血清中 MMP-9、TIMP-1表达水平与肺癌病理特征的关系分析

目的：检测肺癌患者血清MMP-9、TIMP-1水平变化,探讨其与肺癌患者病理特征的关系。方法选取80例肺癌患者为研究对象,另选取30例正常健康者为对照组,ELISA法测定肺癌患者及正常者血清中MMP-9、TIMP-1水平,比较两组之间差异。结果肺癌患者血清MMP-9、TIMP-1水平均显著高于正常者（ P＜0．01）,肺癌患者血清中MMP-9、TIMP-1表达水平与肺癌病理类型、病理分化程度无关（P＞0．05）,与肿瘤体积大小、TNM分期、淋巴结转移、远处转移相关,肿瘤≥3 cm患者血清中MMP-9、TIMP-1水平明显高于肿瘤≤3 cm的患者;Ⅲ＋Ⅳ期患者血清中MMP-9、TIMP-1水平明显高于Ⅰ＋Ⅱ期患者;淋巴结转移患者血清中MMP-9、TIMP-1水平明显高于无淋巴结转移患者;远处转移患者血清中MMP-9、TIMP-1水平明显高于无远处转移患者;肺癌患者MMP-9表达与TIMP-1表达呈正相关（γ＝0．634,P＜0．05）。结论 MMP-9、TIMP-1在肺癌患者中表达与TNM分期、淋巴结转移、远处转移相关,在肺癌侵袭转移中有重要作用,可监测病情发展。     

抗癌防转汤抑制肝癌淋巴道转移及其对MMP-9和CTL影响的研究

目的：探讨抗癌防转汤抑制小鼠肝癌淋巴道转移效果及其机制。方法：采用随机数字表法将小鼠分为正常对照组、荷瘤对照组、低剂量治疗组和高剂量治疗组，建立小鼠肝癌淋巴道转移模型，计算接种后面（21d小鼠抑瘤率）并运用MTT法检测CTL细胞活性及免疫组织化学方法和Western blot检测各组原发瘤及转移瘤基质金属蛋白酶-9（matrix metalloproteinase9，MMP-9）的表达水平，运用统计学分析数据意义。结果：治疗组较对照组，小鼠抑瘤率明显提高，MMP-9在原发瘤、转移瘤表达均减少（P＜0．05），细胞毒性T淋巴细胞（cyto-toxicity T lymphocyte，CTL）活性增强（P〈0．05），而且跟药物浓度呈正相关，P〈0．05。结论：抗癌防转汤有抑制肝癌淋巴道转移的作用，且其与MMP-9的表达水平降低，CTL细胞活性增强有关。     

中肺合剂对S180肉瘤、Lewis肺癌荷瘤小鼠抑瘤作用实验研究

[目的]探讨中肺合剂对S180肉瘤、Lewis肺癌荷瘤小鼠的抑瘤作用,并初步探索其机制.[方法]采用S180肉瘤、Lewis肺癌移植瘤小鼠模型,分荷瘤阴性对照组、低、中、高剂量中肺合剂组和CTX阳性对照组,观察中肺合剂对两种荷瘤小鼠肿瘤生长的抑制作用;运用EnVision免疫组化染色法观察中肺合剂对Lewis肺癌荷瘤小鼠肿瘤组织cvclinD1周期蛋白表达的影响。[结果]中肺合剂低、中、高剂量组和CTX组对移植性荷S180小鼠的抑瘤率分别为16．48％、29．73％、23．51％、41．87％;与阴性对照组相比,中肺合剂低、中、高剂量组和CTX组瘤重均有显著性差异（P〈0．05）。中肺合剂低、中、高剂量组和CTX组对移植性荷Lewis肺癌小鼠的抑制率分别为22．33％、39．02％、25．48％、64．16％;与阴性对照组相比,低剂量组和高剂量组瘤重均有显著性差异（P〈0．05）,中剂量组和CTX化疗组瘤重均有非常显著性差异（P〈0．01）。中肺合剂能下调Lewis肺癌小鼠肿瘤组织cyclinD1蛋白的表达水平,中、高剂量组阳性表达率与阴性对照组相比,有显著性差异（P〈0．051：[结论]中肺合剂对S180和Lewis荷瘤小鼠有明显的抑瘤作用,量-效关系呈抛物线型．其抑瘤作用可能与下调肿瘤组织cyclinD1蛋白表达水平有关。     

