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The Effect of Indomethacin on the Growth of Epidermoid Carcinoma of the Palate in Rats

The Effect of Indomethacin on the Growth of Epidermoid Carcinoma of the Palate in Rats Abstract • The in vivo effect of indomethacin therapy in head and neck cancer was tested using rats (Fisher 344) with implanted epithelial palatal carcinoma. Indomethacin was then given to half of the rats in their drinking water, starting two weeks after tumor implantation. The animals were then killed at four weeks and the tumor volumes were measured. It was found that four (21%) of the 19 rats were complete responders and eight (42%) of the 19 rats were partial responders. The control group showed increased tumor growth in all animals. The experimental group also demonstrated five (26%) of the 19 regional metastases. No metastases were seen in the control group. Indomethacin seems to inhibit local tumor growth, perhaps through its effects on cellular and humoral immunity and its effects on the host-tissue stroma. It also may increase tumor spread through the regional lymphatics or hematogenously. Further animal studies need to be carried out to determine the effect on cancer on a cellular and biochemical level before using it for treatment of cancer in humans. (Arch Otolaryngol 1983;109:719-723) References 1. Hon KU, Bockman RS, Marnett LJ: Prostaglandins and cancer: A review of tumor initiation through tumor metastasis . Prostaglandins 1981;21:833-864.Crossref 2. Goodwin JS: Prostaglandins and host defense in cancer . Med Clin North Am 1981; 65:829-844. 3. Voelkel EF, Tashjian AH, Franklin R, et al: Hypercalcemia and tumor-prostaglandins: The VX2 carcinoma model in the rabbit . Metabolism 1975;24:973-986.Crossref 4. Husby G, Strickland RG, Rigler GL, et al: Direct immunochemical detection of prostaglandin and cyclic nucleotides in human malignant tumors . Cancer 1977;40:1629.Crossref 5. Panje WR: Regression of head and neck carcinoma with a prostaglandin-synthesis inhibitor . Arch Otolaryngol 1981;107:658-663.Crossref 6. Rolland PH, Martin PM, Jacquemier J, et al: Prostaglandin in human breast cancer: Evidence suggesting that an elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells . JNCI 1980;64:1061-1070. 7. Huang CC, Blitzer A, Abramson M: Collagenase and protease activities in head and neck tumors . Otolaryngol Head Neck Surg 1980;88:749-752. 8. Huang CC: Prostaglandin E2, collagenase and protease levels in culture of rat tumor . Otolaryngol Head Neck Surg 1981;89:564-568. 9. Plescia OJ, Smith AH, Grinwich K: Subversion of the immune system by tumor cells and the role of prostaglandins . Proc Natl Acad Sci USA 1975;72:1848-1851.Crossref 10. Picker LJ, Ruff HV, Goldyne ME, et al: Metabolic heterogeneity among human monocytes and its modulation by PGE2 . J Immunol 1980;124:2557-2562. 11. Webb DR, Osheroff PL: Antigen stimulation of prostaglandin synthesis and control of immune responses . Proc Natl Acad Sci USA 1976;73:1300-1304.Crossref 12. Goodwin J, Ceuppens J: Prostaglandins and the immune response to cancer, review . Anticancer Res 1981;1:71-78. 13. Tilden AB, Balch CM: Indomethacin enhancement of immunocompetence in melanoma patients . Surgery 1981;90:77-84. 14. Bennett A, Charlier EM, McDonald AM, et al: Prostaglandins and breast cancer . Lancet 1977;2:624-626.Crossref 15. Blitzer A: Regional behavioral variations of epidermoid carcinoma of the head and neck: A study in an animal model . Laryngoscope 1982; 92:1219-1238.Crossref 16. Lynch NR, Salomon J: Tumor growth inhibition and potentiation of immunotherapy by indomethacin in mice . JNCI 1979;62:117-121. 17. Pollard M, Luckert PH: Indomethacin treatment of rats with dimethylhydrazine-induced intestinal tumors . Cancer Treat Rep 1980;64:1323-1327. 18. Bennett A, Houghton J, Leaper DJ, et al: Cancer growth, response to treatment, and survival time in mice: Beneficial effect of the prostaglandin-synthesis inhibitor flurbiprofen . Prostaglandins 1979;17:179-191.Crossref 19. Pollard M, Luckert PH: Effect of indomethacin on intestinal tumors induced in rats by the acetate derivative of dimethylnitrosamine . Science 1981;214:558-559.Crossref 20. Hial V, Horakova Z, Shaff RE, et al: Alteration of tumor growth by aspirin and indomethacin: Studies with two transplantable tumors in mouse . Eur J Pharmacol 1976;37:367-376.Crossref 21. Maca R, Panje W: Indomethacin-sensitive suppressor cells in patients with head and neck carcinomas . Proc Am Assoc Cancer Res 1980; 21:211. 22. Gasic G, Gasic T, Murphy S: Aspirin: A possible antimetastatic agent: Its effect on tumor spread in mice, abstracted . Proc Am Assoc Cancer Res 1973;14:87. 23. Tutton PJM, Barkia PH: Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth . Br J Cancer 1980; 41:47-51.Crossref 24. Kibbey WE, Bronn DG, Minton JP: Prostaglandins and metastasis . Lancet 1978;1:101.Crossref 25. Bennett A, Berstock DA, Raja B, et al: Survival time after surgery is inversely related to the amounts of prostaglandins extracted from human breast cancers . Br J Pharmacol 1979; 66:451. 26. Galasko CSB, Bennett A: Relationship of bone destruction in skeletal metastases to osteoclast activation and prostaglandins . Nature 1976;263:508-510.Crossref 27. Stringfellow D, Fitzpatrick F: Prostaglandin D2 controls pulmonary metastases of malignant melanoma cells . Nature 1979;282:76-78.Crossref 28. Jubiz W, Frailey J, Smith JB: Inhibitory effect of prostaglandin F2 on the growth of a hormone-dependent rat mammary tumor . Cancer Res 1979;39:998-1000. 29. Santoro MG, Philpott GW, Jaffe BM: Inhibition of B-16 melanoma growth in vivo by a synthetic analogue of PGE2 . Cancer Res 1977; 37:3774-3779. 30. Powles TJ, Alexander P, Millar JL: Enhancement of anticancer activity of cytotoxic chemotherapy with protection of normal tissue by inhibition of prostaglandin synthesis . Biochem Pharmacol 1978;27:1389-1392.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Otolaryngology American Medical Association

