胎盘生长因子及其受体在多发性骨髓瘤中的表达及其与化疗疗效的关系
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摘要
目的:探讨多发性骨髓瘤(MM)中胎盘生长因子(PIGF)及其受体Flt-1的表达与以沙利度胺为基础的化疗疗效的关系。方法:2012年6月至2013年3月在本院确诊的35例MM患者接受以沙利度胺为基础的化疗3个月,根据疗效将患者分组,选择15例非肿瘤患者作为对照。应用RT-PCR和Western blot法检测化疗前后MM组和对照组骨髓中PIGF及其受体Flt-1的表达,并分析其表达水平与化疗疗效的关系。用ELISA方法检测化疗前后患者血清中PIGF及其受体Flt-1的表达水平,并分析其与化疗疗效的关系。结果:MM患者在以沙利度胺为基础的化疗3个月后,化疗有效率为54.3%。治疗前MM患者骨髓中PIGF和Flt-1的表达水平均明显高于对照组(P<0.001),化疗后PIGF和Flt-1的在骨髓中表达水平均明显降低(P<0.001),并且其降低程度与疗效成正相关(r=0.71)。治疗前,M M患者血清中PIGF和Flt-1的浓度均明显高于对照者(P<0.001),化疗后PIGF和Flt-1在血清中浓度明显降低并且其降低程度与疗效成正相关(r=0.87)。结论:PIGF与FLT-1在多发性骨髓瘤中高表达,在以沙利度胺为基础的化疗后明显降低。
Objective:To investigate the expression of PIGF and its receptor Flt-1 in patients with multiple myeloma,and to analyze their correlation with the efficacy of thalidomide-based chemotherapy so as to provide further theoretical basis for individualized treatment.Methods:A total of 35 patients diagnosed as multiple myeloma from June 2012 to March 2013 in our hospital and 15 non-tumor patients as controls were enrolled in this study.MM patients were treated with thalidomide-based chemotherapy for 3 months,and then were grouped according to the curative effecacy.The expression levels of PIGF and Flt-1 were detected in bone marrow of control and MM patient group by RT-PCR and Western blot before and after chemotherapy,their correlation with chemotherapeutic efficacy was analyzed.Serum concentrations of PITG and Flt-1 were detected in control and MM patients before and after chemotherapy by ELISA and their correlation with the chemotherapeutic efficacy was analyzed.Results:The effective rate of three-monthsthalidomide-based chemotherapy was 54.3%in MM patients.The expression levels of PIGF and Flt-1 in MM patients' bone marrow were obviously higher than those in controls.After chemotherapy,PIGF and Flt-1 expression levels significantly reduced and the decline level was positively correlated with curative effecacy(r = 0.71).The serum concentrations of PIGF and Flt-1 in MM patients' bone marrow were obviously higher than those in control.After chemotherapy,serum concentrations of PIGF and Flt-1 were significantly decreased and the decline level positively correlated with curative effecacy(r =0.87).Conclusion:PIGF and FLT-1 are highly expressed in patients with multiple myeloma,and their expression levels positively correlates with curative effecacy of thalidomide-based chemotherapy.
Objective:To investigate the expression of PIGF and its receptor Flt-1 in patients with multiple myeloma,and to analyze their correlation with the efficacy of thalidomide-based chemotherapy so as to provide further theoretical basis for individualized treatment.Methods:A total of 35 patients diagnosed as multiple myeloma from June 2012 to March 2013 in our hospital and 15 non-tumor patients as controls were enrolled in this study.MM patients were treated with thalidomide-based chemotherapy for 3 months,and then were grouped according to the curative effecacy.The expression levels of PIGF and Flt-1 were detected in bone marrow of control and MM patient group by RT-PCR and Western blot before and after chemotherapy,their correlation with chemotherapeutic efficacy was analyzed.Serum concentrations of PITG and Flt-1 were detected in control and MM patients before and after chemotherapy by ELISA and their correlation with the chemotherapeutic efficacy was analyzed.Results:The effective rate of three-monthsthalidomide-based chemotherapy was 54.3%in MM patients.The expression levels of PIGF and Flt-1 in MM patients' bone marrow were obviously higher than those in controls.After chemotherapy,PIGF and Flt-1 expression levels significantly reduced and the decline level was positively correlated with curative effecacy(r = 0.71).The serum concentrations of PIGF and Flt-1 in MM patients' bone marrow were obviously higher than those in control.After chemotherapy,serum concentrations of PIGF and Flt-1 were significantly decreased and the decline level positively correlated with curative effecacy(r =0.87).Conclusion:PIGF and FLT-1 are highly expressed in patients with multiple myeloma,and their expression levels positively correlates with curative effecacy of thalidomide-based chemotherapy.
引文
1李青,李玉明.PCD方案与VAD方案治疗多发性骨髓瘤的临床观察.中国肿瘤临床,2014;41(13):853-855.
