生物免疫治疗联合化疗对食管癌患者血清指标及癌组织survivin蛋白的影响
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摘要
目的探讨DC-CIK联合化疗用于治疗食管癌的临床疗效,及其对患者血清指标和癌组织survivin蛋白表达的影响。方法选取收治的食管癌患者90例。根据手术治疗方式不同分为研究组和对照组,每组45例。研究组患者给予DC-CIK联合化疗进行治疗,对照组给予化疗进行治疗。观察患者的治疗效果,血清中Stathmin、Cyfra21-1、c-met、sMICA水平变化,肿瘤组织中survivin蛋白阳性率以及不良反应状况。结果研究组的疾病控制率为91.11%显著高于对照组的62.22%(P<0.05);治疗后,2组患者血清中Stathmin、Cyfra21-1、c-met、sMICA均较治疗前显著下降(P<0.05),且研究组水平显著低于对照组(P<0.05);研究组患者的癌组织survivin蛋白阳性率为66.67%显著低于对照组的93.33%(P<0.05);在血液学毒性、食管炎症以及肝肾功能方面,2组患者差异无统计学意义(P>0.05);研究组非感染性发热的发生率为71.11%高于对照组的26.67%(P<0.05)。结论 DC-CIK联合化疗能够有效抑制肿瘤细胞活性以及杀灭肿瘤细胞,有效降低患者血清中Stathmin、Cyffa21-1、c-met、sMICA,以及食管癌组织中survivin蛋白的阳性率,且无明显不良反应。
Objective To observe the clinical efficacy of DC-CIK combined with chemotherapy in treatment of esophageal cancer,and its effects on serum indexes and survivin protein expression. Methods A total of 90 patients with esophageal cancer who were admitted and treated in our hospital from May 2015 to May 2017 were enrolled in the study. According to difference therapeutic methods,these patients were divided into research group(n=45) and control group(n=45).The patients in research group were treated by DC-CIK combined with chemotherapy,while the patients in control group were treated by chemotherapy only.The efficacy,the changes of serum levels of Stathmin,Cyfra21-1,c-met,sMICA,the positive rate of survivin protein in tumor tissues and the incidence of adverse reactions were observed and compared between the two grousp.Results The disease control rate in research group was 91.11%,which was significantly higher than that(62.22%) in control group(P<0.05). After treatment,the serum levels of Stathmin,Cyfra21-1,c-met and sMICA in both groups were significantly decreased(P<0.05),moreover,which in research group were significantly lower than those in control group(P<0.05).The positive rate of survivin protein in research group was 66.67%,which was significantly lower than that(93.33%) in control group(P<0.05). There were no significant differences in hematological toxicity,esophageal inflammation,liver and kidney function between the two groups(P>0.05).The incidence rate of non-infectious fever in research group was 71.11%,which was significantly higher than that(26.67%) in control group(P<0.05). Conclusion DC-CIK combined with chemotherapy can effectively inhibit tumor cell activity and kill tumor cells,decrease the serum levels of Stathmin,Cyffa21-1,c-met,sMICA,and the positive rate of survivin protein,without obvious adverse reactions.
Objective To observe the clinical efficacy of DC-CIK combined with chemotherapy in treatment of esophageal cancer,and its effects on serum indexes and survivin protein expression. Methods A total of 90 patients with esophageal cancer who were admitted and treated in our hospital from May 2015 to May 2017 were enrolled in the study. According to difference therapeutic methods,these patients were divided into research group(n=45) and control group(n=45).The patients in research group were treated by DC-CIK combined with chemotherapy,while the patients in control group were treated by chemotherapy only.The efficacy,the changes of serum levels of Stathmin,Cyfra21-1,c-met,sMICA,the positive rate of survivin protein in tumor tissues and the incidence of adverse reactions were observed and compared between the two grousp.Results The disease control rate in research group was 91.11%,which was significantly higher than that(62.22%) in control group(P<0.05). After treatment,the serum levels of Stathmin,Cyfra21-1,c-met and sMICA in both groups were significantly decreased(P<0.05),moreover,which in research group were significantly lower than those in control group(P<0.05).The positive rate of survivin protein in research group was 66.67%,which was significantly lower than that(93.33%) in control group(P<0.05). There were no significant differences in hematological toxicity,esophageal inflammation,liver and kidney function between the two groups(P>0.05).The incidence rate of non-infectious fever in research group was 71.11%,which was significantly higher than that(26.67%) in control group(P<0.05). Conclusion DC-CIK combined with chemotherapy can effectively inhibit tumor cell activity and kill tumor cells,decrease the serum levels of Stathmin,Cyffa21-1,c-met,sMICA,and the positive rate of survivin protein,without obvious adverse reactions.
引文
1 左婷婷,郑荣寿,曾红梅,等.中国食管癌发病状况与趋势分析.中华肿瘤杂志,2016,38:703-708.
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3 Hatogai K,Kitano S,Fujii S,et al.Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma.Oncotarget,2016,7:47252-47264.
4 李永姝.细胞因子诱导杀伤细胞免疫治疗食管癌的研究进展.临床和实验医学杂志,2016,15:1967-1969.
5 Detterbeck FC,Boffa DJ,Kim AW,et al.The eighth edition lung cancer stage classification.Chest,2017,151:193.
6 佘明金,马祖胜,李桂芝,等.奥沙利铂联合5-氟尿嘧啶治疗中晚期食管癌的临床疗效及安全性评价.中国临床药理学杂志,2016,32:508-510.
7 傅剑华,谭子辉.食管癌外科治疗的现状与未来展望.中国肿瘤临床,2016,43:507-510.
