基质金属蛋白酶和组织金属蛋白酶抑制剂在大肠癌中的表达

目的　研究基质金属蛋白酶 (MMPs)及组织金属蛋白酶抑制剂 (TIMPs)在大肠癌中的表达特点 ,与肿瘤发生发展的关系 ,以及在肿瘤治疗中的应用前景。　方法　采用RT PCR方法测定 2 8例大肠癌患者肿瘤组织和周围正常粘膜的基质金属蛋白酶 2 (MMP 2 )、膜型 1 基质金属蛋白酶 (MT1 MMP)、基质溶素 (MMP 7)、组织金属蛋白酶抑制剂 2 (TIMP 2 )、组织金属蛋白酶抑制剂 3(TIMP 3)的mRNA表达状况 ,并将其结果与临床及病理学资料进行统计学分析。　结果　 (1) 2 7例患者肿瘤组织中MMP 7mRNA表达阳性 ,MMP 2、MT1 MMP、TIMP 2和TIMP 3在肿瘤组织和正常粘膜中均有高表达 ;(2 )肿瘤组织中MMP 7mRNA的表达水平与大肠癌患者的Dukes′分期相关 (P <0 0 1) ;(3)淋巴结阳性患者的肿瘤组织TIMP 2表达水平为 (1 2 5± 0 46 )明显高于淋巴结阴性患者的 (0 75± 0 41) ,差异有显著性意义 (P <0 0 1) ;(4)大肠癌患者癌周正常粘膜TIMP 3mRNA表达随患者Duke′s分期的进展和肿瘤浸润深度的增加而降低 (P <0 0 1) ;(5 )TIMPs与MMPs之间无明显相关关系 (P >0 1)。　结论　MMP 7可望成为诊断大肠癌的敏感指标 ;人工诱导TIMP 2、TIMP 3或阻断MMP 7、MMP 2、MT1 MMP的表达可能抑制肿瘤的浸润和转移 ,成为肿瘤治疗的新途径。     

膀胱移行细胞癌组织环氧化酶2和基质金属蛋白酶2 mRNA的表达及相关性

目的:探讨膀胱移行细胞癌组织环氧化酶2(COX-2)和基质金属蛋白酶2(MMP-2)mRNA的表达及两者的相关性。方法:应用RT-PCR方法检测42例膀胱移行细胞癌组织(其中Ta~T1期18例,T2~T4期24例;G1级12例,G2级19例,G3级11例;有转移26例,无转移16例)和5例正常对照膀胱组织COX-2、MMP-2 mRNA的表达,并分析与肿瘤分级分期和转移的关系以及两者的相关性。结果:COX-2 mRNA在Ta~T1期相对表达量为1.038±0.484,T2~T4期为1.489±0.584,均显著高于正常对照膀胱组织(0.460±0.224,P均<0.05);COX-2 mR-NA在G1、G2、G3级分别为0.920±0.442,1.338±0.584,1.632±0.515,均显著高于正常对照膀胱组织(0.460±0.224,P均<0.05)。MMP-2 mRNA在Ta~T1、T2~T4期分别为1.107±0.384,T2~T4期为1.604±0.425,均显著高于正常对照膀胱组织(0.423±0.227,P均<0.05);MMP-2 mRNA在G1、G2、G3级分别为0.971±0.370,1.445±0.378,1.755±0.387,均显著高于正常对照膀胱组织(0.423±0.227,P均<0.05)。COX-2与MMP-2 mRNA表达在有转移及无转移肿瘤组织中分别为1.591±0.455vs0.815±0.430,1.676±0.339vs0.927±0.228,P均<0.01。COX-2与MMP-2 mRNA的表达呈显著正相关(r=0.703,P<0.01)。结论:COX-2与MMP-2 mRNA在膀胱移行细胞癌组织高表达,且随肿瘤分级分期及转移而表达增加,二者在膀胱移行细胞癌的发生发展过程中可能具有协同作用。     

