Quality of life is an important integrative indicator of treatment effectiveness in oncology and reflects patients’ subjective physical, psychological, and social well-being. Data regarding the impact of systemic photodynamic therapy on quality of life in patients with metastatic prostate cancer remains limited. The aim of this study was to evaluate the effect of systemic photodynamic therapy on quality-of-life outcomes in patients with metastatic prostate cancer. A prospective longitudinal study was conducted involving 14 patients with a mean age of 69 years. Quality of life was assessed before and after treatment using the Quality of Life-Cancer Survivor (QOL-CS) questionnaire. Internal consistency of the scales was evaluated using Cronbach’s alpha. Changes in quality-of-life scores were analyzed using the paired Student’s t-test, and effect sizes were calculated using Cohen’s d. The QOL-CS questionnaire demonstrated high reliability (α = 0.91). After treatment, statistically significant improvements were observed in the physical, psychological, and social domains, as well as in the overall quality-of-life score (p < 0.001), with large effect sizes (Cohen’s d > 1.8). Changes in spiritual well-being did not reach statistical significance (p = 0.134). Systemic photodynamic therapy is associated with clinically meaningful improvements in quality of life among patients with metastatic prostate cancer.
The role of prophylactic central neck dissection in patients with differentiated thyroid cancer without clinically evident lymph node involvement remains controversial despite its importance for staging and risk stratification. In this context, intraoperative lymphatic mapping may provide an opportunity to reduce the extent of surgical intervention. The study included 125 patients with cN0 differentiated thyroid cancer who underwent thyroidectomy or hemityroidectomy. Central neck dissection was performed in 98 patients, while 27 patients underwent fluorescence-guided lymphatic mapping using indocyanine green with selective lymph node removal. The mean number of removed lymph nodes was significantly lower in the ICG group (3.67 vs 10.3; p < 0.001), while the rate of metastatic node detection did not differ between groups (33.3% vs 34.7%; p = 0.62). The incidence of transient hypoparathyroidism was comparable (14.8% vs 13.3%; p = 0.74), whereas permanent hypoparathyroidism was observed only in the central neck dissection group (17.3% vs 0%; p = 0.02). However, in the subgroup of patients undergoing thyroidectomy, no difference in transient hypoparathyroidism was found (15.5% vs 15.4%; p = 1.00). Permanent recurrent laryngeal nerve palsy occurred in 4.1% of patients in the control group and was not observed in the ICG group. These findings suggest that fluorescence-guided lymphatic mapping allows selective lymph node removal with a reduced extent of dissection while maintaining a comparable rate of metastatic detection. The differences in postoperative complications appear to be primarily related to the extent of surgery. Further studies are required to evaluate the diagnostic accuracy and long-term outcomes of this approach.
Tuberculosis remains a leading cause of mortality among infectious diseases, with drug resistance posing a major challenge to effective treatment. Macrophages serve as the primary cellular reservoir for M. tuberculosis (MTB), which upon interaction with this pathogen may acquire a complex phenotype with predominantly anti-inflammatory, immunosuppressive properties and establish a metabolically privileged niche that supports intracellular persistence and survival of MTB. In this review, the phenotype of such macrophages is referred to as M2 (alternatively activated macrophages). This review systematizes current strategies for targeted delivery of anti-tuberculosis agents to MTB-infected macrophages using macromolecular and nanoscale carriers. Passive and active targeting approaches are examined, including the engineering of vector properties through ligand conjugation to M2 macrophage receptors. Strategies for reprogramming macrophage functional phenotype and the development of nanoscale biomimetics are discussed. Special emphasis is placed on targeted delivery of photosensitizers to infected cells for antimicrobial photodynamic therapy. The summarized evidence indicates that combined nanotherapeutic approaches, integrating direct antimicrobial activity with modulation of local immune responses, offer promising strategies for overcoming drug resistance and achieving eradication of MTB.
