目的:分析酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)治疗时代Ph^+急性淋巴细胞白血病(Ph^+acute lymphocytic leukemia,Ph^+ALL)两种转录本p190和p210的临床特征及预后等差异,为该类疾病的临床预后分层和个体化治疗提供依据。...目的:分析酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)治疗时代Ph^+急性淋巴细胞白血病(Ph^+acute lymphocytic leukemia,Ph^+ALL)两种转录本p190和p210的临床特征及预后等差异,为该类疾病的临床预后分层和个体化治疗提供依据。方法:回顾性分析2005年1月至2014年12月在我院诊断为Ph^+ALL且使用常规化疗加TKI治疗伴或不伴造血干细胞移植(HSCT)的65例患者临床资料,对比研究p190(n=41)和p210(n=24)两种不同转录本的临床特征及预后差异。结果:在临床特征上,p190组血小板数低于p210组,虽未达到显著性统计学差异,但却具有较为明显的差异趋势(46.3×10~9/L vs 65×10~9/L)(P=0.084);另外可见p190组初治骨髓样本中幼稚细胞比例较p210组有增高趋势(88.4%vs 76.8%)(P=0.096);其他临床特征如性别,年龄,白细胞,血红蛋白,外周血幼稚细胞比例,BCR-ABL/ABL表达水平等,在两组间未见明显差异。在治疗反应上,p190组和p210组在诱导治疗后完全缓解(complete remission,CR)率分别为80%(32/40)和87%(20/23),无明显差异(P=0.732);诱导至第1次完全缓解(the first complete remission,CR1)所需时间也无明显差异(28 vs 29 d)(P=0.922),两组完全缓解后复发率分别为61%(20/33)和43%(9/21),虽未见明显统计学差异(P=0.202),但p190组的复发时间早于p210组,无论是从确诊时间起(212 vs 274 d)(P=0.077)还是从CR1时间起(146 vs 242 d)(P=0.084)。在预后方面,p190组较p210组有较差的5年总生存(P=0.016)和无事件生存(P=0.085)。结论:p190组较p210组具有血小板数偏低,初治骨髓血幼稚细胞数偏高的特点;CR率、CR1所需时间无明显差别,但p190组较易复发且复发时间较早,且5年总生存及无事件生存差于p210组,提示p190阳性患者在CR1后需尽快采取造血干细胞移植等强化治疗,以减少早期复发,进而改善Ph^+ALL病人的整体预后。展开更多
Two DNA fragments, designated as P190CRI (AA1-55) and P190CRV (AA1597-1667)respectively, which encode amino acid residues of conserved region Ⅰ and Ⅴ on the P190 antigen were amplified by polymerase chain reaction f...Two DNA fragments, designated as P190CRI (AA1-55) and P190CRV (AA1597-1667)respectively, which encode amino acid residues of conserved region Ⅰ and Ⅴ on the P190 antigen were amplified by polymerase chain reaction from genomic DNA in FCCl/HN strain of Plasmodium falciparum isolated from Hainan Province, China. It was found that there were five base substitutions in the P190CR V, in comparison with the nucleotide sequences of MAD20 strain. These two fragments sequenced were inserted into pGEX-2T plasmid. E. coli JM109 (DE3) were transformed with the recombinant plasmids and the parental plasmid. The results showed that the two fragments were expressed as high-level C-terminal fusions with glutathione S-transferase (GST). The fusion proteins were easily purified from bacterial lysates by affinity chromatography using glutathione Sepharose 4B.展开更多