基质金属蛋白酶-9及其抑制因子在肾细胞癌组织中的表达和意义

目的　探讨基质金属蛋白酶 9(MMP 9)和金属蛋白酶组织抑制因子 1(TIMP 1)在肾细胞癌中的表达及其与临床病理参数之间的关系。方法　采用免疫组织化学链霉菌抗生物素蛋白过氧化酶 (SP)法检测 5 5例肾细胞癌中MMP 9和TIMP 1的表达情况。结果　MMP 9、TIMP 1蛋白在肾细胞癌和正常肾组织中的阳性表达率各为 63 .63 %和 10 .0 0 % (P <0 .0 5 ) ;60 .0 0 %和10 .0 0 % (P <0 .0 5 )。在肾癌中 ,MMP 9蛋白表达与肿瘤Robson分期、肾包膜侵袭和淋巴结转移密切相关 (P <0 .0 5 ) ,而与组织学类型无关 (P >0 .0 5 ) ;TIMP 1蛋白表达与肾细胞癌的临床病理参数无关 (P >0 .0 5 )。结论　MMP 9蛋白高表达参与了肾癌的发展 ,MMP 9和TIMP 1的平衡失调可能在肾癌的侵袭转移中发挥重要作用。     

MMP-2、MMP-9在膀胱移行细胞癌中的表达及临床意义

目的 探讨基质金属蛋白酶2(MMP2),基质金属蛋白酶9(MMP9)在膀胱移行细胞癌中的表达及临床意义.方法 采用免疫组化SP法和高清晰度彩色医学图文分析系统对35例膀胱移行细胞癌和10例正常膀胱黏膜中MMP-2、MMP-9的表达进行检测分析.结果 MMP-2、MMP-9在膀胱移行细胞癌中呈高表达,且随分期、分级的增高而增高(p＜0.01).结论 MMP-2、MMP-9参与膀胱癌侵袭转移,在膀胱移行细胞癌中的表达对其预后判断具有参考价值.     

MMP-2、MMP-9及TIMP-3在膀胱移行细胞癌中的表达及临床意义

目的探讨基质金属蛋白酶2，9（MMP-2，MMP-9）及金属蛋白酶组织抑制因子3（TIMP-3）在膀胱移行细胞癌中的表达及临床意义。方法采用免疫组化SP法和高清晰度彩色医学图文分析系统对35例膀胱移行细胞癌和10例正常膀胱黏膜中MMP-2，MMP-9，TIMP-3的表达进行检测分析。结果MMP-2，MMP-9在膀胱癌中呈高表达，且随分期、分级的增高而增高；TIMP-3在膀胱癌中亦呈高表达，且与分级呈正相关，但与分期不相关。结论MMP-2，MMP-9和TIMP-3参与膀胱癌侵袭转移，在膀胱移行细胞癌中的表达对其预后判断具有参考价值。     

基质金属蛋白酶-2、9和Ⅳ型胶原在膀胱癌中的表达及意义

我们采用免疫组化方法观察膀胱移行细胞癌 (ＢＴＣＣ)组织中基质金属蛋白酶 2和 9(ＭＭＰ 2 ,ＭＭＰ 9)及Ⅳ型胶原的表达 ,探讨其在ＢＴＣＣ进展中的作用及判断预后的价值。报告如下。材料和方法　收集我院 1988～1995年间手术切除的膀胱癌石蜡包埋组织标本 4 9例。男 4 0例 ,女 9例。年龄 35～ 84岁 ,平均 5 9岁。有随访结果者 4 2例 ,随访时间 3～ 12 0个月。除 1例膀胱全切、1例手术无法切除者外 ,术后复发 2 4例。初发肿瘤 4 1例 ,复发 8例。ＷＨＯ分级 :Ｇ114例 ,Ｇ2 2 3例 ,Ｇ312例。ＵＩＣＣ ＴＮＭ分期 :Ｔ0 1例 ,Ｔ12 4例 ,Ｔ2 10…     

