Peer-rewieved medical journal. The aim of the edition is to promote scientific achievements of Russian medicine in Russia and abroad. The publication of reviews, lectures, essays by leading Russian and foreign experts in the field of fundamental and ...
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Focal spleen sarcoidosis: clinical and diagnostic characteristics
Purpose of the study. Analysis of literature data on cases of spleen sarcoidosis focal manifestations. Materials and methods. A search was conducted for publications in the PubMed database using the keywords "splenic sarcoidosis", "isolated splenic sarcoidosis" and "primary splenic sarcoidosis" for the period from 1944 to 2024. Articles describing clinical observations of spleen sarcoidosis were selected, where it was possible to reliably determine the presence of focal manifestations of spleen sarcoidosis with a descriptive diagnostic picture, morphological verification, as well as additional information about lesions of other organs. Results. The analysis of these articles revealed 128 cases of spleen sarcoidosis, of which isolated focal spleen sarcoidosis was detected in 41 (32.0 %) cases. Combined sarcoidosis (in which the lesion of the spleen was combined with one or two other localizations or was part of a multiple lesion of the entire organism) accounted for 68.0 % of cases. Sarcoidosis developed synchronously or after surgical treatment of cancer in 22 (17.2 %) cases: synchronously – 12 (54.5 %) cases; in the postoperative period – 10 (45.5 %). An analysis of the identified observations is carried out. The main clinical and radiation characteristics of focal sarcoidosis of the spleen, as well as the most common other localizations in our analysis, are highlighted. Conclusion. Spleen lesions can occur in various clinical situations, ranging from asymptomatic patients to critically ill patients. However, focal formations of the spleen are quite rare, which makes it difficult to collect data from large groups of homogeneous morphological forms for analysis and development of criteria for differential diagnosis, therefore, the presence of a focus in the spleen often causes difficulties for specialists to make a diagnosis. The review identifies the incidence rates of focal spleen sarcoidosis and highlights its main clinical and radiation characteristics. Knowledge of these signs makes it possible to differentiate the disease, especially with an isolated lesion.
Possibilities of vaccine therapy for the treatment of glioblastoma
Glioblastoma is the most common and most aggressive primary brain tumor with a median survival of less than two years. Great hopes in the complex treatment of glioblastomas are placed on the use of immunotherapy, including vaccine therapy. Purpose of the study. To reflect the features of the use of vaccine therapy for brain tumors based on the analysis of modern scientific publications and present the results obtained in Russia and abroad. Materials and methods. The literature search was conducted in the Medline, E-library, PubMed systems. Results. The review presents data on unsatisfactory results of standard treatment of glioblastomas, characterizes their biological differences that determine weak sensitivity to most types of antitumor therapy and difficulties arising during vaccination; describes the properties of dendritic cells and their significance for the development of one of the main types of vaccines. The results of non-randomized and few randomized studies on the clinical use of vaccine therapy in Russia and abroad, mainly dendritic cell vaccines (DCVs) in patients with glioblastomas are highlighted. The prospects of personalized vaccination are emphasized; the effect of DCVs on some components of the immune system is described, as well as the dual role of exosomes in the development of a malignant process, resistance to treatment and the possibility of their use in creating vaccines. Information on clinical experience with the use of peptide vaccines and vaccines based on matrix RNA is presented. Conclusion. Despite certain difficulties in the use of vaccine therapy in patients with glioblastomas, encouraging results have been obtained in Russia and abroad. It is emphasized that antitumor vaccines have undoubted potential for the treatment of glioblastomas and are becoming promising methods of immunotherapy that can bring clinical benefit to patients with these most aggressive and difficult to treat malignant tumors.