The study is devoted to the development of an early preclinical method for the diagnosis of age-related macular degeneration using timecorrelated fluorescence microscopy and visible spectroscopy data for the analysis of fluorescence lifetimes and spectra for lipofuscin granules. Lipofuscin granules were obtained from cells of the retinal pigment epithelium of human cadaveric eyes without signs of pathology. To research the fluorescence lifetimes of lipofuscin granules we used the fluorescence excitation method with time-correlated single photon counting technique and the fluorescence lifetimes imaging microscopy (FLIM) method in combination with a superconducting single-photon detector. Photo-oxidized granules were used as a model of age-related macular degeneration. A comparative analysis of the fluorescence lifetimes and spectra before and after photooxidation of lipofuscin granules showed significant differences in the characteristic lifetimes, as well as a shift of the maximum of the fluorescence spectrum to the short-wavelength region. Analysis of the obtained data confirms the possibility of developing a comprehensive method for the spectral and lifetime characterization of fundus autofluorescence. It is necessary to take into account the changes in the contribution of the τlifetime and the shift in the peak of the fluorescence spectrum. This approach will make it possible to determine diagnostic criteria for norm and 2 and τ3 components of the decomposition of the lifetimes curve of fluorescence decay with the longest characteristic pathology in the diagnosis of degenerative diseases of the retina and retinal pigment epithelium. Analysis of the data obtained showed that the FLIM method might become promising for the development of an early preclinical method for the diagnosis of age-related macular degeneration of the retina.
The study evaluated various types of low-intensity photobiomodulatory therapy (PBMT) in reducing acute pain after complex tooth extraction. Complex extraction of maxillary molars and premolars (no more than two teeth, on one side) was performed in 119 patients (aged 18-44 years). In Group 1 (n = 28), PBMT was not performed. In Group 2 (n = 32), pulsed infrared laser radiation in combination with a magnetic mirror tip was used. In Group 3 (n = 30), dental tips with a pulsed infrared laser emitting head were used in the area of the socket formed after tooth extraction. In Group 4 (n = 29), a laser head with a continuous red spectrum was used. The exposure time of the tips and heads in all groups was 3 minutes in the projection of the extracted tooth. All patients underwent PBMT at 1, 24, and 48 hours after surgery. At these same times, acute pain was assessed using a visual analog scale (VAS) and a numerical rating scale (NRS) in millimeters. Acute pain was lowest already on the first postoperative day in the pulsed infrared laser group with a mirror magnetic head. Among the PBMT groups, the continuous red laser demonstrated the worst pain results. In the group without PBMT, pain requiring medical management persisted for up to 48-72 hours after tooth extraction.
Cutaneous melanoma, which accounts for 72-80% of all diagnosed tumors developing from melanin-producing tissue, is an example of a malignancy whose initiation and development, with rare exceptions, are associated with the realization of endogenous pigmentations in the morphological substrate of the tumor. However, the existing diagnostic paradigm for superficial cutaneous melanomas does not take into account the significance of endogenous pigmentations in assessing the tumor's invasive capacity. This article examines the relationship between changes in the biochemical composition of superficial cutaneous melanomas and their invasive capacity, as well as the possibility of using this relationship in melanoma diagnostics. A comparative pathomorphological, ultrastructural, and spectroscopic study of 128 samples of superficial spreading melanoma removed during radical surgical excision was conducted. A higher frequency and diversity of endogenous pigment analytes were detected during the horizontal phase of tumor growth compared to the vertical phase. Diagnostically significant analytes included carotenoid pigments (p=0.02257), porphyrin (p=0.09080), and melanin precursors tyrosine (p=0.01554) and phenylalanine (p=0.01753). The use of a comprehensive pathomorphological and spectroscopic study and multiplex analysis of the obtained results made it possible to simultaneously identify a significant number of statistically confirmed endogenous pigment analytes in superficial melanoma skin samples. These analytes have diagnostic value in assessing the invasive capacity of superficial melanomas.
Studying the interaction of optical wavelength radiation with biological tissues can be used in various biomedical applications, including estimating the absorbed dose of laser radiation during laser-induced therapy. The fraction of absorbed radiation can be estimated using Monte Carlo and adding-doubling simulations. In this paper, we compare the simulation results obtained using the two methods for multilayered models of biological tissues of the trachea and colon. Both methods are used to calculate the absorbed dose based on the specified optical properties of tissues under several types of illumination. Similar incident beam geometries demonstrated repeatability of 94Ѓ}3% for a collimated beam and 95Ѓ}3% for an isotropic/diffuse source. The advantage of the adding-doubling method is its higher computational speed compared to the Monte Carlo method, while Monte Carlo simulation allows for varying a larger number of parameters when specifying the illumination conditions of the sample. The data obtained can be used to optimize dosimetry in photodynamic therapy.
