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Protoporphyrin IX

About: Protoporphyrin IX is a research topic. Over the lifetime, 2250 publications have been published within this topic receiving 65544 citations. The topic is also known as: PpIX.


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Journal ArticleDOI
TL;DR: The results provide a theoretical basis for possible clinical use of ultrasound‐combined ALA or ALA based photodynamic therapy and show that the distribution of PpIX fluorescence in the tumors treated with ultrasound was more homogeneous than that in the tumor given ALA only.
Abstract: BALB/c nude mice bearing WiDr human colon adenocarcinoma were used to determine the effect of ultrasound on the production of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) both in the tumors and in skin overlying the tumors. Ultrasound (1 MHz) with pulsed irradiation at an average intensity of 3 W/cm2 was given 10 min to the tumor area 10 min after administration of ALA (20% in an oil-in-water emulsion applied topically on the surface of the tumor for 30 min to 3 hr). An approximately 45% increase in the amount of PpIX produced by ALA in the tumors was obtained within 1 to 2 hr following ultrasound treatment. In particular, 1 hr after ultrasound treatment, the amount of PpIX in the tumors was at the same level as that 3 hr after ALA application alone. However, pulsed ultrasound irradiation for 5 min or continuous irradiation for 5 or 10 min had no significant effect on the production of PpIX by the tumor 1 hr after topical ALA application. Furthermore, in most cases, the amount of PpIX in the tumors was significantly decreased when ultrasound was given immediately before ALA application. There was no significant change in the ratio of the amount of PpIX in tumor to that in skin after ultrasound treatment. Most likely, the distribution of PpIX fluorescence in the tumors treated with ultrasound was more homogeneous than that in the tumors given ALA only. Our results provide a theoretical basis for possible clinical use of ultrasound-combined ALA or ALA based photodynamic therapy. Int. J. Cancer 78:464–469, 1998. © 1998 Wiley-Liss, Inc.

28 citations

Journal ArticleDOI
TL;DR: Clinical utilization of CP94 to enhance ALA/MAL-PDT could potentially result in greater PPIX accumulation or alternatively could be employed to reduce the length of the required drug-light interval, as clinical investigation is currently underway.
Abstract: Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC, however, appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and may be possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolaevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the efficacies of the novel iron chelator, CP94 (1,2-diethyl-3-hydroxypyridin-4-one hydrochloride), and the established iron chelator, desferrioxamine (DFO), at increasing PPIX fluorescence in cultured human lung fibroblasts and squamous carcinoma cells incubated with ALA/MAL. CP94 was found to produce greater PPIX fluorescence when administered with ALA/MAL than either congener could produce alone. CP94 was also found to be superior to DFO in the enhancement of PPIX fluorescence and could be employed to accumulate the same levels of PPIX within a shorter time period. Clinical utilization of CP94 to enhance ALA/MAL-PDT could potentially result in greater PPIX accumulation or alternatively could be employed to reduce the length of the required drug-light interval. Clinical investigation of this is currently underway.

28 citations

Journal ArticleDOI
TL;DR: It is concluded that the cytochrome apoproteins are synthesized and incorporated into the cytoplasmic membrane of E. coli in the absence of haem synthesis.
Abstract: 1. The reconstitution of oxidase activity in cell-free extracts of a mutant of Escherichia coli K12Ymel, that require 5-aminolaevulinic acid for growth on non-fermentable carbon sources, is described. 2. The reconstitution is dependent on haematin or a haem extract from a prototrophic strain of E. coli , and the product of the reaction has been identified as NADH-reducible cytochrome b . 3. The requirement for haematin cannot be replaced by four other porphyrins. Coproporphyrin III does not inhibit the haematin-dependent reconstitution, mesoporphyrin IX and protoporphyrin IX apparently compete with haematin for a binding site on the cytochrome apoprotein(s) and deuteroporphyrin IX binds to cytochrome apoprotein(s) and cannot be subsequently replaced by haematin. 4. The properties of electron-transport particles from cell-free extracts of the mutant strain, grown aerobically in the presence or absence of 5-aminolaevulinic acid, are described. In the absence of 5-aminolaevulinic acid no detectable cytochromes are produced, and oxidase activities are lowered but there is no apparent effect on the activities of the NADH dehydrogenase and d-lactate dehydrogenase. 5. The reconstitution of oxidase activity by electron-transport particles from cells grown in the absence of 5-aminolaevulinic acid requires ATP and haematin, and the product of the reaction was identified as NADH-reducible cytochrome b . 6. It is concluded that the cytochrome apoproteins are synthesized and incorporated into the cytoplasmic membrane of E. coli in the absence of haem synthesis. The subsequent reconstitution of functional cytochrome(s) requires protohaem, but the nature of the side chain on the 2 and 4 positions of the porphyrin appears to be important.

28 citations

Journal ArticleDOI
TL;DR: In photodynamic therapy the endogenous photosensitizer protoporphyrin IX is synthesized following topical application of aminolaevulinic acid, but different tissues have distinct PpIX‐accumulating properties, due to differences in penetration of ALA through the stratum corneum and/or alterations in the haem cycle.
Abstract: BACKGROUND: In photodynamic therapy the endogenous photosensitizer protoporphyrin IX (PpIX) is synthesized following topical application of aminolaevulinic acid (ALA). However, different tissues have distinct PpIX-accumulating properties, due to differences in penetration of ALA through the stratum corneum and/or alterations in the haem cycle. Preferential PpIX accumulation has been reported in terminally differentiated cell cultures but ex vivo data are lacking. OBJECTIVES: To study the intrinsic PpIX-accumulating capabilities of skin explants from lesional and nonlesional skin in psoriasis and actinic keratosis, with normal skin serving as a control, and to study PpIX accumulation in relation to differentiation status in normal skin. METHODS: Skin explants from patients with psoriasis, actinic keratosis and normal skin were incubated with ALA and PpIX was measured spectrofluorometrically. PpIX was measured in basal (beta1-integrin-positive) and suprabasal (beta1-integrin-negative) keratinocytes in normal skin. In addition, PpIX accumulation was studied in cell cultures at different levels of confluence and after induction of terminal differentiation. RESULTS: No significant differences in PpIX content were found between the different tissues. However, increased PpIX was found in beta1-integrin-negative compared with beta1-integrin-positive cells. In addition, in subconfluent cell cultures less PpIX was found compared with confluent cell cultures. Induction of terminal differentiation in vitro, however, resulted in less PpIX, which was likely to be related to cell volume. CONCLUSIONS: As no significant differences in PpIX synthesis could be found between the different tissue types, these data emphasize the importance of the penetration route of ALA through the stratum corneum. Preferential PpIX accumulation observed in suprabasal epidermal keratinocytes and confluent cell cultures points towards a terminal differentiation-specific effect.

28 citations

Journal ArticleDOI
30 Mar 2015-PLOS ONE
TL;DR: Results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation, and adding sodium ferrous citrate with ALA as a source of iron might increase the specificity of ALA-PDT effects.
Abstract: Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.

28 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202383
2022132
202157
202061
201958
201858