自拟益气抗癌方联合TP方案治疗上皮性卵巢癌疗效及对免疫指标影响
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摘要
目的中药辅助治疗上皮性卵巢癌(epithelial ovarian cancer,EOC)等恶性肿瘤已引起广泛关注。本研究探讨益气抗癌方联合TP方案治疗EOC疗效及对免疫检查点可溶性淋巴细胞活化基因-3(soluble lymphocyte activation gene-3,sLAG-3)、可溶性T细胞免疫球蛋白黏蛋白分子-3(soluble T cell immunoglobulin mucin molecule-3,sTim-3)和可溶性程序性死亡受体-1(soluble programmed cell death protein 1,sPD-1)水平影响。方法选取2012-03-07-2015-05-21郑州市第一人民医院妇科(11例)和郑州市妇幼保健院妇产科(79例)收治的90例EOC患者,随机分为益气抗癌方联合TP方案治疗组45例(观察组)和单纯TP方案治疗组45例(对照组),均行4个周期化疗方案。比较2组近期疗效、远期疗效、骨髓抑制、不良反应情况、免疫检查点sLAG-3、sTim-3及sPD-1水平和T细胞亚群变化。结果观察组治疗总有效率为71.11%,高于对照组的64.44%,但差异无统计学意义;观察组2年生存率为68.89%,高于对照组的46.67%,差异有统计学意义,χ~2=4.555,P=0.033;观察组3年生存率为55.56%,高于对照组的33.33%,差异有统计学意义,χ~2=4.500,P=0.034;对照组和观察组均有不同程度骨髓抑制,但观察组白细胞(white blood cell,WBC)、血红蛋白(hemoglobin,Hb)和血小板(blood platelet,PLT)下降幅度低于对照组;观察组不良反应发生率为20.00%,低于对照组的42.22%,差异有统计学意义,χ~2=5.184,P=0.023;观察组治疗后生活质量改善率为91.11%,高于对照组的68.89%,差异有统计学意义,χ~2=6.944,P=0.008;治疗后,观察组血清sLAG-3水平为53.19±17.42,低于治疗前的139.52±23.83,t=17.300,P<0.001;sTim-3水平为0.96±0.11,低于治疗前的2.92±0.35,t=14.940,P<0.001;sPD-1水平为0.66±0.37,低于治疗前的1.61±0.52,t=9.957,P<0.001。治疗后,观察组CD3+,CD4+和CD4+/CD8+均升高,而对照组患者变化不明显。观察组和对照组患者治疗后Treg均降低,其中观察组降低幅度大于对照组,t=2.361,P=0.021。结论益气抗癌方联合TP方案可改善EOC患者生活质量,降低骨髓抑制和免疫抑制,减轻不良反应,延长患者生存期。
OBJECTIVE Chinese herbal medicines have attracted much attention in the adjuvant treatment of malignant tumors,including epithelial ovarian cancer(EOC).It is of great significance to explore the Chinese herbal medicines with adjuvant therapeutic effects in EOC therapy.The aim of this study was to investigate the efficacy of Yiqi Anticancer Prescription combined with TP regimen in treatment of EOC and its influence on the level of immune checkpoints sLAG-3,sTim-3 and sPD-1.METHODS Ninty cases of EOC patients from 2012-03-07 to 2015-05-21 in the First People's Hospital of Zhengzhou(11 cases)and Women &infants hospital of Zhengzhou(79 cases)were selected and were randomly divided into two groups:45 cases using Yiqi Anticancer Prescription combined with TP regimen(observation group)and45 cases using TP regimen alone(control group),and these two groups were underwent 4 cycles of chemotherapy.The shortterm curative effect,long-term effect,myelosuppression,adverse reaction,serum immune checkpoints sLAG-3,sTim-3 or sPD-1 and T lymphocyte subsets of the two groups were observed and compared.RESULTS The total effective rate of observation group was higher than control group,but the difference was not statistically significant(71.11%vs 64.44%).The 2 and3 years survival rates were significantly higher than the control group(68.89% vs 46.67%,χ~2=4.555,P=0.033;55.56%vs 33.33%,χ~2=4.500,P=0.034).The two groups had different degrees of bone marrow suppression.However,the descending ranges of WBC,Hb and PLT for observation group were lower than control group.In addition,the adverse reaction rate of observation group was also lower than that of control group(20.00%vs 42.22%,χ~2=5.184,P=0.023).The life quality improvement rate of observation group after treatment was significantly higher than control group(91.11%vs 68.89%,χ~2=6.944,P=0.008).The immune checkpoints sLAG-3,sTim-3 and sPD-1 in observation group decreased significantly after treatment,which were lower than that before treatment(53.19±17.42 vs 139.52±23.83,t=17.300,P<0.001;0.96±0.11 vs 2.92±0.35,t=14.940,P<0.001;0.66±0.37 