目的探讨c-Myc、Bcl-2和Bcl-6蛋白表达对原发中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)的预后影响及在治疗方案选择上的指导意义。方法回顾性分析56例PCNSL患者的临床资料,对其病理组织进行免疫组织化学染色(...目的探讨c-Myc、Bcl-2和Bcl-6蛋白表达对原发中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)的预后影响及在治疗方案选择上的指导意义。方法回顾性分析56例PCNSL患者的临床资料,对其病理组织进行免疫组织化学染色(IHC)检测c-Myc、Bcl-2、Bcl-6、CD20、CD10及Mum-1,采用Kaplan-Meier法和COX多因素回归模型进行生存及预后分析,分析上述蛋白表达与预后及治疗方案选择的关系。结果56例PCNSL患者中位总生存时间(OS)25个月,2年生存率为50.0%。COX多因素分析发现,Bcl-2蛋白阳性、c-Myc/Bcl-2蛋白双表达及未予HD-MTX治疗是影响PCNSL患者OS的独立不良预后因素。在予HD-MTX治疗的患者中,c-Myc/Bcl-2蛋白双表达和非双表达患者总体反应率(ORR)分别为42.1%和73.3%,差异有统计学意义(P=0.029)。联用布鲁顿酪氨酸激酶(BTK)抑制剂患者中,非生发中心型(non-GCB)患者的ORR明显高于生发中心型(GCB型)(77.8%vs 16.7%,P=0.041)。结论Bcl-2蛋白阳性表达、c-Myc/Bcl-2蛋白双表达是影响PCNSL患者预后的独立危险因素。HD-MTX为基础的联合化疗可明显延长PCNSL患者生存期,联合BTK抑制剂用于non-GCB型患者可获得较好的ORR。展开更多
Recent genome-wide association studies have identified several lung cancer susceptibility loci. We previously carried out a replication study in male Japanese smokers that focused on chromosome 5p15 (telomerase revers...Recent genome-wide association studies have identified several lung cancer susceptibility loci. We previously carried out a replication study in male Japanese smokers that focused on chromosome 5p15 (telomerase reverse transcriptase) and 3q28 (tumor protein p63) (Shimizu et al., Journal of Cancer Therapy, Vol. 2, No. 5, 2011, pp. 690-696). The current study was performed to confirm the association of traditional susceptibility loci [i.e., alcohol dehydrogenase 1C (ADH1C) and aldehyde dehydrogenase 2 (ALDH2)] in 1039 male Japanese smokers (573 lung cancer patients and 466 healthy control subjects) who were previously enrolled in a study to investigate the low odds ratio for lung cancer risk associated with functionally impaired and deletion polymorphisms in cytochrome P450 2A6 (CYP2A6). The minor allele frequency of rs671 in ALDH2 (0.304) was significantly higher in lung cancer cases than in controls (0.226), with an odds ratio of 1.42 [95% confidence interval (CI) of 1.12 - 1.80, p = 0.0033]. No significant association of rs698 in ADH1C with lung cancer risk was found in this population of male Japanese smokers. For light smokers categorized according to the 50th percentile Brinkman index value among the control subjects (620 daily cigarettes × years) and for the CYP2A6*1 wild-type non-carrier sub-population, significantly high odds ratios of 1.98 and 1.68 (95% CI of 1.28 - 3.06, p = 0.0022, and 1.07 - 2.66, p = 0.025), respectively, were observed for rs671 in ALDH2. The present results support the association of ALDH2 loci with lung cancers and suggest a specific effect of ALDH2 loci resulting in a higher risk of lung cancer in light smokers. CYP2A6 polymorphisms, including copy number polymorphisms, may lower the risk of heavy tobacco use-related lung cancer.展开更多
文摘目的探讨c-Myc、Bcl-2和Bcl-6蛋白表达对原发中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)的预后影响及在治疗方案选择上的指导意义。方法回顾性分析56例PCNSL患者的临床资料,对其病理组织进行免疫组织化学染色(IHC)检测c-Myc、Bcl-2、Bcl-6、CD20、CD10及Mum-1,采用Kaplan-Meier法和COX多因素回归模型进行生存及预后分析,分析上述蛋白表达与预后及治疗方案选择的关系。结果56例PCNSL患者中位总生存时间(OS)25个月,2年生存率为50.0%。COX多因素分析发现,Bcl-2蛋白阳性、c-Myc/Bcl-2蛋白双表达及未予HD-MTX治疗是影响PCNSL患者OS的独立不良预后因素。在予HD-MTX治疗的患者中,c-Myc/Bcl-2蛋白双表达和非双表达患者总体反应率(ORR)分别为42.1%和73.3%,差异有统计学意义(P=0.029)。联用布鲁顿酪氨酸激酶(BTK)抑制剂患者中,非生发中心型(non-GCB)患者的ORR明显高于生发中心型(GCB型)(77.8%vs 16.7%,P=0.041)。结论Bcl-2蛋白阳性表达、c-Myc/Bcl-2蛋白双表达是影响PCNSL患者预后的独立危险因素。HD-MTX为基础的联合化疗可明显延长PCNSL患者生存期,联合BTK抑制剂用于non-GCB型患者可获得较好的ORR。
文摘Recent genome-wide association studies have identified several lung cancer susceptibility loci. We previously carried out a replication study in male Japanese smokers that focused on chromosome 5p15 (telomerase reverse transcriptase) and 3q28 (tumor protein p63) (Shimizu et al., Journal of Cancer Therapy, Vol. 2, No. 5, 2011, pp. 690-696). The current study was performed to confirm the association of traditional susceptibility loci [i.e., alcohol dehydrogenase 1C (ADH1C) and aldehyde dehydrogenase 2 (ALDH2)] in 1039 male Japanese smokers (573 lung cancer patients and 466 healthy control subjects) who were previously enrolled in a study to investigate the low odds ratio for lung cancer risk associated with functionally impaired and deletion polymorphisms in cytochrome P450 2A6 (CYP2A6). The minor allele frequency of rs671 in ALDH2 (0.304) was significantly higher in lung cancer cases than in controls (0.226), with an odds ratio of 1.42 [95% confidence interval (CI) of 1.12 - 1.80, p = 0.0033]. No significant association of rs698 in ADH1C with lung cancer risk was found in this population of male Japanese smokers. For light smokers categorized according to the 50th percentile Brinkman index value among the control subjects (620 daily cigarettes × years) and for the CYP2A6*1 wild-type non-carrier sub-population, significantly high odds ratios of 1.98 and 1.68 (95% CI of 1.28 - 3.06, p = 0.0022, and 1.07 - 2.66, p = 0.025), respectively, were observed for rs671 in ALDH2. The present results support the association of ALDH2 loci with lung cancers and suggest a specific effect of ALDH2 loci resulting in a higher risk of lung cancer in light smokers. CYP2A6 polymorphisms, including copy number polymorphisms, may lower the risk of heavy tobacco use-related lung cancer.
