ORIGINAL ARTICLES
The aim of this study was to analyze the distribution of chlorin type photosensitizers (PS): chlorin e6 (Ce6) and dimethyl ester of chlorin e6 (DME), in human adenocarcinoma HT29 monolayer and multicellular spheroid cell cultures. There is an assumption, that the chemical modification of Ce6 molecules causes a change of intracellular location and the enhanced photosensitizing activity. Indeed, photodynamic therapy on monolayer cell culture with DME showed two times higher photokilling ability comparing with that of non-modified analogue.
Ce6 and DME biodistribution processes in tumor tissue were studied on multicellular tumor spheroids model. Total amount of DME in multicellular tumor spheroids exceeded 1,3 times accumulation of Ce6. According to fluorescence microscopy studies, Ce6 and DME distribution patterns in the spheroids bulk were similar. Application of 2D and 3D tumor models for the analysis of photosensitizer distribution may allow predicting the photosensitizer biodistribution features for photodynamic therapy in vivo.
Optimized irradiation regimens for intraperitoneal photodynamic therapy with porphyrin and phthalocyanine photosensitizers are determined in in vitro and in vivo studies.
The experimental study on НЕр2 cell line showed that reduce of power density for constant light dose increased significantly the efficacy of photodynamic therapy (the reduce of power density from 20-80 mW/cm2 to 10 mW/cm2 had the same results (90% cell death) for half as much concentration of the photosensitizer).
The obtained results were confirmed in vivo in mice with grafted tumor S-37. For light dose of 90 J/cm2 and power density of 25 mW/cm2 none of animals in the experimental group had total resorption of the tumor. For the same light dose and decrease of power density to 12 mW/cm2 total tumor resorption was achieved in 34% of animals, 66% of animals died from phototoxic shock. For twofold decrease of light dose – to 45 J/cm2 with the same low-intensity power density (12 mW/cm2) we managed total tumor resorption in 100% of animals.
In the following studies of optimized irradiation regimen for intrapleural photodynamic therapy the reaction of intact peritoneum of rats on photodynamic exposure was assessed and optimized parameters of laser irradiation, which did not cause necrosis and intense inflammatory reaction of peritoneum, were determined – light dose of 10 J/cm2 with power density of mW/cm2.
Thus, the reasonability for use of low-intensity regimens of irradiation for intraperitoneal photodynamic therapy was confirmed experimentally with possibility of high efficacy of treatment without inflammatory reactions of peritoneum.
Results of autofluorescence dermatoscopy using videodermatoscope «EcoSkin» in patients with different dermatologic diseases are represented. The study included 64 patients, 27 of them had different types of psoriasis, 11 – acne, 3 – rosacea, 5 – eczema, 3 – mite-induced dermatitis, 4 – superficial mycosis of the glabrous skin, 7 – atopic dermatitis, 4 – seborrheic dermatitis. The major changes of autofluorescence were detected in pathological foci in patients with psoriasis. Authors suppose that increased autofluorescence of porphyrins in psoriatic plaques in the study is associated with enhanced prolyferation in pathological tissues and with liver dysfunction. The analysis of autofluorescence images in patients with rosacea, eczema, atopic and mite-induced dermatitis did not show significant difference in autofluorescence images of affected skin comparing with intact skin in same patients. In patients with acne a pattern of spot red-orange autofluorescence of skin in seborrheic areas corresponding with location of openings of pilosebaceous apparatus was detected that was associated by authors with Propionibacterium acnes infection.
LITERATURE REVIEWS
The article summarizes the main mechanisms underlying the radiosensitizing effect of photosensitizers.
According to literature data many authors consider the formation of reactive oxygen species to be the key element in the implementation of the antitumor effect of ionizing radiation, which transfers the photosensitizer molecule from the ground state to the excited state. Their formation leads to the development of oxidative stress. The consequence of the realization of the oxidative stress induced by ionizing radiation is apoptosis of tumor cells.
The first photosensitizers, which radiosensitizing activity was confirmed, were hematoprofyrin and photophryn II. A detailed analysis of the results of experimental studies of radiosensitizing effect of photosensitizers on cell culture and laboratory animals with transplanted lines of malignant gliomas (glioma C6, gliosarcoma 9L, glioblastoma U87-MG) was made.
The method of tumor radiosensitizing by administration of photosensitizers has been tested in patients with recurrent gliomas grade III-IV in a number of oncological centers. The obtained results show its good tolerability and antitumor efficacy.
We have not found publications on the study of the radiosensitizing effect of chlorine-based photosensitizers in the available literature, that makes following studies in this field relevant.
CASE-REPORTS
The article presents a clinical observation of the patient of 38 y.o. with cancer of the left breast stage IIIC урТ4bN3М0L1V1. On the 1st step of the treatment the patient had 2 courses of CAF neoadjuvant chemotherapy, on the 2nd step – extended radical mastectomy on the left with intraoperative photodynamic therapy and closure of the defect with ТRАМ-flap, on the 3rd step – continuation of the chemotherapy (8 courses), on the 4th step – radiation therapy to the chest wall on the left and zones of regional lymph drainage, targeted therapy with herceptin a (1 year). Four years later a silicone implant was inserted into the left breast. Corrective surgery (reduction mammoplasty on the right side) was performed in april, 2017. Currently, the patient has remission of the disease of the left breast, the period of remission accounts for 8 years.
The results of the clinical observation of a female patient with squamous cell carcinoma of the cheek skin treated by the method of photodynamic therapy (PDT) using the photosensitizer of fotoditazin are represented. The patient had single course of PDT. Fotoditazin was injected in a dose of 0.8 mg/kg of body weight as a single intravenous infusion in 0.9% sodium chloride. The irradiation was performed once, 2.5 h after injection of the photosensitizer (power density of laser irradiation – 200-300 mW/cm2, light dose of a single session of 300-350 J/ cm2). There were no side effects after photosensitizer injection and after irradiation. The result of the treatment was defined as partial tumor regression. For nowadays the follow-up period is 2 months. The repeated course of PDT is scheduled.