vs 1.61±0.52,t=9.957,P<0.001).Moreover,CD3+,CD4+and CD4+/CD8+of observation group after treatment were significantly increased,while no significant was observed in control group.In addition,Treg in the observation group and the control group were decreased obviously after treatment,and the descend range in observation group was more significant(t=2.361,P=0.021).CONCLUSION The combination of Yiqi Anticancer Prescription and TP can improve the life quality of patients with EOC,and can reduce the inhibition of bone marrow and immune suppression,and also alleviate the adverse reactions,and prolong survival time.
OBJECTIVE Chinese herbal medicines have attracted much attention in the adjuvant treatment of malignant tumors,including epithelial ovarian cancer(EOC).It is of great significance to explore the Chinese herbal medicines with adjuvant therapeutic effects in EOC therapy.The aim of this study was to investigate the efficacy of Yiqi Anticancer Prescription combined with TP regimen in treatment of EOC and its influence on the level of immune checkpoints sLAG-3,sTim-3 and sPD-1.METHODS Ninty cases of EOC patients from 2012-03-07 to 2015-05-21 in the First People's Hospital of Zhengzhou(11 cases)and Women &infants hospital of Zhengzhou(79 cases)were selected and were randomly divided into two groups:45 cases using Yiqi Anticancer Prescription combined with TP regimen(observation group)and45 cases using TP regimen alone(control group),and these two groups were underwent 4 cycles of chemotherapy.The shortterm curative effect,long-term effect,myelosuppression,adverse reaction,serum immune checkpoints sLAG-3,sTim-3 or sPD-1 and T lymphocyte subsets of the two groups were observed and compared.RESULTS The total effective rate of observation group was higher than control group,but the difference was not statistically significant(71.11%vs 64.44%).The 2 and3 years survival rates were significantly higher than the control group(68.89% vs 46.67%,χ~2=4.555,P=0.033;55.56%vs 33.33%,χ~2=4.500,P=0.034).The two groups had different degrees of bone marrow suppression.However,the descending ranges of WBC,Hb and PLT for observation group were lower than control group.In addition,the adverse reaction rate of observation group was also lower than that of control group(20.00%vs 42.22%,χ~2=5.184,P=0.023).The life quality improvement rate of observation group after treatment was significantly higher than control group(91.11%vs 68.89%,χ~2=6.944,P=0.008).The immune checkpoints sLAG-3,sTim-3 and sPD-1 in observation group decreased significantly after treatment,which were lower than that before treatment(53.19±17.42 vs 139.52±23.83,t=17.300,P<0.001;0.96±0.11 vs 2.92±0.35,t=14.940,P<0.001;0.66±0.37 vs 1.61±0.52,t=9.957,P<0.001).Moreover,CD3+,CD4+and CD4+/CD8+of observation group after treatment were significantly increased,while no significant was observed in control group.In addition,Treg in the observation group and the control group were decreased obviously after treatment,and the descend range in observation group was more significant(t=2.361,P=0.021).CONCLUSION The combination of Yiqi Anticancer Prescription and TP can improve the life quality of patients with EOC,and can reduce the inhibition of bone marrow and immune suppression,and also alleviate the adverse reactions,and prolong survival time.
