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Выпуск опубликован на сайте 17.06.2025 г.

Vol 12, No 2 (2025)
View or download the full issue PDF (Russian)
https://doi.org/10.17709/2410-1893-2025-12-2

Original Articles

10-22 86
Abstract

In modern clinical practice, when deciding on the amount of adjuvant therapy for cancer of the uterine body (UBC), such a factor as a tumor lesion of the lower uterine segment (LUS) is not considered, although a number of studies indicate its possible connection with a more aggressive course of the disease.
Purpose of the study. To study the relationship between tumor involvement of the LUS and traditional clinical and morphological prognostic factors, and the impact of this parameter on the treatment outcomes of early endometrial cancer.
Patients and methods. The study included 506 patients with stage I endometrioid UBC according to the classification of the International Federation of Gynecologists and Obstetricians (FIGO) who underwent surgical or combined treatment at the A. Tsyb Medical Radiological Research Center – Branch of the National Medical Research Radiological Center (Obninsk, Russian Federation) in 2002–2024. The median follow-up was 81.1 months. The patients were divided into two groups depending on the presence or absence of a tumor lesion of the LUS according to the histological conclusion: respectively Group 1–175 (34.6 %) patients, group 2–331 (65.4 %) patients.
Results. LUS involvement was found in 34.6 % of patients. It was found that these patients more often had factors such as lymphovascular invasion (LVI) (p < 0.001) and deep invasion into the myometrium (p < 0.001). Overall, LUS involvement was recorded in 23 % of patients without traditional unfavorable prognostic factors and in 50 % of patients with these factors (p < 0.001). At the same time, more common forms of the disease affecting the pathomorphological stage were more frequently detected in the group of patients with LUS involvement – 20.0 % versus 5.1 % in the group without LUS involvement (p < 0.001). Thus, in cases of LUS involvement, the risk of detecting a more common tumor process after histological examination increases 3.9 times compared to cases without LUS involvement. Survival analysis at the current follow-up period showed a statistically significant decrease in overall and five-year survival rates in patients with stage I UBC with LUS involvement – 87.9 % and 75.3 ± 4.8 %, respectively, compared with 93.4 % and 93.1 ± 2.5 % without LUS involvement (with p = 0.044 and p < 0.001, respectively).
Conclusion. Tumor involvement of the LUS can be considered a potential diagnostic predictor for the detection of more common forms of stage I UBC and a prognostic indicator of an unfavorable outcome of endometrioid disease.

23-34 69
Abstract

Purpose of the study. The objective of the present study was to examine the levels of TGFβ1, EGF, and EGFR in the blood and tissue of morphologically distinct endometrial tumors, including uterine serous carcinoma (USC), clear cell endometrial cancer (CCEC), and G3 endometrioid adenocarcinoma (EAC).
Patients and methods. The study encompassed 61 patients diagnosed with uterine body cancer, including 21 patients with USC, 20 patients with CCEC, and 20 patients with EAC (G3). All patients underwent a thorough morphological verification of the disease, as documented in the postoperative report. The level of epidermal growth factor and its receptor (EGF and EGFR), as well as transforming growth factor (TGFb1), was determined in cytosolic fractions of 10 % tumor homogenates and blood samples using standard ELISA kits. Samples of intact endometrium obtained from patients who underwent surgery for uterine fibroids (n = 20) and blood samples from conditionally healthy women (n = 20) of the same age served as normal indicators. Statistical analysis of the results was performed using the Statistica 10.0 software package.
Results. EAC (G3) was characterized by an increased, compared to the healthy, content of growth factors and their receptors in tumor and blood samples. In tumor samples of CCEC and USC, the level of TGFβ1 was lower by 2.2 times and 1.6 times, respectively, and the concentration of EGF was on average more than 2 times lower, compared to the indicators in the intact endometrium. The content of these same growth factors in blood samples in patients with rare forms of EC exceeded the normative values by 2.1–4.2 times.
Conclusion. The investigation revealed that low levels of EGF were present in tumor samples of rare forms of endometrial cancer, accompanied by unaltered levels of EGFR and TGFβ1. This observation stands in contrast to the elevated concentrations of these growth factors detected in blood samples. The distinctive profile of these growth factors in tumor samples differentiates them from the indicators observed in EAC tissue, where the levels of EGFR and TGFβ1 are augmented. It is plausible that the altered metabolism of non-endometrioid uterine cancers leads to alterations in the biological characteristics of tumors, consequently resulting in a more aggressive clinical course.

