大肠癌及其转移灶中MMP-2和TIMP-2的表达和意义

目的研究基质金属蛋白酶-2（MMP-2）及其抑制物组织基质金属蛋白酶抑制剂-2（TIMP-2）在大肠癌进展中的作用及其临床意义。方法通过免疫组化的方法检测104例大肠癌组织及其转移灶中MMP-2和TIMP-2的表达。结果MMP-2在转移灶中的阳性率（72．1％）显著高于原发灶中的阳性率（53．8％）（P〈0．05）,而TIMP-2在转移灶中的阳性率（35．6％）显著低于原发灶中的阳性率（66．3％）（P〈0．05）;MMP-2和TIMP-2在大肠癌原发及转移灶中表达均具有相关性,且呈负相关。结论MMP-2和TIMP-2的表达与大肠癌转移密切相关,而且转移灶癌细胞MMP-2的表达明显增强,TIMP-2的表达明显下降,可作为临床判断大肠癌恶性程度、转移及预后的重要参考指标。     

血清MMP-3、TIMP-1及HC gp-39在早期RA患者的表达与临床的相关性研究

目的：研究血清基质金属蛋白酶-3（matrix metalloproteinase 3,MMP-3）、金属蛋白酶组织抑制剂-1（tissue inhibitors of metalloproteinase 1,TIMP-1）及人类软骨糖蛋白-39（human cartilage glycoprotein 39,HC gp-39）在早期类风湿关节炎（rheumatoid arthritis,RA）患者的表达及其相关性因素,探讨其在早期RA的可能意义。方法：选取45例病程〈1年的早期RA患者和32例健康查体者,采用酶联免疫吸附试验（ELISA）分别测定血清MMP-3、TIMP-1及HC gp-39水平,同时测定关节肿胀数（SJC）、关节压痛数（TJC）、血沉（ESR）、C反应蛋白（CRP）、类风湿因子（RF）等相关实验室指标。结果：早期RA患者血清MMP-3、TIMP-1及HC gp-39水平明显高于正常对照组（P〈0.01）。不同X线分期各指标差异有统计学意义（P〈0.05）。不同关节功能分级时各指标差异无统计学意义（P〉0.05）。三指标与SJC（P〈0.01）、TJC（P〈0.01）、ESR（P〈0.01）、CRP（P〈0.01）呈正相关,与年龄、病程、晨僵时间、RF无明显相关（P〉0.05）。结论：MMP-3、TIMP-1及HC gp-39在早期RA患者血清中呈高水平表达,可作为反映疾病活动和早期RA患者出现骨侵蚀的有益预测指标。     

恶性葡萄胎患者血清Hcy和MMP-2、TIMP-2检测的临床评价

目的：评估了恶性葡萄胎患者化疗前后血清Hcy和MMP-2、TIMP-2水平的变化及临床意义。方法：应用酶免法和放射免疫分析对32例恶性葡萄胎患者进行了化疗前后血清Hcy和MMP-2、TIMP检测，并与35名正常妇女作比较。结果：恶性葡萄胎患者在化疗前血清Hcy和MMP-2、TIMP-2水平均非常显著地高于正常妇女组（P〈0．01），化疗后6个月未复发的29例中其水平明显下降或接近正常，而复发的3例，其水平又回升到化疗前水平（P〈0．01）。结论：检测恶性葡萄胎患者血清Hcy和MMP-2、TIMP-2水平的变化可作为患者诊断和疗效观察的参考。     

基质金属蛋白酶MMP-2、MMP-9及其抑制因子TIMP-1、TIMP-2在子宫内膜异位症血清中的表达及临床意义

目的探讨基质金属蛋白酶MMP-2、MMP-9及其抑制因子TIMP-1、TIMP-2在子宫内膜异位症（EMs）血清中的表达及临床意义。方法采用双抗体夹心酶联免疫吸附法（ELISA）检测55例EMs患者和30例对照组血清中删P-2,MMP-9、TIMP-1和TIMP-2水平。结果BMs组血清中MMP-2和MMP-9水平显著高于对照组,TIMP-1和TIMP-2水平显著低于时照组（P〈0．05）。Ⅲ-Ⅳ期血清MMP-2和MMP-9水平显著高于Ⅰ-Ⅱ期和对照组,TIMP-1和TIMP-2水平显著低于Ⅰ-Ⅱ期和对照组（P〈0．05）。结论MMP-2、MMP-9与Elds发生和发展相关,TIMP-1、TIMP-2对MMP-2、MMP-9水平调节有重要作用。     

