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Purpose of the study. An analysis of changes in the expression of the VEGF neoangiogenic factor in the tumor tissue of patients with squamous cell carcinoma of the oral mucosa receiving targeted therapy with cetuximab and chemotherapy.Patients and methods. We performed an immunohistochemical study of tumor samples obtained from 60 patients with squamous cell carcinoma of the oral mucosa T3-4N0-1M0. The main group comprised 30 patients who received therapy with cisplatin and fluoruracil plus cetuximab. The control group included 30 patients receiving standard chemotherapy without targeted therapy. Each group was divided into two subgroups with different treatment efficacy: patients sensitive to treatment (n = 17 in the group with cetuximab and n = 12 in the group without cetuximab) and resistant to treatment (n = 13 in the group with targeted therapy and n = 18 in the group with standard chemotherapy).Results. Quantification of the VEGF expression demonstrated minimal numbers of vessels stained positively for this marker in the field of view in patients of the main group sensitive to chemotherapy and cetuximab. The value was 5.3 times lower than initial values, and 4.3 times lower than in the subgroup of patients resistant to the treatment (the data were statistically significant, р = 0.0132 and р = 0.0455, respectively). In the control group, patients who were sensitive to the treatment showed 1.4 times lower values than initially (р = 0.921), and patients who were resistant to the treatment had 1.1 times lower values than initial values (р = 0.936). The data were not statistically significant.Conclusions. The study showed that the number of microvessels in patients resistant to chemotherapy and cetuximab was 4.3 times higher than in patients with effective targeted therapy (р = 0.0455). The differences in the control group were not statistically significant.

Purpose of the study. An analysis of parameters of the blood coagulation system in breast cancer patients after coronavirus disease.Materials and methods. 50 breast cancer patients were divided into groups: the main group included 30 patients after coronavirus disease, the control group 1–20 patients without confirmed COVID‑19, and control group 2–20 non-cancer women after corona‑ virus disease. All cancer patients received appropriate chemotherapy. The following parameters were studied: activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), prothrombin index (PTI), fibrinogen, soluble fibrin monomer complexes (SFMCs), thrombin time (TT), antithrombin III, D-dimer and plasminogen, fibrin degradation products. Blood tests were performed 4–6 weeks after the infection and two negative PCR test results for COVID‑19.Results. Patients of the main group demonstrated differences in INR values after treatment in the subgroups with asymptomatic disease (Me = 1.24) and with mild symptoms (Me = 0.97) U = 10; Z = 2.766; р = 0.0057, in subgroups with asymptomatic disease (Me = 1.24) and with moderate to severe symptoms (Me = 0.98) U = 26.5; Z = 2.199; р = 0.027, and in TT values in subgroups with asymptomatic disease (Me = 14.5) and with moderate to severe symptoms (Me = 16.5) U = 18.5; Z = –2.725; р = 0.0064. The comparison of the parameters in patients after COVID‑19 before (Me = 0.83) and after treatment (Me = 0.4) showed differences in the D-dimer values in patients with moderate to severe disease U = 6.5; Z = –2.2861; р = 0.022 towards their decrease after the therapy. Differences were found in APTT values between the main group (Me = 30.65) and control group 1 (Me = 27.85) U = 119; Z = 3.574; р = 0.00035, in antithrombin values between the main group (Me = 94) and control group 1 (Me = 106) U = 112; Z = 3.713; р = 0.00021, and in SFMCs values between the main group (Me = 17) and control group 1 (Me = 8) U = 180.5; Z = 2.356; р = 0.018.Conclusions. Determination of plasminogen levels can become an independent factor in detecting thrombotic risk in cancer patients who recovered from COVID‑19. Previous infection with COVID‑19 should be considered an additional risk factor for venous thromboembolic complications for cancer patients.

Introduction. Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients.The purpose of study. Clinical evaluation of the efficacy and safety of Eralfon® (epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy.Materials and methods. We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed.Results. Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia.Conclusion. Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.

The development of a new direction in anticancer medical therapy – the use of immune checkpoint inhibitors targeting PD-1/ PD-L1 and CTLA-4 – has significantly changed the approach to tumor treatment in the last few years. The PD1 blocker nivolumab in major registered clinical trials improved overall survival, including in metastatic melanoma, with a favorable toxicity profile. However, its efficacy in patients with brain metastases from melanoma was poorly studied, since the inclusion criteria for most clinical trials do not envisage recruiting such patients. The immune-mediated toxicity of immune checkpoint inhibitors is currently well enough studied. However, cases of cutaneous toxicity are quite rare and present certain difficulties for differential diagnosis and treatment. This article presents two cases of effective nivolumab treatment in patients with generalized BRAFwt and BRAFmut cutaneous melanoma. The first case is of interest due to the presence of brain metastases in the patient. Nivolumab therapy helped achieving complete regression of intracranial metastases with the long-term effect. The second case, in addition to effective treatment, demonstrates a rare manifestation of skin toxicity – vitiligo on the face and upper extremities.

