从VEGF和sVEGFR2探究分子靶向药物舒尼替尼治疗转移性肾癌的机制
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摘要
目的从血管内皮生长因子(VEGF)和可溶性血管内皮生长因子受体2(sVEGFR2)探究分子靶向药物舒尼替尼(Sunitinib)治疗转移性肾癌的机制。方法选取100例转移性肾癌患者,其中50例患者服用Sunitinib进行治疗记为Sunitinib组;另50例患者不服用相关药物,记为不服药组。治疗组50例患者中按照获益与非获益人群分组为获益组(n=25)和非获益组(n=25)。分析所有患者的疗效、并发症、在治疗初始及结束后的肾门淋巴结CT总径值、VEGF和sVEGFR2水平。结果 Sunitinib组患者的疗效提升(P<0.05),Sunitinib治疗的2个亚组与不服药组在电解质紊乱、胃肠道反应(恶心、腹泻、呕吐)、左室射血分数降低、肾功能减退、严重电解质紊乱等并发症发生率有显著性差异(P<0.05)。治疗初始肾门淋巴结个数与血管内皮生长因子水平呈负相关(P<0.05),与可溶性血管内皮生长因子受体2呈正相关(P<0.05)。治疗末期的肾门淋巴结数与血管内皮生长因子水平呈负相关(P<0.05),而与可溶性血管内皮生长因子受体2无相关性(P>0.05)。结论 Sunitinib治疗过程中,病灶的转移与VEGF水平呈显著负相关,与治疗前sVEGFR2水平呈显著正相关。
Objective To explore the mechanism of molecular targeted drug Sunitinib in the treatment of metastatic renal cell carcinoma(RCC)by analyzing the levels of vascular endothelial growth factor(VEGF)and soluble vascular endothelial growth factor receptor 2(sVEGFR2).Methods According to the clinical symptoms,100 patients with metastatic RCC were randomly selected and divided into 2 groups:Sunitinib group(n=50,received Sunitinib treatment),and non-medication group(n=50,took no medication).The Sunitinib group was divided into 2 subgroups:beneficiary group(n=25)and non-beneficiary group(n=25).The clinical efficacy,and VEGF and sVEGFR2 levels of all patients were analyzed.Results Compared with the non-medication group,the Sunitinib group had significantly improved treatment effects(P<0.05).There were significant differences in electrolyte disorders,gastrointestinal reactions(nausea,diarrhea,vomiting),decreased left ventricular ejection fraction,renal dysfunction and severe electrolyte disorders between the two subgroups treated with and without Sunitinib(P<0.05).In the beginning of treatment,the number of hilar lymph nodes was negatively correlated with the level of VEGF,but positively correlated with the level of sVEGFR2(P<0.05).At the end of treatment,the number of hilar lymph nodes was still negatively correlated with the level of VEGF(P<0.05),but not correlated with the level of sVEGFR2(P>0.05).Conclusion In the beginning of Sunitinib treatment,the metastasis of RCC was positively correlated with the level of sVEGFR2,and during the treatment,it was negatively correlated with the level of VEGF.
Objective To explore the mechanism of molecular targeted drug Sunitinib in the treatment of metastatic renal cell carcinoma(RCC)by analyzing the levels of vascular endothelial growth factor(VEGF)and soluble vascular endothelial growth factor receptor 2(sVEGFR2).Methods According to the clinical symptoms,100 patients with metastatic RCC were randomly selected and divided into 2 groups:Sunitinib group(n=50,received Sunitinib treatment),and non-medication group(n=50,took no medication).The Sunitinib group was divided into 2 subgroups:beneficiary group(n=25)and non-beneficiary group(n=25).The clinical efficacy,and VEGF and sVEGFR2 levels of all patients were analyzed.Results Compared with the non-medication group,the Sunitinib group had significantly improved treatment effects(P<0.05).There were significant differences in electrolyte disorders,gastrointestinal reactions(nausea,diarrhea,vomiting),decreased left ventricular ejection fraction,renal dysfunction and severe electrolyte disorders between the two subgroups treated with and without Sunitinib(P<0.05).In the beginning of treatment,the number of hilar lymph nodes was negatively correlated with the level of VEGF,but positively correlated with the level of sVEGFR2(P<0.05).At the end of treatment,the number of hilar lymph nodes was still negatively correlated with the level of VEGF(P<0.05),but not correlated with the level of sVEGFR2(P>0.05).Conclusion In the beginning of Sunitinib treatment,the metastasis of RCC was positively correlated with the level of sVEGFR2,and during the treatment,it was negatively correlated with the level of VEGF.
引文
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[14]NAVONE SE,GUARNACCIA L,CORDIGLIERI C,et al.Aspirin affects tumor angiogenesis and sensitizes human glioblastoma endothelial cells to temozolomide,bevacizumab,and sunitinib impairing VEGF-related signaling[J].World Neurosurg,2018,S1878-8750(18):31863-31871.
