HEMATOPORPHYRIN and HPD: PHOTOPHYSICS, PHOTOCHEMISTRY and PHOTOTHERAPY

Kessel, David

doi:10.1111/j.1751-1097.1984.tb08871.x

Cited by 258 publications

(118 citation statements)

References 82 publications

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“…This is in accordance with early studies and recent reports on vascular constriction in connection with PDT (Selman et al, 1984;Kessel, 1984;Van der Veen et al, 1994;Roberts et al, 1994;Leveckis et al, 1995). A sharply decreased blood flow was also noticed by a gross examination immediately after the irradiation, as the treated area became darker as a result of the treatment.…”

Section: Discussionsupporting

confidence: 92%

Photodynamic therapy using intravenous δ-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats

Svanberg

Liu²,

Wang³

et al. 1996

Br J Cancer

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Summary The efficacy of photodynamic therapy (PDT) using 6-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) sensitisation and laser light at 635 nm was investigated in the treatment of experimental hepatic tumours. The model of liver tumours was induced either by local inoculation or by administration of tumour cells through the portal vein in rats. ALA at a dose of 60 mg kg-' b.w. was intravenously administered 60 min before PDT. PpIX accumulation in tumour, normal liver and abdominal wall muscle was detected by means of laser-induced fluorescence (LIF). Laser Doppler imaging (LDI) was used to determine changes in the superficial blood flow in connection with PDT. Histopathological examinations were performed to evaluate the PDT effects on the tumour and the surrounding liver tissue, including pathological features in the microvascular system. The accumulation of PpIX, as monitored by LIF, showed high fluorescence intensities at about 635 nm in both the hepatic tumour tissue and normal liver and low values in the abdominal wall. LDI demonstrated that the blood flow in the treated tumour and its surrounding normal liver tissue decreased immediately after the PDT, indicating an effect on the vascular system. A large number of thrombi in the irradiated tumour were found microscopically 3 h after the PDT. The tumour growth rate showed a marked decrease when evaluated 3 and 6 days after the treatment. These results show that the ALA-PDT is effective in the inhibition of growth of experimental hepatic tumours.

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Section: Discussionsupporting

confidence: 92%

Photodynamic therapy using intravenous δ-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats

Svanberg

Liu²,

Wang³

et al. 1996

Br J Cancer

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“…The most active component of hematoporphyrin derivative is thought to be the dihematoporphyrin ether [1,2] or ester [3] or even a triether/ester [4]. Hematoporphyrin derivative is selectively retained by malignant tumors [5][6][7], and excitation with red light (630 nm) results in the photodynamic destruction of the tumor tissue.…”

Section: Introductionmentioning

confidence: 99%

Superoxide, hydrogen peroxide and singlet oxygen in hematoporphyrin derivative-cysteine, -NADH and -light systems

Buettner

Hall

1987

Biochimica et Biophysica Acta (BBA) - General Subjects

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Hematoporphyrin derivative and light in the presence of cysteine or glutathione were found to convert oxygen to superoxide and hydrogen peroxide at pH < approx. 6.5, while at pH > 6.5 no superoxide or hydrogen peroxide production was observed. However, at pH values greater than 6.5 the rate of oxygen consumption increased. This rate paralleled the acid dissociation curve of the cysteine thioi group and is consistent with the chemical quenching of tO z by cysteine. The superoxide and hydrogen peroxide formation observed below pH 6.5 appeared not to be related to the singlet oxygen production of hematoporphyrin derivative. In addition, superoxide and hydrogen peroxide production was observed with hematoporphyrin derivative and light in the presence of NADH, both above and below pH 6.5. Direct detection of singlet oxygen luminescence at 1268 nm in the hematoporphyrin derivative-light system (2HzO as solvent) revealed an apparent linear increase in the singlet oxygen emission intensity as the pZH was raised from 7.0 to 10.0. Azide efficiently quenched this observed emission. In addition, at p2H 7.4, 1 mM cysteine resulted in a 40% reduction of the singlet oxygen luminescence, while at pZH 9.4 the signal was quenched by over 95% (under the experimental conditions employed). In total, we interpret these results as consistent with the chemical quenching of to z by the ionized thiol group of cysteine.

