弥漫大B细胞淋巴瘤化疗耐药与细胞因子IL-6、IL-10水平的相关性研究
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摘要
目的：探讨弥漫大B细胞淋巴瘤(DLBCL)患者血清细胞因子白细胞介素(IL)-2、IL-6、IL-8、IL-10、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)表达水平与化疗耐药之间的相关性。
方法：30例DLBCL化疗耐药患者为化疗耐药组,30例DLBCL化疗敏感患者为化疗敏感组,20例健康人作为健康对照组,ELISA法测定两组DLBCL患者治疗前、中、后及对照组血清中IL-2、IL-6、IL-8、IL-10、TNF-α、IFN-γ水平。
结果：化疗耐药组患者血清中的IL-6、IL-10治疗前表达水平明显高于化疗敏感组患者治疗前和对照组表达水平(P值均<0.05),治疗缓解后明显低于治疗前(P=0.02、P=0.015)。DLBCL复发耐药时,患者血清中的IL-6、IL-10又高于缓解时水平(P=0.004、P<0.001)。化疗耐药组III-IV期患者治疗前IL-6水平明显高于Ⅰ-Ⅱ期患者(P<0.05)。其他细胞因子IL-2、IL-8、TNF-α、IFN-γ水平在DLBCL化疗耐药组、DLBCL化疗敏感组、对照组之间差异无统计学意义(P>0.05)。
结论：DLBCL患者血清中的IL-6、IL-10表达水平的高低与DLBCL化疗疗效密切相关,可能与DLBCL细胞耐药有关。
Objective:To investigate the correlation between expression levels of serum cytokines IL-2, IL-6, IL-8, IL-10, TNF-αand IFN-y in patients with diffuse large B-cell lymphoma(DLBCL) and chemotherapy resistance.
Methods:30 cases of DLBCL patients with chemotherapy resistant,30 cases of DLBCL patients with chemotherapy sensitive and 20 cases of healthy individuals as normal control group were enrolled. The levels of serum cytokines IL-2, IL-6, IL-8, IL-10, TNF-αand IFN-y before, during and after treatment in both DLBCL groups and normal control group were detected by ELISA assay.
Results:The expression level of serum IL-6, IL-10 before treatment in DLBCL in patients with chemotherapy resistance were significantly higher than that in DLBCL patients with chemotherapy sensitive and normal control group (P<0.05), however, that after treatment in DLBCL patients with chemotherapy resistance was significantly lower than that before treatment (P=0.02 and P=0.015). The level of serum IL-6, IL-10 in patients with DLBCL recurrence into drug resistance was higher than that during of remission (P=0.004 and P＜0.001). Before treatment, the expression level of serum IL-6 in patients withⅢ-Ⅳstage in chemotherapy resistant group was significantly higher than that in ones withⅠ-Ⅱstage (P<0.05). Levels of IL-2, IL-8, TNF-α, IFN-γin chemotherapy resistant group, chemotherapy sensitive group and the normal control group were no differences. (P>0.05).
Conclusion:The expression levels of the serum IL-6, IL-10 were closely correlated with the chemotherapy efficacy of DLBCL, they may be involved in drug resistance of DLBCL
方法：30例DLBCL化疗耐药患者为化疗耐药组,30例DLBCL化疗敏感患者为化疗敏感组,20例健康人作为健康对照组,ELISA法测定两组DLBCL患者治疗前、中、后及对照组血清中IL-2、IL-6、IL-8、IL-10、TNF-α、IFN-γ水平。
结果：化疗耐药组患者血清中的IL-6、IL-10治疗前表达水平明显高于化疗敏感组患者治疗前和对照组表达水平(P值均<0.05),治疗缓解后明显低于治疗前(P=0.02、P=0.015)。DLBCL复发耐药时,患者血清中的IL-6、IL-10又高于缓解时水平(P=0.004、P<0.001)。化疗耐药组III-IV期患者治疗前IL-6水平明显高于Ⅰ-Ⅱ期患者(P<0.05)。其他细胞因子IL-2、IL-8、TNF-α、IFN-γ水平在DLBCL化疗耐药组、DLBCL化疗敏感组、对照组之间差异无统计学意义(P>0.05)。
结论：DLBCL患者血清中的IL-6、IL-10表达水平的高低与DLBCL化疗疗效密切相关,可能与DLBCL细胞耐药有关。
Objective:To investigate the correlation between expression levels of serum cytokines IL-2, IL-6, IL-8, IL-10, TNF-αand IFN-y in patients with diffuse large B-cell lymphoma(DLBCL) and chemotherapy resistance.
