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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1997-10-23
|
| pubmed:abstractText |
Haematoporphyrin derivatives (HPDs) are potent sensitizers in photodynamic therapy (PDT), associated with prolonged skin photosensitivity. 5-Aminolaevulinic acid (5-ALA), a natural precusor of haem, is converted intracellularly into the photosensitive agent protoporphyrin IX (PPIX), causing direct cytotoxicity after laser light irradiation but limited skin photosensitivity over 1-2 days and higher tumour selectivity. Unfortunately, the use of 5-ALA in PDT has been shown to cause only superficial tissue necrosis. Therefore, a combination of HPD and 5-ALA could be of great clinical value in the treatment of tumours if a synergistic effect of both sensitizers on tumour cell necrosis with less skin photosensitivity could be demonstrated. Human colon adenocarcinoma cells (HT-29) were cultured with either HPD or 5-ALA alone, simultaneously for 24 h with 5-ALA and HPD or in succession with 5-ALA (18 h) followed by HPD (6 h at different concentrations. Intracellular PPIX concentrations were determined by high-performance thin-layer chromatography. Furthermore, PDT was performed with an incoherent light source (lambda = 580-740 nm) using a light dose of 30 J cm(-2) and an output power of 40 mW cm(-2). The intracellular PPIX concentration correlated well with 5-ALA drug dose and incubation time and was highest after single 5-ALA sensitization. In the presence of HPD, either simultaneously or sequentially, PPIX decreased significantly. The PDT effect after simultaneous incubation with both sensitizers for 24 h was not superior to incubation with HPD alone. If 5-ALA incubation (18 h) was followed by HPD (6 h) cytotoxicity after PDT was higher than with either single drug. 5-ALA (80 microg ml(-1)) led to a decrease in tumour cell viability by 40%. A similar effect could be observed when 5-ALA and HPD were sequentially combined allowing for a reduction of the 5-ALA dose from 80 microg ml(-1) in the absence of HPD to 60 microg ml(-1) and 5 microg ml(-1) together with 0.5 microg ml(-1) and 2 microg ml(-1) HPD respectively. We speculate that the enhanced PDT effect after the combined administration of 5-ALA and HPD to cultures of colon carcinoma cells should be even more impressive in the tumour in vivo, since HPD primarily targets the tumour microvasculature and secondarily tumour cells.
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| pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-1277137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-1403373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-1531855,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-2139704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-2146455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-2973528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-3157847,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-3944607,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-6219737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-6606682,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-6616462,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-7594642,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-7669566,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-7698626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-7890239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-7911616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-8142170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-8314306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9328146-8570728
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aminolevulinic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Hematoporphyrins,
http://linkedlifedata.com/resource/pubmed/chemical/Photosensitizing Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Protoporphyrins,
http://linkedlifedata.com/resource/pubmed/chemical/protoporphyrin IX
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0007-0920
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
76
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
878-83
|
| pubmed:dateRevised |
2009-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:9328146-Aminolevulinic Acid,
pubmed-meshheading:9328146-Carcinoma,
pubmed-meshheading:9328146-Colonic Neoplasms,
pubmed-meshheading:9328146-Hematoporphyrins,
pubmed-meshheading:9328146-Humans,
pubmed-meshheading:9328146-Photochemotherapy,
pubmed-meshheading:9328146-Photosensitizing Agents,
pubmed-meshheading:9328146-Protoporphyrins,
pubmed-meshheading:9328146-Tumor Cells, Cultured
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Influence of a haematoporphyrin derivative on the protoporphyrin IX synthesis and photodynamic effect after 5-aminolaevulinic acid sensitization in human colon carcinoma cells.
|
| pubmed:affiliation |
Department of Internal Medicine I, University of Regensburg, Germany.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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