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“…In addition to solid tumours, hairy-cell leukaemia and mycosis fungoides have also been treated with 8-methoxypsoralen and UVA (PUVA) (Honigsmann, 1987). The leading, most widely investigated, photosensitizers in PDT are the haematoporphyrins (HPDPhotofrin II) (Kessel, 1984), which were recently approved for clinical use. However, their use may be limited because of prolonged cutaneous phototoxicity, aggregation tendency, slow metabolism in vivo (Gomer, 1991;Grossweiner, 1994;Jones et al, 1996), as well as limited efficacies in affecting penetrating solid tumours (Orenstein et al, 1996).…”

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confidence: 99%

A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy

et al. 1999

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SummaryThe mechanism of cell death induction by dimethyl tetrahydroxyhelianthrone (DTHe), a new second-generation photodynamic sensitizer, is analysed in human leukaemic cell lines in comparison with the structurally related hypericin. DTHe has a broad range of light spectrum absorption that enables effective utilization of polychromatic light. Photosensitization of HL-60 cells with low doses of DTHe (0.65 µM DTHe and 7.2 J cm -2 light energy) induced rapid apoptosis of ≥90% of the cells. At doses ≥2 µM, dying cells assumed morphological necrosis with perinucleolar condensation of chromatin in HL-60 and K-562 cell lines. Although nuclear fragmentation that is characteristic to apoptosis was prevented, DNA digestion to oligonucleosomes proceeded unhindered. Such incomplete apoptosis was more prevalent with the related analogue hypericin throughout most doses of photosensitization. Despite hypericin being a stronger photosensitizer, DTHe exhibited advantageous phototoxic properties to tumour cells, initiating apoptosis at concentrations about threefold lower than hypericin. Photosensitization of the cells induced dissociation of the nuclear envelope, releasing lamins into the cytosol. DTHe also differed from hypericin in effects exerted on the nuclear lamina, causing release of an 86-kDa lamin protein into the cytosol that was unique to DTHe. Within the nucleus, nuclear envelope lamin B underwent covalent polymerization, which did not affect apoptotic nuclear fragmentation at low doses of DTHe. At higher doses, polymerization may have been extensive enough to prevent nuclear collapse. Hut-78, CD4 + cells were resistant to the photodynamically activated apoptotic pathway. Beyond the tolerated levels of photodynamic damage, these cells died exclusively via necrosis. Hut-78 cells overexpress Bcl-X L as well as a truncated Bcl-X L tr isoform that could contribute to the observed resistance to apoptosis.Keywords: photodynamic therapy; hypericin; dimethyl tetrahydroxyhelianthrone; Bcl-X; Bax; lamin; apoptosis 423British Journal of Cancer (1999) 79(3/4), 423-432 © 1999 Cancer Research Campaign Article no. bjoc.1998 Received Efforts to identify novel efficacious agents for photodynamic therapy led us to evaluate the photodynamically induced cytotoxicities of a newly designed photosensitizer 10,13-dimethyl 1,3,4,6-tetrahydroxyhelianthrone (DTHe) (Figure 1), in leukaemic cell lines. DTHe was chosen because of its dibenzperylenequinone chromophore (seven aromatic rings) that has absorption spectral properties virtually identical to hypocrellins, potent anti-tumoral photosensitizers isolated from the parasitic fungus Hypocrella bambuase which grows in China and Tibet (Diwu, 1990;Diwu, 1995; Miller, 1997). DTHe also shares structural similarities with HY and was anticipated to be a potent photosensitizer owing to its considerable light absorbance in the visible range of the spectrum. The phototoxicity profiles and mechanisms of cell death induction of DTHe were analysed in comparison with those of HY in HL-60, K-562 and Hut-...

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HEMATOPORPHYRIN and HPD: PHOTOPHYSICS, PHOTOCHEMISTRY and PHOTOTHERAPY

Cited by 258 publications

References 82 publications

Photodynamic therapy using intravenous δ-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats

Photodynamic therapy using intravenous δ-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats

Superoxide, hydrogen peroxide and singlet oxygen in hematoporphyrin derivative-cysteine, -NADH and -light systems

A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy

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