bFGF和MMP9在鼻咽癌组织中的表达及其临床意义

目的:探讨碱性成纤维细胞生长因子(bFGF)和基质金属蛋白酶9(MMP9)在鼻咽癌患者中的表达及其临床意义。方法:应用免疫组化方法检测289例鼻咽癌患者活检组织治疗前bFGF和MMP9的表达水平,并分析二者与鼻咽癌患者临床病理特征和预后的关系。结果:289例鼻咽癌组织bFGF和MMP9阳性表达率分别为71.3%和61.6%;bFGF和MMP9的阳性表达与鼻咽癌的N分期和临床分期有显著的相关性(P0.05),且两者的高表达均与鼻咽癌的不良预后显著相关(P0.01);在鼻咽癌组织中Spearman相关分析发现,bFGF的表达与MMP9的表达呈明显正相关(r=0.634,P0.05);亚组分析表明,bFGF和MMP9表达水平均升高的鼻咽癌患者的预后最差。结论:bFGF和MMP9在鼻咽癌组织中的表达升高,且两者与鼻咽癌的不良预后明显相关,联合应用有可能成为鼻咽癌的诊断、治疗及判断预后的生物标志物。     

Matrix metalloproteinase-9 activity is associated with poor prognosis in T3-T4 node-negative colorectal cancer

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel membrane-anchored matrix metalloproteinase (MMP) inhibitor. RECK, MMP-2, and MMP-9 are believed to play crucial roles in tumor progression. This study was designed to examine the prognostic value of RECK, MMP-2, and MMP-9 in conjunction with other clinicopathologic factors in patients of T3-T4 node-negative colorectal cancer. RECK and MMP expression was observed using immunohistochemical analysis of the primary tumor from 89 patients with curatively resected T3-4 N0 colorectal cancer retrospectively. High RECK expression was observed in 51 cases, whereas expression was low in the other 38 cases. MMP-2 and MMP-9 expression was positive in cancer cells in 24 and 33 cases, respectively. RECK and MMP-2 expression was not significantly associated with any clinicopathologic factors. However, expression of MMP-9 was correlated with tumor location. A statistically significant inverse correlation was found between RECK and MMP-2 expression, and a statistically significant correlation was found between MMP-2 and MMP-9 expression. However, no association between RECK and MMP-9 expression was observed. Univariate analysis demonstrated that rectal tumor location, preoperative carcinoembryonic antigen more than 5 ng/mL, positive lymphatic invasion, less than 12 dissected lymph nodes, and positive MMP-9 expression were poor prognostic factors of disease-free survival. A multivariate analysis confirmed that enhanced MMP-9 expression was an independent and significant factor for prediction of a poor prognosis. In addition, positive lymphatic invasion and less than 12 dissected lymph nodes were significant negative prognostic factors. In conclusion, MMP-9 status represents a novel prognostic factor in evaluation of T3-T4 node-negative colorectal cancer.     

基质金属蛋白酶-9和血管内皮生长因子在子痫前期患者胎盘组织中的表达

目的 检测子痫前期患者胎盘组织中RECK、基质金属蛋白酶-9（MMP-9）、血管内皮生长因子（VEGF）的基因表达,探讨它们与胎盘滋养细胞浸润过程的调控关系。 方法 采用RT-PCR、Western blotting、免疫组织化学检测120例妊娠足月剖宫产（正常妊娠、轻度子痫前期、中度子痫前期、重度子痫前期各30例）胎盘组织中RECK、MMP-9、VEGF的基因表达。结果 3组子痫前期患者胎盘组织中MMP-9及VEGF的mRNA表达水平均显著低于正常妊娠组（P<0.05）;重度子痫前期组中RECK mRNA的表达显著高于正常妊娠组（P<0.05）;3组子痫前期患者胎盘组织中MMP-9及VEGF蛋白表达均显著低于正常妊娠组（P<0.05）,中度和重度子痫前期组中RECK蛋白表达显著高于正常妊娠组（P<0.05）。结论 子痫前期患者胎盘中RECK与MMP-9、VEGF之间存在负相关性,它们可能参与了胎盘滋养细胞浅浸润过程的调控。     

