GDP与CHOP方案治疗非特异性外周T 细胞淋巴瘤的临床对比研究

目的:探讨GDP与CHOP方案治疗非特异性外周T细胞淋巴瘤的临床疗效,为临床治疗提供参考。方法:选择2013年1月到2016年1月我院收治的非特异性外周T细胞淋巴瘤患者80例,随机分为GDP组(n=40)和CHOP组(n=40)。GDP组患者给予GDP治疗方案(顺铂+吉西他滨+强的松),CHOP组患者给予CHOP治疗方案(多柔比星+环磷酰胺+长春新碱+强的松),两组患者均治疗6个疗程。比较两组患者临床疗效和不良反应发生情况。结果:GDP组患者近期疗效总有效率为75.00%,明显高于CHOP组的45.00%,差异具有统计学意义(P0.05)。GDP组患者的无进展生存期(PFS)、总生存期(OS)分别为(9.69±1.50)月和(16.72±3.06)月,明显大于CHOP组的(5.16±1.38)月和(10.98±3.37)月,差异具有统计学意义(P0.05)。GDP组患者恶心呕吐的发生率为72.50%,明显低于CHOP组的97.50%,差异具有统计学意义(P0.05)。结论:GDP方案治疗非特异性外周T细胞淋巴瘤的临床疗效明显优于CHOP方案,且不良反应发生率低,值得在临床上推广应用。     

Therapeutic implication of concomitant chromosomal aberrations in patients with aggressive B-cell lymphomas

A subset of diffuse large B-cell lymphomas (DLBCL) harbors concomitant rearrangements of MYC, BCL2 and BCL6 and is characterized by clinical aggressiveness and intrinsic refractoriness to standard chemo-immunotherapy. Commonly identified as “double or triple hit” lymphomas, these diseases represent a therapeutic challenge to chemotherapy-based regimens and likely require a more targeted approach. Herein we summarize the unique biological behavior of double and triple hit lymphomas focusing on the coordinated network of pathways that enable cancer cells to tolerate the oncogenic stress imposed by the co-expression of MYC, BCL2 and BCL6. We discuss how these enabling pathways contribute to the chemo-refractoriness of these tumors. We propose to exploit lymphoma cells' addiction to these oncogenic networks to design combinatorial treatments for this aggressive disease based on the modulation of epigenetically-silenced pathways and decreasing expression and activity of these oncogenic drivers.     

西达本胺诱导胰腺癌细胞凋亡

目的：观察西达本胺对胰腺癌细胞BxPC-3和PANC-1生长抑制及诱导细胞凋亡作用,探讨西达本胺抗胰腺癌的机制。方法：西达本胺处理BxPC-3和PANC-1细胞后,用流式细胞术检测细胞的凋亡率,用罗丹明123和DCFH—DA染色方法测定细胞线粒体膜跨膜电位变化和活性氧（ROS）的产生,用Western印迹检测Bcl-2家族和γH2AX蛋白表达的变化。结果：西达本胺对胰腺癌细胞BxPC-3和PANC-1具有生长抑制和诱导细胞凋亡的作用,且呈时间和剂量依赖关系;处理72h后,胰腺癌细胞内ROS产生增强导致DNA损伤发生,且线粒体跨膜电位明显下降;促凋亡蛋白Bax的表达,抑制抑凋亡蛋白Bcl-2和Mcl—1的表达。结论：西达本胺具有抑制胰腺癌细胞增殖,诱导细胞凋亡的作用;西达本胺增强胰腺癌细胞内ROS的产生并导致DNA损伤,最终诱导细胞凋亡的发生。     

EPOCH-L方案治疗复发难治性T细胞淋巴瘤的临床研究

目的:探讨EPOCH-L方案治疗复发难治性T细胞淋巴瘤的疗效及安全性。方法:回顾性分析解放军某医院2012年1月至2017年1月收治的12例复发难治性T细胞淋巴瘤患者的临床资料,均采用EPOCH-L方案化疗(依托泊苷50 mg/m2第1～4天、吡柔比星10 mg/m2第1～4天、长春地辛1 mg/d第1～4天、环磷酰胺750 mg/m2第5天、泼尼龙60 mg/m2第1～5天、培门冬酶2500 iu/m2第6天)3～6个周期,并随机选取同期进行异基因造血干细胞移植治疗的12例复发难治性T细胞淋巴瘤患者为对照组,比较两组的临床疗效及不良反应的发生情况。结果:随访至2018年1月,EPOCH-L方案组患者取得完全缓解4例(33.3%),部分缓解4例(33.3%),总有效率为66.7%,中位生存期为23.7(7～65)个月,随访期间总生存率为25%;对照组患者中位生存期为9.2(3～60)个月,无病生存率为41.7%,总体生存时间分布差异无统计学意义(P=0.683)。实验组没有患者死于化疗合并症(0.0%),对照组4例死于移植合并症(33.3%),差异有统计学意义(P=0.028)。结论:EPOCH-L方案治疗复发难治性T细胞淋巴瘤的临床效果与异基因造血干细胞移植治疗相当,且安全性较高。     