35-45 40
Abstract

Purpose of the study. To study the concentration of calcium ions, pro- and antiapoptotic proteins (cytochrome C, AIF-1, and Bcl-2) in the mitochondria of endometrioid adenocarcinoma (EA) cells in oncogynecological patients, depending on the degree of differentiation of malignant cells.
Patients and methods. The study included patients who had undergone surgical treatment for endometrial adenocarcinoma (n = 42) and uterine fibroids (n = 14). The patients with endometrial adenocarcinoma were further classified as having highly differentiated (G1) disease, moderately differentiated (G2) disease, or poorly differentiated (G3) disease. The average age of patients with endometrial adenocarcinoma was 60.8 ± 2.9 years, and the average age of patients with fibroids was 49.4 ± 2.5 years. It is noteworthy that the patients in this study did not receive any neoadjuvant treatment. The concentration of cytochrome C (ng/mg protein), AIF (pg/mg protein), Bcl-2 (pg/mg protein), and calcium (mM/mg protein) was determined in the mitochondria of EA, fibroids, and intact uterus cells by ELISA. The statistical analysis of the results was performed using the Statistica 10.0 software package.
Results. A decline in the degree of tumor cell differentiation was accompanied by a decrease in calcium levels within the mitochondria, with G2 and G3 exhibiting an average reduction of 2.0 times compared to the intact uterus. Furthermore, the Bcl-2 content in the tumor mitochondria at G3 demonstrated an average increase of 1.9 times compared to G1 and G2 (p < 0.05). Furthermore, the cytochrome C level at G1 was found to be 2.2 times higher than at G2 and 1.9 times higher (p < 0.05) than at G3. In the mitochondria of cells with G3 differentiation, the highest AIF-1 values were observed, which were 2.1 times higher than in intact cells and 1.9 times higher (p < 0.05) compared to the values in the mitochondria of myoma cells.
Conclusions. It is hypothesized that the process of apoptosis is suppressed in the mitochondria of endometrioid adenocarcinoma cells due to an accumulation of Bcl-2 and a decrease in calcium. This accumulation of Bcl-2 and decrease in calcium activates energy processes, leading to the accumulation of cytochrome C and AIF-1. The severity of the biochemical events identified in the mitochondria of endometrioid adenocarcinoma increases with the degree of malignancy of the tumor cells. This increase in severity appears to contribute to an escalation in the aggressiveness of the tumor.

46-59 47
Abstract

Purpose of the study. The aim of this study was to evaluate the role of [18F]FDG PET/CT for predicting epidermal growth factor receptor (EGFR) gene mutation status in patients with newly diagnosed non-small cell lung cancer (NSCLC).

Patients and methods. This retrospective single center study included 63 patients with newly diagnosed NSCLC who underwent [18F]FDG PET/CT. Acquisition was performed in accordance with the EANM guideline using the Discovery IQ Gen 2 PET/CT system (GE HealthCare). All patients were divided into a mutant group (n = 30) and a wild-type group (n = 33) based on EGFR mutation status. Maximal diameter and volume of each primary tumor lesion were measured, [18F]FDG uptake was analyzed by measurement of SUVmax, SUVpeak, MTV and TLG. TLG was measured using two independent segmentation methods by the following tools: 3D-Isocontour with 41% of SUVmax threshold for PET image (TLG41%) and Solid Lung Lesion Segmentation for deep-inspiration breath-hold CT image (TLGCT). The anatomical volume derived from the second method was used to manually adjust the isocontour threshold for PET image ensuring that tumor MTV is equal to its anatomical volume. Additionally, TLR index was calculated as the ratio of lesion SUVpeak to liver SUVmean. 9 EGFR-mutant patients were excluded from MTV and TLG analysis due to the inability to use both tumor segmentation methods. Acquisition data of NEMA IEC Body Phantom Set NU2-2018 was applied for plotting the recovery coefficients curves that used for following partial volume effect (PVE) correction.

