卷 70, 编号 4 (2025)

Purpose: Analysis of PMAIP1 and BIRC5 gene expression in breast cancer cells after proton exposure, both as monotherapy and in combination with doxorubicin.

Material and methods: The object of the study was MCF-7 cells. Four study groups were formed: a group exposed to ionizing radiation; a group treated with doxorubicin; a group of combined exposure to ionizing radiation and doxorubicin; and an untreated control group. The cells were irradiated at the Prometheus proton radiation complex at the A.F. Tsyb MRSC, with a scanning proton beam at a dose of 4 Gy (proton energy of 100 MeV) in the center of the distributed Bragg peak. The cells were treated with the chemotherapy drug doxorubicin at a concentration of 0.004 mg/ml 24 hours before irradiation. Total RNA was isolated using an RNA Solo kit and quantified spectrophotometrically (NanoDrop ND-1000). Reverse transcription and amplification were performed simultaneously in real time using the OneTube RT-PCR kit with SYBR Green I as a fluorescent indicator.

Results: The analysis showed that doxorubicin suppresses the expression of BIRC5 (up to 0.02), which is consistent with its known apoptogenic activity. However, the combined effect of doxorubicin and radiation leads to an increase in BIRC5 expression (up to 0.63) and a simultaneous decrease in PMAIP1 expression (up to 0.0003). This indicates the launch of complex compensatory cell survival mechanisms aimed at suppressing apoptosis and enhancing DNA repair under conditions of combined cytotoxic stress. A less pronounced decrease in BIRC5 expression during ionizing radiation monotherapy (up to 0.16) compared with doxorubicin (0.02) is probably due to differences in the nature and kinetics of DNA damage induced by these agents. The data obtained indicate the nonlinear nature of the cellular response to combined exposure and emphasize the difficulty of predicting the effectiveness of combined radiotherapy.

Conclusion: The results demonstrate the antagonistic interaction of doxorubicin and ionizing radiation in the regulation of apoptosis in MCF-7 cells, emphasizing the need for further research to optimize combination cancer therapy.

Background: Proton therapy is considered one of the most promising methods in the treatment of complex localized tumors, but still has some shortcomings, which requires the development of new approaches to improve its effectiveness. One of the most promising approaches is the use of radiosensitizers that can enhance the radiation-induced effects of a proton beam. However, the use of 2D tumor cell models for screening potential radiosensitizers is insufficient for the effective translation of the experimental data to the in vivo level. 3D cellular spheroids are a convenient and relevant model for studying new approaches in the therapy of solid tumors, since they allow simulating the conditions of the microenvironment of tumor cells and simulating in vivo conditions, including the presence of an intercellular matrix and the formation of a certain zonality.

Purpose: To create an experimental model of a tumor spheroid based on 4T1 tumor cells irradiated with a proton beam for screening potential nanoradiosensitizers.

Material and methods: In vitro biological activity was assessed using a 4T1 cell line (mouse carcinoma) culture. The hanging drop method was used to form cell spheroids. The spheroids were irradiated with a proton beam at the Bragg peak on at a dose of 0–12 Gr using the “Prometheus” therapeutic proton complex . The clonogenic test was used to analyze the viability and mitotic activity of the cells after irradiation. The growth dynamics of irradiated 3D spheroids has been assessing by analyzing micromorphometry for 8 days after irradiation.

Background

1. Components of innate immunity and carcinogenesis

2. Tumor-associated myeloid cells and myeloid-derived suppressor cells

3. Tumor-associated neutrophils

4. Tumor-associated monocytes/macrophages

5. Natural killers of malignant neoplasm microenvironment

6. Conclusion

Introduction

Digital footprint, digital shadow, digital presence

Digital profile

Digital twin

Similarities and differences

Digital Medical Profile

A digital twin in the healthcare system

Conclusion

Purpose: To assess the radiation risks of digestive system diseases (DSD) in the low and medium dose range (up to 1.5 Gy), considering the influence of other diseases identified in the exposed cohort.

Material and methods: Radiation risks of DSD were studied in the Russian cohort of Chernobyl disaster clean-up workers (liquidators), followed-up in the system of the National Radiation Epidemiological Registry (NRER) from 1986 to 2023. The studied cases of DSD are included in three-digit headings K00–K93 of the International Statistical Classification of Diseases 10th revision (ICD-10). Radiation risks of incidence were assessed in a cohort of 86,623 male liquidators, in which 62,864 diagnoses of DSD were identified. For the assessment of radiation risks of mortality from DSD, the cohort size was 89,567, with 2,793 deaths. The average absorbed dose of whole-body external gamma radiation accumulated by the liquidators during their work was 0.133 Gy, with a maximum dose of 1.5 Gy. Radiation risks were investigated in the framework of linear no-threshold (LNT) model of excess relative risk (ERR), as well as in the form of nonparametric estimates of relative risk (RR) in dose groups.