[15]KAMLI H,GLENDA GC,LI L,et al.Characterisation of the morphological,functional and molecular changes in sunitinib-resistant renal cell carcinoma cells[J].J Kidney Cancer VHL,2018,5(3):1-9.
[16]BRANCHE E,TANG WW,VIRAMONTES KM,et al.Synergism between the tyrosine kinase inhibitor sunitinib and AntiTNF antibody protects against lethal dengue infection[J].Antiviral Res,2018,158(7):1-7.
[17]MAUGE L,MJEAN A,FOURNIER L,et al.Sunitinib prior to planned nephrectomy in metastatic renal cell carcinoma:angiogenesis biomarkers predict clinical outcome in the prospective Phase 2PREINSUT trial[J].Clin Cancer Res,2018,pii:clincanres,2018:1045.
[18]MCDERMOTT DF,HUSENI MA,ATKINS MB,et al.Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma[J].Nat Med,2018,24(6):749-757.
[2]LINEHAN WM,SPELLMAN PT,RICKETTS CJ,et al.Comprehensive molecular characterization of papillary renal cell carcinoma[J].Engl J Med,2016,374(2):135-136.
[3]TANNIR NM,JONASCH E,ALBIGES L,et al.Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma(espn):a randomized multicenter phase 2trial.[J].Eur Urol,2016,69(5):866-874.
[4]褚菁,韩桂燕,张伟,等.转移性透明细胞性肾细胞癌42例临床病理分析[J].临床与实验病理学杂志,2016,32(4):384-387.
[5]WELLS JC,STUKALIN I,NORTON C,et al.Third-line targeted therapy in metastatic renal cell carcinoma:results from the international metastatic renal cell carcinoma database consortium.[J].Eur Urol,2017,71(2):204-205.
[6]HAKIMI AA,REZNIK E,LEE CH,et al.An Integrated metabolic atlas of clear cell renal cell carcinoma.[J].Cancer Cell,2016,29(1):104-116.
[7]ZHOU L,LIU XD,SUN M,et al.Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma[J].Oncogene,2016,35(21):2687-2688.
[8]陈旭,张洪秀,聂明秀,等.肾细胞癌精准靶向治疗的研究进展[J].中国当代医药,2016,23(21):14-18.
[9]EBELE JN,SAUTER G,EPSTEIN JI.Pathology and geneticsof tumours of the urinary system and male genital organs[M].Lyon:iarc Press,2004:12-43.
[10]INNO A,RUSSO GL,SALGARELLO M,et al.The evolving landscape of criteria for evaluating tumor response in the era of cancer immunotherapy:From Karnofsky to iRECIST[J].Tumori,2018,104(2):88-95.
[11]TZER RJ,HUTSON TE,TOMCZAK P,et al.Sunitinib versus interferon alfa in metastatic renal-cell carcinoma[J].Engl J Med,2007,356(2):115-124.
[12]TROTTI A,COLEVAS AD,SETSER A,et al.CTCAE v3.0:development of a comprehensive grading system for the adverse effects of cancer treatment.[J].Semin Radiat Oncol,2003,13(3):176-181.
[13]GAY HA,CAVALIERI R,ALLISON RR,et al.Complete response in a cutaneous facial metastatic nodule from renal cell carcinoma after hypofractionated radiotherapy.[J].Dermatol Online J,2017,13(4):6-8.
[14]NAVONE SE,GUARNACCIA L,CORDIGLIERI C,et al.Aspirin affects tumor angiogenesis and sensitizes human glioblastoma endothelial cells to temozolomide,bevacizumab,and sunitinib impairing VEGF-related signaling[J].World Neurosurg,2018,S1878-8750(18):31863-31871.
[15]KAMLI H,GLENDA GC,LI L,et al.Characterisation of the morphological,functional and molecular changes in sunitinib-resistant renal cell carcinoma cells[J].J Kidney Cancer VHL,2018,5(3):1-9.
[16]BRANCHE E,TANG WW,VIRAMONTES KM,et al.Synergism between the tyrosine kinase inhibitor sunitinib and AntiTNF antibody protects against lethal dengue infection[J].Antiviral Res,2018,158(7):1-7.
[17]MAUGE L,MJEAN A,FOURNIER L,et al.Sunitinib prior to planned nephrectomy in metastatic renal cell carcinoma:angiogenesis biomarkers predict clinical outcome in the prospective Phase 2PREINSUT trial[J].Clin Cancer Res,2018,pii:clincanres,2018:1045.
[18]MCDERMOTT DF,HUSENI MA,ATKINS MB,et al.Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma[J].Nat Med,2018,24(6):749-757.