非霍奇金淋巴瘤中肺耐药相关蛋白的表达及意义

目的 研究非霍奇金淋巴瘸（NHL）中肺耐药相关蛋白（LRP）的表达及其临床意义。方法 应用免疫组化S-P法检测43例NHL患者（其中初治病例32例,复发病例11例）和10例坏死增生性淋巴结炎患者组织中的LRP水平。结果 LRP在NHL患者中表达明显高于坏死增生性淋巴结炎患者（P〈0．05）,而且NHL复发组高于初治组（P〈0．05）。12例随访患者中LRP阴性者治疗效果优于LRP阳性者。结论 LRP过度表达与NHL临床耐药及疗效相关。     

P^27基因蛋白在非霍奇金淋巴瘤中的表达

P2 7是一种具有调控细胞周期 ,诱导细胞分化及凋亡的非特异性多功能分子。我们用免疫组织 SABC法对 46例非霍奇金淋巴瘤 (NHL)的石蜡切片做回顾性的实验研究 ,以观察 P2 7在 NHL各病理组织类型及反应性增生淋巴组织中的表达规律 ,并对其临床意义进行探讨。1　临床资料取 46例 NHL石蜡包埋的组织块。其中男 30例 ,女 1 6例 ,年龄 53± 1 8.7岁。按我国 1 985年的成都 NHL分类标准 ,低度恶性的 NHL1 9例 ,中度恶性的 NHL1 5例 ,高度恶性的 NHL1 2例。另取 7例反应性增生淋巴组织的石蜡包埋组织作块为对照组。按 NHL的临床表现及治…     

PCNA在非霍奇金淋巴瘤中的表达及意义

目的探讨增殖细胞核抗原（PCNA）在非霍奇金淋巴瘤中（NHL）的表达及临床意义。方法采用免疫组化SP方法检测52例NHL及12例淋巴结反应性增生（RH）患者PCNA的表达情况。结果PCNA在RH患者中的阳性表达率明显低于NHL患者;侵袭性NHL患者表达水平明显高于惰性NHL患者。乳酸脱氢酶（LDH）〈250U／L的NHL患者PCNA阳性表达率明显低于LDH〉250U／L者。PCNA阳性表达率〉25％NHL患者平均生存期较阳性表达率〈25％者短。结论PCNA与NHL的发生发展有关,并可对预后判断提供参考依据。     

B7家族在非霍奇金淋巴瘤中的表达及意义

目的 检测B7家族在非霍奇金淋巴瘤（NHL）中的表达,阐明其在NHL中的作用及意义。方法 应用密度梯度离心法分离健康志愿者外周血单个核细胞（PBMCs）,实时荧光定量PCR（RQ-PCR）检测B7家族PD-L1和PD-L2 mRNA在B细胞淋巴瘤（B-NHL）、T细胞淋巴瘤（T-NHL）及NK/T细胞淋巴瘤（NKTL）细胞系中的表达水平。结果 PD-L1和PD-L2 mRNA在NHL各细胞系中呈不同程度表达,T-NHL及NKTL细胞系中其表达量均明显高于正常PBMCs（P＜0.05）,而B-NHL细胞系中PD-L1和PD-L2 mRNA表达量与正常PBMCs相比无明显差异（P＞0.05）。结论 在NHL中,B7家族中PD-L1及PD-L2可能参与了NKTL及T-NHL肿瘤的免疫逃逸,有望成为NKTL及T-NHL肿瘤免疫治疗的新靶点。     

乳腺癌耐药相关蛋白在肝硬化及肝癌组织中的表达

肝癌对化疗药物的敏感性低,其多药耐药是肝癌治疗失败的主要原因.P-糖蛋白(P gP)在肝癌组织中高表达,可能是参与肝癌多药耐药的关键分子[1],然而抑制P-gp的活性,并不能有效逆转肝癌的多药耐药[2].因此,除了P-gp,可能有其他的多药耐药分子共同参与了肝癌的多药耐药.乳腺癌耐药相关蛋白(BCRP)是近年来发现的一个新的多药耐药分子,可排泄多种化疗药物[3-4].已有研究结果显示,BCRP在肝癌中有表达,并可能是肝癌干细胞的一种标志物[5-6].然     

