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SEARCH FOR NEW INHIBITORS OF PROTEIN KINASE SIGNALING PATHWAYS USING MOLECULAR DYNAMICS AND MOLECULAR DOCKING METHODS 利用分子动力学和分子对接方法寻找蛋白激酶信号通路的新抑制剂
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.7
A.A. Glushko, I.P. Kodonidi, E. Frantsiyants, I. Kaplieva, A. S. Chiryapkin, E.V. Sergienko
The development of new therapeutic strategies for the treatment of various diseases associated with impaired protein kinase activity is one of the most urgent tasks in modern medicine. The search for new protein kinase inhibitors is an effective approach in the struggle against cancer. However, the existing protein kinase inhibitors may have limitations in their effectiveness or may produce undesired side effects. Therefore, the development of new methods for searching for new inhibitors, which should be more effective and safe, is a topical issue. One of the promising areas is the use of molecular modeling to search for new protein kinase inhibitors.
开发治疗与蛋白激酶活性受损有关的各种疾病的新疗法是现代医学最紧迫的任务之一。寻找新的蛋白激酶抑制剂是抗击癌症的有效方法。然而,现有的蛋白激酶抑制剂可能在有效性方面存在局限性,或者会产生不良副作用。因此,开发更有效、更安全的新方法来寻找新的抑制剂是一个热点问题。利用分子建模寻找新的蛋白激酶抑制剂是其中一个很有前景的领域。
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引用次数: 0
MOLECULAR CELLULAR EFFECTS BY PROTON AND γ-IRRADIATION IN THE B16 MURINE MELANOMA MODEL IN VIVO 质子和γ-射线在活体 B16 细胞模型中的分子细胞效应
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.27
A. Yakimova, O. Matchuk, E. Selivanova, V.R. Gusarova, V.A. Mosina, S.N. Koryakin, I. Zamulaeva
Proton and photon (γ-) radiation is widely used in modern clinical practice for the treatment of malignant tumors of various locations. The relative biological effectiveness (RBE) of accelerated protons is about 1.1, as follows from the results of experimental studies of clonogenic survival of tumor cells in vitro. But however, despite the low RBE of proton radiation, a number of clinical studies have shown a significant increase in relapse-free and overall survival of patients after proton therapy compared with that after standard radiotherapy using photon radiation. The mechanisms, on which the differences recorded in vivo are based, are of significant scientific and practical interest, but have been poorly studied.
质子和光子(γ-)辐射在现代临床实践中被广泛用于治疗不同部位的恶性肿瘤。根据肿瘤细胞体外克隆存活的实验研究结果,加速质子的相对生物有效性(RBE)约为 1.1。然而,尽管质子辐射的 RBE 很低,但许多临床研究表明,与使用光子辐射的标准放疗相比,质子治疗后患者的无复发生存率和总生存率显著提高。体内记录的差异所基于的机制具有重要的科学和实用价值,但对其的研究却很少。
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引用次数: 0
THE INFLUENCE OF A PERIPHERAL TUMOR ON THE BEHAVIOR OF ANIMALS AND THE STRUCTURE OF NEURONS IN THE PREFRONTAL CORTEX 外周肿瘤对动物行为和前额叶皮层神经元结构的影响
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.18
N. A. Obanina, N.P. Bgatova
Melanoma is the most aggressive of the common forms of skin cancer. Proinflammatory cytokines produced by the tumor and delivered via the circulatory and lymphatic systems can lead to damage to the structures of the central nervous system. Damage to the blood-brain barrier and the endothelium of blood capillaries can cause dysfunction of neurons in the cerebral cortex, induce changes in neural plasticity, cognitive functions and result in the development of depression. Depression is observed in 20% of the cancer patients, and it affects quality of life, treatment effectiveness and survival. Depression has been linked to damage to the prefrontal cortex, which plays an important role in many brain functions, including cognition, emotion regulation, motivation and sociability.
黑色素瘤是常见皮肤癌中最具侵袭性的一种。由肿瘤产生并通过循环和淋巴系统传递的促炎细胞因子可导致中枢神经系统结构受损。对血脑屏障和毛细血管内皮的损害可导致大脑皮层神经元功能障碍,诱发神经可塑性和认知功能的变化,并导致抑郁症的发生。20% 的癌症患者会出现抑郁,它会影响生活质量、治疗效果和生存期。抑郁症与前额叶皮质受损有关,前额叶皮质在认知、情绪调节、动机和社交能力等多项大脑功能中发挥着重要作用。
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引用次数: 0
STRESS IN PATHOGENESIS OF DEVELOPMENT OF TUMOR PATHOLOGY OF THE THYROID GLAND 甲状腺肿瘤病理发展的发病机制中的应激反应
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.29
D.V. Zima, O. R. Khabarov, O. F. Bezrukov, E.Yu. Zyablitskaya
Our experience in the endocrine surgery at our clinics institution has shown a relationship between the appearance of nodules in the thyroid gland and a long-term exposure to stress. At present, the complicated geopolitical circumstances play a role of an active stressor, and until recently, it was also the COVID-19 pandemic, which caused a change in lifestyle, heavy material losses, and loss of loved ones. Oncogenic activity of cells is reflected in an imbalance of markers of proliferation and apoptosis. Many researchers associate thyroid pathology with molecular alterations as diagnostic markers (Styazhkina S.N., 2017; Romashchenko P.N. et al., 2021).
