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DETECTION OF BCL-2 GENE MAJOR BREAKPOINT REGION REARRANGEMENT IN HUMAN B-CELL LYMPHOMAS
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作者 强雅维 施秉银 《Academic Journal of Xi'an Jiaotong University》 2000年第1期5-11,共7页
Objective To investigate the frequency of t(14; 18) in different subtypes of B-cell lymphomas and the ability or the polymerase chain reaction(PCR) to detect this rearrangement in frozen samples. Methods 1o7 cases of ... Objective To investigate the frequency of t(14; 18) in different subtypes of B-cell lymphomas and the ability or the polymerase chain reaction(PCR) to detect this rearrangement in frozen samples. Methods 1o7 cases of B-cell lymphomas were studied uslng DNA extracted from rresh-frozen tissues. The DNA samples were amplified by PCR for bcl-2 MBR/JH. The products of bcl-2/JH rearrangement were hybridized with an internal olignucleotide probe or bcl-2 MBR. Results The rearranged bcl-2MBR/JH gene was detected in 13 of the 25(52. o% ) follicular center lymphomas, according to REAL classification: 8 of 11 (72. 7%) grade 1, 2 of 5(40. 0%) grade I, and 3 of 90 (33. 3%) grade, 17 of 82(2o. 8%) cases or difruse large B-cell lymphomas were found to have detectable bel-2 MBR/J. rearrangement- Conclusion The rrequency or bcl-2 MBR/JH rearrangement in diffuse large B-cell lymphomas is significantly lower than those in follicular center lympkomas(X2= 9. 28, P <o. oo5), suggesting that bcl2/JH rearrangements occur mainly in follicular center lymphomas. in addition, the result of reconstruction experiments suggest that amplification or bcl-2 MBR/JH rearrangements by PCR is both sensitive and specific for detection of t (14; 18 ) translocation. 展开更多
关键词 bcl-2 gene major breakpoint region (MBR) polymerase chain reaction(PCR) b-cell lymphomas
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The Expression and Significance of CyclinD2 and Bcl-2 in Diffuse Large B-cell Lymphoma
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作者 Qiushuang Ma Huijuan Geng +4 位作者 Yafei Zhao Jirui Sun Xing Zhou Haiying Yao Jinku Zhang 《Proceedings of Anticancer Research》 2020年第6期5-8,共4页
Objective:To study the expression and significance of cyclinD2 and Bcl-2 in diffuse large B-cell lymphoma.Methods:This project used immunohistochemical methods to detect the expression of cyclinD2 and Bcl-2 in 120 cas... Objective:To study the expression and significance of cyclinD2 and Bcl-2 in diffuse large B-cell lymphoma.Methods:This project used immunohistochemical methods to detect the expression of cyclinD2 and Bcl-2 in 120 cases of diffuse large B-cell lymphoma and 80 cases of reactive hyperplasia of lymphoid tissue.The materials were collected from the hospital from January 2018 to 2020.In March 2015,120 patients had lymphoma tissue removed during the month of surgery.The postoperative pathological diagnosis was DLBCL.Another 80 cases of lymphoid hyperplasia(RLH)tissues were selected as controls.Results:CyclinD2 and BCL-2 expression were not statistically different in patients with diffuse large B-cell lymphoma in different ages,genders,locations,tissue types,and degree of differentiation;but statistically significant in different Ann Arbor stages,immunotypes,IPI index and first treatment efficacy.Conclusion:This research not only has important theoretical value,but also important economic value and social significance. 展开更多
关键词 CYCLIND2 bcl-2 lymphoma
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Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP 被引量:2
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作者 Yan Qin Haizhu Chen +9 位作者 Peng Liu Changgong Zhang Jianliang Yang Lin Gui Xiaohui He Liqiang Zhou Shengyu Zhou Shiyu Jiang Hongxin Jiang Yuankai Shi 《Cancer Biology & Medicine》 SCIE CAS CSCD 2022年第6期893-909,共17页
Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma(DLBCL)are available.This study aimed to comprehensively describe BCL2 genetic... Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma(DLBCL)are available.This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients,and examine correlation of BCL2,TP53 and other genetic alterations with outcomes in patients treated with R-CHOP.Methods:Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL.MYC,BCL2,and BCL6 protein expressions were detected by immunohistochemistry.Results:The presence of BCL2 alterations significantly correlated with poor progression-free survival(PFS)(5-year PFS:13.7%vs.40.8%;P=0.003)and overall survival(OS)(5-year OS:34.0%vs.70.9%;P=0.036).Importantly,patients who harbored BCL2 gain/amplifications(BCL2GA/AMP)also had a remarkably inferior 5-year PFS(11.1%vs.38.3%;P<0.001)and OS(22.1%vs.69.6%;P=0.009).In contrast,neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival.Multivariable analyses showed that the presence of BCL2 alterations,especially BCL2GA/AMP,TP53 mutations,and International Prognostic Index(IPI)were significantly associated with inferior PFS and OS.Novel prognostic models for OS were constructed based on 3 risk factors,including BCL2 alterations(Model 1)or BCL2GA/AMP(Model 2),TP53 mutations,and IPI,to stratify patients into 4 risk groups with different survival outcomes.Conclusions:This study showed that DLBCL patients treated with R-CHOP,BCL2 alterations,especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes,which were independent of the IPI.The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP,but further validation of the prognostic models is still warranted. 展开更多
关键词 BCL2 TP53 genetic alterations diffuse large b-cell lymphoma PROGNOSIS
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Bcl-2 GENE REARRANGEMENT DETERMINED BY PCR AS AMEAN TO DETECT MINIMAL RESIDUAL DISEASE INMALIGNANT LYMPHOMAS
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作者 向直富 卢玉英 +3 位作者 赖永榕 陈燕 李慧玉 邹萍 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1999年第1期49-52,共4页
Objective: To develop a sensitive method to detect minimal residual disease and to elucidate the significance of bcl-2 gene rearrangement in diagnosis and treatment of malignant lymphoma. Methods: Using polymerase cha... Objective: To develop a sensitive method to detect minimal residual disease and to elucidate the significance of bcl-2 gene rearrangement in diagnosis and treatment of malignant lymphoma. Methods: Using polymerase chain reaction (PCR) to detect bcl-2 gene rearrangement and using serial dilution method to define the sensitivity of PCR. Results: In 9 different malignant lymphoma cell lines, Su-DHL-4 and Su-DHL-6 were shown bcl-2(MBR)/JH rearrangement, the sensitivity of PCR was 1:105. In 16 patients with follicular lymphoma, the peripheral blood and bone marrow were PCR positive in 4 cases both at initial diagnosis and after complete remission. Conclusion: Detection of bcl-2 gene rearrangement by PCR provides a sensitive and specific assay of minimal residual disease. It is helpful to improve staging of disease, prognosis and evaluation of the treatment results. 展开更多
关键词 lymphoma Polymerase chain reaction bcl-2 gene Gene rearrangement
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Total saponins in Rubus parvifolius L.induce lymphoma cells apoptosis through upregulated Bax/Fas and downregulated Bcl-2 in vivo and in vitro
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作者 Xiao-Feng Xu Ru-Bin Cheng +1 位作者 Xue-Jin Zhang Rui-Lan Gao 《Traditional Medicine Research》 2019年第2期99-108,共10页
