Biomedical subjects

K Symonowicz

Publications and source records attributed to K Symonowicz.

7 recordsLinked to original sources

PubMed2007

Photodynamic therapy combined with a cysteine proteinase inhibitor synergistically decrease VEGF production and promote tumour necrosis in a rat mammary carcinoma.

OBJECTIVES: Photodynamic therapy (PDT) and inhibition of cathepsin B proteases by cystatin (cysteine proteinase inhibitor, CPI) are potential new tumour treatment modalities. We have investigated the efficacy of PDT and CPI alone and in combination on a solid mammary carcinoma transplanted into Wistar rats. MATERIALS AND METHODS: Intraperitoneally injected single doses of chlorine e6 or HpD as photosensitizers were excited at 630 nm (90 J/cm(2)). CPI (500 micro g per animal) was injected around the tumour daily during the 8-day treatment. Inoculation of tumour was either on day 1 of the protocol, or 8 days before. On day 8, tumour size was measured, tumour necrosis and vascularization were determined based on haematoxylin and eosin (H&E)-stained sections and serum vascular endothelial growth factor (VEGF) levels measured using an enzyme-linked immunosorbent assay kit. RESULTS: No differences (two-way anova) were found for treatments started with various time lags. At doses where CPI or PDT alone had no or negligible effect, their combination caused a marked (P < 0.001) decrease in serum VEGF, paralleled by a significant decrease in tumour size and number of capillary vessels, and a significant increase in necrosis (up to 80% of the tumour tissue). CONCLUSIONS: The combination of PDT and CPI could be a useful approach in tumour therapy as the two agents appear to be synergistic and probably decrease VEGF production by the tumour tissue.

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PubMed1999

New potent sensitizers for photodynamic therapy: 21-oxaporphyrin, 21-thiaporphyrin and 21,23-dithiaporphyrin induce extensive tumor necrosis.

New sensitizers for photodynamic therapy (PDT) are reported. These compounds, namely 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin, reveal some of the properties required for such therapy. Their physicochemical, chemical and pharmacological features meant that we could use them in the treatment of transplantable BFS1 fibrosarcoma in Balb/c mice. New sensitizers and the well-known chlorin e6 (Ce6) were used in doses of 2.5, 5.0, 7.5 and 10.0 mg/kg body weight, given intraperitoneally and followed by light irradiation, the total light doses being 50, 100 and 150 J/cm(2) within 24 h after injection. The effectiveness of new sensitizers in PDT was evaluated with in terms of tumor necrosis intensity, the survival time of treated animals, the rate of tumor response (complete/partial/no response), and skin photosensitivity. These results were compared to results obtained in analogous conditions after Ce6-PDT. Distribution studies revealed that the highest concentration of new compounds occurred within 24 h after injection. The results of these experiments confirmed that 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin can be considered as potent tumor photosensitizers that do not exert any unwanted effects, primarily skin photosensitization. We suggest that these porphyrins are possible sensitizers to be applied in clinical PDT.

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PubMed1999

[Clinical applications of photodynamic therapy in the treatment of laryngeal lesions].

Photodynamic therapy (PDT) has been used in the treatment of laryngeal lesions. The disorders comprised primary dysplasia and leukoplakia of the vocal cords. The patients after diagnosis were subjected to the therapy. Six hours prior to the light irradiation the patients received 4% solution of delta-aminolevulinic acid (ALA) during 30 minutes inhalation. After 6 hours all the changes were irradiated using 400 nm wavelength light from 300 W halogen lamp (range: 380-420 nm) in order to visualize them. Next, the wavelength was tuned to 650 nm (range 620-680 nm) and the total dose 120 J/cm2 for all cases. Control examinations in patients revealed complete response of the lesions within 2-3 months after PDT.

Adult↗

PubMed1998

5-Aminolevulinic acid photodynamic therapy of transplantable colon adenocarcinoma in BALB/c mice.

