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Reduced incidence of rat colon cancer metastases by perioperative immunostimulation with maleic anhydride-divinyl ether-2 (MVE-2)

  • Published:
Diseases of the Colon & Rectum

Abstract

Intra-abdominal operations result in profound immunodepression during a period when tumor cells are released into the systemic and portal circulations. This combination may augment tumor metastases. The authors have developed a model in which rat colon carcinoma cells transplanted into the portal vein consistently induce hepatic metastases by four weeks, and death within nine weeks. Additionally, the authors have shown that perioperative treatment with levamisole significantly reduces the incidence of metastases. This study tested whether maleic anhydride-divinyl ether-2 (MVE-2), a known immunostimulant, would produce similar effects.

Rats pretreated with MVE-2 the day before and day of tumor implantation developed fewer metastases (34 percent of animals treated with MVE-2, compared with 5 percent of animals not treated with MVE-2 had≤two liver metastases). Eighteen percent of MVE-2-treated rats developed no hepatic metastases. Comparison of median liver weights between the MVE-2-treated group and the nontreated, tumor-bearing group was significant (P=0.03) and the MVE-2-treated animals had significantly prolonged survival (P=0.04). The authors conclude that the perioperative period is critical for the implantation and growth of metastases and that perioperative immunostimulation may be a factor in decreasing the incidence of metastases. This model may have relevance to the adjuvant treatment of human colonic cancer.

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References

  1. Cochran AJ, Spilig WSG, Mackie RM, Thomas CE. Postoperative depression of tumor directed cell-mediated immunity in patients with malignant disease. Br Med J 1972;4:67–70.

    Article  PubMed  CAS  Google Scholar 

  2. Hunt PS, Trotter S. Lymphocyte response after surgery and blood transfusion. J Surg Res 1976;21:57–61.

    Article  PubMed  CAS  Google Scholar 

  3. Kinnaert P, Mahieu A, Mahieu M, Van Geertruyden N. Effect of surgical trauma on delayed type hypersensitivity. J Surg Res 1983;34:227–30.

    Article  PubMed  CAS  Google Scholar 

  4. Park S, Brody JI, Wallace HA, Blakemore WS. Immunosuppressive effect of surgery. Lancet 1971;1:53–5.

    Article  PubMed  CAS  Google Scholar 

  5. Roth JA, Golub SH, Grimm EA, Eilber FR, Morton DC. Effects of operation on immune response in cancer patients; sequential evaluation ofin vitro lymphocyte function. Surgery 1976;79: 46–51.

    PubMed  CAS  Google Scholar 

  6. Slade MS, Simmons RL, Yunis E, Greenberg LJ. Immunodepression after major surgery in normal patients. Surgery 1975;78:363–72.

    PubMed  CAS  Google Scholar 

  7. Tarpley JL, Twomey PL, Catalona WJ, Chretien PB. Suppression of cellular immunity by anesthesia and operation. J Surg Res 1977;22:195–201.

    Article  PubMed  CAS  Google Scholar 

  8. Windle R, Bell PR. Lymphoblast transformation following adjuvant treatment of an induced colonic cancer with Levamisole and Fluorouracil. Cancer Immunol Immunother 1982;12: 267–71.

    Article  CAS  Google Scholar 

  9. Fielding LP, Wells BW. Survival after primary and after staged resection for large bowel obstruction caused by cancer. Br J Surg 1974;61:16–8.

    PubMed  CAS  Google Scholar 

  10. Weese JL, Gilbertson EM, Syrjala SE, Starling JR. Prevention of rat colon cancer metastases by perioperative immunostimulation. Surgery 1984;420–6.

  11. Chirigos MA, Stylos WA. Immunomodulatory effect of various molecular-weight maleic anhydride-divinyl ethers and other agentsin vivo. Cancer Res 1980;40:1967–72.

    PubMed  CAS  Google Scholar 

  12. Milas L, Hersh EM, Hunter N. Therapy of artificial and spontaneous metastases of murine tumors with maleic anhydride-divinyl ether-2. Cancer Res 1981;41:2378–85.

    PubMed  CAS  Google Scholar 

  13. Oldham RK, Thurman GB, Talmadge JE, Stevenson HC, Foon KA. Lymphokines, monoclonal antibodies and other biologic response modifiers in the treatment of cancer. Cancer 1984;54: 2795–806.

    Article  PubMed  CAS  Google Scholar 

  14. Rios A, Rosenblum M, Powell M, Hersh E. Phase I study of MVE-2 therapy in human cancer. Cancer Treat Rep 1983;67:239–43.

    PubMed  CAS  Google Scholar 

  15. Rinehart JJ, Young DC, Neidhart JA. Evaluation of the immunological and toxicological properties of MVE-2 in phase I trials. Cancer Res 1983;43:2358–62.

    PubMed  CAS  Google Scholar 

  16. Stolfi RL, Martin DS. Therapeutic activity of maleic anhydridevinyl ether copolymers against spontaneous, autochthonous murine mammary tumors. Cancer Treat Rep 1978;62:1791–6.