Methods:30 cases of DLBCL patients with chemotherapy resistant,30 cases of DLBCL patients with chemotherapy sensitive and 20 cases of healthy individuals as normal control group were enrolled. The levels of serum cytokines IL-2, IL-6, IL-8, IL-10, TNF-αand IFN-y before, during and after treatment in both DLBCL groups and normal control group were detected by ELISA assay.
Results:The expression level of serum IL-6, IL-10 before treatment in DLBCL in patients with chemotherapy resistance were significantly higher than that in DLBCL patients with chemotherapy sensitive and normal control group (P<0.05), however, that after treatment in DLBCL patients with chemotherapy resistance was significantly lower than that before treatment (P=0.02 and P=0.015). The level of serum IL-6, IL-10 in patients with DLBCL recurrence into drug resistance was higher than that during of remission (P=0.004 and P＜0.001). Before treatment, the expression level of serum IL-6 in patients withⅢ-Ⅳstage in chemotherapy resistant group was significantly higher than that in ones withⅠ-Ⅱstage (P<0.05). Levels of IL-2, IL-8, TNF-α, IFN-γin chemotherapy resistant group, chemotherapy sensitive group and the normal control group were no differences. (P>0.05).
Conclusion:The expression levels of the serum IL-6, IL-10 were closely correlated with the chemotherapy efficacy of DLBCL, they may be involved in drug resistance of DLBCL
引文
1、白血病·淋巴瘤编辑委员会.难治性非霍奇金淋巴瘤的诊断标准.白血病·淋巴瘤,2007,16：349.
2、Ohsawa M, Ikura Y, Fukushima H, et al. Immunohistochemical expression of multidrug resistance proteins as a predictor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma [J]. Oncology,2005,68(4-6):422-431
3、钱素英,毛联钢,吴宁宁,等BCRP及MDR1在非霍奇金淋巴瘤的表达及预后分析.实用肿瘤杂志,2009,24：266-268.
4、李斌,钟美佐,唐陶富,等.COX-2和P-gp在B细胞非霍奇金淋巴瘤组织中表达的相关性研究.癌症,2007,26：851-855.
5、阳文捷,宋向群.Bcl-2和Bcl-6与淋巴瘤相关性的研究进展.中华肿瘤防治杂志,2006,13：1755-1758.
6、蒋会勇,李慧灵,胡海,等.弥漫大B细胞淋巴瘤t(14；18)易位及bcl-2基因扩增的检测.中华病理学杂志,2007,2：84-89.
7、杨啊晶,王雪梅,李电东,等.p53及其信号通路在肿瘤耐药分子机制中的研究进展.中国新药杂志,2007,16：7-11.
8、袁晓露.弥漫大B细胞淋巴瘤信号通路与耐药研究进展.白血病·淋巴瘤,2008,18：76-78
9、LinWW, KarinM. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007,1:1175-1183.
10、杨文琪,刘玉华.恶性淋巴瘤患者血清IL-6水平变化及其临床意义.上海医学检验杂志,2003,18：410.
11、Moore KW, deWaal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001,19:683-765.
12、Kube D, Hua TD, von Bonin F, et al. Effect of Interleukin-10 Gene Polymorphisms on Clinical Outcome of Patients with Aggressive Non-Hodgkin's Lymphoma:An Exploratory Study [J]. Clin Cancer Res 2008,14:3777-3784
13、Bowman T,Garcia R,Turkson J,Jove R.STATs in oncogenesis. Oncogene,2000, 19:2474-2488
14、Hirano T,Ishihara K,Hibi M.Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors.Oncogene.2000,19:2548-2556.
