Enhancement of photodynamic therapy in gastric cancer cells by removal of iron
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TLDR
Accumulation of PPLX and ultimately the efficacy of PDT could be improved by modulating both ends of the haem biosynthetic pathway by removal of available iron with desferrioxamine.Abstract:
BACKGROUND: Aminolaevulinic acid (ALA) is an endogenous substrate in the haem biosynthetic pathway. Protoporphyrin IX (PPIX), the immediate haem precursor in the pathway, has photoexcitable properties. Exogenous ALA has been used previously as a precursor agent in photodynamic therapy (PDT). Its main advantage is a short half-life and hence reduced incidence of skin photosensitivity. ALA can be toxic, however, causing, for example, transient increases in liver enzyme concentrations when given systemically and this may be dose related. AIM: To assess whether accumulation of PPLX and ultimately the efficacy of PDT could be improved by modulating both ends of the haem biosynthetic pathway. METHODS: Gastric cancer cells (MKN 28) were incubated with ALA (0-1000 mumolar) and desferrioxamine (0-800 mumolar) for 24 hours before exposure to argon-pumped dye laser (630 nm) at different energy levels (0-40 J/cm2). Cell viability was assessed by use of the methyl-tetrazolium (MTT) assay four hours after exposure to light. RESULTS: Total PPIX accumulation increased linearly with increasing extracellular concentrations of ALA up to 1 mmolar (r = 0.973, pread more
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Journal ArticleDOI
Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer
Malgorzata Wachowska,Angelika Muchowicz,Malgorzata Firczuk,Magdalena Gabrysiak,Magdalena Winiarska,Malgorzata Wanczyk,Kamil Bojarczuk,Jakub Golab +7 more
TL;DR: Since PpIX is a potent photosensitizer this metabolic pathway can be exploited in photodynamic therapy (PDT), this is an already approved therapeutic strategy making ALA one of the most successful prodrugs used in cancer treatment.
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Targeted Photodynamic Therapy
TL;DR: Photodynamic therapy (PDT) is an emerging modality for the treatment of various neoplastic and non‐neoplastic pathologies.
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The effect of an iron chelating agent on protoporphyrin IX levels and phototoxicity in topical 5‐aminolaevulinic acid photodynamic therapy
TL;DR: In 5‐aminolaevulinic acid (ALA)‐photodynamic therapy (PDT), the prodrug ALA is endogenously converted to the active sensitizer protoporphyrin IX (PpIX), while further conversion of PpIX to haem requires iron.
Journal ArticleDOI
Direct Comparison of δ-Aminolevulinic Acid and Methyl-Aminolevulinate-Derived Protoporphyrin IX Accumulations Potentiated by Desferrioxamine or the Novel Hydroxypyridinone Iron Chelator CP94 in Cultured Human Cells
Andrew Pye,Alison Curnow +1 more
TL;DR: The use of iron chelators in combination with ALA or MAL was shown to significantly increase the amount of PpIX accumulating in the fetal lung fibroblasts and epidermal carcinoma cells; while minimal enhancement was observed in the normal skin cells investigated.
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In Vivo and In Vitro Studies of Bacillus subtilis Ferrochelatase Mutants Suggest Substrate Channeling in the Heme Biosynthesis Pathway
TL;DR: The enzyme was studied in the bacterium Bacillus subtilis, for which the ferrochelatase three-dimensional structure is known, and the function of Q63 remains unclear, it is suggested that S54 is involved in substrate reception or delivery of the enzymatic product.
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Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor
TL;DR: The protective effect against photodynamic inactivation of the TA-3 cells afforded by 1,3-diphenylisobenzofuran coupled with the nearly quantitative formation of the singlet oxygen-trapping product indicates that Singlet oxygen is the probable agent responsible for toxicity in this system.
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Photodynamic Therapy in Oncology: Mechanisms and Clinical Use
TL;DR: Clinically, this therapy has been chiefly used for palliation of endobronchial and esophageal obstruction, as well as for treatment of bladder carcinomas, skin malignancies, and brain tumors, and the future of PDT rests in defining its use either as an intraoperative adjuvant to marginal surgical procedures or as a primary treatment for superficial malignancy.
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TL;DR: For large areas of Bowen's disease, particularly in anatomically difficult areas and in elderly patients, PDT using ALA may constitute a single simple alternative outpatient treatment to existing therapies.
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Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX--a pilot study
Jaroslaw Regula,A. J. MacRobert,A Gorchein,G Buonaccorsi,Sally Thorpe,G M Spencer,A R Hatfield,Sg Bown +7 more
TL;DR: Photodynamic therapy with systemically administered ALA may be a promising technique for the treatment of small tumours and areas of dysplasia such as in Barrett's oesophagus.