大鼠卵泡发育过程中基质金属蛋白酶-2，-9的作用

目的：探讨基质金属蛋白酶-2,-9（MMP-2,-9）在大鼠卵泡发育的组织重建中的作用。方法：采用原位杂方法检测动情周期大鼠卵泡中MMP-2,-9mRNAs的基因表达变化,并通过密度扫描方法对原位杂交结果进行半定量分析。结果：在动情周期中,各情期卵巢中卵泡的颗粒细胞和发育良好的卵泡的膜细胞中均可检测到MMP-2m-RNA的杂交信号;MMP-9mRNA的表达始于已发育良好的窦前卵泡的膜细胞,此后在小窦状卵泡、窦状卵泡及排卵前卵泡的膜细胞中均检测到MMP-9mRNA的杂交信号。结论：MMP-2,-9可能通过其基因的表达变化参与卵泡的发育过程。     

肺动脉高压肺血管重建大鼠基质金属蛋白酶3基因表达

目的 探讨基质金属蛋白酶3（MMP－3）mRNA转录在肺动脉高压肺血管重建中的可能作用。方法 利用野百合碱（MCT）诱导的大鼠肺动脉高压埃,药右心导管介入测定大鼠肺动脉平均压,RT－PCR法检测不同时间点大鼠肺组织MMP－3mRNA表达水平以及比色法测定主肺动脉段羟脯氨酸含量。结果 实验第21d肺动脉压力已明显升高,以第28d为最高,而大鼠肺组织MMP－3mRNA表达水平以第7d最高,第14、21、28d依次逐渐下调,第21d已接近正常水平,而主肺动脉段羟脯氨酸含量第14d异常降低,以后随肺动脉压力的升高而升高。结论 MMP－3早期转录水平升高可能与肺血管基底膜降解有关,参与对肺血管重建的触发作用,实验后期转录水平下调可能是导致细胞外基质积聚的重要原因之一。     

MMPs和TIMPs在卵巢上皮性肿瘤中表达的分析

目的　体内组织重建和生理过程中基质金属蛋白酶 (MMPs)和特异性抑制剂 (TIMPs)保持着动态平衡 ,不同的TIMP对不同的MMP具有不同的亲和性 ,本课题旨在研究MMP2、MMP9、TIMP1和TIMP2在卵巢上皮性肿瘤中的表达及其作用。方法　收集 1 996年 5月～ 2 0 0 1年 5月在浙江大学医学院附属妇产科医院行手术切除 ,并用福尔马林固定、石蜡包埋的 1 32例病例 ,运用免疫组织化学染色法检测。结果　MMP2、MMP9、TIMP1和TIMP2均表达于细胞胞浆内 ,均随着上皮性卵巢肿瘤恶性程度的增加 ,表达增强 ;在有淋巴结转移的患者中表达明显高于无淋巴结转移者 ;且MMP9 TIMP1、MMP2 TIMP2比例在恶性卵巢上皮性肿瘤中明显增高 ;相关性分析表明MMP2和TIMP2、MMP9和TIMP1间存在相关性 (P <0 0 0 0 1 )。结论　MMP2、MMP9、TIMP1和TIMP2与卵巢上皮性肿瘤的演化、侵袭过程关系密切     

甲状腺乳头状癌MMP-2、MMP-9、TIMP-1和TIMP-2表达对肿瘤侵袭转移的影响

目的　研究甲状腺乳头状癌基质金属蛋白酶 2 ,9(MMP 2 ,MMP 9)及其组织基质蛋白抑制剂 1,2 (TIMP 1,TIMP 2 )表达对肿瘤侵袭转移的影响。方法　采用免疫组织化学S P法 ,检测 65例甲状腺乳头状癌组织中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 76.9%、87.7%、76.9%和 61.5 %。MMP 2和MMP 9表达与淋巴结转移和肿瘤侵袭程度呈正相关 (P <0 .0 1,P <0 .0 5 )。TIMP 1表达与淋巴结转移和侵袭程度呈负相关 (P <0 .0 5 )。TIMP 2表达与淋巴结转移呈负相关 (P <0 .0 5 ) ,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 .0 1)。结论　MMP 2、MMP 9、TIMP 1和TIMP 2表达与甲状腺乳头状癌的侵袭转移密切相关 ,是临床判断甲状腺乳头状癌转移有价值的参考指标     

力尔凡对直肠癌MMP-7表达的影响及其临床意义

目的:评价力尔凡对直肠癌MMP蛳7表达的影响及临床意义。方法:将32例低位直肠癌患者随机分为力尔凡治疗组与对照组,治疗组在术前瘤体内注射力尔凡后接受手术治疗,对照组仅接受手术治疗,并通过免疫组化法分别检测两组MMP蛳7的表达。结果:MMP蛳7在对照组与力尔凡治疗组的表达明显高于对照组,分别为85.7 %,68.7 %,有显著性差异;对照组中Dukes B期和C期MMP蛳7的表达有显著性差异。结论:术前瘤体内注射力尔凡,可明显降低直肠癌MMP蛳7的表达,在Dukes C期比B期更明显。     

