Effective thermal penetration depth in photo-irradiated ex vivo human tissues.

OBJECTIVE: In this work, a model of bioheat distribution is discussed for ex vivo human tissue samples, and the thermal penetration depth measurements performed on several tissues are presented. BACKGROUND DATA: Optical radiation is widely applied in the treatment and diagnosis of different pathologies. A power density of incident light at 100 mW/cm(2) is sufficiently high enough to induce a temperature increase of >5°C in irradiated human tissue. In this case, knowledge of the thermal properties of the tissue is needed to achieve a better understanding of the therapeutic effects. METHOD: The application of the diffusion approximation of the radiative transfer equation for the distribution of optical radiation, the experimental setup, and the results thereof are presented and discussed. RESULTS: The effective thermal penetration depth in the studied tissues has been determined to be in the range of 4.3-7.0 mm. CONCLUSIONS: The effective thermal penetration depth has been defined, and this could be useful for developing models to describe the thermal effects with a separate analysis of the tissue itself and the blood that irrigates it.

Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: results of a Phase Ib/IIa study.

NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but it is minimally or not expressed at all on most normal human tissues. A Phase Ib/IIa clinical trial was carried out in patients with advanced cutaneous and ocular malignant melanomas, to evaluate immunogenicity and toxicity of an intramuscularly administered cancer vaccine and composed by NeuGcGM3 in a proteoliposome of Neisseria meningitides with Montanide ISA 51 as adjuvant. Twenty two patients were included, twelve at dose level of 200 microg and 10 at 400 microg. The first five doses were administered every other week and then monthly until 9 doses. 12 patients received additional immunizations. Vaccination induced specific anti-NeuGcGM3 IgM, IgG and IgA antibodies responses. Titers of IgM were greater for the highest vaccine doses. Vaccination also elicited DTH response in 45.5% of patients in the lower doses and 77.8% in the higher doses. Toxicities were mostly grade 1 or 2, according CTC-NCI criteria. Interestingly, 3 patients developed vitiligo at the lower dose (none in the highest dose) although the nominal antigen NeuGcGM3 is not present in melanocytes. Survival analysis was not the goal of this Phase I trial; nevertheless, the fact that seven patients are alive for more than 2 years after inclusion is noteworthy. Safety and immunogenicity with NeuGcGM3 vaccine treatment in advanced melanoma patients were established. The prognostic value of autoimmunity and the possibilities of dissociating anti-tumor immunity from autoimmunity deserve further research.