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Photodynamic therapy for human malignant mesothelioma in the nude mouse
1Division of Cardiothoracic Surgery, University of Rochester School of Medicine and Dentistry, New York 14642.
Abstract:
Photodynamic therapy (PDT) utilizes a photoactivatable preparation, Photofrin II, which selectively localizes in cancerous tissue and produces substances toxic to that tissue when activated by light. Whether PDT would be able to selectively destroy human malignant mesothelioma was investigated by using a human-derived malignant mesothelioma tumor subcutaneously implanted in nude mice. Human malignant mesothelioma was grown subcutaneously to a size of 0.2-0.4 cm3. Selective retention of Photofrin II was studied by measuring light-induced inhibition of cytochrome c oxidase activity in tumor, heart, and lung. Photofrin II was retained in greater quantities in tumor than in heart or lung at 24 hr after injection. Using laser light at 630 nm under varying conditions, tumor growth was measured every 2 days following PDT for 18 days. All PDT regimens were successful in destroying malignant mesothelioma. Photofrin II at 5 mg/kg was superior to 2 mg/kg (P less than 0.005), light delivered at 50 mW/cm2 x 2 hr was superior to that delivered at 200 mW/cm2 x 30 min (P less than 0.05), and a total fluence of 180 J/cm2 was equivalent to 360 J/cm2 in affecting tumor growth. Ten of 12 mice treated at 50 mW/cm2 became tumor-free and remained so for 30 days following treatment. We concluded that PDT was effective against human malignant mesothelioma in a nude mouse model without adversely affecting the animal. A role for PDT in treating patients with malignant mesothelioma may exist.
Insights
Photodynamic therapy (PDT) effectively destroyed human malignant mesothelioma in mice using Photofrin II and laser light. This cancer treatment showed promise, with many mice becoming tumor-free without adverse effects.
Area of Science:
- Oncology
- Biochemistry
- Photomedicine
Background:
- Photodynamic therapy (PDT) uses a photosensitizer (Photofrin II) activated by light to destroy cancer cells.
- Photofrin II selectively accumulates in cancerous tissue, producing toxic substances upon light activation.
Purpose of the Study:
- To investigate the efficacy of PDT in selectively destroying human malignant mesothelioma xenografts in nude mice.
- To determine optimal PDT parameters for mesothelioma treatment.
Main Methods:
- Human malignant mesothelioma xenografts were established in nude mice.
- Selective retention of Photofrin II was assessed by measuring cytochrome c oxidase inhibition.
- Mice received PDT with varying Photofrin II doses and laser light conditions (630 nm).
- Tumor growth was monitored for 18 days post-treatment.
Main Results:
- Photofrin II demonstrated greater retention in tumor tissue compared to heart and lung at 24 hours.
- All PDT regimens successfully destroyed mesothelioma xenografts.
- A dose of 5 mg/kg Photofrin II and light delivery at 50 mW/cm² for 2 hours were superior parameters.
- Ten of 12 mice treated with optimal parameters achieved complete tumor remission and remained tumor-free for 30 days.
Conclusions:
- PDT is an effective treatment for human malignant mesothelioma in a preclinical mouse model.
- The treatment demonstrated selectivity, sparing healthy tissues.
- PDT warrants further investigation for clinical application in treating malignant mesothelioma.