P27kip1与细胞周期素D3在非霍奇金淋巴瘤中的表达、定位及相互关系

目的探讨P27^kip1和细胞周期素（cyclin）D3在非霍奇金淋巴瘤（NHL）中的表达、定位、相互关系及意义.方法采用免疫组织化学方法检测100例NHL患者病理标本及20例反应性增生淋巴结标本中P27^kip1、cyclin D3及细胞增殖指标Ki-67的表达.采用Western blot、免疫荧光双标法和激光共聚焦技术检测3种淋巴瘤细胞系细胞内P27^kip1和cyclin D3的表达、定位.结果 P27^kip1在NHL组织中的阳性率低于反应性增生淋巴结,且与肿瘤侵袭性以及增殖活性（Ki-67指数,Ki-67 LI）呈负相关;cyclin D3在NHL组织中的阳性率高于反应性增生淋巴结,且与肿瘤侵袭性以及增殖活性呈正相关;P27^kip1与cyclin D3呈负相关.但在少数病例出现P27^kip1的异常高表达并伴有cyclin D3和Ki-67的高表达.P27^kip1与cyclin D3在3种淋巴瘤细胞系的表达水平不一,在Raji细胞中P27^kip1与cyclin D3共同高表达并且共定位.结论 P27^kip1的低表达,cyclin D3的高表达与多数NHL的发生发展有关;部分病例或细胞系中P27^kip1的异常高表达及其与cyclin D3相互作用可能是NHL发生的另一机制.     

p16和细胞周期蛋白D1蛋白在口腔鳞癌中的表达及其意义

目的　研究口腔鳞癌组织中p16及细胞周期蛋白D1(cyclin D1)表达以及与临床生物学特性和细胞增殖的关系。方法　采用免疫组化方法检测49例原发性口腔鳞癌组织及20例正常口腔黏膜组织中p16及cyclin D1蛋白的表达水平，Ki-67作为细胞增殖活性的指标也被检测。结果　p16在口腔鳞癌中阳性表达率显著低于正常口腔黏膜组织(P<0.05)，cyclin D1蛋白和Ki-67在口腔鳞癌中阳性表达率显著高于正常口腔黏膜组织(P<0.05) ；cyclin D1蛋白过表达与临床分级及淋巴结转移有关(P值分别<0.05)，p16缺失表达与淋巴结转移有关(P<0.05)；p16负表达和cyclin D1过表达与细胞增殖评价因子Ki-67呈负相关(r=-0.598和-0.658, P<0.05)。结论　在鳞癌的发生发展过程中，p16的缺失表达和cyclinD1的过表达两者可能单独或共同参与。p16的缺失可能还与口腔鳞癌细胞的分化、转移及增值和预后有关。     

Ileocolonic lymphomas: a series of 16 cases

BACKGROUND: Colonoscopic and clinical differences between primary ileocolonic mucosa-associated lymphoid tissue (MALT) lymphoma and mantle cell lymphoma (MCL) have not been defined. METHODS: We reviewed colonoscopic and clinical features in eight patients with primary MALT lymphoma and eight patients with MCL in the terminal ileum and/or colorectum. All cases were examined for CD5 and/or cyclin D1 expression. RESULTS: Endoscopic features of MALT lymphoma were characterized as protrusions that were covered with normal-appearing mucosa with or without ulceration. The gross appearances of MALT lymphomas were categorized as solitary (4 patients), multiple (3 patients), and multiple lymphomatous polyposis (MLP) (1 patient). The gross features of MCL at endoscopy were categorized as multiple protrusions (2 patients), and MLP (6 patients). The clinical stages of patients with MCL were more advanced than in patients with MALT lymphoma. CONCLUSIONS: Solitary or multiple protrusions at an early clinical stage is the most common presentation pattern of patients with MALT lymphoma, but an MLP appearance at an early stage is also possible. On the other hand, MLP appearance with an advanced clinical stage is the main presentation pattern in patients with MCL, although multiple protrusions with an early clinical stage is also possible. Histological and immunohistochemical investigation including that of cyclin D1 and CD5 expression is essential to make the final diagnosis.     