    PubMed  CAS  Google Scholar 

  17. Ward JM, Yamamoto RS, Weisburger JH, Benjamin T. Brief communication: transplantation of chemically induced metastatic mucinous adenocarcinomas of the jejunum and colon in rats. J Natl Cancer Inst 1973;51:1997–9.

    PubMed  CAS  Google Scholar 

  18. Lehmann EL. Wilcoxon rank sum test. In: Nonparametrics: statistical methods based on ranks. San Francisco: Holden-Day, 1975: 5–13.

    Google Scholar 

  19. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966;50:163–70.

    PubMed  CAS  Google Scholar 

  20. Storer EH, Goldberg SM, Nivatvongs S. Colon, rectum and anus. In: Schwartz S, ed. Principles of surgery. 2nd ed. New York: McGraw-Hill, 1979:1225.

    Google Scholar 

  21. Turnbull RB, Fisher ER. The cytotoxic demonstration and significance of tumor cells in the mesenteric venous blood in patients with colorectal carcinoma. Surg Gynecol Obstet 1955;100:102–8.

    PubMed  Google Scholar 

  22. Cole WH. The mechanisms of spread of cancer. Surg Gynecol Obstet 1973;137:853–71.

    PubMed  CAS  Google Scholar 

  23. Cole WH, Roberts SS, Webb RS, Strehl FW, Oates GD. Dissemination of cancer with special emphasis on vascular spread and implantation. Ann Surg 1965;161:753–70.

    Article  PubMed  CAS  Google Scholar 

  24. Roberts S, Watne A, McGrath R, McGrew E, Cole WH. Technique and results of isolation of cancer cells from the circulating blood. Arch Surg 1958;76:334–46.

    CAS  Google Scholar 

  25. Nissen-Meyer R, Kjellgren K, Malmio K, Mansson B, Norin T. Surgical adjuvant chemotherapy: results with one short course with cyclophosphamide after mastectomy for breast cancer. Cancer 1978;41:2088–98.

    Article  PubMed  CAS  Google Scholar 

  26. Brown JM. A study of mechanism by which anticoagulation with warfarin inhibits blood-borne metastases. Cancer Res 1973; 33:1217–24.

    PubMed  CAS  Google Scholar 

  27. Hoover HC, Ketcham AF. Decreasing experimental metastases formation with anticoagulation and chemotherapy. Surg Forum 1975;26:173–4.

    PubMed  Google Scholar 

  28. Ryan JJ, Ketcham AS, Wexler H. Reduced incidence of spontaneous metastases with long-term coumadin therapy. Ann Surg 1968;168:163–8.

    Article  PubMed  CAS  Google Scholar 

  29. Honn KV, Cicone B, Skoff A. Proctacyclin: a potent antimetastatic agent. Science 1981;212:1270–2.

    Article  PubMed  CAS  Google Scholar 

  30. Clark J, Hall AW, Moossa AR. Treatment of obstructing cancer of the colon and rectum. Surg Gynecol Obstet 1975;141:541–4.

    PubMed  CAS  Google Scholar 

  31. Copeland EM, MacFadyen BV, Dudrick SJ. Effect of intravenous hyperalimentation on established delayed hypersensitivity in the cancer patient. Ann Surg 1976;184:60–4.

    Article  PubMed  CAS  Google Scholar 

  32. Law DK, Dudrick SJ, Abdou NI. The effects of protein calorie malnutrition on immune competence of the surgical patient. Surg Gynecol Obstet 1974;139:257–66.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. the Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin

    James L. Weese M.D., Ellen M. Gilbertson B.A., Stephen E. Syrjala Ph.D., Paul D. Whitney Ph.D. & James R. Starling M.D.

  2. the Department of Biostatistics, University of Wisconsin-Madison, Madison, Wisconsin

    James L. Weese M.D., Ellen M. Gilbertson B.A., Stephen E. Syrjala Ph.D., Paul D. Whitney Ph.D. & James R. Starling M.D.

  3. William S. Middleton Veterans Administration Hospital, Madison, Wisconsin

    James L. Weese M.D., Ellen M. Gilbertson B.A., Stephen E. Syrjala Ph.D., Paul D. Whitney Ph.D. & James R. Starling M.D.

  4. Department of Surgery, University of Wisconsin, G5/348, 600 Highland Avenue, 53792, Madison, Wisconsin

    James L. Weese M.D., Ellen M. Gilbertson B.A., Stephen E. Syrjala Ph.D., Paul D. Whitney Ph.D. & James R. Starling M.D.

Authors
  1. James L. Weese M.D.
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  2. Ellen M. Gilbertson B.A.
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  3. Stephen E. Syrjala Ph.D.
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  4. Paul D. Whitney Ph.D.
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  5. James R. Starling M.D.
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Additional information

Supported by grants from the Veterans Administration and from University Surgical Associates.

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Weese, J.L., Gilbertson, E.M., Syrjala, S.E. et al. Reduced incidence of rat colon cancer metastases by perioperative immunostimulation with maleic anhydride-divinyl ether-2 (MVE-2). Dis Colon Rectum 28, 217–221 (1985). https://doi.org/10.1007/BF02554033

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  • DOI: https://doi.org/10.1007/BF02554033

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