genomics and epigenomics

  • 文章类型: Journal Article
    睾丸生殖细胞肿瘤(TGCT)因其出色的生存率而被广泛认可。通常归因于它们对以顺铂为基础的疗法的高度敏感性。尽管如此,一部分患者出现顺铂耐药,对于其他治疗选择不成功的人,其中约20%将在早期因疾病进展而死亡。已经进行了一些努力以试图找到顺铂抗性的分子基础。然而,这种现象仍然没有得到充分理解,这限制了有效生物标志物和精准医学方法的开发,作为可以改善这些患者临床结局的替代方法。为了提供综合景观,我们回顾了TGCT患者中归因于化学反应的最新基因组和表观基因组特征,强调我们如何通过TGCT对治疗特别过敏的相同机制来对抗顺铂耐药。在这方面,我们探索耐药TGCT的持续治疗方向和新靶点,以指导未来的临床试验.通过我们对最近发现的探索,我们得出的结论是,epidrugs是有希望的治疗方法,可以帮助恢复耐药肿瘤的顺铂敏感性,为患者的利益提供更好的预后的潜在途径。
    Testicular germ-cell tumors (TGCT) have been widely recognized for their outstanding survival rates, commonly attributed to their high sensitivity to cisplatin-based therapies. Despite this, a subset of patients develops cisplatin resistance, for whom additional therapeutic options are unsuccessful, and ~20% of them will die from disease progression at an early age. Several efforts have been made trying to find the molecular bases of cisplatin resistance. However, this phenomenon is still not fully understood, which has limited the development of efficient biomarkers and precision medicine approaches as an alternative that could improve the clinical outcomes of these patients. With the aim of providing an integrative landscape, we review the most recent genomic and epigenomic features attributed to chemoresponse in TGCT patients, highlighting how we can seek to combat cisplatin resistance through the same mechanisms by which TGCTs are particularly hypersensitive to therapy. In this regard, we explore ongoing treatment directions for resistant TGCT and novel targets to guide future clinical trials. Through our exploration of recent findings, we conclude that epidrugs are promising treatments that could help to restore cisplatin sensitivity in resistant tumors, shedding light on potential avenues for better prognosis for the benefit of the patients.
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  • 文章类型: Journal Article
    创伤性脑损伤仍然是全球死亡和残疾的主要原因。尽管存在现有的预测模型,但结果预测中的大量不确定性仍然是规则。此外,尽管临床前数据非常有希望,中度和重度TBI神经保护策略的随机临床试验(RCT)未能证明显著的治疗效果.需要更好的预测模型,因为现有的经过验证的方法在预测不良结果方面更有用,并且不包括生物标志物,基因组学,蛋白质组学,代谢组学,等。长期以来被认为是TBI患者护理中的“游戏规则改变者”的侵入性神经监测显示出好坏参半的结果,支持其广泛使用的证据水平仍然不足。这部分是由于该疾病在其病因上的极端异质性,病理学和严重程度。目前,急性创伤性脑损伤(TBI)的诊断集中在神经系统检查和神经影像学工具,如CT扫描和MRI,它的治疗在很大程度上是使用“一刀切”的方法来面对的,这给我们留下了许多悬而未决的问题。精准医学是一种考虑基因个体差异的TBI治疗创新方法,环境,和生活方式,并已扩展到整个医疗领域。在这篇文章中,我们简要探讨了TBI的精准医学领域,包括用于治疗决策的生物标志物,多模式神经监测,和基因组学。
    Traumatic brain injury remains a leading cause of death and disability across the globe. Substantial uncertainty in outcome prediction continues to be the rule notwithstanding the existing prediction models. Additionally, despite very promising preclinical data, randomized clinical trials (RCTs) of neuroprotective strategies in moderate and severe TBI have failed to demonstrate significant treatment effects. Better predictive models are needed, as the existing validated ones are more useful in prognosticating poor outcome and do not include biomarkers, genomics, proteonomics, metabolomics, etc. Invasive neuromonitoring long believed to be a \"game changer\" in the care of TBI patients have shown mixed results, and the level of evidence to support its widespread use remains insufficient. This is due in part to the extremely heterogenous nature of the disease regarding its etiology, pathology and severity. Currently, the diagnosis of traumatic brain injury (TBI) in the acute setting is centered on neurological examination and neuroimaging tools such as CT scanning and MRI, and its treatment has been largely confronted using a \"one-size-fits-all\" approach, that has left us with many unanswered questions. Precision medicine is an innovative approach for TBI treatment that considers individual variability in genes, environment, and lifestyle and has expanded across the medical fields. In this article, we briefly explore the field of precision medicine in TBI including biomarkers for therapeutic decision-making, multimodal neuromonitoring, and genomics.
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