目的:探讨治疗前淋巴细胞与C反应蛋白比值(LCR)对结外NK/T细胞淋巴瘤(ENKTL)预后的判断价值。方法:回顾性分析郑州大学第一附属医院收治的203例初诊为ENKTL患者的临床资料,ROC曲线得到LCR预测5 a总生存期(OS)的最佳截断值,并根据截断值...目的:探讨治疗前淋巴细胞与C反应蛋白比值(LCR)对结外NK/T细胞淋巴瘤(ENKTL)预后的判断价值。方法:回顾性分析郑州大学第一附属医院收治的203例初诊为ENKTL患者的临床资料,ROC曲线得到LCR预测5 a总生存期(OS)的最佳截断值,并根据截断值将患者分为两组,绘制Kaplan-Meier生存曲线,采用Cox回归分析无进展生存期(PFS)和OS的影响因素。结果:LCR预测5 a OS的最佳截断值为0.19,低LCR组患者预后较差(P<0.001)。Cox回归分析结果表明,低LCR组ENKTL患者预后较差,PFS和OS的HR(95%CI)分别为0.462(0.336~0.636)和0.381(0.275~0.527)。结论:治疗前LCR可影响ENKTL预后,低LCR患者的预后较差。展开更多
The B-cell lymphoma-extra large （Bcl-xL） is a mitochondrial anti-apoptotic protein that plays a role in neuroprotection. However, during excitotoxic stimulation, Bcl-xL undergoes caspase-dependent cleavage and produ...The B-cell lymphoma-extra large （Bcl-xL） is a mitochondrial anti-apoptotic protein that plays a role in neuroprotection. However, during excitotoxic stimulation, Bcl-xL undergoes caspase-dependent cleavage and produces a fragmented form, △N-Bcl-xL. Accumulation of △N-Bcl-xL is associated with mitochon- drial dysfunction and neuronal death. Therefore, strategies to inhibit the activity or formation of △N-Bcl- xL protect the brain against excitotoxic injuries. Our team found that the pharmacological inhibitor △BT- 737 exerts dose dependent effects in primary neurons. When primary hippocampal neurons were treated with 1 μM ABT-737, glutamate-mediated mitochondrial damage and neuronal death were exacerbated, whereas 10 nM △BT-737, a 100-fold lower concentration, protected mitochondrial function and enhanced neuronal viability against glutamate toxicity. In addition, we suggested acute vs. prolonged formation of △N-Bcl-xL may have different effects on mitochondrial or neuronal functions. Unlike acute production of △N-Bcl-xL by glutamate, overexpression of △N-Bcl-xL did not cause drastic changes in neuronal viability. We predicted that neurons undergo adaptation and may activate altered metabolism to compensate for △N-Bcl-xL-mediated mitochondrial dysfunction. Although the detailed mechanism of ABT-mediated neurotoxicity neuroprotection is still unclear, our study shows that the mitochondrial membrane protein △N-Bcl-xL is a central target for interventions.展开更多
AIM:To investigate the association between prognosis of rectal cancer treated with chemoradiotherapy(CRT) and expression of sensitive-to-apoptosis(SAG),B-cell lymphoma-extra large(Bcl-X L) and Bcl-2 homologous antagon...AIM:To investigate the association between prognosis of rectal cancer treated with chemoradiotherapy(CRT) and expression of sensitive-to-apoptosis(SAG),B-cell lymphoma-extra large(Bcl-X L) and Bcl-2 homologous antagonist/killer(Bak).METHODS:Real-time quantitative polymerase chain reaction was used to determine the expression of proteins of interest,namely SAG,Bcl-X L,Bak and β-actin,in rectal carcinoma patients who had a follow-up period of 3 years after CRT.Biopsy specimens were excised from the rectal tumor preceding CRT.RESULTS:SAG,Bcl-X L and Bak proteins showed significant correlations with each other.In multivariate analysis,patients with high vs low SAG expression showed a statistically significant difference in 2-year survival rates:56% vs 73%,respectively(P = 0.056).On the other hand,there were no significant correlations between the expression levels of all three genes and metastatic rates or tumor responses to CRT.Mean overall survival in the patients with elevated SAG expression was 27.1 mo ± 3.9 mo [95% confidence interval(CI):19.3-34.9],and in patients with reduced expression,it was 32.1 mo ± 2.5 mo(95% CI:27.3-36.9).The corresponding values for Bcl-X L were 28.0 mo ± 4.1 mo(95% CI:19.9-36.1) and 31.7 mo ± 2.9 mo(95% CI:26.0-37.5),and those for Bak were 29.8 mo ± 3.7 mo(95% CI:22.5-37.2) and 30.6 mo ± 2.4 mo(95% CI:25.5-35.0),respectively.CONCLUSION:Two-year survival rates significantly correlated with low SAG expression,and SAG may be a candidate gene for good prognosis,independent of therapeutic response of different individuals.展开更多
