浸润性乳腺癌中IGF-1的表达及其意义

目的探讨浸润性乳腺癌中IGF-1的表达及生物学意义。方法应用免疫组化EnVision法检测62例浸润性乳腺癌组织中IGF-1蛋白的表达水平。结果腋淋巴结转移者中IGF-1阳性率高于无腋淋巴结转移者(P<0.05);组织学分级Ⅲ级者,IGF-1阳性率明显高于组织学分级Ⅰ、Ⅱ级者(P<0.01)。结论IGF-1蛋白是乳腺癌浸润和转移过程中的潜在生物学标志,其表达的检测对乳腺癌的浸润程度、转移特性有一定临床价值。     

Wnt2和β-catenin在乳腺癌及其配对癌旁乳腺组织中的表达与临床意义

目的探讨Wnt2和β-catenin在乳腺癌及其配对癌旁乳腺组织中的表达与临床意义。方法采用RT-PCR法检测7份乳腺癌及其配对癌旁乳腺组织中Wnt2和β-catenin基因mRNA的转录水平;免疫组织化学方法检测40份浸润性乳腺导管癌及其配对癌旁乳腺组织中Wnt2和β-catenin蛋白的表达水平;分析Wnt2和β-catenin与乳腺癌临床病理特征的相关性及二者联合检测与乳腺癌恶性程度及淋巴结转移的相关性。结果乳腺癌组织中Wnt2和β-catenin基因mRNA的相对转录水平均显著高于配对癌旁乳腺组织(P0.05)。Wnt2在配对癌旁乳腺组织细胞质中呈弱表达,在浸润性乳腺导管癌组织细胞质中呈高表达,乳腺癌Wnt2阳性表达率(77.5%)显著高于配对癌旁乳腺组织(15.0%)(P0.05);配对癌旁乳腺组织中β-catenin均表达于细胞膜中,在浸润性乳腺导管癌组织细胞质及细胞核中均有表达,异常表达率为67.5%(27/40)。Wnt2和β-catenin的表达与浸润性乳腺导管癌患者年龄无关(P0.05),与乳腺癌临床分期、病理组织学分级及淋巴结转移有关(P0.05)。Wnt2和β-catenin均为阳性表达者的肿瘤恶性程度和淋巴结转移的发生率显著高于两者均为阴性或两者之一为阳性表达者(P0.05)。结论 Wnt2和β-catenin表达在乳腺癌发生和侵袭转移中可能起重要作用,本实验为进一步探讨Wnt2和β-catenin在乳腺癌发病机制中的作用奠定了基础。     

78例大肠癌Cox-2,p53及C-erbB-2表达分析

目的探讨人大肠癌COX-2、p53、C-erbB-2表达及其与与临床病理特征的关系。方法应用S-P免疫组化方法,观察78例大肠癌中COX-2、p53、C-erbB-2的表达情况。结果Cox-2,p53及C-erbB-2阳性表达率在大肠癌分别为82.1%、67.9%、61.5%。在TNMⅢ Ⅳ期患者阳性表达率分别显著高于TNMⅠ Ⅱ期(P<0.05)。Cox-2及p53的表达率在肿瘤有淋巴结转移病例中分别显著高于肿瘤无淋巴结转移病例(P<0.05)。结论大肠癌的Cox-2,p53及C-erbB-2的表达与TNM分期和疾病进展等相关。三者联合检测可为大肠癌的恶性程度及预后的判断提供有效证据。     

VEGF与MMP-9在结肠癌中的表达及临床病理意义

目的探讨VEGF和MMP-9在结肠癌中的表达及临床意义。方法采用免疫组化S-P法检测71例结肠癌组织和18例正常肠粘膜组织中VEGF与MMP-9的表达水平。结果 MMP-9和VEGF在结肠癌组织中的表达明显高于正常肠粘膜(P<0.05),在临床晚期组中表达明显高于早期组(P<0.05),在有淋巴结转移组中表达明显高于无淋巴结转移组(P<0.05)。结论 MMP-9和VEGF在结肠癌组织中的表达和浸润深度、淋巴结转移有关。     

早期乳腺癌保留乳房治疗13年疗效观察

目的评价早期乳腺癌保留乳房治疗的远期疗效。方法57例乳腺癌病人年龄32～67岁,平均年龄46.3岁。选择指征:(1)肿瘤直径<3cm。(2)肿瘤距乳头>3cm。(3)单发肿瘤。(4)查体腋下无质硬淋巴结。按乳腺癌TNM分期为0期、I期、IIA期病人。手术方法是肿瘤扩大切除,将肿瘤连同周围2cm正常组织一并切除。根据切缘快速病理检查结果阴性保乳,反复阳性需改行改良根治术。本组病人部分I期、II期在术后行化疗、全部放疗及部分内分泌治疗。结果本组病例切缘均为阴性,腋下淋巴结无转移者46例,1～3枚淋巴结转移者11例,随访13年,局部复发率5.4%(2/57),总生存率91%(52/57)。美容效果满意率87.7%(50/57)。结论(1)保乳手术治疗早期乳腺癌与同期乳腺癌根治术有相同的生存率。(2)保留乳房外形提高病人生存质量。(3)术前严格掌握手术适应证,术后规范综合治疗是保乳手术获得良好疗效的保证。     

