MMP-2、TIMP-2在食管鳞状细胞癌中的表达及其临床意义

目的探讨基质金属蛋白酶2（MMP-2）、基质金属蛋白酶组织抑制剂2（TIMP-2）与食管鳞状细胞癌（ES-CC）生物学行为之间的关系。方法采用免疫组化法检测MMP-2、TIMP-2在ESCC中的表达。结果有无淋巴结转移、不同浸润深度、不同临床分期的ESCC患者MMP-2的阳性表达率有统计学差异（P均〈0.05）,有无淋巴结转移、不同临床分期患者的TIMP-2阳性表达率也有统计学差异（P均〈0.05）。结论MMP-2、TIMP-2平衡破坏是ESCC发生、侵袭、转移、甚至影响预后的重要因素,二者均可作为判断ESCC恶性生物学行为的标记物。     

鼻腔鳞状细胞癌组织中MMP-2、MMP-9、TIMP-1、TIMP-2的表达变化及意义

目的 观察鼻腔鳞状细胞癌组织中基质金属蛋白酶(MMP)-2、MMP-9及组织金属蛋白酶抑制剂(TIMP)-1、TIMP-2的表达变化,并探讨其意义.方法 鼻腔鳞状细胞癌患者45例(观察组),鼻窦炎或过敏性鼻息肉患者30例(对照组),采用免疫组化法检测各组MMP-2、MMP-9、TIMP-1、TIMP-2,分析各指标间及与鼻腔鳞状细胞癌临床病理特征的相关性.结果 观察组MMP-2、MMP-9、TIMP-1、TIMP-2阳性率分别为57.8％、62.2％、66.7％、73.3％,对照组分别为23.3％、13.3％、56.7％、26.7％,两组MMP-2、MMP-9、TMP-2比较P均＜0.05.MMP-2表达与鼻腔鳞状细胞癌TNM分期、淋巴结转移、分化程度有关(P均＜0.05),MMP-9、TIMP-2与鼻腔鳞状细胞癌TNM分期、分化程度有关(P均＜0.05).鼻腔鳞状细胞癌中MMP-2与TMP-2表达呈正相关(r=0.64,P＜0.05).结论 MMP-2、MMP-9及TIMP-2表达与鼻腔鳞状细胞癌的浸润、转移及预后密切相关.     

MMP-2、TIMP-2在脑膜瘤组织中的表达及临床意义

目的探讨基质金属蛋白酶-2（MMP-2）与基质金属蛋白酶组织抑制因子-2（TIMP-2）在脑膜瘤组织中的表达及意义。方法选择恶性脑膜瘤标本15份（恶性组）,良性脑膜瘤标本20份（良性组）,采用免疫组化sP法检测两组MMP-2和TIMP-2表达情况,采用spe蛐an等级相关分析法检测两指标的相关性。结果恶性组及良性组MMP-2阳性表达率分别为73．3％（11／15）、15％（3／20）,TIMP-2阳性表达率分别为13．3％（2／15）、80％（16／20）,两组比较P均〈0．01。脑膜瘤中MMP-2与TIMP-2表达呈负相关（r=-0．545,P〈0．01）。结论MMP-2可作为判断肿瘤恶变的指标,TIMP-2可作为肿瘤非恶变的指标,两指标检测可用于指导脑膜瘤的治疗及预后评估。     

食管鳞状细胞癌组织中VEGF、MMP-9的表达及意义

目的观察食管鳞状细胞癌（鳞癌）组织中血管内皮细胞生长因子（VEGF）和基质金属蛋白酶-9（MMP-9）的表达,并探讨其临床意义。方法采用免疫组化SP法检测60例手术切除的食管鳞癌组织、癌旁组织、切缘正常食管黏膜组织中的VEGF和MMP-9。结果食管鳞癌组织中的VEGF和MMP-9在明显高于癌旁组织和正常食管黏膜（P均〈0.05）。食管鳞癌组织中的VEGF和MMP-9与淋巴转移、浸润深度、TNM分期有关（P均〈0.05）。食管鳞癌组织中的VEGF和MMP-9呈正相关（r=0.421,P〈0.05）。结论食管鳞癌组织中VEGF和MMP-9表达增高。二者与食管鳞癌的发生发展有关。     