糖尿病大鼠血管糖基化终产物含量与其受体的ICAM—1表达的关系

探讨糖尿病大鼠血管组织糖基化终产物（AGEs)含量与其受体（RAGE）和细胞间粘附因子－1（ICAM－1）表达的关系。复制糖尿病大鼠模型,采用荧光法、RT－PCR及原位杂交方法检测主动脉及心肌组织的AGEs含量以及RAGE和ICAM－1基因的表达。发现糖尿病大鼠主动脉和心肌组织AGEs含量升高（P＜0．01）;RAGE和ICAM－1基因表达增强（P＜0．05－0．05）;AGEs含量与RAGE及ICAM－1呈明显正相关（P＜0．01）;氨基胍治疗可缓解上述指标的变化。提示 AGEs可诱导RAGE和ICAM－1的表达。推测AGEs-RAGE相互作用是引起糖尿病血管内皮细胞功能紊乱和损伤的关键环节。     

系统性红斑狼疮患者外周血单个核细胞RECK的表达及其与基质金属蛋白酶-9的关系

目的 探讨系统性红斑狼疮(SEE)患者PBMC RECK(reversion-inducing cysteine-richprotein with kazal motif)的表达及其与基质金属蛋白酶-9(MMP-9)的关系.方法 分别用Western blot及RT-PCR检测SLE患者及健康对照组PBMC上RECK的蛋白及mRNA水平,同时检测MMP-9mRNA的水平.加入植物血凝素(PHA)刺激后检测3者的表达变化及刺激后MMP-9的分泌情况并与空白对照组比较.结果 与健康对照组相比,患者组RECK蛋白及mRNA水平降低,MMP-9 mRNA水平增高,分泌MMP-9的能力高于健康对照组.与空白对照相比,PHA刺激后,患者组及对照组RECK蛋白及mRNA表达均降低,MMP-9 mRNA水平升高,MMP-9分泌均增多.RECK的表达与MMP-9的分泌呈负相关.结论 RECK可能通过抑制MMP-9的分泌在SEE发病过程中起重要作用,对其的调控可望为SLE治疗提供新的方向.     

温筋通对糖尿病大鼠心血管组织糖基化终产物的形成及其受体和ICAM-1表达的影响

目的:研究中药复方温筋通(WJT)对糖尿病大鼠心血管糖基化终产物(AGEs)的形成以及AGEs受体(RAGE)和细胞间粘附因子-1(ICAM-1)表达的影响。方法:用链脲佐菌素复制糖尿病大鼠模型。采用荧光法、RT-PCR和原位杂交的方法对心血管组织AGEs的沉积以及RAGE和ICAM-1的表达进行检测。结果:WJT治疗组AGEs形成量明显低于糖尿病模型组(P＜0.01),其治疗作用与AG相当;RAGE和ICAM-1主要在内皮细胞表达,其表达量与AGEs的沉积量呈明显正相关(P＜0.01)。结论:WJT可明显降低糖尿病大鼠主动脉和心肌组织AGEs的形成量以及RAGE和ICAM-1的表达。     

Expression of TWIST,an inducer of epithelial-mesenchymal transition,in nasopharyngeal carcinoma and its clinical significance

Epithelial-mesenchymal transition (EMT) has been implicated in the development of a number of cancers. An important EMT inducer, TWIST, has been detected to be over-expressed in a variety of tumors, but rarely been studied in nasopharyngeal carcinoma (NPC). This study aimed to examine TWIST expression and its association with clinicopathological factors and prognosis in NPC. A total of 65 NPC and 20 normal samples were involved in the present study. RT-PCR and immunohistochemistry were used to examine the mRNA and protein expressions of TWIST in NPC and normal tissues. The relationship of TWIST expression levels with clinical features and prognosis of NPC patients were analyzed. The positive rate of TWIST expression was markedly higher in NPC tissues than that in normal tissues. Over-expression of TWIST was correlated with N stage and the presence of distant metastasis. Patients with positive TWIST expression had a significantly shorter overall survival time relative to patients with negative TWIST expression. The data suggest that TWIST over-expression has a correlation with lymphatic and distant metastasis in NPC. Moreover, it might be a novel biomarker for prediction of advanced tumor progression and a potential unfavorable prognostic factor as well as a potential treatment target for NPC.     