2 Becker N.Epidemiology of multiple myeloma.Recent Results Cancer Res,2011;183:25-35.
3 Hatjiharissi E,Terpos E,Papaioannou M,et al.The combination of intermediate doses of thalidomide and dexamethasone reduces bone marrow micro-vessel density but not serum levels of angiogenic cytokines in patients with refractory/relapsed multiple myeloma.Hematol Oncol,2004;22(4):159-168.
4 李玉娟,郭冬梅,滕清良.Notch1和VEGF在多发性骨髓瘤发生发展中的作用,山东医药,2011;51(11):108-109.
5 李欣,魏秀珍,刘晋玮,等.多发性骨髓瘤患者血清中VEGF水平的临床意义.中国实验血液学杂志,2014;22(001):108-111.
6 Fischer C,Jonckx B,Mazzone M,et al.Anti-Pl GF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels.Cell,2007;131(3):463-475.
7 Barlogie B,Tricot G,Anaissie E.Thalidomide in the management of multiple myeloma.Semin Oncol,2001;28(6):577-582.
8 Durie GB,Harousseau JL,Miguel JS,et al.International uniform response criteria for multiple myeloma.Leukemia,2006;20(9):1467-1473.
9 Vacca A,Ribatti D,Roncali L,et al.Bone marrow angiogenesis and progression in multiple myeloma,Br J Haematol,1994;87(3):503-508.
10 Pruneri G,Ponzoni M,Ferreri AJ,et al.Microvessel density,a surrogate marker of angiogenesis,is significantly related to survival in multiple myeloma patients.Br J Haematol,2002;118(3):817-820.
11 Podar,Klaus,,Kenneth C.Anderson.Targeting Multiple Myeloma Tumor Angiogenesis:Focus on VEGF.Advances in Biology and Therapy of Multiple Myeloma,Advances in Biology and Therapy of Multiple Myeloma:Volume 1,chapter 15,2013;283-299.
12 Fischer C,Mazzone M,Jonckx B,et al.FLT1 and its ligands VEGFB and Pl GF:drug targets for anti-angiogenic therapy.Nat Rev Cancer,2008;8(12):942-956.
13 杜朝阳,杨如玉.沙利度胺维持治疗多发性骨髓瘤的临床疗效观察.中国实用医刊,2014;41(15):54-56.
14 黄文添,陆森,陆粤就,等.浅析反应停在多发性骨髓瘤治疗中的临床应用.医学理论与实践,2014;27(9):1176-1177.
2 Becker N.Epidemiology of multiple myeloma.Recent Results Cancer Res,2011;183:25-35.
3 Hatjiharissi E,Terpos E,Papaioannou M,et al.The combination of intermediate doses of thalidomide and dexamethasone reduces bone marrow micro-vessel density but not serum levels of angiogenic cytokines in patients with refractory/relapsed multiple myeloma.Hematol Oncol,2004;22(4):159-168.
4 李玉娟,郭冬梅,滕清良.Notch1和VEGF在多发性骨髓瘤发生发展中的作用,山东医药,2011;51(11):108-109.
5 李欣,魏秀珍,刘晋玮,等.多发性骨髓瘤患者血清中VEGF水平的临床意义.中国实验血液学杂志,2014;22(001):108-111.
6 Fischer C,Jonckx B,Mazzone M,et al.Anti-Pl GF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels.Cell,2007;131(3):463-475.
7 Barlogie B,Tricot G,Anaissie E.Thalidomide in the management of multiple myeloma.Semin Oncol,2001;28(6):577-582.
8 Durie GB,Harousseau JL,Miguel JS,et al.International uniform response criteria for multiple myeloma.Leukemia,2006;20(9):1467-1473.
9 Vacca A,Ribatti D,Roncali L,et al.Bone marrow angiogenesis and progression in multiple myeloma,Br J Haematol,1994;87(3):503-508.
10 Pruneri G,Ponzoni M,Ferreri AJ,et al.Microvessel density,a surrogate marker of angiogenesis,is significantly related to survival in multiple myeloma patients.Br J Haematol,2002;118(3):817-820.
11 Podar,Klaus,,Kenneth C.Anderson.Targeting Multiple Myeloma Tumor Angiogenesis:Focus on VEGF.Advances in Biology and Therapy of Multiple Myeloma,Advances in Biology and Therapy of Multiple Myeloma:Volume 1,chapter 15,2013;283-299.
12 Fischer C,Mazzone M,Jonckx B,et al.FLT1 and its ligands VEGFB and Pl GF:drug targets for anti-angiogenic therapy.Nat Rev Cancer,2008;8(12):942-956.
13 杜朝阳,杨如玉.沙利度胺维持治疗多发性骨髓瘤的临床疗效观察.中国实用医刊,2014;41(15):54-56.
14 黄文添,陆森,陆粤就,等.浅析反应停在多发性骨髓瘤治疗中的临床应用.医学理论与实践,2014;27(9):1176-1177.