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31.
Donnelly RF Ma LW Juzenas P Iani V McCarron PA Woolfson AD Moan J 《Photochemistry and photobiology》2006,82(3):670-675
In clinical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) of skin tumors it is desirable to develop vehicles that minimize the penetration of ALA through normal stratum corneum and maximize it through the compromised stratum corneum of the tumors to improve tumor selectivity. We have designed a bioadhesive patch, which may be able to achieve this aim. It induces levels of protoporphyrin IX (PpIX) in skin overlying tumors similar to those induced by the proprietary cream (Porphin) but at the same time induces less PpIX to form in normal skin and at distant sites. The mechanisms of action of the patch, as compared with that of the cream, were studied by means of Cuprophan barriers that mimic compromised tumor stratum corneum and in a mouse model with transplanted tumors. 相似文献
32.
ACTION SPECTRA FOR HEMATOPORPHYRIN DERIVATIVE AND PHOTOFRIN II WITH RESPECT TO SENSITIZATION OF HUMAN CELLS IN VITRO TO PHOTOINACTIVATION 总被引:1,自引:0,他引:1
Abstract— Exposure of Raji cells to haematoporphyrin derivative (HPD) and red light caused marked cytotoxicity. This was completely inhibited under anaerobic conditions. By using sodium dithionite in aqueous solutions, precise and graded oxygen concentrations could be achieved. Cytotoxicity was directly proportional to the oxygen concentration of the medium until a maximum was reached at a pO2 of 90 mm Hg. Sodium dithionite did not affect the viability of test cells and did not alter the chromatographic profile of HPD. Dithionite did not interfere with the uptake of HPD by cells. Dependency of phototoxicity upon aerobic conditions suggests that the cytotoxic agent is derived from oxygen and is consistent with the hypothesis that singlet oxygen and/or oxygen-derived free radicals play an important role in photochemotherapy with HPD. 相似文献
33.
N C Yates J Moan A Western 《Journal of photochemistry and photobiology. B, Biology》1990,4(4):379-390
Metal naphthalocyanine complexes (MNCSs) absorb light in the near-IR spectral region (760 nm) where tissue penetration is optimal and they have been proposed as agents for photodynamic therapy (PDT). Sulphonated derivatives of tris-(2,3-naphthalocyanato) bis-chloroaluminium(III) and zinc(II) with various degrees of sulphonation were prepared. Cellular uptake, aggregation in cellular environments, cytotoxicity and photosensitizing properties were studied. Three of the four dyes studied were taken up by cells to a satisfactory degree and were not cytotoxic at the concentration used (10 micrograms ml-1). The least sulphonated sample of zinc naphthalocyanine produced some phototoxic effects (LD50 = 1.12 J cm-2). All the other samples of sulphonated naphthalocyanine were found to be aggregated inside the NHIK 3025 cells, preventing any significant PDT effect. 相似文献
34.
Human cervix carcinoma cells of the line NHIK 3025 were incubated for 18 h with tetra(4-sulfonatophenyl)porphine (TPPS4) and further incubated for 1-29 h in sensitizer free medium before exposure to light. After 1 h in sensitizer free medium only a 20% further loss of TPPS4 was observed within the next 28 h. During the time in sensitizer free medium, each TPPS4 molecule became more efficient in sensitizing single cells to photoinactivation. This enhanced photosensitizing efficiency of TPPS4 correlated well with the enhanced fluorescence yield of TPPS4. In some experiments the cells were exposed to a light dose inactivating 10% of the cells after incubation for 1 h in sensitizer free medium and a second graded light dose given 4-28 h later. Exposure of the cells to the first light dose led to loss of 60% of TPPS4 from the cells. Despite the significant loss of sensitizer from the cells the fluorescence yield of TPPS4 from each cell was found to increase (e.g. by 100% 4 h after light exposure). The enhanced fluorescence yield of cell bound TPPS4 was followed by a 1.6-2.5-fold increase in sensitivity of each cell to second light dose. Thus, a small light dose increased the photosensitivity of TPPS4-loaded NHIK 3025 cells for several hours after the first light exposure. The advantageous effect of light fractionation was reduced by a significantly enhanced loss of sensitizer induced by the first light exposure. The optimal time between the two fractions of light seems to be 30-90 min. 相似文献
35.
Abstract— Yeast cells are inactivated by treatment with hematoporphyrin and light. The inactivation, which is mediated by singlet oxygen (1 O2 ), is enhanced by the presence of phosphate and chloride. Neither phosphate nor chloride has any influence on the yield of 1 O2 . Possible mechanisms for the enhancement are briefly discussed. 相似文献
36.
Johan Moan Kristian Berg Jerry C. Bommer Andre Western 《Photochemistry and photobiology》1992,56(2):171-175
Human carcinoma cells (NHIK 3025 cells) and Chinese hamster cells (V79 cells) were incubated with AlPcS1, AlPcS2 and AlPcS4, phthalocyanines with different lipophilicity but with similar photochemical properties when in monomeric solutions. The absorption- and fluorescence spectra of the dyes in the cells were recorded as well as their action spectra with respect to sensitizing cells to photoinactivation. These spectra show that under the present conditions AlPcS1 is strongly aggregated in both cell lines; AlPcS2 is aggregated in V79 cells but much less so in NHIK 3025 cells. A main finding is that the shapes of the action spectra are similar to that of the fluorescence excitation spectra, but not to the absorption spectra, indicating that the photosensitizing effects of the dyes are mainly due to their monomeric fraction in the cells. AlPcS2 and AlPcS4 localize intracellularly mainly in lysosomes while AlPcS1 was found to be more diffusely distributed in cells. As measured per quantum of fluorescence emitted, AlPcS1 and AlPcS2 are more efficient sensitizers than AlPcS4. The difference in efficiency between AlPcS2 and AlPcS4 is supposedly due to a different localization pattern on the suborganelle level. 相似文献
37.