非霍奇金淋巴瘤发生细胞周期D1蛋白高表达及其临床意义

目的：了解细胞周期D1蛋白高表达在我国非霍奇金淋巴瘤（NHL）中的发生情况及其临床意义。方法：收集我院就诊的162例NHL患者外周血、骨髓、淋巴组织标本，运用免疫组化方法检测细胞涂片与组织切片的细胞周期D1蛋白表达，分析NHL细胞周期D1蛋白表达的临床意义；记录NHL患者的临床资料，包括患者性别、年龄、临床分期、结外病变、生活自理性、血清乳酸脱氢酶（LDH）水平等国际预后指标。对照组为20例粒细胞白血病和20例骨髓正常者。结果：在162例NHL中检出21例（13％）细胞周期D1蛋白高表达。发生细胞周期D1蛋白高表达的NHL均为B淋巴细胞型，符合套细胞淋巴瘤的特征，国际预后指标高，化疗完全缓解率低。结论：本组162例NHL患者中，有13％NHL患者发生细胞周期D1蛋白高表达，诊断为套细胞淋巴瘤，是一种常见的NHL，预后差。     

Ezrin和Akt在非霍奇金淋巴瘤组织中的表达及意义

采用免疫组化SP方法检测66例非霍奇金淋巴瘤（NHL）及10例淋巴结良性病变（LNBC）组织中Ezrin、Akt表达情况,分析其相关性及与NHL组织学类型的关系。结果Ezrin在NHL组织中的阳性表达率明显低于LNBC组织（P〈0．01）;Akt在NHL组织中的表达显著高于LNBC组织（P〈0．05）;惰性NHL组织Ezrin和Akt表达水平略高于侵袭性NHL组织,但均无统计学意义;NHL组织中Ezrin与Akt表达水平呈正相关（r=0．383,P〈0．01）。认为Ezrin和Akt表达异常与NHL发生有关,此可能与Ezrin和Akt之间存在某种分子联系有关。     

LRP与MRP在乳腺癌组织中的表达及意义

目的研究乳腺癌组织中肺耐药蛋白（LRP）、多药耐药相关蛋白（MRP）的表达及其意义。方法应用流式细胞术检测51例乳腺癌组织中LRP及MRP的表达情况,分析其与患者年龄、肿瘤大小、腋窝淋巴结转移及雌激素受体（ER）、孕激素受体（PR）表达状态等因素的关系,并探讨两者表达的相关性。结果LRP、MRP相对表达水平（用荧光强度表示）分别为0.46±0.84、1.51±1.57;除MRP与肿瘤大小相关外,两者与患者年龄、腋窝淋巴结转移、激素受体等均无相关性;乳腺癌组织中LRP与MRP表达水平间存在高度正相关（r=0.434,P=0.004）。结论部分乳腺癌具有原发性耐药,多药耐药表型隐含在乳腺癌组织中,不受化学药物的诱导,与恶性表型同时发生,且不受疾病发展的影响;MRP与肿瘤细胞增殖能力有一定关系,在肿瘤的发展过程中起重要作用;LRP似未参与乳腺癌的多药耐药机制,但与MRP在引起乳腺癌耐药方面具很大的协同性。     