Secondary malignant neoplasms are important late complications after chemotherapy and/or radiotherapy in cancer patients. Therapy-related malignancies include acute leukemia, myelodysplastic syndrome （MDS）, lymphoma...Secondary malignant neoplasms are important late complications after chemotherapy and/or radiotherapy in cancer patients. Therapy-related malignancies include acute leukemia, myelodysplastic syndrome （MDS）, lymphoma, and solid tumors. However, secondary acute lymphoid leukemia or chronic myeloid leukemia （CML） is rarely reported. Here, we present a patient with P190BCR-ABL-positive CML following S-I plus oxaliplatin therapy for gastric adenocarcinoma. The patient has given written informed consent for the use of his medical data.展开更多
miR-190-5p是小分子非编码RNA,参与调控肺腺癌细胞的增殖和转移。对miR-190-5p调控肺腺癌细胞的增殖和转移的机制深入研究会帮助了解到肺腺癌的发生机制和探究潜在的药物干预靶点。本文研究了miR-190-5p对肺腺癌A549细胞的增殖和转移的...miR-190-5p是小分子非编码RNA,参与调控肺腺癌细胞的增殖和转移。对miR-190-5p调控肺腺癌细胞的增殖和转移的机制深入研究会帮助了解到肺腺癌的发生机制和探究潜在的药物干预靶点。本文研究了miR-190-5p对肺腺癌A549细胞的增殖和转移的影响,解释了miR-190-5p促进肺腺癌生长的机制;通过感染miR-190-5p的慢病毒表达系统,克隆了稳定过表达miR-190-5p的肺腺癌A549细胞系;通过生物信息学方法和荧光素酶报告实验确认了miR-190-5p的靶基因。结果发现,稳定过度表达的miR-190-5p能促进A549细胞的增殖和转移;确定了miR-190-5p的靶点是PH域富含亮氨酸重复的蛋白磷酸酶1(Leucine-rich repeat-rich protein phosphatase 1 in the PH domain,PHLPP1),miR-190-5p降低PHLPP1蛋白水平;稳定表达的miR-190-5p增加了A549细胞中E盒结合锌指蛋白1(E box-binding zinc finger protein1,TCF8/ZEB1)、锌指转录因子(Zinc finger transcription factor,Snail)、具有凝血酶原基序的解体蛋白和金属蛋白酶1(a disintegrin and metalloproteinase with thrombospondin motifs 1,ADAMTS1)的表达和蛋白激酶B(protein kinase B,AKT)在Ser473的磷酸化,而过表达PHLPP1削弱了miR-190-5p的功能,降低了miR-190-5p促进A549细胞的增殖、迁移和侵袭能力;miR-190-5p通过抑制PHLPP1的表达而增强了A549细胞的增殖和转移。这表明,miR-190-5p可能可以作为肺腺癌治疗的潜在靶点。展开更多
文摘目的:分析酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)治疗时代Ph^+急性淋巴细胞白血病(Ph^+acute lymphocytic leukemia,Ph^+ALL)两种转录本p190和p210的临床特征及预后等差异,为该类疾病的临床预后分层和个体化治疗提供依据。方法:回顾性分析2005年1月至2014年12月在我院诊断为Ph^+ALL且使用常规化疗加TKI治疗伴或不伴造血干细胞移植(HSCT)的65例患者临床资料,对比研究p190(n=41)和p210(n=24)两种不同转录本的临床特征及预后差异。结果:在临床特征上,p190组血小板数低于p210组,虽未达到显著性统计学差异,但却具有较为明显的差异趋势(46.3×10~9/L vs 65×10~9/L)(P=0.084);另外可见p190组初治骨髓样本中幼稚细胞比例较p210组有增高趋势(88.4%vs 76.8%)(P=0.096);其他临床特征如性别,年龄,白细胞,血红蛋白,外周血幼稚细胞比例,BCR-ABL/ABL表达水平等,在两组间未见明显差异。在治疗反应上,p190组和p210组在诱导治疗后完全缓解(complete remission,CR)率分别为80%(32/40)和87%(20/23),无明显差异(P=0.732);诱导至第1次完全缓解(the first complete remission,CR1)所需时间也无明显差异(28 vs 29 d)(P=0.922),两组完全缓解后复发率分别为61%(20/33)和43%(9/21),虽未见明显统计学差异(P=0.202),但p190组的复发时间早于p210组,无论是从确诊时间起(212 vs 274 d)(P=0.077)还是从CR1时间起(146 vs 242 d)(P=0.084)。在预后方面,p190组较p210组有较差的5年总生存(P=0.016)和无事件生存(P=0.085)。结论:p190组较p210组具有血小板数偏低,初治骨髓血幼稚细胞数偏高的特点;CR率、CR1所需时间无明显差别,但p190组较易复发且复发时间较早,且5年总生存及无事件生存差于p210组,提示p190阳性患者在CR1后需尽快采取造血干细胞移植等强化治疗,以减少早期复发,进而改善Ph^+ALL病人的整体预后。