Purpose:To investigate the effect of total saponins of Rubus parvifolius L.(TSRP)on lymphoma Raji cells and further discuss its mechanism.Methods:The model of nude mice bearing Raji cells was established,the volume,we... Purpose:To investigate the effect of total saponins of Rubus parvifolius L.(TSRP)on lymphoma Raji cells and further discuss its mechanism.Methods:The model of nude mice bearing Raji cells was established,the volume,weight and inhibition rate of the transplanted tumor were analyzed and compared after different concentrations of TSRP treatment.Cell apoptosis and expression of Bcl-2,Bax,Fas proteins were detected by TUNEL and immunohistochemiscal method respectively.Effects of TSRP on cell proliferation were tested with MTT assay in vitro.Cell apoptosis and expression of Caspase-9,Caspase-3,Bcl-2,Bax and Fas proteins were tested with DAPI staining and Western blot.Results:TSRP significantly reduced the volume and tumor weight of Raji subcutaneous transplanted tumor and induced the apoptosis of Raji cells in vivo.The tumor inhibition rate of high-dose(100 mg/kg)TSRP is 90.84%.The TUNEL test results show that the fluorescence intensity of the tumor issue treated with TSRP is significantly improved.Compared with the control group,the fluorescence intensity of high-concentration TSRP is 82.43 ± 7.81,which is significantly different(P<0.001).The results of immunohistochemistry test showed that the Bcl-2 expression of Raji cell treated with TSRP is obviously reduced,and Bax expression is obviously increased.Meanwhile,compared with that of control group,Fas expression is obviously reduced.MTT assay showed that TSRP can significantly inhibit proliferation of Raji cells with dose dependence.The inhibition rate of 400 μg/mL TSRP is 53.46 ± 4.90%(P<0.001).DAPI staining results showed that TSRP can significantly induce cell apoptosis.According to Western blot results,it is found that TSRP can significantly inhibit activity of Bcl-2 and increase Bax expression,and TSRP can also inhibit Fas expression.Meanwhile,expression of Caspase-9 and Caspase-3 is also increased.Conclusion:TSRP could inhibit the proliferation of lymphoma via induction of apoptosis in a time and dose-dependent manner.Apoptotic signaling induced by TSRP was characterized by up-regulating Bax,Fas and Caspase-8 protein expression,and down-regulating of Bcl-2 protein expression. 展开更多
关键词 Total SAPONINS of RUBUS parvifolius L. bcl-2 BAX FAS APOPTOSIS lymphoma
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Detection of apoptotic cells and immunohistochemical study of bcl-2 and p53 gene protein in primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma
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作者 肖华亮 王东 +1 位作者 李增鹏 牟江洪 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2000年第3期71-75,共5页
To identify the apoptotic cells in gastric MALT lymphoma and its relationship between bcl-2 and p53 gene expression. Methods: TdT-mediated dUTP biotin Nick End labeling (TUNEL) and immuno-histochemistry ABC method we... To identify the apoptotic cells in gastric MALT lymphoma and its relationship between bcl-2 and p53 gene expression. Methods: TdT-mediated dUTP biotin Nick End labeling (TUNEL) and immuno-histochemistry ABC method were used to display apoptotic cells and the gene protein expression of bcl-2 and p53 independently. Results: Apoptotic indices (AI) in high-grade MALT lymphomas were significantly higher than in mixed-grade group and low-grade group (P<0.05). Bcl-2 was expressed in 83% of low-grade tumors, 61.6% of the median-grade tumors and 43.7% of high-grade tumors. An inverse correlation was observed between the expression of bcl-2 and apoptotic indices. Only 27 cases were p53 positive. The frequency of p53 positivity was significantly increased as the histologic grade advanced (P<0.05). There was also an inverse correlation between the expression of bcl-2 and p53. Conclusion: Apoptosis may be important in tumors development and transmission. p53 and bcl-2 were important regulatory genes of apoptosis and may be associated with transformation from low- grade to high-grade lymphomas. 展开更多
关键词 apoptosis IMMUNOHISTOCHEMISTRY GENES p53 bcl-2 mucosa-associated lymphoid tissue lymphoma