基质金属蛋白酶-2、金属蛋白酶组织抑制因子-2表达与滑膜肉瘤转移、肿瘤血管生成的关系及其预后意义

目的探讨滑膜肉瘤肿瘤细胞中基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制因子-2（TIMP-2）的表达情况及其预后意义。方法采用免疫组织化学SP法检测72例滑膜肉瘤肿瘤细胞中MMP-2、TIMP-2的表达情况,收集每例临床病理学参数并统计生存率、以CD31标记检测微血管密度（MVD）并分析与生存率的关系。结果（1）MMP-2、TIMP-2的表达阳性率分别为84．7％（61／72）和83．3％（60／72）,二者表达强度呈负相关关系（r=-0．290,P=0．013）。（2）有转移病例出现MMP-2高表达和TIMP-2低表达的比例明显高于无转移病例（分别P=0．010,P=0．002）。（3）MMP-2高表达病例的MVD明显大于其低表达者（P=0．005）,TIMP-2高表达病例的MVD明显小于其低表达者（P=0．048）。（4）单因素和多因素生存分析均显示TIMP-2低表达与患者预后不良有关（分别P=0．002,P=0．016）。结论MMP-2和TIMP-2表达异常可能与滑膜肉瘤的转移及肿瘤血管生成有关,TIMP-2低表达可能提示患者预后不良。     

胎膜中MMP-2/TIMP-2表达与胎膜早破关系的研究

目的探讨基质金属蛋白酶-2（MMP-2）及其抑制因子-2（TIMP-2）在自发性胎膜早破孕妇的胎膜中的变化及其意义。方法收集胎膜早破确诊病例30例,同期收集正常妊娠择期剖宫产30例。采用免疫组织化学PV9000法检测MMP-2及TIMP-2在胎膜中的表达。结果1.所选两组标本感染率比较差别无统计学意义（χ^2=2.857,P=0.091）;2.PROM组胎膜组织结构明显疏松,羊膜与绒毛膜之间的区域普遍较对照组增宽;3.早破组与正常组在HE染色后着色深浅有异,早破组略显淡;4.MMP-2在胎膜早破产妇胎膜中的表达高于正常妊娠剖宫产组阳性率分别为100%,46.67%差异有显著性（U=5.849,P=0.000）;5.TIMP-2在胎膜早破产妇胎膜中的表达低于正常妊娠剖宫产组,差异无显著性（U=1.690,P=0.091）。结论胎膜早破的发生可能与MMP-2的表达上调有关。     

子宫腺肌症与肿瘤转移相关基因之间关系的研究

目的：探讨肿瘤转移相关基因在子宫腺肌症发生中的作用。 方法： 采用免疫组织化学方法，对43例子宫腺肌症患者、22例对照组（正常子宫内膜）的nm23-H1、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、膜型1-基质金属蛋白酶（MT1-MMP）和基质金属蛋白酶组织抑制因子-1（TIMP-1）的表达进行研究。 结果： 子宫腺肌症中，MMP-2、MMP-9和MT1-MMP的表达水平明显高于对照组（P<0.01），nm23-H1和TIMP-1的表达水平无显著差异（P>0.05）。 结论： MMP-2、MMP-9和MT1-MMP在子宫腺肌症的发病过程中可能起重要的作用。     

ACS患者动脉粥样斑块稳定性相关细胞因子变化的临床意义

目的：探讨急性冠脉综合征（ACS）病人血清中的细胞因子基质金属蛋白酶-1（MMP-1）、金属蛋白酶组织抑制剂-1（TIMP1）、sICAM-1、sVCAM-1水平与冠状动脉粥样硬化斑块稳定性的相关性及临床意义。方法：用ELISA检测ACS病人血清中sICAM-1、sVCAM-1、MMP-1、TIMP-1水平,并与正常对照组进行比较分析。结果：ACS组血清sICAM-1、sVCAM-1、MMP-1、TIMP-1水平均非常明显地高于正常对照组（P〈0.01）。结论：外周血中sICAM-1、sVCAM-1、MMP-1、TIMP-1水平增高与ACS相关,能反映冠脉粥样硬化斑块的稳定情况,可作为评价冠状动脉粥样硬化斑块稳定性与病变严重程度的一个参考指标。     