引文
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[3]杜雪莲,王聪,刘明,等.紫杉醇加卡铂与吉西他滨为基础联合化疗序贯用药对降低上皮性卵巢癌复发的临床研究[J].中国实用妇科与产科杂志,2015,31(1):59-64.
[4]李宁,田永巍,高岭,等.卵巢癌恶性腹腔积液TP方案静脉联合循环热灌注化疗临床疗效分析[J].中华肿瘤防治杂志,2017,24(2):119-123.
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[7]朱熠,张国楠.卵巢癌、输卵管癌和腹膜癌FIGO 2013分期和临床意义的解读[J].肿瘤预防与治疗,2015,28(5):291-294.
[8]崔伟,刘爱珍,谢琼,等.黄芪多糖联合新辅助化疗TP方案对宫颈癌患者免疫抑制细胞Treg和MDSC的影响[J].华南国防医学杂志,2018,32(4):30-33.
[9]Torre LA,Trabert B,DeSantis CE,et al.Ovarian cancer statistics,2018[J].CA Cancer J Clin,2018,68(4):284-296.
[10]Zhang C,Deng WY,Li N,et al.Clinical observation and therapeutic evaluation of intravenous pump of recombinant human endostatin combined with TP regimen in treating patients with advanced ovarian cancer[J].Chronic Dis Transl Med,2015,(3):158-162.
[11]杨均.TP方案化疗对上皮性卵巢癌患者免疫功能的影响及意义[J].中国实验诊断学,2014,18(5):797-798.
[12]Davoodzadeh GM,Kardar GA,Saeedi Y,et al.Exhaustion of Tlymphocytes in the tumor microenvironment:significance and effective mechanisms[J].Cell Immunol,2017,17(11):983-1000.
[13]管艳芹,刘建群,吴秀芳.西黄丸联合TP方案治疗晚期卵巢癌术后疗效及免疫功能的影响[J].河北医药,2015,37(22):3429-3431.
[14]Wu M,Chen X,Lou J,et al.Changes in regulatory T cells in patients with ovarian cancer undergoing surgery:Preliminary results[J].Int Immunopharmacol,2017,47(4):244-250.
[15]Pietzner K,Nasser S,Alavi S,et al.Checkpoint-inhibition in ovarian cancer:rising star or just a dream?[EB/OL].J Gynecol Oncol,2018,29(6):e93[2019-02-18].https://www.onacademic.com/detail/journal_1000040852933810_ed94.html.
[16]Li YL,Sun BG,Xiang T,et al.Effect of invigorating spleen and detoxification decoction on MHCⅠ/MHCⅡin spleen-deficiency liver cancer rats survival[J].J Chin Med Mat,2014,37(3):454-460.
[17]Guo Q,Li J,Lin H.Effect and molecular mechanisms of traditional Chinese medicine on regulating tumor immunosuppressive microenvironment[J].Biomed Res Int,2015,2015(2):261620.
[18]Chang Y,Zhao Y,Zhan H,et al.Bufalin inhibits the differentiation and proliferation of human osteosarcoma cell line hMG63-derived cancer stem cells[J].Tumour Biol,2014,35(2):1075-1082.
[19]庄旭升,张欣.益气抗癌方联合含奥沙利铂方案TACE术对原发性肝癌血清肿瘤相关巨噬细胞及相关细胞因子水平的影响[J].中华中医药学刊,2018,36(5):1202-1205.
[20]Liu P,Zhao H,Luo Y.Anti-aging implications of astragalus membranaceus(huangqi):a well-known Chinese tonic[J].Aging Dis,2017,8(6):868-886.
[2]Rosen B,Laframboise S,Ferguson S,et al.The impacts of neoadjuvant chemotherapy and of debulking surgery on survival from advanced ovarian cancer[J].Gynecol Oncol,2014,134(3):462-467.