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Effect of rituximab combined with CVAD regimen on serum VEGF and β2-MG levels in patients with primary gastrointestinal B-cell lymphoma
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作者 Shi-Tong Zhang Ai-Min Wang +4 位作者 Zhi-Hui Sun Jing-Jing Song Xiao-Yu Xuan WeiLiu Xin-Chun Tian 《Journal of Hainan Medical University》 2019年第12期20-23,共4页
Objective:To investigate the clinical effect of rituximab combined with CVAD regimen in patients with primary gastrointestinal B-cell lymphoma and serum vascular endothelial growth factor (VEGF) andβ2 microglobulin (... Objective:To investigate the clinical effect of rituximab combined with CVAD regimen in patients with primary gastrointestinal B-cell lymphoma and serum vascular endothelial growth factor (VEGF) andβ2 microglobulin (β2-MG) The impact of the level.Methods:Eighty-four patients with primary gastrointestinal B-cell lymphoma treated from May 2014 to December 2015 were enrolled. Based on the random number table, all the patients were divided into a control group (n=42) and an observation group (n=42). The control group was treated with CVAD. The observation group was treated with rituximab on the basis of the control group. The effect of the patients was evaluated after 3 courses of treatment. The patients were followed up for 3 years after treatment. US RECIST 1.1 was used to evaluate the short-term efficacy on the patients;VEGF, TNF receptor-associated factor 6 (TRAF6) and B-cell lymphoma factor-6 (Bcl-6) levels were measured by enzyme-linked immunosorbent assay;β2-MG level test was implemented to compare the short-term efficacy, biochemical indicators, incidence of toxic side effects and long-term survival rate of the two groups. Results: The short-term efficacy rate of the observation group was 76.19%, which was higher than that of the control group (50.00%) (P<0.05). The levels of VEGF, TRAF6, Bcl-6, andβ2-MG were lower in the observation group after 3 courses of treatment than that in the control group (P<0.05);there was no significant difference in the incidence of neutropenia, gastrointestinal reactions, sepsis, infection, infusion-related reactions and cardiovascular events between the observation group and the control group (P>0.05);The 1-year long-term survival rate after treatment was not statistically significant (P>0.05). The long-term survival rate of the observation group was higher than that of the control group at 2 and 3 years after treatment (P<0.05).Conclusion: The combination of rituximab and CVAD in patients with primary gastrointestinal B-cell lymphoma can improve short-term efficacy, lower VEGF andβ2-MG levels, and lower incidence of side effects. It can improve the long-term survival rate of patients and is worthy of promotion and application. 展开更多
关键词 RITUXIMAB CVAD REGIMEN PRIMARY GASTROINTESTINAL b-cell lymphoma Short-term efficacy Vascular endothelial growth factor β 2 MICROGLOBULIN
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The Expression and Significance of CyclinD2,MPGES-1,Bcl2 in Diffuse Large B-cell Lymphoma
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作者 Qiushuang Ma Peng Lin +4 位作者 Bingjuan Zhou Yafei Zhao Ling Li Jinku Zhang Jirui Sun 《Proceedings of Anticancer Research》 2021年第2期53-56,共4页
Objective:To study the expression and significance of cell cycle proteins CyclinD2,mPGES-1,Bcl2 in diffuse large B-cell lymphoma.Methods:Choose lymphoma and sexually hyper-plastic lymphoid tissues as control.Immunohis... Objective:To study the expression and significance of cell cycle proteins CyclinD2,mPGES-1,Bcl2 in diffuse large B-cell lymphoma.Methods:Choose lymphoma and sexually hyper-plastic lymphoid tissues as control.Immunohistoc-hemical methods were used to detect the expression of CyclinD2,mPGES-1,and Bcl2,and to compare the positive expression rates of CyclinD2,MPGES-1 and Bcl2 in diffuse large B-cell lymphoma and reactive proliferative lymphoid tissues to compare their diffusion