B淋巴增殖性疾病的SOX11、cyclin D1、cyclin D2和cyclin D3的表达研究

目的 探讨各B淋巴增殖性疾病(B-LPD)中SOX11、cyclin D1、cyclin D2和cyclin D3表达的差异和相关性,以及与慢性淋巴细胞白血病(CLL)患者临床特征的关系.方法 采用实时定量逆转录PCR(qRT-PCR)技术检测154例B-LPD患者与12例健康对照SOX11、cyclin D1、cyc...     

p16和cyclin D_1蛋白在鼻咽癌组织中的表达及其意义

目的　探讨鼻咽癌组织中p16和cyclinD1蛋白的表达及其意义。方法　应用免疫组化S P法检测p16和cyclinD1蛋白在 85例鼻咽癌和 18例鼻咽部炎性黏膜组织中的表达。结果　 85例鼻咽癌中p16的表达率为 41 2 %(35 / 85 ) ;cyclinD1的过表达率为 6 3 5 % (5 4/ 85 )。 18例鼻咽部炎性黏膜中 ,p16的表达率为 10 0 % ;cyclinD1的表达全部为阴性。高分化鳞癌p16的表达率为 75 0 % (6 / 8) ,低分化鳞癌为 38 2 % (2 6 / 6 8) ,两者差异显著 (P <0 0 5 )。有淋巴结转移的p16表达率为 2 8 6 % (14/ 49) ,无淋巴结转移的为 5 8 3% (2 1/ 36 ) ,两者差异非常显著 (P <0 0 1)。 35例p16 ( )的癌组织中有 2 8例cyclinD1呈过表达 ;5 0例p16 (- )的癌组织中有 2 6例cyclinD1呈过表达。结论　p16的缺失表达和cyclinD1的过表达两者可能单独或共同参与了鼻咽癌的发生发展过程。p16的缺失可能还与鼻咽癌细胞的分化、转移有关     

Livin在非霍奇金淋巴瘤中表达的临床意义

本研究旨在探讨凋亡抑制因子Livin在非霍奇金淋巴瘤组织中的表达及其临床意义。应用免疫组织化学法检测Livin蛋白在30例非霍奇金淋巴瘤(non-Hodgkin′s lymphoma,NHL)患者及11例淋巴结反应性增生(reac-tive hyperplasia of lymph node)患者淋巴结中的表达,并应用real-time PCR对其中20例非霍奇金淋巴瘤、10例淋巴结反应性增生及4例正常人的淋巴结组织中Livin mRNA表达水平进行检测,分析livin蛋白和mRNA表达与NHL患者临床表现及其特征的相关性。结果表明,NHL患者淋巴结组织中Livin mRNA表达水平与正常淋巴结组织以及淋巴结反应性增生组织比较均显著增高(RQ中位数分别为12.4vs0.34和12.4vs0.61)(p0.01)。30例非霍奇金淋巴瘤中有16例Livin蛋白表达阳性,阳性率为53.3%;11例淋巴结反应性增生患者仅1例表达阳性,阳性率为9.1%;而且观察到Livin蛋白主要在细胞浆中表达,在胞核内极少见有表达。研究还显示,无论是LivinmRNA表达还是蛋白表达均与NHL的临床分期(p=0.023;p=0.009)、B症状(p=0.015;p=0.026)、血β2微球蛋白(β2-MG,p=0.031;p=0.012)及血清乳酸脱氢酶(LDH,p=0.037;p=0.007)密切相关,而两者的表达与年龄、性别及分型无明显相关性(p0.05)。结论:Livin mRNA及蛋白在NHL患者中表达增高,并与临床多项指标存在相关性,因此Livin表达水平对评价患者临床分期及预后可能具有重要的指导意义;对Livin在NHL中的作用机制的深入探讨将有助于揭示NHL的发生、发展及治疗的机理,并有望成为NHL未来治疗的重要突破点。     

