数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
证据级别：摘要级。本条依据 PubMed 结构化摘要与元数据撰写，付费墙全文未获取、未逐节核验，本站未做任何数值推算补全。
研究问题
Dysregulation of the cyclin D1-CDK4/6-Rb axis and the PI3K/Akt/mTOR pathway are hallmark features of proliferative disorders, including lymphangioleiomyomatosis (LAM), a rare lung disease characterized by TSC1/2 loss and hyperactive mTORC1.
方法
These findings offer a potential strategy for alternative or combination treatments in patients with lymphangioleiomyomatosis.
核心结论
We investigated the impact of the CDK4/6i palbociclib on mTORC1 signaling in TSC2-null human-derived cells, TSC2-deficient mouse embryonic fibroblasts (MEFs), and cellular breast cancer models.；Mechanisms of crosstalk of cell cycle and mTOR pathways, and effect of palbociclib on autophagic and cell death markers were assessed.；Pre-clinical therapeutic efficacy was validated in vivo using a novel chick chorioallantoic membrane (CAM) xenograft model of LAM.；Palbociclib treatment robustly suppressed mTORC1 activity across multiple genetic backgrounds. ‖ 结论：These findings identify CDK4/6 as a critical regulator that not only suppresses hyperactive mTORC1 activity in different cellular contexts but also blocks pro-survival autophagy by converting a growth-suppressive response into apoptotic cell death.
局限
未能获取全文，具体设计细节、失访与统计学处理无法核验。
对本项目的价值
★★★☆☆ 营养感知与自噬轴决定"干预窗口 + 剂量方案"，是组合疗法的时间锚。
原文题录
- 英文标题：CDK4/6 inhibition suppresses mTOR activity and growth in lymphangioleiomyomatosis (LAM).
- 期刊与标识：Biochim Biophys Acta Mol Basis Dis · PMID 42946026 · DOI 10.1016/j.bbadis.2026.168513**
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
关于本文的文献来源：本站依据 IMA 知识库「五刊监控·深度文献卡片」（SOP §4.2 摘要级）撰写，依据期刊公开摘要与 PubMed 元数据；付费墙全文未获取之处已标注「待补全文」，未做任何数值推算补全。