基质金属蛋白酶等几种酶类与卵巢恶性肿瘤浸润转移关系的研究及诊断模型的建立
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摘要
卵巢癌死亡率在妇科肿瘤中居首位。尽管肿瘤减灭术及以铂类为基础的联合化疗在卵巢癌的治疗中起到了积极的作用,但因缺乏有效的早期诊断方法,70%的患者初诊时已为晚期患者。手术及化疗后复发率高、易出现耐药,因而患者的5年生存率长期停留在30%左右。基质酶类通过降解细胞外基质(ECM)在肿瘤的侵袭和转移中起了关键性的作用。因此,本课题探讨MMP-9, Hpa, CL与卵巢恶性肿瘤发生、发展、转移及其预后价值,构建了三种酶类联合诊断卵巢癌浸润转移诊断模型并对模型进行验证。最后,对已发表的基质酶类组织含量表达相关研究内容的文献进行META分析,用循证医学的观点对有争议的问题进行分析,从中找到解决问题的线索,以期更好、更快地解决上述卵巢巢癌酶学诊断中的主要问题。
血清MMP-9、Hpa、CL的检测对卵巢癌浸润转移判断的临床价值目的：探讨卵巢肿瘤患者外周血基质酶类的表达及与其临床病理的相关性。方法：采用ELISA酶联免疫吸附法检测了217例卵巢恶性肿瘤、101例卵巢良性肿瘤及101例正常对照的血清中几种基质酶含量的表达,将结果与临床及病理资料进行统计学分析。
结果：恶性卵巢肿瘤患者血中基质酶含量的表达均显著高于良性组及正常对照组,差异有显著性(P<0.05)；在恶性卵巢肿瘤患者血清中,基质酶类的表达与病理类型无关,与临床分期、组织分化程度有关；CL表达与腹腔转移有关,Hpa表达与远处转移有关,MMP-9表达与腹腔转移有关。相关分析显示血清CL与CA125的相关系数为0.051,P=0.434。P>0.05,二者无明显相关性。血清Hpa与CA125的相关系数为0.183,P=0.005。两者呈正相关,即Hpa含量越高患者,CA125含量也越高；血清mmp9与CA125的相关系数为0.131,P=0.044,两者呈正相关,即MMP-9含量越高患者,CA125含量也越高。
结论：基质酶类的表达与卵巢恶性肿瘤的发生,发展有关,并与恶性肿瘤的浸润转移有关。认为几种基质酶类有望在临床上成为判断侵袭、转移的指标之一。
血清基质酶类含量联合检测判断卵巢恶性肿瘤浸润转移诊断模型的建立及验证
目的：构建了三种酶类联合诊断卵巢癌浸润转移诊断模型并对模型进行验证。
方法：采用SAS8.0软件包进行统计学分析。模型建立方法采用logistic回归。以250例血清样本三种酶类含量来建立回归模型,168例血清样本三种酶类含量用于验证所得到模型,并与CA125检测结果进行对比。
结果：最终所建诊断模型为：
Logit(P)=14.90-43.24xCL-33.12xhl-43.80xml+71.08x(CLxhl)+55.83x(CLxml)
1.模型对于肿瘤性质判断的灵敏度为86.4%,特异度为82.1%,ROC曲线下面积为0.935,P值为0.000,灵敏度及特异度均高于任一种标志物单一检测,故本模型用于判断卵巢恶性肿瘤有显著意义。
2.模型对于肿瘤浸润转移判断的灵敏度为70.4%,特异度为63.9%,ROC曲线下面积为0.732, P值为0.000,灵敏度及特异度均高,故本模型用于判断卵巢恶性肿瘤浸润转移有显著意义。
结论：本研究所建模型具有较好的诊断效能,在判断肿瘤性质及进展程度时的灵敏度特异度均较高。本实验尽可能收集多的血清样本,但样本量毕竟有限。如能更加大量增加样本量,对模型进行调试及完善,使其更加接近肿瘤实际演进情况,则以诊断模型协助诊断恶性肿瘤有望成为新的辅助诊断模式。
液态芯片检测血清MMP-9、Hpa、CL的临床验证试验
目的：探讨液态芯片卵巢肿瘤患者外周血基质酶类的表达及与其临床病理的相关性。
方法：运用流式荧光法检测了96例卵巢恶性肿瘤、79例卵巢良性肿瘤及55例正常对照的血清中几种基质酶含量的表达,将结果与临床及病理资料进行统计学分析。
结果：
1.恶性卵巢肿瘤患者血中基质酶含量的表达均显著高于良性组及正常对照组,差异有显著性(P<0.05)；在恶性卵巢肿瘤患者血清中,基质酶类的表达与病理类型无关。
2.液态芯片法检测基质酶对于判断卵巢肿瘤性质的判断灵敏度分别为：CL84.3%,Hpa 72.3%,MMP-973.5%；特异度分别为：CL76.0%,Hpa 84.0%,MMP-988.0%。
3.液态芯片法检测基质酶对于判断卵巢肿瘤转移的判断灵敏度分别为：CL867.9%,Hpa 62.5%,MMP-975.0%；特异度分别为：CL66.7%,Hpa 63.0%,MMP-963.0%。
