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Proceedings Paper

Nicotinamide augments the survival and incidence of apoptosis in glioma cells following photodynamic therapy in vitro
Author(s): Stuart K. Bisland; Nayan Modi; Brian C. Wilson
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Paper Abstract

The ability to customize photodynamic therapy (PDT) parameters with regards to timing and dosing of administered drug and light can be beneficial in determining target specificity and mode of cell death. Sustained, low level PDT or metronomic PDT (mPDT) may afford enhanced apoptotic cell death. This is of particular importance when considering PDT for the treatment of brain tumors as unlike apoptosis, necrotic cell death often leads to inflammation with increased intracranial pressure. The ability, therefore, to 'fine tune' PDT in favour of apoptosis is paramount. We have studied both acute (one time treatment) PDT (aPDT) and mPDT delivery strategies in combination with nicotinamide (NA) in an attempt to maximize the number of tumor cells dieing by apoptosis. Using several different glioma cell lines (9L, U87-MG and CNS-1) we now confirm that NA provides a dose-dependent (0.1-0.5 mM) increase in apoptotic cells following d-aminolevulinic acid-mediated aPDT or mPDT. Furthermore, using the 9L cell line stably transfected with the luciferase gene, NA was shown to delay the depletion of bioluminscence signal in aPDT and mPDT treated cells, inferring that adenosine triphosphate levels are maintained for longer following NA treatment. NA has previously been reported as promoting neuronal and vascular cell survival in normal brain following a number of neurological insults in which reactive oxygen species are implicated including, stroke, Alzheimer's disease and toxin-induced lesions. It is likely that the effects of NA reflect its capacity as an antioxidant as well as its ability to inhibit poly (adenosine diphosphate-ribose) polymerase-mediated depletion of ATP. Our results indicate that NA may prove therapeutically advantageous when used in combination with PDT treatment of brain tumors.

Paper Details

Date Published: 9 December 2004
PDF: 14 pages
Proc. SPIE 5578, Photonics North 2004: Photonic Applications in Astronomy, Biomedicine, Imaging, Materials Processing, and Education, (9 December 2004); doi: 10.1117/12.566180
Show Author Affiliations
Stuart K. Bisland, Princess Margaret Hospital (Canada)
Nayan Modi, Princess Margaret Hospital (Canada)
Brian C. Wilson, Princess Margaret Hospital (Canada)
Univ. of Toronto (Canada)

Published in SPIE Proceedings Vol. 5578:
Photonics North 2004: Photonic Applications in Astronomy, Biomedicine, Imaging, Materials Processing, and Education
Marc Nantel; Glen Herriot; Graham H. McKinnon; Leonard MacEachern; Robert A. Weersink; Rejean Munger; Andrew Ridsdale, Editor(s)

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