TIMP-1基因在人乳腺癌、结肠癌和宫颈癌细胞中转录水平的差异

<正>基质金属蛋白酶抑制剂(TIMPs)是抑制基质金属蛋白酶MMPs)活性的多功能因子家族,主要分为TIMP-1、TIMP-2、TIMP-3和TIMP-4四种,其中TIMP-1是一种相对分子质量为28500的糖蛋白。最近很多学者发现,TIMP-1基因在乳腺癌患者组织中高表达,并被认为是乳腺癌患者一种新的预后因     

甲状腺乳头状癌血小板生长因子表达与肿瘤分期的相关性研究

目的 甲状腺乳头状癌组织内生长因子的表达水平可能影响甲状腺乳头状癌生长方式,进而影响患者预后.PDGF,VEGF与肿瘤的生长和浸润密切相关.本研究主要探讨PTC患者PLT水平、PDGF和VFGF表达及肿瘤生长方式的关系.方法 实验随机选取Ⅰ/Ⅱ期和Ⅲ/Ⅳ期PTC各30倒,并对2组惠者的PLT水平,甲状腺癌组织内.PDGF、VEGF表达水平进行检测,并对PLT水平.癌组织有无浸润和转移以及PDGF、VEGF表达水平之问的相关性进行了分析.结果 Ⅲ/Ⅳ期患者的PLT水平、PDGFB表达水平明显高于Ⅰ/Ⅱ期患者,PLT表达水平与PDGFB表达水平呈正相关,VEGF表达水平与肿瘤尺寸以及甲状腺外浸润呈正相关.结论 血液中PLI水平较高的PTC患者肿瘤组织局部的PLT浓度相应增高,高浓度的PLT分泌大量PDGFB,激活了肿瘤细胞内的MAPK信号传导系统,导致了细胞生长信号的高表达,从而促进了细胞的生长和增殖.VEGF表达水平较高者PTC肿瘤体积较大,腺体外浸润发生率高.PDGF-B与VDGF的相对高表达可能与PTC临床预后不良有关.     

喉癌组织中P53与微血管密度相关性

目的　探讨P5 3蛋白在喉癌中的表达及其与血管生成和转移的相关性。方法　通过免疫组化SP法检测 4 2份喉癌患者标本中P5 3蛋白表达及微血管密度 (microve -ssedensity ,MVD)。结果　喉癌组织中P5 3蛋白阳性表达率为 4 7 6 2 % ,MVD平均为 35 .79,标准差为 9.4 9。淋巴结转移的肿瘤中P5 3阳性表达及MVD明显高于非转移组 ,P5 3蛋白阳性表达标本中MVD值较高的现象多于有颈淋巴结转移的喉癌。结论　突变型P5 3基因的表达对喉癌肿瘤微血管生成及肿瘤颈淋巴结转移可能具有协同作用。     

凋亡抑制因子survivin在喉鳞癌中表达及其临床意义

目的　探讨凋亡抑制因子survivin在喉鳞癌中的表达及临床意义。方法　应用免疫组化SABC方法检测 5 4例喉鳞癌手术切除标本石蜡切片组织中survivin的表达 ,并以 10例声带息肉组织为对照。结果　survivin在声带息肉中不表达 ;在 5 4例喉鳞癌中 ,38例 ( 70 .4 % )表达阳性 ;survivin阳性表达率与喉癌患者的年龄、性别、肿瘤大小、临床分型无相关性 (P >0 .0 5 ) ,与喉癌临床分期、组织学分级、淋巴结转移呈正相关 (P <0 .0 5 )。结论　凋亡抑制因子survivin的异常表达所引起的凋亡抑制与喉鳞癌的发生发展相关 ,可作为肿瘤诊断、预后和治疗的一个新指标。     

血管内皮生长因子反义基因真核表达载体的构建及其对乳腺癌细胞的生长抑制作用

目的构建反义血管内皮生长因子(VEGF165)基因真核表达载体,分析该基因对乳腺癌细胞的生长抑制作用。方法将人VEGF165cDNA反向克隆至pcDNA3真核表达载体中,构建VEGF165反义基因的真核表达载体,转染人乳腺癌细胞MCF-7,观察转染前后MCF-7细胞的VEGF165表达及细胞生长周期。结果所构建的VEGF165反义基因真核表达载体转染MCF-7细胞后,VEGF165表达下降,细胞生存率下降,G1期细胞数量增加,S期细胞数量减少,细胞增殖能力降低。结论成功构建了VEGF165反义基因表达载体,该基因对乳腺癌细胞的生长具有明显的抑制作用。     