Results. Medians of lesions’ maximal diameters and volumes in the mutant and wild-type groups were, respectively: 3 [2.5; 4] and 3.6 [2.5; 4.4] cm, 7 [5.2; 14.7] and 12.1 [4.6; 24.4] ml. Medians of PET-metrics in the mutant and wild-type groups were, respectively: SUVmax without PVE correction (PVE) – 6.6 [3.6; 9.3] and 8.5 [6.4; 10], after correction (cPVE) – 5.7 [3.2; 7.6] and 6.8 [5.4; 8.1]; PVE SUVpeak – 5.7 [2.8; 7.6] and 6.6 [5.2; 8.8], cPVE SUVpeak – 5.2 [3; 6.8] and 6.7 [4.7; 7.7]; PVE MTV41% – 5.4 [3.3; 10.4] and 9 [3.6; 16.2], cPVE MTV41% – 5.2 [3.3; 10.1] and 6.2 [3.6; 11.7]; PVE TLG41% – 21.5 [9.2; 37.8] and 36.9 [10.2; 78], cPVE TLG41% – 28.9 [16; 46.4] and 24.9 [12.9; 66.4]; PVE TLGCT – 27.8 [11.5; 52.1] and 54.7 [14.4; 123], cPVE TLGCT – 31 [14.7; 51.7] and 35.8 [16.2; 82.6]; PVE TLR – 3 [2; 5.2] and 4 [3; 5.3], cPVE TLR – 3 [2.1; 4.5] and 3.6 [2.7; 5]. No significant differences in lesions’ maximal diameters, volumes, evaluated PVE and cPVE PET-metrics were found between the mutant and wild-type groups of patients (p > 0,05).

Conclusion. Our results suggest that [18F]FDG PET/CT has no significant value for predicting the EGFR gene mutation status in patients with newly diagnosed NSCLC.

60-69 58
Abstract

Purpose of the study. To evaluate the impact of the COVID-19 pandemic on the structure of surgical thyroid pathology among the population of the Republic of Crimea and Sevastopol City in 2019–2024 through a retrospective data analysis.
Patients and methods. A retrospective analysis of the data (patient medical records, electronic databases) was carried out. Patients were divided into four groups: pre-pandemic, pandemic, and post-pandemic (early and late periods). A total of 1038 cases were analyzed (684 from Crimea, 354 from Sevastopol). Only histological data from surgical specimens were included. Statistical analysis was performed using StatTech v. 4.7.1, applying Pearson’s chi-square (with Holm correction) and Cramer’s V tests. Differences were considered statistically significant at p < 0.05.
Results. Analysis of 2019–2024 data revealed significant changes in the structure of surgical thyroid pathology in Crimea and Sevastopol. The post-pandemic period had an increased proportion of malignant neoplasms: thyroid cancer frequency in Crimea rose by 9.8–11.5 % (p < 0.05) and in Sevastopol by 9.8–33. 5 % (p < 0.001). Papillary carcinoma became dominant, increasing from 24.7 % to 31.0 % in Crimea and reaching 57.6 % in Sevastopol. Crimea recorded higher lymph node metastasis (up to 38.6 %,  p = 0.003) and capsular invasion (26.3 %, p < 0.001), while Sevastopol showed multicentric tumor growth during the pandemic (31.9 %, p = 0.003). A surge in toxic goiter at the pandemic peak (Crimea: 10.8 % to 26.6 %; Sevastopol: 1.6 % to 11.7 %) normalized by 2024. Gender analysis confirmed women’s predominance among patients (85–92 %), particularly in the menopausal period.
Conclusion. The COVID-19 pandemic caused delayed diagnosis and increased aggressive thyroid cancer forms, linked to restricted routine care and the virus’s direct impact on thyroid tissue. The rise in aggressive thyroid cancer subtypes, including metastatic and invasive forms, reflects postponed surgeries and screening during restrictions, underscoring the need for enhanced screening programs. These findings highlight the importance of adapting healthcare systems to global crises, including reserving resources for oncology care and developing early diagnostic algorithms.