15、侯淑玲,乔丽娟,张巧花等淋巴瘤细胞膜P糖蛋白、信号转导与转录激活因子3及bcl-2表达水平与化疗耐药的相关性.白血病·淋巴瘤,2009,18：732-734.
16、Alas S., Emmanouilides C., Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. Clin. Cancer Res,2001,7:709-723.
17、Frassanito M. A., Cusmai A., Iodice G., Dammacco F. Autocrine interleukin-6 production and highly malignant multiple myeloma:relation with resistance to drug-induced apoptosis. Blood,2001,97:483-489.
18、Alas S, Bonavida B, Inhibition of Constitutive STAT3 Activity Sensitizes Resistant Non-Hodgkin's Lymphoma and Multiple Myeloma to Chemotherapeutic Drug-mediated Apoptosis, Clinical Cancer Research,2003,9:316-326.
1.钱素英,毛联钢,吴宁宁,等BCRP及MDR1在非霍奇金淋巴瘤的表达及预后分析[J].Journal of practical Oncology,2009,24:266-268.
2.阳文捷,宋向群.BcI-2和BcI-6与淋巴瘤相关性的研究进展[J].中华肿瘤防治杂志,2006,13：1755-1758.
3.蒋会勇,李慧灵,胡海等.弥漫弥漫大B细胞淋巴瘤t(14；18)易位及bcl2基因扩增的检测[J].中华病理学杂志,2007,36：84-89.
4.朱远东,徐卫,李建勇。p53基因改变与淋巴瘤[J].中华血液学杂志,2009,30：712-714。
5.杨啊晶,王雪梅,李电东等。P53及其信号通路在肿瘤耐药分子机制中的研究进展[J].中国新药杂志,2007,16：7-11.
6.Kamata H, Mitani S, Fujiwara, M et al. Mutation of the p53 tumour suppressor gene and overexpression of its protein in 62 Japanese non-Hodgkin's lymphomas. [J]. Clin Exp Med, 2007,7:39-46.
7. Visco C, Canal F, Parolini C, el al. The impact of p53 and p21(wafl)expression on the survival of patients with the germinal center phenotype of diffuse large B—cell lymphoma. [J]. Haematologica,2006,91:687-690.
8.郑改焕,金先庆,郭玉霞,等。新基因日A117在淋巴瘤细胞中的耐药相关功能研究[J].肿瘤,2009,29：315-318.
9.李斌,钟美佐,唐陶富等。COX-2和P-gp在B细胞非霍奇金淋巴瘤组织中表达的相关性研究[J].癌症,2007,26：851-855。
10.罗克枢,黄晓赤。恶性肿瘤多药耐药标记的检测及其临床意义[J].现代临床医学,2007,33：31-32.
11. Gardner ER, Figy WD, Sparreboom A. Pharmacogenomics of the human ATP-binging cassette transporter ABCG2[J]. Curr Pharmac-ogenomics,2006,4:331-344.
12.钱素英,毛联钢,吴宁宁,等。BCRP及MDR1在非霍奇金淋巴瘤接受化疗患者的表达及临床意义[J].现代实用医学,2009,21：427-431.
13.李乐,苏丽萍,马莉赵,等。非霍奇金淋巴瘤多药耐药的实验研究[J].中华肿瘤杂志,2009,31：199-202.
14.窦红菊,胡钧培.凋亡调节蛋白survivin在弥漫大B细胞淋巴瘤中的研究进展[J].中国实验血液学杂志,2008,16：1487-1490.
15. Watanuki-MiyauchiR, KojimaY, TsurumiH,et al. Expression of survivin and of antigen detected by a novel monoclonal antibody, T332, is associated with outcome of diffuse large B-cell lymphoma and its subtypes. [J]. Pathol Int,2005,55:324-330。
16.杨敏,陈琦,陈羽。非霍奇金淋巴瘤患者血管内皮生长因子、抗凋亡因子Bcl-2与多药耐药关系的初步探讨[J]。陕西医学杂志,2006,35：289-291
17.周宁,弥漫大B细胞淋巴瘤血管生长因子表达水平检测及临床意义[J].江西医药,2007,42：657-659.
