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吉非替尼治疗的非小细胞肺癌患者可溶性白细胞介素-2受体水平升高。

Elevation of soluble interleukin-2 receptor in patients with non-small cell lung cancer treated with gefitinib.

作者信息

Kanazawa Shigenori, Yamaguchi Kazuyuki, Kinoshita Yoshimi, Komiyama Yutaka, Muramatsu Mikiko, Nomura Shosaku

机构信息

First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan.

出版信息

J Cancer Res Clin Oncol. 2006 Nov;132(11):719-25. doi: 10.1007/s00432-006-0120-x. Epub 2006 Jul 12.

Abstract

PURPOSE

We previously reported that plasma thromboxan B(2), soluble P-selectin, and serum regulated on activation, normal T-cell expressed and secreted (RANTES) were elevated after gefitinib treatment. We hypothesized that gefitinib could activate T-lymphocytes via activated platelets, and so we measured serum levels of soluble interleukin-2 receptor (sIL-2R) in patients medicated with gefitinib.

METHODS

Twenty-one patients with non-small cell lung cancer (NSCLC) were entered into this study. All patients received gefitinib over 2 weeks without severe adverse effects. Blood samples were withdrawn from all patients before and after the administration of gefitinib and plasma soluble P-selectin, serum RANTES, and serum sIL-2R were measured by enzyme-linked immunosolvent assay. In addition, we carried out the basic study of the interleukin-2 receptor (IL-2R) expression on CD4(+) lymphocytes by RANTES.

RESULTS

Plasma soluble P-selectin, serum RANTES, and serum sIL-2R levels increased significantly in patients receiving gefitinib treatment for 1 and 2 weeks. RANTES did not induce the expression of IL-2R on CD4(+) lymphocyte. However, the anti-CD3 monoclonal antibody-induced expression of IL-2R was enhanced by the addition of RANTES.

CONCLUSION

Our finding indicated that lymphocytes were activated by gefitinib treatment. We think that sIL-2R elevation after gefitinib administration may be a factor positively effecting patients with NSCLC. It is deemed possible that the effect of gefitinib is induced not only by its blocking of the tyrosine kinase of epidermal growth factor receptor but also by antitumor immunity via its activation of T-cells.

摘要

目的

我们之前报道过,吉非替尼治疗后血浆血栓素B2、可溶性P选择素以及血清中受激活调节正常T细胞表达和分泌因子(RANTES)水平升高。我们推测吉非替尼可能通过激活的血小板激活T淋巴细胞,因此我们检测了接受吉非替尼治疗患者的血清可溶性白细胞介素-2受体(sIL-2R)水平。

方法

21例非小细胞肺癌(NSCLC)患者纳入本研究。所有患者接受为期2周的吉非替尼治疗,未出现严重不良反应。在给予吉非替尼前后采集所有患者的血样,采用酶联免疫吸附测定法检测血浆可溶性P选择素、血清RANTES和血清sIL-2R。此外,我们进行了RANTES对CD4(+)淋巴细胞白细胞介素-2受体(IL-2R)表达的基础研究。

结果

接受吉非替尼治疗1周和2周的患者血浆可溶性P选择素、血清RANTES和血清sIL-2R水平显著升高。RANTES未诱导CD4(+)淋巴细胞上IL-2R的表达。然而,添加RANTES可增强抗CD3单克隆抗体诱导的IL-2R表达。

结论

我们的研究结果表明吉非替尼治疗可激活淋巴细胞。我们认为吉非替尼给药后sIL-2R升高可能是对NSCLC患者产生积极影响的一个因素。吉非替尼的作用可能不仅是通过阻断表皮生长因子受体的酪氨酸激酶,还可能是通过激活T细胞产生抗肿瘤免疫。

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