Melanoma is the most aggressive type of skin cancer with the highest mortality rate, with surgery being the standard treatment. In this study, the effect of indocyanine green nanoemulsion in an animal model was evaluated for the treatment of cutaneous melanoma, using photothermal therapy. Different irradiation protocols, and nanoICG intratumoral and systemic delivery ways were tested. Macroscopic and histological analyses and Kaplan-Meier curves for animal survival are presented for comparison of the different investigated protocols.
Non melanoma skin cancer (NMSC) can be seen as a multifaceted problem, considered primarily as a public health problem whose impact on society considers the morbidity and cost aspects of the treatment. It is a social problem, affecting all those who depend exclusively on the Brazilian public health system and need to wait months to receive any type of treatment. From the economic point of view, to treat all patients diagnosed with NMSC, it is necessary a big investment. Finally, the problem is logistical, since the territorial extension of Brazil and its population distribution do not enable the adequate care in all the places, which requires reallocation of patients from small cities to reference centers. Based on these facts, PDT for small skin lesions may be one of the best solutions from an economic point of view. Being a treatment that is easy for the training of professionals and enables to be performed in an ambulatory environment, minimizing post-treatment effects, this study shows that the cost of implementing the procedure on a large scale is extremely adequate for the national public health service. Using a strategy involving companies, national bank and medical partners, equipment, medication and protocols were tested in a multicenter study. With results collected over 5 years from a national program to implement PDT for non melanoma skin cancer over the Brazilian territory, we could reach a great economic evaluation of advances concerning the use of PDT for skin cancer.
It is estimated that up to 75% of the sexually active population is infected with this human papillomavirus virus (HPV). Condylomas acuminate are benign lesions caused by this virus. This study aims to compare photodynamic therapy (PDT) and administration of 70% trichloroacetic acid (TAA) in the condylomas. Each patient is treated weekly until total removal of the lesions, with one of treatment options. In the patients treated with PDT, a Brazilian 20% methyl aminulevulinate cream were applied in the region and incubated by 3 hours and the lesions were illuminated with the CERCa®. This Brazilian system is composed of LEDs emitting at 630 nm which was initially designed for the treatment of cervical intraepithelial neoplasia (CIN) and this study showed the need to develop new devices for illumination of the anus-genital region. During the illumination, a total dose of 150 J/cm2 is delivered over 21 minutes. 22 patients have participated of this clinical study, totaling 15 patients treated with TAA and 8 with PDT, with a complete treatment for 33% using TAA and 75% for PDT. Besides the results of complete response, it is important to highlight that 2 patients showed recurrence for TAA and 4 patients discontinued the treatment with TAA, while, for PDT, there were no cases both recurrence and withdrawal. Therefore, besides the preliminary results obtained with this project show that PDT has been more effective than TAA, it was possible to plan and develop new equipment to ensure greater range of light.
Photodynamic therapy, a technique used for several diseases, when carried out in blood vessels, leads to their destruction. However, vessel recovery is observed some time later, which can be an angiogenic process (formation of new blood vessels) induced by the therapy itself or blood reperfusion. For the investigation of this vascular process after photodynamic therapy, the chorioallantoic membrane (CAM) model of chicken eggs was used. Photodynamic therapy was performed on membrane vessels with the Photogem photosensitizer, at a concentration of 10 μg/mL, and light subdoses to avoid leading the embryo to death. Light doses of 6 and 15 J/cm2 were established for the experiments and a decrease in vessel density 3 hours after photodynamic therapy was observed, with an increase 24 hours later. For quantification of these effects, an equation was determined and a routine of MATLAB was designed to determine the percentage of area occupied by blood vessels in the images, which were performed before, every 30 minutes for the first 3 hours after treatment and 24 hours later. Furthermore, for an analysis of the distribution of large and small vessels, the length and diameter of each vessel in the images were measured with the ImageJ software, which enabled to verify that the smaller vessels are most affected 3 hours after the therapy, with an increase in the number of these vessels after 24 hours.
