胆脂瘤:分子发病机制和潜在治疗方向的最新综述。

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bingwen Xing, Yalong Dang, Kai Xi
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引用次数: 0

摘要

胆脂瘤是中耳角化鳞状上皮的异常积聚,是一种局部侵袭性的组织学良性病变。它的骨侵蚀能力导致严重的并发症,包括听力丧失、面神经麻痹和颅内感染。慢性炎症是其发病机制的核心,促炎介质如TNF-α、IL-1β和IL-6激活信号通路,如NF-κB、JAK/STAT和MAPK。这些途径有助于上皮细胞的过度增殖和由基质金属蛋白酶(MMPs)介导的细胞外基质降解。上皮细胞行为的失调,包括角化细胞功能的改变和e -钙粘蛋白介导的粘附减少,可能促进病变的形成和扩大。此外,涉及生长因子(如EGF, TGF-β)的异常信号和通过RANKL途径的破骨细胞活性失调有助于增强骨侵蚀和组织侵袭。新兴研究强调了c-MYC原癌基因、microrna和Sonic hedgehog信号在疾病进展中的潜在作用,为疾病的发病机制提供了更深入的了解。目前的治疗主要包括手术切除,但高复发率强调需要辅助治疗策略。潜在的未来方向包括调节关键通路,如NF-κB、MMP活性和RANKL信号,以及探索与生长因子和细胞粘附相关的干预措施。将分子研究与临床研究相结合对于制定减少复发和改善患者预后的策略至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cholesteatoma: An Updated Review of Molecular Pathogenesis and Potential Therapeutic Directions.

Cholesteatoma, an abnormal accumulation of keratinized squamous epithelium in the middle ear, occurs as a locally invasive but histologically benign lesion. Its capacity for bone erosion leads to significant complications, including hearing loss, facial nerve paralysis, and intracranial infections. Chronic inflammation is central to its pathogenesis, with proinflammatory mediators like TNF-α, IL-1β, and IL-6 activating signaling pathways, such as NF-κB, JAK/STAT, and MAPK. These pathways contribute to epithelial hyperproliferation and extracellular matrix degradation mediated by Matrix Metalloproteinases (MMPs). Dysregulation of epithelial cell behavior, involving altered keratinocyte function and reduced E-cadherin-mediated adhesion, may facilitate lesion formation and expansion. Furthermore, aberrant signaling involving growth factors (e.g., EGF, TGF-β) and dysregulation of osteoclast activity via the RANKL pathway contribute to enhanced bone erosion and tissue invasion. Emerging research highlights potential roles of the c-MYC proto-oncogene, microRNAs, and Sonic hedgehog signaling in disease progression, offering deeper insights into the pathogenesis. Current management primarily involves surgical excision, yet high recurrence rates emphasize the need for adjunctive therapeutic strategies. Potential future directions include modulating key pathways, such as NF-κB, MMP activity, and RANKL signaling, as well as exploring interventions related to growth factors and cell adhesion. Integrating molecular insights with clinical research is essential for developing strategies to reduce recurrence and improve patient outcomes.

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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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