文摘目的:探讨治疗前淋巴细胞与C反应蛋白比值(LCR)对结外NK/T细胞淋巴瘤(ENKTL)预后的判断价值。方法:回顾性分析郑州大学第一附属医院收治的203例初诊为ENKTL患者的临床资料,ROC曲线得到LCR预测5 a总生存期(OS)的最佳截断值,并根据截断值将患者分为两组,绘制Kaplan-Meier生存曲线,采用Cox回归分析无进展生存期(PFS)和OS的影响因素。结果:LCR预测5 a OS的最佳截断值为0.19,低LCR组患者预后较差(P<0.001)。Cox回归分析结果表明,低LCR组ENKTL患者预后较差,PFS和OS的HR(95%CI)分别为0.462(0.336~0.636)和0.381(0.275~0.527)。结论:治疗前LCR可影响ENKTL预后,低LCR患者的预后较差。
文摘The B-cell lymphoma-extra large （Bcl-xL） is a mitochondrial anti-apoptotic protein that plays a role in neuroprotection. However, during excitotoxic stimulation, Bcl-xL undergoes caspase-dependent cleavage and produces a fragmented form, △N-Bcl-xL. Accumulation of △N-Bcl-xL is associated with mitochon- drial dysfunction and neuronal death. Therefore, strategies to inhibit the activity or formation of △N-Bcl- xL protect the brain against excitotoxic injuries. Our team found that the pharmacological inhibitor △BT- 737 exerts dose dependent effects in primary neurons. When primary hippocampal neurons were treated with 1 μM ABT-737, glutamate-mediated mitochondrial damage and neuronal death were exacerbated, whereas 10 nM △BT-737, a 100-fold lower concentration, protected mitochondrial function and enhanced neuronal viability against glutamate toxicity. In addition, we suggested acute vs. prolonged formation of △N-Bcl-xL may have different effects on mitochondrial or neuronal functions. Unlike acute production of △N-Bcl-xL by glutamate, overexpression of △N-Bcl-xL did not cause drastic changes in neuronal viability. We predicted that neurons undergo adaptation and may activate altered metabolism to compensate for △N-Bcl-xL-mediated mitochondrial dysfunction. Although the detailed mechanism of ABT-mediated neurotoxicity neuroprotection is still unclear, our study shows that the mitochondrial membrane protein △N-Bcl-xL is a central target for interventions.
基金Supported by Marmara University Research Fund, No. SAG-DKR-140305-0089
文摘AIM:To investigate the association between prognosis of rectal cancer treated with chemoradiotherapy(CRT) and expression of sensitive-to-apoptosis(SAG),B-cell lymphoma-extra large(Bcl-X L) and Bcl-2 homologous antagonist/killer(Bak).METHODS:Real-time quantitative polymerase chain reaction was used to determine the expression of proteins of interest,namely SAG,Bcl-X L,Bak and β-actin,in rectal carcinoma patients who had a follow-up period of 3 years after CRT.Biopsy specimens were excised from the rectal tumor preceding CRT.RESULTS:SAG,Bcl-X L and Bak proteins showed significant correlations with each other.In multivariate analysis,patients with high vs low SAG expression showed a statistically significant difference in 2-year survival rates:56% vs 73%,respectively(P = 0.056).On the other hand,there were no significant correlations between the expression levels of all three genes and metastatic rates or tumor responses to CRT.Mean overall survival in the patients with elevated SAG expression was 27.1 mo ± 3.9 mo [95% confidence interval(CI):19.3-34.9],and in patients with reduced expression,it was 32.1 mo ± 2.5 mo(95% CI:27.3-36.9).The corresponding values for Bcl-X L were 28.0 mo ± 4.1 mo(95% CI:19.9-36.1) and 31.7 mo ± 2.9 mo(95% CI:26.0-37.5),and those for Bak were 29.8 mo ± 3.7 mo(95% CI:22.5-37.2) and 30.6 mo ± 2.4 mo(95% CI:25.5-35.0),respectively.CONCLUSION:Two-year survival rates significantly correlated with low SAG expression,and SAG may be a candidate gene for good prognosis,independent of therapeutic response of different individuals.
