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Photodynamic therapy mediated by 5-aminolevulinic acid suppresses gliomas growth by decreasing the microvessels

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Summary

Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.

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References

  1. Ed WZ. Neurosurgery: Intracranial tumor. Wuhan: Hubei Science and Technology Press, 2004,397–400

    Google Scholar 

  2. Sathornsumetee S, Rich JN. New treatment strategies for malignant gliomas. Expert Rev Anticancer Ther, 2006,6(7):1087–1104

    Article  CAS  PubMed  Google Scholar 

  3. Aoki T, Hashimoto N, Matsutani M. Management of glioblastoma. Expert Opinion Pharmacother, 2007,8(18): 3133–3146

    Article  CAS  Google Scholar 

  4. Tomankova K, Kolarova H, Kolar P, et al. Study of cytotoxic effect of photodynamically and sonodynamically activated sensitizers in vitro. Toxicol In Vitro, 2009,23(8):1465–1471

    Article  CAS  PubMed  Google Scholar 

  5. Leman JA, Morton CA. Photodynamic therapy: applications in dermatology. Expert Opin Biol Ther, 2002,2(1):45–53

    Article  CAS  PubMed  Google Scholar 

  6. Barr H, Kendall C, Stone N. Photodynamic therapy for esophageal cancer: a useful and realistic option. Technol Cancer Res Treat, 2003,2(1):65–76

    Article  PubMed  Google Scholar 

  7. McGillis ST, Fein H. Topical treatment strategies for non-melanoma skin cancer and precursor lesions. Semin Cutan Med Surg, 2004,23(3):174–183

    Article  PubMed  Google Scholar 

  8. Svatek RS, Kamat AM, Dinney CP. Novel therapeutics for patients with non-muscle-invasive bladder cancer. Expert Rev Anticancer Ther, 2009,9(6):807–813

    Article  CAS  PubMed  Google Scholar 

  9. Pogue BW, Gibbs-Strauss S, Valdes PA, et al. Review of neurosurgical fluorescence imaging methodologies. IEEE J Sel Top Quantum Electron, 2010,16(3):493–505

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Redmond RW, Gamlin JN. A compilation of singlet oxygen yields from biologically relevant molecules. Photochem Photobiol, 1999,70(4):391–475

    Article  CAS  PubMed  Google Scholar 

  11. Fotinos N, Campo MA, Popowycz F, et al. 5-Aminolevulinic acid derivatives in photomedicine: Characteristics, application and perspectives. Photochem Photobiol, 2006,82(4):994–1015

    Article  CAS  PubMed  Google Scholar 

  12. Leggett CL, Gorospe EC, Murad MH, et al. Photodynamic therapy for unresectable cholangiocarcinoma: a comparative effectiveness systematic review and meta-analyses. Photodiagnosis Photodyn Ther, 2012,9(3):189–195

    Article  PubMed  Google Scholar 

  13. Peng Q, Nesland JM. Effects of photodynamic therapy on tumor stroma. Ultrastruct Pathol, 2004,28(5–6):333–340

    Article  PubMed  Google Scholar 

  14. Eljamel MS, Goodman C, Moseley H. ALA and Photofrin fluorescence-guided resection and repetitive PDT in glioblastoma multiforme: a single centre phase III randomised controlled trial. Lasers Med Sci, 2008,23(4):361–367

    Article  PubMed  Google Scholar 

  15. Stepp H, Beck T, Pongratz T, et al. ALA and malignant glioma: fluorescence-guided resection and photodynamic treatment. J Environ Pathol Toxicol Oncol, 2007,26(2):157–164

    Article  CAS  PubMed  Google Scholar 

  16. Cao Y, Zhang MZ, Zhao JZ, et al. Photodynamic diagnosis and fluorescence-guided resection of malignant gliomas: a report of 15 cases. Zhonghua Wai Ke Za Zhi (Chinese), 2005,43(5):334–338

    Google Scholar 

  17. Zimmermann A, Ritsch-Marte M, Kostron H. mTHPC-mediated photodynamic diagnosis of malignant brain tumors. Photochem Photobiol, 2001,74(4):611–616

    Article  CAS  PubMed  Google Scholar 

  18. Huang Z. A review of progress in clinical photodynamic therapy. Technol Cancer Res Treat, 2005,4(3):283–293

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Yoo JO HK. New insights into the mechanisms for photodynamic therapy-induced cancer cell death. Int Rev Cell Mol Biol, 2012,295:139–174

