TP53 缺失通过上调 NF-κB-IFN-β-MHC-Ia 信号促进骨肉瘤对 NK 细胞的抵抗
TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Long-Term Survival, Illness Severity, and Time-to-Treatment Analysis in Dogs with Immune-Mediated Hemolytic Anemia Following Intravenous Allogeneic Mesenchymal Stem Cell Therapy: A Multicohort Follow-Up Study.
Long-Term Survival, Illness Severity, and Time-to-Treatment Analysis in Dogs with Immune-Mediated Hemolytic Anemia Following Intravenous Allogeneic Mesenchymal Stem Cell Therapy: A Multicohort Follow-Up Study.
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犬类类固醇难治性免疫介导性溶血性贫血(IMHA)具有较高的早期死亡率,而15%-30%对皮质类固醇为基础的治疗无效的病例代表了一个有效选择很少且治疗窗口不断缩窄的群体。
在此前的一项回顾性研究中,静脉注射异体间充质干细胞(MSC)治疗在43只类固醇难治性IMHA患犬中取得了76.7%的血液学成功率。本项多队列随访研究扩展了该工作,通过表征来自同一数据库的137例符合条件患者的疾病严重程度、治疗时间和长期生存情况。在对全部137例符合条件患者(包括非存活队列 n = 57 和寿命登记队列 n = 80)的Kaplan-Meier分析中,主要队列的中位生存期为1,695天(4.6年),而在方案可评估队列(n = 120)中未达到中位生存期。估计1年生存率分别为56.9%(95% CI:48.2%-64.7%)和65.0%(95% CI:55.7%-72.8%),生存概率在8.1年随访期内稳定在约52%。
在57例非存活者中,51例有足够的诊断数据以计算犬溶血性贫血客观评分(CHAOS)评分;三分之二(66.7%)在诊断时达到高风险阈值(CHAOS 3)。这超过了已发表的多中心参考人群估计的约50%,表明Safari非存活队列在就诊时富集了重症患犬。非存活者的中位治疗后生存期为8天(IQR:3-38),仅接受一剂MSC的患犬生存期明显短于接受两剂或以上的患犬(中位4天 vs. 19天,P < 0.01),这与暴发性疾病限制了治疗的完成而非治疗失败相一致。从诊断到治疗的延迟在存活者中比非存活者更短(中位数13天 vs. 25天),这一探索性发现值得前瞻性评估。综合来看,这些发现提示非存活反映了基础疾病的严重程度,而对MSC治疗有反应的犬具有持久多年缓解的潜力。
Steroid-refractory immune-mediated hemolytic anemia (IMHA) in dogs carries high early mortality, and the 15%-30% of cases that fail corticosteroid-based therapy represent a population with few effective options and a narrowing treatment window. In a prior retrospective study, intravenous allogeneic mesenchymal stem cell (MSC) therapy achieved a 76. 7% hematological success rate in 43 dogs with steroid-refractory IMHA. The present multicohort follow-up study extends that work by characterizing illness severity, time-to-treatment, and long-term survival across 137 eligible patients from the same database. In Kaplan-Meier analysis of all 137 eligible patients, comprising both the nonsurvivor cohort ( n = 57) and the lifespan registry ( n = 80), median survival was 1,695 days (4. 6 years) in the primary cohort and was not reached in the protocol-assessable cohort ( n = 120). Estimated 1-year survival was 56. 9% (95% CI: 48. 2%-64. 7%) and 65. 0% (95% CI: 55. 7%-72. 8%), respectively, and the survival probability stabilized at approximately 52% through 8.
1 years of follow-up. Among the 57 nonsurvivors, 51 had sufficient diagnostic data to calculate a Canine Hemolytic Anemia Objective Score (CHAOS) score; two-thirds (66. 7%) met the high-risk threshold (CHAOS 3) at diagnosis. This exceeds the approximately 50% estimated from a published multicenter reference population, indicating that the Safari nonsurvivor cohort was enriched for severely ill dogs at presentation. Median post-treatment survival in nonsurvivors was 8 days (IQR: 3-38), and dogs receiving only one MSC dose had markedly shorter survival than those receiving two or more (median 4 vs.
19 days, P < 0. 01), consistent with fulminant disease limiting completion of therapy rather than treatment failure. Diagnosis-to-treatment delay was shorter in survivors than in nonsurvivors (median 13 vs. 25 days), an exploratory finding warranting prospective evaluation. Taken together, these findings suggest that nonsurvival reflects the severity of the underlying disease and that dogs who respond to MSC therapy have potential for durable multiyear remission.
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