Therapeutic approaches to pulmonary metastases in colorectal cancer
Pulmonary metastases of colorectal cancer (CRC) represent a significant clinical problem that requires a multidisciplinary approach in determining treatment tactics. To date, there are no prognostic scales and algorithms that make it possible to stratify patients with metastatic lung damage and give preference to surgical treatment, systemic or radiotherapy. Purpose of the study. To systematize data on treatment methods for pulmonary metastases of CRC and to evaluate the influence of prognostic factors on survival rates in this cohort of patients. Materials and methods. The analysis of publications for 2000–2025 in the PubMed and Google Scholar databases was carried out using the keywords: "colorectal cancer", "pulmonary metastases", "thoracoscopic surgery", "stereotactic radiation therapy", "circulating tumor DNA". Studies that do not correspond to the topic, duplicate data, and work on metastatic lung damage in other nosologies are excluded. Results. The results of treatment in the group of patients with pulmonary metastases of CRC are significantly influenced by many characteristics of the tumor. These include the number of metastatic foci, the presence or absence of affected mediastinal lymph nodes, and the level of cancer-­ embryonic antigen (CEA). A prognostically unfavorable factor is a history of metastatic liver damage and KRAS/BRAF mutations. The localization of the primary tumor among patients with oligometastatic CRC is also significant: the left-sided localization of the primary tumor is characterized by better overall survival rates than with the right-­sided lesion. Conclusion. Surgical resection for pulmonary metastases is the standard of treatment in the group of patients with oligometastatic CRC. Therapeutic tactics for each individual case should be determined by a multidisciplinary team, considering the biological and genetic characteristics of the tumor. In the presence of negative prognosis factors, adjuvant systemic therapy can improve long-term treatment outcomes. Modern treatment approaches for pulmonary metastases are based on data from retrospective studies, which highlights the need for prospective randomized trials and the importance of developing standardized algorithms.
Identification, screening and experimental approbation of the biological activity of Vaccinium praestans Lamb. fruit extract
Early manifestation of age‑associated diseases is linked to pathological free radical formation and the development of chronic oxidative stress. Vaccinium praestans Lamb (redberry, klopovka) is of practical interest for the prevention of such diseases as a potential source of natural antioxidants. Purpose of the study. To identify phenolic compounds in V. praestans fruits, screen their potential biological activity, and experimentally determine the antioxidant activity of V. praestans fruit liquid extract in vitro and in vivo. Materials and methods. The composition of phenolic compounds in the liquid extract of V. praestans fruits was analyzed using high‑performance liquid chromato‑mass‑spectrometry (HPLC–MS/MS). Total soluble phenolic compounds were quantified using the Folin–Ciocalteu method. Preliminary screening of biological activity of the identified phenolic compounds was performed using the PASS online computational prediction tool. Antioxidant activity of the extract was evaluated using the ABTS and FRAP assays. The effect of the extract on the antioxidant defense system of rats was assessed by modeling oxidative stress induced by carbon tetrachloride administration. Results. Ten phenolic compounds were identified in the liquid extract of V. praestans fruits, including quercetin glycosides, catechin, cyanidin glycosides, hydroxycinnamic acids, and their derivatives. The total phenolic content in the liquid extract of V. praestans fruits was 9.1 ± 0.12 mg‑GAE/mL. Preliminary biological activity screening indicated that the identified phenolic compounds may exhibit antioxidant, anticancer, antihypoxic, and cytoprotective activities. Antiradical activity of the liquid extract was confirmed using ABTS and FRAP assays. In the rat oxidative stress model, administration of the V. praestans liquid extract reduced malondialdehyde (MDA) levels by 20.57 % and increased total antiradical activity (TAA) 1.72‑fold compared with the control group (p < 0.05). Conclusion. The study expands current knowledge on the chemical composition and pharmacological activity spectrum of V. praestans fruits.
For the 70th Anniversary Elena M. Frantsiyants
Computed tomography in terms of transposition of the great arteries
Transposition of the great arteries (TGA) is one of the most complex congenital heart defects, which requires surgical intervention in the first days after the birth of a child. The article describes a unique clinical case of a patient with TGA who underwent two- stage surgical correction in childhood with long-term complications 30 years after surgery. In the presented clinical case, computed tomography (CT) with contrast and ECG synchronization demonstrated advantages over echocardiography (EchoCG), becoming the determining method for choosing a further treatment strategy. The importance of CT diagnostics was due to the following advantages: three-­dimensional visualization of conduit degeneration (calcification, 72 % stenosis), accurate assessment of right ventricular remodeling, diagnosis of subclinical thrombosis of the distal branches of the pulmonary artery, quantitative analysis of right ventricular function, visualization of collateral circulation, detection of ascites and signs of liver fibrosis. The analysis of the presented clinical observation demonstrates the possibilities of X-ray imaging methods and emphasizes the need to monitor patients after TGA correction.
