Selection of Patients by Membrane Transporter Expressions for Aminolevulinic Acid (ALA)-Guided Photodynamic Detection of Peritoneal Metastases

Selection of Patients by Membrane Transporter Expressions for Aminolevulinic Acid (ALA)-Guided Photodynamic Detection of Peritoneal Metastases

Author(s)

Yutaka Yonemura, Yoshio Endo, Emel Canbay, Yang Liu, Haruaki Ishibashi, Kazuyoshi Takeshita, Akiyoshi Mizumoto, Masamitu Hirano, Nobuyuki Takao, Masumi Ichinose, Yan Li, Shun-ichirou Ogura

Download Full PDF DOI: 10.18483/ijSci.802 Downloads: 71 Views: 210 Pages: 66-77

Volume 4 - September 2015 (09)

Abstract

Background. Photodynamic diagnosis (PDD) with 5-aminolevulinic acid (ALA) was used to detect peritoneal metastasis (PM). This study was done to verify the roles of the expressions of the peptide transporter PEPT1 and ATP-binding cassette transporter ABCG2 genes on the selection of patients in ALA PDD. Methods. The study group comprised 138 patients with PM. After oral administration of 5-ALA, PM was evaluated by PDD. Tissue protoporphyrin IX (PpIX) levels, and PEPT1/ABCG2 mRNA expressions were determined. Results. The tumor detection rate on PDD was 45.6% (63/138). PDD is a safe technique for the detection of PM from ovarian cancer, mesothelioma, and colorectal cancer. PpIX levels of ALA-PDD-positive PM were significantly higher than those of ALA-PDD-negative PM. The PpIX levels in PM that simultaneously expressed PEPT1 and ABCG2 mRNA were significantly higher than those in PM that expressed either PEPT1 or ABCG2 mRNA, as well as PM that expressed neither PEPT1 nor ABCG2 mRNA. PM with PEPT1 mRNA up-regulation showed simultaneous up-regulation of ABCG2 mRNA. PpIX accumulates in PM with PEPT1 up-regulation. At the same time, PpIX may be excreted into stromal tissue through ABCG2 transporter, resulting in the accumulation of excess PpIX in the stromal tissue near cancer cells. Conclusions. Preoperative evaluations of the expressions of the PEPT1 and ABCG2 genes by RT-PCR methods might facilitate the selection of patients most likely to benefit from ALA-PDD.

Keywords

Aminolevulinic Acid; Photosensitizer; Photodynamic Diagnosis; Peritoneal Surface Malignancies; PEPT1; ABCG2, Ferrochelatase

References

  1. P. Piso, P. Slowik, F. Popp, et al. "Safety of gastric resections during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis," Ann Surg Oncol. 2009 16: 2188-2194.
  2. P. H. Sugarbaker., "Peritonectomy procedures," Ann Surg 1995: 221: 29-42.
  3. Verwaal VJ, Bruin S, Boot Het al."8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer", Ann of Surgl Oncol 2008: 15: 2426-2432.
  4. Hino H, Murayama Y, Nakanishi M, et al. 5-aminolevulinic acid-mediated photodynamic therapy using light-emitting diodes of different wavelength in a mouse model of peritoneally disseminated gastric cancer. J Surg Res. 2013: 285:119-126.
  5. Liu Y, Endo Y, Fujita T, Ishibashi H et al. Cytoreductive surgery under aminolevulinic acid-mediated photodynamic diagnosis plus hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis from ovarian cancer and primary peritoneal carcinoma: Results of a phase I trialo. Ann Surg Oncol. 2014:24: 4256-462
  6. Jichlinski P, Forre M, Mizeret J et al., Clinical evaluation of a method for detecting superficial transitional cell carcinoma of the bladder by light-induced fluorescence of photoporphyrin IX following topical aplication of 5-aminolevulinic acid: Preliminary results. Laser in Surg Med. 1997:20:402-408.
  7. Murayama Y, Ichikawa D, Koizumi N et al. Staging fluorescence laparoscopy for gastric cancer by using 5-aminolevulinic acid. Anticancer Res. 2012: 32:5421-528.
  8. Canbay E, Ishibashi H, Sako S et al Photodynamic detection and management of intraperitoneal spreading of primary peritoneal papillary serous carcinoma in a man: a case report. Surg Today. 2014: 44:373-377
  9. Hagiya Y, Endo Y, Yonemura Y et al/ Pivotal roles of peptide transporter PEPT1 and ATP-binding cassette (ABC) transporter ABCG2 in 5-aminolevulinic acid (ALA)-based photocytotoxicity of gastric cancer cells in vitro. Photodiag Photodynamic Therapy. 2012:
  10. Sugarbaker PH, Alderman R, Edwards G, et al.Prospective mortality and mrbidity assessment of cytoreductive surgery plus perioperative intraperitoneal chemotherapy to treat peritonel dissemination of appendiceal mucinous malignancy. Ann Surg Oncol. 2006:13:635-644, DOI:10.1245/ASO.2006.03.079
  11. Kaneko S. Photodinamic applications (PDD, PDT) using aminolevulinic acid in neurosurgery. Pp119-140, Aminolevulinic acid. Science, technology and application., Ed by Okura I, and Tanaka TR., SBI ALA Promo Co., Ltd
  12. Rodoriguez L, Batle A, Di Verosa G, et al., Study of the mechanisms of uptake of 5-aminolevulinic acid derivatives by PEPT1 and PET2 transporters as a tool to improve photodynamic therapies of tumours. Int J Biochem Cell Biol. 2006;28:1530-9.
  13. Hagiya Y, Furuhara H, Matsumoto K et al., Expression levels of PEPT1 and ABCG2 play key roles in 5-aminolevulinic acid (ALA)-induced tumor specific protoporphyrin IX(PpIX)accumulation in bladder cancer. Photodiag PhotodynTher. 2013: 10:288-295.
  14. Zhitaker CJ, Battah SH, Foryth MJ et al/. Photosensitization of pancreatic tumour cells by delta-aminolevulinic acid esters. Anticancer Drug Des. 2000: 15:161-170
  15. Ishikawa T. The ATP-dependent glutathione S-conjugate export pump. Trends Biochem Sci. 1992: 17:463-9
  16. Toyoda Y, Hagiya Y, Adachi Tet al MRP class of human ATP binding cassette (ABC) transporterhistorical background and new research directions. Xenobiotica. 2008: 38:833-862

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International Journal of Sciences is Open Access Journal.
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Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.

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