formation.B-cell lymphoma was analyzed for its clinicopathological features.Results:The positive expression rate of CyclinD2,mPGES-1 and Bcl2 in diffuse large B-cell lymphoma is higher than that in reactive proliferative lymphoid tissue,and the difference between the two is statistically significant.There was no statistical difference in CyclinD2,mPGES-1 and Bcl2 in diffuse large B-cell lymphoma between patients according to the age,sex,location,tissue type and degree of differentiation.Conclusion:CyclinD2,mPGES-1 and Bcl2 are highly expressed in patients with diffuse large B-cell lymphoma,and can be used as reference indicators for evaluating the malignant degree and efficacy of dysplasia. 展开更多
关键词 CYCLIND2 MPGES-1 BCL2 Diffuse large b-cell lymphoma CLINICOPATHOLOGY
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Bcl-2蛋白家族在PT孔开放中的作用 被引量:3
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作者 张旭(综述) 王松坡(审校) 《实用肿瘤学杂志》 CAS 2011年第2期175-178,共4页
PT孔(permeability transition pore,PT孔)是位于线粒体内外膜之间的由多种蛋白组成的复合体。它在线粒体介导的细胞凋亡中起重要作用,开放后会对细胞造成严重后果。PT孔的开放受到多种因素的调节,其中Bcl-2(B-cell lymphoma-... PT孔(permeability transition pore,PT孔)是位于线粒体内外膜之间的由多种蛋白组成的复合体。它在线粒体介导的细胞凋亡中起重要作用,开放后会对细胞造成严重后果。PT孔的开放受到多种因素的调节,其中Bcl-2(B-cell lymphoma-2)蛋白家族是重要的调节因子,其可作用于门孔的多个组成蛋白,并均可诱使PT孔开放,从而导致线粒体跨膜电位下降和细胞色素C(CytochromeC,CytC)等物质释放,最终引起细胞凋亡。Bcl-2蛋白家族参与PT孔各组分调控的机制是目前研究的热点,本文就此做一综述。 展开更多
关键词 bcl-2蛋白家族 PT lymphoma 线粒体介导 细胞凋亡 b-cell 跨膜电位下降 调节因子
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缺血再灌注损伤与细胞凋亡及相关基因Bcl-2 被引量:1
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作者 王悦 仇树林 《中国美容医学》 CAS 2008年第6期946-948,共3页
缺血再灌注损伤是各种器官及组织移植过程中导致早期失去功能的最主要原因。近年来,越来越多的研究证实,细胞凋亡是造成移植物缺血再灌注损伤早期细胞死亡的主要方式。现将缺血再灌注损伤时细胞凋亡及相关基因B-细胞淋巴瘤/白血病-2... 缺血再灌注损伤是各种器官及组织移植过程中导致早期失去功能的最主要原因。近年来,越来越多的研究证实,细胞凋亡是造成移植物缺血再灌注损伤早期细胞死亡的主要方式。现将缺血再灌注损伤时细胞凋亡及相关基因B-细胞淋巴瘤/白血病-2原癌基因(B-cell lymphoma/leukemia-2.Bcl-2)以及其调控机制的相关研究进展综述如下。 展开更多
关键词 缺血再灌注损伤 细胞凋亡 基因bcl-2 lymphoma B-细胞淋巴瘤 损伤早期 组织移植 细胞死亡
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Prognostic Significance of BCL2 Protein in Diffuse Large Cell Lymphoma of Head and Neck;Relation to Response to Chemotherapy 被引量:1
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作者 Heba A. Elhendawy Afaf T. Ibrahiem +1 位作者 Hoda S. Elmahdi Amany M. Omar 《Open Journal of Pathology》 2020年第2期76-92,共17页
Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that displays a highly variable clinical outcome. It is a neoplasm of large transformed B cells with a diffuse growth pattern. DLBCL is the most common ... Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that displays a highly variable clinical outcome. It is a neoplasm of large transformed B cells with a diffuse growth pattern. DLBCL is the most common type of non-Hodgkin’s lymphoma (NHL) (31% of all cases). Approximately half of patients with DLBCL are cured with current chemotherapy regimens. The purpose of this study was to evaluate BCl2 expression in 45 patients diagnosed with DLBCL of head and neck region and correlate the level of its immunohistochemical expression with different clinicopathological variables with emphasis upon patients’ age, gender, nodal or extra-nodal location of lymphoma, patients’ response to chemotherapy, progression-free survival (PFS) and overall survival (OS). A retrospective analysis of 45 patients diagnosed to have DLBCL. A cut off value of ≥ 50% protein expression denoted BCL2 positivity. Out of 45 cases, 36 cases (80%) revealed BCL2 positive expression and 9 cases (20%) were BCL2 negative. We found statistically significant differences in BCL2 expression regarding different patients’ responses to chemotherapy, patients’ OS and PFS (p ≤ 0.05). No statistically significant differences in BCL2 expression regarding the patients’ Ann Arbor clinical stage, age group and tumor site (nodal or extra-nodal, p > 0.05) using the Chi-square test. BCL2 expression was analyzed in relation to 5 years OS and PFS using Kaplan Meier curves and Log Rank test for survival analysis. Cases that demonstrated BCL2 positivity revealed shortened OS and PFS with highly statistically significant differences among the studied variables (p = 0.000). We also found that patients who respond well to the chemotherapeutic regimen had negative BCL2 expression, the differences were statistically significant (p = 0.015). In conclusion, BCL2 expression could be considered a predictor for patients’ chemotherapeutic response, OS and PFS. 展开更多