8 Mao Q,Li L,Zhang C,et al.Clinical effects of immunotherapy of DC-CIK combined with chemotherapy in treating patients with metastatic breast cancer.Pakistan Journal of Pharmaceutical Sciences,2015,28:1055-1058.
9 Banchereau J,Steinman RM.Dendritic cells and the control immunity.Nature,1998,392:245-252.
10 Liu X,Sun N,Dong Y,et al.Anticancer effects of adenovirus-mediated calreticulin and melanoma-associated antigen 3 expression on non-small cell lung cancer cells.International Immunopharmacology,2015,25:416.
11 Yelei Guo,Weidong Han.Cytokine-induced killer (CIK)cells:from basic research to clinical translation.Cancer,2015,34:99-107.
12 Kuang XY,Chen L,Zhang ZJ,et al.Stathmin and phospho-stathmin protein signature is associated with survival outcomes of breast cancer patients.Oncotarget,2015,6:22227-22238.
13 Chiyomaru T,Seki N,Inoguchi S,et al.Dual regulation of receptor tyrosine kinase genes EGFR and c-Met by the tumor-suppressive microRNA-23b/27b cluster in bladder cancer.International Journal of Oncology,2015,46:487-496.
14 梁晶,贾新凤,韩福才.肺癌患者外周血中MMP-7mRNA、sMICA、VEGF的表达及其与侵袭转移的关系.肿瘤防治研究,2016,43:508-512.
15 季禹乔,孙明忠,朱晖,等.血清miRNA-21与肿瘤标志物CEA、CYFRA21-1、NSE对早期非小细胞肺癌的诊断价值.中国实验诊断学,2017,21:576-581.
16 邱会林,丁伟,周建英.凋亡抑制蛋白Survivin在人非小细胞肺癌中的表达及其与COX-2蛋白表达和细胞凋亡的关系.浙江预防医学,2005,17:1-2.
17 Shintani M,Sangawa A,Yamao N,et al.Immunohistochemical expressi- on of nuclear and cytoplasmic survivin in gastrointestinal carcinoma.International Journal of Clinical & Experimental Pathology,2013,6:2919-2927.
18 奚小祥,陈浩.短期DC-CIK生物免疫疗法治疗中晚期食管癌患者的疗效观察.实用临床医药杂志,2016,20:116-117.
19 郑劼,江龙委,姚露,等.DC-CIK细胞治疗晚期结直肠癌的临床疗效.中国肿瘤生物治疗杂志,2015,22:459-464.
2 沈文斌,祝淑钗.食管癌术后患者放化疗临床应用研究进展.肿瘤防治研究,2015,42:535-540.
3 Hatogai K,Kitano S,Fujii S,et al.Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma.Oncotarget,2016,7:47252-47264.
4 李永姝.细胞因子诱导杀伤细胞免疫治疗食管癌的研究进展.临床和实验医学杂志,2016,15:1967-1969.
5 Detterbeck FC,Boffa DJ,Kim AW,et al.The eighth edition lung cancer stage classification.Chest,2017,151:193.
6 佘明金,马祖胜,李桂芝,等.奥沙利铂联合5-氟尿嘧啶治疗中晚期食管癌的临床疗效及安全性评价.中国临床药理学杂志,2016,32:508-510.
7 傅剑华,谭子辉.食管癌外科治疗的现状与未来展望.中国肿瘤临床,2016,43:507-510.
8 Mao Q,Li L,Zhang C,et al.Clinical effects of immunotherapy of DC-CIK combined with chemotherapy in treating patients with metastatic breast cancer.Pakistan Journal of Pharmaceutical Sciences,2015,28:1055-1058.
9 Banchereau J,Steinman RM.Dendritic cells and the control immunity.Nature,1998,392:245-252.
10 Liu X,Sun N,Dong Y,et al.Anticancer effects of adenovirus-mediated calreticulin and melanoma-associated antigen 3 expression on non-small cell lung cancer cells.International Immunopharmacology,2015,25:416.
11 Yelei Guo,Weidong Han.Cytokine-induced killer (CIK)cells:from basic research to clinical translation.Cancer,2015,34:99-107.
12 Kuang XY,Chen L,Zhang ZJ,et al.Stathmin and phospho-stathmin protein signature is associated with survival outcomes of breast cancer patients.Oncotarget,2015,6:22227-22238.
13 Chiyomaru T,Seki N,Inoguchi S,et al.Dual regulation of receptor tyrosine kinase genes EGFR and c-Met by the tumor-suppressive microRNA-23b/27b cluster in bladder cancer.International Journal of Oncology,2015,46:487-496.
14 梁晶,贾新凤,韩福才.肺癌患者外周血中MMP-7mRNA、sMICA、VEGF的表达及其与侵袭转移的关系.肿瘤防治研究,2016,43:508-512.
15 季禹乔,孙明忠,朱晖,等.血清miRNA-21与肿瘤标志物CEA、CYFRA21-1、NSE对早期非小细胞肺癌的诊断价值.中国实验诊断学,2017,21:576-581.
16 邱会林,丁伟,周建英.凋亡抑制蛋白Survivin在人非小细胞肺癌中的表达及其与COX-2蛋白表达和细胞凋亡的关系.浙江预防医学,2005,17:1-2.
17 Shintani M,Sangawa A,Yamao N,et al.Immunohistochemical expressi- on of nuclear and cytoplasmic survivin in gastrointestinal carcinoma.International Journal of Clinical & Experimental Pathology,2013,6:2919-2927.
18 奚小祥,陈浩.短期DC-CIK生物免疫疗法治疗中晚期食管癌患者的疗效观察.实用临床医药杂志,2016,20:116-117.
19 郑劼,江龙委,姚露,等.DC-CIK细胞治疗晚期结直肠癌的临床疗效.中国肿瘤生物治疗杂志,2015,22:459-464.