Secondary upper limb lymphedema remains one of the most significant complications of surgical and radiation treatment of breast cancer and is characterized by progressive impairment of lymphatic drainage, chronic inflammation, and soft tissue fibrosis. In cases of pronounced anatomical and functional damage to lymphatic collectors, the effectiveness of conservative therapy and lymphovenous anastomoses is limited, necessitating the use of physiological microsurgical reconstruction techniques. Vascularized lymph node transfer (VLNT) is considered a pathogenetically substantiated approach to restoring lymphatic drainage, combining the mechanical ≪lymphatic pump≫ effect with stimulation of lymphangiogenesis through growth factor secretion. Imaging modalities of the lymphatic system, including indocyanine green (ICG) lymphography and lymphoscintigraphy, play a crucial role in patient selection and in the assessment of surgical outcomes by enabling visualization of dermal backflow, collector obliteration, and the formation of new lymphatic pathways. The paper presents a clinical case of a patient with stage IIA lymphedema following comprehensive breast cancer treatment, in whom the absence of clinical improvement after lymphovenous bypass served as an indication for delayed breast reconstruction with a free DIEP flap combined with inguinal vascularized lymph node transfer. Postoperative follow-up demonstrated a reduction in limb volume, decreased dermal backflow, and the appearance of linear lymphatic flow patterns in the transplant area. These findings confirm the potential of vascularized lymph node transfer as a component of a comprehensive surgical strategy for the treatment of secondary lymphedema in patients after combined breast cancer therapy.
The Center for Photodynamic Therapy of the Hospital of the Medical Center of the Administrative Department of the President of the Republic of Kazakhstan has clinical experience in treating cutaneous metastases of breast cancer. This paper presents the results of clinical observation of a patient with metastatic breast cancer who underwent combined photodynamic therapy, including systemic photomodification of blood and local irradiation of metastatic lesions. This clinical case is of particular interest since the patient did not receive standard antitumor treatments such as chemotherapy or hormone therapy. This was due to advanced age and decreased tolerance to aggressive treatment regimens associated with comorbidities, which limited the feasibility of conventional therapy. Despite the absence of systemic treatment, the use of combined photodynamic therapy resulted in a pronounced positive clinical response. A reduction in the size and infiltration of cutaneous metastatic lesions, as well as an improvement in the patient’s general condition and quality of life, were observed. These findings demonstrate the potential of photodynamic therapy as an effective and safe alternative therapeutic approach for metastatic breast cancer, particularly in clinical situations where the use of standard treatment protocols is impossible or contraindicated.
The task of developing a decision support system in neurooncology based on optical-spectral analysis of intracranial tumor tissue is associated with several challenges inherent in working with biomedical data. These include the high dimensionality of the feature vector with a relatively small sample size, data gaps, and sample imbalances due to the varying frequencies of various diagnoses. Analysis of correlations between features of the tumors under study will allow both the restoration of data gaps and their augmentation (artificial expansion of the training dataset by creating modified versions of existing examples). This paper presents an analysis of the dependence of various optical-spectral characteristics on the tumor cell/tissue content in the sample and the cross-correlations between various features.
Acne is one of the most common dermatosis in young people. 85% of cases occur in patients between 12 and 24 years old. Duration of the disease, severe form, frequent recurrences of acne, autotraumatization lead to development of symptoms complex postural, manifested in the form of scarring changes, dyschromia, reduced elasticity, increased porosity and mildew. Acne complications occur in 95% of patients. Development of an effective method for the correction of acne complications is a topical problem of modern dermatology and cosmetology. The article describes the method of application of photodynamic therapy with an outer gel photosensitizer based on E6 chloride in patients with severe form of acne after prior treatment with systemic retinoids. The morphofunctional indicators of the skin and the composition of the microbiome in the dynamics were studied. As a result of the course of photodynamic therapy, resolution of scarring was observed in 97,2% of patients, disappearance of pigmentation on cheeks and skin on the forehead in 89,1% and 91,9% of patients respectively, restoration of elasticity in 100% of subjects, decrease in oiliness on the cheeks and skin in 91% and 94,5 % of patients respectively.The exact exposure of the photosensitizing gel when applied externally to the scar tissue, the time range of its highest concentration and optimal duration of the procedure were determined. As a result of the application of photodynamic therapy, the skin relief was leveled, its oiliness decreased, the pigmentation disappeared and the elasticity was restored. In the microbiota of seborrheic sites, normal flora predominated over pathogenic. This method proved to be effective in the correction of the postural.