尿中基质金属蛋白酶-9及组织金属蛋白酶抑制剂-1在慢性肾脏病中的临床意义

目的：探讨尿液中基质金属蛋白酶-9（MMP -9）和组织金属蛋白酶抑制剂-1（TIMP -1）水平及其与尿蛋白、肾功能的关系。方法：将69例慢性肾脏病（CKD）分为小量蛋白尿（〈1．0 g/24 h）、中等量蛋白尿（〉1．0 g,〈3．5 g/24 h）、大量蛋白尿组（≥3．5 g/24 h）;20例健康体检者作为对照组者。用酶联免疫吸附法（ELISA 法）测定尿液中 MMP -9和 TIMP -1的水平,同时测定血尿素氮（BUN）、肌酐（Cr）,分析它们之间的关系。结果：（1）CKD 各组尿 MMP -9及 TIMP -1水平均显著高于健康对照组（均 P 〈0．01）,3组间 MMP -9差异无统计学意义（P 〉0．05）;大量蛋白尿组 TIMP -1显著高于中、小蛋白量组（P 〈0．01）,但中、小蛋白尿组之间差异无统计学意义（P 〉0．05）。（2）大、中量蛋白尿组血 BUN、Scr 均显著高于小量蛋白尿组（P 〈0．01）。（3）尿 TIMP -1与尿蛋白（r =0．412,P 〈0．01）及 Scr（r =0．263,P 〈0．05）均呈正相关。尿 MMP -9与尿蛋白、Scr 均无相关性（均 P 〉0．05）。结论：CKD 时肾内促进 ECM 降解和抑制降解酶均增高,但抑制降解作用大于促进降解作用。尿中 TIMP -1明显增高且与尿蛋白量、Scr 均成正相关,故尿中 TIMP -1可以间接反映 ECM 聚积和纤维化。     

基质金属蛋白酶9及组织型基质金属蛋白酶抑制因子1在大鼠外伤性脑水肿中的表达及意义

目的 探讨大鼠脑损伤中基质金属蛋白酶9(MMP9)及组织型基质金属蛋白酶抑制因子1(TIMP1)的表达变化规律及意义.方法 采用Feeney自由落体法制作大鼠轻度脑损伤模型,采用干湿重法测定脑组织含水量;采用逆转录-聚合酶链反应(RT-PCR)法对大鼠脑损伤模型中MMP9及TIMP1 mRNA进行检测并分析两者比值.结果 实验组脑组织含水量(BWC),MMP9mRNA及TIMP1 mRNA表达量及两者比值均明显高于对照组,P值分别为0.013、0.000、0.000及0.011,差异有统计学意义(P<0.05),MMP9 mRNA与TIMP1mRNA表达量及两者比值与BWC均呈正相关,r值分别为0.654、0.355(P<0.05).结论 MMP9/TIMP1的比例失衡可能在外伤性脑水肿的发生发展过程中起重要作用.     

基质金属蛋白酶-7和组织型金属蛋白酶抑制因子-1在膀胱移行细胞癌中的表达及意义

目的探讨基质金属蛋白酶-7（MMP-7）和金属蛋白酶组织抑制因子-1（TIMP-1）在膀胱移行细胞癌中的表达及意义。方法应用免疫组织化学技术检测60例膀胱移行细胞癌[Ⅰ级25例,Ⅱ级15例,Ⅲ级20例;浅表性膀胱癌（T1a-T1）29例,浸润性（T2-T4）31例]和5例正常膀胱组织中MMP-7和TIMP-1的表达情况,X2检验分析其表达与膀胱移行细胞癌分级分期的关系。结果MMP-7和TIMP-1在正常膀胱组织中不表达,而在膀胱移行细胞癌组织表达较强。60例膀胱移行细胞癌标本中MMP-7阳性表达40例（66．7％）。MMP-7的阳性表达率与肿瘤的病理分级显著相关,而与肿瘤的临床分期无明显相关性。60例膀胱移行细胞癌标本中TIMP-1阳性表达32例（53．3％）。TIMP-1在不同的组织分化程度,不同临床分期之间均差异无统计学意义（P〉0．05）。而MMP-7／TIMP-1表达比值与肿瘤的病理分级显著相关。结论MMP-7及MMP-7／TIMP-1比值可反映膀胱移行细胞癌的恶性程度,为膀胱移行细胞癌的预后判断提供一种新的参考指标。     