国产利妥昔单抗治疗弥漫大B细胞淋巴瘤的疗效及安全性

摘要 目的：探讨弥漫大B细胞淋巴瘤患者采用国产利妥昔单抗为基础的化疗方案的疗效及安全性。方法：回顾性分析2020年3月至2022年5月份在安徽省第二人民医院血液内科诊治的弥漫大B淋巴瘤患者31例,均接受国产利妥昔单抗为基础的联合方案化疗,其中非生发中心来源的弥漫大B细胞淋巴瘤患者25例,生发中心来源的弥漫大B细胞淋巴瘤患者6例。21~28 d为一个疗程,这些患者至少接受2~8个疗程的联合化疗,并且2个疗程以后进行疗效评估及不良反应监测。结果：①本研究31例弥漫大B细胞淋巴瘤患者接受利妥昔单抗为基础的联合化疗方案治疗后,疗效评估为完全缓解CR 16例（51.6%）,部分缓解PR 10例（32.3%）,疾病稳定SD 2例（6.5%）,疾病进展PD 3例（9.7%）,总体反应率ORR 83.9%。②31例弥漫大B细胞淋巴瘤患者接受国产利妥昔单抗治疗后,常见的不良反应发生率依次为：血液学毒性29.0%（9/31）,包括中性粒细胞减少、血小板减少等等。其次为感染19.4%（6/31）、消化道症状16.1%（5/31）,包括腹痛、腹泻、便秘等等。所有常见不良反应经过对症处理后均可好转。仅有1例患者发生过敏反应3.2%（1/31）,1例患者因病情严重而死亡。结论：国产利妥昔单抗在弥漫大B细胞淋巴瘤患者的治疗中具有良好的临床疗效及安全性,不良反应较少,值得进一步探讨和应用。     

Comparative clinical pharmacokinetics of antibody-drug conjugates in first-in-human Phase 1 studies

Although there are currently more than 30 antibody-drug conjugates (ADC) in clinical development for the treatment of blood cancers and solid tumors, comparison of their clinical pharmacokinetics (PK) is challenging because of the large number of, and differences between, the targets, ADC constructs, dosing regimens, and patient populations. In this review, we standardized the evaluation, using non-compartmental PK data reported at Cycle 1, i.e., following the first drug administration of what is usually a repeated-dose treatment, in monotherapy. We report ADC clinical PK properties, dosing regimen, determination of doses ranges and associated maximum tolerated doses. We also evaluated the effect of structural characteristics and target types (hematological vs. solid tumors) on PK. In addition, we discuss how integration of PK/pharmacodynamics approaches on top of classical dose escalation in first-in-human studies may improve dosing regimen determination for subsequent phases of clinical development.     

Hyper-CVAD/MA治疗复发或难治性弥漫大B 细胞淋巴瘤的临床研究

目的:探讨Hyper-CVAD/MA方案治疗复发或难治弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的疗效及安全性。方法:观察26例经系统化疗后复发或难治的DLBCL患者接受Hyper-CVAD/MA方案化疗,21-28天为1周期,连续2个周期评价疗效及安全性,分析生存情况。结果:全组26例患者中,总有效率为46.15%,其中完全缓解(complete remission,CR)3例(11.54%),部分缓解(partial remission,PR)9例(34.61%),全组患者中位生存时间为10(2-25)个月,1年和2年总生存率分别为28.57%、14.29%。不良反应主要表现为III-IV度骨髓抑制及继发的肺部感染,其他包括胃肠道反应、口腔炎、肝功能异常等。结论:Hyper-CVAD/MA治疗复发难治DLBCL有一定的疗效,且患者可耐受,可作为二线方案的一个选择。     

西达本胺对人前列腺癌DU145及PC3细胞凋亡的影响

目的:研究西达本胺对前列腺癌DU145、PC3细胞生长抑制及凋亡调控的作用。方法:设置西达本胺浓度分别为4、8、16、32和64μmol/L的5个处理组和对照组(未加西达本胺),分别处理DU145、PC3细胞不同时间,采用MTT法检测细胞的增殖抑制情况,用倒置显微镜观察细胞形态,用流式细胞仪进行细胞凋亡分析,用免疫印迹法检测细胞内Bax、Bcl-2、caspase-3、caspase-9的表达水平。结果:与对照组比较,西达本胺处理组可使细胞明显变圆、体积缩小、脱壁细胞增多;MTT法检测显示,随着西达本胺浓度的增加和作用时间的延长,对DU145、PC3细胞的增殖抑制作用增强,并呈时间、剂量正相关(P<0.01);流式细胞术显示,对照组和16、64μmol/L西达本胺组细胞凋亡率分别为42.24%、50.23%;随着西达本胺浓度的增加,Bcl-2的表达呈下调趋势,Bax、caspase-3、caspase-9的表达呈上调趋势,呈剂量正相关。结论:西达本胺对前列腺癌DU145、PC3细胞生长具有明显的抑制作用,作用机制可能与Bax、Bcl-2、caspase-3及caspase-9凋亡信号通路有关。     

