Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model

  • Authors:
    • Sigeaki Yanase
    • Jouji Nomura
    • Yoshihiko Matsumura
    • Takayuki Nagata
    • Tasuku Fujii
    • Toshiro Tagawa
  • View Affiliations

  • Published online on: August 1, 2006     https://doi.org/10.3892/ijo.29.2.365
  • Pages: 365-373
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Abstract

In this study, the effectiveness and mechanism of combination therapy of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) with simultaneous hyperthermia (HT) on human-derived osteosarcoma in vivo were examined. A tumor model was prepared by subcutaneously implanting human osteosarcoma into nude mice and local injection of ALA was selected as the administration route. This study demonstrated that both ALA-PDT and the combination of ALA-PDT with HT exhibited significant inhibitory effects on tumor growth. In the group with high total energy, the growth inhibition rates of tumor were 52.3% in ALA-PDT, and 27.3% in ALA-PDT with simultaneous HT (PDT+HT), and the synergetic index was 1.76, demonstrating that the inhibitory effect on tumor growth in ALA-PDT was significantly increased by simultaneous use of HT. In the histological findings, after ALA-PDT, necrosis was observed in the area from the surface to a depth of 2 mm, and only a slight effect was confirmed in deeper layers. On the other hand, after PDT+HT, necrosis was observed in layers even deeper than 2 mm below the surface. Furthermore, based on the immunohistochemical findings of the expression of carbonic anhydrase IX, while weak expression of CAIX was observed after ALA-PDT in an area relatively close to the surface, a positive area extended to the deeper layers after PDT+HT compared with ALA-PDT. In conclusion, PDT+HT demonstrated a significant inhibitory effect on tumor growth of human-derived osteosarcoma, and a synergistic interaction of simultaneous HT. This suggests the possibility that ALA-PDT is useful, not only for the treatment of superficial tumors but also for deep-seated mesenchymal tumors, such as osteosarcoma. Furthermore, the mechanism of the synergistic interaction suggested that ALA-PDT was effective in the deep area of tumors due to the increase of blood flow by mild hyperthermia.

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August 2006
Volume 29 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yanase S, Nomura J, Matsumura Y, Nagata T, Fujii T and Tagawa T: Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model. Int J Oncol 29: 365-373, 2006
APA
Yanase, S., Nomura, J., Matsumura, Y., Nagata, T., Fujii, T., & Tagawa, T. (2006). Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model. International Journal of Oncology, 29, 365-373. https://doi.org/10.3892/ijo.29.2.365
MLA
Yanase, S., Nomura, J., Matsumura, Y., Nagata, T., Fujii, T., Tagawa, T."Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model". International Journal of Oncology 29.2 (2006): 365-373.
Chicago
Yanase, S., Nomura, J., Matsumura, Y., Nagata, T., Fujii, T., Tagawa, T."Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model". International Journal of Oncology 29, no. 2 (2006): 365-373. https://doi.org/10.3892/ijo.29.2.365