TLR4介导高迁移率族蛋白致系统性红斑狼疮肾损害的作用研究

目的 探讨高迁移率族蛋白1(HMGB1)致红斑性狼疮肾损害的作用机制与Toll样受体4(Toll-like receptor 4,TLR4)表达的相关性.方法 ELISA检测12例健康对照组、16例系统性红斑狼疮(systemic lupus eqrthematosus,SLE)无肾脏损害和18例狼疮性肾炎(lupus nephritis,LN)患者血清中HMGB1、基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶组织抑制剂-2(TIMP-2)的表达情况;流式细胞术检测外周血CD3/TLR4和CD14/TLR4表达情况;分离外周血单个核细胞(PBMC),RT-PCR检测HMGB1 mRNA的表达变化.结果 HMGB1 mRNA相对表达量及血清中HMGB1蛋白在LN组明显高于SLE组和健康对照组;流式细胞术显示CD14+的单核细胞表面HMGB1受体TLR4在LN组表达最高(P＜0.05),且与尿蛋白呈正相关(P＜0.01);LN患者血清中MMP-2和TIMP-2蛋白的浓度明显低于SLE和健康对照组,同时MMP-2/TIMP-2比值下降.HMGB1 mRNA及CD14+/TLR4+与MMP-2/TIMP-2比值均呈显著负相关;LN组患者血清中HMGB1蛋白水平与蛋白尿呈正相关,与MMP-2/TIMP-2比值呈显著负相关.结论 HMGB1是狼疮性肾炎发病中的重要细胞因子;HMGB1可能部分通过TLR4激活PBMC,降低MMP-2/TIMP-2的活性,从而引起蛋白尿.     

MMP-2,TIMP-1在肝细胞癌中的表达及临床意义

目的:探讨基质金属蛋白酶-2(MMP-2)及抑制剂-1(TIMP-1)在人肝癌及癌旁组织中的表达及其与肝癌侵袭转移的关系.方法:应用免疫组织化学法研究50例肝癌及癌旁组织中MMP-2和TIMP-1的表达.结果:MMP-2在肝癌和癌旁组织表达阳性率分别为76%和72%,明显高于正常肝组织的表达(P<0.01)a TIMP-1在肝癌组织和癌旁组织中的表达阳性率分别为58%和56%,高于正常肝组织中的表达(P<0.01).而MMP-2洋相表达率与肝细胞癌的转移、淋巴浸润、包膜形成和肿瘤分化有关(P<0.05).而TIMP-1的表达与癌组织的转移,淋巴结浸润和包膜形成有关(P<0.05).结论:MMP-2,TIMP-1在肝癌及癌旁组织中的表达明显增高,可能对于判断肝癌的浸润、转移有重要价值.     

肿瘤M2-PK和NSE联检在小细胞肺癌诊断中的价值

目的：探讨肿瘤M2型丙酮酸激酶（Tumor M2-PK）和神经元特异性烯醇化酶（NSE）在小细胞肺癌（SCLC）早期诊断中的价值。方法：采用酶联免疫吸附法和电化学发光免疫分析仪（Eleesys2010）分别检测32例SCLC患者及50例肺良性疾病患者外周血中Tumor M2-PK和NSE的含量。结果：SCLC患者Tumor M2-PK和NSE水平明显高于肺良性疾病患者，差异有统计学意义（P〈0．01）。单个检测Tumor M2-PK、NSE及联检Tumor M2-PK和NSE（Tumor M2-PK＋NSE）的敏感性分别为46．9％（15／32）、59．4％（19／32）及68．8％（22／32），特异性分别为92％（46／50）、90％（45／50）及84％（42／50）。结论：Tumor M2-PK和NSE对于小细胞肺癌的辅助诊断有一定的临床意义。联检Tumor M2-PK和NSE可提高小细胞肺癌的诊断敏感性。     

Differential expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer: implications for tumour progression

