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[散发性和放射性甲状腺肿瘤中的RET/PTC基因重排:分子遗传学、放射生物学和分子流行病学]

[RET/PTC Gene Rearrangements in the Sporadic and Radiogenic Thyroid Tumors: Molecular Genetics, Radiobiology and Molecular Epidemiology].

作者信息

Ushenkova L N, Koterov A N, Biryukov A P

出版信息

Radiats Biol Radioecol. 2015 May-Jun;55(3):229-49.

Abstract

A review of molecular genetic, radiobiological and molecular epidemiological studies of gene (chromosome) rearrangements RET/PTC in the cells of the thyroid gland as well as the laws in relation to radiation exposure in vitro, in vivo and human populations identified with them are submitted. The data on the c-RET gene and its chimeric constructs with the gene-donors (RET/PTC rearrangements) are considered. The information about the history of the RET/PTC discovery, their types, carcinogenic potential and specificity both to tumor and non-tumor thyroid disease especially for papillary thyroid carcinoma are provided. The data (seven studies) on the induction of RET/PTC after irradiation of tumor and normal thyroid cells in vitro and mice are reviewed. The mechanisms of RET/PTC induction may be associated with DNA double strand breaks and oxidative stress. Some information (three publications) about the possibility of RET/PTC induction by low doses of radiation with low LET (to 0.1 Gy) is given and it is concluded that their potential evidentiary is generally weak. The achievements in the molecular epidemiology of RET/PTC frequency for exposed and unexposed cohorts are stated. At the same time it is noted that, despite the vast array. of data accumulated from 30 countries of the world and more than 20 years of research, the formed provisions are weakly confirmed statistically and have no base corresponding to the canons of evidence-based medicine. The possibility of use of the RET/PTC presence or their frequencies as markers of the papillary thyroid carcinomas and, specifically, their radiogenic forms, is considered. In the first case the answer may be positive, while in the second, the situation is characterized by uncertainty. Based to the above mentioned we came to a conclusion about the need of a pooled or meta-analysis of the totality of the published data.

摘要

本文综述了甲状腺细胞中基因(染色体)重排RET/PTC的分子遗传学、放射生物学和分子流行病学研究,以及与之相关的体外、体内辐射暴露规律和人类群体研究。文中讨论了c-RET基因及其与基因供体的嵌合构建体(RET/PTC重排)的数据。提供了关于RET/PTC发现的历史、其类型、致癌潜力以及对肿瘤和非肿瘤性甲状腺疾病(特别是甲状腺乳头状癌)的特异性的信息。回顾了关于体外照射肿瘤和正常甲状腺细胞以及小鼠后诱导RET/PTC的相关数据(七项研究)。RET/PTC的诱导机制可能与DNA双链断裂和氧化应激有关。给出了一些关于低LET低剂量辐射(至0.1 Gy)诱导RET/PTC可能性的信息(三篇出版物),并得出结论,其潜在证据通常较弱。阐述了暴露和未暴露队列中RET/PTC频率的分子流行病学研究成果。同时指出,尽管从世界30个国家积累了大量数据且进行了20多年的研究,但所形成的观点在统计学上得到的证实较弱,且没有符合循证医学规范的依据。考虑了将RET/PTC的存在或其频率用作甲状腺乳头状癌,特别是其放射源性形式的标志物的可能性。在第一种情况下,答案可能是肯定的,而在第二种情况下,情况尚不确定。基于上述情况,我们得出结论,需要对已发表的数据进行汇总或荟萃分析。

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