c-FLIP、bcl-xS和caspase-3在乳腺癌中的表达及其临床意义

目的：探讨c—FLIP、bcl—xS和caspase-3在乳腺癌发生发展中的意义。方法：采用RT—PCR技术检测57例浸润性乳腺癌组织和癌周组织中c—FLIP、bcl—xS和caspase-3表达及其与肿瘤临床特征之间的关系。结果：与癌周组织相比，乳腺癌组织中c—FLIP呈过表达，其阳性率及半定量测定均明显高于癌周组织；c—FLIP表达与肿瘤的组织分级之间有显著相关性，随组织分级增高表达升高。而bcl—xS和caspase-3低表达，其阳性率及半定量测定均明显低于癌周组织。随分级增高，bcl—xS表达下降，同时临床Ⅰ期乳腺癌bcl—xS的表达阳性率明显高于Ⅱ期、Ⅲ期乳腺癌。结论：c—FLIP过表达、bcl—xS和caspase-3低表达是促进乳腺癌发生发展的因素之一，有望作为判断和监测乳腺癌预后的指标。     

恶性血液病细胞p16蛋白的表达及其意义

目的探讨抑癌基因蛋白p16在恶性血液病细胞中的表达及其意义。方法应用免疫组化方法检测43例恶性血液病细胞表面p16蛋白的表达情况,以7例正常人骨髓单个核细胞作为对照。结果恶性血液病细胞p16蛋白表达阳性率(72.1%)明显低于正常人骨髓单个核细胞(100.0%)(P<0.05),其中淋巴细胞白血病显著低于非淋巴细胞白血病(P<0.05)。对恶性血液病患者进行诱导缓解治疗后,p16蛋白阴性组完全缓解率为8.3%(1/12),明显低于p16蛋白阳性组(25.8%,8/31)(P<0.05)。结论p16蛋白在恶性血液病中表达减弱,它与淋巴细胞白血病的发生更为密切,并具有一定的预后判断价值。     

凋亡在正常造血及恶性血液病中的意义

细胞凋亡(apoptosis)是由基因控制的细胞程序化死亡,在维持机体平衡状态方面有积极的生物学意义.凋亡受抑在肿瘤发生和对化疗耐药中起重要作用,对细胞凋亡机制的研究有助于恶性血液病治疗策略的改进.而bcl-2和p53基因是调节细胞凋亡的重要分子,它们功能的改变与人类肿瘤凋亡受抑有关.下面就其对细胞凋亡的调控以及在正常造血系统和恶性血液病中的表达作一简要综述.     

抑制血管生成在治疗恶性血液病中的意义

众所周知,血管生成与实体瘤的生长、扩增和转移直接相关.血管内皮生长因子(VEGF)及其受体FLT-1为血管生长速度和程度的重要决定因素,过度表达则肿瘤生长迅速.纤维母细胞生长因子(FGF)-2为内皮细胞和纤维母细胞分裂原介导血管生成.恶性血液病也不例外.此领域已成为热点研究课题之一.     

40例恶性血液病p170表达及意义

目的 :研究 p170表达、免疫分型在恶性血液病中的临床意义。方法 :40例恶性血液病患者用异硫氰荧光与间接免疫标记法、流式细胞仪及软件系统进行检测和分析。结果 :初治恶性血液病患者 p170阳性表达率45 .0 % ,初治急性白血病外周血 p170高表达占 30 .7%。结论 :p170、CD34以及白血病两系抗原共表达三者间有明显相关性。同时它们又分别是一独立的负性预后指标 ,有利于指导临床医师采用个体化治疗。     

40例恶性血液病p170表达及意义

目的：研究p170表达，免疫分型在恶性血液病的临床意义。方法：４０例恶性血液病患者用异硫氰荧光与间接免疫标记法，流式细胞仪及软件系统进行检测和分析。结果：初治恶性血液病患者p170阳性表达率４５．０％，初治急性白血病外周p170高表达占３０．７％，结：p170、CD34以及白血病两系抗原共表达三者间有明显相关性。同时它们又分别是一独立的负性预后指标，有利于指导临床医师采用个体化治疗。     