18.杨文琪,刘玉华恶性淋巴瘤患者血清IL6水平变化及其临床意义[J]..上海医学检验杂志,2003,18：410
19. Moore KW, deWaal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. [J]Annu Rev Immunol 2001,19:683-765.
20. Dieter Kube, Thanh-Duc Hua, Frederike von Bonin, et al. Effect of Interleukin-10 Gene Polymorphisms on Clinical Outcome of Patients with Aggressive Non-Hodgkin's Lymphoma: An Exploratory Study [J]. Clin Cancer Res 2008;14:3777-3784
21. Hirano T,Ishihara K,Hibi M.Roles of STAT3 in mediating the cell growth,differentiation and survival signals relayed through the IL-6 family of cytokine receptors. [J] Oncogene.2000, 19:2548-2556
22.侯淑玲,乔丽娟,张巧花等淋巴瘤细胞膜P糖蛋白、信号转导与转录激活因子3及bcl-2表达水平与化疗耐药的相关性[J].白血病·淋巴瘤,2009,18：732-734.
23. Alas S., Emmanouilides C., Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. [J].Clin. Cancer Res.2001,7:709-723.
24. Frassanito M. A., Cusmai A., lodice G., Dammacco F. Autocrine interleukin-6 production and highly malignant multiple myeloma:relation with resistance to drug-induced apoptosis. [J]. Blood,2001,97:483-489.
25.归薇,麦羡霞,苏文。淋巴瘤与粘附分子相关性的研究[J].国外医学输血及血液学分册2002,25：511-514.
26.王昭霞,邹亚伟。造血微环境与血液肿瘤耐药[J].中华生物医学工程杂志,2007,13：415-417.
27. Margaret E. Tome, David B. F. Johnson, Ijsa M. Rimsza, et al. Aredox signature score identmes di{mse large B—cell lymphoma patients with a poor prognosis[J].B100d,2005, 106:3594—3601.
28. Ohsawa M, Ikura Y, Fukushima H, et al. Immunohistochemical expression of multidrug resistance proteins as a predictor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma[J]. Oncology,2005,68:422-431.
29.袁晓露.弥漫大B细胞淋巴瘤信号通路与耐药研究进展.白血病·淋巴瘤,2008,18：76-78。
30.Lam LT, Davis RE, Pierce J, et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups Of diffuse large B—cell lymphoma defined by gene expression prOfliling[J]. Clin Callcer Res,2005,11:28—40.
31. Barancik M, Bohacova V, Sedlak J, et al. LY294002, a specific inhibitor of P13K /Akt kinase pathway, antagonizes P—glycoprotein—mcdiated multidrug resistance[J]. Eur J Pharm Sci,2006,29:426—434.
32. Espinosa I, Briones J, Bordes R, et al.Membrane pkc-beta2 prote in expression predicts for poor response to chemotherapy and survival in patients with diffuse large B-cell lymphoma.Ann Hematol,2006,85:597-603.
33. Vega MI, Huerta—Yepez S, Jazirehi AR, et al. Rituximab(chimeric anti～ CD20)sensitizes B—NHL cell lines to Fas—induced apoptosis [J]Oncogene,2005,24: 8114—8127.
2、Ohsawa M, Ikura Y, Fukushima H, et al. Immunohistochemical expression of multidrug resistance proteins as a predictor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma [J]. Oncology,2005,68(4-6):422-431
3、钱素英,毛联钢,吴宁宁,等BCRP及MDR1在非霍奇金淋巴瘤的表达及预后分析.实用肿瘤杂志,2009,24：266-268.
4、李斌,钟美佐,唐陶富,等.COX-2和P-gp在B细胞非霍奇金淋巴瘤组织中表达的相关性研究.癌症,2007,26：851-855.
5、阳文捷,宋向群.Bcl-2和Bcl-6与淋巴瘤相关性的研究进展.中华肿瘤防治杂志,2006,13：1755-1758.
6、蒋会勇,李慧灵,胡海,等.弥漫大B细胞淋巴瘤t(14；18)易位及bcl-2基因扩增的检测.中华病理学杂志,2007,2：84-89.
7、杨啊晶,王雪梅,李电东,等.p53及其信号通路在肿瘤耐药分子机制中的研究进展.中国新药杂志,2007,16：7-11.
