Tocilizumab, a proposed therapy for the cachexia of Interleukin6-expressing lung cancer.
Tocilizumab, a proposed therapy for the cachexia of Interleukin6-expressing lung cancer.
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DOI：
10.1371/journal.pone.0102436
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Takahashi K
中科院分区：
文献类型：
--
作者：
Ando K;Takahashi F;Kato M;Kaneko N;Doi T;Ohe Y;Koizumi F;Nishio K;Takahashi K
我们先前报道了IL-6在癌症恶病质小鼠模型中的作用，目前记录了一名患者，其中抗IL-6受体抗体托珠单抗显著改善了IL-6过表达肺癌诱导的恶病质。尽管有缓解癌症恶病质的潜力，但托珠单抗尚未被批准用于这种临床用途。因此，在我们计划的托珠单抗临床试验之前，我们设计了这里描述的两项研究，以评估肺癌患者的IL-6水平和托珠单抗在人类癌症恶病质小鼠模型中的作用。首先，我们检测了肺癌患者血清IL-6水平，并分析了其与恶病质和生存的关系。接下来，我们检查了托珠单抗（MR 16 -1）的啮齿动物类似物在实验性恶病质模型中的作用。恶病质组血清IL-6水平高于无恶病质组。在化疗耐药肺癌患者中，高IL-6血清水平与生存率密切相关，影响其预后的临界水平为21 pg/mL。同时，移植表达IL-6的刘易斯肺癌细胞引起小鼠恶病质，然后接受MR 16 -1或0.9%盐水。两组的肿瘤生长相似;然而，MR 16 -1组体重减轻较少，保持更好的食物和水摄入量，血液中的恶病质特征较轻。MR 16 -1还延长了LLC-IL 6移植小鼠的存活（36.6天对28.5天，p = 0.016）。 我们的临床和实验研究表明，血清IL-6是评价恶病质和化疗耐药转移性肺癌患者预后的替代标志物，托珠单抗具有改善预后和改善恶病质的潜力，从而改善患者的生活质量。这一结果极大地鼓励了我们的临床试验，以评估托珠单抗治疗血清IL-6升高患者的安全性和有效性。
We previously reported the role of IL-6 in a murine model of cancer cachexia and currently documented a patient in whom tocilizumab, anti-IL-6 receptor antibody, dramatically improved cachexia induced by IL-6 over-expressing lung cancer. Despite this potential to alleviate cancer cachexia, tocilizumab has not been approved for this clinical use. Therefore, preceding our planned clinical trial of tocilizumab, we designed the two studies described here to evaluate the levels of IL-6 in patients with lung cancer and the effect of tocilizumab in a murine model of human cancer cachexia. First, we measured serum IL-6 levels in patients with lung cancer and analyzed its association with cachexia and survival. Next, we examined the effect of a rodent analog of tocilizumab (MR16-1) in the experimental cachexia model. Serum IL-6 levels were higher in patients with cachexia than those without cachexia. In patients with chemotherapy-resistant lung cancer, a high IL-6 serum level correlated strongly with survival, and the cut-off level for affecting their prognosis was 21 pg/mL. Meanwhile, transplantation of IL-6-expressing Lewis Lung Carcinoma cells caused cachexia in mice, which then received either MR16-1 or 0.9% saline. Tumor growth was similar in both groups; however, the MR16-1 group lost less weight, maintained better food and water intake and had milder cachectic features in blood. MR16-1 also prolonged the survival of LLC-IL6 transplanted mice (36.6 vs. 28.5 days, p = 0.016). Our clinical and experimental studies revealed that serum IL-6 is a surrogate marker for evaluating cachexia and the prognosis of patients with chemotherapy resistant metastatic lung cancer and that tocilizumab has the potential of improving prognosis and ameliorating the cachexia that so devastates their quality of life. This outcome greatly encourages our clinical trials to evaluate the safety and efficacy of tocilizumab treatment for patients with increased serum IL-6.
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影响因子：
82.9
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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作者：
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作者：
AKAIKE, H
通讯作者：
AKAIKE, H