文摘Two DNA fragments, designated as P190CRI (AA1-55) and P190CRV (AA1597-1667)respectively, which encode amino acid residues of conserved region Ⅰ and Ⅴ on the P190 antigen were amplified by polymerase chain reaction from genomic DNA in FCCl/HN strain of Plasmodium falciparum isolated from Hainan Province, China. It was found that there were five base substitutions in the P190CR V, in comparison with the nucleotide sequences of MAD20 strain. These two fragments sequenced were inserted into pGEX-2T plasmid. E. coli JM109 (DE3) were transformed with the recombinant plasmids and the parental plasmid. The results showed that the two fragments were expressed as high-level C-terminal fusions with glutathione S-transferase (GST). The fusion proteins were easily purified from bacterial lysates by affinity chromatography using glutathione Sepharose 4B.
文摘Secondary malignant neoplasms are important late complications after chemotherapy and/or radiotherapy in cancer patients. Therapy-related malignancies include acute leukemia, myelodysplastic syndrome （MDS）, lymphoma, and solid tumors. However, secondary acute lymphoid leukemia or chronic myeloid leukemia （CML） is rarely reported. Here, we present a patient with P190BCR-ABL-positive CML following S-I plus oxaliplatin therapy for gastric adenocarcinoma. The patient has given written informed consent for the use of his medical data.
文摘miR-190-5p是小分子非编码RNA,参与调控肺腺癌细胞的增殖和转移。对miR-190-5p调控肺腺癌细胞的增殖和转移的机制深入研究会帮助了解到肺腺癌的发生机制和探究潜在的药物干预靶点。本文研究了miR-190-5p对肺腺癌A549细胞的增殖和转移的影响,解释了miR-190-5p促进肺腺癌生长的机制;通过感染miR-190-5p的慢病毒表达系统,克隆了稳定过表达miR-190-5p的肺腺癌A549细胞系;通过生物信息学方法和荧光素酶报告实验确认了miR-190-5p的靶基因。结果发现,稳定过度表达的miR-190-5p能促进A549细胞的增殖和转移;确定了miR-190-5p的靶点是PH域富含亮氨酸重复的蛋白磷酸酶1(Leucine-rich repeat-rich protein phosphatase 1 in the PH domain,PHLPP1),miR-190-5p降低PHLPP1蛋白水平;稳定表达的miR-190-5p增加了A549细胞中E盒结合锌指蛋白1(E box-binding zinc finger protein1,TCF8/ZEB1)、锌指转录因子(Zinc finger transcription factor,Snail)、具有凝血酶原基序的解体蛋白和金属蛋白酶1(a disintegrin and metalloproteinase with thrombospondin motifs 1,ADAMTS1)的表达和蛋白激酶B(protein kinase B,AKT)在Ser473的磷酸化,而过表达PHLPP1削弱了miR-190-5p的功能,降低了miR-190-5p促进A549细胞的增殖、迁移和侵袭能力;miR-190-5p通过抑制PHLPP1的表达而增强了A549细胞的增殖和转移。这表明,miR-190-5p可能可以作为肺腺癌治疗的潜在靶点。