8、袁晓露.弥漫大B细胞淋巴瘤信号通路与耐药研究进展.白血病·淋巴瘤,2008,18：76-78
9、LinWW, KarinM. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007,1:1175-1183.
10、杨文琪,刘玉华.恶性淋巴瘤患者血清IL-6水平变化及其临床意义.上海医学检验杂志,2003,18：410.
11、Moore KW, deWaal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001,19:683-765.
12、Kube D, Hua TD, von Bonin F, et al. Effect of Interleukin-10 Gene Polymorphisms on Clinical Outcome of Patients with Aggressive Non-Hodgkin's Lymphoma:An Exploratory Study [J]. Clin Cancer Res 2008,14:3777-3784
13、Bowman T,Garcia R,Turkson J,Jove R.STATs in oncogenesis. Oncogene,2000, 19:2474-2488
14、Hirano T,Ishihara K,Hibi M.Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors.Oncogene.2000,19:2548-2556.
15、侯淑玲,乔丽娟,张巧花等淋巴瘤细胞膜P糖蛋白、信号转导与转录激活因子3及bcl-2表达水平与化疗耐药的相关性.白血病·淋巴瘤,2009,18：732-734.
16、Alas S., Emmanouilides C., Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. Clin. Cancer Res,2001,7:709-723.
17、Frassanito M. A., Cusmai A., Iodice G., Dammacco F. Autocrine interleukin-6 production and highly malignant multiple myeloma:relation with resistance to drug-induced apoptosis. Blood,2001,97:483-489.
18、Alas S, Bonavida B, Inhibition of Constitutive STAT3 Activity Sensitizes Resistant Non-Hodgkin's Lymphoma and Multiple Myeloma to Chemotherapeutic Drug-mediated Apoptosis, Clinical Cancer Research,2003,9:316-326.
1.钱素英,毛联钢,吴宁宁,等BCRP及MDR1在非霍奇金淋巴瘤的表达及预后分析[J].Journal of practical Oncology,2009,24:266-268.
2.阳文捷,宋向群.BcI-2和BcI-6与淋巴瘤相关性的研究进展[J].中华肿瘤防治杂志,2006,13：1755-1758.
3.蒋会勇,李慧灵,胡海等.弥漫弥漫大B细胞淋巴瘤t(14；18)易位及bcl2基因扩增的检测[J].中华病理学杂志,2007,36：84-89.
4.朱远东,徐卫,李建勇。p53基因改变与淋巴瘤[J].中华血液学杂志,2009,30：712-714。
5.杨啊晶,王雪梅,李电东等。P53及其信号通路在肿瘤耐药分子机制中的研究进展[J].中国新药杂志,2007,16：7-11.
6.Kamata H, Mitani S, Fujiwara, M et al. Mutation of the p53 tumour suppressor gene and overexpression of its protein in 62 Japanese non-Hodgkin's lymphomas. [J]. Clin Exp Med, 2007,7:39-46.
7. Visco C, Canal F, Parolini C, el al. The impact of p53 and p21(wafl)expression on the survival of patients with the germinal center phenotype of diffuse large B—cell lymphoma. [J]. Haematologica,2006,91:687-690.
8.郑改焕,金先庆,郭玉霞,等。新基因日A117在淋巴瘤细胞中的耐药相关功能研究[J].肿瘤,2009,29：315-318.
9.李斌,钟美佐,唐陶富等。COX-2和P-gp在B细胞非霍奇金淋巴瘤组织中表达的相关性研究[J].癌症,2007,26：851-855。
10.罗克枢,黄晓赤。恶性肿瘤多药耐药标记的检测及其临床意义[J].现代临床医学,2007,33：31-32.
11. Gardner ER, Figy WD, Sparreboom A. Pharmacogenomics of the human ATP-binging cassette transporter ABCG2[J]. Curr Pharmac-ogenomics,2006,4:331-344.
12.钱素英,毛联钢,吴宁宁,等。BCRP及MDR1在非霍奇金淋巴瘤接受化疗患者的表达及临床意义[J].现代实用医学,2009,21：427-431.