Possibilities of using Dopplerography in squamous intraepithelial neoplasia of the cervix
Improvements in screening programs have significantly increased the number of newly diagnosed cases of cervical cancer at the in situ stage. However, the methods used are not always sufficiently sensitive and specific. Determination of blood flow indices in the uterine arteries and cervical arteries during transvaginal ultrasound examination (TVUS) with Dopplerography can be considered as an additional screening method. Purpose of the study. To assess the relationship between the blood flow indices of the uterine and cervical arteries with different degrees of squamous cell intraepithelial neoplasia of the cervix TVUS with Dopplerography. Patients and methods. The study included 60 patients. The 1st study group included 20 patients with high grade squamous intraepithelial lesion (HSIL) infected with HPV of high carcinogenic risk (mainly types 16 and 18). The 2nd group included 20 patients with low grade squamous intraepithelial lesion (LSIL) and HPV of low carcinogenic risk. The control group included 20 healthy female patients. All patients underwent a comprehensive transabdominal and TVUS was performed in real time on Ressona 7, Mindray (Germany) ultrasound machines. Resistance index (RI) of the uterine arteries and cervical vessels were measured by Doppler ultrasound and calculated automatically for each identified artery. Statistical analysis was performed using Microsoft Excel 365 and SPSS 20.0 software packages. Differences were considered statistically significant at p < 0.05. Results. According to the results of the analysis of variance the RI of the cervical arteries in the 1st study group (0.37 (0.25–0.57)) was significantly lower (p < 0.001). In the 2nd study group (0.63 (0.59–0.67)), there was a tendency to decrease (p = 0.09) compared with the control group (0.70 (0.61–0.73)). The analysis of the parameters within the two study groups revealed a significant (p < 0.001) decrease in cervical artery pressure in group 1 (0.37 (0.25–0.57)) compared with group 2 (0.63 (0.59–0.67)). No correlation was noted in the correlation analysis of the RI of the cervical arteries and uterine arteries in Study Group I and II. Conclusion. The use of TVUS with Dopplerography in combination with other screening methods can be used as an additional method to improve the results of early diagnosis and treatment of precancerous diseases of the cervix.
Features of uveal melanoma clinical course
Purpose of the study. Analysis of the clinical characteristics of patients with uveal melanoma to determine the features of the disease course. Patients and methods. The study included 223 patients with a diagnosis of uveal melanoma who were examined at the NMRC for Oncology, the Russian Federation Ministry of Health, in the period from 2019 to 2024. All patients underwent a standard ophthalmological examination, and computed tomography of the orbits, chest, and abdominal organs was performed. Using the methods of standard descriptive statistics, patient data were analyzed in order to identify the ratio of the following: gender, age, location of the neoplasm and its size, the degree of spread of the primary tumor, metastasis and clinical symptoms. Results. In the study group, the number of male patients was 92 people (41.2 %) and female patients – 131 people (58.8 %). The average age of all patients was 61.3 ± 0.9 years. The incidence among female patients is higher than among male patients, especially at the age of 60 to 74 years. The most common localization of uveal melanoma is the choroid, which accounted for 85.6 % (191 patients). Tumors with degree of spread of T2 and T3 were predominant – 70 (31.4 %) and 76 (34.1 %) people, respectively. Medium and large tumors were diagnosed in a larger number of patients – 30.9 % and 40.4 %, respectively. Among all patients, distant metastases were detected in 11.6 %. The main site of metastasis is the liver (61 %). To a lesser extent, metastatic lesions were found in the lungs and bones (9–13 %), as well as the kidneys, adrenal glands, pancreas and brain (3–7 %). A wide range of symptoms and consequences of the spread of the primary tumor was revealed. Conclusion. The variety of clinical symptoms in uveal melanoma depends on the location and extent of the tumor. Understanding the features of the development of the disease and its manifestations contributes to timely diagnosis and effective treatment.
