Abstract

Numerous recent studies in experimental oncology have shown that the results of fundamental research at the current methodological level can serve as a sound basis for use in clinical practice. The aims of the present work were to assess the inhibitory effect of exogenous lactoferrin (LF) at doses of 1 and 10 mg/kg animal weight on the Walker-256 carcinosarcoma in vivo and the safety of its use, the distinctive features of changes in tumor tissue cytoarchitectonics, and the disturbances of energy metabolism and essential homeostasis at the tumor and organism level and to characterize the associative relationships and mechanisms that underlie these changes. Outbred rats were either administered exogenous LF nine times intraperitoneally at doses of 1 and 10 mg/kg body weight after Walker-256 carcinosarcoma grafting or served as control animals. The morphological analysis method was used for the evaluation of changes in tumor cytoarchitectonics under the influence of LF. The Hayashi cytogenetic method was used to assess the safety of exogenous LF. The content of essential elements was determined by atomic emission spectroscopy, and an atomic biochemical and enzyme-linked immunosorbent analyzer was used to evaluate the parameters of energy metabolism. Exogenous LF at the investigated doses inhibited the growth of Walker-256 carcinosarcoma, as is evident from the unidirectional changes in tumor architectonics: segregation of tumor cells, pycnosis, hyperchromatosis of the nuclei, necrobiosis and necrosis phenomena, and the resulting overall decrease in the tumor cell numbers; the effects on the blood vessels included dilation, wall thinning, and hemorrhage. The changes in the bioenergetic phenotype of tumor cells consisted in a decrease in glucose and lactate content. The homeostasis of essential elements, such as calcium, iron, and zinc, in the tumor tissue and blood plasma was disrupted by LF. The mechanisms that can underlie the specified effect of LF were inferred from the comparison of the abnormalities of tumor cytoarchitectonics, the vascular bed in particular, and the specific changes in the metabolic profiles of the tumors under the influence of exogenous LF.

中文翻译：

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外源乳铁蛋白影响下Walker-256癌肉瘤的形态特征和代谢谱的变化

摘要

最近在实验肿瘤学上的许多研究表明，在当前方法学水平上的基础研究结果可以作为临床实践的良好基础。本工作的目的是评估剂量为1和10 mg / kg动物体重的外源性乳铁蛋白（LF）在体内对Walker-256癌肉瘤的抑制作用及其使用的安全性，变化的独特特征。肿瘤组织的细胞结构学研究，以及在肿瘤和生物体水平上的能量代谢紊乱和基本稳态，并描述了这些变化背后的关联关系和机制。在Walker-256癌肉瘤移植后，以1和10 mg / kg体重的剂量对外来大鼠进行腹膜外腹膜内9次腹腔注射，或作为对照动物。形态学分析方法用于评估LF影响下肿瘤细胞结构的变化。Hayashi细胞遗传学方法用于评估外源性LF的安全性。通过原子发射光谱法测定必需元素的含量，并使用原子生化和酶联免疫吸附分析仪评估能量代谢的参数。从研究剂量的外源性LF抑制了Walker-256癌肉瘤的生长，这从肿瘤结构学的单向变化可以明显看出：肿瘤细胞的分离，脓疱病，细胞核过度增生，坏死和坏死现象，以及由此导致的总体下降。肿瘤细胞数量；对血管的影响包括扩张，壁变薄和出血。肿瘤细胞生物能表型的变化在于葡萄糖和乳酸含量的降低。LF破坏了肿瘤组织和血浆中钙，铁和锌等基本元素的体内平衡。通过比较肿瘤细胞建筑学的异常，尤其是血管床，以及在外源性LF的影响下肿瘤代谢特征的特定变化，可以推断出可能导致LF特定作用的机制。