免疫组织化学在评估具有可疑抗肿瘤作用的化合物的致病机制方面的可能性。第一部分:过程活性的一般指标

M. A. Akimenko, O. A. Voronova, M. S. Alkhuseyn-Kuliaginova, A. B. Alnikin, N. A. Kornienko, M. Dodokhova, M. V. Gulyan, I. Kotieva
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引用次数: 0

摘要

尽管化疗药物种类繁多,但寻找和研究据称具有抗肿瘤作用的新化合物仍然具有现实意义。对药理活性物质作用下发生的病理过程进行形态学诊断,是对据称具有抗肿瘤作用的化合物进行临床前研究的最重要组成部分。最好使用免疫组化方法,通过肿瘤进展活动的间接标志物来研究实验动物器官和系统在肿瘤进程发展的不同阶段可能产生的细胞毒性作用。在恶性肿瘤的动态发展过程中,对实质器官和肿瘤组织进行形态学检查比生化研究更有参考价值和依据。本研究的目的是对肿瘤进程活性的标志物进行比较分析,以便在具有可疑抗肿瘤活性的化合物的临床前研究中更有效地使用形态学和免疫组化研究方法,评估其在肿瘤进程活性检测中的应用前景。本文使用 Scopus、Web of Science、PubMed 和 eLIBRARY 数据库进行文献检索。本文概述了目前用于评估实验中恶性过程活性的分子生物学标记物:转化生长因子 beta 1 (TGF-β1)、Ki-67、肿瘤坏死因子α (TNF-α)、p53、聚-ADP-核糖聚合酶 1 (PARP-1) 和抗-8-羟基-2'-脱氧鸟苷 (8-OHdG)、β III 管蛋白、p120 连环素、β 肌动蛋白。所列标记物均为间接标记物,只能以单一模式用于抗肿瘤和抗转移活性的筛选研究,根据有效性原则对大量化合物进行排序。在对领军化合物的药理活性进行深入研究时,有必要进行全面的免疫组化研究。我们对文献数据的分析证实了选择最佳、灵敏、经济可行且负担得起的标记物的重要性,这反过来又会导致诊断面板的改进及其标准化,从而简化其过渡到临床实践的过程。
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The possibilities of immunohistochemistry for assessing the pathogenetic mechanisms of action of compounds with a suspected antitumor effect. Part I. General indicators of the process activity
Despite the wide arsenal of chemotherapeutic agents, the search and study of new compounds with an alleged antitumor effect is relevant. Morphological diagnostics of pathological processes occurring under the action of pharmacologically active substances is the most important component of preclinical research of compounds with an alleged antitumor effect. It is advisable to use information about the possible cytotoxic effect of candidates for antitumor drugs using an immunohistochemical method for studying organs and systems of experimental animals at different stages of the development of the tumor process by indirect markers of tumor progression activity. Morphological examination of parenchymal organs and tumor tissue in the dynamics of the development of malignant neoplasm is more informative and evidence-based than biochemical research. The aim of the study is to conduct a comparative analysis of markers of tumor process activity for more effective use of morphological and immunohistochemical research methods in the preclinical study of compounds with suspected antitumor activity to assess the prospects for their use with the detection of tumor process activity. The literature search was carried out using the Scopus, Web of Science, PubMed and eLIBRARY databases. The paper presents an overview of current molecular biological markers for assessing the activity of the malignant process in the experiment: Transforming Growth Factor beta 1 (TGF-β1), Ki-67, Tumor necrosis factor alpha (TNF-α), p53, Poly-ADP-ribose polymerase 1 (PARP-1) and Anti-8-Hydroxy-2'-deoxyguanosine (8-OHdG), beta III Tubulin, p120 Catenin, Beta Actin. The listed markers are indirect and can be used in a single mode only for screening studies of antitumor and antimetastatic activity in which a large number of compounds are sorted according to the principle of effectiveness. When conducting an in-depth study of the pharmacological activity of the leader compounds it is necessary to perform a comprehensive immunohistochemical study. Our analysis of the literature data confirms the importance of selecting optimal, sensitive, economically feasible and affordable markers, which in turn leads to the improvement of diagnostic panels and their standardization to simplify their transition into clinical practice.
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