We present results of preliminary studies on 5-aminolevulinic acid (5-ALA)-photodynamic therapy (PDT). In order to assess the effectiveness of 5-ALA-PDT we have used BALB/c mice transplanted subcutaneously with mouse colon adenocarcinoma C51. 5-ALA in the dose of 50 mg/kg was given intraperitoneally and 5 h later tumors were exposed to light at total doses from 50 to 75 J/cm2, wavelength 630+/-20 nm and light intensity 200 mW/cm2. Several time points following 5-ALA injections have been used to measure protoporphyrin IX (PpIX) concentration in different tissues from unirradiated mice. PDT effects were evaluated with regard to survival time, tumor response and necrosis depth. The main finding in our tumor model was that the optimum tumor to skin ratio of PpIX occurs within 5 h after sensitizer injection. 5-ALA-PDT resulted in prolongation of survival time of treated mice as compared to control animals and, in some cases, in complete response of tumors. PDT also caused increase in tumor necrosis, while no skin photodamage was observed.

Aminolevulinic Acid↗

PubMed1997

In vivo tumor necrosis factor-alpha induction following chlorin e6-photodynamic therapy in Buffalo rats.

Photodynamic therapy may induce in the in vivo conditions the cytokine tumor necrosis factor-alpha in Buffalo rats. The sensitizer, i.e. chlorin e6, in the doses 2.5, 5.0 and 7.5 mg/kg of body weight followed by light treatment with total doses 50, 100, 150, 200 and 250 J/cm2 resulted in the increase of serum levels of the cytokine. The levels of tumor necrosis factor-alpha have been determined at different time points using enzyme-linked immunosorbent assay (ELISA). In control animals these levels did not exceed the mean value of 189 pg/ml, whereas in photodynamically treated rats the levels were almost 3-4 times higher. The entire experiment has been carried out on healthy animals; control, tumor-bearing rats have also been included to the present experiment.

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PubMedDate not supplied

5,20-bis(4-sulphophenyl)-10,15-bis (2-methoxy-4-sulphophenyl)-21-thiaporphyrin as a new potent sensitizer in photodynamic therapy.

The main purpose of the study was to investigate the effectiveness of a new photosensitizer for photodynamic therapy. 5,20-bis(4-sulphophenyl)-10,15-bis (2-methoxy-4-sulphophenyl)-21-thiaporphyrin (21-thiaporphyrin) was compared to chlorin e6 and tetra(m-hydroxyphenyl)porphyrin (m-THPP) for its ability to sensitize tumors and skin to light. Chlorin e6 and m-THPP induced a strong tumor and skin photosensitization. In contrast, the same doses of 21-thiaporphyrin produced no skin sensitization and gave approximately 10 mm tumor necrosis after light exposure, in comparison to the 5-6 mm necrosis induced by chlorin e6 or m-THPP under identical conditions. 21-Thiaporphyrin, tested as a potential photosensitizer, induced no skin sensitization even at doses as high as 7.5 mg/kg body weight. 21-Thiaporphyrin presents a high potency in tumor sensitizing, i.e. a feature required for an efficient photosensitizer in photodynamic therapy applications.

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PubMedDate not supplied

Tumor histopathology following new sensitizers: dithiaporphyrin- and sulfoxaporphyrin-mediated photodynamic therapy.

BACKGROUND: Our main aim was to evaluate tumor histopathology following new sensitizer-mediated photodynamic therapy (PDT). MATERIALS AND METHODS: In order to complete our studies we decided to use photosensitizers, i.e. dithiaporphyrin (DTP) and sulfoxaporphyrin (OXA) in combination with halogen lamp irradiation of presensitized tumors. The doses of sensitizers were: 2.5, 5.0, 7.5 and 10.0 mg/kg of body weight and total light doses were: 50, 100 and 150 J/sq.cm at the selected wavelength. Following such a treatment we have evaluated tumor necrosis of BFS1 fibrosarcoma growing on BALB/c mice. Together with tumor necrosis evaluation we have examined skin response to photodynamic treatment. RESULTS: We have found that both new sensitizers caused significant tumor damage at no skin alterations. The induction of tumor necrosis seemed to be dose dependent, i.e. higher photodynamic doses (sensitizer dose x light dose) resulted in more severe damage to the tumors than the lower doses. CONCLUSION: Our study showed that BFS1 fibrosarcoma is highly sensitive to PDT after application of new sensitizers. Both compounds can be considered as potent tumor photosensitizers in future clinical trials.

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