Evaluation on the curative effect of sorafenib tosylate in patients with hepatocellular carcinomavia regulatory T cells
-
摘要:
目的从T细胞免疫角度评价甲苯磺酸索拉非尼(多吉美)治疗原发性肝癌（HCC）患者的疗效评价 方法将肝癌患者分为多吉美组与对照组各30例，在治疗前、治疗6个月及12个月分别检测HCC患者外周血调节性T细胞(Treg）及其细胞因子白介素10（IL-10）及转化生长因子b1（TGF-b1）含量的检测；检测其甲胎蛋白（AFP）及丙氨酸氨基转移酶(ALT)含量；计算12月随访月的存活情况。 结果（1）治疗6个月后，两组上述3者的水平已较明显下降（P<0.05），且治疗12月后下降更为显著（P<0.05）。在组间比较方面，治疗12个月后，多吉美组Treg、IL-10及TGF-b1均显著低于对照组（P<0.05），且多吉美组在治疗第6个月时已明显低于对照组；（2）随访期内多吉美组的AFP及ALT水平均明显低于对照组（分别为P=0.000,0.001）；（3）相关性分析发现，Treg、IL-10及TGF-b1三者之间与呈正相关性；以上这三者当中的任意一者，与AFP及ALT均呈正相关性；（4）随访的12给月内多吉美组2组死亡，而对照组为5人，但两组的死亡例数构成无统计学差异（P=0.067），但多吉美组的12月内平均生存时间显著长于对照组（P=0.041）。 结论甲苯磺酸索拉非尼可有效抑制Treg及其细胞因子，且降低AFP浓度，这可能是该药取得较好临床效果的机制之一。 Abstract:Objective To evaluate the curative effect of sorafenib tosylate in patients with hepatocellular carcinoma (HCC) via regulatory T cells. Methods The HCC patients were divided into control group and the beauty of messenger 30 cases, before and during treatment, treatment for 6 months and 12 months respectively detection HCC patients peripheral regulatory T cells (Treg) and cytokine interleukin 10 (IL-10) and transformation growth factor b1 (TGF-b1) content detection; Testing the alpha-fetoprotein (AFP) and alanine aminotransferase (ALT) content; 12 months follow-up calculation on survival situation. Results 1) treatment for 6 months later, two groups of the above three level is decreased obviously (P<0.05), and the treatment after December drop more significant (P<0.05). Comparison between groups, treatment after 12 months, beauty messenger Treg group, IL-10 and TGF-b1 were significantly lower than that in control group (P<0.05), and the messenger beauty group in the treatment of 6 months already was significantly lower than the control group.1) during the period of follow-up messenger beauty group of AFP and ALT levels were significantly lower than that in control group (respectively, P=0.000, 0.001). 3) the correlation analysis found that Treg, IL-10 and TGF-b1 between three parturients; More than any of these three things, and AFP and ALT are of parturients. 4) follow-up of 12 months to messenger beauty group 2 group of death, and control group for five people, but two groups of death number constitute no statistically significant (P=0.067), but the beauty of the messenger group 12 month average survival time was significantly longer than that in control group (P=0.041). Conclusion Toluene sulfonic acid sorafenib can inhibit the Treg and cell factor, and reduce the AFP concentration, this may be the drug with good clinical effect of the mechanism. -
表 1 两组患者不同时间段的Treg及其细胞因子的含量比较（x±s）
分组 Treg IL-10 TGF-b1 治疗前 治疗6 个月 治疗12 个月 治疗前 治疗6 个月 治疗12 个月 治疗前 治疗6 个月 治疗12 个月 多吉美组 8.73±2.52b 6.06±±1.85a 3.47±0.49ab 7.15±1.94b 4.96±1.71a 2.48±0.79ab 5.39±2.13b 4.10±1.96a 1.92±0.83ab 对照组 8.54±2.61b 7.18±1.98a 5.29±1.38ab 6.93±1.87b 4.49±1.63a 3.58±1.28ab 5.13±2.41 4.48±2.02 3.27±1.65ab t 0.813 -1.772 -2.265 0.936 0.762 -1.554 0.882 -0.72 -2.237 P 0.382 0.037 0.008 0.145 0.258 0.021 0.362 0.417 0.01 与治疗前比较,aP<0.05; 与治疗6个月比较,bP<0.05. 
