benzoporphyrin-d and Skin-Neoplasms

The authors previously observed that antiangiogenic scheduling of photodynamic therapy (PDT) was effective in causing tumor regression through hemostasis. It would thus be expected that photosensitizer entrapped in polycation liposomes (PCLs) would be efficiently taken up in tumor-derived angiogenic vascular endothelial cells due to the strong electrostatic adhesion between the polycation and the plasma membrane, thus resulting in enhanced phototherapeutic efficacy.. Tumors and angiogenesis were induced by subcutaneous injection of Meth-A sarcoma cells into 5-week-old male BALB/c mice. PDT treatment was performed by an intravenous (i.v.) injection of benzoporphyrin derivative monoacid ring A (BPD-MA)-entrapped liposomes or the PCLs (0.25 mg/kg in terms of BPD-MA), followed by exposure to a laser light of 689 nm with 150 J/cm(2) of fluence 15 minutes post injection.. As a result of PDT on angiogenesis-model mice prepared by the dorsal air sac technique, neovascular destruction after laser irradiation was observed when BPD-MA entrapped in PCLs was used. Furthermore, strong suppression of tumor growth was identified by the PCL-mediated PDT treatment along with a prolonged life span for the mice. Destruction of angiogenic vessels and subsequent tumor cell apoptosis were observed after PCL-mediated PDT treatment in an immunofluorescence study. Interestingly, the biodistribution of the injected BPD-MA that was delivered by PCLs indicated invariable photosensitization levels in tumor tissues.. The study revealed that antiangiogenic PDT treatment using a low dose of BPD-MA entrapped in PCLs efficiently induced the destruction of angiogenic vessels and subsequent tumor suppression by vessel occlusion.

Topics: Air Sacs; Amines; Animals; Apoptosis; Endothelium, Vascular; Fluorescent Antibody Technique; Green Fluorescent Proteins; Hydrocarbons; In Situ Nick-End Labeling; Liposomes; Luminescent Proteins; Male; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Photochemotherapy; Photosensitizing Agents; Platelet Endothelial Cell Adhesion Molecule-1; Polyamines; Polyelectrolytes; Polyethyleneimine; Porphyrins; Sarcoma, Experimental; Skin Neoplasms

Photodynamic therapy with benzoporphyrin derivative monoacid ring A and red light (PDT-BPD) has been used to treat human choroidal hemangiomas, and may be useful for cutaneous vascular lesions. The potential for PDT-BPD to inhibit selectively vascular tumor growth was tested in a mouse angiosarcoma model, of which the tumor growth mimics the proliferative phase of hemangiomas. Vascular tumors arising after intradermal injection of immortalized murine endothelial cells were exposed to 50 to 150 J per cm2 of 690 nm laser light 15 min after intravenous injection of 1 mg per kg BPD. Tumor volume and gross response were followed after PDT-BPD and compared with control tumors receiving no treatment, light alone, or BPD alone. At 2 wk, hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling stained tumor sections was performed. There was a selective, fluence-dependent inhibition of tumor growth after PDT-BPD (p< or =0.05), typically with eradication of tumors exposed to higher fluences. A common effect was the replacement of tumor by small scar. Surrounding PDT-BPD exposed normal skin showed no changes. Based on these results, we conclude that PDT-BPD can lead to selective eradication of these tumors. Further studies investigating the efficacy of PDT-BPD for human hemangiomas are warranted.

Topics: Animals; Apoptosis; Cell Division; Cell Line, Transformed; Disease Models, Animal; Hemangiosarcoma; In Situ Nick-End Labeling; Light; Male; Mice; Mice, Nude; Necrosis; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin Neoplasms; Vascular Neoplasms

Photodynamic therapy (PDT) involves laser light excitation of a tumor-localizing photosensitizer to destroy neoplasms. Benzoporphyrin derivative (BPD) is a new photosensitizer with several favorable characteristics.. Studies were designed to: 1) assess the efficacy of BPD-mediated PDT in treating in vivo squamous cell carcinomas (SCC); 2) obtain dosimetry data for BPD and laser parameters; and 3) establish clinical and histologic correlates of BPD-induced tumor regression.. Human SCC was implanted into nude mice. One group received BPD followed by laser light of 150 J/cm2 from an argon-pumped dye laser at 690 nm. Three control groups included laser energy alone, BPD alone, and no treatment.. At day 21 posttreatment only PDT-treated tumors showed a statistically significant decrease in tumor volume and complete cure rate. Clinical resolution (scar) correlated perfectly with histologic resolution (scar).. Human SCC in a nude mouse model responds to BPD-mediated PDT.

Topics: Anaplasia; Animals; Carcinoma, Squamous Cell; Cell Nucleus; Cicatrix; Humans; Laser Therapy; Male; Mice; Mice, Nude; Neoplasm Invasiveness; Photochemotherapy; Porphyrins; Radiation-Sensitizing Agents; Remission Induction; Skin Neoplasms; Tumor Cells, Cultured

Topics: Humans; Laser Therapy; Photochemotherapy; Photosensitizing Agents; Porphyrins; Radiation-Sensitizing Agents; Skin Neoplasms