70-80 53
Abstract

Purpose of the study. To study the effect of sequential release of peptide extracts (PEE) from the pineal gland and pituitary gland of reindeer (Rangifer tarandus) on endogenous regulatory proteins (hypoxia-inducible factor 1 alpha (HIF1α), peroxisome proliferatoractivated receptor gamma (PPARγ), soluble phosphoenolpyruvate carboxykinase 1 (PEPCK) and melatonin in the blood serum of male rats under conditions of experimental light desynchronosis.
Materials and methods. Modeling of light desynchronization was carried out on two-month laboratory white outbred male rats weighing 180 ± 20 g in the number of 144 individuals. The animals were divided by the method of randomization into three main groups: 1st group represented the control, in which the normal lighting regimen was modeled (LED lighting 500 lux day/night 12/12); the 2nd group was kept in the regimen of constant illumination; the third group was kept in a regimen of constant darkness. The formation of light desynchronization was carried out for 30 days. During the first 14 days of the formation of light desynchronosis, the rats were intranasally being administered with the test substances. After 30 days from the beginning of the experiment, the rats were euthanized for the collection of biological material. The blood serum HIF1α, PPARγ, PCK1 and melatonin levels of laboratory animals were analyzed by the enzyme immunoassay method (EIA).
Results. The use of PEE in two doses during light deprivation has reduced the concentration of HIF1α in the blood serum, indicating improved oxygen utilization in the tissues of experimental animals. PEE in two doses has caused a sharp increase in the concentration of the transcription factor in blood serum PPARγ, which promotes the initiation of processes regulating the exchange of lipids and carbohydrates in adipose tissue. The application of peptide extracts in two doses has revealed a decrease in the activity of PCK1 under constant illumination. With constant exposure to PEE in doses 100 mg/kg, it promotes an increase in the concentration of melatonin in the blood serum, approximately equal to the level of the control group.
Conclusion. The study revealed the chronobiotic effects of PEE on the concentration of regulatory proteins and melatonin in the blood serum of male rats in the conditions of light desynchronization. It should also be noted that these effects differ from the known effects of the delta-sleep inducing peptide, which may be due to a different mechanism of molecular action.

81-89 73
Abstract

Modern understanding of melanoma carcinogenesis and progression highlights the importance of identifying risk factors and prognosis at early stages.
Purpose of the study. Analysis of clinical characteristics in patients with skin melanoma.
Patients and methods. A retrospective analysis of the medical records of 142 patients with skin melanoma has been carried out. Data on age, gender, tumor localization, disease stage according to the American Joint Committee on Cancer (8th ed., 2017), histological types according to the WHO classification (2022), as well as treatment methods and disease outcomes have been analyzed.
Results. Among the studied patients with skin melanoma, women predominated – 78 cases (54.9 %), men – 64 cases (45.1 %). The average age of patients was 63 ± 5.6 years, ranging from 29 to 88 years. Melanoma was most frequently diagnosed at advanced stages: stages IIIA–IIID were detected in 53 patients (37.3 %), stages IIA–IIC – in 40 (28.2 %), and stages 0 and IA–IB – in 16 (11.3 %) and 33 (23.2 %) patients, respectively. The predominant histological types were nodular melanoma (48.6 %) and superficially spreading melanoma (38.7 %). The most common tumor localizations were the skin of the lower extremities (32.3 %) and the back (30.9 %). In 23 patients (16.2 %) with disease progression, metastases were detected in the brain, lymph nodes, liver, lungs, and bones.
Conclusions. The carried-out analysis can help clarify the clinical and morphological features of skin melanoma and improve diagnostic and therapeutic approaches.

Review

90-105 73
Abstract

Despite advances in chemotherapy and targeted therapy, resistance and systemic toxicity limit the clinical efficacy of current treatments of colorectal cancer (CRC).
Purpose of the study. To analyze published experimental studies on the peptide drug CIGB‑552, which targets COMMD1, and its potential use in the treatment of CRC.
Materials and methods. We conducted a literature search in NCBI MedLine (PubMed), Google Scholar, and Web of Science databases using a list of keywords that included: «CIGB‑552», «COMMD1», «NF-κB», «inflammation», «HIF1A», «hypoxia», «SOD1», «oxidative stress» and “colorectal cancer”. Original studies and reviews published in the last five were used, except for publications related to CIGB‑552, for which all studies published since 2013 were reviewed.
Results. Analysis of literature shows that the peptide CIGB‑552 inhibits NF-κB via COMMD1‑mediated ubiquitination of RELA and stabilization of NFKBIA, suppresses HIF1A-driven angiogenesis, and disrupts SOD1 activity to induce oxidative stress. Preclinical studies demonstrated tumor regression in xenograft models and disease stabilization in pet dogs with spontaneous tumors. Synergistic effects with chemotherapy were observed in vitro and in vivo, enhancing apoptosis and chemosensitivity. In the Phase I clinical trial, the main adverse event was a transient, mild pruritic rash, without hematological or organ toxicity. Pharmacokinetic data showed rapid clearance of the peptide from the circulation, suggesting long-term effective use. Mechanistic studies suggest preferential activity of the peptide in aggressive CRC subtypes: CMS4 and CMS1.
Conclusion. CIGB‑552's multimodal targeting of NF-κB, HIF1A, and oxidative stress impacts key resistance mechanisms in CRC, particularly in KRAS- or BRAF-mutated tumors (30–50 % of cases). The favorable safety profile, synergistic potential with chemotherapy, and predicted efficacy in high-risk subtypes warrant expanded clinical evaluation to optimize dosing and confirm therapeutic benefit.

