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恶性胸膜间皮瘤患者治疗期间可溶性间皮素的动力学

Kinetics of soluble mesothelin in patients with malignant pleural mesothelioma during treatment.

作者信息

Grigoriu Bogdan D, Chahine Bachar, Vachani Anil, Gey Thomas, Conti Massimo, Sterman Daniel H, Marchandise Genevieve, Porte Henri, Albelda Steven M, Scherpereel Arnaud

机构信息

INSERM Unit 774, Institut Pasteur of Lille, Lille, France.

出版信息

Am J Respir Crit Care Med. 2009 May 15;179(10):950-4. doi: 10.1164/rccm.200807-1125OC. Epub 2009 Feb 6.

Abstract

RATIONALE

Previous data suggested that serum levels of soluble mesothelin (SM) are related to tumor size and may have prognostic significance in malignant pleural mesothelioma (MPM).

OBJECTIVES

We tested the hypothesis that this marker could also be useful for monitoring response to treatment.

METHODS

Serial measurements of SM were determined in 40 patients diagnosed with MPM and subjected to gene-transfer therapy using intrapleural infusion of an adenoviral vector expressing human IFN-beta or conventional treatment (mainly chemotherapy).

MEASUREMENTS AND MAIN RESULTS

In patients with baseline SM levels greater than 1 nM/L and disease progression after therapy, SM levels increased by 2.1 nM/L at two, 5.2 nM/L at four and 1.3 nM/L at 6 months. Patients with initial SM below 1 nM/L had a similar but more moderate increase of SM over time. Patients who responded to treatment or were considered stable had an initial small decrease of SM followed by a return to baseline values after 6 months of follow-up. In patients with baseline SM levels greater than 1 nM/L, increasing levels were associated with a significantly shorter median survival than in patients with stable or decreasing SM levels (4.4 vs. 27.7 months; P = 0.012).

CONCLUSIONS

Increasing serum levels of SM were associated with disease progression and worse outcome, whereas stable or decreasing values suggested response to treatment. If confirmed in larger series, SM could be used to monitor patients with malignant pleural mesothelioma under treatment.

摘要

理论依据

既往数据表明,可溶性间皮素(SM)血清水平与肿瘤大小相关,且可能在恶性胸膜间皮瘤(MPM)中具有预后意义。

目的

我们检验了这一标志物也可用于监测治疗反应的假设。

方法

对40例诊断为MPM并接受基因转移治疗(通过胸腔内注入表达人干扰素-β的腺病毒载体)或传统治疗(主要为化疗)的患者进行了SM的系列测量。

测量指标及主要结果

基线SM水平大于1 nM/L且治疗后疾病进展的患者,治疗后2个月时SM水平升高2.1 nM/L,4个月时升高5.2 nM/L,6个月时升高1.3 nM/L。初始SM低于1 nM/L的患者随着时间推移SM有类似但更温和的升高。对治疗有反应或病情稳定的患者,SM最初有小幅下降,随访6个月后恢复至基线值。基线SM水平大于1 nM/L的患者中,与SM水平稳定或下降的患者相比,SM水平升高与中位生存期显著缩短相关(4.4个月对27.7个月;P = 0.012)。

结论

血清SM水平升高与疾病进展及更差的预后相关,而稳定或下降的值提示对治疗有反应。如果在更大规模的研究中得到证实,SM可用于监测接受治疗的恶性胸膜间皮瘤患者。

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