Changes of skin perfusion after photodynamic therapy for port wine stain.
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OBJECTIVE: To obtain an objective assessment of the curative effectiveness of photodynamic therapy (PDT) for port wine stain (PWS), we investigate the relationship between the microvascular perfusion changes of PWS and the blanching of the lesions before and after PDT. METHODS: Twenty-four patients (18 females and 6 males with a total of 28 lesions) suffering from PWS were treated with PDT. The lesions of various extents were located on the face and neck. After intravenous injection of photosensitizer hepatoporphyrin derivative (HpD), the copper vapor laser was adopted as light source and the lesions of PWS were irradiated. The laser Doppler perfusion imager (LDI) was used to measure the microcirculatory perfusion of PWS before and after PDT and comparison with the normal skin was done. RESULTS: All the lesions showed remarkable decrease of tissue perfusion after PDT. It was shown that the mean, maximal and minimal values of tissue perfusion in the pre-treatment group were significantly higher than those in control group (P < 0.01). Six months after PDT, the mean, maximal and minimal values of perfusion with the lesions were reduced, with significant difference from pre-treatment group (P < 0.01), but no significant difference from control's. The colors of lesions were correlated with decrease of microcirculatory perfusion, which became lightened close to normal skin color without causing any scarring. CONCLUSIONS: PDT is one of the most effective modalities for PWS. The microcirculation perfusion can reflect the degrees of PWS objectively. The curative effectiveness of PDT for PWS is due to tissue microcirculation response. (+info)
The role of microvascular damage in photodynamic therapy: the effect of treatment on vessel constriction, permeability, and leukocyte adhesion.
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Intravital microscopy of the rat cremaster muscle was used to evaluate changes in vessel constriction, vessel permeability, and leukocyte adhesion during and after photodynamic therapy (PDT). Animals were given Photofrin doses of 0-25 mg/kg i.v. 24 h before treatment. Cremaster muscles were exposed to 135 J/cm2 light at 630 nm. Animals given 5 mg/kg Photofrin showed no vessel constriction or increase in vessel permeability to albumin. Doses of 10 and 25 mg/kg Photofrin caused a dose-related constriction of arterioles which was observed within the first minutes of illumination at the higher drug dose. After the initial constriction, arteriole response to PDT was biphasic in nature, with some vessels relaxing to nearly control levels while others remained fully constricted. Constriction of venules occurred only at the highest porphyrin dose studied (25 mg/kg) and was delayed in comparison to arteriole constriction. Photofrin doses which produced arteriole constriction also caused an increase in venule permeability to albumin, which occurred shortly after the start of light treatment and was progressive with time. Leakage began at specific sites along the venule wall but became uniform along the entire length of the venule by 1 h after treatment. Changes in the adherence of polymorphonuclear leukocytes to venule endothelium were also observed with PDT. Photofrin doses of 25 mg/kg and 45 J/cm2 light were sufficient to cause polymorphonuclear leukocytes to become adherent to the vessel wall. A second group of animals was given indomethacin trihydrate to examine the involvement of cyclooxygenase products such as thromboxane in vessel response to PDT. Animals given 5 mg/kg indomethacin intraarterially 1 h before light treatment showed no constriction of arterioles or venules at all Photofrin and light doses studied. No increases in venule permeability to albumin were seen in this group of animals. This suggests that cyclooxygenase products including thromboxane are important in causing vessel constriction and changes in permeability during PDT. The initiating event which causes the release of these vasoactive agents remains unknown. (+info)
Is bronchoscopic photodynamic therapy a therapeutic option in lung cancer?
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This study addresses whether photodynamic therapy (PDT) is a valid therapeutic option in lung cancer treatment. A total of 24 articles were reviewed in two categories: advanced (G1) and early (G2) disease. Details considered included the following: 1) number of patients in each series; 2) staging; 3) methodology; 4) mortality; 5) morbidity; 6) survival; 7) relief of symptoms; and 8) concomitant treatments. G1 (636 patients) had severe endobronchial obstructive cancer and PDT was primarily for symptom relief. G2 (517 patients) had early stage cancer and were treated with PDT for curative intent. There was no procedure-related mortality in either group. G1 had a 5-28% incidence of skin sensitivity. Haemoptysis occurred in two series; one fatal, an incidence of 2.2%. Almost all patients had symptomatic relief. Patients with lower disease stage and better performance status had improved survival rates. G2 had a 8-28% incidence of sunburn. Three patients in one series (38 patients) had haemoptysis. Survival after 5 yrs in complete remission/response patients was 70%. This review suggests that bronchoscopic photodynamic therapy has indications in selected lung cancer patients with early or advanced stage disease. However, in the absence of a formal comparative study, no claim can be made of its superiority over other endobronchial therapies. (+info)
Interstitial photodynamic therapy in a rat liver metastasis model.
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Photodynamic therapy (PDT) of hepatic tumours has been restricted owing to the preferential retention of photosensitizers in liver tissue. We therefore investigated interstitial tumour illumination as a means of selective PDT. A piece of colon carcinoma CC531 was implanted in the liver of Wag/Rij rats. Photofrin was administered (5 mg kg-1 i.v.) 2 days before laser illumination. Tumours with a mean (+/- s.e.) diameter of 5.7 +/- 0.1 mm (n = 106, 20 days after implantation) were illuminated with 625 nm light, at 200 mW cm-1 from a 0.5 cm cylindrical diffuser and either 100, 200, 400, 800 or 1600 J cm-1. Control groups received either laser illumination only, Photofrin only or diffuser insertion only. Short-term effects were studied on the second day after illumination by light microscopy and computer-assisted integration of the circumference of damaged areas. Long-term effects were studied on day 36. To determine the biochemistry of liver damage and function, serum ASAT and ALAT levels were measured on day 1 and 2, and antipyrine clearance on day 1. Tumour and surrounding liver necrosis increased with light dose delivered (P < 0.001). Best long-term results were obtained at 800 J cm-1 with complete tumour remission in 4 out of 6 animals. No deterioration in liver function was found. The results of this study show the ability of interstitial PDT to cause major destruction of tumour tissue in the liver combined with minimal liver damage. (+info)
Photofrin and light induces microtubule depolymerization in cultured human endothelial cells.