Background. Breast cancer is one of the most common malignancies and one of the leading causes of cancer deaths among women in the Russian Federation. The prognosis of the disease is largely determined by thebiological subtype of the tumor. Her2-positive breast cancer is characterized by an aggressive course and unfavorable prognosis. The use of pertuzumab, a recombinant humanized monoclonal antibody to the human epidermal growth factor receptor 2, significantly improved immediate and long-term treatment outcomes. The aim of the study was to evaluate treatment outcomes in patients with Her2-positive molecular subtype of breast cancer receiving chemotherapy combined with a dual anti-Her2 blockade, and to assess the intensityand incidence of side effects. Material and methods. Between 2015 and 2018, 37 patients with Her2-positive breast cancer received chemotherapy combined with a dual anti-HER2 blockade (docetaxel 75 mg/m2 i/v on day 1 + trastuzumab 6 mg/kg (loading dose 8 mg/kg) i/v on day 1 + pertuzumab 420 mg (loading dose 840 mg) i/v on day 1 once every 3 weeks). The mean age of the patients was 45.6 ± 11.6 years. Results. Neoadjuvant pertuzumab in combination with trastuzumab and docetaxel resulted in pathological complete response in 12 % of patients and pathological partial response in 36 % of patients. Among patients who received the above neoadjuvant therapy regimen, disease progression was observed in 4 % of patients. The most common side effects were weakness and fatigue (5.4 % of cases) and grade I–II leukopenia (5.4 %).Conclusion. The study demonstrated the efficacy of antitumor therapy with pertuzumab in combination with trastuzumab and docetaxel as well as the absence of severe side effects associated with this treatment regimen in patients with Her2-positive breast cancer.

Patients with brain metastases of HER2-positive breast cancer (BC) is a special group of patients who are difficult to treat and have a short life expectancy. The possibilities of whole brain radiotherapy, stereotactic radiosurgery and surgery in such patients are rather limited. Trastuzumab emtansine (T-DM1) showed potential activity in this subset of patients. T-DM1 is an antibody-chemical conjugate (ADC) that delivers directly to HER2-positive cancer cells, thereby limiting damage to healthy tissue. At this point, the efficacy of trastuzumab emtansine has been demonstrated in several randomized trials as a second and subsequent lines of therapy for advanced breast cancer with a favorable toxicity profile of the drug. This article describes a clinical case of a patient with luminal B HER-2 positive breast cancer who, underwent stereotactic radiosurgery and was treated with trastuzumab emtansine as a the second line of treatment for disease progression with metastatic brain lesions after trastuzumab/pertuzumab-containing therapy. Partial regression of metastases with long-term duration of the effect was achieved treatment with trastuzumab emtazine has been being continued for 24 months. Tolerability of therapy was good: thrombocytopenia 2 degree was the main among side effects. The effect has been persisted for 2 years and the patient continues the treatment. Discussion of the results of real clinical practice with well-known studies was carried out.

Introduction: Squamous cell carcinoma of the oral cavity is one of the most common head and neck cancers with an aggressive course and high mortality rates. The aim of the study was to determine the EGFR expression levels in tumor tissues in patients with squamous cell carcinoma of the tongue and oral mucosa depending on the efficacy of the therapy. Material and methods: The study included 60 patients with squamous cell carcinoma of the tongue and oral mucosa T3-4N0-1M0. The main group included 30 patients receiving chemotherapy (cisplatin/fluorouracil) in combination with targeted therapy with cetuximab. The control group included 30 patients receiving chemotherapy without cetuximab. Both groups were divided into two subgroups: sensitive and resistant. Results: In treatment-resistant patients of the main group with cetuximab, the average EGFR expression was twice lower than the initial levels (p = 0.0080) and 1.7 times higher than in treatment-resistant patients of the control group (p = 0.0157). In treatment-sensitive patients, the average EGFR expression was 19.8 times lower (p = 0.0020) than initial values and 14.9 times higher (p = 0.0067) than in treatment-sensitive controls. Conclusions: A natural decrease in the EGFR expression in tumor tissues due to the targeted therapy was revealed. However, some patients were resistant to cetuximab, which dictates the need to search for predictors of targeted therapy efficacy in patients with locally advanced squamous cell carcinoma of the tongue and oral mucosa.