肾透明细胞癌中MMP-2、TIMP-2的表达及意义

采用免疫组化S-P法检测52例肾透明细胞癌明胶酶A（MMP-2）、金属蛋白酶2组织抑制剂（TIMP-2）表达情况,结果浸润被膜和淋巴结转移组肾透明细胞癌MMP-2的表达明显高于无被膜浸润和无淋巴结转移组（P〈0．05）IMMP-2与肿瘤浸润和淋巴结转移呈正相关,而TIMP-2与其呈负相关（P〈0．05）。表明MMP-2、TIMP-2可作为肿瘤进展及估计预后的参考指标。     

宫颈鳞癌组织中MMP-2、MMP-9的表达变化及意义

目的观察宫颈鳞癌组织中基质金属蛋白酶（MMP）-2、MMP-9的表达变化,并探讨其临床意义。方法采用免疫组化SP法检测46例宫颈鳞癌（A组）、34例宫颈原位癌（B组）和20例正常宫颈上皮（c组）组织中的MMP-2和MMP-9。结果A、B、C组MMP-2蛋白阳性率分别为78．3％（36／46）、50．0％（17／34）、25．0％（5／20）,A组与B、C组比较,P均〈0．01;B、C组间比较,P〉0．05。A、B、C组MMP-9蛋白阳性率分别为71．7％（33／46）、70．6％（24／34）、25％（5／20）,A、B组与C组比较,P均〈0．01;A、B组间比较,P〉0．05。MMP-2、MMP-9蛋白表达与宫颈鳞癌淋巴结转移有关（P均〈0．05）。MMP-2和MMP-9在宫颈鳞癌中的表达呈正相关（L=0．372,P〈0．05）。结论宫颈鳞癌组织中MMP-2-和MMP-9高表达,MMP-2、MMP-9与宫颈癌的发生发展有关。     

黄酒多酚对LDLR－/－小鼠MMP-2、MMP-9、TIMP-1、TIMP-2表达和动脉粥样硬化斑块的影响

目的　观察黄酒是否可以通过黄酒多酚发挥对动脉粥样硬化斑块的抑制作用并探讨其可能机制。方法　40只6周龄雄性低密度脂蛋白受体敲除（LDLR^－/－）小鼠,高脂饲料喂养诱导形成动脉粥样硬化模型,随机分为高脂对照组、瑞舒伐他汀组、黄酒多酚10　mg/（kg·d）组、黄酒多酚30　mg/（kg·d）组和黄酒多酚50　mg/（kg·d）组,每组8只,分别予以无菌水、10　mg/（kg·d）瑞舒伐他汀和10、30、50　mg/（kg·d）黄酒多酚干预。16周后处死小鼠,检测血脂,观察胸腹主动脉粥样硬化情况,Western　blot测定胸主动脉组织内基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）、组织型基质金属蛋白酶抑制剂1（TIMP-1）及组织型基质金属蛋白酶抑制剂2（TIMP-2）的表达,明胶酶谱法测定主动脉弓动脉粥样硬化处MMP-2和MMP-9的活性。结果　与高脂对照组相比,总胆固醇（TC）和低密度脂蛋白胆固醇（LDLC）在黄酒多酚组和瑞舒伐他汀组明显下降（P<0.01）,甘油三酯（TG）在瑞舒伐他汀组明显下降（P<0.01）,在黄酒多酚组差异不明显（P>0.05）,在黄酒多酚组与瑞舒伐他汀组差异明显（P<0.05）;5组间高密度脂蛋白胆固醇（HDLC）水平差异无统计学意义（P>0.05）。与高脂对照组相比,主动脉粥样硬化面积在瑞舒伐他汀组和黄酒多酚10、30、50　mg/（kg·d）组分别减少74.14%、18.51%、40.09%、38.42%（P<0.01）,不同浓度黄酒多酚组主动脉粥样硬化面积与瑞舒伐他汀组比较差异显著（P<0.01）。黄酒多酚和瑞舒伐他汀均能明显抑制MMP-2、MMP-9的表达和活性（P<0.01）,增强TIMP-1、TIMP-2的表达（P<0.01）。结论　黄酒多酚具有类似瑞舒伐他汀的作用,能够调节血脂,在抑制MMP-2、MMP-9表达和活性的同时增强TIMP-1、TIMP-2的表达,减轻动脉粥样硬化斑块的形成,这可能是黄酒对心血管系统的保护机制之一。     