金属蛋白酶抑制基因RECK和基质金属蛋白酶2、9在膀胱癌组织中的表达及意义

我们采用RT—PCR方法检测金属蛋白酶抑制基因RECK及基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）基因在43例膀胱癌（TCC）组织标本中的表达，探讨以上基因与TCC侵袭、转移等生物学行为的关系。现报告如下。     

Expression of matrix metalloproteinase-7 and tissue inhibitor of metalloproteinase-2 in human endometrial carcinoma

<正>Objective:To investigate the expression of matrix metalloproteinase-7(MMP-7) and its tissue inhibitor (TIMP-2) in endometrial carcinoma and analyze their significance in endometrial cancer's invasion and metastasis. Methods:Endometrial tissues were collected from 64 patients with endometrial carcinoma,20 patients with endometrial hyperplasia and 20 normal women.The expressions of MMP-7,TIMP-2 in endometrium were measured by immuohistochemistry. Results;Expressions of MMP-7,TIMP-2 in endometrium of patients with endometrial carcinoma were significantly higher than those in normal endometrium(P0.05).MMP-7 expression increased with surgical-pathological staging,depth of myometrial invasion,histologic grades and lymph node metastasis(P0.05),while TIMP-2 expression was related to lymph node metastasis(P0.05).TIMP-2 expression in endometrial cancer was significantly higher than that in hyperplastic endometrium(P0.05).Expressions of TIMP-2 and MMP-7 in endometrium of patients with endometrial carcinoma were positively correlated(r=0.654,P0.001). Conclusion:Highly expressed MMP-7 and TIMP-2 in endometrium may be related to development,invasion and metastasis of endometrial cancers.     

非气腹手助腹腔镜肾盂癌根治术(附4例报告)

目的　探索非气腹手助腹腔镜肾、输尿管、部分膀胱切除术治疗肾盂癌的方法。　方法　自 2 0 0 1年 7月至 2 0 0 1年 11月使用自制非气腹装置实施非气腹手助腹腔镜治疗肾盂癌 4例。　结果　手术时间平均 170分钟 ,失血量 195ml。术后未使用镇痛剂 ,平均恢复进食时间 2 8天。术后随访 1～ 4个月 ,未见肿瘤复发。　结论　手助非气腹腹腔镜肾输尿管膀胱部分切除术治疗肾盂癌具有手术时间短、对病人心肺功能损害小、出血少、病人术后恢复快、操作简单易学等优点     

Sarcomatoid transitional cell carcinoma originating from a duplicated renal pelvis

A case of sarcomatoid transitional cell carcinoma of the renal pelvis is reported. It was distinguished from carcinosarcoma by immunohistochemical study. The tumor was difficult to distinguish from a renal parenchymal tumor in imaging studies because it originated from a duplicated renal pelvis.     

An unusual case of transitional cell carcinoma of renal pelvis presenting with brain metastases

We report a rare case, who had presented with a constellation of neurological symptoms (due to multiple brain metastases), but without any urological symptoms, to the department of neurosurgery. The patient was managed with gamma knife stereotactic radiosurgery for the metastatic lesions. During an evaluation for primary, he was found to be having transitional cell carcinoma (TCC) of right renal pelvis, for which palliative radical nephroureterectomy was performed, following which he received four cycles of paclitaxel and carboplatin chemotherapy. The patient is alive with stable disease at 22-months follow-up.     

Matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in the peripheral blood of patients with various glomerular diseases and their implication in pathogenetic lesions: study based on an enzyme-linked assay and immunohistochemical staining

Background Various glomerular diseases progress to end-stage renal failure due to an accumulation of the mesangial matrix (MM) and a thickening of the glomerular basement membrane (GBM). Both the MM and GBM are consistently metabolized through the synthesis and destruction of the matrix. Such synthesis is influenced by transforming growth factor-β (TGF-β) and other factors, whereas the destruction is presumed to be mediated by both matrix metalloproteinases (MMPs) and inhibitors of matrix metalloproteinases (TIMPs). Based on such evidence, we tried to detect MMP-2, MMP-9, and TIMP-1 in the peripheral blood of patients with various glomerular diseases. Methods Serum was used to detect MMP-2 and TIMP-1, while plasma was used to detect MMP-9. These enzymes were detected using an enzyme-linked assay. Results The findings showed an increased level of MMP-2 in patients with a alteration of GBM, typically membranous nephropathy (MN), regardless of the differences in their etiological processes. In contrast, MMP-9 did not show a strong association with any specific glomerular abnormalities. However, it mainly tended to increase in patients with MM accumulation. In addition, the localization of MMP-2, MMP-9, and TGF-β1 was studied using immunohistochemical staining. MMP-2 was demonstrated to exist in the glomerular capillary loop (GCL) as well as in the mesangial cells and the mesangial matrix. MMP-9 was found to exist in mesangial cells and the matrix, GCL, infiltrated neutrophils, and some tubular epithelial cells. Positive staining for TGF-β1 in GCL was found to be associated with an increased level of MMP-2 in patients with MN, whereas in MM such positive staining was not necessarily associated with an increased level of MMP-9. Conclusions These results therefore suggest that MMP-2 plays an important role in the degradation of GBM, while MMP-9 only moderately affects the degradation of MM.     

肾盂癌P16蛋白的表达及意义

目的 探讨Ｐ１６蛋白与肾盂癌病分级、临床分期、预后及肿瘤增生活性的关系。方法：采用免疫组织化学技术对３１例肾盂癌标本中Ｐ１６蛋白表达进行检测。结果 ３１能盂癌Ｐ１６蛋白表达阳性率为５８．１％，其中Ⅰ级、Ⅱ级和Ⅲ级肿瘤阳性率分别为７５．０％、６６．７％和２５．０％（Ｐ〈０．０５），Ｔ１～Ｔ２和Ｔ３～Ｔ４期肿瘤阳性率分别为６６．７％和４６．２％（Ｐ〈０．０５）。显示Ｐ１６蛋白表达阳性率随肾盂癌病理分级     

Significance of circulating matrix metalloproteinase-9 to tissue inhibitor of metalloproteinases-2 ratio as a predictor of disease progression in patients with metastatic renal cell carcinoma receiving sunitinib

ObjectivesTo assess the significance of circulating matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as predictors of disease progression in patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib.Materials and methodsCirculating levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in sera from 52 patients with mRCC treated with sunitinib were measured at the baseline and on the first day of each treatment cycle until progression using enzyme-linked immunosorbent assays.ResultsThe baseline level of MMP-9 in nonresponders to sunitinib was significantly higher than that in responders, whereas the baseline level of TIMP-2 in nonresponders was significantly lower than that in responders. However, there were no significant differences in the serum levels of MMP-2 and TIMP-1 between responders and nonresponders. The serum MMP-9/TIMP-2 ratio at the baseline in nonresponders was also significantly higher than that in responders. Univariate analysis showed that the MMP-9/TIMP-2 ratio, but not MMP-9 and TIMP-2 levels, was significantly correlated with progression-free survival, and the MMP-9/TIMP-2 ratio, in addition to the Memorial Sloan-Kettering Cancer Center classification and C-reactive protein level, appeared to be independently associated with progression-free survival on multivariate analysis. Furthermore, despite the lack of significant differences in the serum levels of MMP-9 and TIMP-2 between the baseline and the time of progression, the MMP-9/TIMP-2 ratio at the time of progression was significantly elevated compared with the baseline ratio.ConclusionsAn imbalance between the serum MMP-9 and TIMP-2 levels could be a novel biomarker to predict disease progression in patients with mRCC under treatment with sunitinib.     

