Skip to main content

Advertisement

SpringerLink
Log in

Advantages of laserphyrin compared with photofrin in photodynamic therapy for bile duct carcinoma

  • Original article
  • Published:
Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

Background

The aim of this study was to compare the effects of laserphyrin-PDT (L-PDT) on biliary cancer with those of the conventional photosensitizer, photofrin-PDT (P-PDT).

Methods

An animal tumor model was established by inoculation of NOZ cells in 4-week-old male BALB/c mice. The laser light wavelength was set at 630 nm for P-PDT and 660 nm for L-PDT, at a frequency of 10 Hz. Each group received a total energy flux of 60 J/cm2. The proportion of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling)-positive cells, expression of VEGF (vascular endothelial growth factor) and the PCNA (proliferating cell nuclear antigen)-labeling index (LI) were assessed after PDT.

Results

L-PDT had significantly more potent apoptotic effects at 48 and 72 h after light exposure compared with P-PDT (P < 0.001). The mean PCNA-LI was significantly lower in the L-PDT group than the P-PDT group and the index was significantly lower at several time points after PDT (6, 12, 24, 48 and 72 h after laser light exposure) in the L-PDT than P-PDT (P < 0.001 vs. control). The cell proliferative activity was significantly decreased at 12 and 24 h after P-PDT compared with the control (P < 0.001). VEGF expression was significantly higher at 3 h after L-PDT compared with the control (P < 0.05), whereas it was significantly higher at many time points after P-PDT (3, 6, 48 and 72 h; P < 0.05 vs. control).

Conclusions

L-PDT is a better approach for biliary cancer than the conventional P-PDT, based on its potent apoptotic and cytostatic effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. McCaughan JS Jr, Mertens BF, Cho C, Barabash RD, Payton HW. Photodynamic therapy to treat tumors of the extrahepatic biliary ducts. A case report. Arch Surg. 1991;126:111–3.

    PubMed  Google Scholar 

  2. Witzigmann H, Berr F, Ringel U, Caca K, Uhlmann D, Schoppmeyer K, et al. Surgical and palliative management and outcome in 184 patients with hilar cholangiocarcinoma: palliative photodynamic therapy plus stenting is comparable to r1/r2 resection. Ann Surg. 2006;244:230–9.

    Article  PubMed  Google Scholar 

  3. Ortner MA, Liebetruth J, Schreiber S, Hanft M, Wruck U, Fusco V, et al. Photodynamic therapy of nonresectable cholangiocarcinoma. Gastroenterology. 1998;114:536–42.

    Article  PubMed  CAS  Google Scholar 

  4. Berr F, Wiedmann M, Tannapfel A, Halm U, Kohlhaw KR, Schmidt F, et al. Photodynamic therapy for advanced bile duct cancer: evidence for improved palliation and extended survival. Hepatology. 2000;31:291–8.

    Article  PubMed  CAS  Google Scholar 

  5. Rumalla A, Baron TH, Wang KK, Gores GJ, Stadheim LM, de Groen PC. Endoscopic application of photodynamic therapy for cholangiocarcinoma. Gastrointest Endosc. 2001;53:500–4.

    Article  PubMed  CAS  Google Scholar 

  6. Ortner ME, Caca K, Berr F, Liebetruth J, Mansmann U, Huster D, et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology. 2003;125:1355–63.

    Article  PubMed  Google Scholar 

  7. Zoepf T, Jakobs R, Arnold JC, Apel D, Riemann JF. Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy. Am J Gastroenterol. 2005;100:2426–30.

    Article  PubMed  CAS  Google Scholar 

  8. Zoepf T. Photodynamic therapy of cholangiocarcinoma. HPB (Oxford). 2008;10:161–3.

    CAS  Google Scholar 

  9. Nanashima A, Yamaguchi H, Shibasaki S, Ide N, Sawai T, Tsuji T, et al. Adjuvant photodynamic therapy for bile duct carcinoma after surgery: a preliminary study. J Gastroenterol. 2004;39:1095–101.

    Article  PubMed  Google Scholar 

  10. Gao Fei, Bai Yu, Shu-Ren Ma, Liu Feng, Zhao-Shen Li. Systematic review: photodynamic therapy for unresectable cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2010;17:125–31.

    Article  PubMed  Google Scholar 

  11. Gomer CJ, Rucker N, Ferrario A, Wong S. Properties and applications of photodynamic therapy. Radiat Res. 1989;120:1–18.