Results: For incidence, the estimate of the excess relative risk per dose unit is ERR/Gy=0.33, for mortality the estimate is ERR/Gy=0.81. These DSD radiation risk estimates are comparable to ERR/Gy=0.63 and ERR/Gy=0.74 for incidence and mortality from solid malignant neoplasms (MN) in the same cohort. Among liquidators with diagnoses of MN, the radiation risk of DSD incidence is statistically significantly (p=0.03) increased almost twofold, to ERR/Gy=0.64. The practical dose threshold for late mortality from DSD, estimated by the LNT model, is in the range of 0.160–0.860 Gy, with a mean value of 0.280 Gy. This is 20 times lower than the 6 Gy dose threshold adopted by the ICRP for early DSD mortality (up to 10 days after exposure). Similar estimates of dose thresholds for DSD incidence are in the range of 0.006–0.042 Gy. Nonparametric estimates of relative radiation risks (RR) confirm the correctness of LNT models of DSD radiation risk.

Conclusions: In the range of low and medium doses (up to 1.5 Gy) radiation-induced DSDs have significant properties of stochastic effects and fit into the LNT risk model. Further accumulation of data in the NRER system will make it possible to investigate the characteristics of DSD that are inherent in late tissue reactions (progression over time, increase in their severity with increasing dose and dependence on the health of the organism as a whole).

Purpose: To describe the semiotics of neoplasms of small vessels of the liver according to computed tomography, to present a possible differential diagnosis

Material and methods: Patient S., 52 years old, underwent computed tomography (CT) of the abdominal cavity with intravenous contrast due to a sharp increase in liver formation before the planned surgery. According to CT data, a large hypervascular formation measuring 198×146×247 mm was detected in the left lobe of the liver. The feeding extrahepatic arteries and draining hepatic veins are significantly dilated. Newly formed vessels and aneurysmally dilated arteriovenous shunts up to 29 mm in size were noted in the structure of the formation. A hemihepatectomy was performed. According to the results of morphological and immunohistochemical studies, a diagnosis of «Neoplasm of small vessels of the liver» was made.

Results: the disease «neoplasm of small vessels of the liver» (HSVN) became known in 2016 after the publication of an article by Ryan M. Gill et al. This is a vascular tumor that occupies an intermediate position between a hemangioma and an angiosarcoma. Currently, it is believed that the disease is benign. Several dozen confirmed cases are known. Due to hypervascularity, the tumor must be differentiated from angiosarcoma, hepa- and cholangiocellular cancer, hypervascular metastasis, as well as benign tumors such as hemangioma, focal nodular hyperplasia, and adenoma. In our case, the distinctive feature of the tumor was a significant expansion of the feeding extrahepatic arteries and draining main hepatic veins, aneurysmal expansion of arteriovenous shunts in the structure and the absence of signs of invasion of surrounding vessels and organs.

Conclusion: In the differential series of hypervascular liver tumors, in the presence of pronounced arterial blood supply, the presence of arteriovenous shunts in the structure and the absence of signs of infiltrative growth, neoplasm of small liver vessels should be considered.

Purpose: To evaluate the significance of quantitative and qualitative parameters of lymphoscintigraphy, their correlation with each other and with the clinical stage of lymphedema in patients undergoing surgery for breast cancer with advanced lymphodissection.

Material and methods: 285 patients with lymphedema were examined from October 2022 to July 2023. After intradermal injection of the radiopharmaceutical ^99mTc-nanotope (particle size 5-80 nm) into the first interdigital spaces of both hands, 40 MBq per point, exercises with a rubber expander were performed for 30 minutes. Planar images were obtained 2 hours after injection on a gamma camera and a qualitative description of the images was performed. The quantitative asymmetry index (QIA) was also used, for which the areas of interest were outlined in ovals and shifted to the contralateral side: forearm, shoulder, axillary and subclavicular zones.

