目的探讨EB病毒(Epstein-Barr virus,EBV)在原发性扁桃体弥漫大B细胞淋巴瘤(primary tonsillar diffuse large B cell lymphoma,PTDLBCL)内的感染情况及其临床病理学意义。方法采用EBV编码微小RNA(EBV encoded miRNA,EBERs)原位杂交(in ...目的探讨EB病毒(Epstein-Barr virus,EBV)在原发性扁桃体弥漫大B细胞淋巴瘤(primary tonsillar diffuse large B cell lymphoma,PTDLBCL)内的感染情况及其临床病理学意义。方法采用EBV编码微小RNA(EBV encoded miRNA,EBERs)原位杂交(in situ hybridization,ISH)和EBV潜伏膜蛋白1(latent membrane protein 1,LMP1),PCR检测EBV在PTDLBCL(n=81)和原发性非扁桃体弥漫大B细胞淋巴瘤(primary nontonsillar diffuse large B cell lymphoma,PNTDLBCL)(n=42)、鼻腔NK/T细胞淋巴瘤(n=10)及慢性扁桃体炎(n=20)中的感染情况,并分析差异。结果 ISH结果显示,PTDLBCL中EBV的阳性率高于PNTDLBCL(t=5.603,P=0.018)。检测PTDLBCL中EBV,PCR阳性率显著高于ISH(t=11.139,P=0.001)。EBV阳性PTDLBCL者预后优于阴性者(t=5.683,P=0.017);与患者年龄、部位及性别的差异无统计学意义。结论EBV在PTDLBCL中高表达,其存在与患者预后正相关。检测PTDLBCL的EBV,LMP1PCR的敏感度高于EBERs ISH,而EBERs ISH的特异度高于LMP1PCR。展开更多
弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）是成人淋巴瘤中较常见的一种类型，其在临床表现、组织形态和预后等方面具有较大的异质性。DLBCL患者的诊断、预后评估等相关实验室检查需抗凝外周血样，我们在临床工作中遇...弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）是成人淋巴瘤中较常见的一种类型，其在临床表现、组织形态和预后等方面具有较大的异质性。DLBCL患者的诊断、预后评估等相关实验室检查需抗凝外周血样，我们在临床工作中遇到DLBCL患者外周抗凝血样出现异常凝集，现报告其中1例典型病例并进行相关文献复习，以提高对该疾病的认识。展开更多
<strong>Objective</strong>: Exploring the expression characteristics of CRP/ALB (CAR) in DLBCL patients and its value in prognostic judgment. <strong>Methods:</strong> We collected the basic in...<strong>Objective</strong>: Exploring the expression characteristics of CRP/ALB (CAR) in DLBCL patients and its value in prognostic judgment. <strong>Methods:</strong> We collected the basic information, clinical characteristics, laboratory examinations and follow-up prognosis of 142 newly diagnosed DLBCL patients with relatively complete data in our hospital and performed statistical analysis. We used X-tile analysis software to obtain the best cut-off value of CAR (0.33), compared the clinical characteristics and survival of patients in the high CAR group and the low CAR group, and compared the survival status with the IPI scoring system. <strong>Results:</strong> 1) There were significant differences in staging, grouping, IPI scores, extranodal involvement, LDH levels, <em>β</em>2-microglobulin, CA125, and Hb levels between the high CAR group and the low CAR group (all <em>P</em> < 0.05). 2) According to the survival curve, the OS of the high CAR group was significantly shorter than that of the low CAR group (<em>P</em> < 0.01), and the one-year, three-year and five-year survival conditions of high CAR group were all shorter than those of low CAR group. 3) COX analysis showed that high CAR is an independent poor prognostic factor for DLBCL patients. 4) A comparative analysis of OS, three-year and five-year survival showed that the combination of CAR and IPI was significantly better than the IPI system, and there was no significant difference in the evaluation value of the prognosis between CAR alone and IPI alone. <strong>Conclusion:</strong> High CAR value, like the IPI scoring system, is an independent poor prognostic factor of DLBCL, can be used as a reliable indicator of prognosis. And CAR can also be combined with IPI to evaluate the prognosis of DLBCL, of which the effect is better than that of IPI alone.展开更多
Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study ai...Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.展开更多
Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular st...Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.展开更多
文摘目的探讨EB病毒(Epstein-Barr virus,EBV)在原发性扁桃体弥漫大B细胞淋巴瘤(primary tonsillar diffuse large B cell lymphoma,PTDLBCL)内的感染情况及其临床病理学意义。方法采用EBV编码微小RNA(EBV encoded miRNA,EBERs)原位杂交(in situ hybridization,ISH)和EBV潜伏膜蛋白1(latent membrane protein 1,LMP1),PCR检测EBV在PTDLBCL(n=81)和原发性非扁桃体弥漫大B细胞淋巴瘤(primary nontonsillar diffuse large B cell lymphoma,PNTDLBCL)(n=42)、鼻腔NK/T细胞淋巴瘤(n=10)及慢性扁桃体炎(n=20)中的感染情况,并分析差异。结果 ISH结果显示,PTDLBCL中EBV的阳性率高于PNTDLBCL(t=5.603,P=0.018)。检测PTDLBCL中EBV,PCR阳性率显著高于ISH(t=11.139,P=0.001)。EBV阳性PTDLBCL者预后优于阴性者(t=5.683,P=0.017);与患者年龄、部位及性别的差异无统计学意义。结论EBV在PTDLBCL中高表达,其存在与患者预后正相关。检测PTDLBCL的EBV,LMP1PCR的敏感度高于EBERs ISH,而EBERs ISH的特异度高于LMP1PCR。
文摘弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）是成人淋巴瘤中较常见的一种类型，其在临床表现、组织形态和预后等方面具有较大的异质性。DLBCL患者的诊断、预后评估等相关实验室检查需抗凝外周血样，我们在临床工作中遇到DLBCL患者外周抗凝血样出现异常凝集，现报告其中1例典型病例并进行相关文献复习，以提高对该疾病的认识。
文摘<strong>Objective</strong>: Exploring the expression characteristics of CRP/ALB (CAR) in DLBCL patients and its value in prognostic judgment. <strong>Methods:</strong> We collected the basic information, clinical characteristics, laboratory examinations and follow-up prognosis of 142 newly diagnosed DLBCL patients with relatively complete data in our hospital and performed statistical analysis. We used X-tile analysis software to obtain the best cut-off value of CAR (0.33), compared the clinical characteristics and survival of patients in the high CAR group and the low CAR group, and compared the survival status with the IPI scoring system. <strong>Results:</strong> 1) There were significant differences in staging, grouping, IPI scores, extranodal involvement, LDH levels, <em>β</em>2-microglobulin, CA125, and Hb levels between the high CAR group and the low CAR group (all <em>P</em> < 0.05). 2) According to the survival curve, the OS of the high CAR group was significantly shorter than that of the low CAR group (<em>P</em> < 0.01), and the one-year, three-year and five-year survival conditions of high CAR group were all shorter than those of low CAR group. 3) COX analysis showed that high CAR is an independent poor prognostic factor for DLBCL patients. 4) A comparative analysis of OS, three-year and five-year survival showed that the combination of CAR and IPI was significantly better than the IPI system, and there was no significant difference in the evaluation value of the prognosis between CAR alone and IPI alone. <strong>Conclusion:</strong> High CAR value, like the IPI scoring system, is an independent poor prognostic factor of DLBCL, can be used as a reliable indicator of prognosis. And CAR can also be combined with IPI to evaluate the prognosis of DLBCL, of which the effect is better than that of IPI alone.
基金supported by the National Natural Science Foundation of China(82260716)the Key Research and Development Program of Ningxia(2023BEG02010).
文摘Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.
基金supported by the National Italian Research Council(CNR)“Progetto DSB.AD007.305.001”to Monica Rinaldi。
文摘Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.
