Abstract
The Sonodynamically induced antitumor effect of a gallium‐porphyrin complex, ATX‐70, was evaluated in mice bearing colon 26. In order to find the optimum timing for the ultrasonic exposure after the administration of ATX‐70, the ATX‐70 concentrations in the plasma, skin, and tumor were measured and analyzed. Antitumor effect was estimated by measuring the tumor size. When used alone, ultrasound showed a slight antitumor effect, which became increasingly significant as the dose of ATX‐70 was increased, while use of ATX‐70 alone had no significant effect. At an ATX‐70 dose of 2.5 mg/kg or higher, the average tumor size decreased to smaller than a half by three days after the ultrasonic exposure. This was smaller than a third of the size of the untreated tumors on the same day. From these results, it is concluded that ATX‐70 significantly sensitizes tumors to ultrasound, demonstrating a synergistic antitumor effect.
Keywords: Ultrasound, Porphyrin complex, Colon 26, Antitumor effect, Sonodynamic therapy
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REFERENCES
- 1. ) Lele , P. P.Local hyperthermia by ultrasound . In “ Physical Aspects of Hyperthermia ,” ed. , Nussbaum G. H. , pp. 393 – 440 ( 1982. ). Am. Inst. Phys. , New York . [Google Scholar]
- 2. ) Kremkau , F. W.Cancer therapy with ultrasound . J. Clin. Ultrasound 7 , 287 – 300 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Akimoto , R.An experimental study on the enhancement of the effect of anti‐cancer drug by ultrasound . J. Jpn. Soc. Cancer Ther. 3 , 562 – 570 ( 1985. ). [PubMed] [Google Scholar]
- 4. ) Yumita , N. , Okumura , A. , Nishigaki , R. , Umemura , K. and Umemura , S.The combination treatment of ultrasound and anti‐tumor drugs on Yoshida sarcoma . Jpn. J. Hyperthermic Oncol. 3 , 175 – 182 ( 1987. ). [Google Scholar]
- 5. ) 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]
- 6. ) 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]
- 7. ) 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]
- 8. ) Umemura , S. , Yumita , N. , Nishigaki , R. and Umemura , K.Mechanism of cell damage by ultrasound in combination with hematoporphyrin . Jpn. J. Cancer Res. 81 , 955 – 960 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. ) Yumita , N. , Nishigaki , R. , Umemura , K. and Umemura , S.Synergetic effect of ultrasound and hematoporphyrin on sarcoma 180 . Jpn. J. Cancer Res. 81 , 304 – 308 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Umemura , S. , Yumita , N. , Nishigaki , R. and Umemura , K. , Sonochemical activation of hematoporphyrin: a potential modality for cancer treatment . Proc. 1989 IEEE Ultrasonics Symp. , 955 – 960 ( 1989. ). [Google Scholar]
- 11. ) Nakajima , S. , Maeda , T. , Omote , Y. , Hayashi , H. , Yamazaki , K. , Kobo , Y. , Takemura , S. , Shindo , Y. and Sakata , I.Tumor localizing Ga‐porphyrin complex (ATX‐70) as a new photosensitizer excited with YAG‐laser . J. Jpn. Soc. Laser Med. 10 , 225 – 228 ( 1989. ) ( in Japanese ). [Google Scholar]
- 12. ) Umemura , S. , Yumita , N. and Nishigaki , R.Enhancement of ultrasonically induced cell damage by a gallium‐porphyrin complex, ATX70 . Jpn. J. Cancer Res. 84 , 582 – 588 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. ) Yumita , N. , Nishigaki , R. , Umemura , K. , Morse , P. D. , Swartz , H. M. , Cain , C. A. and Umemura , S.Sonochemical activation of hematoporphyrin; an ESR study . Radiat. Res. 138 , 171 – 176 ( 1994. ). [PubMed] [Google Scholar]
- 14. ) Kessel , D. , Jeffers , R. , Fowlkes , J. B. and Cain , C.Porphyrin‐induced enhancement of ultrasound cytotoxicity . Int. J. Radiat. Biol. 66 , 221 – 228 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Corbett , T. H. , Grisworld , D. P. , Roberts , B. J. , Jr. , Peckham , J. and Schabel , F. M. , Jr.A mouse colon‐tumor model for experimental therapy . Cancer Chemother. Rep. 5 , 169 – 186 ( 1975. ). [Google Scholar]
- 16. ) Drug Evaluation Branch, National Cancer Institute . “ Instruction 245 ” ( 1977. ).
- 17. ) Tsukagoshi , S. , Tashiro , T. , Tsuruo , T. and Inaba , M.Random screening of potential anti‐cancer agents in Japan. VI . Jpn. J. Cancer Chemother. 21 , 1301 – 1557 ( 1994. ) ( in Japanese ). [PubMed] [Google Scholar]
- 18. ) Bellnier , D. A. , Ho , Y. K. , Panday , R. K. , Missert , J. R. and Dougherty , T. J.Distribution and elimination of Photofrin II in mice . Photochem. Photobiol. 50 , 221 – 228 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Kessel , D.Porphyrin‐lipoprotein association as a factor in porphyrin localization . Cancer Lett. 33 , 183 – 188 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Umemura , S. and Kawabata , K. , Enhancement of sonochemical reactions by second‐harmonic superimposition . Proc. 1993 IEEE Ultrasonics Symp. , 917 – 920 ( 1993. ). [Google Scholar]
- 21. ) Yumita , N. , Nishigaki , R. , Umemura , K. and Umemura , S.Study on sonodynamic therapy . Jpn. J. Med. Ultrason. 18 , 537 – 546 ( 1991. ) ( in Japanese ). [Google Scholar]