Ciliary body melanoma (CBM) accounts for up to 20% of uveal melanoma cases and presents challenges for organ-preserving treatment due to its peripheral location and proximity to critical ocular structures. This study presents the first clinical results evaluating the efficacy and safety of isolated transscleral photodynamic therapy (TSPDT) with a chlorin e6 photosensitizer in 7 patients with CBM. The procedure was performed using an «ALOD-01» laser system (λ=662 nm) and standardized irradiation parameters (energy density 519.5 J/cm², accounting for power loss during scleral transmission). The mean follow-up period was 19.0±5.9 months and demonstrated high local tumor control: complete regression was achieved in 4 patients, and partial regression in 3 patients. A statistically significant reduction in tumor height (from 4.69±2.58 mm to 1.36±1.14 mm; p=0.0062) and basal diameter (from 8.54±3.56 mm to 6.65±3.70 mm; p=0.016) was accompanied by a pronounced vasculo-occlusive effect, manifested as complete tumor avascularity in the majority of patients according to ultrasound with color Doppler Imaging (CDI). Echodenstitometry recorded a statistically significant decrease in mean acoustic density from 35.53±1.26 dB to 28.97±0.83 dB (p=0.0002), which may indicate tumor tissue destruction. No intra– or postoperative complications were recorded throughout the observation period, and a trend towards stable visual acuity was noted. The obtained data suggest that TSPDT is a promising minimally invasive organ-preserving method for treating CBM, requiring further investigation to define its role as either a standalone or combined therapy.
Oncological diseases represent a global healthcare challenge, and the development of new effective therapeutic strategies remains a pressing task. Chemotherapy and photodynamic therapy (PDT) are key treatment modalities, however, their application is associated with side effects, systemic toxicity, and the development of drug resistance. In recent years, combined approaches, including the use of pH-sensitive delivery systems, have been actively investigated. The present study was dedicated to the investigation of the pH-dependent hydrolysis of a chlorin e6 hydrazide derivative, acting as a potential photosensitizer (PS) for combined anticancer therapy. Hydrazide fragments, due to their lability in the weakly acidic environment of the tumor microenvironment (pH 4.5-6.0), are promising for the creation of targeted drug delivery systems. The decomposition of the hydrazide fragment was studied spectrophotometrically in an acetate buffer (pH 5.0) over 120 minutes. Spectral changes (bathochromic shift, appearance of a maximum at 688 nm) were recorded, indicating the formation of a protonated precursor compound. A linear dependence of product accumulation on time was obtained, characteristic of zero-order reactions. A high coefficient of determination confirmed the adequacy of the obtained model. This approach ensures controlled release of active components and demonstrates the potential of the developed PS for enhancing PDT efficacy and reducing the systemic toxicity of chemotherapy.
Nowadays, the problem of malignant neoplasms management remains a priority task. To achieve further progress in cancer treatment, it is necessary to focus on existing but still undervalued methods. One of these approaches is photodynamic therapy (PDT), which can be used in combination with surgery as well as with other antitumor drugs without any risk of inducing cross-resistance. Being miner invasive and selective in tumor targeting, and having no risk of complications, the technique is attractive for application in oncologic pediatrics as an innovation capable of expanding the range of therapeutic techniques. The aim of the study was to investigate the effectiveness of intraoperative photodynamic therapy in children with stage III–IV nephroblastoma. The study included 66 patients aged 0–11 years with stage III and IV nephroblastoma. The patients of the control group (35 children) underwent surgical treatment in combination with chemotherapy and radiation therapy according to the SIOP protocol. The patients of the main group (31 children) underwent therapy according to the SIOP protocol, but in combination with intraoperative PDT. The 5-year survival rate in the main group was 90.3%, in the control group – 71.4% (p = 0.05). The recurrence rate in the main group was 9.7%, in the control group – 11.4%. Thus, high therapeutic efficacy of PDT during intraoperative irradiation of the tumor bed after its removal has been demonstrated. The technique contributes to the increased survival rate of patients with retroperitoneal tumors, which is a promising method to be used in pediatric oncological practice.