13.李乐,苏丽萍,马莉赵,等。非霍奇金淋巴瘤多药耐药的实验研究[J].中华肿瘤杂志,2009,31：199-202.
14.窦红菊,胡钧培.凋亡调节蛋白survivin在弥漫大B细胞淋巴瘤中的研究进展[J].中国实验血液学杂志,2008,16：1487-1490.
15. Watanuki-MiyauchiR, KojimaY, TsurumiH,et al. Expression of survivin and of antigen detected by a novel monoclonal antibody, T332, is associated with outcome of diffuse large B-cell lymphoma and its subtypes. [J]. Pathol Int,2005,55:324-330。
16.杨敏,陈琦,陈羽。非霍奇金淋巴瘤患者血管内皮生长因子、抗凋亡因子Bcl-2与多药耐药关系的初步探讨[J]。陕西医学杂志,2006,35：289-291
17.周宁,弥漫大B细胞淋巴瘤血管生长因子表达水平检测及临床意义[J].江西医药,2007,42：657-659.
18.杨文琪,刘玉华恶性淋巴瘤患者血清IL6水平变化及其临床意义[J]..上海医学检验杂志,2003,18：410
19. Moore KW, deWaal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. [J]Annu Rev Immunol 2001,19:683-765.
20. Dieter Kube, Thanh-Duc Hua, Frederike von Bonin, et al. Effect of Interleukin-10 Gene Polymorphisms on Clinical Outcome of Patients with Aggressive Non-Hodgkin's Lymphoma: An Exploratory Study [J]. Clin Cancer Res 2008;14:3777-3784
21. Hirano T,Ishihara K,Hibi M.Roles of STAT3 in mediating the cell growth,differentiation and survival signals relayed through the IL-6 family of cytokine receptors. [J] Oncogene.2000, 19:2548-2556
22.侯淑玲,乔丽娟,张巧花等淋巴瘤细胞膜P糖蛋白、信号转导与转录激活因子3及bcl-2表达水平与化疗耐药的相关性[J].白血病·淋巴瘤,2009,18：732-734.
23. Alas S., Emmanouilides C., Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. [J].Clin. Cancer Res.2001,7:709-723.
24. Frassanito M. A., Cusmai A., lodice G., Dammacco F. Autocrine interleukin-6 production and highly malignant multiple myeloma:relation with resistance to drug-induced apoptosis. [J]. Blood,2001,97:483-489.
25.归薇,麦羡霞,苏文。淋巴瘤与粘附分子相关性的研究[J].国外医学输血及血液学分册2002,25：511-514.
26.王昭霞,邹亚伟。造血微环境与血液肿瘤耐药[J].中华生物医学工程杂志,2007,13：415-417.
27. Margaret E. Tome, David B. F. Johnson, Ijsa M. Rimsza, et al. Aredox signature score identmes di{mse large B—cell lymphoma patients with a poor prognosis[J].B100d,2005, 106:3594—3601.
28. Ohsawa M, Ikura Y, Fukushima H, et al. Immunohistochemical expression of multidrug resistance proteins as a predictor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma[J]. Oncology,2005,68:422-431.
29.袁晓露.弥漫大B细胞淋巴瘤信号通路与耐药研究进展.白血病·淋巴瘤,2008,18：76-78。
30.Lam LT, Davis RE, Pierce J, et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups Of diffuse large B—cell lymphoma defined by gene expression prOfliling[J]. Clin Callcer Res,2005,11:28—40.
31. Barancik M, Bohacova V, Sedlak J, et al. LY294002, a specific inhibitor of P13K /Akt kinase pathway, antagonizes P—glycoprotein—mcdiated multidrug resistance[J]. Eur J Pharm Sci,2006,29:426—434.
32. Espinosa I, Briones J, Bordes R, et al.Membrane pkc-beta2 prote in expression predicts for poor response to chemotherapy and survival in patients with diffuse large B-cell lymphoma.Ann Hematol,2006,85:597-603.
33. Vega MI, Huerta—Yepez S, Jazirehi AR, et al. Rituximab(chimeric anti～ CD20)sensitizes B—NHL cell lines to Fas—induced apoptosis [J]Oncogene,2005,24: 8114—8127.