实时灰阶超声造影鉴别诊断浅表良恶性淋巴结

目的 探讨实时灰阶CEUS早期鉴别诊断浅表良恶性淋巴结的价值。方法 对48例患者的56个肿大浅表淋巴结进行常规超声和实时灰阶CEUS,观察淋巴结造影灌注模式,分析时间-强度曲线(TIC)形态,并测量开始增强时间(AT)、达峰时间(TTP)、峰值强度(PI)、平均渡越时间(MTT)和曲线下面积(AUC)。 结果 病理结果示良性淋巴结23个,恶性淋巴结33个,包括转移性淋巴结20个、恶性淋巴瘤13个。良性淋巴结大多表现为自淋巴结门开始的均匀增强(16/23,69.57%),转移性淋巴结半数表现为自周边开始的不均匀增强(10/20,50.00%),恶性淋巴瘤多表现为均匀增强(7/13,53.85%)。良性淋巴结中19个(19/23,82.61%)TIC呈快退型,转移性淋巴结中17个(17/20,85.00%)、恶性淋巴瘤中12个(12/13,92.31%)TIC呈慢退型。良恶性淋巴结AT、TTP差异无统计学意义(P均>0.05);良性淋巴结PI值与转移性淋巴结差异无统计学意义(P>0.05),且均显著低于恶性淋巴瘤(P均<0.05);转移性淋巴结和恶性淋巴瘤MTT和AUC均显著高于良性淋巴结(P均<0.05)。 结论 CEUS中良恶性淋巴结造影模式、TIC及定量参数存在差异,有助于鉴别诊断。     

肺癌组织中细胞周期蛋白D1的检测及其意义

检测细胞周期蛋白Ｄ１（ＣｙｃｌｉｎＤ１）在肺癌及癌前病变和正常肺组织的表达,探讨它在肺癌诊断中的作用及其与生物学行为的关系。方法收集肺癌及癌前病变和正常肺组织,采用免疫组化ＳＰ法检测ＣｙｃｈｎＤ１的表达。结果正常肺组织和鳞状化生的支气管上皮未见ＣｙｃｌｉｎＤ１表达,在轻－中－重度不典型增生、原位癌、浸润癌,ＣｙｃｌｉｎＤ１表达的阳性率逐渐升高,阳性细胞数也增多,肺癌组织中ＣｙｃｌｉｎＤ１表达的总阳性率为５６．４％。低分化癌的阳性率高于中高分化癌（Ｐ＜０．０５）：无论鳞癌还是腺癌,ＣｙｃｌｉｎＤ１阳性组的增殖活性高于阴性组（Ｐ＜０．０５）。肺鳞癌有淋巴结转移组ＣｙｃｌｉｎＤ１的阳性率高于无转移组（Ｐ＜０．０５）。结论ＣｙｃｌｉｎＤ１表达与肺癌的发生和增殖有关,而且ＣｙｃｌｉｎＤ１表达是支气管粘膜上皮癌变的早期事件,提示ＣｙＣｌｉｎＤ１可作为判断肿瘤发生可能性的标记物,在肺癌的早期诊断中可能具有重要意义。ＣｙＣｌｉｎＤ１表达与肺鳞癌分化不良及淋巴结转移有关,可能是预后不良的标志。     

套细胞淋巴瘤发病机制的研究进展

套细胞淋巴瘤(MCL)是一种侵袭性的非霍奇金淋巴瘤(NHL),该病的经典遗传学标志为t(11;14)(q13;q32)移位和细胞周期蛋白(cyclin) D1过表达,以难治和易复发为临床特征,并且总体预后不良.近年,随着对MCL细胞遗传学及分子发病机制研究的不断深入,靶向药物的开发与应用,使得该病的临床疗效有所提高.本文就近年来MCL发病机制中细胞遗传学、信号通路、转录因子、肿瘤微环境等改变的研究最新进展作一综述,旨在为MCL的早期诊断和靶向治疗提供新的方向.     