    Article  PubMed  CAS  Google Scholar 

  12. Roberts WG, Shiau FY, Nelson JS, Smith KM, Berns MW. In vitro characterization of monoaspartyl chlorin e6 and diaspartyl chlorin e6 for photodynamic therapy. J Natl Cancer Inst. 1988;80:330–6.

    Article  PubMed  CAS  Google Scholar 

  13. Ferrario A, Kessel D, Gomer CJ. Metabolic properties and photosensitizing responsiveness of mono-l-aspartyl chlorin e6 in a mouse tumor model. Cancer Res. 1992;52:2890–3.

    PubMed  CAS  Google Scholar 

  14. Roberts WG, Smith KM, McCullough JL, Berns MW. Skin photosensitivity and photodestruction of several potential photodynamic sensitizers. Photochem Photobiol. 1989;49:431–8.

    Article  PubMed  CAS  Google Scholar 

  15. Kasuya K, Shimazu M, Suzuki M, Kuroiwa Y, Usuda J, Itoi T, et al. Novel photodynamic therapy against biliary tract carcinoma using mono-L-aspartyl chlorine e6: basic evaluation for its feasibility and efficacy. J Hepatobiliary Pancreat Sci. 2010;17:313–21.

    Article  PubMed  Google Scholar 

  16. Kato H, Furukawa K, Sato M, Okunaka T, Kusunoki Y, Kawahara M, et al. Phase II clinical study of photodynamic therapy using mono-l-aspartyl chlorin e6 and diode laser for early superficial squamous cell carcinoma of the lung. Lung Cancer. 2003;42:103–11.

    Article  PubMed  Google Scholar 

  17. Nonaka T, Nanashima A, Nonaka M, Uehara M, Isomoto H, Asahina I, et al. Analysis of apoptotic effects induced by photodynamic therapy in a human biliary cancer cell line. Anticancer Res. 2010;30:2113–8.

    PubMed  CAS  Google Scholar 

  18. Uehara M, Sano K, Wang ZL. Enhancement of the photodynamic antitumor effect by streptococcal preparation OK-432 in the mouse carcinoma. Cancer Immunol Immunother. 2000;49:401–9.

    Article  PubMed  CAS  Google Scholar 

  19. Wu LC, D’Amelio F, Fox RA, Polyakov I, Daunton NG. Light microscopic image analysis system to quantify immunoreactive terminal area apposed to nerve cells. J Neurosci Methods. 1997;74:89–96.

    Article  PubMed  CAS  Google Scholar 

  20. Oleinick NL, Morris RL, Belichenko I. The role of apoptosis in response to photodynamic therapy: what, where, why, and how. Photochem Photobiol Sci. 2002;1:1–21.

    Article  PubMed  CAS  Google Scholar 

  21. Luo Y, Chang CK, Kessel D. Rapid initiation of apoptosis by photodynamic therapy. Photochem Photobiol. 1996;63:528–34.

    Article  PubMed  CAS  Google Scholar 

  22. Gomer CJ, Ferrario A, Luna M, Rucker N, Wong S. Photodynamic therapy: combined modality approaches targeting the tumor microenvironment. Lasers Surg Med. 2006;38:516–21.

    Article  PubMed  Google Scholar 

  23. Dougherty TJ. An update on photodynamic therapy applications. J Clin Laser Med Surg. 2002;20:3–7.

    Article  PubMed  Google Scholar 

  24. Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, et al. Photodynamic therapy. J Natl Cancer Inst. 1998;90:889–905.

    Article  PubMed  CAS  Google Scholar 

  25. Ahmad N, Mukhtar H. Mechanism of photodynamic therapy-induced cell death. Methods Enzymol. 2000;319:342–58.

    Article  PubMed  CAS  Google Scholar 

  26. Usuda J, Okunaka T, Furukawa K, Tsuchida T, Kuroiwa Y, Ohe Y, et al. Increased cytotoxic effects of photodynamic therapy in IL-6 gene transfected cells via enhanced apoptosis. Int J Cancer. 2001;93:475–80.

    Article  PubMed  CAS  Google Scholar 

  27. Mathews MB, Bernstein RM, Franza BR Jr, Garrels JI. Identity of the proliferating cell nuclear antigen and cyclin. Nature. 1984;309:374–6.

    Article  PubMed  CAS  Google Scholar 

  28. Bravo R, Frank R, Blundell PA, Macdonald-Bravo H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 1987;326:515–7.