Abstract The efficiency of different sensitizers for photodynamic therapy (PDT) was tested using a model system with a C3H mammary carcinoma growing subcutaneously on the dorsal side of mouse feet. Growth curves were constructed from which growth delay and doubling time in the regrowth phase were calculated. As PDT induced oedema in the mouse foot, this model system also allowed assessment of normal tissue response.
The following sensitizers were tested: hematoporphyrin derivative (HpD), Photofrin II (PII), tetraphenylporphinetetrasulfonate (TPPS4 ), acridine orange (AO), phthalocyanine tetrasulfonate (PCTS), Al- and Zn-phthalocyanine tetrasulfonate (A1PCTS and ZnPCTS). For tumor control, the following sensitizer efficiencies were found: PII > HpD > AIPCTS > TPPS4 >>> ZnPCTS, PCTS, AO. With regard to sensitizing normal-tissue damage: PII > AIPCTS, TPPS4 > HpD, ZnPCTS, PCTS. The results suggest that AIPCTS should be further evaluated for use in PDT. 相似文献
The following sensitizers were tested: hematoporphyrin derivative (HpD), Photofrin II (PII), tetraphenylporphinetetrasulfonate (TPPS
38.
The temperature dependence of the uptake phase of 5-aminolevulinic acid (ALA) and the following production phase of protoporphyrin IX (PpIX) in normal mouse skin was investigated. A cream containing 20% ALA was topically applied on the skin for 10 min. The amount of ALA-induced PpIX was evaluated by measuring the fluorescence of PpIX from the treated skin. No measurable amount of PpIX was found in the skin immediately after 10 min application of ALA. The penetration of ALA into the skin was almost temperature independent while the following production of PpIX was found to be a strongly temperature-dependent process. Practically no PpIX was formed in the skin as long as skin temperature was kept low (12 degrees C). 相似文献
39.
Juzenas P Sharfaei S Moan J Bissonnette R 《Journal of photochemistry and photobiology. B, Biology》2002,67(1):11-17
Accumulation of protoporphyrin IX (PpIX) was investigated in normal skin and UV-induced tumours in hairless mice after topical application of a cream containing 2, 8 or 16% of 5-aminolevulinic acid methyl ester (ALA-Me). Higher levels of PpIX were measured in tumours compared to normal skin. The maximal amount of PpIX was reached at 1.5, 3 and 4 h after 2, 8 and 16% ALA-Me application, respectively. Higher tumour to normal skin PpIX fluorescence ratios were measured after application of 8 and 16% ALA-Me than after application of 2%. After irradiation with a broad spectrum of visible light from a slide projector, more than 90% of PpIX was bleached by fluences of 36 and 48 J/cm2, at fluence rates of 10 and 40 mW/cm2 respectively. At these fluences, the PpIX photobleaching rate was significantly higher (P<0.05) in normal mouse skin than in tumours. In addition, for a given fluence, more PpIX was photobleached at the lower fluence rate (10 mW/cm2) than at the higher fluence rate (40 mW/cm2) in normal skin (P<0.001) as well as in tumours (P<0.05) after exposure to 24 J/cm2 of light. In conclusion, the highest tumour to normal skin PpIX ratio was observed 3 h after application of 8% ALA-Me, suggesting that light exposure should be performed at this time in order to achieve an optimal PDT effect in this tumour model. 相似文献
40.
Epidemiological Support for an Hypothesis for Melanoma Induction Indicating a Role for UVA Radiation 总被引:5,自引:0,他引:5
An hypothesis for melanoma induction is presented: UV radiation absorbed by melanin in melanocytes generates products that may activate the carcinogenic process. Products formed by UV absorption in the upper layers of the epidermis cannot diffuse down as far as to the melanocytes. Thus, melanin in the upper layer of the skin may be protective, while that in melanocytes may be photocarcinogenic. Observations that support this hypothesis include: (1) Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians, but the ratio of their incidence rates of cutaneous malignant melanoma to that of squamous cell carcinoma is larger than the corresponding ratio for Caucasians. (2) Albino Africans, as compared with normally pigmented Africans, seem to have a relatively small risk of getting cutaneous malignant melanomas compared to nonmelanomas. This is probably also true for albino and normally pigmented Caucasians. (3) Among sun-sensitive, poorly tanning persons, frequent UV exposures are associated with increased risk of melanoma, whereas among sun-resistant, well-tanning persons, increased frequency of exposure is associated with decreased melanoma risk. (4) It is likely that UVA, being absorbed by melanin, might have a melanoma-inducing effect. This is in agreement with some epidemiological investigations which indicate that sun-screen lotions may not protect sufficiently against melanoma induction. The relative latitude gradient for UVA is much smaller than that for UVB. The same is true for the relative latitude gradient of cutaneous malignant melanoma as compared with squamous cell carcinoma and basal cell carcinoma. Under the assumption that the average slopes of the curves relating incidence rates with fluences of carcinogenic UV radiation are similar for melanomas and nonmelanomas, these facts are in agreement with the assumption that UVA plays a significant role in the induction of melanomas in humans. This is in agreement with the experimental results with Xiphophorus. 相似文献