Cervical cancer is the fourth most frequent cancer in women worldwide. For Brazil, there are estimated 16,370 new cases of cervical cancer for each year of the biennium of 2018-2019, with an estimated risk of 15.43 cases per 100,000 women, occupying the third position [1]. Persistent infection with Human papillomavirus (HPV) has been identified as the major cause of the Cervical Intraepithelial Neoplasia (CIN), a precursor of cervical cancer. The classification of CIN is based on the cellular features to discriminate dysplasia levels, being CIN 1 as mild dysplasia and CIN 2/3 as moderate or severe dysplasia [2]. Cervical cancer can be prevented with a early CIN diagnosis and treatment [3].
Photodynamic therapy (PDT) is a treatment modality that can be indicated for several cancer types and pre-cancer lesions. One of the main applications of PDT is the treatment of superficial skin lesions such as basal cell carcinoma, Bowen’s disease and actinic keratosis. Three elements are necessary in PDT, a photosensitizer (PS); light at specific wavelength to be absorbed by the PS, and molecular oxygen. A typical PS used for skin lesion is protoporphyrin IX (PpIX), which is an intrinsic PS; its production is stimulated by a pro-drug, such as 5-aminolevulinic acid (ALA). Before starting a treatment, it is very important to follow up the PpIX production (to ensure that enough PS was produced prior to a PDT application) and, during a PDT session, to monitor its photodegradation (as it is evidence of the photodynamic effect taking place). The aim of this paper is to present a unique device, LINCE (MMOptics - São Carlos, Brazil), that brings together two probes that can, respectively, allow for fluorescence imaging and work as a light source for PDT treatment. The fluorescence probe of the system is optically based on 400 nm LED (light emitting diodes) arrays that allow observing the fluorescence emission over 450 nm. The PDT illumination probe options are constituted of 630 nm LED arrays for small areas and, for large areas, of both 630 nm and 450 nm LED arrays. Joining both functions at the same device makes PDT treatment simpler, properly monitorable and, hence, more clinically feasible. LINCE has been used in almost 1000 PDT treatments of superficial skin lesions in Brazil, with 88.4% of clearance of superficial BCC.
Photodynamic Therapy (PDT) is a type of cancer treatment that is based on the interaction of light (with specific
wavelength), a photosensitizing agent and molecular oxygen. The photosensitizer (PS) is activated by light and reacts
with oxygen resulting in the production of singlet oxygen that is highly reactive and responsible for the cell death. The
Chick Chorioallantoic Membrane (CAM) model is a transparent membrane that allows visualization and evaluation of
blood vessels and structural changes, where a tumor model was developed. Two induction tumor models were
investigated: tumor biopsy or cell culture. It was used a murine melanoma cell B16F10 in culture and a biopsy from a
xenograft tumor in hairless mouse. Two PS were tested: Photodithazine® and Photogem®, a chlorine and porphyrin
compounds, respectively. Using intravenous administration, the light-drug interval was of 30 minutes, 1 and 3 hours.
Illumination was performed at 630 nm and 660 nm, and the vascular and tumor response was monitored and analyzed.
The PS distribution was checked with confocal microscopy. This model can be useful to study several parameters of
PDT and the effect of this therapy in the cancer treatment since it allows direct visualization of its effects.
The purpose of this study is the assembly and characterization of a custom-made non-linear microscope. The microscope allows the adjustment for in vitro, in vivo and ex vivo imaging of biological samples. Two galvanometer mirrors conjugated by two spherical mirrors are used for the lateral scan and for the axial scan a piezoeletric stage is utilized. The excitation is done using a tunable femtosecond Ti: Sapphire laser. The light is focused in tissue by an objective lens 20X, water immersion, numerical aperture of 1.0, and working distance of 2.0 mm. The detection system is composed by a cut off filter that eliminates laser light back reflections and diverse dichroic filters can be chosen to split the emitted signal for the two photomultiplier detector. The calibration and resolution of the microscope was done using a stage micrometer with 10 μm divisions and fluorescent particle slide, respectively. Fluorescence and second harmonic generation images were performed using epithelial and hepatic tissue, the images have a sub-cellular spatial resolution. Further characterization and differentiation of tissue layers can be obtained by performing axial scanning. By means of the microscope it is possible to have a three dimensional reconstruction of tissues with sub-cellular resolution.
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