Mechanisms of sexual dimorphism in the pathogenesis of sarcomas

G. A. Belitsky, T. Fetisov, P. A. Shtompel, E. Lesovaya, B. Bokhyan, M. Yakubovskaya, K. Kirsanov
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Abstract

Sarcomas of non-genital organs affect women 1.5–3 times less often than men. The mechanism of such dimorphism is studied at various levels, mainly in the field of influence on the pathogenesis of sex hormones and their receptors, the effect of which is significantly related to the histogenesis of the tumor, its localization, the mechanism of malignant transformation and the stage of progression. Sex hormone receptors are often found in the early stages of tumor development and are lost during progression. At the same time, the expression of the same receptors in tumors of different histogenesis sometimes correlates with the opposite prognosis of the disease and sensitivity to hormonal therapy. For example, in uterine leiomyosarcomas, the expression of estrogen and androgen receptors correlates with a better prognosis and greater effectiveness of therapy, and in osteo- and fibrosarcomas, vice versa. Estrogens stimulate proliferation of osteosarcoma cells, and androgens that of rhabdomyosarcoma and small round cell tumor, which growth is inhibited by antiandrogens used in the treatment of prostate cancer. In this regard, when trying to include a hormonal component in a therapeutic complex, an individual study of the hormonal sensitivity of the tumor is necessary. One of the methodological approaches to this could be testing a culture of tumor cells from surgical material for sensitivity to agonists/antagonists of hormonal receptors separately and in combination with chemotherapy drugs.
肉瘤发病机制中的性双态性机制
非生殖器官肉瘤对女性的影响是男性的 1.5-3 倍。人们从不同层面研究了这种二态性的机理,主要是性激素及其受体对发病机理的影响,性激素及其受体的作用与肿瘤的组织发生、定位、恶性转化机制和进展阶段有很大关系。性激素受体通常出现在肿瘤发生的早期阶段,并在肿瘤发展过程中消失。同时,不同组织发生机制的肿瘤中相同受体的表达有时与疾病的预后和对激素治疗的敏感性相反。例如,在子宫白肌瘤中,雌激素和雄激素受体的表达与较好的预后和较高的治疗效果相关,而在骨肉瘤和纤维肉瘤中则相反。雌激素刺激骨肉瘤细胞增殖,雄激素刺激横纹肌肉瘤和小圆细胞瘤细胞增殖,而治疗前列腺癌的抗雄激素可抑制这些细胞的生长。因此,当试图在治疗复合物中加入激素成分时,有必要对肿瘤的激素敏感性进行单独研究。方法之一是从手术材料中培养肿瘤细胞,分别测试其对激素受体激动剂/拮抗剂的敏感性,以及与化疗药物联合使用的敏感性。
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