AIMS: To investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer (NMSC) and to compare their expression between different tumour types and with clinicopathological factors. METHODS AND RESULTS: A study of 11 normal skin, 29 Bowen's disease (BD), 40 squamous cell carcinoma (SCC) and 38 basal cell carcinoma (BCC) samples for MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out using immunohistochemistry and in situ hybridization. The expression of all metalloproteinases was greater in tumours than in normal skin. MMP-2 and MMP-9 expression was more extensive in the stroma of SCC than of BCC or BD. TIMP-1 expression was greater in the stroma of BCC than of SCC or BD and TIMP-2 expression was greater in the stroma of SCC than of BD. There was a correlation between increased metalloproteinase expression and depth of lesion (MMP-2 and TIMP-2), inflammation (MMP-2, MMP-9, TIMP-1 and TIMP-2) and microvessel density (MMP-2, MMP-9 and TIMP-2). CONCLUSIONS: MMP-2, MMP-9, TIMP-1 and TIMP-2 play an important role in the pathogenesis of non-melanoma skin cancer, but differ significantly in their expression levels between the tumour types examined. The immunoexpression of these proteins may be useful indicators of cutaneous cancer invasion and progression.     

Serum insulin-like growth factor (IGF)-I and IGF-binding proteins in lung cancer patients.

Many studies have shown that insulin-like growth factors (IGF-I & IGF-II) are implicated in the autocrine and paracrine growth of various tumors. Alterations in serum IGFs and IGF-binding proteins (IGFBPs) profiles have been reported in lung cancer. In this study, we measured serum levels of IGF-I and IGFBPs in 41 patients with lung cancer (small cell lung cancer, SCLC, 9; non-small cell lung cancer, NSCLC, 32) by radioimmunoassay and Western ligand blot (WLB). The serum IGF-I level in patients with lung cancer was significantly lower than in controls (207.9+/-62.6 vs 281.3+/-53.9 ng/mL, p<0.01). Patients with NSCLC showed significantly lower serum levels of IGF-I compared with SCLC patients (194.0+/-62.9 vs 258.4+/-27.8 ng/mL, p<0.01). Patients with squamous cell carcinoma tended to show lower serum levels of IGF-I than in those with adenocarcinoma (187.9+/-63.6 vs 215.9+/-59.5 ng/mL, p>0.05). The concentration of IGFBP-3 in lung cancer was 48% of that found in controls by WLB. The serum level of IGFBP-2 was markedly elevated in patients with lung cancer compared with controls (1303.7+/-618.0 vs 696.2+/-300.5, p<0.01). However, there was no significant difference between SCLC and NSCLC groups. This result showed that serum level of IGF-I/IGFBPs may be useful markers for diagnosing and identifying tumor types in lung cancer and further studies are needed.     

血浆明胶酶检测在慢性肾脏疾病中的临床意义

目的:通过观察慢性肾脏病(CKD)患者血清MMP2,MMP9的变化与血肌酐的关系,探讨对CKD患者行MMPs检测的临床意义.方法:用ELISA法对60例CKD患者和40例健康对照组的血清MMP2、MMP9进行检测,分析CKD患者血清MMP2、MMP9与血肌酐(Scr)的相关性.结果:CKD患者血清MMP2、Scr显著高于对照组(P＜0.001),而血清MMP9、eGFR显著低于对照组(P＜0.05).CKD患者Scr与血清MMP2正相关(r=0.276,P＜0.05),与血清MMP9负相关(r=-0.389,P＜0.01).结论:CKD患者血清MMP2升高,MMP9降低,可能促进CKD的进展.     

Growth pattern correlates with the distribution of basement membrane and prognosis in lung adenocarcinoma

Lung adenocarcinoma frequently has a histologic heterogeneity, particularly with regard to its cell morphology and growth pattern, with or without stromal desmoplasia. However, little is known about the relationship between morphologic heterogeneity and the destruction of BM. We selected 147 foci showing different growth patterns studied in 76 patients with lung adenocarcinoma and examined immunohistochemically the distribution of BM antigens, as well as the expression of MMPs and TIMP-2. BM antigens were more highly preserved in foci of the BAC growth pattern (94.7%) than in those of the papillary/acinar (24.5%) and solid patterns (16.1%) (p<0.01). MMP-2-positive cancer cells were significantly more frequent in poorly preserved foci of BM antigens than in preserved foci (p<0.05). The population of TIMP-2-positive cancer cells showed a positive correlation with BM preservation (p<0.05). However, no significant relationship between growth pattern and expression of MMP-9 and -14 was found. BM antigens had almost totally disappeared in desmoplastic foci. Multivariate analyses revealed that pathologic stage and high expression of TIMP-2 were independent prognostic factors. These findings indicate that the histologic heterogeneity of lung adenocarcinomas is partly related to the cancer cell-stromal interaction, in particular through BM preservation or destruction, which was mainly affected by cancer cell expression of MMP-2 and TIMP-2 in lung adenocarcinomas.     