基质金属蛋白酶-2、9在喉鳞状细胞癌患者血清中的表达

目的探讨基质金属蛋白酶(MMP)-2、9在喉鳞状细胞癌(LSCC)患者血清中的表达水平及与临床特征的相关性。方法采用SDSPAGE Zymography法检测56例LSCC患者及40例正常对照组血清中MMP-2、MMP-9水平。结果喉癌患者血清MMP-2、MMP-9浓度明显高于正常对照组(P0.05),其血清MMP-2、MMP-9浓度升高与淋巴结转移显著相关(P0.05),与肿瘤原发部位、病理分级无明显相关性(均P0.05)。血清MMP-9浓度与肿瘤临床分期无明显相关性。血清MMP-2浓度在T4期中明显升高,与其他分期之间差异显著(均P0.05)。结论血清MMP-2、MMP-9在喉癌患者中的浓度明显升高,有助于喉癌的诊断;可能对预测淋巴结转移具有一定作用,并可成为喉癌手术方案选择的依据。     

TIMP-2、MMP-2和MT1-MMP在活化肝星状细胞中的表达及对细胞外基质合成分泌的影响

目的 研究金属蛋白酶组织抑制剂-2(TIMP-2)、基质金属蛋白酶-2(MMP-2)和膜型基质金属蛋白酶-1(MT1-MMP)在活化肝星状细胞(HSCs)中的表达,观察其对细胞外基质(ECM)合成分泌的影响.方法 原代分离培养大鼠HSCs活化后,分别给予40～160 pmol化学合成经修饰抗TIMP-2 siRNA进行干预,检测培养细胞上清液透明质酸(HA)、Ⅲ型前胶原(PCⅢ)和羟脯氨酸(Hyp)的含量,采用荧光实时定量PCR法检测TIMP-2、MMP-2、MT1-MMP、MMP-13、COL Ⅰ和COL Ⅲ mRNA的表达,western印迹检测TIMP-2、MT1-MMP和MMP-13蛋白表达及明胶酶谱法检测MMP-2蛋白表达.结果 应用化学合成经修饰抗TIMP-2 siRNA后,TIMP-2、MMP-2、MT1-MMP、COL Ⅰ和COL Ⅲ的表达明显降低,而MMP-13的表达则明显增加,培养细胞上清液中HA、PCⅢ和Hyp的含量也明显减少.结论 TIMP-2通过MT1-MMP介导MMP-2的活化,抑制TIMP-2的表达,MT1-MMP和MMP-2的表达随之降低,而HSCs合成分泌ECM也相应减少.     

黏膜成熟T细胞和NK细胞淋巴瘤组织中TIMP-2与MMP-9表达及意义

采用免疫组化S-P法检测59例黏膜成熟T细胞和NK细胞淋巴瘤（以下称淋巴瘤）患者瘤组织（淋巴瘤组）与31例鼻咽黏膜淋巴组织反应性增生患者（增生组）增生组织中基质金属蛋白酶抑制剂-2（TIMP-2）和基质金属蛋白酶-9（MMP-9）表达情况。结果淋巴瘤组TIMP-2和MMP-9阳性率分别为81．36％、83．05％,增生组阳率分别为100％、32．26％,TIMP-2和MMP-9表达率与临床分期、血管侵犯和生存期均无显著性关系。两组TIMP-2和MMP-9表达均无明显相关性（r=-0．007,P〉0．05）。提示TIMP-2和MMP-9表达异常在淋巴瘤发生中可能起重要作用,MMP-9可作为鉴别淋巴瘤性质的标志物。     