应用组织微阵列技术分析甲状腺乳头状癌MMP-2、MMP-9、TIMP-1和TIMP-2表达

目的研究基质金属蛋白酶2，9（MMP-2，MMP-9）及其组织抑制剂1，2（TIMP—1，TIMP-2）在甲状腺乳头状癌组织中的表达与肿瘤侵袭转移的关系，探讨组织微阵列技术的可行性。方法采用组织微阵列技术结合免疫组织化学S—P法检测甲状腺乳头状癌组织MMP-2、MMP-9、TIMP-1和TIMP-2的表达。结果MMP-2、MMP-9、TIMP-1和TIMP-2在甲状腺乳头状癌组织中的阳性表达率分别为78．8％（82／104）、83．7％（87／104）、71．2％（74／104）和57．7％（60／104）。MMP-2和MMP-9阳性表达与肿瘤侵袭程度和淋巴结转移呈正相关（P〈0．05，P〈0．01）。TIMP-1和TIMP-2阳性表达与淋巴结转移呈负相关（P〈0．01，P〈0．05），与侵袭程度无明显相关性。MMP-9与TIMP-1表达有显著相关性，且呈负相关（P〈0．05）。结论甲状腺乳头状癌组织中MMP-2和MMP-9的高表达与TIMP-1和TIMP-2的相对低表达可能促进肿瘤的侵袭和转移。组织微阵列是检测多样本组织的1种高效、低耗、可比性强的分子病理学研究工具。     

人参皂苷Rg3与顺铂对荷卵巢癌裸鼠免疫功能及肿瘤相关蛋白的影响

[目的]观察人参皂苷Rg3联合顺铂对荷高转移人卵巢癌细胞系HO．8910PM转移瘤裸鼠白细胞介素．2（IL-2）、干扰素-γ（INF-γ）及nm23、血管内皮生长因子（VEGF）及增殖细胞核抗原（PCNA）的影响。[方法]移植瘤裸鼠随机分成6组腹腔给药：荷瘤空白对照组fA组）;不同Rg3浓度药物组：2．5mg／kg（B组）、5mg／kg（C组）和lOmg／kg（D组）;Rg3和顺铂联用组（E组）以及顺铂阳性对照组（F组）。分别测定各组裸鼠转移瘤体积变化、IL-2、INF-γ、nm23、VEGF及PCNA的变化情况。[结果]与A组比较,E组（P〈0．05）和F组（P〈0．01）小鼠血清中IL-2、INF-γ含量均能显著降低;B（P〈0．05）、C、D和E（P〈0．01）组小鼠移植瘤组织nm23的表达均增强。Rg3给药后,小鼠移植瘤组织VEGF、PCNA表达均呈下降趋势。[结论]人参皂苷Rg3和顺铂联用具有协同抗肿瘤及减毒的作用。Rg3可能通过增强mm23的表达．使VEGF及PCNA表达呈下降趋势等多途径产生抗肿瘤作用。     

肺癌血清基质金属蛋白酶-2及其组织抑制因子的表达

[目的]探讨基质金属蛋白酶MMP-2及其组织抑制因子-2（TIMP-2）在肺癌中的表达。[方法]采用ELISA法对45例肺癌患者血清中的MMP-2及TIMP-2进行测定，并与15份正常血清进行对照分析。[结果]肺癌患者同对照组比较，血清中MMP-2及TIMP-2浓度均显著升高（t=7．79，P〈0．01；t=6．69，P〈0．01）。Ⅰ、Ⅱ、Ⅲ期肺癌患者间血清MMP-2和TIMP-2水平均有显著性差异（F=42．29，P〈0．01；F=5．12，P〈0．05）。分期级别增加，血清MMP-2／TIMP-2比值依次升高，有显著性差异（F=5．33，P〈0．01）。[结论]MMP-2在肺癌发生发展中具有重要的作用。     

