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Annals of Surgical Oncology

, Volume 5, Issue 3, pp 241–247 | Cite as

In vitro and in vivo effects of photodynamic therapy on murine malignant melanoma

  • Riad Haddad
  • Amir Blumenfeld
  • Annette Siegal
  • Ofer Kaplan
  • Meir Cohen
  • Yehuda Skornick
  • Hanoch Kashtan
Original Articles

Abstract

Background: The role of photodynamic therapy (PDT) in the treatment of malignant melanoma is not well defined, nor is it known whether the dark melanoma cells absorb the light used in PDT.

Methods:In vitro studies: 2×105 B16 murine melanoma cells were incubated with aluminum phthalocyanine (AlpcS4, 2.5 mg/kg) and were then subjected to photoradiation (50, 100 or 200 J/cm2). Viability was then assessed.In vivo studies: Histology: C57/B1 mice received 2×105 B16 cells subcutaneously and were randomized into study (PDT) and three control groups. AlpcS4 2.5 mg/kg was injected intraperitoneally and the mice were exposed to light (100 J/cm2). After 24 hours they were sacrificed and underwent autopsies. Survival: 40 mice were randomized into PDT (40 J/cm2) and control groups and were monitored for 50 days. Tumor growth: 40 mice were randomized into one control and three treatment groups (PDT on day 3, 6, or 12 after injection with B16 cells), and were monitored for 50 days. Temperature: Tumor temperatures before and at the end of PDT were recorded.

Results:In vitro studies: PDT caused a decrease in cell viability to 15.5±0.7%, 11.5±2.1%, and 1.5±0.7% (at 50, 100, and 200 J/cm2, respectively;P<.001). A significant reduction in thymidine incorporation was noted at all energy levels.In vivo studies: Histology: PDT caused massive tumor necrosis. Survival: PDT prolonged the survival of mice (41±13.4 days) compared to controls (15.8±3.8 days,P<.001). Tumor growth: 31 days after injection with B16 cells, the tumor size was 2.6±0.3 cm in the control group and 1.6±0.2, 0.9±0.3, and 1.0±0.4 cm in the PDT groups (days 3, 6 and 12, respectively;P<.01). Temperature: PDT increased skin temperature to 42.8°C±1.3°C, 45.3°C±3.5°C, and 51.7°C±2.7°C at 40, 60, and 100 J/cm2, respectively (P<.01).

Conclusions: Photodynamic therapy was found to have significant effects in experimental melanoma in mice. The role of PDT in human melanoma remains to be studied.