    Article  CAS  PubMed  Google Scholar 

  20. Karmakar S, Banik NL, Patel SJ, et al. 5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Neurosci Lett, 2007,415(3):242–247

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Kamoshima Y, Terasaka S, Iwasaki Y. Photodynamic therapy mediated with 5-aminolevulinic acid for C6 glioma spheroids. Hokkaido Igaku Zasshi, 2008,83(3):167–173

    CAS  PubMed  Google Scholar 

  22. Kamoshima Y, Terasaka S, Kuroda S, et al. Morphological and histological changes of glioma cells immediately after 5-aminolevulinic acid mediated photodynamic therapy. Neurol Res, 2011,33(7):739–746

    Article  CAS  PubMed  Google Scholar 

  23. Weidner N. Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol, 1995,147(1):9–19

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Hu SS, Cheng HB, Zheng YR, et al. Effects of photodynamic therapy on the ultrastructure of glioma cells. Biomed Environ Sci, 2007,20(4):269–273

    CAS  PubMed  Google Scholar 

  25. Stummer W, Tonn JC, Mehdorn HM, et al. Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. J Neurosurg, 2011,114(3):613–623

    Article  PubMed  Google Scholar 

  26. Hirschberg H, Sun CH, Krasieva T, et al. Effects of ALA-mediated photodynamic therapy on the invasiveness of human glioma cells. Lasers Surg Med, 2006,38(10):939–945

    Article  PubMed  Google Scholar 

  27. Hirschberg H, Spetalen S, Carper S, et al. Minimally invasive photodynamic therapy (PDT) for ablation of experimental rat glioma. Minim Invasive Neurosurg, 2006,49(3):135–142

    Article  CAS  PubMed  Google Scholar 

  28. Wu SM, Ren QG, Zhou MO, et al. Protoporphyrin IX production and its photodynamic effects on glioma cells, neuroblastoma cells and normal cerebellar granule cells in vitro with 5-aminolevulinic acid and its hexylester. Cancer Lett 2003,200(2):123–131

    Article  CAS  PubMed  Google Scholar 

  29. Otake M, Nishiwaki M, Kobayashi Y, et al. Selective accumulation of ALA-induced PpIX and photodynamic effect in chemically induced hepatocellular carcinoma. Br J Cancer 2003,89(4):730–736

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Vrouenraets MB, Visser GW, Snow GB, et al. Basic principles, applications in oncology and improved selectivity of photodynamic therapy. Anticancer Res, 2003,23(1B):505–522

    CAS  PubMed  Google Scholar 

  31. Silva JN, Filipe P, Morliere P, et al. Photodynamic therapies: principles and present medical applications. Biomed Mater Eng, 2006,16(4 Suppl):S147–S154

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Wei Yi  (易 伟), Hai-tao Xu  (徐海涛), Dao-feng Tian  (田道锋), Li-quan Wu  (吴立权), Shen-qi Zhang  (张申起), Long Wang  (王 龙), Bao-wei Ji  (冀保卫), Xiao-nan Zhu  (朱晓楠), Humphrey Okechi, Gang Liu  (刘 刚) & Qian-xue Chen  (陈谦学)

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  1. Wei Yi  (易 伟)
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  2. Hai-tao Xu  (徐海涛)
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  3. Dao-feng Tian  (田道锋)
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  4. Li-quan Wu  (吴立权)
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  5. Shen-qi Zhang  (张申起)
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  6. Long Wang  (王 龙)
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  7. Bao-wei Ji  (冀保卫)
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  8. Xiao-nan Zhu  (朱晓楠)
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  9. Humphrey Okechi
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  10. Gang Liu  (刘 刚)
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  11. Qian-xue Chen  (陈谦学)
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Corresponding author

Correspondence to Qian-xue Chen  (陈谦学).

Additional information

Both authors contributed equally to this work.

This work was supported by the grants from the National Natural Science Foundation of China (No. 30973073, 81172402 and 81372683).

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Yi, W., Xu, Ht., Tian, Df. et al. Photodynamic therapy mediated by 5-aminolevulinic acid suppresses gliomas growth by decreasing the microvessels. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 259–264 (2015). https://doi.org/10.1007/s11596-015-1421-6

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  • DOI: https://doi.org/10.1007/s11596-015-1421-6

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