Antitumor activity of tropolone JO-122(2) in subcutaneous CDX models of cancer
Purpose of the study. The present study investigates the antitumour effect of tropolone 2-(1,1‑dimethyl‑1H-benzo[e]indolin‑2‑yl)-5,6,7‑trichloro‑1,3‑tropolone (JO‑122(2)) in monotherapy and in combination with fluorouracil in subcutaneous CDX models of gastric cancer. Materials and methods. The experimental work was conducted on female BALB/c Nude mice (n = 32), with ages ranging from 6 to 8 weeks. The CDX models were created by subcutaneous administration of a tumor culture of human gastric adenocarcinoma (AGS) in a dose of 5 × 106 cells per mouse. After the tumors reaching a volume of 70–100 mm³, the animals were divided into four groups of eight individuals each, with the objective of ensuring minimal variation in the mean tumor node volume between groups. The efficacy of the therapeutic intervention was evaluated by measuring the inhibition of tumor growth (TGI %). The statistical data processing was performed using the Microsoft Excel 2013 and STATISTICA 12 software packages. The Mann–Whitney U test was utilized to evaluate the disparities between the experimental and control groups. Differences were considered statistically significant at p < 0.05. Results. Consequently, subcutaneous CDX models of gastric adenocarcinoma were obtained. The study demonstrated that the administration of JO‑122(2) as a monotherapy did not result in a statistically significant impact on the growth of tumor nodes. The most significant antitumor activity was observed in the group administered combination therapy (JO‑122(2) + 5‑fluorouracil). The mean value of tumor node volumes at the conclusion of the experiment (on day 29 after the commencement of treatment) in this group was 513.98 ± 56.50 mm³, whereas in the control group it was 915.08 ± 49.93 mm³. A comparison of tumor growth rates between the groups receiving 5‑fluorouracil monotherapy and combination therapy revealed statistically significant differences as early as the 22nd day of the experiment. Furthermore, the highest TPO value was observed in the group administered the combination of drugs, at 43.83 %. Conclusion. The results demonstrated a more effective antitumor effect on gastric adenocarcinoma models when tropolone was used in combination with a cytostatic. This finding suggests the potential for further investigation into the properties of this compound and the possibility of extending its study.
Morphological and laboratory factors associated with recurrence risk in non-metastatic seminoma pT1–pT2: a retrospective analysis
Purpose of the study. To perform a comparative analysis of clinical data and morphological features in patients with non‑metastatic seminoma, as well as to identify prognostic criteria for the administration of adjuvant antitumor therapy. Patients and methods. This retrospective study was conducted at the National Medical Radiological Research Centre and included data from patients with non‑metastatic seminoma (n = 96) who underwent orchifuniculectomy. Medical records were reviewed with assessment of clinical and anamnestic data, laboratory parameters (alpha‑fetoprotein (AFP), beta‑human chorionic gonadotropin (β‑hCG), and lactate dehydrogenase (LDH)), and morphological tumor characteristics. Patients were stratified into three recurrence risk groups (low, intermediate, and high) according to current clinical guidelines. Results. Comparative analysis revealed statistically significant associations between the high‑risk recurrence group and several clinico‑morphological parameters: tunica albuginea invasion (χ² = 23.626, p < 0.001), tumor necrosis (χ² = 6.579, p = 0.038), and elevated β‑hCG levels (χ² = 1.039, p < 0.001). Analysis of AFP and LDH levels did not show significant differences between stages or risk groups. Conclusion. The results of this retrospective study expand current understanding of factors associated with recurrence risk in non‑metastatic seminoma and emphasize the need for a personalized approach to risk group stratification.
CIGB-552: Anticancer peptide with multimodal mechanisms and clinical promise for colorectal cancer
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.
Prognostic potential of tumor lesions of the lower uterine segment in early endometrioid cancer of the uterine body
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.
Features of some growth factors content in tumors and blood plasma in patients with rare forms of endometrial cancer
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.
Computed tomography in terms of thoracic outlet syndrome diagnosis
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.
Surgical thyroid pathology in Crimea and Sevastopol: the way COVID-19 pandemic altered the frequency and structure of diseases
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.
Changes in the concentration of melatonin and endogenous proteins regulating carbohydrate and lipid metabolism in rats under conditions of light desynchronosis with pharmacological correction by peptide extracts from the pineal gland and pituitary gland of the reindeer (Rangifer tarandus)
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.
Comparative analysis of clinical, morphological and prognostic parameters of non-metastatic skin melanoma
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.
Concentrations of pro- and anti-apoptotic proteins, as well as calcium ions in mitochondria of endometrioid adenocarcinoma cells depending on the degree of its differentiation
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.
Value of [18F]FDG PET/CT for predicting epidermal growth factor receptor gene mutation status in patients with newly diagnosed non-small cell lung cancer: a retrospective single center study
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.