白血病多药耐药基因和多药耐药相关蛋白基因的表达及临床研究

白血病是造血系统常见的恶性肿瘤 ,化疗是白血病治疗的主要手段 ,但白血病细胞产生的多药耐药是导致化疗失败的主要原因。多药耐药基因(ｍｄｒｌ)和多药耐药相关蛋白基因 (ＭＲＰ)的过度表达是引起白血病多药耐药发生的重要机制之一。本文应用半定量ＲＴ ＰＣＲ方法同时检测 40例急性白血病和慢性粒细胞白血病急变患者的ｍｄｒｌ和ＭＲＰ的表达水平 ,并探讨了它们与临床耐药的关系。1　对象与方法1 .1 　 研究对象40例患者均为我院 1 999年 7月～ 2 0 0 0年 5月住院患者 ,男 2 5例 ,女 1 5例 ,中位年龄 37岁 ( 4～ 68岁 )。初治组 2 7例 ,复…     

p63、Bcl-2和PCNA蛋白在B细胞非霍奇金淋巴瘤中的表达及意义

目的 探讨p63、Bcl-2和增殖细胞核抗原(PCNA)蛋白在B细胞非霍奇金淋巴瘤(B-NHL)发生、发展中的作用.方法 应用免疫组化染色法检测p63、Bcl-2及PCNA蛋白在50份B-NHL组织和20份反应性增生淋巴组织中的表达,分析各指标间及与B-NHL临床病理参数的关系.结果 p63、Bcl-2和PCNA蛋白在B-NHL组织中阳性表达率分别为60％、78％和80％,在反应性增生淋巴组织中的阳性表达率分别为5％、35％和35％,两两比较P均＜0.05;p63与Bcl-2、PCNA蛋白表达均呈正相关,r=0.453、0.800(P＜0.001或0.01);三指标与患者年龄、B-NHL病理类型等临床病理参数均无明显关系(P均＞0.05).结论 p63可能与Bcl-2、PCNA协同参与B-NHL的发生,具体机制尚需进一步研究.     

Acquired resistance to activated protein C in breast cancer patients

In 56 women with a lymph-node-positive breast carcinoma and 28 matched healthy control subjects, the sensitivity to activated protein C (APC-sr) was determined with an APC resistance test that quantifies the effect of APC on thrombin generation initiated via the extrinsic coagulation pathway. Carriers of the Factor V Leiden mutation were excluded from the study. Significant resistance to APC was found in the breast cancer patients: median APC-sr 2.02 vs 1.03 in the healthy control subjects (P < 0.001). No difference in APC-sr was found between patients with metastases and without metastases. In patients with metastases, protein S levels were significantly elevated compared with patients without metastases and healthy control subjects: 108.0%vs 96.0% and 94.5% (P = 0.008 and P = 0.007). The APC-sr correlated with protein S in the control subjects and in patients without metastases but not in patients with metastases. The disturbance of the haemostatic balance probed by the tissue-factor-based APC resistance test might contribute to the cancer-related hypercoagulability.     

Sorcin表达受抑乳腺癌多药耐药细胞株MCF-7／A02对化疗药物敏感性的观察

目的观察可溶性耐药相关钙结合蛋白基因（Sorcin）表达受抑乳腺癌多药耐药细胞株MCF-7／A02对化疗药物敏感性的影响,并探讨其机制。方法将MCF-7／A02细胞分为两组,观察组转染针对Sorcin基因的siRNA,对照组不转染。MTT法检测细胞对阿霉素（ADR）、依托泊苷（VP-16）、高三尖杉酯碱（HHT）、长春新碱（VCR）的敏感性,用流式细胞仪检测细胞对碱性蕊香红-123（Rho-123）的外排功能及VP16处理后的细胞凋亡率,Western blot法检测细胞中的Bcl-2、Bax蛋白。结果观察组ADR、VP-16、HHT、VCR的IC50分别为（19．92±1．29）、（31．47±2．36）、（4．19±0．27）、（2．96±0．23）μg／ml,对照组分别为（111．57±5．60）、（144．77±20．43）、（24．30±0．43）、（5．89±0．28）μg／ml,两组比较,P均〈0．01。观察组细胞凋亡率为9．15％±0．25％,对照组为4．10％±0．12％,两组比较,P〈0．01。观察组细胞内Rho-123的荧光强度为6．34±0．86,对照组为5．42±0．73,两组比较,P〉0．05。观察组细胞中Bcl-2、Bax蛋白表达量为0．59±0．032、1．80±0．03,对照组分别为0．69±0．025、1．94±0．04,两组比较,P均〈0．05。结论抑制Sorcin表达可显著增强MCF-7／A02细胞对化疗药物的敏感性;这种作用可能与其调节Bcl-2／Bax通路促进MCF-7／A02细朐凋亡有关。     