MMP-9、LMP-1蛋白在鼻咽癌中的表达及其与远处转移的相关性研究

目的：研究基质金属蛋白酶-9（MMP-9）、潜伏膜蛋白-1（LMP-1）在鼻咽癌中的表达及其对鼻咽癌远处转移的影响。方法：收集83例鼻咽癌患者的临床资料及鼻咽部瘤体活检组织蜡块。采用免疫组化s—P法检测标本中MMP-9、LMP-1的表达。结果：MMP-9阳性表达率为65％（54／83）,其表达与颈淋巴结转移、远处转移关系密切（P〈0．05）。LMP-1阳性表达率为57％（47／83）,其表达与颈淋巴结转移、远处转移关系密切（P〈0．05）;且与MMP-9表达呈显著正相关（rJ=0．327,P〈0．05）。鼻咽癌远处转移的危险因素是临床分期（Ⅲ、Ⅳ期）、颈淋巴结N,阳性、MMP-9阳性表达、LMP-1阳性表达（P〈0．05）。MMP-9、LMP-1均为阳性表达者远处转移风险更高（P〈0．05）。结论：MMP-9、LMP-1阳性表达与远处转移明显相关,可作为鼻咽癌远处转移的预测指标。     

MMP-2、TIMP-2在口腔鳞状细胞癌中表达的临床病理研究

[目的]研究口腔鳞状细胞癌（OSCC）组织中基质金属蛋白酶-2（MMP-2），基质金属蛋白酶组织抑制因子-2（TIMP-2）的表达。[方法]采用免疫组化SP法检测60例OSCC、35例非典型增生、20例止常口腔黏膜中MMP-2、TIMP-2的表达情况。[结果]OSCC中MMP-2、TIMP-2的表达均高于非典划增生组（P〈0．05），在非典型增生组中表达高于正常口腔黏膜组（R＜0．05）。MMP-2的表达与肿瘤细胞分化程度、淋巴结转移密切相关（P〈0．05），与年龄、肿瘤大小、TNM分期无关（P〉0．05）。TIMP-2与肿瘤的淋巴结转移密切相关（P〈0．05），与年龄、肿瘤大小、肿瘤细胞分化程度、TNM分期无关（P〉0．05）。淋巴结转移组中MMP-2／TIMP-2比值显著高于无淋巴结转移组（P〈0．05）。[结论]MMP-2、TIMP-2是OSCC转移的重要生物学标志，MMP-／TIMP-2比值对评估淋巴结转移的潜能有重要意义。     

rmh-TNF协同顺铂抗小鼠Lewis肺癌血管生成的作用

目的：观察重组改构人肿瘤坏死因子（recombinant mutant human tumor necrosis factor，rmh-TNF）协同顺铂（cisplatin，又称DDP）抗小鼠Lewis肺癌血管生成的作用。方法：建立C57BL／6小鼠Lewis肺癌模型，随机分为4个治疗组：生理盐水对照组、rmh-TNF（150万U／kg）组、DDP（6．15mg／kg）组、联合用药组（DDP＋rmh—TNF）。接种肿瘤细胞后12d开始瘤内注射药物3d，RT-PCR法测定瘤组织中HIF—1α的表达，免疫组化法检测肿瘤组织血管内皮生长因子（vascular endothelial growth factor，VEGF）、激酶结构域受体（kinase domain region receptor，KDR）、微血管密度（microvascular density receptor，MVD）的表达，流式细胞术测定基质金属蛋白酶2（matrix metallopmteinase-2，MMP-2）的表达。结果：对照组、rmh-TNF组、DDP组和联合用药组小鼠肿瘤组织中的MVD数分别为（24．76±1．28）、（18．95±1．22）、（19．53±1．15）、（10．43±1．05），两单药组的MVD数明显低于对照组（P〈0．05）；联合用药组低于两单药组（P〈0．05）。HIF-1αmRNA相对表达水平分别为（0．171±0．004）、（0．138±0．006）、（0．134±0．006）、（0．095±0．006），两单药组较对照组明显下降（P〈0．05），联合用药组明显低于两单药组（P〈0．05）。肿瘤组织中MMP-2蛋白的荧光指数FI值依次为（1．000±0．000）、（0．875±0．020）、（0．848±0．127）、（0．545±0．107），单药组的MMP-2蛋白的（FI）值较对照组明显下降（P〈0．05），联合用药组明显低于两单药组（P〈0．05）。单药组VEGF、KDR表达均明显低于对照组（P〈0．05），联合用药组的表达均低于各单药组（P〈0．05）。结论：rmh—TNF能够增强DDP抗小鼠Lewis肺癌血管生成的作用。     