[3]杜雪莲,王聪,刘明,等.紫杉醇加卡铂与吉西他滨为基础联合化疗序贯用药对降低上皮性卵巢癌复发的临床研究[J].中国实用妇科与产科杂志,2015,31(1):59-64.
[4]李宁,田永巍,高岭,等.卵巢癌恶性腹腔积液TP方案静脉联合循环热灌注化疗临床疗效分析[J].中华肿瘤防治杂志,2017,24(2):119-123.
[5]Imai Y,Hasegawa K,Matsushita H,et al.Expression of multiple immune checkpoint molecules on T cells in malignant ascites from epithelial ovarian carcinoma[J].Oncol Lett,2018,15(5):6457.
[6]Mittica G,Genta S,Aglietta M,et al.Immune checkpoint inhibitors:a new opportunity in the treatment of ovarian cancer?[J].Int J Mol Sci,2016,17(7):1169.
[7]朱熠,张国楠.卵巢癌、输卵管癌和腹膜癌FIGO 2013分期和临床意义的解读[J].肿瘤预防与治疗,2015,28(5):291-294.
[8]崔伟,刘爱珍,谢琼,等.黄芪多糖联合新辅助化疗TP方案对宫颈癌患者免疫抑制细胞Treg和MDSC的影响[J].华南国防医学杂志,2018,32(4):30-33.
[9]Torre LA,Trabert B,DeSantis CE,et al.Ovarian cancer statistics,2018[J].CA Cancer J Clin,2018,68(4):284-296.
[10]Zhang C,Deng WY,Li N,et al.Clinical observation and therapeutic evaluation of intravenous pump of recombinant human endostatin combined with TP regimen in treating patients with advanced ovarian cancer[J].Chronic Dis Transl Med,2015,(3):158-162.
[11]杨均.TP方案化疗对上皮性卵巢癌患者免疫功能的影响及意义[J].中国实验诊断学,2014,18(5):797-798.
[12]Davoodzadeh GM,Kardar GA,Saeedi Y,et al.Exhaustion of Tlymphocytes in the tumor microenvironment:significance and effective mechanisms[J].Cell Immunol,2017,17(11):983-1000.
[13]管艳芹,刘建群,吴秀芳.西黄丸联合TP方案治疗晚期卵巢癌术后疗效及免疫功能的影响[J].河北医药,2015,37(22):3429-3431.
[14]Wu M,Chen X,Lou J,et al.Changes in regulatory T cells in patients with ovarian cancer undergoing surgery:Preliminary results[J].Int Immunopharmacol,2017,47(4):244-250.
[15]Pietzner K,Nasser S,Alavi S,et al.Checkpoint-inhibition in ovarian cancer:rising star or just a dream?[EB/OL].J Gynecol Oncol,2018,29(6):e93[2019-02-18].https://www.onacademic.com/detail/journal_1000040852933810_ed94.html.
[16]Li YL,Sun BG,Xiang T,et al.Effect of invigorating spleen and detoxification decoction on MHCⅠ/MHCⅡin spleen-deficiency liver cancer rats survival[J].J Chin Med Mat,2014,37(3):454-460.
[17]Guo Q,Li J,Lin H.Effect and molecular mechanisms of traditional Chinese medicine on regulating tumor immunosuppressive microenvironment[J].Biomed Res Int,2015,2015(2):261620.
[18]Chang Y,Zhao Y,Zhan H,et al.Bufalin inhibits the differentiation and proliferation of human osteosarcoma cell line hMG63-derived cancer stem cells[J].Tumour Biol,2014,35(2):1075-1082.
[19]庄旭升,张欣.益气抗癌方联合含奥沙利铂方案TACE术对原发性肝癌血清肿瘤相关巨噬细胞及相关细胞因子水平的影响[J].中华中医药学刊,2018,36(5):1202-1205.
[20]Liu P,Zhao H,Luo Y.Anti-aging implications of astragalus membranaceus(huangqi):a well-known Chinese tonic[J].Aging Dis,2017,8(6):868-886.