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

We examined whether two functional polymorphisms (g.-1306C>T and g.-735C>T) in matrix metalloproteinase (MMP)-2 gene are associated with preeclampsia (PE) or gestational hypertension (GH), and whether they modify MMP-2 or tissue inhibitor of metalloproteinase (TIMP)-2 plasma concentrations in these hypertensive disorders of pregnancy. We studied 130 healthy pregnant (HP), 130 pregnant with GH, and 133 pregnant with PE. Genomic DNA was extracted from whole blood and genotypes for g.-1306C>T and g.-735C>T polymorphisms were determined by Real Time-PCR, using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by ELISA. The main findings were that pregnant with PE have higher plasma MMP-2 and TIMP-2 concentrations than HP (P<0.05), although the MMP-2/TIMP-2 ratios were similar (P>0.05). Moreover, pregnant with GH have elevated plasma MMP-2 levels and MMP-2/TIMP-2 ratios compared to HP (P<0.05). While MMP-2 genotypes and haplotypes are not linked with hypertensive disorders of pregnancy, MMP-2 genotypes and haplotypes are associated with significant alterations in plasma MMP-2 and TIMP-2 concentrations in preeclampsia (P<0.05). Our findings may help to understand the relevance of MMP-2 and its genetic polymorphisms to the pathophysiology of hypertensive disorders of pregnancy. It is possible that patients with PE and the MMP-2 haplotype combining the C and T alleles for the g.-1306C>T and g.-735C>T polymorphisms may benefit from the use of MMPs inhibitors such as doxycycline. However, this possibility remains to be determined.     

宫颈癌中MMP-2及TIMP-2的表达及其临床意义

目的 :通过检测基质金属蛋白酶 - 2 (MMP - 2 )及基质金属蛋白酶组织抑制物 - 2 (TIMP - 2 )在宫颈癌中的表达 ,探讨其与宫颈癌侵袭转移的关系。方法 :采用免疫组化S -P法检测 5 1例宫颈癌和 16例正常宫颈组织中MMP - 2和TIMP - 2的表达情况。结果 :MMP - 2、TIMP - 2在正常宫颈上皮组织中均无表达 ,在宫颈癌组织中的阳性表达率分别为 74 .5 % (38/ 5 1)、4 7.1% (2 4 / 5 1) ,有显著性差异 (P <0 .0 1)。MMP - 2、TIMP - 2的表达与组织学类型无关 ,但与临床分期、细胞分化程度、淋巴结转移有关。结论 :MMP - 2、TIMP - 2的表达与宫颈癌的侵袭转移有关 ,MMP - 2、TIMP - 2可作为预测宫颈癌侵袭转移潜能和临床预后的指标。     

基质金属蛋白酶-2、3及其组织抑制剂TIMP-1在子宫内膜异位症中的表达

目的探讨基质金属蛋白酶(MMP-2、MMP-3)及其抑制剂(TIMP-1)在子宫内膜异位症发生及发展中的作用.方法采用免疫组化SP法分别测定MMP-2、MMP-3 、TIMP-1在卵巢子宫内膜异位症异位内膜60例(A组),子宫腺肌症异位内膜40例(B组),子宫肌瘤子宫内膜30例(对照组C)的表达强度.结果 A、B组中MMP-2、MMP-3的表达强度明显高于对照组(P<0.05)而TIMP-1的表达明显低于对照组(P<0.05);A、B组间MMP-2、MMP-3 、TIMP-1 的表达无明显差异(P>0.05).结论在子宫内膜异位症中MMP-2、MMP-3的过度表达及TIMP-1的低表达可能与内异症的发生与发展有关.