PTHLH在鼻咽癌细胞系及组织中表达上调

目的检测PTHLH在鼻咽癌细胞系及组织中的表达水平,从理论上初步探讨其在鼻咽癌发生发展过程中所起的作用。方法实时荧光定量PCR（FQ—PCR）检测PTHLH在7个鼻咽癌细胞系的表达情况,RT—PCR检测PTHLH在鼻咽癌及非癌鼻咽组织中的表达,免疫组化鉴定其在鼻咽癌及鼻咽上皮组织中蛋白水平的表达。结果PTHLH在鼻咽癌细胞系中的表达上调,以HONE1细胞中表达最高。RT—PCR分析显示PTHLH mRNA在鼻咽癌组织中表达明显上调（61．1％）,免疫组化检测鼻咽癌石蜡标本（49例）发现,PTHLH蛋白在鼻咽癌组织中表达明显高于鼻咽上皮组织（12例）（P〈0．001）。结论PTHLH基因在鼻咽癌细胞及组织中表达增高,提示其可能参与了鼻咽癌的发生发展,有望成为分子生物学诊断的靶点。     

鼻咽癌组织中c-IAP2的表达及其临床意义

目的 探究细胞凋亡抑制蛋白2(cellular inhibitor of apoptosis protein 2,c-IAP2)在鼻咽癌组织中的表达以及临床意义.方法 回顾性分析95例鼻咽癌患者的肿瘤组织和40例正常患者的鼻咽组织及临床预后资料,分别利用RT-PCR、Western印迹以及免疫组织化学染色检测上述组织中...     

血清白细胞介素-6、白细胞介素-17和基质金属蛋白酶9水平与一氧化碳中毒迟发性脑病的关系

目的 探讨白细胞介素(IL)-6)、IL-17和基质金属蛋白酶9(MMP9)与一氧化碳中毒迟发性脑病(DEACMP)的关系.方法 随机抽取58例体检健康人群为对照组,抽取71例DEACMP患者为实验组,采用酶联免疫吸附试验(ELISA)检测DEACMP患者血清中IL-6、IL-17和MMP9的表达水平.结果 和对照组相比,轻重度DEACMP患者血清中IL-6和MMP9表达水平升高(F=22.47、F=36.51,P＜0.05),其中在重度DEACMP患者血清中升高最显著;IL-17表达水平未有显著变化,差异无统计学意义(F=19.62,P＞0.05).Pearson相关分析显示,DEACMP患者血清IL-6和MMP9浓度呈正相关(r=0.58,P＜0.05).结论 DEACMP患者血清中IL-6和MMP9的表达水平与一氧化碳中毒的程度和预后密切相关.     

Expression of MMP9 and CD147 in invasive squamous cell carcinoma of the uterine cervix and their implication