MMP-2和MMP-9在膀胱移行细胞癌组织中的表达及临床意义

目的：探讨膀胱肿瘤组织巾MMP-2及MMP-9表达与膀胱移行细胞癌（TCCB）临床病理分期分级的关系。方法：选择同济医院2004年1～12月间手术治疗的TCCB患者38例作为实验组,以16例附带癌旁正常黏膜或膀胱镜下活检正常膀胱黏膜作为对照组。运用免疫组织化学SP法检测MMP-2及MMP-9在膀胱组织中的表达。结果：MMP-2和MMP-9在实验组的表达显著高于对照组（P〈0．01）,且与肿瘤临床分期呈显著正相关（r=0．51361,P〈0．01）,与肿瘤病理分级也呈正相关（r=0．59818,P〈0.05）。结论：TCCB患者膀胱组织中高表达的MMP-2及MMP-9与肿瘤细胞侵袭和转移密切相关,联合检测MMP-2及MMP-9,对TCCB的早期诊断及判断预后有参考价值。     

膀胱癌中MMP-2、TIMP-2的表达及其与浅表性肿瘤复发的关系

目的：研究基质金属蛋白酶－2（MMP－2）和金属蛋白酶组织抑制因子－2（TIMP－2）在膀胱癌中的表达以及它们与肿瘤临床病理因素和复发的关系。方法：用免疫组织化学SP法检测46例膀胱移行细胞癌标本中MMP－2、TIMP－2的表达，并将它们与肿瘤临床和病理参数相比较。结果：在46例膀胱癌中，MMP－2、TIMP－2的阳性率分别为47.8%和58.7%，TIMP－2在间质中的表达率为47.8%。MMP－2表达率随着肿瘤理分级、临床分期的升高而增加，而TIMP－2表达率则呈下降趋势，但在浅表性膀胱癌（Ta-T1）中，TIMP－2的表达与MMP－2相似，随着肿瘤分期分级的升高而增加，TIMP－2间质表达阳性组中浅表性膀胱癌的2年复发率显著高于表达阴性组。结论：MMP－2和TIMP－2的相互作用对于膀胱癌的侵袭发展发挥了重要作用。TIMP－2在间质中表达可作为判断浅表性膀胱癌复发的预后指标。     

Transitional cell carcinoma of the renal pelvis and ureter: Outcome and patterns of relapse in patients treated with postoperative radiation

We assessed the records of 101 patients with locally advanced transitional cell carcinoma (TCC) of the renal pelvis and ureter treated with postoperative radiation therapy to determine outcome and patterns of failure. Locally advanced disease (i.e., T3–4N0 or N+ disease) was identified in 65 patients. Postoperative radiation was used to treat 86 patients, with a median dose of 35 Gy in 20 fractions over 4 weeks to the tumor bed and regional lymph nodes. There were 15 patients with no residual disease who were offered no further therapy. No patient received postoperative chemotherapy. Prognostic factors were examined using univariate and multivariate analysis, and the patterns of failure were identified after postoperative irradiation. Median follow-up was 9.3 years, during which 76 deaths occurred. The 5-year overall survival was 43% and 10-year survival was 23%. A multivariate analysis identified T3 category, lymph node involvement, and age at diagnosis as significant prognostic factors for survival. Tumor grade was a significant prognostic factor on univariate analysis but not on multivariate analysis. Failure analysis showed that only 36% of patients with locally advanced disease remained relapse free. For this group of patients, distant metastases developed in 53%, and locoregional failured occurred in 35% despite postoperative irradiation. Locoregional failure occurred in 95% of patients with nodal involvement who received postoperative radiation, and 77% of those developed distant relapse. This leads us to conclude that patients with resected locally advanced (T3, T4N0, N+) TCC of the upper urinary tracts have a high risk of relapse and death from disease despite postoperative radiotherapy. Because the main feature of the disease is early distant failure, post-operative chemotherapy is required to improve the outcome for this group of patients.