目的探讨以左旋门冬酰胺酶(L-ASP)为基础的化疗方案联合放疗治疗ⅠE和ⅡE期结外鼻型NK/T细胞淋巴瘤(ENKTL)患者的疗效,及门冬酰胺合成酶(ASNS)的表达水平与L-ASP治疗ENKTL疗效之间的关系。方法回顾性分析2008年5月至2013年5月ⅠE期和ⅡE...目的探讨以左旋门冬酰胺酶(L-ASP)为基础的化疗方案联合放疗治疗ⅠE和ⅡE期结外鼻型NK/T细胞淋巴瘤(ENKTL)患者的疗效,及门冬酰胺合成酶(ASNS)的表达水平与L-ASP治疗ENKTL疗效之间的关系。方法回顾性分析2008年5月至2013年5月ⅠE期和ⅡE期ENKTL患者119例,按治疗方式分为单纯放疗(RT)组(n=27)、CHOP或CHOP样化疗方案联合放疗(RT+CHOP)组(n=33)和以L-ASP为基础的化疗方案联合放疗(RT+L-ASP)组(n=59)。放疗总剂量DT 50~60 Gy,L-ASP 6000 U/m^2静滴,d1~d7。比较RT组、RT+CHOP组和RT+L-ASP组ENKTL患者的疗效;采用RTPCR和免疫组化法分别检测ASNS m RNA和蛋白表达水平,并分析其与疗效之间的关系。结果 RT+L-ASP组的有效率(RR)为91.5%,显著优于RT组的74.1%和RT+CHOP组的69.7%(P=0.007,P=0.030)。RT+L-ASP组的中位总生存时间(OS)为49个月,高于RT组的28个月(P=0.017),但与RT+CHOP组(31个月)的差异无统计学意义(P=0.077);RT+L-ASP组的中位无进展生存时间(PFS)为47个月,高于RT组的25个月和RT+CHOP组的17个月,差异均有统计学意义(P=0.018,P<0.001)。Cox比例风险回归分析显示,Ann Arbor分期和β2微球蛋白是影响OS的独立预后因素;治疗方案和近期疗效是影响PFS的独立因素。3组最常见的不良反应为骨髓抑制和肝肾功能损伤,RT+L-ASP组有8例患者出现过敏反应。近期疗效好的患者的ASNS m RNA和蛋白表达水平明显低于疗效较差的患者。ASNS m RNA表达分别与OS和PFS呈负相关(r=-0.60,P=0.01;r=-0.65,P=0.004);ASNS蛋白表达与OS和PFS亦呈负相关(r=-0.77,P<0.001;r=-0.71,P<0.001)。结论对于ⅠE期和ⅡE期ENKTL患者,以L-ASP为基础的化疗方案联合放疗的疗效优于单纯放疗和CHOP或CHOP样化疗方案联合放疗。ASNS的表达,尤其是蛋白表达水平,可作为L-ASP治疗ⅠE期和ⅡE期ENKTL疗效的预测指标。展开更多
As the chemotherapeutic resistance of extranodal NK/T-cell lymphoma(ENKTL) rises year by year, searching for novel chemoprevention compounds has become imminent. Gambogic acid(GA) has recently been shown to have anti-...As the chemotherapeutic resistance of extranodal NK/T-cell lymphoma(ENKTL) rises year by year, searching for novel chemoprevention compounds has become imminent. Gambogic acid(GA) has recently been shown to have anti-tumor effects, but its role and underling mechanism in ENKTL are rather elusive. In the present study, we showed that GA inhibited the cell growth and potently induced the apoptosis of ENKTL cells in vitro in a time-and concentration-dependent manner. Furthermore, GA induced cell death through endoplasmic reticulum stress(ERS) mediated suppression of Akt signaling pathways and finally the release of the caspase-3 proteases. Overall, our data provided evidences supporting GA as a potential therapeutic agent for ENKTL, which may facilitate further preclinical development of anti-tumor drugs.展开更多
Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr...Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr virus and are prevalent in East Asia and Latin America.Except for that of limited-stage ENKL,the prognosis of both diseases was poor in the previous decade.The advent of non-anthracycline-based chemoradiotherapy has contributed to an improvement in ENKL prognosis,but there is still room for further treatment progress.Recently,the high efficacy of PD-1 antibody was reported in relapsed or refractory ENKL patients.This was later supported by the finding that PD-L1/PD-L2 genetic alterations are frequently observed in ENKL and ANKL patients.Due to the rarity of the disease,a standard treatment for ANKL remains to be established.Currently,allogeneic stem cell transplantation is the only curative treatment,and this is even applicable to chemo-resistant ANKL patients.In this review,we focus on recent treatment approaches for NK/T cell lymphomas including novel agents.展开更多
文摘目的探讨以左旋门冬酰胺酶(L-ASP)为基础的化疗方案联合放疗治疗ⅠE和ⅡE期结外鼻型NK/T细胞淋巴瘤(ENKTL)患者的疗效,及门冬酰胺合成酶(ASNS)的表达水平与L-ASP治疗ENKTL疗效之间的关系。方法回顾性分析2008年5月至2013年5月ⅠE期和ⅡE期ENKTL患者119例,按治疗方式分为单纯放疗(RT)组(n=27)、CHOP或CHOP样化疗方案联合放疗(RT+CHOP)组(n=33)和以L-ASP为基础的化疗方案联合放疗(RT+L-ASP)组(n=59)。放疗总剂量DT 50~60 Gy,L-ASP 6000 U/m^2静滴,d1~d7。比较RT组、RT+CHOP组和RT+L-ASP组ENKTL患者的疗效;采用RTPCR和免疫组化法分别检测ASNS m RNA和蛋白表达水平,并分析其与疗效之间的关系。结果 RT+L-ASP组的有效率(RR)为91.5%,显著优于RT组的74.1%和RT+CHOP组的69.7%(P=0.007,P=0.030)。RT+L-ASP组的中位总生存时间(OS)为49个月,高于RT组的28个月(P=0.017),但与RT+CHOP组(31个月)的差异无统计学意义(P=0.077);RT+L-ASP组的中位无进展生存时间(PFS)为47个月,高于RT组的25个月和RT+CHOP组的17个月,差异均有统计学意义(P=0.018,P<0.001)。Cox比例风险回归分析显示,Ann Arbor分期和β2微球蛋白是影响OS的独立预后因素;治疗方案和近期疗效是影响PFS的独立因素。3组最常见的不良反应为骨髓抑制和肝肾功能损伤,RT+L-ASP组有8例患者出现过敏反应。近期疗效好的患者的ASNS m RNA和蛋白表达水平明显低于疗效较差的患者。ASNS m RNA表达分别与OS和PFS呈负相关(r=-0.60,P=0.01;r=-0.65,P=0.004);ASNS蛋白表达与OS和PFS亦呈负相关(r=-0.77,P<0.001;r=-0.71,P<0.001)。结论对于ⅠE期和ⅡE期ENKTL患者,以L-ASP为基础的化疗方案联合放疗的疗效优于单纯放疗和CHOP或CHOP样化疗方案联合放疗。ASNS的表达,尤其是蛋白表达水平,可作为L-ASP治疗ⅠE期和ⅡE期ENKTL疗效的预测指标。
基金supported by the National Natural Science Foundation of China(Nos.81502588 and 81370673)Agency of Jiangsu Province Science and Technology(Nos.2013035 and BK20151018)+2 种基金the Key Medical subjects of Jiangsu Province(No.BL2014078)Research Office of Jiangsu Cancer Hospital(No.ZK201401)the Key Discipline of Jiangsu Province(2016-2020)
文摘As the chemotherapeutic resistance of extranodal NK/T-cell lymphoma(ENKTL) rises year by year, searching for novel chemoprevention compounds has become imminent. Gambogic acid(GA) has recently been shown to have anti-tumor effects, but its role and underling mechanism in ENKTL are rather elusive. In the present study, we showed that GA inhibited the cell growth and potently induced the apoptosis of ENKTL cells in vitro in a time-and concentration-dependent manner. Furthermore, GA induced cell death through endoplasmic reticulum stress(ERS) mediated suppression of Akt signaling pathways and finally the release of the caspase-3 proteases. Overall, our data provided evidences supporting GA as a potential therapeutic agent for ENKTL, which may facilitate further preclinical development of anti-tumor drugs.
文摘Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr virus and are prevalent in East Asia and Latin America.Except for that of limited-stage ENKL,the prognosis of both diseases was poor in the previous decade.The advent of non-anthracycline-based chemoradiotherapy has contributed to an improvement in ENKL prognosis,but there is still room for further treatment progress.Recently,the high efficacy of PD-1 antibody was reported in relapsed or refractory ENKL patients.This was later supported by the finding that PD-L1/PD-L2 genetic alterations are frequently observed in ENKL and ANKL patients.Due to the rarity of the disease,a standard treatment for ANKL remains to be established.Currently,allogeneic stem cell transplantation is the only curative treatment,and this is even applicable to chemo-resistant ANKL patients.In this review,we focus on recent treatment approaches for NK/T cell lymphomas including novel agents.