Predicting the outcome in non-Hodgkin lymphoma with molecular markers

The World Health Organization classification divides non-Hodgkin lymphomas into B-cell, T-cell and natural killer-cell lymphomas. They are heterogeneous in epidemiology, histopathology and outcome. Clinical prognostic indices rely only on patient factors and staging. Molecular prognostic markers reflect the intrinsic lymphoma biology, measure tumour load and may provide novel therapeutic targets. Lymphomagenesis involves mutations, deletions or dysregulations of genes critical in the control of cell cycle and apoptosis, which are in turn prognostically important. Genome-wide gene expression profiling, either by allowing lymphomas to be classified according to different stages of lymphoid maturation, or by defining specific gene expression signatures, is also of prognostic significance. In lymphomas where viral infections of the neoplastic cells occur, quantification of viral copies is a surrogate marker for tumour load and hence prognosis. Molecular markers together with patient and clinicopathological features will provide more accurate prognostic models for risk stratification, in order to improve treatment outcome.     

BCRP基因在乳腺癌组织中的表达及意义

目的　研究乳腺癌耐药蛋白 (BCRP)基因在乳腺癌组织中的表达水平 ,探讨其与肿瘤病理分期、淋巴结转移的关系。方法　采用实时荧光定量 RT- PCR检测 5 1例乳腺癌患者癌组织和癌旁组织中 BCRP基因表达。结果　 BCRP基因在乳腺癌组织中的阳性表达率、表达水平均显著高于癌旁组织 (P<0 .0 1、<0 .0 5 ) ;BCRP基因在 、 、 期乳腺癌组织中的表达水平无显著性差异 (P>0 .0 5 ) ;有淋巴结转移者的 BCRP基因表达水平显著高于无淋巴结转移者 (P<0 .0 5 )。结论　 BCRP基因表达水平与肿瘤病理分期无关 ,与淋巴结转移有关 ,BCRP基因过表达可能在乳腺癌的多药耐药中起较重要的作用。     

Up‐regulation of breast cancer resistance protein expression in hepatoblastoma following chemotherapy: A study in patients and in vitro

Aim: Hepatoblastoma (HB), the most common pediatric malignant liver tumor, is treated with chemotherapy to facilitate surgical resection. Previous studies suggest that HB acquires chemoresistance via increased expression of multidrug resistance protein 1 (MDR1, ABCC1). There is no well established evidence that this also occurs in the clinical setting and little is known about the effects of chemotherapeutic treatments on HB in situ. Methods: Clinical and histopathological features and expression patterns of ABC transporters in diagnostic needle biopsies from 7 HBs taken before chemotherapy were compared with those in surgically resected tumors. To understand the mechanism s leading to chemoresistance we also investigated the involvement of hypoxia on protein expression and functional activity of drug transporters (BCRP and MDR1) in cultures of HepG2 human HB cells. Results: We found that chemotherapeutical treatment of HBs led to an increased expression of the breast cancer resistance protein (BCRP, ABCG2) in all patients studied. There was no change in the expression pattern of MDR1 or other ABC transporters. Chemotherapy‐induced specific vascular abnormalities associated with areas of necrosis and fibrosis were seen in all cases, suggesting tumor hypoxia. The observations of increased BCRP expression in hypoxic areas of three‐dimensional HepG2 aggregates and the enhanced BCRP function in monolayer cultures of HepG2 cells under hypoxic conditions, support a role for hypoxia in enhanced BCRP expression. Conclusions: Chemotherapeutical treatment of HB leads to vascular alterations that modify the tumor microenvironment, and increased BCRP expression in which hypoxia might play a role. No evidence was found for upregulation of MDR1 in HBs as suggested from previous experimental studies.     

