• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>other >Primary Immunodeficiency and Cancer Predisposition Revisited: Embedding Two Closely Related Concepts Into an Integrative Conceptual Framework
【2h】

Primary Immunodeficiency and Cancer Predisposition Revisited: Embedding Two Closely Related Concepts Into an Integrative Conceptual Framework

机译：再次探讨原发性免疫功能低下和癌症的易感性：将两个紧密相关的概念嵌入一个整合的概念框架

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Common understanding suggests that the normal function of a “healthy” immune system safe-guards and protects against the development of malignancies, whereas a genetically impaired one might increase the likelihood of their manifestation. This view is primarily based on and apparently supported by an increased incidence of such diseases in patients with specific forms of immunodeficiencies that are caused by high penetrant gene defects. As I will review and discuss herein, such constellations merely represent the tip of an iceberg. The overall situation is by far more varied and complex, especially if one takes into account the growing difficulties to define what actually constitutes an immunodeficiency and what defines a cancer predisposition. The enormous advances in genome sequencing, in bioinformatic analyses and in the functional in vitro and in vivo assessment of novel findings together with the availability of large databases provide us with a wealth of information that steadily increases the number of sequence variants that concur with clinically more or less recognizable immunological problems and their consequences. Since many of the newly identified hard-core defects are exceedingly rare, their tumor predisposing effect is difficult to ascertain. The analyses of large data sets, on the other hand, continuously supply us with low penetrant variants that, at least in statistical terms, are clearly tumor predisposing, although their specific relevance for the respective carriers still needs to be carefully assessed on an individual basis. Finally, defects and variants that affect the same gene families and pathways in both a constitutional and somatic setting underscore the fact that immunodeficiencies and cancer predisposition can be viewed as two closely related errors of development. Depending on the particular genetic and/or environmental context as well as the respective stage of development, the same changes can have either a neutral, predisposing and, in some instances, even a protective effect. To understand the interaction between the immune system, be it “normal” or “deficient” and tumor predisposition and development on a systemic level, one therefore needs to focus on the structure and dynamic functional organization of the entire immune system rather than on its isolated individual components alone.
机译：普遍的理解表明，“健康的”免疫系统的正常功能可以保护并预防恶性肿瘤的发展，而遗传受损的人可能会增加其表现的可能性。这种观点主要基于由高渗透性基因缺陷引起的具有特定形式的免疫缺陷的患者中此类疾病的发病率上升，并且显然受到这种疾病的支持。正如我将在此处回顾和讨论的那样，这些星座仅代表冰山一角。总体而言，情况更加复杂多样，尤其是如果考虑到越来越多的困难来定义什么实际上构成免疫缺陷以及什么是癌症易感性。基因组测序，生物信息学分析以及新发现的功能性体外和体内评估的巨大进展以及大型数据库的可用性为我们提供了丰富的信息，这些信息稳步增加了临床上一致认可的序列变体的数量。或更难以识别的免疫学问题及其后果。由于许多新发现的硬核缺陷极为罕见，因此难以确定其肿瘤易感性。另一方面，对大数据集的分析不断为我们提供了低渗透性变异体，这些变异体至少在统计学上显然是肿瘤的诱因，尽管它们与各个携带者的具体相关性仍需要逐一仔细评估。 。最后，在体质和躯体环境中影响相同基因家族和途径的缺陷和变异强调了以下事实：免疫缺陷和癌症易感性可以被视为与发育密切相关的两个错误。取决于特定的遗传和/或环境背景以及相应的发育阶段，相同的变化可能具有中性，易感性，在某些情况下甚至具有保护作用。要了解免疫系统之间的相互作用（无论是“正常”还是“缺陷”）与肿瘤在系统水平上的易感性和发展，因此，需要着重于整个免疫系统的结构和动态功能组织，而不是孤立的免疫系统单独的组件。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号