Release of clotting factors from photosensitized endothelial cells: A possible trigger for blood vessel occlusion by photodynamic therapy

Ben‐Hur, E.; Heldman, Eli; Crane, Stephen W.; Rosenthal, I.

doi:10.1016/0014-5793(88)80294-1

Cited by 46 publications

(20 citation statements)

References 10 publications

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“…Increase in the therapeutic ratio using alternative photosensitisers and/or modulating the PDT effect in normal brain is a worthwhile goal. Assuming that damage to normal brain is caused by vascular stasis, triggered by damage to the endothelium, protection might be achieved by clearance of the photosensitiser from the BBB before light treatment or bleaching of the photosensitiser at the onset of light treatment (Patterson and Wilson, 1994) to prevent endothelial cell damage, or suppression of clotting factor release after the endothelial cell layer is damaged (Ben Hur et al, 1988), or by administration of thromboxane inhibitors to prevent vascular stasis (Fingar et al, 1993). Detailed subcellular photosensitiser uptake studies, for example using confocal fluorescence microscopy (M Olivo, unpublished results), can play an important role in evaluating the possible efficacy of some of these interventions.…”

Section: Resultsmentioning

confidence: 99%

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy

Lilge

Olivo²,

Schatz³

et al. 1996

Br J Cancer

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Section: Resultsmentioning

confidence: 99%

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy

Lilge

Olivo²,

Schatz³

et al. 1996

Br J Cancer

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“…This, and the release of the vasoactive substances prostaglandin and thromboxane, which cause vasoconstriction and platelet aggregation (Fingar et al, 1992), may result in congestion of the capillaries. Similarly, blockage of the capillaries can be effected by thrombi formation due to the release of various clotting factors from the damaged endothelial cells (Ben-Hur et al, 1988) or to the production of tumour necrosis factor by PDT-treated macrophages (Chaplin, 1991). The fibrinous material that we observed only in the sinusoids of treated tumours may be a result of the photohaemolysis of RBCs, whereby the cells eventually lyse leaving a fibrin clot and cell debris.…”

Section: Sensitizermentioning

confidence: 84%

The photodynamic response of two rodent tumour models to four zinc (II)-substituted phthalocyanines

Cruse-Sawyer

Griffiths²,

Dixon³

et al. 1998

Br J Cancer

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Summary Four novel zinc (I1)-substituted phthalocyanines, varying in charge and hydrophobicity, were evaluated in vivo as new photosensitizers for photodynamic therapy. Two rat tumours with differing vascularity were used: a mammary carcinoma (LMC,) and a fibrosarcoma (LSBD1), with vascular components six times higher in the latter (10.8% ± 1.5) than in the former (1.8% ± 1.4). Each sensitizer was assessed for tumour response relative to normal tissue damage, and optimum doses were selected for further study, ranging from 0.5 to 20 mg kg-'. Interstitial illumination of the tumours was carried out using a 200-gm-core optical fibre with a 0.5 cm length of diffusing tip, at either 680 or 692 nm, depending on the sensitizer. Light doses of between 200 and 600 J were delivered at a rate of 100 mW from the 0.5-cm diffusing section of the fibre. Maximum mean growth delays ranged from 9 to 13.5 days depending on sensitizer and type of tumour, with the most potent photosensitizer appearing to be the cationic compound. Histopathological changes were investigated after treatment to determine the mechanism by which tumour necrosis was effected. The tumours had the appearance of an infarct and, under the conditions used, the observed damage was shown to be mainly due to ischaemic processes, although some direct tumour cell damage could not be ruled out.Keywords: photodynamic therapy; zinc phthalocyanines; rodent tumours; ischaemia Photodynamic therapy (PDT) is a method of cancer treatment that has been clinically applied to the eradication or palliation of tumours at various sites, including bladder (Benson, 1985), brain (Kaye et al, 1987), lung (Okunaka et al, 1991), chest wall (Sperduto et al, 1991), skin (Caimduff et al, 1994) and oesophagus (Moghissi et al, 1995). The only photosensitizer so far approved for general use is Photofrin, which is a complex mixture of porphyrin monomers and oligomers. However, this drug also has relatively low light absorption in the red region of the spectrum, where light penetration in tissue is greatest, and also induces a prolonged skin photosensitivity (Richter et al, 1991).To overcome the problems associated with the limited depth of light penetration, chemical purity and stability, low absorption coefficient and skin photosensitivity, possible alternatives to the haematoporphyrin photosensitizers have been investigated. One such group is the phthalocyanines, which are synthetic porphyrin analogues. A number of phthalocyanine compounds have been tested in vitro (Chan et al, 1991;Boyle et al, 1993) and in vivo (Barr et al, 1991;Boyle et al, 1992) and show sufficient potential for clinical use to merit further investigation. They demonstrate strong absorbance in the red region of the spectrum and the potential for a greater PDT effect is enhanced by the increased tissue penetration by light of longer wavelength. They also appear to induce a smaller degree of skin photosensitivity than haematoporhyrin derivative (HPD) under experimental conditions (Roberts et al, 1989) and the compounds st...

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“…Different mechanisms for the vascular occlusion due to PDT were discussed; however, the main reason is thought to be a huge release of factor VIII or thromboxin after PDT from the damaged endothelial cells, leading to aggregation of thrombocytes. 25 Because of thisespecially at threshold irradiation-a primary apposition thrombosis may occur at the vessel intima, leading to turbulence in the blood flow and consecutive apposition of material at this site and finally to occlusion of the complete vessel lumen. This process is known to be dynamic, depending on dye concentration, radiance exposure, and time of irradiation.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the New Photosensitizer Tookad (WST09) for Photodynamic Vessel Occlusion of the Choroidal Tissue in Rabbits

Framme

Sachs

Flucke

et al. 2006

Invest. Ophthalmol. Vis. Sci.

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T-PDT has the potential to achieve selective choroidal vessel occlusion with proper parameter selection, such as (1) 2.5 mg/kg, 5 minutes, 100 J/cm2; (2) 5 mg/kg, 5 minutes, 25 J/cm2; or (3) 5 mg/kg, 15 minutes, 50 J/cm2; however, slight damage to the photoreceptors cannot be ruled out. RPE proliferation indicates primary RPE damage due to PDT, also described with the use of all other photosensitizers.

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Release of clotting factors from photosensitized endothelial cells: A possible trigger for blood vessel occlusion by photodynamic therapy

Cited by 46 publications

References 10 publications

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy

The photodynamic response of two rodent tumour models to four zinc (II)-substituted phthalocyanines

Evaluation of the New Photosensitizer Tookad (WST09) for Photodynamic Vessel Occlusion of the Choroidal Tissue in Rabbits

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