Matrix metalloproteinase 9 (MMP9) and CD147 play a role in invasion and metastasis of many types of human malignancies. The correlation of the expression of MMP9 and CD147 with invasion and metastasis of invasive squamous cell carcinoma (SCC) of the uterine cervix has not been examined. In the present study, RT-PCR assay was used to detect the expression level of MMP9 mRNA semiquantitatively, and immunohistochemical stain was adapted to evaluate the score of CD147 on the cell membrane or in the cytoplasm of tumor cells of 65 cases of invasive squamous cell carcinoma of the uterine cervix and 21 cases of chronic cervitis tissues. MMP9 and CD147 expression in correlation with invasion, metastasis, and differentiation of invasive SCC of the uterine cervix was analyzed statistically. We found that MMP9 and CD147 expression was elevated significantly in tumor tissue compared to the control (cervical epithelium of chronic cervitis) (P<0.01). In the comparison of MMP9 and CD147 expression in 47 cases with lymph node metastasis and 18 cases without lymph node metastasis, there was a significantly higher expression of MMP9 and CD147 in the group with lymph node metastasis (P<0.05 for MMP9, P<0.01 for CD147). MMP9 expression was significantly higher in 24 cases of poor differentiation than in 41 cases of moderate differentiation (P<0.05). No difference was found in CD147 expression between poor and moderate differentiation (P>0.05). No significant difference in MMP9 and CD147 expression levels was obtained between 26 cases of FIGO stage I tumors and 39 cases of stage II tumors (P>0.05 for MMP9, P>0.05 CD147). There was no correlation between MMP9 or CD147 expression levels and the resected tumor size (P>0.05). The positive correlation (r=0.568, P<0.001) of MMP9 expression and CD147 score was seen in the tumor tissues of 65 cases. The data in this study show that MMP9 and CD147 expression are correlated with invasion, metastasis of squamous cell carcinoma of the uterine cervix, and that MMP9 expression is correlated with poor differentiation of invasive squamous cell carcinoma of the uterine cervix.     

Co‐expression of TLR‐9 and MMP‐13 is associated with the degree of tumour differentiation in prostate cancer

In vitro experiments demonstrated that stimulation of Toll‐like receptor 9 (TLR‐9) by synthetic TLR‐9 ligands induces the invasion of TLR‐9‐expressing prostate cancer cells through matrix metalloproteinase 13 (MMP‐13). However, the clinical value of TLR‐9 and MMP‐13 co‐expression in the pathophysiology of the prostate is unknown. In the study, we evaluated the expression levels and clinical significance of the TLR‐9 and MMP‐13 in a series of prostate tissues. One hundred and eighty prostate tissues including prostate cancer (PCa) (n = 137), high‐grade prostatic intraepithelial neoplasia (HPIN) (n = 18) and benign prostatic hyperplasia (BPH) (n = 25) were immunostained for the TLR‐9 and MMP‐13 markers. Subsequently, the correlation between the TLR‐9 and MMP‐13 staining scores and clinicopathological parameters was obtained. Higher expressions of TLR‐9 and MMP‐13 were found in PCa and high‐grade prostatic intraepithelial neoplasia compared to benign prostatic hyperplasia tissues. Among PCa samples, a positive relationship was revealed between the MMP‐13 expression and Gleason score (P < 0.001). There was a significant correlation between TLR‐9 expression and regional lymph node involvement (P = 0.04). The expression patterns of TLR‐9 and MMP‐13 markers demonstrated a reciprocal significant correlation between the two markers in the same series of prostate samples (P < 0.001). Furthermore, the Gleason score of TLR‐9^high/MMP‐13^high and TLR‐9^low/MMP‐13^low phenotypes showed a significant difference (P = 0.002). Higher expressions of TLR‐9 and MMP‐13 can confer aggressive behaviour to PCa. Therefore, these markers may be used as a valuable target for tailored therapy of PCa.     

MMP9、TIMP1及VEGF在子宫内膜异位症患者在位内膜的表达

研究基质金属蛋白酶 9(matrixmetalloproteinase 9,MMP9)及其抑制剂 (tissueinhibitorofmetalloproteinase 1,TIMP1)和血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)在子宫内膜异位症 (endometriosis,EM)患者的在位内膜中的表达。采用免疫组化SP法分别检测 4 5例EM(研究组 )在位内膜及 32例子宫肌瘤 (对照组 )的在位内膜中MMP9、TIMP1及VEGF的表达。MMP9、TIMP1、MMP9 TIMP1和VEGF在研究组和对照组的表达分别为 0 336 ,0 2 76 ;0 2 5 3,0 2 6 7和 1 2 93,1 0 34;0 372 ,0 2 88。其中MMP9、MMP9 TIMP1和VEGF在研究组中的表达显著高于对照组内膜 (P <0 0 1)。EM患者的在位内膜中MMP9、VEGF高表达可能是EM发生发展的重要原因。诊刮筛选出高MMP9、VEGF表达的在位内膜可望成为预测和诊断EM的方法之一。     