SKI-Ⅱ联合顺铂对人胃癌裸鼠移植瘤抑制作用及其机制探讨

目的：研究鞘氨醇激酶-1（sphingosine kinase-1,SphKl）在胃癌裸鼠移植瘤血管生成中的作用及其作用机制。方法：建立人胃癌SGC7901裸鼠移植瘤模型后,将荷瘤小鼠随机分为4组,分别予以腹腔注射生理盐水、SKI-Ⅱ、顺铂和SKI-Ⅱ联合顺铂干预治疗,1次／周,共3周。每隔3d测1次肿瘤大小,绘制肿瘤生长曲线,计算抑瘤率;蛋白质印迹法法检测瘤体中SphKl和VEGF的表达;免疫组化方法检测瘤体SphKl、VEGF和CD34的表达情况及计算瘤体内瘤体微血管密度（mierovessel densitv,MVD）。结果：与生理盐水组相比,3组治疗组均有抑制肿瘤生长作用,SKI-Ⅱ组和顺铂组抑瘤率分别为（48．694-1．39）％和（75．24±1．19）％;其中以SKI-1I联合顺铂组抑瘤作用最为明显,抑瘤率达（90．25±1．53）％,各组抑瘤率之间差异有统计学意义,F=1865,P〈0．001。免疫组化结果示,SKI- Ⅱ和SKI—Ⅱ联合顺铂组SphKl蛋白表达分别为（45．62±7．54）％和（20．50±5．96）％,VEGF蛋白表达分别为（45．38±7．82）％和（22．25±4．74）％,瘤体内的MVD为15．12±1．55和9．384-1．92,与对照组差异有统计学意义,P〈0．001。单用顺铂对SphKl表达（82．50±5．95）％）、VEGF的表达（83．25±4．40）％及瘤体内MVD（24．50±5．42）的影响差异无统计学意义,P〉0．05。Pearson相关分析显示,瘤体组织SphKl与VEGF的表达呈正相关,r=0．968,P〈0．001;瘤体组织MVD计数与VEGF表达呈正相关,r=0．862,P〈O．001。蛋白质印迹法检测结果示,SKI-Ⅱ及SKl-Ⅱ联合顺铂组可显著下调SphKl和VEGF的表达,P〈0．001,单用顺铂对SphKl和VEGF的表达差异无统计学意义,P值分别为0．083和0．165。结论：下调SphKl的表达后,可减少VEGF合成与分泌,并抑制肿瘤血管生成,可能是抑制裸鼠胃癌移植瘤生长的途径之一。     

Increased plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung and breast cancer are altered during chest radiotherapy