基于AFM单细胞力谱技术的淋巴瘤细胞黏附力测量

细胞黏附在细胞生理功能中起着重要的调控作用,对细胞黏附行为进行定量研究有助于理解生命活动内在机制.原子力显微镜（AFM）的出现为研究溶液环境下微纳尺度生物系统的生物物理特性提供了强大工具,特别是AFM单细胞力谱（SCFS）技术可以对单细胞黏附力进行测量.但目前利用SCFS技术进行的研究主要集中在贴壁细胞,对于动物悬浮细胞黏附行为进行的研究还较为缺乏.本文利用AFM单细胞力谱技术（SCFS）对淋巴瘤细胞黏附行为进行了定量测量.研究了淋巴瘤细胞与其单克隆抗体药物利妥昔（利妥昔单抗与淋巴瘤细胞表面的CD20结合后激活免疫攻击）之间的黏附力,分析了利妥昔浓度及SCFS测量参数对黏附力的影响,并对淋巴瘤细胞之间的黏附力进行了测量.实验结果证明了SCFS技术探测动物悬浮细胞黏附行为的能力,加深了对淋巴瘤细胞黏附作用的认识,为单细胞尺度下生物力学探测提供了新的可能.     

7th Cancer Scientific Forum of the Cancérop?le Lyon Auvergne Rh?ne-Alpes: March 20–21, 2012, Lyon,France

The Innovative Approaches in Anti-Cancer Monoclonal Antibodies meeting, held on March 20, 2012 in Lyon, was organized by Cancéropôle Lyon Auvergne-Rhône-Alps in partnership with the French competitiveness cluster Lyonbiopôle. CLARA is one of the seven cancer research clusters within France in charge of facilitating Translational Oncology Research by taking into account the objectives of the French National Cancer Plans I and II and, in coordination with the French National Cancer Institute and local authorities (mainly Grand Lyon, Rhône County and Rhône-Alpes Region), to perform economic development of research findings. The contribution of lectures by outstanding speakers as described in this report, the organization of two-round tables: “Antibody treatment in cancer: Unmet needs in solid tumors and hematological malignancies,” and “From chimeric to more than human antibodies,” together with face-to-face meetings, was shared by over 230 participants. The lectures provided an overview of the commercial pipeline of monoclonal antibody (mAb) therapeutics for cancer; discussion of the distinction between biosimilar, biobetter and next generation therapeutic antibodies for cancer; updates on obinutuzumab and the use of mAbs in lymphoma; and discussion of antibody-drug conjugates.     

7th Cancer Scientific Forum of the Cancéropôle Lyon Auvergne Rhône-Alpes

The Innovative Approaches in Anti-Cancer Monoclonal Antibodies meeting, held on March 20, 2012 in Lyon, was organized by Cancéropôle Lyon Auvergne-Rhône-Alps in partnership with the French competitiveness cluster Lyonbiopôle. CLARA is one of the seven cancer research clusters within France in charge of facilitating Translational Oncology Research by taking into account the objectives of the French National Cancer Plans I and II and, in coordination with the French National Cancer Institute and local authorities (mainly Grand Lyon, Rhône County and Rhône-Alpes Region), to perform economic development of research findings. The contribution of lectures by outstanding speakers as described in this report, the organization of two-round tables: “Antibody treatment in cancer: Unmet needs in solid tumors and hematological malignancies,” and “From chimeric to more than human antibodies,” together with face-to-face meetings, was shared by over 230 participants. The lectures provided an overview of the commercial pipeline of monoclonal antibody (mAb) therapeutics for cancer; discussion of the distinction between biosimilar, biobetter and next generation therapeutic antibodies for cancer; updates on obinutuzumab and the use of mAbs in lymphoma; and discussion of antibody-drug conjugates.     

Dose-rate effects of 8-methoxypsoralen plus 365-NM irradiation on cell killing in Saccharomyces cerevisiae.

Tow types of dose-rate effect that alter the survival response of haploid yeast cells to 8-methoxypsoralen (8-MOP) plus treatment with irradiation at 365 nm were studied. (1) When the concentration of 8-MOP was varied between 9.2 X 10(-5) and 2.3 X 10(-8) M and the dose rate of 365-nm irradiation kept constant, the efficiency of the irradiation for killing increased relatively to that of 8-MOP whe the concentration of 8-MOP decreased. This indicated that there was no strict reciprocity between radiation dose and concentration of drug. (2) When the dose rate of radiation was varied between 0.66 X 10(3) and 108 X 10(3) J m-2 h-1 and the concentration of 8-MOP was kept constant, the survival of wild-type cells increased strikingly at low dose rates of radiation as compared with high dose rates. Cells responded more to changes at low dose rates than to equal changes a high dose rates. The high resistance of wild-type cells to 8-MOP plus radiation delivered at low dose rates absent from rad 1-3 cells defective in excision-repair. This suggests that the dose-rate effect seen in wild-type cells depended at least in part on an active excision-repair function. At low dose rates of radiation, the shoulder of the survival curve for rad1-3 cells, i.e. the ability to accumulate sub-lethal damage, was increased by a factor of about 2 when compared with that seen at a high dose rate. Thus it is likely that at low dose rates a repair function other than excision-resynthesis may operate in rad1-3 cells.