巨噬细胞移动抑制因子提高鼻咽癌细胞体外侵袭能力

目的　研究巨噬细胞移动抑制因子 (MIF)体外提高鼻咽癌细胞侵袭能力的原因 ,探讨鼻咽癌细胞早期发生侵袭和转移的机制。方法　采用微孔迁移分析法 (micron migrationassay)检测鼻咽癌细胞株CNE 1、CNE 2在细胞因子MIF诱导下通过 8μm直径微孔的细胞数量变化 ,采用Western蛋白印迹法、流式细胞术和酶联免疫吸附法检测侵袭转移相关因子基质金属蛋白酶 2、9(MMP2 ,MMP9)及白介素 8(IL 8)在此过程中的相应改变。结果　 (1)经MIF诱导后 ,CNE 1通过 8μm微孔的细胞数由原来的 2 3 7± 11 0 2增加至 113 7± 2 0 9,CNE 2则由原来的 3 4 7± 7 41增加至 3 11 3± 48 9,差异均呈显著性 (P =0 0 0 5,P =0 0 0 1)。 (2 )经MIF诱导后 ,癌细胞表达MMP9蛋白的细胞比例均明显增加 ,CNE 1细胞由 2 8 5%± 2 45%增加至 82 4%± 3 49% (P =0 0 0 1) ,而CNE 2细胞则由刺激前的 3 2 8%± 3 48%增加至 86 1%± 1 62 % (P =0 0 0 2 )。同时癌细胞MMP9蛋白表达强度也显著增强 ,CNE 1和CNE 2细胞MMP9蛋白的平均相对强度均比诱导前提高 3倍以上 (P <0 0 5)。但MIF刺激前后 ,MMP2蛋白的细胞表达数量和表达强度在两株细胞中却未见明显变化 (P值均大于 0 0 5)。 (3 )MIF诱导后 ,CNE 2细胞培养上清液中的IL 8浓度为 12     

Abnormal expression of matrix metalloproteinase-9 (MMP9) correlates with clinical course in Chinese patients with endometrial cancer

Aims and background: The aim of the present study was to analyze the expression of matrix metalloproteinase-9 (MMP9) in endometrial cancer and its correlation with clinicopathologic features in Chinese patients, including the survival of patients with endometrial cancer. Methods: Using immunohistochemistry analysis, we analyzed MMP9 protein expression in clinicopathologically characterized 128 endometrial cancer (EC) cases with age ranging from 30 to 85 years (median=51.6 years) and 30 endometrial atypical hyperplasia (EAH) and 30 normal endometrium (NE). Cases with greater than or equal to 6 and less than 6 with the score value of cytoplasmic MMP9 immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of MMP9 and clinical features was analyzed in EC cases. Results: Immunohistochemical analysis revealed that the protein expression of MMP9 detected in EC tissues was higher than that in the EAH tissues and NE tissues (P=0.006). In addition, high levels of MMP9 protein were positively correlated with the status of lymph node metastasis (P=0.044) and the histopathological grade (P<0.05) of EC patients. Patients with higher MMP9 expression did not correlate with EC patients'' clinical outcome in China. Multivariate analysis suggested that status of lymph node metastasis and depth of myometrial invasion, but not MMP9 expression level, were significantly correlated with patients'' survival. Conclusion: MMP9 is highly expressed in ECs and correlates with the progression of ECs, but not be helpful in predicting the prognosis of EC patients.