Aim. Study of VEGF-A and TGF-β growth factors in tumor tissue bioptates in patients with squamous cell carcinoma of the tongue and floor of the oral cavity depending on the effectiveness of polychemotherapy targeted therapy with cetuximab.Patients and methods. The study included 30 patients with squamous cell carcinoma of the tongue and mouth floor mucosa (T3-4N0-1M0). All patients received 2 cycles of therapy: cisplatin 100 mg/m2 , intravenously, day 1, 5-fluorouracil 1000 mg/m2 /day, intravenously, 96-hour continuous infusion in combination with targeted therapy (cetuximab 400 mg/ m2 on day 1 in a loading dose, then 250 mg/m2 on days 8 and 15). Patients were divided into two subgroups: target sensitivity of patients (partial regression and stabilization) n = 17 and target resistance (progression) n = 13. Levels of growth factors VEGF-A and TGF-β were determined in tumor tissue bioptates by ELISA using standard test systems (Bender Med System, Austria). Statistical processing of results was performed using the Statistica 6.0 program (Stat-Soft, 2001).Results. Polychemotherapy with cetuximab in some patients (n = 13), antitumor therapy with cetuximab did not result in statistically significant changes in levels of VEGF-A, TGF-β and the VEGF-A/TGF-β ratio compared to the initial values. In other patients (n = 17), the studied markers in tumor tissue bioptates were statistically significantly different from the initial values: VEGF-A was decreased by 1.46 times, TGF-β by 2.96 times, while the VEGF-A/TGF-β ratio was twice elevated.Conclusions. The results on levels of growth factors VEGF-A and TGF-β, as well as the VEGF-A/TGF-β ratio, are of a certain prognostic value and can be used as criteria for evaluating the efficacy of antitumor therapy in patients with squamous cell carcinoma of the tongue and mouth floor mucosa.

The authors analysed the efficacy and safety of Nab-paclitaxel (Nab-R) monotherapy in patients with metastatic breast cancer with visceral crisis (VC) in the second- and further-line chemotherapy. The objective response rate (ORR) was 35.3% (6 of 17 persons). The most frequent side effects were general weakness, nausea, symptoms of peripheral neuropathy. The degree of toxicity did not exceed 1–2 in 60% of cases. The median time to progression was 7.8 months. (95% CI 6–10.6). The median overall survival for patients with VC was 14.9 months. (95% CI 12.0–16.9). Efficacy and controlled toxicity of Nab-P allows its use in pre-treated patients, including ones with VC.

Abstract The emergence of new primate-specific genes is an essential factor in human and primate brain development and functioning. POU2F1/Oct-1 is a transcription regulator in higher eukaryotes which is involved in the regulation of development, differentiation, stress response, and other processes. We have demonstrated that the Tigger2 transposon insertion into the POU2F1 gene which occurred in the primate lineage led to the formation of an additional exon (designated the Z-exon). Z-exon-containing primate-specific Oct-1Z transcript includes a short upstream ORF (uORF) located at its 5’-end and the main ORF encoding the Oct-1Z protein isoform (Pou2F1 isoform 3, P14859-3), which differs from other Oct-1 isoforms by its N-terminal peptide. The Oct-1Z-encoding transcript is expressed mainly in human brain cortex. Under normal conditions, the translation of the ORF coding for the Oct-1Z isoform is repressed by uORF. Under various stress conditions, uORF enables a strong increase in the translation of the Oct-1Z-encoding ORF. Increased Oct-1Z expression levels in differentiating human neuroblasts activate genes controlling stress response, neural cell differentiation, brain formation, and organogenesis. We have shown that the Oct-1Z isoform of the POU2F1/Oct-1 transcription factor is an example of a primate-specific genomic element contributing to brain development and cellular stress defense.

This article aims to analyze the process of national identity formation, which is considered a pivotal concept in contemporary social and humanitarian sciences. The authors explore various dimensions of national identity, ranging from its historical roots to its present-day developmental trends. The focal point of this study revolves around elucidating the determining factors behind the formation and evolution of national identity, as well as its distinctive nature. Consequently, the article not only appeals to researchers but also to a wide readership interested in sociology, history, and cultural studies. Methods: In this article, we will delve into three distinct approaches to comprehending identity -- philosophical, psychological, and sociological. Each of these perspectives brings a different lens to the study of identity, shedding light on its complexities and nuances. Through the use of methods such as systematic review, historical analysis, and literature analysis, the authors have critically examined the views of various scholars on the concept of national identity. By exploring these different approaches, we hope to gain a deeper understanding of the multifaceted nature of identity and how it shapes our sense of self and belonging. [ABSTRACT FROM AUTHOR]

The evolution of corporate reporting in today's world is heavily influenced by a growing emphasis on environmental sustainability and the evaluation of its impact on the environment, as well as the assessment of a company's environmental responsibility, ecological attractiveness, and competitiveness. Traditional accounting and corporate reporting methods are proving inadequate to fulfil the information needs of a diverse array of stakeholders who play a pivotal role in making strategic decisions. This concept seeks to divulge information regarding the environmental impact and ecological footprint of a company, showcasing the interplay between the company's operations and their environmental consequences. The focus is on the future outlook, aligned with the company's strategic objectives and business model. The development of tools for environmental analysis in the corporate world is an essential means of putting these theoretical principles into practice. The importance of this study lies in its potential to provide a theoretical foundation for evaluating a company's agricultural performance through integrated reporting metrics, which in turn will establish a set of indicators reflecting the achievement of both short-term and long-term environmental objectives of the company. All of these factors, in our perspective, underscore the significance of this study and the practical implications of the results it yields. [ABSTRACT FROM AUTHOR]