Cytogenetics of mantle cell lymphoma

AIM: To determine the type and rate of secondary chromosomal aberrations and role in pathogenesis of mantle cell lymphoma (MCL). MATERIAL AND METHODS: Standard cytogenetic examination (SCE) and fluorescent in situ hybridization (FISH) with tests for 11q22/ATM, 13q14, 17p13/p53, 9p21/p16 and chromosome 12 centromere were made in 28 patients. RESULTS: Secondary chromosomal aberrations were detected in 22 patients. Chromosomal abnormalities occurring in more than 2 cases include deletions 6q15-q23 (53% cases); 11q22/ATM (50%); 9p21 (36%, in half the cases deletion 9p21 was biallele); 13q14 (32%); trisomy 3/3q, monosomy 20 and deletions/translocations 1q and 1p (27% and 20%) and deletion 17p13/p53 (18%). Trisomies 12/12q, 6 and 18/18q, monosomies 2 and 16, deletions/translocations 2p and 16p were found in 2 cases each. The FISH technique identified 9 chromosomal anomalies missed at SCE. Deletions 6q15-q23 were seen in patients with privalent lesions of lymph nodes. Deletions 11q, 13q14, 9p21 and 17p13 occur more frequently in transformation and the blastoid variant. Monosomy 20 was found only in patients with large cell transformations. This was the only cytogenetic defect characteristic for transformed cases, in contrast to denovoblastoid ones. Thus, deletions 6q, 11q23, 13q14 and 9p21 are typical for MCL. Deletions 9p21 and 17p13 are more characteristic for large cell variants of the tumor. Deletion 17p13 occurs at the terminal stage of the disease in rapidly growing tumor mass and resistance to chemotherapy. FISH technique is effective in detection of submicroscopic rearrangements especially small deletions. No significant differences were found between transformed and de novo blastoid cases. This shows that the blastoid variant is not a specific biological form, it is rather a less typical manifestation of the disease due to some preclinical cytogenetic disorders. CONCLUSION: Progression and transformation of MCL are related to mutation of proapoptotic genes and genes proteins of which are inhibitors of active complexes of D1 cycline. Specification of these mechanisms requires further investigations in patients with different clinicomorphological forms of the disease at various stages of the disease.     

肝癌中cyclin D1和cyclin E的表达及其意义

目的 :研究cyclinD1和cyclinE蛋白在肝癌中的表达和意义。方法 :用免疫组化方法检测肝癌组织 5 0例 ,癌旁组织 2 2例 ,正常肝组织 9例中cyclinD1和cyclinE蛋白的表达。结果 :cyclinD1和cyclinE只在肝癌中有过度表达 ,其过度表达与肿瘤分化程度和有无肝内转移相关。结论 :本试验表明 :cyclinD1和cyclinE过度表达可反应肝癌的侵袭力 ,它们与肝癌的发生发展密切相关。     

Cyclin A与PCNA在B细胞性非霍奇金淋巴瘤中的表达

目的 探讨细胞周期蛋白A(cyclin A)和增殖细胞核抗原(PCNA)在B细胞性非霍奇金淋巴瘤(B-NHL)中的表达及意义。方法 采用免疫组织化学法检测65例B-NHL及20例反应性增生淋巴结中cyclin A和PCNA蛋白的表达情况。结果 cyclin A和PCNA在B-NHL中的平均标记指数(1abel index,LI)明显高于反应性增生性淋巴结(生发中心以外的淋巴组织);侵袭性B-NHL中cyclin A的LI和PCNA的LI均高于惰性组;cyclin A与PCNA的表达成正相关。结论 cyclin A和PCNA的高表达与B-NHL的发生发展有关,cyclin A的LI与PCNA LI可以作为衡量B-NHL恶性程度的重要指标。     

套细胞淋巴瘤中P53基因的研究进展

套细胞淋巴瘤(mantle cell lymphoma,MCL)是2001年WHO淋巴造血组织肿瘤新分类中的一种独立的B细胞非霍奇金淋巴瘤,几乎所有的MCL都有t(11;14)(q13;q32)易位,此易位使11q13上的BCL-1癌基因(cyclin D1)与14q32上的IgH基因重排,导致cyclin D1过度表达,促进细胞由G1期进入S期而使G1期缩短。MCL临床病程和转归呈异质性,许多临床和实验室特征可影响其预后,其中P53基因的异常与MCL的病程及转归密切相关。本文就P53基因的缺失、突变与MCL的关系,P53异常患者的治疗作一综述。     

Vision with spatial light modulator simulating multifocal contact lenses in an adaptive optics system

Visual simulators are useful tools to provide patients experience of multifocal vision prior to treatment. In this study, commercially available center-near aspheric multifocal contact lenses (MCLs) of low, medium, and high additions were mapped on a spatial light modulator (SLM) and validated on a bench. Through focus visual acuity (TFVA) was measured in subjects through the SLM and real MCLs on the eye. A correlation metric revealed statistically significant shape similarity between TFVA curves with real and simulated MCLs. A Bland-Altman analysis showed differences within confidence intervals of ±0.01 logMAR for LowAdd/MediumAdd and ±0.06 logMAR for HighAdd. Visual performance with simulated MCLs outperformed real MCLs by ∼20%. In conclusion, SLM captures the profile of center-near MCLs and reproduces vision with real MCLs, revealing that the MCL profile and its interactions with the eye’s optics (and not fitting aspects) account for the majority of the contributions to visual performance with MCLs.