Key words

Melanoma PDT Hyperthermia 

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References

  1. 1.
    Dougherty TJ. Photosensitization of malignant tumors.Sem Surg Oncol 1986;2:24–37.Google Scholar
  2. 2.
    Lui H, Anderson RR. Photodynamic therapy in dermatology: recent developments.Dermatol Clin 1993;11:1–13.PubMedGoogle Scholar
  3. 3.
    Tse DT, Kertsen RC, Anderson RL. Hematoporphyrin derivative photoradiation therapy in managing nevoid basal cell carcinoma syndrome. A preliminary report.Arch Ophthalmol 1984;102:990–4.PubMedGoogle Scholar
  4. 4.
    Wilson BD, Mang TS, Cooper M, Stoll H. Use of photodynamic therapy for the treatment of extensive basal cell carcinoma.Facial Plast Surg 1989;6:185–9.PubMedGoogle Scholar
  5. 5.
    Lui H. Photodynamic therapy in dermatology with porfimer sodium and benzoporphyrin derivative: an update.Semin Oncol 1994;21(6):11–4.PubMedGoogle Scholar
  6. 6.
    Kashtan H, Haddad R, Yossiphov Y, Bar-On S, Skornick Y. Photodynamic therapy of colorectal cancer using a new light source, from in-vitro studies to a patient treatment.Dis Colon Rectum 1996;39:379–83.CrossRefPubMedGoogle Scholar
  7. 7.
    Hisazumi H, Miyoshi N, Misaki T. Whole bladder wall photoradiation therapy for carcinoma in-situ of the urinary bladder.J Urol 1984;131:884–7.PubMedGoogle Scholar
  8. 8.
    Favilla I, Barry WR, Gosbell A, Ellims P, Burgess F. Phototherapy of posterior uveal melanoma.Br J Ophthalmol 1991;75:718–21.PubMedGoogle Scholar
  9. 9.
    Nelson JS, McCullough JL, Berns MW. Photodynamic therapy of human malignant melanoma xenografts in athymic nude mice.J Natl Cancer Inst 1988;80:56–60.PubMedGoogle Scholar
  10. 10.
    Peng Q, Moan J, Kongshaug M, et al. Sensitizer for photodynamic therapy of cancer: a comparison of the tissue distribution of photofrin II and aluminum phthalocyanine tetrasulfonate in nude mice bearing a human malignant tumor.Int J Cancer 1991;48:258–64.PubMedGoogle Scholar
  11. 11.
    Malik Z, Dishi M, Garini Y. Fourier transform multipixel spectroscopy and spectral imaging of protoporphyrin in single melanoma cells.Photochem Photobiol 1996;63:635–41.Google Scholar
  12. 12.
    Ben-Hur E, Rosenthal I. The phthalocyanines: a new class of mammalian cell-photosensitizers with a potential for cancer phototherapy.Int J Radiat Biol 1985;47:145–7.Google Scholar
  13. 13.
    Berg C, Bommer JC, Moan J. Evaluation of sulfonated aluminum phthalocyanines for use in photochemotherapy. Cellular uptake studies.Cancer Lett 1989;44:7–15.CrossRefPubMedGoogle Scholar
  14. 14.
    Leunig M, Leunig A, Lankes P, Goetz E. Evaluation of photodynamic therapy-induced heating of hamster melanoma and its effect on local tumour eradication.Int J Hyperthermia 1994;10:297–306.PubMedGoogle Scholar
  15. 15.
    Biolo R, Jori G, Soncin M, et al. Effect of photosensitizer delivery system and irradiation parameters on the efficiency of photodynamic therapy of B16 pigmented melanoma in mice.Photochem Photobiol 1996;63:224–8.PubMedGoogle Scholar
  16. 16.
    Eisenthal A, Rosenberg SA. Cross-linking of anti-B16 melanoma monoclonal antibodies to LAK cells: possible role in the therapy of B16 melanoma.Clin Exp Metastasis 1988;5:387–94.Google Scholar
  17. 17.
    Wilson BD, Mang TS, Stoll H, Jones C, Cooper M, Dougherty TJ. Photodynamic therapy for treatment of basal cell carcinoma.Arch Dermatol 1992;128:1597–1601.CrossRefPubMedGoogle Scholar
  18. 18.
    Kennedy J. HPD photoradiation therapy for cancer at Kingston and Hamilton. In: Kessel D, Dougherty TJ, eds.Porphyrin Photosensitization. New York: Plenum Press, 1983:53–62.Google Scholar
  19. 19.
    Bruce RA. Photoradiation of choroidal malignant melanoma. In: Dioron DR, Gomes CJ, eds.Porphyrin Localization and Treatment of Tumors. New York: Alan R. Liss, 1984:777–85.Google Scholar
  20. 20.
    Dougherty TJ, Cooper MT, Mang TS. Cutaneous phototoxic occurrences in patients receiving PhotofrinO.Lasers Surg Med 1990;10:485–8.PubMedGoogle Scholar
  21. 21.
    Ito AS, Azzellini GC, Sliva SC, Serra O, Szabo AG. Optical absorption and fluorescence spectroscopy studies of ground state melanin-cationic porphyrins complexes.Biophys Chem 1992;45:79–89.CrossRefPubMedGoogle Scholar
  22. 22.
    Spikes JD. Phthalocyanines as photosensitizers in biological systems for the photodynamic therapy of tumors.Photochem Photobiol 1986;43:691–9.PubMedGoogle Scholar
  23. 23.
    Peng QJ, Nesland J, Moan JF, Evensen JF, Kongshaug M, Rimington C. Localization of fluorescent Photofrin II and aluminum phthalocyanine tetrasulfonate in transplanted human malignant tumor LOX and normal tissue of nude mice using highly light-sensitive video intensification microscopy.Int J Cancer 1990;45:972–80.PubMedGoogle Scholar
  24. 24.
    Rosenthal I. Phthalocyanines as photodynamic sensitizers.Photochem Photobiol 1991;53:859–70.PubMedGoogle Scholar
  25. 25.
    van Hillegersberg R, Kort WJ, Paul Wilson JH. Current status of photodynamic therapy in oncology.Drugs 1994;48:510–26.PubMedGoogle Scholar
  26. 26.
    Matsumoto N, Saito H, Miyosho N, Nakanishi K, Fukuda M. Combination effect of hyperthermia and photodynamic therapy on carcinoma.Arch Otolaryngol Head Neck Surg 1990;116:824–9.PubMedGoogle Scholar
  27. 27.
    Mang T. Combination studies of hyperthermia induced by the Nd:Yag laser as an adjuvant to photodynamic therapy.Lasers Surg Med 1990;10:173–8.PubMedGoogle Scholar
  28. 28.
    Glassberg E, Lewandowski L, Halich C, Lask G, Uitto J. Hyperthermia potentiates the effects of aluminum phthalocyanine tetrasulfonate-mediated photodynamic toxicity in human malignant and normal cell lines.Lasers Surg Med 1991;11:432–9.PubMedGoogle Scholar
  29. 29.
    Polla LL, Margalis RJ, Dover JS et al. Melanosomes are a primary target of Q-switched ruby laser irradiation in guinea pig skin.J Invest Dermatol 1982;89:281–6.Google Scholar

Copyright information

© The Society of Surgical Oncology, Inc. 1998

Authors and Affiliations

  • Riad Haddad
    • 1
  • Amir Blumenfeld
    • 1
  • Annette Siegal
    • 2
    • 3
  • Ofer Kaplan
    • 1
  • Meir Cohen
    • 1
  • Yehuda Skornick
    • 1
  • Hanoch Kashtan
    • 1
  1. 1.From the Department of Surgery “A”Tel-Aviv Sourasky Medical CenterIsrael
  2. 2.Department of PathologyHasharon Hospital, Petach-TikvaIsrael
  3. 3.the Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael

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