关键词 DIFFUSE Large b-cell lymphoma BCL2 CHEMOTHERAPY OS PFS
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Bcl-2与Bax基因在子宫内膜癌治疗中的作用 被引量:1
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作者 吴培英 《护理研究(下旬版)》 2010年第12期3343-3343,共1页
关键词 BAX基因 子宫内膜癌 bcl-2 lymphoma 细胞死亡形式 治疗 细胞凋亡 凋亡相关基因
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Therapeutic effects of human umbilical cord-derived mesenchymal stem cells against acute tubular necrosis quantified through measures of iNOS, BMP-7 and Bcl-2
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作者 Fang Li Feng Xiong +6 位作者 Yun Zhang Yuying Li Hongmei Zhao S. Charles Cho Thomas E. Ichim Xiaofei Yang Xiang Hu 《Open Journal of Regenerative Medicine》 2013年第2期31-38,共8页
Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. In... Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-7 (BMP-7) and B-cell lymphoma 2 (Bcl-2) are surrogate markers of renal tubular epithelial regeneration and subsequent recovery of renal function following ATN. Methods: Serum creatinine (Scr) and blood urea nitrogen (BUN), as well as expression of iNOS, BMP-7 and Bcl-2 in gentamycin-induced ATN rat kidneys was investigated after human umbilical cord-derived mesenchymal stem cell (HUC-MSC) transplantation. Immunohistochemical staining was performed in 3 groups of rats: gentamycin-induced ATN treated with HUC-MSC, gentamycin-induced ATN without HUC-MSC, and untreated rats not receiving any treatments. Results: HUC-MSC transplantation led to a reduction in Scr and BUN in the kidneys of rats with gentamycin-induced ATN. Expression of iNOS in the HUC-MSC treated group occurred later and the expression levels were much lower during gentamycin-induced ATN compared to rats with ATN that were not treated with HUC-MSC. The expression of BMP-7 and Bcl-2 in the MSC-transplanted group was significantly increased compared to both control groups of rats with injured and healthy renal tubules. Conclusions: HUC-MSCs induce renal protection in a rat model of gentamycin-induced ATN, which is associated with reduced iNOS expression and up-regulation of Bcl-2 and BMP-7. 展开更多
关键词 Acute Tubular Necrosis (ATN) Human Umbilical Cord-Derived Mesenchymal STEM CELL (HUC-MSC) STEM CELL Transplantation Inducible Nitric Oxide Synthase (INOS) Bone Morphogenetic Protein-7 (BMP-7) b-cell lymphoma 2 (bcl-2)
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B细胞淋巴瘤/白血病-2和半胱氨酸蛋白-3在神经元损伤后的变化
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作者 籍婷婷 孙义 张析哲 《实用医技杂志》 2015年第1期45-48,共4页
B细胞淋巴瘤/白血病-2(B-cell lymphoma/leukemia2,Bcl-2)和半胱氨酸蛋白酶(Caspase)-3是调控细胞凋亡的关键因素。Bcl-2可以对抗细胞凋亡,Caspase-3是细胞凋亡的主要诱导者,在凋亡执行中起到核心作用,二者在细胞凋亡过程中... B细胞淋巴瘤/白血病-2(B-cell lymphoma/leukemia2,Bcl-2)和半胱氨酸蛋白酶(Caspase)-3是调控细胞凋亡的关键因素。Bcl-2可以对抗细胞凋亡,Caspase-3是细胞凋亡的主要诱导者,在凋亡执行中起到核心作用,二者在细胞凋亡过程中既相互联系又相互制约。脑缺血再灌注损伤后,Bcl-2的过度表达可以使活化的Caspase-3阻断,保护脑组织,缺血早期二者均呈上调趋势,Bcl-2的表达随缺血时间的延长进一步减少。 展开更多
关键词 B细胞淋巴瘤/白血病-2 半胱氨酸蛋白酶 神经元损伤 Caspase-3 脑缺血再灌注损伤 抗细胞凋亡 lymphoma bcl-2
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Cardiac differentiation is modulated by anti-apoptotic signals in murine embryonic stem cells
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作者 Amani Yehya Joseph Azar +4 位作者 Mohamad Al-Fares Helene Boeuf Wassim Abou-Kheir Dana Zeineddine Ola Hadadeh 《World Journal of Stem Cells》 SCIE 2024年第5期551-559,共9页
