Affiliation:
1. Max Planck Institute for Molecular Genetics, Germany
Abstract
Photodynamic Therapy (PDT) involves administration of a photosensitizer (PS) either systemically or locally, followed by illumination of the lesion with visible light. PDT of cancer is now evolving from experimental treatment to a therapeutic alternative. Clinical results have shown that PDT is at least as efficacious as standard treatments of malignancies of the skin and Barrett’s esophagus. Hemes and heme proteins are vital components of essentially every cell in virtually all eukaryote organisms. Protoporphyrin IX (PpIX) is produced in cells via the heme synthesis pathway from the substrate aminolevulinic acid (ALA). Exogenous administration of ALA induces accumulation of (PpIX), which can be used as a photosensitiser for tumor detection or photodynamic therapy. Although the basis of the selectivity of ALA-based PDT or photodiagnosis is not fully understood, it has sometimes been correlated with the metabolic rate of the cells, or with the differential enzyme expressions along the heme biosynthetic pathway in cancer cells. An in silico analysis by modeling may be performed in order to determine the functional roles of genes coding enzymes of the heme biosynthetic pathway like ferrochelatase. Modeling and simulation systems are a valuable tool for the understanding of complex biological systems. With PyBioS, an object-oriented modelling software for biological processes, we can analyse porphyrin metabolism pathways.
Reference27 articles.
1. Biosynthesis of heme in mammals, biochimica et biophysica acta (BBA).;R. S.Ajioka;Molecular Cell Research,2006
2. Novel molecular defects of the ?-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria
3. Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans
4. December). Ferrochelatase, a novel target for photodynamic therapy of cancer.;G.Bhasin;Oncology Reports,1999
5. Ferrochelatase gene mutations in erythropoietic protoporphyria: Focus on liver disease.;F.-P.Chen;Cell Mol Biol (Noisy-le-grand),2002