MMP-2和TIMP-2在胃癌组织中的表达及其意义

目的　探讨基质金属蛋白酶 -2 (MMP -2 )和组织基质金属蛋白抑制剂 -2 (TIMP -2 )在胃癌组织中的表达及其与侵袭程度、淋巴结转移的关系。方法　应用免疫组织化学S P法对 96例胃癌组织MMP -2和TIMP -2表达情况进行检测。结果　MMP -2和TIMP -2在胃癌组织中表达的阳性率分别为 64 .6%和 3 0 .2 %。MMP -2和TIMP -2的表达与淋巴结转移、侵袭程度有显著相关性 (P <0 .0 1,P <0 .0 5 ) ,与组织学类型、分化程度无显著相关性 (P >0 .0 5 )。结论　MMP -2和TIMP -2的表达与胃癌淋巴结转移、肿瘤侵袭程度密切相关 ,可作为判断胃癌生物学行为和预后的参考指标。     

Marimastat对裸鼠原位种植人胃癌生长和转移抑制的实验研究

目的 探讨基质金属蛋白酶抑制剂Marimastat对胃癌生长和转移的抑制作用。方法 采用人胃腺癌细胞株SGC—7901完整组织块棵鼠原位种植，建立胃癌转移模型。移植7天后开始腹腔内注射Marimastat，隔天1次，剂量为0mg/kg(对照组)、10mg/kg、30mg/kg、60mg/kg(治疗组)，共用8周，第9周处死动物，测量原位肿瘤大小、抑瘤率、肿瘤微血管密度(MVD)、MMP—9的高表达率、观察肿瘤转移情况。结果 治疗组原位肿瘤瘤重明显较对照组轻，肿瘤肝脏转移、腹膜转移、肿瘤组织微血管密度和肿瘤组织MMP—9高表达率与对照组比较，均有显著性差异(P＜0．05)，且与Marimastat剂量呈正相关。结论 Marimastat对体内胃癌的生长及转移均有抑制作用。     

基质金属蛋白酶在肺癌组织中的表达及临床意义

目的 探讨基质金属蛋白酶(MMP2、MMP9)及其抑制物(TIMP1、TIMP2)在肺癌组织中的表达及与肺癌临床分期、淋巴结转移的关系。方法 用免疫组织化学的方法观察肺癌组织MM2、MMP9、TIMP1、TIMP2的表达。结果 肺癌组织中MMP2、MMP9、TIMP1、TIMP2的表达显著高于正常肺组织,与临床分期、淋巴结转移有显著相关性。临床分期越高,MMP2、MMP9的表达越强,TIMP1、TIMP2的表达越弱。结论 MMP2、MMP9参与肺癌的侵袭和转移,是值得重视的生物学标志。     

抗癌作用新靶点及其抑制剂的研究进展

针对靶点分子或某种发生发展机制来设计抗肿瘤药物的研究工作已取得了相当大的成就.这类药物的特异性强,疗效显著,因此,针对这些新靶点进行药物设计可以使抗肿瘤药物的研究产生一次新的革命.本综述旨在讨论目前抗肿瘤药物研究的潜在的新靶点以及它们相应的抑制剂或拮抗剂.     

基质金属蛋白酶-9及其组织抑制因子在戒烟大鼠肺组织中的表达

目的　研究基质金属蛋白酶 -9(MMP -9)及其组织抑制因子 -1(TIMP -1)在戒烟大鼠肺组织中的表达及可能作用机制。方法　建立吸烟肺气肿大鼠模型 ,5 0只雄性Wistar大鼠 ,随机分为 4月、6月对照组和吸烟 4月、6月组、戒烟组 (每组 10只 ) ,用原位杂交和免疫组化等方法观察肺组织基质金属蛋白酶 -9(MMP -9)、金属蛋白酶组织抑制因子 -1(TIMP -1)的mRNA及蛋白的表达 ,用免疫组化法观察IV型胶原在肺内的表达。结果　与相应的对照组相比 ,吸烟 4、6月组MMP -9、TIMP -1在肺组织表达均显著上升 ( P <0 0 1) ;与吸烟 4月组相比 ,戒烟组肺组织MMP -9mRNA及蛋白的表达均明显减少 ( P <0 0 5 ) ,而TIMP -1表达明显上升 (P <0 0 5 ) ,IV型胶原表达增加 (P <0 0 5 ) ;与吸烟 4月组相比 ,戒烟组血气分析改善。结论　戒烟能阻止阻塞性肺气肿进一步发展 ,可能通过抑制MMP -9和增强TIMP -1表达发挥作用     

Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expressions

Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.     