食管鳞癌组织中MMP-2和E-cadherin的表达及其意义

目的探讨食管鳞癌组织和食管鳞癌细胞系Eca109、EC9706中MMP-2和E—cadherin的表达及其与食管鳞癌临床病理特征的关系。方法应用免疫组化S-P法检测100例食管鳞癌组织及食管鳞癌细胞系Eca109、EC9706中MMP-2和E—cadherin蛋白的表达,应用RT—PCR技术检测两株细胞系中MMP-2mRNA和E—cadherinmR—NA的表达。结果食管鳞癌组织中MMP-2蛋白阳性率明显高于正常黏膜组织（P〈0．01）,且与癌组织的分化程度、浸润深度、淋巴结转移密切相关（P〈0．05）;E—cadhefin蛋白在食管鳞癌组织中阳性率明显低于正常黏膜组织（P〈0．01）,与癌组织分化程度、有无淋巴结转移呈负相关（P〈0．05）,与浸润深度无明显相关性（P〉0．05）;MMP-2和E—cadherin在食管鳞癌中的表达呈负相关（P〈0．01）;细胞系中MMP-2mRNA和E—cadherinmRNA的表达有显著性差异（P〈0．01）。结论食管鳞癌组织中MMP-2呈高表达;E—cadherin呈低表达,二者对食管癌的发生、浸润转移具有相反的调节作用;联合检测其变化可更准确预测食管癌的恶性生物学行为。     

Expression and clinical significance of CtBP2 in human esophageal squamous cell carcinoma

<正>Objective To explore the expression of C-terminal binding protein 2(Ct BP2)in human esophageal carcinoma and its relationship with clinicopathological parameters and survival.Methods The expression levels of CtBP2 in eight cases of fresh frozen specimens of esophageal squamous cell carcinoma(ESCC)and the adjacent e-     

基质金属蛋白酶-9和组织金属蛋白酶抑制剂-1在食管鳞癌中的表达

目的探讨基质金属蛋白酶-9（MMP-9）和组织金属蛋白酶抑制剂-1（TIMP-1）在食管鳞癌中的表达及其临床意义。方法用免疫组化和Western blot法分别检测41例食管鳞癌患者的癌及相应正常组织中MMP-9和TIMP-1的表达变化。结果食管鳞癌组织中MMP-9阳性表达率与食管癌淋巴结及静脉转移有关；MMP-9的阳性表达率与表达量均显著高于TIMP-1；MMP-9和TIMP-1的表达呈负相关。结论MMP-9与食管鳞癌的侵袭转移有关，其机制可能与食管鳞癌组织中的MMP-9／TIMP-1平衡失调有关；MMP-9与TIMP-1联合检测有助于食管鳞癌生物学行为的判断。     

Expression of midkine and its clinical significance in esophageal squamous cell carcinoma

AIM: TO investigate the expression of midkine in esophageal squamous cell carcinoma (ESCC) and analyze its relationship with clinicopathological features. METHODS: RT-PCR and immunocytochemical staining were used to detect the expression of midkine mRNA and protein in EC109 cells, respectively. Then the expression of midkine in 66 cases of ESCC samples were detected by immunohistochemistry using monoclonal antibodies against human midkine. RESULTS: Midkine was expressed in EC109 cell by RT-PCR and immunocytochemistry. The immunoreactivity was detected in 56.1% (37/66) of the ESCC samples. The expression of midkine was found in cytoplasm of tumor cells. Notably, the intensity of midkine was stronger at the area abundant in vessels and the invading border of the tumors. Midkine was more intensely expressed in well differentiated tumors (76.9%) than in moderately and poorly differentiated tumors (43.1% and 41.2%, respectively) (P<0.05). There was no statistically significant correlation between midkine expression and gender, age, clinical stage, lymph node metastasis or survival in ESCC. CONCLUSION: Midkine is overexpressed in ESCC. It may play a role in tumor angiogenesis and invasion. The expression of midkine is correlated with tumor cell differentiation in ESCC. The more poorly tumor cells differentiate, the weaker midkine expresses.     

Expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 in esophageal squamous cell carcinoma

正Objective To analyze the expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 (ESCCAL-1) in esophageal squamous cell carcinoma (ESCC) tissues.Methods From August 2011 to May 2013, 73 patients with ESCC,who received radical resection in the First Affiliated Hospital of Zhengzhou University and Henan Cancer Hospi-     

Expression of MMP—2,TIMP—2 protein and the ratio of MMP—2／TIMP—2 in gallbladder carcinoma and their significance

AIM: To study the correlation between expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 and clinicalpathological parameters of patients with gallbladder carcinoma.METHODS: Carcinomas (n=45) and polypoid lesions (n=15) of the gallbladder were studied for the expression of MMP-2 and TIMP-2 protein by immunohistochemical avidin-biotin-complex method and image analysis. Clinicalpathological data of patients with gallbladder carcinoma such as histological type, grade of differentiation, level of infiltration, liver invasion and lymph node involvement, etc, were recorded.RESULTS: There was significant difference between the average level (1.123±0.108 VS 1.030±0.054, P=0.002) of MMP-2, the ratio (1.050±0.013 VS0.937±0.078, P=0.003) of MMP-2/TIMP-2 in gallbladder carcinomas and in polypoid lesions of the gallbladder. Significant difference was found between the expression of MMP-2 in early stage and advanced tumors, but there was no correlation between MMP-2 protein expression and histological type, differentiation degree, infiltration level, lymph node involvement or liver invasion. Although no difference was observed between TIMP-2 expression and histological type or differentiation degree, signific ant difference was found between TIMP-2 expression and different Nevin stage, infiltration level, local lymph node involvement or liver invasion (1.168±0.067 VS1.048±0.075, 1.170±0.062 vs 1.039±0.06g, 1.039±0.076 VS1.147±0.083, 1.048±0.074 vs 1.103±0.095, P＜0.05). MMP-2/TIMP-2 ratio did not correlate with histological type, grade of differentiation and liver invasion, but significant differences were found between MMP-2/TIMP-2 ratio and different Nevin stage, infiltration level and lymph node involvement in patients with carcinoma of gallbladder.CONCLUSION: TIMP-2 and MMP-2/TIMP-2 ratio could reflect more accurately biological characteristic of gallbladder carcinoma and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis, in the judgment of invasion or metastasis and the estimate of prognosis in patients with gallbladder carcinomas.     

趋化因子受体4在Barrett食管、食管腺癌和食管鳞状细胞癌中的表达及其意义

目的 了解趋化因子受体（CXCR4）在Barrett食管（BE）、食管腺癌和食管鳞状细胞癌中的表达,及其与病理分化程度、临床分期及淋巴结转移之间的关系.方法 应用免疫组织化学SP法对正常食管黏膜56例、BE 80例（其中伴多灶性异型增生22例）、食管腺癌25例和食管鳞状细胞癌组织48例标本中CXCR4的表达进行检测,并用仪器对表达结果进行图像分析,然后进行统计学分析.结果 （1）CXCR4在大部分BE、食管腺癌和食管鳞状细胞癌中呈阳性表达（其阳性率分别为78.8%、68.0%、83.3%）,3组间差异无统计学意义（P＞0.05）,而在正常食管黏膜组中呈阴性或弱阳性表达（阳性率为39.3%）,差异有统计学意义（P＜0.01）;（2）CXCR4在BE、食管腺癌和食管鳞状细胞癌的表达与性别、年龄、病变发生位置均无关（P＞0.05）;（3）CXCR4在BE无异型增生和BE伴多灶性异型增生组织标本中的表达差异无统计学意义（P＞0.05）;（4）CXCR4在食管腺癌高分化较中-低分化者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）;（5）CXCR4在食管鳞状细胞癌表达水平在肿瘤TNM分期的Ⅲ-Ⅳ级较Ⅰ-Ⅱ级者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）,高分化较中-低分化则明显更高（P＜0.01）.结论 CXCR4的表达上调可能是食管腺癌和鳞癌的一个普遍特征,与食管病理组织学类型无关,其表达在BE阶段就已上调,并与食管腺癌和鳞癌的分化程度,有无淋巴结转移和TNM分期有一定相关性.CXCR4的表达对BE、食管腺癌和鳞癌的诊断具有指导价值,有可能成为肿瘤治疗的一个新靶点.     

