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The effect of photodynamic therapy (...

Liu, Weiguo.

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The effect of photodynamic therapy (PDT) on epidermal growth factor receptor and interleukin-6 cytokine signaling, and tyrosine kinase inhibitors enhance the efficacy of PDT by increasing intracellular accumulation of photosensitizers.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The effect of photodynamic therapy (PDT) on epidermal growth factor receptor and interleukin-6 cytokine signaling, and tyrosine kinase inhibitors enhance the efficacy of PDT by increasing intracellular accumulation of photosensitizers./
Author:	Liu, Weiguo.
Description:	132 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-08, Section: B, page: 4171.
Contained By:	Dissertation Abstracts International66-08B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3184673
ISBN:	9780542257834

The effect of photodynamic therapy (PDT) on epidermal growth factor receptor and interleukin-6 cytokine signaling, and tyrosine kinase inhibitors enhance the efficacy of PDT by increasing intracellular accumulation of photosensitizers.
Liu, Weiguo.

The effect of photodynamic therapy (PDT) on epidermal growth factor receptor and interleukin-6 cytokine signaling, and tyrosine kinase inhibitors enhance the efficacy of PDT by increasing intracellular accumulation of photosensitizers. - 132 p.

Source: Dissertation Abstracts International, Volume: 66-08, Section: B, page: 4171.

Thesis (Ph.D.)--State University of New York at Buffalo, 2005.

Photodynamic therapy (PDT) is a treatment for cancer which combines the administration of a drug, known as a photosensitizer, with light. When the photosensitizer is irradiated with the light, it produces singlet oxygen which is toxic for cells. In this study, we combined photodynamic therapy with tyrosine kinase inhibitors (TKIs). Our hypothesis is that TKIs can enhance PDT efficacy. Three TKIs, AG1478, Iressa, and Gleevec were combined with either 5-aminolevulinic acid (ALA)- or 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH)-PDT. In the treatment of an epidermal growth factor receptor (EGFR) positive cell line, FaDu, EGFR specific TKIs (AG1478 and Iressa) increased the phototoxicity of ALA-PDT only when they were used before ALA-PDT but had no effect on HPPH-PDT. To elucidate the mechanism we investigated the effect of PDT on EGFR and interleukin-6 (IL-6) cytokine signaling, along with the effect of TKIs on intracellular accumulation of photosensitizers. We found that ALA- and HPPH-PDT induced similar immediate biological responses in cells including: general dephosphorylation of proteins at tyrosine sites; phosphorylation of a 70 kD protein; decrease of EGFR expression; cross-linking of STAT and EGFR proteins; and transient loss of cells' responsiveness to EGF and IL-6 cytokines. In addition, we found that EGFR specific TKIs increased the production of protoporphyrin IX (PpIX) from ALA, while EGF decreased PpIX production and consequently protected FaDu cells from ALA-PDT. When TKIs were combined with ALA- or HPPH-PDT in the treatment of EGFR negative cells that expressed breast cancer resistance protein (BCRP)/ABCG2, the inhibitors enhanced the phototoxicitiy of PDT by increasing intracellular accumulation of the two photosensitizers. This occurred through the blocking of BCRP-mediated photosensitizer transport by the inhibitors. We also found that multimeric Photofrin was not a substrate for the BCRP/ABCG2 pump, nor was a modified HPPH conjugated with lactose. These findings may help understand mechanisms of PDT-induced cytotoxicity and cell survival from PDT. They suggest approaches to combining PDT with clinically available molecular targeting agents to maximize efficacy with decreased side effects.

ISBN: 9780542257834Subjects--Topical Terms:

1017719
Biology, Molecular.

The effect of photodynamic therapy (PDT) on epidermal growth factor receptor and interleukin-6 cytokine signaling, and tyrosine kinase inhibitors enhance the efficacy of PDT by increasing intracellular accumulation of photosensitizers.
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