Clinical Case Reports

106-113 61
Abstract

Thoracic outlet syndrome (TOS) comprises a group of clinical syndromes caused by congenital or acquired compression of the brachial plexus or subclavian vessels during their passage through the superior thoracic aperture.
Clinical manifestations vary by TOS type: neurogenic form (arm pain/paresthesia, hand muscle weakness, thenar atrophy), venous form (limb edema/cyanosis, visible collaterals, subclavian vein thrombosis), arterial form (arm ischemia, distal emboli, subclavian artery aneurysms).
The modern diagnostic algorithm includes physical examination (Edson test, Wright test, hyperabduction test) and instrumental diagnostic methods. These include radiography to detect bone abnormalities, ultrasound with Doppler to assess blood flow, MRI to assess soft tissue structures, and CT angiography, which is the "gold standard" for diagnosing vascular forms of TOS.
In the presented case, dynamic CT angiography revealed a rare instance of bilateral TOS in a patient with a long-standing history of shoulder girdle pain, caused by clavicular hyperostosis, dynamic subclavian vein compression, chronic thrombosis signs.
TOS requires comprehensive diagnostics with advanced imaging. Dynamic CT angiography is the preferred confirmatory method. Early diagnosis prevents severe complications (thrombosis, ischemia). Personalized 3D modeling enhances treatment outcomes and surgical planning. Thus, an integrated diagnostic approach helps to prevent the progression of the disease and helps in planning surgical treatment.

114-123 54
Abstract

The brain is one of the rarest locations of prostate cancer (PC) metastasis with a frequency of less than 2 %. PC metastases in the brain are associated with an unfavorable prognosis due to severe symptoms, which, as a rule, significantly impairs the quality of life. The median survival rate of such patients ranges from 2 to 12 months after diagnosis. The prognosis of survival is determined by the variant of the histological structure of the primary tumor, timely treatment of the underlying disease, size, localization and number of metastatic foci in the brain. Due to the rarity of the condition, there are currently no major clinical studies on metastatic brain damage in prostate cancer and no treatment algorithm has been developed for this group of patients.
This article presents clinical observations of patients with prostate cancer with metastatic brain damage. The influence of the localization of metastatic foci on the prognosis of the disease was analyzed, the clinical characteristics of patients with intracranial metastases were detailed, treatment methods and survival outcomes were described.
Clinical observations of 2 patients who received combination therapy, i.e. hormonal therapy in combination with chemotherapy, surgery and radiation treatment for the area of distant metastasis in the brain. In the first clinical case, survival after detection of the disease was 16 months, after detection of metastatic brain lesion – 12 months, in the second clinical case – 13 months and 2 months, respectively. During magnetic resonance imaging (MRI) of the brain, a metastatic lesion of the right occipital lobe was detected in 1 case and the right hemisphere of the cerebellum in 2 cases of observation. In both cases, an MRI scan of the pelvis revealed a locally advanced prostate tumor. According to a comprehensive radiological examination, distant metastases were verified in patients, and metachronous brain damage occurred. The cause of death of the patients was the progression of prostate cancer in the form of metastatic brain damage.
In clinical practice, brain metastases in prostate cancer as an isolated lesion are extremely rare. A description of the clinical condition of patients and the severity of the disease is important in presenting the treatment experience for this category of patients.



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ISSN 2410-1893 (Online)