Mechanism & Role of Cyclooxygenase-2
Up-Regulation By Photodynamic Therapy

By Nico Hendrickx
Acta Biomedica Lovaniensia, No. 356
June 2006
Leuven University Press
ISBN: 9058675289
139 pages, Illustrated, 6 ¼” x 9 ½”
$87.50 Paper Original

Contents include:
Table of contents
List of publications
Chapter 1. General introduction
1. Photodynamic therapy
1.1. PDT in medicine: a historical perspective
1.2. Mechanism of action
1.3. Photosensitizers
2. Cell fate after photodynamic therapy
2.1. Brief introduction to apoptosis
2.2. Cell death pathways in PDT
2.3. Signaling pathways in PDT
3. Cyclooxygenase-2
3.1. Cyclooxygenase isozymes
3.2. Mechanisms of catalysis and inhibition
3.3. Regulation of expression
3.4. COX-2 in cancer and in response to drug therapy
Chapter 2. Aims and outline of the study
Chapter 3. Materilas and methods
1. Materials
2. Experimental procedures
2.1. Cell culture
2.2. Cell photosensitization
2.3. Preparation of cell extracts and Western blotting
2.4. Caspase assay
2.5. Immunoprecipitation and protein kinase assay
2.6. Asessment of cell viability
2.7. Cell death assay
2.8. Transient transfections
2.9. Luciferase reporter assay
2.10. Cell cycle analysis
2.11. Electrophoretic mobility shift assay (EMSA)
2.12. (Ca²+ )cyt measurements with Indo-1
2.13. Arachidonic acid release
2.14. PGE2 and VEGF measurement
2.15. RT-PCR
2.16. RNA stability assay
2.17. Endothelial cell migration
Chapter 4. Signaling pathways mediating the up-regulation of cyclooxygenase-2 in PDT-treated cancer cells
1. Introduction
2. Results
2.1. Hypericin-mediated PDT of cancer cells leads to up-regulation of COX-2
2.2. Cyclooxygenase-2 is up-regulated by the restricted activation of p38 MAPK
2.3. NF-?B is not involved in the up-regulation of COX-2 by hypericin-PDT
2.4. COX-2 mRNA is stabilized by p38 MAPK in hypericin-PDT treated cells
2.5. The mechanisms of COX-2 up-regulation by PDT are photosensitizer specific
2.6. The cox-2 gene is transcriptionally regulated upon PPME-PDT
Chapter 5. On the role of p38 MAPK-COX-2 cascade in hypericin-based PDT
1. Introduction
2. Results
2.1. PDT induces rapid rise in (Ca²+)cyt and cPLA2 generated arachidonic acid release
2.2. PLA2-generated arachidonic acid contributes to apoptosis and to p38 MAPK activation following hypericin-PDT
2.3. p38a supports survival after PDT injury
2.4. The COX-2 antagonist NS398 does not significantly sensitize cells to PDT-induced apoptosis
2.5. Inhibition of p38 MAPK abolishes PGE2 and VEGF release
2.6. Targeted p38 MAPK inhibition suppresses tumor-associated endothelial cell migration
Chapter 6. General discussion and perspectives
1. Signaling pathways mediating the up-regulation of cyclooxygenase-2 in PDT treated cells
2. On the role of p38 MAPK-COX-2 cescade in PDT


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