The use of UV-C radiation for the treatment of tumors is a stand-alone therapeutic intervention that can induce cellular apoptosis and is independent of photosensitizer or oxygen concentration in tumor. To explore the potential of using X-ray excited UV-C luminescent nanoparticles as a basis for creating drugs to improve radiation therapy, two colloidal solutions of monoclinic La1–x Prx PO4 nanoparticles with different morphologies of large nanofibers (x = 0.02) or small nanorods (x = 0.05) were prepared using a microwave-assisted hydrothermal method. Comparison of X-ray excited UV-C luminescence of colloidal solutions showed approximately 6.3 times higher brightness for larger nanoparticles. The intrinsic and X-ray-induced cytotoxicity of the prepared colloidal solutions on the viability of cancerous Mh22a and healthy L929 cell cultures were studied using MTT assay and fluorescence microscopy. Fluorescence microscopy showed differences in the types of cell death (apoptosis or necrosis) after incubation with nanofiber or nanorod samples. X-ray irradiation was performed in two modes with different voltage on the X-ray tube (50 and 80 kV) and the same radiation dose (8 Gy). Groups of cells incubated with nanoparticles and irradiated with 50 kV mode showed greater death rate. According to MTT analysis, irradiation of cells incubated with La0.98 Pr0.02 PO4 nanofibers at a concentration of 2 mg/mL reduced survival by 20-30%, and at the same time, according to fluorescence microscopy data, the number of cells undergoing apoptosis exceeded the number of cells that died through necrosis and reached 50-70%. Quantitative analysis of the relative number of dead cells caused by X-ray-induced cytotoxicity of La0.95 Pr0.05 PO4 nanorods did not reveal statistically significant results in reducing cell viability.
Polycationic photosensitizers have previously demonstrated high in vitro efficacy against lung cancer cells, including cancer stem cells, and low dark cytotoxicity. Polycationic phthalocyanines have high quantum yield of singlet oxygen and photostability. In addition, it is possible to relatively simply introduce different metal-complexing agents and substituents into phthalocyanine macrocycles, which enables varying their photophysical characteristics. In this work, we studied photophysical properties of photosensitizers based on polycationic phthalocyanine derivatives with different chemical structure with strong absorption in the long wavelength region (680–690 nm). The studied photosensitizers exhibit negligible aggregation in the 1–100 μM concentration range and show very high phototoxicity in an in vitro study on A549 lung carcinoma cells (IC50 of 60–100 nM for ZnPcChol8 and 100–300 nM for 4αZnPc4+ and 4αβZnPc4+, depending on the light dose), and low dark cytotoxicity.
In this paper we studied the photodynamic activity (the rate of molecular oxygen utilization during irradiation) of methylene blue (MB) in erythrocyte suspensions in vitro. Using spectroscopy and confocal microscopy with fluorescent sensors for singlet oxygen and other active oxygen species, it was shown that with an increase in the MB concentration (10–100 mg/kg), the molar photodynamic activity decreases. It was found that 5–10% of the MB added to erythrocytes tightly binds to the erythrocyte membranes, and the generation of singlet oxygen (¹O₂) is suppressed in favor of type I reactions (formation of H₂O₂, O₂•⁻, •OH). Another 40% of the MB added to erythrocytes is converted into a colorless leuco form, but is reoxidized back to MB under photodynamic exposure. The maximum relative quantum yield of ¹O₂ generation (φΔ ) among those measured in erythrocyte suspensions was 0.014 for a 10 mg/kg MB concentration, which is an order of magnitude lower than the values for MB in organic solvents and for the aluminum sulfonated phthalocyanine comparison photosensitizer (PS) (φΔ = 0.38). Interaction with erythrocytes (aggregation, reduction to the leuco form, competition for oxygen) explains the decrease in the MB efficiency under physiological conditions compared to organic solvents. The obtained results are important from the point of view of optimizing the systemic use of MB in photodynamic therapy.
The article presents a clinical case of successful elimination of mechanical jaundice by means of a course of photodynamic therapy in a patient with a malignant neoplasm of the major duodenal papilla and multimorbid concomitant pathology. The patient, admitted with a clinical picture of mechanical jaundice, after additional examination was given a final diagnosis - moderately differentiated adenocarcinoma of the major duodenal papilla, stage IIa (T2N0M0), complicated by moderate mechanical jaundice. After primary stenting, a series of three consecutive courses of combined systemic and local photodynamic therapy were performed with a three-month interval between them. During the last course, stent migration into the duodenum was detected. Nevertheless, the complex therapy allowed to effectively eliminate the manifestations of mechanical jaundice, stabilize the patient's condition, prevent further growth of the primary tumor, restore the patency of the ducts of the major duodenal papilla and avoid relapses of mechanical jaundice, despite the migration of the stent. This experience demonstrates the promise of the photodynamic approach for solving complex clinical situations associated with tumor damage to the biliary system and allows to consider this method as an alternative in situations of high risk of complications of traditional surgery.