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。     

基质金属蛋白酶-2、E-钙黏附素和DNA含量与胃癌侵袭、转移的相关性研究

目的 :探讨基质金属蛋白酶 - 2 (MMP- 2 )、E-钙黏附素 (E- cadherin)在胃癌组织中的表达和癌细胞核 DNA含量与胃癌侵袭、转移的相关性。方法 :对 83例胃癌组织、2 5例正常胃组织进行了上述 3个指标的检测。结果 :正常胃黏膜中 MMP- 2呈阴性表达 ,E- cadherin呈强阳性表达。胃癌组织中 MMP- 2表达呈阳性 ,阳性率为 78.3% (6 5 / 83) ,MMP- 2表达强度与胃癌分化程度、淋巴结转移、浸润深度、弥漫性生长、 TNM分期显著相关 (P<0 .0 5 ) ;而 E- cadherin的阳性率明显减低为16 .9% (14 / 83) ,E- cadherin表达减低与胃癌细胞分化差、浸润深度、弥漫性生长、淋巴结转移密切相关 (P<0 .0 5 )。 DNA指数在胃癌组织和正常胃组织分别为 1.4 7± 0 .2 3和 0 .97± 0 .15 (P<0 .0 1) ;DNA指数与胃癌的分化程度、浸润深度、生长方式、淋巴结转移有相关性 (P<0 .0 1)。结论 :MMP- 2、E- cadherin表达和 DNA含量与胃癌浸润转移密切相关 ,三者在癌组织中水平的变化属胃癌细胞重要的恶性生物学特征 ,其检测有助于对胃癌患者的转移及预后作出判断     

Expression of invasion markers CD44v6/v3, NM23 and MMP2 in laryngeal and hypopharyngeal carcinoma

Twelve laryngeal squamous cell carcinoma cases (7 laryngeal and 5 hypopharyngeal cancer; 15 samples) were analysed by immunohistochemistry for the expression of invasion markers CD44v6/v3, NM23 and matrix metalloproteinase, MMP2. The laryngeal epithelium showed CD44v6⁺v3⁺NM23^- /MMP2^- phenotype. When tumors were grouped into TNM categories the phenotype of the T2 and T3 tumors was similar, characterised by decreased CD44v3⁺ and lack of MMP2 expressions. Meanwhile the NM23 expression was more frequent in T3 tumors. In T4 stage the frequency of NM23 and MMP2 positive cases increased (5/6 and 4/6, respectively) but there was no correlation with the appearence of lymph node metastasis. Comparison of the phenotype of laryngeal and hypopharyngeal tumors, irrespective of the TNM stages, revealed characteristic differences: T2 stage laryngeal tumors showed decreased CD44v3 and occasional NM23 and MMP2 positivity, while in T3 stage these tumors were characterised by increased frequency of NM23 positivity. The phenotype of the hypopharyngeal tumors was significantly different with a high frequency of MMP2 positive cases (5/6) and NM23⁺1ow CD44v3⁺ phenotype. The sharp differences in the phenotypes of laryngeal and hypopharyngeal carcinomas were connected to the differences in their invasive capacity unlike to the size of the tumors, since the T4 stage hypopharyngeal tumors had a significantly smaller size than laryngeal ones, even at lower stages. This work was supported by the Hungarian Ministry of Welfare: ETT No: T-11-100/93     

口腔鳞状细胞癌中MMP9、CD44v6表达及其意义

[目的]研究基质金属蛋白酶-9（matrix metalloproteinase-9,MMP9）、CD44拼接变异体6（CD44 splice variant 6,CD44v6）在口腔鳞状细胞癌（OSCC）中的表达及其相互关系.[方法]应用S-P免疫组化法检测82例口腔鳞状细胞癌,40例口腔黏膜鳞状上皮非典型增生和30例正常口腔黏膜中MMP9和CD44v6的表达.[结果]（1）MMP9在OSCC组中的阳性率（84.1%）显著高于非典型增生组（17.5%）和正常口腔黏膜组（6.6%）.MMP9的阳性表达率与淋巴结转移、肿瘤分化程度相关.（2）CD44v6在OSCC组中的阳性率（78.4%）显著高于非典型增生组（30.0%）和正常口腔黏膜（13.3%）.CD44v6的高表达率与淋巴结转移相关.（3）OSCC中MMP9的表达与CD44v6表达呈正相关.[结论]MMP9、CD44v6对OSCC发生过程具有重要意义,MMP9和CD44v6的表达在OSCC淋巴结转移过程中可能呈协同作用.     

Expression of matrix metalloproteinase-2 and mutant p53 is increased in hydatidiform mole as compared with normal placenta

Matrix metalloproteinases (MMPs) are group of enzymes thought to play an important role in trophoblastic and tumor invasion. The aim of our study was to investigate the trophoblastic expression of MMPs and p53 in normal trophoblast and hydatidiform moles (HM). Paraffin sections of 45 specimens, including 14 complete hydatidiform moles (CM), 15 partial hydatidiform moles (PM), 8 atypical partial hydatidiform moles (aPM), and 8 controls were selected. Classification of HM was established on histologic criteria and supported by the DNA ploidy results. Tissue sections from each case were immunostained with monoclonal antibodies, cytokeratin-7, MMP-2, MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1, and p53 wild type (p53wt) and mutant types (mutp53). Staining for cytokeratin-7 revealed a positive reaction in 93% of the samples. MMP-2 was mainly expressed in the syncytiotrophoblast of HM and found in 62% of aPM, 60% PM, and 93% CM. The mutp53 was mainly and focally expressed in syncytiotrophoblastic cells and was found in 63% of aPM, 80% PM, and 93% CM. Expression of MMP-2 and mutp53 was both significantly greater in HM vs control group (P < 0.05) and greater in CM vs PM and aPM (P < 0.05). No significant difference was observed for cytokeratin-7, MMP-9, TIMP-1, and p53wt between the HM subgroups and between HM and control group. MMP-2 and mutp53 are overexpressed in HM as compared with normal trophoblast and might participate in the invasive behavior of the HM.