食管鳞癌组织中STAT3蛋白的表达及临床意义

目的 探讨食管鳞癌组织和癌旁正常黏膜组织中信号转导子和转录激活子3（STAT3）的表达及与食管鳞癌发生发展的关系.方法 应用免疫组化SP法检测122例食管鳞癌及其癌旁正常黏膜组织中STAT3蛋白的表达.结果 食管鳞癌组织中STAT3蛋白表达阳性率为89.3%,明显高于癌旁正常黏膜组织的77%（P＜0.05）.Ⅰ级、Ⅱ级、Ⅲ级食管鳞癌组织中STAT3蛋白的阳性率分别为73.7%、89.5%和100%,Ⅲ级中STAT3蛋白的阳性率显著高于Ⅰ级（P＜0.05）.浸润至深层（深肌层和外膜）的食管鳞癌组织中STAT3蛋白阳性表达率为92.8%,明显高于浸润至浅层（黏膜和浅肌层）食管鳞癌组织的76%（P＜0.05）.STAT3的表达与淋巴结转移无关（P＞0.05）.结论 STAT3蛋白过度表达与食管鳞癌的发生发展及恶性演进有关,STAT3有望成为评估食管癌预后的一个新标志物.     

内皮抑素在食管鳞癌中的表达及其意义

目的研究内皮抑素在食管鳞癌中的表达及其意义。方法采用免疫组化SP法检测内皮抑素在62例食管鳞癌中的表达。结果食管鳞癌组织内皮抑素阳性表达率高于切缘组织和食管良性病组织（P〈0．01）,食管鳞癌内皮抑素表达水平与原发肿瘤的浸润深度、远处转移情况、细胞分化程度、临床TNM分期均有密切关系（P均〈0．05）,而与原发肿瘤部位、区域淋巴结转移状况以及食管鳞癌患者的年龄、性别、饮食习惯、家族史等均无明显关系（均P〉0．05）。结论内皮抑素可能在抑制食管鳞癌侵袭和转移过程中发挥重要作用,可以作为判断其预后的指标之一。     

Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma.

Purpose Matrix metalloproteinases (MMPs) are known to play an important role in extracellular matrix remodeling during the process of tumor invasion and metastasis. However, little is known about their role in preinvasive lesions and early esophageal carcinomas.Method Immunohistochemical analysis of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression was carried out in paraffin-embedded sections of surgically resected esophageal squamous cell carcinoma (ESCC) (58 cases) and paired distal normal esophageal tissues (44 cases) and correlated with clinicopathological parameters.Result Overexpression of MMP-2 and MMP-9 proteins was observed in 39 (67%) and 32 (55%) of the 58 ESCCs, respectively localized in tumor cell cytoplasm and stromal elements. Histological evaluation of hematoxylin- and eosin-stained 44 matched distal normal esophageal tissue sections revealed that 26 comprised of normal epithelium, while 15 tissues showed evidence of dysplasia and three tissues showed hyperplasia. Interestingly, 12 (80%) and 13 (87%) of these 15 dysplasias showed immunostaining for MMP-2 and MMP-9 proteins, respectively. Low levels of MMP-2 and MMP-9 were observed in 10 (38%) and 6 (23%) of 26 matched histologically normal esophageal tissues, respectively. Higher MMP-2 immunopositivity was observed in well and moderately differentiated SCCs in comparison with poorly differentiated tumors. The expression of MMP-2 was significantly reduced with the progressive de-differentiation of esophageal SCCs (P =0.03). Overexpression of MMP-2 and MMP-9 in dysplasia as well as SCC suggests that these alterations occur in early stages of esophageal tumorigenesis.Conclusion Increased levels of MMP-2 and MMP-9 proteins in ESCCs as compared to normal esophageal tissues suggest their association with esophageal tumorigenesis. Increased levels of these MMPs are observed in majority of dysplasias analyzed herein, indicating that these alterations may be early events in esophageal tumorigenesis. In-depth studies are warranted to determine their role in development and progression of esophageal cancer.