PURPOSE: Does the release of plasma matrix metalloproteinase-9 (MMP-9) by radiation-activated airway epithelial cells and infiltrating inflammatory cells play a role in the radiation damage or repair process in the lungs? We evaluated lung damage by ionizing radiation using plasma levels of MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and MMP-3 as biologic markers of tissue damage, and also their relationship to changes in pulmonary epithelial permeability, clinical signs and symptoms, and lung structural changes. METHODS AND MATERIALS: Seven serial studies were conducted in each of 8 patients undergoing chest radiotherapy (RT) for lung or breast cancer, beginning before the first treatment (baseline) and then biweekly to approximately 100 days during and after RT. Chest radiographs were monitored for each patient. Sandwich enzyme-linked immunoassays (ELISA) were used to measure plasma MMP-3, MMP-9, and TIMP-1 levels. Lung permeability was evaluated by measuring the rate of epithelial clearance of approximately 150 microCi ( approximately 5.6 MBq) inhaled (99m)Tc diethylenetriamine pentaacetate aerosol (DTPA). RESULTS: Lung and breast cancer resulted in very high plasma levels of MMP-9 (126-893 ng/mL) and TIMP-1 (496-8985 ng/mL) in all subjects studied before initiation of RT. This compares with plasma MMP-9 and TIMP-1 values in healthy volunteers of 29 +/- 11 ng/mL and 436 +/- 86 ng/mL, respectively. RT was followed by a sharp decrease in plasma MMP-9 within the first 2 weeks, but without a corresponding change in TIMP-1. In contrast, plasma MMP-3 levels, which are generally increased with inflammation, were elevated in only 1 of 5 subjects. CONCLUSION: Lung and breast cancer are associated with high plasma levels of MMP-9 and TIMP-1. These high baseline plasma levels of MMP-9 were reduced in the first 2 weeks of RT in 7 of 8 subjects, and TIMP-1 plasma levels remained high in all subjects. The decrease in plasma MMP-9 after initiation of chest RT appears to reflect a suppressive effect on cancer-induced cellular responses rather than a primary role for MMP-9 in radiation-induced lung damage. Likewise, the lack of a rise in plasma MMP-3 levels does not support a role for MMP-3 in tissue injury or repair in the lung. It remains to be determined whether plasma MMP-9 measurements will serve as a useful parameter in predicting cancer relapse.     

Expression of type IV collagen, metalloproteinase-2, metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in laryngeal squamous cell carcinomas

Objective: To investigate the significance of type IV collagen, metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression in laryngeal squamous cell carcinomas (LSCCs). Methods: Expression was quantified in 44 LSCC and 22 adjacent non-cancer normal tissues using a streptavidin-peroxidase conjugated immunohistochemistry and associations between the levels of the four proteins and clinicopathological characteristics in LSCC were analyzed. Results: Significantly different expression of all four proteins was observed in LSCC and adjacent non-cancer normal tissues (P<0.05). Expression of type IV collagen correlated with primary cancer status (P = 0.04), clinical stage (P = 0.04) and histological grade (P = 0.01). Expression of MMP-9 correlated with the location of the tumor (P = 0.04), cervical node metastasis (P = 0.02) and prognosis (P = 0.02). The (MMP-2+MMP-9)/TIMP-1 score was associated with the prognosis of LSCC (P < 0.01). Conclusions: This study suggests that expression of type IV collagen and its regulators is strongly associated with the development of LSCC. Type IV collagen and MMP-9 may be more valuable than MMP-2 and TIMP-1 for the evaluation of clinical characteristics. Regulation of type IV collagen may contribute to the balance of MMPs and TIMPs in LSCC.     

MMP-2、MMP-9及TIMP-2、TIMP-1在宫颈鳞癌中的表达及其意义

目的:探讨基质金属蛋白酶MMP-2、MMP-9及其组织抑制物TIMP-2、TIMP-1在宫颈鳞癌组织中的表达,及其间比值与宫颈鳞癌侵袭、转移的关系。方法:应用RT-PCR技术检测33例宫颈鳞癌和30例慢性宫颈炎组织中MMP-2、MMP-9、TIMP-2、TIMP-1mRNA表达水平。结果:(1)MMP-2、MMP-9在宫颈鳞癌组织中表达高于慢性宫颈炎组织,其表达值随癌的分期、病理分级的增高及淋巴结的浸润和转移而升高,TIMP-2、TIMP-1的表达则相反(P<0·01)。(2)宫颈鳞癌组织的分期、病理分级与MMPs/TIMPs值成正相关。结论:MMP-2,MMP-9,TIMP-2,TIMP-1的表达与宫颈鳞癌的发生发展密切相关,MMPs/TIMPs可能是评价宫颈鳞癌分期和病理分级的—个可靠指标。     

Matrix metalloproteinases 1 and 3, tissue inhibitor of metalloproteinase-1 and the complex of metalloproteinase-1/tissue inhibitor in plasma of patients with prostate cancer