Results: In the first degree, lymph nodes of all groups are more often detected (p<0.001), there is no reflux in the shoulder and forearm (p<0.001), more often with intact lymph ducts. In the second degree, reflux in the shoulder and forearm is significantly more often visualized (p<0.001). In the third degree, lymph nodes of all groups are more often not detected and reflux into the subcutaneous lymph networks of the shoulder and forearm is not visualized (p<0.001), more often without visualization of the lymph ducts. The disease was statistically significantly diagnosed at an earlier stage at a younger age (p=0.01). Also, a more severe degree of lymphedema was detected with an increase in BMI (p<0.001). Statistically significantly, with a previous history of remote radiation therapy, lymph nodes in the supra/subclavian region were detected less frequently (p=0.007). In the presence of reflux in the forearm area, the median of the QIA values ​in the forearm area was significantly higher than in the absence of reflux: Me=5 versus Me=1. In the presence of reflux in the shoulder area, the QIA in the forearm area was significantly higher than in the absence of reflux: Me=3 versus Me=1, respectively. Also, in the presence of reflux in the shoulder area, the median of the QIA in the forearm area was significantly higher than in the absence of reflux: Me=6 versus Me=2, respectively.

Conclusions: Statistically significant correlation indicators were obtained between quantitative and qualitative parameters of lymphoscintigraphy with each other and with the clinical stage of lymphedema, which made it possible to develop criteria for staging the severity of lymphostasis based on them. Lymphoscintigraphy also allows you to determine the nature of the increase in the volume of the upper limb (lymphatic, fibrous), which is a necessary criterion for choosing a plan of rehabilitation measures.

Purpose: To compare treatment plans on the Prometheus proton therapy complex (PTC) and a linac in terms of dose distribution parameters and radiation doses on organs at risk.

Material and methods: The study included 20 adult patients who were treated on the Prometheus PTC in 2019–2020 for recurrent malignant gliomas. Comparative planning was carried out in the XIO radiation therapy planning system with the preparation of 3D-conformal photon radiation therapy plans using intensity modulated radiotherapy technology (IMRT) based on one set of contours of the irradiated volumes.

Results: Dose-volume histograms were constructed for all volumes, dose parameters were taken into account to assess the coverage of target volumes and compliance with safety criteria for organs at risk. The average dose to the entire brain volume during proton therapy ranged from 4.54 to 20.63 Gy, the median was 6.74 Gy. The average dose during photon therapy planning ranged from 5.9 to 32.48 Gy, the median was 21.2 Gy. The average difference in radiation load to the entire brain volume was 15.24 Gy (p < 0.001). The mean maximum dose to the brainstem during proton therapy ranged from 0.01 to 51.35 Gy, median 9.77 Gy. The mean dose when planning photon therapy using the IMRT technique ranged from 1.6 to 55.1 Gy, median 44.37 Gy. The mean difference was 34.6 Gy (p < 0.003). The mean maximum dose to the optic nerve during proton therapy ranged from 0 to 25.19 Gy, median 2.15 Gy. The mean dose in the photon therapy plan was 0 to 51.35 Gy, median 21.05 Gy. The reduction in the mean difference in dose load when using proton therapy was 18.9 Gy (p< 0.001).The average maximum dose to the chiasm during intensity-modulated proton therapy ranged from 0 to 32.9 Gy, median 0.38 Gy. A similar dose when calculating photon therapy doses ranged from 1.4 Gy to 54.3 Gy, median 28.47 Gy. The average difference in the dose load on the optic nerve in favor of proton therapy was 28.09 Gy (p< 0.001). The average value of the homogeneity index of protons was 0.16 (CI 95 % 0.14–0.18), photons – 0.13 (CI 95 % 0.11–0.14), p=0.00158.

Conclusion: Proton therapy during repeated courses of radiation therapy demonstrates a significant reduction in the dose load on risk organs when compared with photon therapy on a linear accelerator. Repeated irradiation of high-grade gliomas using an active scanning proton beam is a promising direction due to the reduction in overall toxicity of treatment and the possibility of delivering radiation doses close to radical ones.

Purpose: Demonstrate the possibility of using ^99mTc-PSMA SPECT/CT to visualize Hodgkin’s lymphoma at the diagnostic stage, as well as during therapy.

Material and methods: The patient diagnosed with Hodgkin’s lymphoma underwent standard studies – computed tomography with intravenous contrast, as well as PET/CT with ¹⁸F-FDG. Additionally, ^99mTc-PSMA SPECT/CT was performed.

Results: A clinical case of Hodgkin’s lymphoma with mediastinal lesions in a young patient is described. The possibility of modern nuclear medicine methods in the diagnosis of Hodgkin’s lymphoma is demonstrated. SPECT/CT with ^99mTc-PSMA was performed as an alternative diagnostic method when it is impossible to perform PET/CT with ¹⁸F-FDG at the stage of specific treatment.

Conclusion: The article presents a clinical case of Hodgkin’s lymphoma with mediastinal involvement in a young patient. The capabilities of SPECT/CT with ^99mTc-PSMA for visualization of mediastinal lesions was demonstrated.