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癌症患者初始剂量表柔比星/多西他赛后的血浆高迁移率族蛋白 B-1

Plasma HMGB-1 after the initial dose of epirubicin/docetaxel in cancer.

机构信息

Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna, Austria.

出版信息

Eur J Clin Invest. 2013 Mar;43(3):286-91. doi: 10.1111/eci.12043. Epub 2013 Jan 25.

Abstract

BACKGROUND

The response of breast cancer patients to neoadjuvant chemotherapy (NCT) is highly heterogeneous, and reliable predictive instruments remain to be defined. High-mobility group box-1 (HMGB-1) protein is a cell death marker, which is easily detectable in plasma. We hypothesized that the initial dose of NCT with epirubicin/docetaxel induces changes in plasma HMGB-1 which could allow for an early prediction of response to therapy.

MATERIALS AND METHODS

First, we analysed whether epirubicin/docetaxel releases HMGB-1 from HCC1143 breast cancer cells in vitro. Thereafter, plasma HMGB-1 levels before and 1-4 days after the first dose of epirubicin/docetaxel-based NCT were determined in 41 breast cancer patients and correlated with pathological response to treatment.

RESULTS

Treatment of HCC1143 cells with epirubicin/docetaxel resulted in a significant HMGB-1 release in vitro. In vivo, HMGB-1 levels increased significantly only in responders (pathological complete response or partial remission, n = 22) but not in nonresponders (stable or progressive disease, n = 19).

CONCLUSION

Our data suggest that early dynamic changes of plasma HMGB1 could be a promising biomarker to predict the final response to NCT in breast cancer patients.

摘要

背景

乳腺癌患者对新辅助化疗(NCT)的反应具有高度异质性,可靠的预测工具仍有待确定。高迁移率族蛋白 B1(HMGB-1)蛋白是一种细胞死亡标志物,在血浆中很容易检测到。我们假设,表阿霉素/多西紫杉醇的初始 NCT 剂量会引起血浆 HMGB-1 的变化,从而可以早期预测对治疗的反应。

材料和方法

首先,我们分析了表阿霉素/多西紫杉醇是否会从 HCC1143 乳腺癌细胞中释放 HMGB-1。然后,在 41 名乳腺癌患者中,在接受表阿霉素/多西紫杉醇为基础的 NCT 第一剂前和第 1-4 天测定血浆 HMGB-1 水平,并与治疗的病理反应相关联。

结果

表阿霉素/多西紫杉醇处理 HCC1143 细胞导致体外 HMGB-1 明显释放。在体内,仅在应答者(病理完全缓解或部分缓解,n = 22)中 HMGB-1 水平显著增加,而在无应答者(稳定或进展性疾病,n = 19)中则没有增加。

结论

我们的数据表明,血浆 HMGB1 的早期动态变化可能是预测乳腺癌患者对 NCT 最终反应的有前途的生物标志物。

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