MRP1 mRNA、GST-π mRNA在食管癌组织中的表达及意义

目的探讨多药耐药相关蛋白MRP1和谷胱甘肽-S-转移酶GST-π在食管癌组织中的表达水平以及与食管癌生物学特性的关系.方法采用RT-PCR、凝胶电泳半定量方法检测48例食管癌组织中MRP1mRNA和GST-π mRNA的表达,并采用SAS6.12统计软件分析它们在不同TNM临床病理分期中的表达情况.结果 MRP1mRNA、GST-π mRNA 在食管癌组织中表达阳性率分别为83.3%、90.7%;随着浸润程度的增加,MRP1mRNA和GST-π mRNA表达均有增高趋势,但无统计学意义(P＞0.05);二者在有淋巴结转移组和有远端转移组中的表达均明显高于无淋巴结转移组和无远端转移组( P＜0.05). 结论 MRP1和GST-π在食管癌的原发性多药耐药中可能起重要作用; 它们在食管癌组织中的表达与浸润程度无关,与有无淋巴结转移和有无远端转移有关,MRP1 mRNA和GST-π mRNA表达的增高可能是食管癌较高临床病理分期的标志;对这两个基因的检测有助于临床预测预后及指导用药.     

竞争性RT—PCR定量检测AFP mRNA在肝癌组织中的表达

通过检测外周血AFP mRNA可确定原发性肝细胞癌(hepatocellular carcinoma，HCC)表达高低与肝癌复发、转移及预后密切相关^[1-3]。本文建立了一种具有内参照的定量检测AFP mRNA的竞争性RT-PCR方法，并初步对肝癌组织及癌旁组织中AFP mRNA的表达进行定量分析，现报道如下。     

骨髓切片和涂片观察在恶性血液病诊断中的意义

 目的 应用骨髓切片和涂片相结合,观察骨髓组织和细胞形态学的变化,对120例初发的血液病患者的骨髓进行切片和涂片的结果分析,以期得到形态学诊断的新途径。方法 收集恶性血液病病例120份。一步法抽吸骨髓,常规方法涂片染色,塑料包埋法制作组织切片;恶性血液病的诊断参照2001年WHO分型标准。结果 骨髓活检与骨髓涂片相结合,在诊断骨髓纤维化、低增生MDS、骨髓转移癌和骨髓坏死,骨髓组织切片的诊断符合率高于穿刺涂片。对于淋巴瘤骨髓侵犯的病例,骨髓组织切片中更容易找到有特征的淋巴瘤细胞;对慢性粒细胞白血病（CML）病例,组织切片较穿刺涂片提前找到诊断急变的证据。结论 骨髓形态学检验,将组织切片与穿刺涂片相结合,互为补充,可以有效地提高恶性血液病的诊断水平。     

循环miRNA在恶性血液病中的研究进展

循环miRNA是一类非编码小RNA分子,可作为许多疾病特别是恶性肿瘤的生物标记物,近年来研究发现,在不同的恶性血液疾病中miRNA具有不同的表达谱,并且对疾病的诊断、疗效及预后评估具有重要提示作用,本文对循环miRNA的来源、功能及循环miRNA与恶性血液病的关系进行综述。     

Hepcidin在恶性血液病贫血患者中的表达及临床意义

目的:探讨铁调素(hepcidin)在恶性血液病贫血患者中的表达,并对hepcidin与白细胞介素6 (interleukin-6,IL-6)、血红蛋白(hemoglobin,Hb)、血清铁和铁蛋白表达水平进行相关性分析。方法:收集80例恶性血液病贫血患者外周血,分别检测hepcidin、IL-6、Hb、血清铁和铁蛋白的表达水平,并以30例健康人群作为对照;使用SPSS 21.0软件对实验结果进行统计学分析。结果:恶性血液病贫血患者血清中hepcidin、IL-6、Hb、血清铁和铁蛋白的表达量分别为(61.93±19.98) μg/L、(5.56±1.17) ng/L、(96.68±12.35) g/L、(9.85±1.09) μmol/L和329.42(299.70~459.06) μg/L;健康对照组相对应的表达量分别为(21.35±7.38) μg/L、(2.52±1.28) ng/L、(140.07±7.71) g/L、(19.95±4.25) μmol/L和95.72(76.56~131.42) μg/L,两组差异均具有统计学意义(P<0.01)。恶性血液病男性贫血患者中hepcidin、IL-6和Hb的表达量均高于女性患者(P<0.05);中度贫血患者hepcidin、IL-6和铁蛋白的表达量均高于轻度贫血患者,Hb和血清铁表达量低于轻度贫血患者(P<0.01)。线性回归分析结果显示hepcidin与Hb、血清铁含量呈负相关,与IL-6、铁蛋白含量呈正相关(P<0.05)。结论:Hepcidin在恶性血液病贫血患者中高表达,并与贫血程度相关,提示hepcidin在恶性血液病贫血发生中具有重要作用。     

