talaporfin and Fibrosarcoma

The positive clinical results associated with photodynamic therapy (PDT) have led to an expanded need to identify the cellular targets and molecular responses associated with this treatment. Increased knowledge regarding the mechanisms of action associated with PDT-mediated cytotoxicity should contribute to the continued advancement of this therapy. This report focuses on recent studies analyzing PDT resistance and examining stress protein and early response gene activation induced by photosensitizer mediated oxidative stress. Recurring observations from these studies indicate that subcellular targets and cellular responses associated with PDT can vary significantly for different photosensitizers.

Topics: Animals; Antineoplastic Agents; Cell Division; Dihematoporphyrin Ether; Drug Resistance, Neoplasm; Female; Fibrosarcoma; Gene Expression Regulation; Heat-Shock Response; HSP70 Heat-Shock Proteins; Mice; Mice, Inbred C3H; Oxidative Stress; Photosensitizing Agents; Porphyrins; Proto-Oncogenes; Transcriptional Activation; Tumor Cells, Cultured

The effect of photodynamic therapy (PDT) on the vascular system has a significant role in tumor tissue destruction. We investigated the contribution of vascular damage to the antitumor effects of PDT and analyzed the quantitative vascular changes after PDT. Fibrosarcoma-bearing BALB / c male mice were injected with mono-L-aspartyl chlorin e6 (NPe6) at a dose of 0.25, 5 or 15 mg / kg, and photoradiation was performed with a diode laser 10 min, 2 h or 24 h after injection, respectively. Ten minutes after injection of 0. 25 mg / kg, NPe6 was found to be present only in plasma, while at 2 h after injection of 5 mg / kg it was present in both plasma and tumor, and 24 h after injection of 15 mg / kg it was present only in the tumor. The antitumor effects observed in the 5 mg / kg-2 h and 0. 25 mg / kg-10 min groups were virtually the same, whereas the effect in the 15 mg / kg-24 h group was weaker. The damage to the tumor vasculature and tumor cells in the 15 mg / kg-24 h group occurred later than under the other conditions, and vascular damage in the tumor-surrounding tissue was also less marked even 24 h after PDT. These results suggested that the plasma NPe6 concentration during laser irradiation contributed more than the tumor NPe6 concentration to the antitumor effect, and that the minimal damage to blood vessels around the tumor at the low plasma NPe6 concentration may be one reason for the failure to obtain a marked antitumor effect.

Topics: Animals; Antineoplastic Agents; Blood Vessels; Fibrosarcoma; Male; Mice; Mice, Inbred BALB C; Photochemotherapy; Photosensitizing Agents; Porphyrins; Time Factors

The authors performed photodynamic therapy (PDT), avoiding any hyperthermic effects, using a newly developed diode laser and photosensitizer, mono-L-aspartyl chlorin e6 (NPe6), of Meth-A fibrosarcoma implanted in mice and achieved tumor therapeutic benefit. The photodynamic light treatment was performed 5 h following the photosensitizer administration. With 5.0 mg/kg NPe6 and light doses of 50, 100, 150 and 200 J/cm2, the tumor cure rates were 20, 50, 70 and 90%, respectively. With 100 J/cm2 laser exposure and NPe6 doses of 1.25, 2.5, 5.0, 7.5 and 10.0 mg/kg, the tumor cure rates were 0, 20, 50, 70 and 90%, respectively. A charge-coupled device (CCD) camera system was employed to measure the NPe6 fluorescence intensity correlating with the residual amount of the photosensitizer at deferent depth from the tumor surface. The ratios of the NPe6 fluorescence intensity at 3 mm from the tumor surface following 50, 100, 150 and 200 J/cm2 laser exposure to no laser exposure were 0.73, 0.36, 0.22 and 0.16, respectively. With samples sectioned at 1 mm depth, after 50 J/cm2 and the same photosensitizer dose (5 mg/kg) this ratio was 0.19. These results suggest that a certain increase in the tumor tissue level of NPe6 and a certain increase of laser light dose reaching deeper layer of tumor caused an increase in percent cure. In addition, the effectiveness of PDT depends on the total laser dose reaching deeper layers of tumors. Furthermore, the effectiveness of PDT tends to correlate with the amount of NPe6 photobleaching by PDT.

Topics: Animals; Antineoplastic Agents; Female; Fibrosarcoma; Lasers; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Photochemotherapy; Photosensitizing Agents; Porphyrins

We have developed a new high-power red (664 nm) laser diode system for photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6). Meth-A fibrosarcoma cells (1 x 10(6)) were implanted subcutaneously in the right hind leg of 4-week-old BALB/c female mice. One week later, diode laser irradiation was applied 5 h after the intravenous administration of NPe6 to each tumor-bearing mouse. In the first study, the time course of intratumor temperature increase during PDT was measured by using a 23-guage thermocouple hypodermic needle at a depth of 2 mm from the tumor surface. In the second study, 6 groups of 10 to 17 tumor-bearing mice were treated with the diode laser 5 h after intravenous administration of NPe6 at the dose of 1.25, 2.5, 5.0 or 7.5 mg/kg i.v. per mouse. Total photoirradiation ranged from 0 to 150 J/cm2 and the dose rate was adjusted to 100 mW/cm2. Percentages of cures were determined from numbers of mice apparently disease-free 50 days after treatment. The results showed that this diode laser is effective in PDT of implanted fibrosarcoma after NPe6 administration. It also confirmed that the therapeutic effects of PDT were not due to hyperthermia. Moreover, the diode laser beam was demonstrated by CCD technology to be uniform in intensity throughout the photoirradiated field.

Topics: Animals; Female; Fibrosarcoma; Laser Therapy; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Photochemotherapy; Porphyrins