4.液态芯片法检测基质酶含量,判断卵巢恶性肿瘤性质的检验效能总体上优于ELISA法,尤其在判断肿瘤良恶性时的特异度明显高于ELISA法。
5.液态芯片法与ELISA法检测卵巢恶性肿瘤转移与否的检验效能相差不多。
结论：液态芯片是可同时、快速、准确检测多种肿瘤标志物的综合技术,其灵敏度和特异度均高,有望用于肿瘤标志物检测。
基质酶类在卵巢恶性肿瘤组织中表达的Meta分析
目的：评价基质酶类在卵巢组织中的含量对肿瘤性质的判断。
方法：检索CBMdisc光盘数据库、EMBASE数据库MEDLINE数据库,确定纳入标准,筛选符合纳入标准的2000年1月至2009年12月公开国内外发表的文献16篇。通过各研究间的异质性分析及固定效应、随机效应两种模型的综合分析得出生存结果,统计学方法采用Cochrane协作网提供的软件包RevMan 4.2.10。
结果：在MMP-9表达的研究中,纳入的7个研究,OR=11.43,OR95%C1为6.78,19.27,P<0.00001。基质金属蛋白酶在恶性及非恶性卵巢肿瘤组织中含量有统计学差异；研究间无异质性。
2.在Hpa表达的研究中,纳入的6个研究,OR=8.62,OR95%CI为4.57,15.28,P<0.00001。乙酰肝素酶在恶性及非恶性卵巢肿瘤组织中含量有统计学差异；研究间无异质性。
3.在CL表达的研究中,纳入的3个研究,OR=2.70,OR95%CI为0.26,27.97,P=0.41。组织蛋白酶在恶性及非恶性卵巢肿瘤组织中含量无统计学差异；研究间存在异质性。
结论：Meta分析的结果说明恶性组基质蛋白酶及乙酰肝素酶的表达显著高于非恶性组,组织蛋白酶未见差异。由于目前的循证医学证据均是一些分散的小样本病例,基质酶类在恶性卵巢中的表达作用,尚需要大规模多中心的研究。根据现有研究结果,基质酶类有望成为最新的卵巢肿瘤标志物。
Mortality of ovarian cancer is the highest in gynecological malignancies. Despite the platinum-based chemotherapy and cytoreductive surgery has played a positive role in ovarian cancer management,70% of patients still displays at advanced stage in first diagnosis with newly method due to lacking of effective early diagnosis. The relapse and resistance after surgery and chemotherapy cause the 5-year survival rate has still remained about 30%. Matrix metalloproteinases is known to play an important role in cancer cell invasion by mediating the degradation of extracellular matrix (ECM). In this study, firstly, we sought to explore the relationship between MMP-9, Hpa, CL expressions and clinic-pathologic pattern in ovarian cancer. Secondly, It is also to explore the role of MMP-9, Hpa,CL in invasion and metastatic of ovarian cancer. Thirdly, we also construct and validate an ovarian cancer metastasis diagnosis model which is comprehensive judged by MMP-9, Hpa and CL. Finally, we have made a META analysis of the stroma enzymes expression of relevant researches which have been published in the tissue, and analysis the issues in dispute with evidence-based medicine method.