The Effect of Indomethacin on the Growth of Epidermoid Carcinoma of the Palate in Rats

Archives of Otolaryngology , Volume 109 (11) – Nov 1, 1983

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References (35)

Publisher
American Medical Association
Copyright
Copyright © 1983 American Medical Association. All Rights Reserved.
ISSN
0003-9977
DOI
10.1001/archotol.1983.00800250013003
Publisher site
See Article on Publisher Site

Abstract

Abstract • The in vivo effect of indomethacin therapy in head and neck cancer was tested using rats (Fisher 344) with implanted epithelial palatal carcinoma. Indomethacin was then given to half of the rats in their drinking water, starting two weeks after tumor implantation. The animals were then killed at four weeks and the tumor volumes were measured. It was found that four (21%) of the 19 rats were complete responders and eight (42%) of the 19 rats were partial responders. The control group showed increased tumor growth in all animals. The experimental group also demonstrated five (26%) of the 19 regional metastases. No metastases were seen in the control group. Indomethacin seems to inhibit local tumor growth, perhaps through its effects on cellular and humoral immunity and its effects on the host-tissue stroma. It also may increase tumor spread through the regional lymphatics or hematogenously. Further animal studies need to be carried out to determine the effect on cancer on a cellular and biochemical level before using it for treatment of cancer in humans. (Arch Otolaryngol 1983;109:719-723) References 1. Hon KU, Bockman RS, Marnett LJ: Prostaglandins and cancer: A review of tumor initiation through tumor metastasis . Prostaglandins 1981;21:833-864.Crossref 2. Goodwin JS: Prostaglandins and host defense in cancer . Med Clin North Am 1981; 65:829-844. 3. Voelkel EF, Tashjian AH, Franklin R, et al: Hypercalcemia and tumor-prostaglandins: The VX2 carcinoma model in the rabbit . Metabolism 1975;24:973-986.Crossref 4. Husby G, Strickland RG, Rigler GL, et al: Direct immunochemical detection of prostaglandin and cyclic nucleotides in human malignant tumors . Cancer 1977;40:1629.Crossref 5. Panje WR: Regression of head and neck carcinoma with a prostaglandin-synthesis inhibitor . Arch Otolaryngol 1981;107:658-663.Crossref 6. Rolland PH, Martin PM, Jacquemier J, et al: Prostaglandin in human breast cancer: Evidence suggesting that an elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells . JNCI 1980;64:1061-1070. 7. Huang CC, Blitzer A, Abramson M: Collagenase and protease activities in head and neck tumors . Otolaryngol Head Neck Surg 1980;88:749-752. 8. Huang CC: Prostaglandin E2, collagenase and protease levels in culture of rat tumor . Otolaryngol Head Neck Surg 1981;89:564-568. 9. Plescia OJ, Smith AH, Grinwich K: Subversion of the immune system by tumor cells and the role of prostaglandins . Proc Natl Acad Sci USA 1975;72:1848-1851.Crossref 10. Picker LJ, Ruff HV, Goldyne ME, et al: Metabolic heterogeneity among human monocytes and its modulation by PGE2 . J Immunol 1980;124:2557-2562. 