Prognostic significance of isochromosome 17q in hematologic malignancies

Isochromosome 17q [i(17q)] with its two identical long arms is formed by duplication of the q arm and loss of the short p arm. The breakpoint in chromosome 17 that allows the formation of this isochromosome is located at 17p11.2, and the ~240 kb region with its large, palindromic, low-copy repeat sequences are present here. The region is highly unstable and susceptible to a variety of genomic alterations which may be induced by or without toxic agents. One molecular consequence of i(17q) development is the obligatory loss of a single TP53 allele of the tumor suppressor P53 protein located at 17p13.1. Isochromosome 17q is involved in cancer development and progression. It occurs in combination with other chromosomal defects (complex cytogenetics), and rarely as a single mutation. The i(17q) rearrangement has been described as the most common chromosomal aberration in primitive neuroectodermal tumors and medulloblastomas. This isochromosome is also detected in different hematological disorders. In this article, we analyze literature data on the presence of i(17q) in proliferative disorders of the hematopoietic system in the context of its role as a prognostic factor of disease progression. The case reports are added to support the presented data. Currently, there are no indications for the use of specific treatment regimens in the subjects with a presence of the isochromosome 17q. Thus, it is of importance to continue studies on the prognostic role of this abnormality and even single cases should be reported as they may be used for further statistical analyses or meta-analyses.     

c-FLIP在骨肉瘤中的表达及其临床意义

目的:探讨c-FLIP(细胞型Fas相关死亡域样白介素-1β转换酶抑制蛋白)在骨肉瘤组织中的表达情况,分析其表达与临床病理特征和预后的关系。方法:收集47例临床资料完整石蜡包埋的骨肉瘤肿瘤标本,25例骨软骨瘤标本,8例正常的骨组织标本,用免疫组化SP法和蛋白质印记法测定c-FLIP的表达水平,分析其表达与肿瘤组织学性状和预后的关系。结果:骨肉瘤标本中c-FLIP表达的阳性率是83%(39/47),而在骨软骨瘤标本中表达的阳性率是16%(4/25),两者比较P<0.01;结合临床资料分析,c-FLIP蛋白表达与患者年龄、发病次数、肿瘤体积、病理类型及有无转移无关(P>0.05),而与临床Ennecking分期有关(P<0.05)。结论:c-FLIP蛋白的过量表达在骨肉瘤的发生发展中可能起重要的作用。     

非髓性白血病的其他恶性血液病中DNMT3A基因突变的检测及临床意义

目的:了解DNMT3A基因突变在非髓性白血病的其他恶性血液肿瘤患者中的发生率、分布情况及临床意义.方法:选取196例非髓性白血病的其他血液肿瘤患者为研究对象,提取患者外周血基因组DNA,针对DNMT3A基因突变热点R882位点设计引物,采用聚合酶链式反应(PCR)法扩增DNMT3A基因23号外显子整个编码区基因片段,再将扩增产物纯化后测序,分析DNMT3A基因突变在本组恶性血液病患者中的发生率、分布情况及临床意义.结果:在57例非霍奇金淋巴瘤及34例骨髓增生异常综合征患者中各检出1例伴DNMT3A基因突变,在25例急性淋巴细胞白血病、45例多发性骨髓瘤和35例骨髓增殖性肿瘤患者中均未检测到DNMT'3A基因突变.结论:非髓性白血病的其他血液肿瘤患者中DNMT3A基因突变少见,伴DNMT3A基因突变的1例T淋巴母细胞白血病/淋巴瘤患者预后不良,联合去甲基化药物的化疗方案使伴该基因突变的1例骨髓增生异常综合征患者一度获得血液学完全缓解,但短期内转为急性白血病并发严重感染死亡.     

Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies

Ribonucleotide reductases catalyze the de novo biosynthesis of deoxyribonucleosides for DNA synthesis. Increased ribonucleotide reductases activity has been associated with malignant transformation and tumor cell growth. The ribonucleotide reductases inhibitors may bind with the R1 subunit of the enzyme (Class 1) or the nonheme iron (Class 2). This review focuses on the therapeutic use of ribonucleotide reductases inhibitors in hematologic malignancies. Hydroxyurea, fludarabine and cladribine have established roles in the management of hematologic malignancies, while other ribonucleotide reductases inhibitors, such as gemcitabine, tezacitabine and heterocyclic carboxaldehyde thiosemicarbazones (e.g., triapine) are being evaluated in clinical trials.     