The Detection of MMP-9, Hpa and CL on Tumor Invasion and Metastasis and Its Clinical Significance
Objective:To explore the matrix enzyme on peripheral blood expression and its relationship with the clinic and pathological characteristics in ovarian carcinomas.
Methods:Serum levels of CA125, MMP-9,Hpa and CL in patients with 217 cases of ovarian cancers, 101cases of benign tumors and 101 healthy women as controls were determined by enzyme linked immunosorbent assay(ELISA). Statistical method was used to analyze the clinical and pathological characterization by the analysis of the result.
Results:The serum levels of stroma enzymes in ovarian cancers was significantly higher than that in the benign tumors and the control group(p<0.05); The serum expression of stroma enzymes was not associated with pathology types, but associated with pathological types, clinical stage and degree of differentiation. The expression of CL, MMP-9 is associated with peritoneal metastasis. The expression of Hpa is associated with distant metastasis. Correlation analysis showed the relationship between the serum levels of the CL and CA125 is 0.051 and P=0.434, P>0.05, no significant correlation between these two stroma enzymes. Correlation analysis showed the relationship between the serum levels of the Hpa and CA125 is direct correlation, and r=0.183, P=0.005. Correlation analysis showed the relationship between the serum levels of the MMP-9 and CA125 is direct correlation, and r=0.131, P=0.044.
Conclusion:The results showed that serum expression levels of These stroma enzymes was correlated with carcinogenesis and progress of ovarian cancer and was expected to become as indicators for judging invasion and metastasis.
The Establish and Validation of the combined Mathematical Diagnosis Model of serum levels of Stroma enzymes of Ovarian Cancer
Objective:To establish the combined diagnosis model of serum levels of stroma enzymes of ovarian cancer and validate the model's effectiveness.
Methods:The statistical analysis method (SAS 8.0 software) is used to analyze the mathematical model. The establish method of the diagnosis model is logistic Regresion by using 250 matrix enzyme cases.168 cases was used to validate the model's effectiveness. The comparison result was made between the new model and CA125.
Results:The established mathematical diagnosis model is: Logit(P)=14.90-43.24xCL-33.12xhl-43.80xml+71.08x(CLxhl)+55.83x(CLxml)
1. Model to judge the nature of the sensitivity of the tumor is 86.4%, specificity is 82.1%, ROC area under the curve is 0.935, P= 0.000. Sensitivity and specificity are higher than any other markers which were detected, so this model is used to determine ovarian cancer are significant.
2. Model to judge tumor invasion and metastasis's sensitivity is 70.4%, specificity is 63.9%, ROC area under the curve is 0.732, P= 0.000, sensitivity and specificity are high, so this model is used to judge the invasion and metastasis of ovarian cancer is significant.
Conclusion:The model in this study has good diagnostic performance. The sensitivity and specificity of progressing in determining the nature and extent of tumor are high. In this study, many of serum samples collected as much as possible, but the sample size is limited. If a more substantial increase in sample size, debuging and improving the model so that it closer to the actual tumor evolution. It is expected to become as indicators for judging invasion and metastasis.
Clinical Value of Liquid Biochip in detection MMP-9, Hpa and CL's value of serum
Objective:To explore the matrix enzyme on peripheral blood liquid biochip expression and its relationship with the clinic and pathological characteristics in ovarian carcinomas.
Methods:Serum levels of CA125, MMP-9,Hpa and CL in patients with 96 cases of ovarian cancers,79cases of benign tumors and 55 healthy women as controls were determined by flow fluorescence assay. Statistical method was used to analyze the clinical and pathological characterization by the analysis of the result.
Results:
1. Patients with malignant ovarian tumor expression levels of matrix enzymes were significantly higher than benign group and control group, the difference is significant (P<0.05); in serum of patients with malignant ovarian tumors, the expression of matrix enzymes and pathological types has no relationship.
2. liquid silicon substrate enzyme assay for determining the quality of judging the sensitivity of ovarian cancer are:CL 84.3%, Hpa 72.3%, MMP-973.5%; specificity, respectively:CL 76.0%, Hpa 84.0%, MMP-988.0%.
3. Liquid silicon substrate enzyme assay for the judgement to judge the sensitivity of ovarian tumor metastasis are:CL 867.9%, