目的:分析复发/难治原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)患者临床特点并探讨其影响预后的因素,为临床诊疗提供依据。方法:选取复旦大学附属华山医院2006年10月至2015年8月确诊的64例复发/难治PCNS...目的:分析复发/难治原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)患者临床特点并探讨其影响预后的因素,为临床诊疗提供依据。方法:选取复旦大学附属华山医院2006年10月至2015年8月确诊的64例复发/难治PCNSL患者的病例资料、治疗方案、实验室辅助检查指标进行回顾性分析。采用Cox回归多因素分析。结果:单因素和多因素分析结果显示,首次无疾病进展生存期(progression-free survival of first time,PFS1)≤1年、Karnofsky评分(Karnofsky performance score,KPS)<70分为影响复发/难治PCNSL预后的独立危险因素。PFS1≥1年患者中位第二次无疾病进展生存期(median progression-free survival of secondtime,mPFS2)和中位第二次总生存时间(median overall survival of second time,mOS2)分别为19个月和21个月,而PFS1<1年患者mPFS2和mOS2分别为10个月和14个月。复发/难治时KPS评分≥70分患者与KPS评分<70分患者mPFS2分别为40个月和10个月,mOS2分别为43个月和12个月。另外,单因素分析首次复发/难治PCNSL患者选用含有大剂量甲氨蝶呤(high-dose methotrexate,HD-MTX)化疗方案的mPFS2为18个月,而选用不含HD-MTX化疗方案的mPFS2为10个月,差异具有统计学意义。多因素分析结果显示,挽救方案为影响患者PFS的相关因素;单因素分析结果显示,挽救方案含有HD-MTX与不含有HD-MTX组的mOS2分别为23个月和12个月,差异无统计学意义,考虑与样本量较小有关。结论:PFS1≤1年、KPS评分<70分是影响复发/难治PCNSL预后的独立危险因素。首次复发/难治PCNSL患者挽救治疗继续给予HD-MTX为基础的化疗方案可能会提高患者的远期疗效。展开更多
The zebrafish sensory posterior lateral line(pLL)has become an attractive model for studying collective cell migration and cell morphogenesis.Recent studies have indicated that chemokine,Wnt/β-catenin,Fgf,and Delta-N...The zebrafish sensory posterior lateral line(pLL)has become an attractive model for studying collective cell migration and cell morphogenesis.Recent studies have indicated that chemokine,Wnt/β-catenin,Fgf,and Delta-Notch signaling pathways participate in regulating pLL development.However,it remains unclear whether TGFβsignaling pathway is involved in pLL development.Here we report a critical role of TGFβ1 in regulating morphogenesis of the pLL primordium(pLLP).The tgfβ1a gene is abundantly expressed in the lateral line primordium.Knockdown or knockout of tgfβ1a leads to a reduction of neuromast number,an increase of inter-neuromast distance,and a reduced number of hair cells.The aberrant morphogenesis in embryos depleted of tgfβ1a correlates with the reduced expression of atoh1a,deltaA,and n-cadherin/cdh2,which are known important regulators of the pLLP morphogenesis.Like tgfβ1a depletion,knockdown of smad5 that expresses in the pLLP,affects pLLP development whereas overexpression of a constitutive active Smad5 isoform rescues the defects in embryos depleted of tgfβ1a,indicating that Smad5 mediates tgfβ1a function in pLLP development.Therefore,TGFβ/Smad5 signaling plays an important role in the zebrafish lateral line formation.展开更多
Prpf4 （pre-mRNA processing factor 4）, a key component of spliceosome, plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects. In this study, we charac...Prpf4 （pre-mRNA processing factor 4）, a key component of spliceosome, plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects. In this study, we characterized a zebrafish prpf4t243 mutant harboring a Tol2 transposon-based gene trap cassette in the third intron of the prpf4 gene. Cells in the brain and spinal cord gradually undergo p53-dependent apoptosis after 28 hpf in prpf4t243 mutants, suggesting that a widespread function of prpf4 in neural cell survival. In addition, prpf4 is essential for survival of posterior lateral line primordial （pLLP） cells, prpf4 deficiency perturbs Fgf, Wnt/β-catenin and chemokine signaling pathways and impairs pLLP migration. RNA-Seq analysis suggests that prpf4 deficiency may impair spliceosome assembly, leading to compensatory upregulation of core spliceosomal genes and alteration of pre-mRNA splicing. Taken together, our studies uncover an essential role of prpf4 in pre-mRNA splicing, cell survival and pLLP migration.展开更多
文摘目的:分析复发/难治原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)患者临床特点并探讨其影响预后的因素,为临床诊疗提供依据。方法:选取复旦大学附属华山医院2006年10月至2015年8月确诊的64例复发/难治PCNSL患者的病例资料、治疗方案、实验室辅助检查指标进行回顾性分析。采用Cox回归多因素分析。结果:单因素和多因素分析结果显示,首次无疾病进展生存期(progression-free survival of first time,PFS1)≤1年、Karnofsky评分(Karnofsky performance score,KPS)<70分为影响复发/难治PCNSL预后的独立危险因素。PFS1≥1年患者中位第二次无疾病进展生存期(median progression-free survival of secondtime,mPFS2)和中位第二次总生存时间(median overall survival of second time,mOS2)分别为19个月和21个月,而PFS1<1年患者mPFS2和mOS2分别为10个月和14个月。复发/难治时KPS评分≥70分患者与KPS评分<70分患者mPFS2分别为40个月和10个月,mOS2分别为43个月和12个月。另外,单因素分析首次复发/难治PCNSL患者选用含有大剂量甲氨蝶呤(high-dose methotrexate,HD-MTX)化疗方案的mPFS2为18个月,而选用不含HD-MTX化疗方案的mPFS2为10个月,差异具有统计学意义。多因素分析结果显示,挽救方案为影响患者PFS的相关因素;单因素分析结果显示,挽救方案含有HD-MTX与不含有HD-MTX组的mOS2分别为23个月和12个月,差异无统计学意义,考虑与样本量较小有关。结论:PFS1≤1年、KPS评分<70分是影响复发/难治PCNSL预后的独立危险因素。首次复发/难治PCNSL患者挽救治疗继续给予HD-MTX为基础的化疗方案可能会提高患者的远期疗效。
基金This work was financially supported by grants from the National Natural Science Foundation of China(#31371460)Major Science Programs of China(#2012CB945101 and#2011CB943800)。
文摘The zebrafish sensory posterior lateral line(pLL)has become an attractive model for studying collective cell migration and cell morphogenesis.Recent studies have indicated that chemokine,Wnt/β-catenin,Fgf,and Delta-Notch signaling pathways participate in regulating pLL development.However,it remains unclear whether TGFβsignaling pathway is involved in pLL development.Here we report a critical role of TGFβ1 in regulating morphogenesis of the pLL primordium(pLLP).The tgfβ1a gene is abundantly expressed in the lateral line primordium.Knockdown or knockout of tgfβ1a leads to a reduction of neuromast number,an increase of inter-neuromast distance,and a reduced number of hair cells.The aberrant morphogenesis in embryos depleted of tgfβ1a correlates with the reduced expression of atoh1a,deltaA,and n-cadherin/cdh2,which are known important regulators of the pLLP morphogenesis.Like tgfβ1a depletion,knockdown of smad5 that expresses in the pLLP,affects pLLP development whereas overexpression of a constitutive active Smad5 isoform rescues the defects in embryos depleted of tgfβ1a,indicating that Smad5 mediates tgfβ1a function in pLLP development.Therefore,TGFβ/Smad5 signaling plays an important role in the zebrafish lateral line formation.
基金financially supported by grants from the National Natural Science Foundation of China (Nos.31522035,31371460 and 31590832)
文摘Prpf4 （pre-mRNA processing factor 4）, a key component of spliceosome, plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects. In this study, we characterized a zebrafish prpf4t243 mutant harboring a Tol2 transposon-based gene trap cassette in the third intron of the prpf4 gene. Cells in the brain and spinal cord gradually undergo p53-dependent apoptosis after 28 hpf in prpf4t243 mutants, suggesting that a widespread function of prpf4 in neural cell survival. In addition, prpf4 is essential for survival of posterior lateral line primordial （pLLP） cells, prpf4 deficiency perturbs Fgf, Wnt/β-catenin and chemokine signaling pathways and impairs pLLP migration. RNA-Seq analysis suggests that prpf4 deficiency may impair spliceosome assembly, leading to compensatory upregulation of core spliceosomal genes and alteration of pre-mRNA splicing. Taken together, our studies uncover an essential role of prpf4 in pre-mRNA splicing, cell survival and pLLP migration.
