (1974a)

    Google Scholar 

  • Scott, M.T.: Potentiation of the tumor-specific immune response by Corynebacterium parvum. J. Nat. Cancer Inst. 55, 65–72 (1975)

    Google Scholar 

  • Suit, H.D.: Hyperthermia in the treatment of tumors. In: Wizenberg, M.J., Robinson, J.E. (Eds.): Proceedings of the International Symposium on Cancer Therapy by Hyperthermia and Radiation. Amer. Coll. Radiol, Chavy Chase. Md., pp. 107–114 (1976)

    Google Scholar 

  • Szmigielski, S., Bielec, M.: Hypertermia w leczeniu nowotworow zlosliwych. Post. Hig. Med. Dosw. 30, 459–492 (1976)

    Google Scholar 

  • Szmigielski,S., Janiak,M., Hryniewicz,W., Pulverer,G.: Inhibition of growth of Sarcoma 180 by microwave hyperthermia, Colcemide and Streptolysin S. Radio Sciences (Suppl.) (in press) (1977)

  • Szmigielski, S., Jeljaszewicz, J., Pulverer, G.: Granulopoiesis in rabbits treated with cytostatic agents and during experimental staphylococcal infections. In: Jeljaszewicz, J. (Ed.): Staphylococci and Staphylococcal Infections, pp. 773–782. Stuttgart, New York: G. Fischer Verlag 1976.

    Google Scholar 

  • Thrall, D.E., Gerweck, L.E., Gillette, E.L., Dewey, W.C.: Response of cells in vitro and tissues in vivo to hyperthermia and X-irradiation. Adv. Radiation Biol. 6, 211–227 (1976)

    Google Scholar 

  • Waithe, W., Hathaway, P., Hirschhorn, K.: Protein synthesis in stimulated lymphocytes. Clin. Exp. Immunol. 9, 903–912 (1971)

    Google Scholar 

  • Weir, D.M.: Handbook of experimental immunology, 2nd Ed. Oxford, London: Blackwell Scientific Publication 1973

    Google Scholar 

  • Wizenberg, M.J., Robinson, J.E. (Eds.): Proceedings of the International Symposium on Cancer Therapy by Hyperthermia and Radiation. Amer. Coll. Radiol., Chavy Chase, Md. pp. 1–305 1976

    Google Scholar 

  • Woodruff, M.F.A., Dunbar, N.: Effect of local injection of Corynebacterium parvum on the growth of a murine fibrosarcoma. Brit. J. Cancer 32, 34–41 (1975)

    Google Scholar 

  • Woodruff, M.F.A., Warner, N.L.: Effects of Corynebacterium parvum on tumor growth in normal and athymic (nude) mice. J. Nat. Cane. Inst. 58, 111–116 (1977)

    Google Scholar 

  • Wolfe, S.A., Tracey, D.E., Henney, C.S.: Induction of “natural killer” cells by BCG. Nature 262, 584–586 (1976)

    Google Scholar 

  • Zatz, H.M., Lance, E.M.: The distribution of chromium-51 labeled lymphoid cells in the mouse. Cell Immunol. 1, 3–16 (1970)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by research grants 05-339-C from the US Public Health Service and PR-6-210-02 from the Polish Governmental Program

Rights and permissions

Reprints and permissions

About this article

Cite this article

Szmigielski, S., Janiak, M., Hryniewicz, W. et al. Local microwave hyperthermia (43° C) and stimulation of the macrophage and T-lymphocyte systems in treatment of Guerin epithelioma in rats. Z. Krebsforsch. 91, 35–48 (1978). https://doi.org/10.1007/BF00305970

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00305970

Key words

Navigation