11. Webb DR, Osheroff PL: Antigen stimulation of prostaglandin synthesis and control of immune responses . Proc Natl Acad Sci USA 1976;73:1300-1304.Crossref 12. Goodwin J, Ceuppens J: Prostaglandins and the immune response to cancer, review . Anticancer Res 1981;1:71-78. 13. Tilden AB, Balch CM: Indomethacin enhancement of immunocompetence in melanoma patients . Surgery 1981;90:77-84. 14. Bennett A, Charlier EM, McDonald AM, et al: Prostaglandins and breast cancer . Lancet 1977;2:624-626.Crossref 15. Blitzer A: Regional behavioral variations of epidermoid carcinoma of the head and neck: A study in an animal model . Laryngoscope 1982; 92:1219-1238.Crossref 16. Lynch NR, Salomon J: Tumor growth inhibition and potentiation of immunotherapy by indomethacin in mice . JNCI 1979;62:117-121. 17. Pollard M, Luckert PH: Indomethacin treatment of rats with dimethylhydrazine-induced intestinal tumors . Cancer Treat Rep 1980;64:1323-1327. 18. Bennett A, Houghton J, Leaper DJ, et al: Cancer growth, response to treatment, and survival time in mice: Beneficial effect of the prostaglandin-synthesis inhibitor flurbiprofen . Prostaglandins 1979;17:179-191.Crossref 19. Pollard M, Luckert PH: Effect of indomethacin on intestinal tumors induced in rats by the acetate derivative of dimethylnitrosamine . Science 1981;214:558-559.Crossref 20. Hial V, Horakova Z, Shaff RE, et al: Alteration of tumor growth by aspirin and indomethacin: Studies with two transplantable tumors in mouse . Eur J Pharmacol 1976;37:367-376.Crossref 21. Maca R, Panje W: Indomethacin-sensitive suppressor cells in patients with head and neck carcinomas . Proc Am Assoc Cancer Res 1980; 21:211. 22. Gasic G, Gasic T, Murphy S: Aspirin: A possible antimetastatic agent: Its effect on tumor spread in mice, abstracted . Proc Am Assoc Cancer Res 1973;14:87. 23. Tutton PJM, Barkia PH: Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth . Br J Cancer 1980; 41:47-51.Crossref 24. Kibbey WE, Bronn DG, Minton JP: Prostaglandins and metastasis . Lancet 1978;1:101.Crossref 25. Bennett A, Berstock DA, Raja B, et al: Survival time after surgery is inversely related to the amounts of prostaglandins extracted from human breast cancers . Br J Pharmacol 1979; 66:451. 26. Galasko CSB, Bennett A: Relationship of bone destruction in skeletal metastases to osteoclast activation and prostaglandins . Nature 1976;263:508-510.Crossref 27. Stringfellow D, Fitzpatrick F: Prostaglandin D2 controls pulmonary metastases of malignant melanoma cells . Nature 1979;282:76-78.Crossref 28. Jubiz W, Frailey J, Smith JB: Inhibitory effect of prostaglandin F2 on the growth of a hormone-dependent rat mammary tumor . Cancer Res 1979;39:998-1000. 29. Santoro MG, Philpott GW, Jaffe BM: Inhibition of B-16 melanoma growth in vivo by a synthetic analogue of PGE2 . Cancer Res 1977; 37:3774-3779. 30. Powles TJ, Alexander P, Millar JL: Enhancement of anticancer activity of cytotoxic chemotherapy with protection of normal tissue by inhibition of prostaglandin synthesis . Biochem Pharmacol 1978;27:1389-1392.Crossref

Journal

Archives of OtolaryngologyAmerican Medical Association

Published: Nov 1, 1983

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