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We present new approaches to treat both primary cutaneous and ocular melanoma, with potential to reduce metastatic spread In mouse models optical clearing combined with dual-photosensitizer PDT is used to treat primary cutaneous xenogafts. Two-photon PDT is used in ocular melanoma of extraocular (conjunctival) or intraocular (uveal) melanoma. Immune effects are investigated in immunocompetent mice using blood biomarkers and by tumor re-challenge. In vitro studies in pigmented and non-pigmented melanoma cells show melanin-mediated photosensitization as a novel mechanism of action of 2-γ PDT. Full-thickness primary tumor eradication has been achieved: ∼1 and 4 mm in immune deficient and competent mice, respectively. Marked reduction in metastatic tumor burden is observed in the latter. These studies reopen the possibility of PDT as an effective modality in melanoma. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a well-described technique that is primarily used for thin and superficial tumors. Despite the advantages of immune response upregulation, high complete response rates and excellent cosmetics and preservation of tissue structure, the limited light penetration into tissue complicates achieving full-thickness/large-volume treatment of pigmented, thicker, deep-seated or diffuse metastatic tumors1. Reported in vitro studies in melanoma and breast cancer cells show increased expression of major histocompatibility complex I after the combination of psoralen and X-radiation, which is representative of a potential immune response upregulation2. The aim here is to investigate the clinical photosensitizer Verteporfin (VP) as a radiosensitizer to achieve deep tissue penetration while retaining immune upregulation, and thereby enhance tumor-specific radiation responses in pancreatic cancer3 and melanoma4, which are aggressive tumors with high metastatic potential and low survival rates. In vitro studies were carried out with bioluminescent human pancreatic cancer (Panc-1-Luc-2) and murine melanotic melanoma (B16F10) cell lines. The cells were irradiated using 225 kVp (XRAD) or 6 MeV (Linac) X-ray beams, and the treatment response was measured by clonogenicity. In all cases, the presence of VP in the cells reduced survival compared with X-ray only controls: e.g. the group irradiated in the Linac, which includes a contribution from VP activation by X-ray induced Cherenkov light, reached up to 5 Logs of cell death after a single fraction of 10 Gy. In the ex-ovo model, duck eggs at 8 days post fertilization were engrafted with 15 µL (∼5 × 107) of Panc-1-Luc-2 or B16F10-Luc cells. Treatment was given 3 days later using topical VP administration with irradiation 1.5 h later. Combining a single fraction of 5 Gy with 5 µg/mL VP gave >2-fold reduction of the bioluminescence compared to <1 fold for radiation alone. After 3 daily fractions, the in ovo tumors treated with VP + radiation showed undetectable bioluminescence signal until sacrificed at 2 d after the last fraction. These studies are intended primarily to generate baseline response data for radiodynamic therapy with different nanoparticle formulations, including both lipid-porphyrin porphysomes and metal nanoclusters. ACKNOWLEDGEMENTS This work is supported by the Canadian Institutes of Health Research, The Terry Fox research institute and a Tri-Council NRFR grant. L. Pires is supported by the Banting Fellowship. [ABSTRACT FROM AUTHOR]

This study aimed to assess the photodynamic effect of Phonozen, a newly developed photosensitizer, on varied illumination wavelength of 405 nm and 664 nm in a mouse model with peritoneal carcinomatosis. Peritoneal carcinomatosis was induced by IP injection of 1 × 106 MKN45-luc cells to 9 week old female athymic nude mice. Ten days after induction, PDT was performed on 60 mice injecting Phonozen 3 hours before PDT. Twenty mice for each group underwent intra-peritoneal catheterization and underwent (A)no irradiation, irradiation with (B) 405nm, and (C) 664 nm for 1hour, delivering 50J per mouse. Fifteen of each group were observed for 20 weeks for survival analysis and five of each group were sacrificed 2 days after for quantitative assessment of necrosis status. Both irradiation approach with 405 nm and 664 nm significantly prolonged the survival of PC mice over control group. No survival difference were observed between two irradiated group. Semiquantitative assessment showed significantly higher proportion of responder following irradiation of 405 nm than 664 nm. Phonozen shows effective photodynamic tumoricidal effect. Activated by same power, 405 nm is more effective than 664nm for treatment of PC mice model [ABSTRACT FROM AUTHOR]

Summary: Non-melanoma skin cancer is the most prevalent cancer type in Brazil and worldwide. Photodynamic therapy (PDT) is a noninvasive technique with excellent cosmetic outcome and good curative results, when used for the initial stages of skin cancer. A Brazilian program was established to determine the efficacy of methyl aminolevulinate (MAL)-PDT, using Brazilian device and drug. The equipment is a dual device that combines the photodiagnosis, based on widefield fluorescence, and the treatment at 630nm. A protocol was defined for the treatment of basal cell carcinoma with 20% MAL cream application. The program also involves the training of the medical teams at different Brazilian regions, and with distinct facilities and previous PDT education. In this report we present the partial results of 27 centers with 366 treated BCC lesions in 294 patients. A complete response (CR) was observed in 76.5% (280/366). The better response was observed for superficial BCC, with CR 160 lesions (80.4%), when compared with nodular or pigmented BCC. Experienced centers presented CR of 85.8% and 90.6% for superficial and nodular BCC respectively. A high influence of the previous doctor experience on the CR values was observed, especially due to a better tumor selection. [Copyright &y& Elsevier]