Clinical characteristics and treatment outcome of infants with non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) is rarely observed during infancy and data on its incidence, characteristics and outcome are scarce. The present study aimed to assess the prevalence, clinical presentation and treatment results of all infants who were diagnosed with NHL between October 1986 and December 2002 among 2084 patients treated according to the NHL-BFM (Berlin-Frankfurt-Münster) multicentre trials 86, 90 and 95. We identified 20 (1%) infants with NHL including five with T-cell lymphoblastic lymphoma (T-cell LBL), seven with precursor B-cell LBL (pB-cell LBL), two with a mature Burkitt neoplasm, five with anaplastic large cell lymphoma (ALCL) and one with peripheral T-cell lymphoma (PTCL). The PTCL patient, 3/7 pB-cell LBL and 1/5 ALCL patients relapsed. One patient each from the T-cell LBL and Burkitt lymphoma groups suffered from a second malignancy and one patient each with ALCL and Burkitt leukaemia died from treatment-related toxicity. The 5-year event-free survival rate was 53 +/- 12% for the 20 cases. This study has provided preliminary evidence that infants with NHL have a dismal prognosis and showed that infant NHL differed to lymphomas in older patients with respect to the distribution of gender, histopathologic subtypes as well as the ratio of T- to pB-cell LBL and the frequency of relapses of pB-cell LBL.     

siRNA逆转乳腺癌细胞MDR1及MDR3介导阿霉素耐药的研究

目的探讨小分子干扰RNA(siRNA)对多药耐药基因MDR1及MDR3介导的乳腺癌MCF-7/ADR细胞耐阿霉素的逆转作用。方法pSuppressorNeoABCB1(针对MDR1的siRNA)及ABCB4(针对MDR3的siRNA)质粒转染MCF-7/ADR及MCF-7细胞(乳腺癌亲本细胞株),流式细胞术检测细胞凋亡,MTT检测MCF-7/ADR细胞对阿霉素的半数抑制浓度(IC50),RT-PCR检测MDR1及MDR3mRNA的表达。结果转染pSup-pressorNeoABCB1的MCF-7/ADR细胞凋亡率(18.21%±1.65%)高于转染pSuppressorNeoABCB4的细胞凋亡率(9.07%±2.17%),P<0.05;二者与转染空载体组的细胞凋亡率(0.2%±0.36%)相比,P均<0.01;pSuppressorNeoABCB1质粒对阿霉素的相对逆转效应高于pSuppressorNeoABCB4质粒(P<0.05);两个质粒转染组的MDR1和MDR3mRNA表达均受到明显抑制(P均<0.01)。结论针对MDR1及MDR3基因的siR-NA可逆转乳腺癌细胞对阿霉素的耐药性。     

VNCOP-B plus rituximab therapy in elderly patients with aggressive B-cell non-Hodgkin lymphoma: A multicenter experience

CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) plus rituximab is a standard chemotherapy used to treat patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). However, among elderly patients, this regimen has not been completely satisfactory in its efficacy and safety. We report our clinical experience in 8 collaborative institutions to determine if the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone, and bleomycin) combination therapy plus rituximab was effective and safe to treat elderly patients with aggressive B-NHL. Between September 2004 and December 2007, 23 previously untreated patients, median age 73 years, 50.0% classified as high-intermediate/high-risk on the standard International Prognostic Index (IPI) entered this trial. Complete remission rate was 90.5%, with a 100% overall response rate (RR) at the end of induction therapy; overall survival (OS) rate at 3 years was 76.4% (median follow-up 744 days), with an 82.6% 3-year progression-free survival (PFS) rate (median follow-up 744 days). The most common grade 3/4 toxicities were hematologic, including neutropenia in 75.0% of the patients despite prophylactic administration of granulocyte colony-stimulating factor (G-CSF), febrile neutropenia in 30.0%, respectively. There was no treatment-related mortality (TRM). Rituximab not only combined with chemotherapy but also given sequentially improved survival. R-VNCOP-B could be another option for elderly patients who are not considered to tolerate in receiving R-CHOP.