我们诊所内分泌外科的经验表明,甲状腺结节的出现与长期处于压力之下有一定的关系。目前,复杂的地缘政治环境扮演着积极压力源的角色,直到最近,COVID-19大流行也造成了生活方式的改变、严重的物质损失和亲人的离去。细胞的致癌活动反映在增殖和凋亡标志物的失衡上。许多研究人员将甲状腺病理学与作为诊断标志的分子改变联系起来(Styazhkina S.N.,2017;Romashchenko P.N.等人,2021)。
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引用次数: 0
VIROLOGICAL RESPONSE AND EFFECTIVENESS OF CHEMORADIATION THERAPY FOR ANAL CANCER: RELATIONSHIP AND PREDICTIVE CAPABILITIES 肛门癌的病毒学反应和化学放疗的有效性:关系和预测能力
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.30
T. A. Zykova, M. Gusareva, E. A. Shevyakova, E. Frantsiyants, E.A. Tolmacheva, M. Zinkovich, N. G. Kosheleva, A. Solntseva
The effectiveness of chemoradiation therapy (CRT) is conventionally assessed in terms of achieving clinical complete response (CCR), overall and event-free survival. Anal cancer (AR) is considered as one of the cancer diseases with a proven etiological agent: the human papillomavirus (HPV). The search for biomarkers to predict the effectiveness of CRT is always relevant, and an assessment of virological response (VR) may be useful for this purpose. Aim: To compare rates of clinical complete response (CCR) and virological response (VR) to CRT for anal cancer.
化学放疗(CRT)的疗效通常根据临床完全反应(CCR)、总生存期和无事件生存期来评估。肛门癌(AR)被认为是已证实病原体为人类乳头瘤病毒(HPV)的癌症疾病之一。寻找预测 CRT 疗效的生物标志物一直都很重要,而病毒学应答(VR)评估可能对这一目的有用。目的:比较肛门癌 CRT 的临床完全应答率 (CCR) 和病毒学应答率 (VR)。
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引用次数: 0
THE PATH TO GOOD HEALTH IS THROUGH MITOCHONDRIAL TRAINING.INTERMITTENT HYPOXIC TRAINING AS THE MAIN METHOD 健康之路在于线粒体训练,间歇性缺氧训练是主要方法
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.26
T. Voronina
All human health, from the cellular level to overall well-being, is inextricably linked to the health of our mitochondria. This article delves into the concept of mitochondrial training, focusing on Hypoxic Intermittent Training (HIT) as a central method for improving mitochondrial function. It is becoming increasingly clear that various diseases, stress, shock, inflammation, aging, and organ failure are primarily the result of respiratory problems that directly affect mitochondrial health. The regulation of metabolism is closely related to gas exchange, and the composition of the gases we breathe regulates our metabolism. Our main goal is to promote efficient mitochondrial function, a key biological imperative.
人类的所有健康,从细胞层面到整体健康,都与线粒体的健康密不可分。本文将深入探讨线粒体训练的概念,重点介绍低氧间歇训练(HIT),它是改善线粒体功能的核心方法。人们越来越清楚地认识到,各种疾病、压力、休克、炎症、衰老和器官衰竭主要是呼吸问题直接影响线粒体健康的结果。新陈代谢的调节与气体交换密切相关,我们呼吸的气体成分调节着我们的新陈代谢。我们的主要目标是促进线粒体的高效功能,这是生物学的关键要求。
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引用次数: 0
THREE-DIMENSIONAL IN VITRO MODELS FOR STUDYING THE CHEMOSENSITIVITY OF BREAST CANCER CELLS 用于研究乳腺癌细胞化学敏感性的三维体外模型
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.6
S.Yu. Filippova, S. V. Timofeeva, T. V. Chembarova, I. Mezhevova, L.N. Vashchenko, E. Kechedzhieva, E.A. Andreyko
Scientists agree that three-dimensional tumor cell cultures reflect the in vitro biological features of malignant tumors to a greater extent than it is the case with the conventional monolayer cultures. In particular, the results of assessing the effectiveness of anticancer drugs obtained in three-dimensional cell models are considered as more accurate and consistent with the tumor response in vivo, where sensitivity is usually lower than that found in the in vitro experiments. Some of the most developed cellular models are structures obtained using three-dimensional bioprinting, which include not only malignant cells, but also biogels to imitate the chemical and mechanical properties of the extracellular matrix of the tumor.
