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Journal of Biomedical Optics

Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action
Author(s): Carl-Jørgen Arum; Odrun A. Gederaas; Hans E. Krokan; Duan Chen; Chun-Mei Zhao; Eivind L. P. Larsen; Lise L. Randeberg; Lars O. Svaasand; Astrid Hjelde
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Paper Abstract

Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

Paper Details

Date Published: 1 February 2011
PDF: 6 pages
J. Biomed. Opt. 16(2) 028001 doi: 10.1117/1.3536536
Published in: Journal of Biomedical Optics Volume 16, Issue 2
Show Author Affiliations
Carl-Jørgen Arum, St. Olavs Hospital (Norway)
Odrun A. Gederaas, Norwegian Univ. of Science and Technology (Norway)
Hans E. Krokan, Norwegian Univ. of Science and Technology (Norway)
Duan Chen, Norwegian Univ. of Science and Technology (Norway)
Chun-Mei Zhao, Norwegian Univ. of Science and Technology (Norway)
Eivind L. P. Larsen, Norwegian Univ. of Science and Technology (Norway)
Lise L. Randeberg, Norwegian Univ. of Science and Technology (Norway)
Lars O. Svaasand, Norwegian Univ. of Science and Technology (Norway)
Astrid Hjelde, Norwegian Univ. of Science and Technology (Norway)


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