We analyzed blood plasma concentrations of matrix metalloproteinase-1 and -3 (MMP-1; MMP-3), the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the complex MMP-1/TIMP-1, and looked for any correlation with prostate cancer stage. These components were measured by ELISA tests specific for these proteins in healthy male controls (n = 35), and in patients with benign prostatic hyperplasia (BPH; n = 29), with prostate cancer (PCa) without metastasis (T2,3pN0M0; n = 29) and with PCa with metastatic disease (T2,3,4pN1,2M1; n = 18). Mean values of MMP-1 and of the complex MMP-1/TIMP-1 were not different among the 4 groups studied. The mean MMP-3 and especially TIMP-1 concentrations were significantly higher in PCa patients with metastases compared with controls, BPH and PCa patients without metastases. Ten of these 18 patients had TIMP-1 concentrations higher than the upper reference limit. TIMP-1 concentrations were correlated with staging but not with grading. Our results point towards plasma TIMP-1 concentration as a potential marker of malignant progression of PCa. Int. J. Cancer 74:220-223, 1997. © 1997 Wiley-Liss, Inc.     

基质金属蛋白酶和组织金属蛋白酶抑制剂表达失衡与胃癌浸润转移的关系

背景和目的：基质金属蛋白酶－9（matrix metalloproteinase-9,MMP-9)及其相应的组织金属蛋白酶抑制剂－1（tissue inhibifor of metalloproteinase-1 TIMP-1)在肿瘤细胞浸润和转移过程中起重要的调节作用,本研究观察二者在胃癌中的共表达情况,探讨其表达失衡与胃癌浸润转移和预后的关系。方法：应用免疫组化方法检测256例胃癌细胞MMP－9、TIMP－1和细胞增殖核抗原Ki-67的表达,并行回顾性随访。结果：胃癌侵及肌层以上者的MMP－9表达（70．13％）明显高于胃癌仅限于粘膜及粘膜下层者（42．50％,P＜0．05）,MMP－9表达与肿瘤细胞增殖指数、淋巴结转移呈正相关,TNM分期高者MMP－9表达（75．00％）高于TNM分期低者（46．15％,P＜0．05）;TIMP－1的表达与胃癌浸润程度、淋巴结转移及TNM分期呈负相关（Pearson列联系数分别为0．1688,0．3556和0．3004,P＜0．05）。胃癌组织中MMP－9和TIMP－1表达失衡有4种类型,其中MMP－9表达超过TIMP－1者胃癌发生浆膜浸润、淋巴结转移的比例明显高于TIMP－1表达超过MMP－9者或二者表达平衡者（P＜0．05）,而术后胃癌患者的生存率情况则相反,MMP－9表达超过TIMP－1者术后生存率明显低于TIMP－1表达超过MMP－9者（P＜0．05）。结论：MMP－9阳性表达与胃癌浸润转移呈正相关,而TIMP－1阳性表达与胃癌浸润转移呈负相关,二者在胃癌浸润转移中的关系表现为MMP－9促进肿瘤转移为主,TIMP－1对胃癌有独立的抑制作用,MMP－9阳性表达而TIMP－1阴性表达者提示胃癌患者预后不良。     

Adhesion induces matrix metalloproteinase-9 gene expression in ovarian cancer cells

The processes of cell invasion includes adhesion, proteolysis of extracellular matrix (ECM) and migration. It is not only related to cancer cells metastasis, but also involved in infiltration of immune effector cells,embryogenesis and angiogenesis. During the invasioncells attach and spread on the ECM, secrete proteinase to hydrolyze ECM, and then move through interstitial stroma. Matrix metalloproteinases (MMP), especially MMP-2 and MMP-9, play an important role in this processe[1,2].…     

Angelica sinensis suppresses human lung adenocarcinoma A549 cell metastasis by regulating MMPs/TIMPs and TGF-β1