BACKGROUND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage embryos.ESCs exhibit a unique combination of self-renewal potency,... BACKGROUND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage embryos.ESCs exhibit a unique combination of self-renewal potency,unlimited proliferation,and pluripotency.The latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ layers.Multiple regulatory networks guide ESCs,directing their self-renewal and lineage-specific differentiation.Apoptosis,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic development.How-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly understood.AIM To investigate the regulatory impact of apoptosis on the early differentiation of ESCs into cardiac cells,using mouse ESC(mESC)models-mESC-B-cell lym-phoma 2(BCL-2),mESC-PIM-2,and mESC-metallothionein-1(MET-1)-which overexpress the anti-apoptotic genes Bcl-2,Pim-2,and Met-1,respectively.METHODS mESC-T2(wild-type),mESC-BCL-2,mESC-PIM-2,and mESC-MET-1 have been used to assess the effect of potentiated apoptotic signals on cardiac differentiation.The hanging drop method was adopted to generate embryoid bodies(EBs)and induce terminal differentiation of mESCs.The size of the generated EBs was measured in each condition compared to the wild type.At the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the control.At the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:Troponin T,GATA4,and NKX2.5.Additionally,troponin T protein expression was evaluated through immunofluorescence and western blot assays.RESULTS Our findings showed that the upregulation of Bcl-2,Pim-2,and Met-1 genes led to a reduction in the size of the EBs derived from the manipulated mESCs,in comparison with their wild-type counterpart.Additionally,a decrease in the count of beating cardiomyocytes among differentiated cells was observed.Furthermore,the mRNA expression of three cardiac markers-troponin T,GATA4,and NKX2.5-was diminished in mESCs overexpressing the three anti-apoptotic genes compared to the control cell line.Moreover,the overexpression of the anti-apoptotic genes resulted in a reduction in troponin T protein expression.CONCLUSION Our findings revealed that the upregulation of Bcl-2,Pim-2,and Met-1 genes altered cardiac differentiation,providing insight into the intricate interplay between apoptosis and ESC fate determination. 展开更多
关键词 Mouse embryonic stem cells SELF-RENEWAL Apoptosis Cardiac differentiation b-cell lymphoma 2 PIM-2 Metallothionein-1
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HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression 被引量:2
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作者 Cancan LUO Tiantian YU +1 位作者 Ken H.YOUNG Li Yu 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2022年第8期666-681,共16页
Diffuse large B-cell lymphoma(DLBCL) is an aggressive type of non-Hodgkin’s lymphoma. A total of 10%-15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2(BCL2) ... Diffuse large B-cell lymphoma(DLBCL) is an aggressive type of non-Hodgkin’s lymphoma. A total of 10%-15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2(BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL;however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase(HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL. 展开更多
关键词 Diffuse large b-cell lymphoma(DLBCL) Histone deacetylase(HDAC)inhibitor Venetoclax MYC BCL2 TP53
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Prognostic Significance of Apoptosis Regulators in B-Cell Chronic Lymphocytic Leukemia
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作者 Ahmad Baraka Shereen El Shorbagy +4 位作者 Ola M. Elfarargy Rasha Haggag Lobna A. Abdelaziz Salah F. Elsayed Khaled A. Elbana 《Journal of Cancer Therapy》 2017年第4期360-385,共26页
Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL.... Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL. The study aimed to clarify the prognostic role of MCL-1, BCL-2 and BCL-2/ Bax ratio in B-CLL. Patients & method: Estimation of MCL-1, BCL-2 and Bax expressions by a flow cytometry in 45 B-CLL patients and the prognostic value of these markers were correlated with other well-known established prognostic markers and treatment response. Results: MCL-1 was expressed in 60% of cases while BCL-2 was expressed in 82.2% of cases. MCL-1 expression was significantly high in male gender, short lymphocyte doubling time (LDT), and high expression of CD 38 (p β2M, CD38 expression), low ZAP-70 expression, splenomegaly and higher Rai stage were significantly increased in patients with high expression of BCL-2 (p β2M, high C-D38 expression, low ZAP-70 expression, the poor cytogenetic and splenomegaly in patients with high expression of BCL-2/ Bax ratio (p In conclusion: MCL-1, BCL-2 expressions and BCL-2/Bax ratio could be useful potential predictive and prognostic markers in B-CLL. 展开更多
关键词 MYELOID Cell LEUKEMIA 1 b-cell lymphoma 2 BAX b-cell Chronic LYMPHOCYTIC LEUKEMIA
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帕瑞昔布钠对痫性发作大鼠海马神经元凋亡及Bcl-2、Bax、Caspase-3表达的影响 被引量:3
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作者 宋伏虎 李传翔 +3 位作者 张海星 黄海城 刘彬 樊仕才 《中华神经医学杂志》 CAS CSCD 北大核心 2014年第6期595-599,共5页
目的研究帕瑞昔布钠对痫性发作大鼠海马神经元凋亡及B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、caspase-3蛋白表达的影响。方法30只SD大鼠采用数字随机表法分为3组(n=10):帕瑞昔布钠组和致痫组大鼠分别以4mg/kg帕瑞... 目的研究帕瑞昔布钠对痫性发作大鼠海马神经元凋亡及B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、caspase-3蛋白表达的影响。方法30只SD大鼠采用数字随机表法分为3组(n=10):帕瑞昔布钠组和致痫组大鼠分别以4mg/kg帕瑞昔布钠和等体积生理盐水腹腔注射处理3d后,腹腔注射3mmoL/kg新鲜配制的氯化锂,20h后腹腔注射30mg/kg盐酸匹罗卡品;对照组予腹腔注射与4mg/kg帕瑞昔布钠等体积的生理盐水,不造模。观察3组大鼠行为学变化;造模7d后取材,TUNEL染色评价神经元凋亡情况;Western blotting检测Bcl-2、Bax和caspase-3蛋白表达水平。结果所有致痫大鼠均非常易激惹,帕瑞昔布钠组自发性痫性发作(SRS)次数比致痫组明显减少,差异有统计学意义(P〈0.05)。与对照组比较,致痫组大鼠海马Bcl-2、Bax、caspase-3表达水平增加,Bcl-2/Bax比值升高,差异有统计学意义(P〈0.05)。与致痫组比较,帕瑞昔布钠组大鼠海马Bcl-2、Bax、caspase-3表达水平降低,Bcl-2/BaX比值降低,差异有统计学意义(P〈0.05)。与对照组比较,帕瑞昔布钠组及致痫组大鼠海马TUNEL阳性细胞数均增多,差异有统计学意义(P〈0.05);与致痫组比较,帕瑞昔布钠组大鼠海马TUNEL阳性细胞数降低,差异有统计学意义(P〈0.05)。结论帕瑞昔布钠能减少海马神经元凋亡,抑制Bax、caspase-3蛋白的表达,影响Bcl-2蛋白的表达。其机制可能与帕瑞昔布钠作用于Bcl-2/Bax和caspase-3凋亡通路相关。 展开更多
关键词 帕瑞昔布钠 癫痫 B细胞淋巴瘤 白血病-2 bcl-2相关X蛋白 caspase-3
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发酵冬虫夏草菌粉对糖尿病大鼠肾脏细胞凋亡及Bcl-2、Bax表达的影响 被引量:4
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作者 陈骅 刘占全 +1 位作者 张海松 柳嘉 《江苏医药》 CAS 北大核心 2014年第2期153-155,共3页
目的探讨发酵冬虫夏草菌粉对糖尿病大鼠肾脏细胞凋亡及B细胞淋巴瘤/白血病2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达的影响。方法 24只SD大鼠均分为糖尿病(A)组、治疗(B)组和对照(C)组,A、B组饲喂高糖高脂饲料8周并注射链脲佐菌素30mg/kg建立... 目的探讨发酵冬虫夏草菌粉对糖尿病大鼠肾脏细胞凋亡及B细胞淋巴瘤/白血病2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达的影响。方法 24只SD大鼠均分为糖尿病(A)组、治疗(B)组和对照(C)组,A、B组饲喂高糖高脂饲料8周并注射链脲佐菌素30mg/kg建立糖尿病大鼠模型,C组饲喂普通饲料作对照。B组成模后予发酵冬虫夏草菌粉200mg·kg-1·d-1灌胃8周,A、C组予等体积无菌水灌胃。计算三组内生肌酐清除率(CCr)、24-h尿白蛋白排泄率(UAER),流式细胞术检测肾脏细胞凋亡率,免疫组化法检测肾组织Bcl-2和Bax蛋白表达。结果与C组相比,A、B组CCr降低,24-h UAER、肾脏细胞凋亡率和肾组织Bcl-2和Bax表达升高(P<0.05或P<0.01)。与A组相比,B组CCr和肾小管上皮细胞Bcl-2表达升高,24-h UAER、肾脏细胞凋亡率和肾小管上皮细胞Bax表达降低(P<0.05)。结论发酵冬虫夏草菌粉能抑制糖尿病大鼠肾脏细胞凋亡,与影响Bcl-2/Bax基因表达有关。 展开更多
关键词 发酵冬虫夏草菌粉 糖尿病肾病 B细胞淋巴瘤 白血病2 bcl-2相关Ⅹ蛋白 b-cell lymphoma leukemia-2
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胎膜早破孕妇生殖道B族链球菌感染胎膜组织中Cx43和Bcl-2及Bax蛋白的表达 被引量:4
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作者 燕筠 李伟 周琳 《中华医院感染学杂志》 CAS CSCD 北大核心 2022年第3期458-461,共4页
目的 研究孕妇生殖道B族链球菌(GBS)感染与胎膜早破(PROM)的关系及对胎膜组织中缝隙连接蛋白43(Cx43)、B细胞淋巴瘤基因-2(Bcl-2)和Bcl-2相关X蛋白(Bax)的影响。方法 选取2018年12月-2020年12月东南大学附属中大医院妇产科收治的PROM孕... 目的 研究孕妇生殖道B族链球菌(GBS)感染与胎膜早破(PROM)的关系及对胎膜组织中缝隙连接蛋白43(Cx43)、B细胞淋巴瘤基因-2(Bcl-2)和Bcl-2相关X蛋白(Bax)的影响。方法 选取2018年12月-2020年12月东南大学附属中大医院妇产科收治的PROM孕妇91例和健康孕妇90名分别为PROM组和对照组,分析生殖道GBS感染情况以及胎膜组织中Cx43、Bcl-2和Bax蛋白阳性率。结果 PROM组和对照组GBS感染率分别为53.85%和25.56%,比较有统计学差异(P<0.05);PROM组Cx43和Bcl-2蛋白阳性率均低于对照组,Bax蛋白阳性率高于对照组(P<0.05);PROM组GBS阳性组孕妇Cx43蛋白和Bcl-2蛋白阳性率低于阴性组,Bax蛋白阳性率高于阴性组(P<0.05)。结论 孕妇生殖道GBS感染是PROM重要危险因素,其作用机制可能与胎膜组织Cx43、Bcl-2和Bax蛋白表达异常有关。 展开更多
关键词 孕妇 生殖道感染 B族链球菌 胎膜早破 缝隙连接蛋白43 B细胞淋巴瘤基因-2 bcl-2相关X蛋白
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