Modulation of Matrix Metalloproteinase and TIMP-1 Expression by TGF-β1 in Cultured Human RPE Cells

In order to investigate the effects of TGF-β1 on the expression of MMP-2, -9 and TIMP1 in human retinal pigment epithelial (RPE) cells, the third-sixth passage cultured RPE cells were treated with TGF-β~ at different concentrations (0.01, 0. 1, 1.0, 10 ng/mL), the expression of MMP-2, -9 and TIMP-1 mRNA was detected by semi-quantitative RT-PCR assays. MMP-2, -9 and TIMP-1 mRNA were expressed in the cultured RPE cells. The values of MMP-2/β-actin in the cells treated with 0.1, 1.0, 10 ng/mL TGF-β1 were 1.04±0.04, 1.07±0.02 and 1.11±0.03, respectively, significantly higher than in the control group (0. 96±0.03, P＜0. 05-0. 01). The expression of MMP-2 mRNA could be up-regulated by TGF-β1, in a dose-dependent manner. The expression of MMP-9 mRNA in the cultured RPE cells was slightly up-regulated by various TGF-β1 concentrations treatment. The values of TIMP-1/β-actin in the cells treated with 0.01 and 0. 1 ng/mL TGF-β1 were 0. 85±0.01 and 0.97 ± 0.02 respectively, significantly lower than in the control group (1.07±0.04, P＜0.01), indicating that the expression of TIMP-1 mRNA was down-regulated by TGF-β1 at low concentrations. But along with the increase of TGF-β1 concentrations (1.0 and 10 ng/mL), the expression of TIMP-1 mRNA was slightly up-regulated, not significantly different from that in the control group (P＞0.05). It was concluded that TGF-β1 might play an important role in the up-regulation of the expression of MMP-2 in RPE cells and result in a directional shift in the balance between MMP and TIMP. This may be facilitated for RPE cells to migrate in the pathogenesis of vitreoretinopathy.     

类风湿关节炎治疗前后血清基质金属蛋白酶-3及普通实验室指标的比较

目的分析比较血清基质金属蛋白酶-3(matrixmetalloproteinase-3,MMP-3)、血沉(ESR)、类风湿因子(RF)、C反应蛋白(CRP)等在类风湿关节炎(rheumatoidarthritis,RA)患者治疗前后的变化,为RA的疗效判断提供新的指标。方法分别测定45例初诊RA患者血清中MMP-3、ESR、RF、CRP水平及治疗后的上述指标,进行比较。结果45例RA患者治疗后此4项指标较治疗前均有不同程度的下降,且差异均有统计学意义(P<0.01)。以平均下降率表示:ESR下降率最大,CRP次之,MMP-3位居第3,RF最小。但在不同X线分期时,各指标的下降率不同。结论MMP-3可作为除ESR、CRP、RF外的判断RA疗效的指标。     

COX-2 基因与基质金属蛋白酶在星形细胞瘤中的表达及二者相关性研

 目的 探讨COX-2基因与基质金属蛋白酶在星形细胞瘤中的表达及二者相关性。方法 用原位杂交的方法检测星形细胞瘤组织中COX-2 mRNA的表达；用Ultrasensitive S-P法(链霉素抗生物素蛋白-过氧化物免疫组化染色)检测同等标本中基质金属蛋白酶-2和基质金属蛋白酶-9蛋白的表达；并将COX-2 mRNA与基质金属蛋白酶的表达作相关性分析。结果 COX-2 mRNA及MMP2、MMP9在星形细胞瘤中高度表达，表达阳性率分别为62．69％、56．70％和58．20％；COX-2 mRNA与MMP2和MMP9均有正相线性关系，Pearson积距相关系数分别为0．260、0．347，P<0．05。结论 COX-2基因和基质金属蛋白酶在星形细胞瘤组织中的表达密切相关，说明它在星形细胞瘤向周围组织侵袭中起重要作用。