The use of hypomethylating agents in the treatment of hematologic malignancies

Epigenetic alterations, such as DNA methylation and histone modifications, are abnormal in cancer cells, and the use of the hypomethylating agents 5-azacitidine and decitabine are important additions to our arsenal of active cancer drugs, especially for the treatment of the myelodysplastic syndromes and acute myeloid leukemia. Most effective are repeated cycles of the drugs given at doses much lower than originally tested. Typical overall response rates (complete responses + partial responses + hematologic improvement) for both drugs are in the range of 40 - 50%. These agents are generally very well tolerated, with myelosuppression being the major side effect. Postulated to work through hypomethylation of DNA causing induction of gene expression, the precise mechanism of action of these agents is not yet clear. Future studies are likely to combine these agents with other drugs like the histone deacetylase inhibitors that act in related pathways.     

c-FLIP在骨肉瘤中的表达及其临床意义

目的：探讨c-FLIP（细胞型Fas相关死亡域样白介素-1β转换酶抑制蛋白）在骨肉瘤组织中的表达情况,分析其表达与临床病理特征和预后的关系。方法：收集47例临床资料完整石蜡包埋的骨肉瘤肿瘤标本,25例骨软骨瘤标本,8例正常的骨组织标本,用免疫组化SP法和蛋白质印记法测定c-FLIP的表达水平,分析其表达与肿瘤组织学性状和预后的关系。结果：骨肉瘤标本中c-FLIP表达的阳性率是83%（39/47）,而在骨软骨瘤标本中表达的阳性率是16%（4/25）,两者比较P〈0.01;结合临床资料分析,c-FLIP蛋白表达与患者年龄、发病次数、肿瘤体积、病理类型及有无转移无关（P〉0.05）,而与临床Ennecking分期有关（P〈0.05）。结论：c-FLIP蛋白的过量表达在骨肉瘤的发生发展中可能起重要的作用。     

Clinical effects and applications of the gut microbiome in hematologic malignancies

The gut microbiome and its effects on host immunity have exciting implications for cancer prognosis and therapy. Examples in allogeneic hematopoietic stem cell transplantation (allo-SCT) demonstrate the role of the gut microbiome as a biomarker for clinical outcomes, and animal models demonstrate how microbiota manipulation may augment therapeutic responses. There are multiple mechanisms that gut microbiota may have in affecting distant tumor environments, including control of cytokine release, dendritic cell activation, and T-cell lymphocyte stimulation. Recently, there has been a marked interest in understanding interactions between host and microbiome in hematologic malignancies. This review summarizes the current understanding of the gut microbiome and its impact on leukemia, lymphoma, multiple myeloma, and allo-SCT and highlights several broad methods for targeting the gut microbiome in therapeutic trials.     

Changes in mortality associated with different hematologic malignancies during the pandemic in the United States

Patients with hematologic malignancies are at increased risk of adverse COVID-19 outcomes; nonetheless, only sparse population-based data are available on mortality related to hematologic cancers during the pandemic. Number of deaths and age-standardized mortality rates for specific hematologic malignancies selected either as the underlying cause of death (UCOD), or mentioned in death certificates (multiple causes of death-MCOD) were extracted from the US National Center for Health Statistics, CDC WONDER Online Database. Joinpoint analysis was applied to identify changes in mortality trends from 1999 to 2021, and to estimate the annual percent change with 95% Confidence Intervals (CI) across time segments. Among the most common malignancies, chronic lymphocytic leukemia showed marked peaks in the monthly number of deaths attributed to COVID-19 during epidemic waves; acute myeloid leukemia showed the least variation, and non-Hodgkin lymphoma and multiple myeloma were characterized by an intermediate pattern. Age-standardized death rates relying solely on the UCOD did not show significant variations during pandemic years. By contrast, rates based on MCOD increased by 14.0% (CI, 10.2–17.9%) per year for chronic lymphocytic leukemia, by 5.1% (CI, 3.1–7.2%) for non-Hodgkin lymphoma and by 3.2% (CI, 0.3–6.1%) per year for multiple myeloma. Surveillance of mortality based on MCOD is warranted to accurately measure the impact of the COVID-19 pandemic and of other epidemics, including seasonal flu, on patients with hematologic malignancies, and to assess the effects of vaccination campaigns and other preventive measures.