In this study we investigated the potential effects of Angelica sinensis on the growth and metastasis in human lung adenocarcinoma A549 cells. In?vitro the Cck-8 assays showed that Angelica sinensis had weak antiproliferative effect on A549 cells only at high concentration. The cell adhesion assay showed that Angelica sinensis decreased the adhesive ability of A549 cells in a dose- and time-dependent manner. Transwell invasion and migration assay showed that Angelica sinensis reduced the invasive and migratory abilities of A549 cells in a dose-dependent manner. In?vivo the animal experiments showed that Angelica sinensis suppressed lung metastasis of nude mice at high concentration. Then, we attempted to clarify the mechanisms of anti-metastatic activities of Angelica sinensis. The results showed Angelica sinensis inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), it involved the down-regulation of the expressions of MMP-2 and MMP-9 at both the protein and mRNA levels, which may be associated with Angelica sinensis suppressing the expression of TGF-β1. It also involved the increase of the tissue inhibitors of metalloproteinases TIMP-2, but TIMP-1 decreased upon incubation of A549 cells with Angelica sinensis. The results suggest that Angelica sinensis might exert anti-growth and anti-metastasis activity against lung cancer cells through the decrease of MMP-2, MMP-9, TGF-β1 and TIMP-1 and increase of TIMP-2.     

miR-143、MMP-2和TIMP-1在哈萨克族食管癌组织中的表达及其临床病理意义

目的: 探讨在新疆哈萨克族食管癌组织中miR-143、基质金属蛋白酶-2(MMP-2) 和基质金属蛋白酶抑制剂-1(TIMP-1)的表达及其临床意义。方法: 根据前期芯片检测结果,通过靶点预测软件PicTar TargetScan和miRanda预测miR-143可能与肿瘤相关的靶基因。并采用实时荧光定量PCR方法检测30例哈萨克族食管癌组织及相应癌旁组织中miR-143、MMP-2和TIMP-1的表达水平,分析其与临床病理特征的关系。结果: miR-143在哈萨克族食管癌组织中表达较远端癌旁组织中明显降低,差异有统计学意义(P=0.000);miR-143低表达与分化程度、淋巴结转移、临床分期相关(P依次为0.042、0.039、0.007);MMP-2、TIMP-1在哈萨克族食管癌组织中表达均较远端癌旁组织中增高,差异均有统计学意义(P=0.026和P=0.021);MMP-2高表达与淋巴结转移正相关(r=0.367 P=0.037);miR-143与MMP-2、TIMP-1的表达均呈负相关(r依次为-0.442、-0.410,P均<0.05),MMP-2与TIMP-1的表达呈正相关(r=0.794,P=0.000)。结论: miR-143与MMP-2、TIMP-1表达失调共同参与哈萨克族食管癌的发生发展过程,MMP-2和TIMP-1可能是miR-143的靶基因。     

基质金属蛋白酶及其抑制剂在非小细胞肺癌组织中的表达及临床意义

目的：探讨MMP-2、MMP-9、TI MP-1和TI MP-2在非小细胞肺癌（non-small cell lung cancer,NSCLC）组织中的表达及临床意义。方法：用免疫组化法测定124例NSCLC组织、124例癌旁组织和10例良性肺病组织（错构瘤）中MMP-2、MMP-9、TI MP-1和TI MP-2的表达。结果：在NSCLC组织中,MMP-2、MMP-9、TI MP-1和TI MP-2表达水平显著高于癌旁组织和良性肿瘤（P均〈0.05）。MMP-2在鳞癌组织中的表达水平显著高于腺癌和腺鳞癌（P〈0.05）;TI MP-2在鳞癌中的表达水平显著高于腺癌（P〈0.05）;MMP-9和TI MP-1在腺癌组织中的表达水平显著高于鳞癌（P〈0.05）。在NSCLC组织中,随着TNM分期增加,MMP-2、MMP-9、TI MP-1和TI MP-2的表达水平增加（P均〈0.05）。MMP-2、MMP-9、TI MP-1和TI MP-2在淋巴结转移组中的表达水平显著高于无淋巴结转移组（P均〈0.05）。MMP-2、MMP-9、TI MP-1和TI MP-2在低分化组中的表达水平显著高于高分化组（P均〈0.05）。MMP-9在女性组中的表达水平显著高于男性组（P〈0.05）。MMP-2、MMP-9、TI MP-1和TI MP-2之间的表达水平呈显著性正相关（P均〈0.05）。结论：MMP-2、MMP-9、TI MP-1和TI MP-2均参与NSCLC的形成且与NSCLC临床病理特征关系密切,同时可能是判断预后的较好评价指标。