下载: 导出CSV
表 2 随访期内两组情况的情况比较（x±s）
分组 n AFP ALT 12 月内死亡例数 第1 个12 月内平均生存时间（月） 多吉美组 30 16.78±8.96 38.29±16.11 2 9.38±2.29 对照组 30 52.01±21.36 54.58±23.19 5 7.82±1.68 统计量 t=-12.922 t=-8.821 χ2=1.992 t=1.882 P 0 0.001 0.067 0.041
下载: 导出CSV
-
[1] Kakita N, Kanto T, Itose I, et al. Comparative analyses of regulatory T cell subsets in patients with hepatocellular carcinoma:a crucial role of CD25(-)FOXP3(-)T cells[J]. Int J Cancer, 2012, 131(11): 2573-83. doi: 10.1002/ijc.v131.11 [2] Pedroza-Gonzalez A, Verhoef C, Ijzermans JN, et al. Activated tumor-infiltrating CD4 + regulatory T cells restrain antitumor immunity in patients with primary or metastatic liver Cancer[J]. Hepatology, 2013, 57(1): 183-94. doi: 10.1002/hep.26013 [3] Cabrera R, Ararat M, Xu Y, et al. Immune modulation of effector CD4+and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma[J]. Cancer Immunol Immunother, 2012, 6 (8): 112-4. [4] 刘辉, 朱争艳, 王鹏, 等. 原发性肝癌患者CD4~+CD25~+CD127~ (low)调节性T细胞的检测及意义[J]. 中国肿瘤临床, 2011, 38(22): 1377-80. http://www.cnki.com.cn/Article/CJFDTOTAL-ZGZL201122007.htm [5] 佚名. 标题为空[J]. 张国伟索拉非尼治疗原发性肝癌的不良反应及其处理中国临床药理学与治疗学, 2011, 16(10): 1157-9. [6] 郭美姿, 江华, 牛完萍, 等. 高龄肝癌患者CD4+CD25+调节性T细胞及转化生长因子-β1检测的临床意义[J]. 中华老年医学杂志, 2012, 31(7): 589-92. http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_zhlnyx201207013 [7] 沈顺利, 梁力建. 调节性T细胞与原发性肝癌的免疫治疗[J]. 中华肝胆外科杂志, 2010, 16(4): 314-7. http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_zhgdwk201004021 [8] Flörcken A, Takvorian A, Van Lessen A, et al. Sorafenib,but not sunitinib,induces regulatory T cells in the peripheral blood of patients with metastatic renal cell carcinoma[J]. Anticancer Drugs, 2012, 23(3): 298-302. doi: 10.1097/CAD.0b013e32834ee2b1 [9] Busse A, Asemissen AM, Nonnenmacher AA, et al. Immunomodulatory effects of sorafenib on peripheral immune effector cells in metastatic renal cell carcinoma[J]. Eur J Cancer, 2011, 47(5): 690-6. doi: 10.1016/j.ejca.2010.11.021 [10] Desar IM, Jacobs J, Hulsbergen-vandekaa CA, et al. Sorafenib reduces the percentage of tumour infiltrating regulatory T cells in renal cell carcinoma patients[J]. Int J Cancer, 2011, 129(2): 507-12. doi: 10.1002/ijc.25674 [11] Kakita N, Kanto T, Itose I, et al. Comparative analyses of regulatory T cell subsets in patients with hepatocellular carcinoma: A crucial role of CD25-FOXP3-T cells[J]. Int J Cancer, 2012, 131 (11): 2573-83. doi: 10.1002/ijc.v131.11 [12] Chen KJ, Lin SZ, Zhou L, et al. Selective recruitment of regulatory T cell through CCR6-CCL20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis[J]. PLoS One, 2011, 6(9): e24671. doi: 10.1371/journal.pone.0024671 -
点击查看大图
图(1) / 表(2)
计量
- 文章访问数: 645
- HTML全文浏览量: 208
- PDF下载量: 0
- 被引次数: 0