科学家们一致认为,三维肿瘤细胞培养物比传统的单层培养物更能反映恶性肿瘤的体外生物学特征。特别是,在三维细胞模型中获得的抗癌药物疗效评估结果被认为更准确,更符合体内肿瘤的反应,而体内肿瘤的敏感性通常低于体外实验。一些最先进的细胞模型是利用三维生物打印技术获得的结构,其中不仅包括恶性细胞,还包括用于模仿肿瘤细胞外基质化学和机械特性的生物凝胶。
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引用次数: 0
A MODERN APPROACH TO DISEASE MODELING FOR THE DEVELOPMENT OF ONCOLOGY DRUGS 开发肿瘤药物的现代疾病建模方法
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.12
V. Khokhlova, O. Bezborodova, G. V. Trunova, E. A. Plotnikova, N. Morozova, A. Plyutinskaya, M. S. Vorontsova, Yu. B. Venediktova, E. Nemtsova, A. Pankratov, P. V. Shegai
Oncological diseases are characterized by the complexity of pathogenesis and demonstrate a number of specific signs, such as uncontrolled proliferation, stimulation of angiogenesis, activation of invasion and metastasis. Molecular genetic testing to examine genetic abnormalities in tumor cells has been increasingly using in oncology. With an accumulation of the data on the repertoire of mutations or other events in the patient’s tumors, new goals for the development of more targeted and specific antitumor therapies appear. For example, membrane proteins EGFR, HER-2, PSMA and C-met are identified as such targets. Despite the large volume of research conducted, no more than 11% of the total drug candidates are approved by regulatory authorities for clinical use. This is often due to their lack of effectiveness and the incomparability of the results obtained in preclinical trials in animal models with actual results in patients. Therefore, the development of experimental approaches for modeling tumor processes in laboratory animals is an urgent problem.
肿瘤疾病的特点是发病机制复杂,并表现出许多特殊征兆,如增殖失控、刺激血管生成、激活侵袭和转移。在肿瘤学中,越来越多地使用分子基因检测来检查肿瘤细胞的基因异常。随着患者肿瘤中突变或其他事件的数据不断积累,开发更具针对性和特异性的抗肿瘤疗法的新目标也随之出现。例如,膜蛋白表皮生长因子受体(EGFR)、HER-2、PSMA 和 C-met 被确定为此类靶点。尽管开展了大量研究,但只有不超过 11% 的候选药物被监管机构批准用于临床。这通常是由于这些药物缺乏有效性,以及在动物模型中进行的临床前试验结果与患者的实际结果无法比较。因此,开发在实验动物中模拟肿瘤过程的实验方法是一个亟待解决的问题。
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引用次数: 0
FEATURES OF GROWTH AND DEVELOPMENT OF B16 MELANOMA IN SEXUALLY MATURE MALE C57BLACK/6 MICE IN MODELING POST-TRAUMATIC STRESS DISORDER 性成熟雄性 C57black/6 小鼠 B16 黑色素瘤在创伤后应激障碍模型中的生长发育特征
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.15
M. V. Kondashevskaya, V. Aleksankina, V.V. Kudelkina, M. A. Kozlova, D. Areshidze
It is well known that extraordinary stress or chronic exposure to stressors is characterized by adverse immunological consequences due to stress-induced immunosuppression. It has been established that stress causes an increased incidence of malignant tumors and also worsens the prognosis in patients with already existing tumors. Among the mechanisms of carcinogenesis under stress, there is an increase in the level of cortisol, which has a significant inhibitory effect on the immune system and the secretion of pro-inflammatory interleukins. Post-traumatic stress disorder (PTSD) involves inactivation of the hypothalamic-pituitary-adrenal (HPA) axis and decreased secretion of cortisol in humans, or corticosterone in rats and mice. However, the question of whether PTSD is a risk factor for the development of cancer or tumor growth remains practically undeveloped.
众所周知,超常压力或长期暴露于压力源的特点是,压力诱发的免疫抑制会造成不良的免疫后果。已经证实,压力会导致恶性肿瘤的发病率增加,还会使已患有肿瘤的病人的预后恶化。在压力致癌的机制中,皮质醇水平的增加对免疫系统和促炎性白细胞介素的分泌有显著的抑制作用。创伤后应激障碍(PTSD)涉及下丘脑-垂体-肾上腺轴(HPA)失活,人类皮质醇分泌减少,大鼠和小鼠皮质酮分泌减少。然而,创伤后应激障碍是否是癌症发病或肿瘤生长的风险因素,这一问题实际上仍未得到深入研究。
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引用次数: 0
MicroRNA miR-204-5p IS A REGULATOR OF APOPTOSIS IN DACARBAZINE-RESISTANT MELANOMA CELLS 微RNA miR-204-5p 是抗达卡巴嗪骨髓细胞凋亡的调节因子
Pub Date : 2023-11-01 DOI: 10.18137/cardiometry.2023.29.conf.19
N.V. Palkina
Therapy for skin melanoma in its disseminated form is ineffective, among other things, due to the development of tumor cell resistance, mediated by various mechanisms. The acquisition of a stable cell phenotype is associated both with genetic and epigenetic changes mediated by the regulatory non-coding microRNA molecules.
对扩散型皮肤黑色素瘤的治疗效果不佳,主要是因为肿瘤细胞在各种机制的介导下产生了抗药性。获得稳定的细胞表型既与遗传有关,也与由非编码微 RNA 调控分子介导的表观遗传变化有关。
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引用次数: 0
期刊
Cardiometry
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