Abstract
The antitumor effects of combined use of ultrasound (US) and a photosensitizer, hematoporphyrin (Hp), were determined in mice bearing sarcoma 180. In order to find the optimum timing of the US irradiation after the administration of Hp, the Hp concentrations in the tumor and in the plasma were determined and were analyzed pharmacokinetically. Antitumor effects were evaluated by measuring the tumor size and the tumor weight. Hp alone showed no antitumor effect but US alone showed a slight antitumor effect. The combined treatment with US and Hp showed marked synergistic effects on sarcoma 180 (inhibition ratio was 74% of the control). From these results, the enhancement of antitumor effect is thought to be caused by the sensitization of tumor cells to US mediated by Hp.
Keywords: Ultrasound, Hematoporphyrin, Sarcoma 180, Antitumor effect
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REFERENCES
- 1. ) Dougherty , T. J. , Kaufman , J. E. , Goldfarb , A. , Weishaupt , K. R. , Boyle , D. G. and Mittleman , A.Photoradiation therapy for treatment of malignant tumors . Cancer Res. , 38 , 2628 – 2635 ( 1978. ). [PubMed] [Google Scholar]
- 2. ) Tomio , L. , Zorat , P. L. , Corti , F. , Calzavara , F. , Reddi , E. and Jori , J.Effect of hematoporphyrin and red light on AH130 solid tumor in rats . Acta Radiol. Oncol. , 22 , 49 – 53 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Hayata , Y. , Kato , H. , Konaka , C. , Ono , J. and Takizawa , N.Hematoporphyrin derivative and laser photoradiation in the treatment of lung cancer . Chest , 81 , 269 – 277 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Spikers , J. D.Phthalocyanines as photosensitizer in biological systems and for the photodynamic therapy of tumors . Photochem. Photobiol. , 43 , 691 – 699 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Yumita , N. , Okumura , A. , Nishigaki , R. , Umemura , K. and Umemura , S.The combination treatment of ultrasound and antitumor drugs on Yoshida sarcoma . Jpn. J. Hypertherm. Oncol. , 3 , 175 – 182 ( 1987. ). [Google Scholar]
- 6. ) Kremkau , F. W.Cancer therapy with ultrasound . J. Clin. Ultrasound , 7 , 287 – 300 ( 1979. . [DOI] [PubMed] [Google Scholar]
- 7. ) Cheng , A. Y. and Neyzaril , A.Deep local hyperthermia for cancer therapy: external electromagnetic and ultrasound techniques . Cancer Res. , 44 , 4736s – 4744s ( 1984. ). [PubMed] [Google Scholar]
- 8. ) Yumita , N. , Nishigaki , R. , Umemura , K. and Umemura , S.Hematoporphyrin as a sensitizer of cell‐damaging effect of ultrasound . Jpn. J. Cancer Res. , 80 , 219 – 222 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. ) Dougherty , T. J. , Grindery , G. B. , Weishaupt , K. R. and Boyle , D. G.Photoradiation therapy. II. Cure of animal tumors with hematoporphyrin and light . J. Natl. Cancer Inst. , 55 , 115 – 121 ( 1975. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Charles , J. G. and Dougherty , T. J.Determination of [3H] and [14C]hematoporphyrin derivative distribution in malignant and normal tissue . Cancer Res. , 39 , 146 – 151 ( 1979. ). [PubMed] [Google Scholar]
- 11. ) Lipson , R. L. , Baldes , A. M. and Olson , A. M.The use of derivative of hematoporphyrin in tumor detection . J. Natl. Cancer Inst. , 26 , 1 – 8 ( 1961. ). [PubMed] [Google Scholar]
- 12. ) Bugelski , P. J. , Porter , C. W. and Dougherty , T. J.Auto‐radiographic distribution of hematoporphyrin derivative in normal and tumor tissue of the mouse . Cancer Res. , 41 , 4606 – 4612 ( 1981. ). [PubMed] [Google Scholar]
- 13. ) Moan , J.Porphyrin photosensitization and phototherapy . Photochem. Photobiol. , 43 , 681 – 690 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Das , M. , Mukhtar , H. , Dixit , R. and Bickers , D.Role of active oxygen species in the photodestruction of micro‐somal cytochrome P‐450 and associated monooxygenases by hematoporphyrin derivative in rats . Cancer Res. , 45 , 608 – 615 ( 1985. ). [PubMed] [Google Scholar]
- 15. ) Das , M. , Mukhtar , H. , Greenspan , E. R. and Bickers , D. R.Photoenhancement of lipid peroxidation associated with the generation of reactive oxygen species in hepatic microsomes of hematoporphyrin derivative‐treated rats . Cancer Res. , 45 , 6328 – 6330 ( 1985. ). [PubMed] [Google Scholar]
- 16. ) Umemura , K. , Yumita , N. , Nishigaki , R. and Umemura , S.The enhancement of antitumor effect of the drug by ultrasound . Proc. Jpn. Cancer Assoc., 47th Annu. Meet. , 663 ( 1988. ) ( in Japanese ). [Google Scholar]
- 17. ) Kawasaki , S. , Inoue , S. and Sano , S.Photodynamic guanine modification by hematoporphyrin is specific for single‐stranded DNA with singlet oxygen as a mediator . Biochem. J. , 261 , 6090 – 6095 ( 1986. ). [PubMed] [Google Scholar]
- 18. ) Cannistaro , S. and Vorst , A. V.Photosensitization by hematoporphyrin: ESR evidence for free radical induction in unsaturated fatty acids and for singlet oxygen production . Biochem. Biophys. Res. Commun. , 74 , 1177 – 1185 ( 1977. ). [DOI] [PubMed] [Google Scholar]