    Article  PubMed  CAS  Google Scholar 

  29. Wong Kee Song LM, Wang KK, Zinsmeister AR. Mono-l-aspartyl chlorin e6 (NPe6) and hematoporphyrin derivative (HpD) in photodynamic therapy administered to a human cholangiocarcinoma model. Cancer. 1998;82:421–7.

    Article  PubMed  CAS  Google Scholar 

  30. Kobayashi W, Liu Q, Matsumiya T, Nakagawa H, Yoshida H, Imaizumi T, et al. Photodynamic therapy upregulates expression of Mac-1 and generation of leukotriene B(4) by human polymorphonuclear leukocytes. Oral Oncol. 2004;40:506–10.

    Article  PubMed  CAS  Google Scholar 

  31. Moan J, Sommer S. Oxygen dependence of the photosensitizing effect of hematoporphyrin derivative in NHIK 3025 cells. Cancer Res. 1985;45:1608–10.

    PubMed  CAS  Google Scholar 

  32. Henderson BW, Fingar VH. Relationship of tumor hypoxia and response to photodynamic treatment in an experimental mouse tumor. Cancer Res. 1987;47:3110–4.

    PubMed  CAS  Google Scholar 

  33. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992;359:843–5.

    Article  PubMed  CAS  Google Scholar 

  34. Eyssen-Hernandez R, Ladoux A, Frelin C. Differential regulation of cardiac heme oxygenase-1 and vascular endothelial growth factor mRNA expressions by hemin, heavy metals, heat shock and anoxia. FEBS Lett. 1996;382:229–33.

    Article  PubMed  CAS  Google Scholar 

  35. Ferrario A, von Tiehl KF, Rucker N, Schwarz MA, Gill PS, Gomer CJ. Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. Cancer Res. 2000;60:4066–9.

    PubMed  CAS  Google Scholar 

  36. Jiang F, Zhang ZG, Katakowski M, Robin AM, Faber M, Zhang F, et al. Angiogenesis induced by photodynamic therapy in normal rat brains. Photochem Photobiol. 2004;79:494–8.

    Article  PubMed  CAS  Google Scholar 

  37. Ohtani K, Usuda J, Ichinose S, Ishizumi T, Hirata T, Inoue T, et al. High expression of GADD-45alpha and VEGF induced tumor recurrence via upregulation of IL-2 after photodynamic therapy using NPe6. Int J Oncol. 2008;32:397–403.

    PubMed  CAS  Google Scholar 

  38. Benckert C, Jonas S, Cramer T, Von Marschall Z, Schäfer G, Peters M, et al. Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells. Cancer Res. 2003;63:1083–92.

    PubMed  CAS  Google Scholar 

  39. Mancino A, Mancino MG, Glaser S, Alpini G, Bolognese A, Izzo L, et al. Estrogens stimulate the proliferation of human cholangiocarcinoma by inducing the expression and secretion of vascular endothelial growth factor. Dig Liver Dis. 2008;41:156–63.

    Article  PubMed  Google Scholar 

  40. Hida Y, Morita T, Fujita M, Miyasaka Y, Horita S, Fujioka Y, et al. Vascular endothelial growth factor expression is an independent negative predictor in extrahepatic biliary tract carcinomas. Anticancer Res. 1999;19:2257–60.

    PubMed  CAS  Google Scholar 

  41. Möbius C, Demuth C, Aigner T, Wiedmann M, Wittekind C, Mössner J, et al. Evaluation of VEGF A expression and microvascular density as prognostic factors in extrahepatic cholangiocarcinoma. EJSO. 2007;33:1025–9.

    PubMed  Google Scholar 

Download references

Acknowledgments

This investigation was supported by Grants-in-Aid for Scientific Research from the Ministry of Education (#21591777), Science, Sports and Culture of Japan.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 8528501, Japan

    Takashi Nonaka, Atsushi Nanashima, Yoshikazu Nonaka & Takeshi Nagayasu

  2. Division of Surgical Oncology, Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 8528501, Japan

    Mihoko Nonaka & Masataka Uehara

  3. Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 8528501, Japan

    Hajime Isomoto

Authors
  1. Takashi Nonaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atsushi Nanashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mihoko Nonaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masataka Uehara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hajime Isomoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshikazu Nonaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takeshi Nagayasu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Atsushi Nanashima.

About this article

Cite this article

Nonaka, T., Nanashima, A., Nonaka, M. et al. Advantages of laserphyrin compared with photofrin in photodynamic therapy for bile duct carcinoma. J Hepatobiliary Pancreat Sci 18, 592–600 (2011). https://doi.org/10.1007/s00534-011-0377-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00534-011-0377-6

Keywords

Search

Navigation