Survivin在结直肠癌组织中的表达及其临床意义

目的探讨凋亡抑制因子Survivin在结直肠癌组织中的表达及其与各临床病理因素之间的相关性。方法应用RT-PCR技术检测58份结直肠癌组织及其癌旁正常组织标本中Survivin基因的表达,回顾性分析其与诸多临床病理因素间的相关性。结果在58份结直肠癌组织中,Survivin基因的阳性表达率为84.5%,而在癌旁正常组织中均不表达,二者差异有统计学意义。在癌组织中,Survivin的表达与患者的年龄、性别、肿瘤大小、部位及组织分化程度无明显相关性,但与Dukes分期及有无淋巴结转移密切相关。结论Survivin基因在结直肠癌组织中高表达,并与病理分期、有无淋巴结转移等恶性临床病理特征有密切相关性,提示Survivin在结直肠癌的发生、发展及预后中发挥重要作用。     

小剂量长春新碱和恩度联合用药对横纹肌肉瘤皮下移植瘤的抑制作用

目的研究小剂量长春新碱(Vincristine,VCR)和恩度(Endostar,Endo)联合用药对横纹肌肉瘤(Rhabdomyosarcoma,RMS)BALB/c裸鼠皮下移植瘤的生长抑制作用,并探讨其机制。方法经BALB/c裸鼠右侧腋部皮下注射RMS细胞PLA-802悬液,建立RMS的皮下移植瘤动物模型;接种RMS后第8天,将选模成功的裸鼠随机分为对照组(注射生理盐水)、VCR组、Endo组和联合组,注射部位均为腹腔,注射体积均为0.2 ml/(只.日),每3 d称重1次,并测量肿瘤的长短径,计算肿瘤体积,绘制肿瘤生长曲线,2周后处死裸鼠,称量瘤重,并计算抑瘤率;RT-PCR和Western blot法检测移植瘤细胞中血管内皮生长因子(Vascular endothelial growth factor,VEGF)基因mRNA的转录水平和蛋白的表达水平;免疫组化法检测VEGF和CD31的分布和表达。结果裸鼠接种PLA-802细胞第8天,RMS裸鼠模型复制成功,裸鼠成瘤率为84%(42/50);联合组裸鼠体重和移植瘤的体积、重量均明显小于对照组、VCR组和Endo组(P<0.01);VCR组、Endo组和联合组抑瘤率分别为31.41%、20.75%和48.41%;与对照组相比,VCR组、Endo组和联合组裸鼠移植瘤细胞中VEGF基因mRNA的转录水平和蛋白表达水平均显著下降,且以联合组下降最明显(P<0.05);免疫组化结果显示,联合组VEGF和CD31的表达水平明显低于其他3组。结论小剂量VCR和Endo对RMS的皮下移植瘤的生长具有明显的抑制作用,而联合用药能起到增效作用,其机制可能是通过抑制肿瘤的血管生成而发挥其抑制作用。     

Expression of CD40 and CD40L in Gastric Cancer Tissue and Its Clinical Significance

To study expression of CD40 and CD40L in gastric cancer tissue we assessed gastric cancer patients admitted to the Department of Gastroenterology of The First Affiliated Hospital of Soochow University and control subjects. Gastric cancer and normal (from around tumours) tissue samples were obtained from patients. Venous blood samples (gastric cancer and ulcer groups) were drawn on the morning of the day before surgery for the measurement of peripheral sCD40L. The expression of CD40 in gastric carcinoma specimens was examined immuno-histochemically. The clinicopathological factors, including age, sex, tumor size, gross appearance, degree of cellular differentiation, histological classification, depth of tumor invasion, lymph node metastasis, peritoneal dissemination, and TNM stage were analyzed according to the different expression of CD40. The results indicated a high CD40 expression in gastric cancer tissues. This positive expression of CD40 revealed a significant (P < 0.05) correlation with lymphatic metastasis and tumor TNM stage in gastric cancer patients. It is concluded that higher CD40 expression existed in expanding type tumors and could play an important role in clinical diagnosis of gastric cancer patients.     

Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer

Early detection and discovery of new therapeutic targets are urgently needed to improve the breast cancer treatment outcome. Here we conducted an official clinical trial with cross-validation to corroborate human plasma Hsp90α as a novel breast cancer biomarker. Importantly, similar results were noticed in detecting early-stage breast cancer patients. Additionally, levels of plasma Hsp90α in breast cancer patients were gradually elevated as their clinical stages of regional lymph nodes advanced. In orthotopic breast cancer mouse models, administrating with recombinant Hsp90α protein increased both the primary tumor lymphatic vessel density and sentinel lymph node metastasis by 2 and 10 times, respectively. What is more, Hsp90α neutralizing antibody treatment approximately reduced 70% of lymphatic vessel density and 90% of sentinel lymph node metastasis. In the in vitro study, we demonstrated the role of extracellular Hsp90α (eHsp90α) as a pro-lymphangiogenic factor, which significantly enhanced migration and tube formation abilities of lymphatic endothelial cells (LECs). Mechanistically, eHsp90α signaled to the AKT pathway through low-density lipoprotein receptor-related protein 1 (LRP1) to upregulate the expression and secretion of CXCL8 in the lymphangiogenic process. Collectively, this study proves that plasma Hsp90α serves as an auxiliary diagnosis biomarker and eHsp90α as a molecular mediator promoting lymphangiogenesis in breast cancer.     

TMPRSS4 as a Poor Prognostic Factor for Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is characterized by the lack of immunohistochemical staining for estrogen receptors (ER), progesterone receptors (PR), and lack of overexpression or amplification of human epidermal growth factor receptor 2 (HER2). Our aim was to investigate the expression of transmembrane protease, serine 4 (TMPRSS4) in TNBC patients and its possible relationship to the outcome of the disease. A total of 72 TNBC patients and 109 non-TNBC patients who were diagnosed between 2003 and 2008 were enrolled in this study. Immunohistochemistry was used to compare the expression pattern of TMPRSS4 in TNBC and non-TNBC groups, and the prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression in TNBC patients. The rate of high expression of TMPRSS4 was significantly higher in TNBC group than that in non-TNBC group. High expression of TMPRSS4 was significantly correlated with lymph node metastasis, histological grade, and tumor size. TNBC patients with high TMPRSS4 expression showed the poorer overall survival (OS) and disease-free survival (DFS) than those patients with low TMPRSS4 expression. In multivariate analysis, only lymph node metastasis and TMPRSS4 expression were the independent prognostic factors for OS and DFS in TNBC. Our study provides evidence that TMPRSS4 expression is associated with lymph node metastasis, tumor size, and histological grade in TNBC patients, and also is an independent prognostic factor for TNBC.     

The Consequences of Soluble Epoxide Hydrolase Deletion on Tumorigenesis and Metastasis in a Mouse Model of Breast Cancer

Epoxides and diols of polyunsaturated fatty acids (PUFAs) are bioactive and can influence processes such as tumor cell proliferation and angiogenesis. Studies with inhibitors of the soluble epoxide hydrolase (sEH) in animals overexpressing cytochrome P450 enzymes or following the systemic administration of specific epoxides revealed a markedly increased incidence of tumor metastases. To determine whether PUFA epoxides increased metastases in a model of spontaneous breast cancer, sEH^-/- mice were crossed onto the polyoma middle T oncogene (PyMT) background. We found that the deletion of the sEH accelerated the growth of primary tumors and increased both the tumor macrophage count and angiogenesis. There were small differences in the epoxide/diol content of tumors, particularly in epoxyoctadecamonoenic acid versus dihydroxyoctadecenoic acid, and marked changes in the expression of proteins linked with cell proliferation and metabolism. However, there was no consequence of sEH inhibition on the formation of metastases in the lymph node or lung. Taken together, our results confirm previous reports of increased tumor growth in animals lacking sEH but fail to substantiate reports of enhanced lymph node or pulmonary metastases.     

Characteristics of TIMP1, CD63, and β1-Integrin and the Functional Impact of Their Interaction in Cancer

Tissue Inhibitor of Metalloproteases 1, also known as TIMP-1, is named for its well-established function of inhibiting the proteolytic activity of matrix metalloproteases. Given this function, many studies were carried out to verify if TIMP-1 was able to interrupt processes such as tumor cell invasion and metastasis. In contrast, many studies have shown that TIMP-1 expression is increased in several types of tumors, and this increase was correlated with a poor prognosis and lower survival in cancer patients. Later, it was shown that TIMP-1 is also able to modulate cell behavior through the induction of signaling pathways involved in cell growth, proliferation, and survival. The mechanisms involved in the regulation of the pleiotropic functions of TIMP-1 are still poorly understood. Thus, this review aimed to present literature data that show its ability to form a membrane complex with CD63 and β1-integrin, and point to N-glycosylation as a potential regulatory mechanism of the functions exerted by TIMP-1. This article reviewed the characteristics and functions performed individually by TIMP1, CD63, and β1-integrin, the roles of the TIMP-1/CD63/β1-integrin complex, both in a physiological context and in cancer, and the regulatory mechanisms involved in its assembly.