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Endothelial cells were cultured from human umbilical veins and incubated with Photofrin (1 microgram/ml). Cells were then exposed to light, and cytoplasmic microtubule (MT) status was monitored by immunofluorescence microscopy using alpha-tubulin antibody. As early as 15 min following irradiation, a light dose-dependent depolymerization of MT was observed. At sublethal light doses, this effect was transient, with MT repolymerizing within 2-3 h. Cellular ATP levels were monitored to determine whether diminished ATP levels were correlated with MT depolymerization. No correlation was found, since ATP levels remained at a constant value near 50% of unirradiated controls during a time interval in which transient MT depolymerization was observed. Cell viability was monitored by trypan blue exclusion. Transient MT depolymerization occurred at photodynamic doses that produced essentially no decrease in cell viability, while at higher doses, irreversible MT depolymerization was observed prior to loss of viability. Since MT are unstable at intracellular calcium levels greater than 1 microM, we postulate that MT depolymerization results from increases in intracellular calcium caused by photodynamic insult. MT are important in maintaining cell shape. Disruption of MT in endothelial cells due to photodynamic therapy could result in or contribute to exposure of the thrombogenic subendothelium or could alter vascular permeability in the treatment area. (+info)
Photofrin uptake by murine macrophages.
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The uptake of Photofrin by murine peritoneal macrophages in vivo and in vitro was examined. Cellular Photofrin content was measured either by performing a fluorometric assay or by using 14C-labeled drug. For comparison, the uptake of Photofrin by murine SCCVII tumor cells (squamous cell carcinoma) was also examined under the same conditions. The data demonstrate that macrophages have a much greater capacity for Photofrin uptake than SCCVII tumor cells. Photofrin contents at 24 h after drug administration (25 mg/kg) measured 420 +/- 90 (SD), 74 +/- 15, and 15 +/- 2 ng/micrograms of cell protein for peritoneal macrophages, tumor-associated macrophages, and SCCVII tumor cells, respectively. Factors that modify macrophage activity also influence the uptake of the drug by macrophages. The results support the assumption that Photofrin uptake by macrophages is dominated by phagocytosis of highly aggregated components of the drug. In vivo accumulated Photofrin material in peritoneal macrophages, tumor-associated macrophages, and tumor cells has shown very similar in vitro clearance from all three cell types. Only 20-30% of Photofrin was lost from the cells during the initial 24 h, mainly between 1 and 4 h of clearance incubation. (+info)
Distribution of Photofrin between tumour cells and tumour associated macrophages.
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Photofrin levels in cells derived from SCCVII tumours, excised from mice that previously received the drug, were measured using a fluorescence activated cell sorter (FACS). Concomitantly, in the same cells the FACS was used to measure fluorescein isothiocyanate (FITC) fluorescence that originated from FITC-conjugated antimouse IgG added to the cell suspension before sorting. This later measurement enabled discrimination between IgG negative tumour malignant cells and IgG positive host cells (primarily macrophages). In addition, cellular Photofrin content in 'tumour' and 'host' cells sorted by FACS was determined by chemical extraction. The measurements were performed for the time intervals 1-96 h post Photofrin administration. The data showed consistently higher Photofrin levels in the 'host cells', i.e., tumour associated macrophages (TAM), than in 'tumour' cells. On a per cell basis, at any time point studied there was a minimum of 1.7 times more Photofrin in 'host' than in 'tumour cells', while at 4-12 h postadministration, ratios of up to 3.0 times were observed. This corresponds to ratio values greater than 9, when based on Photofrin content per micrograms cell protein. (+info)
Early diagnosis of cancer by detecting the chemiluminescence of hematoporphyrins in peripheral blood lymphocytes.
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Early detection and optimal treatment are the most effective means to improve cancer mortality. Mass screening for cancer has yielded a marked reduction of cancer mortality in the United States. Simple and effective methods are expected for screening of malignancy. Hematoporphyrin derivatives (HPDs) are known to accumulate in cancer cells; thus, HPD has been used for local diagnosis and photodynamic therapy of cancer. The lymphocytes of cancer patients also demonstrate the active uptake of HPD and this phenomenon has been applied for the diagnosis of cancer. In the present study, we have developed a novel method for measurement of the chemiluminescence of HPD in peripheral blood lymphocytes. HPD is composed of hematoporphyrin and its oligomers. Seven cancer patients and seven controls were recruited for this study. The primary cancers included two prostate cancers (one without metastasis and the other with lung metastasis), a renal cancer, a lung adenocarcinoma with systemic metastasis, two gallbladder cancers with lung metastasis, and a colon cancer with liver metastasis. HPD in lymphocytes was measured using a highly sensitive chemiluminescence analyzer with laser light irradiation to detect photoemission by (1)O(2) from HPD. The intensity of chemiluminescence exhibited a linear correlation with the concentrations of HPD. In addition, the level of HPD in lymphocytes was significantly higher in cancer patients than that in healthy volunteers (p < 0.05). These results suggest that detection of the chemiluminescence of HPD in lymphocytes could be a sensitive and simple method for cancer diagnosis and screening. (+info)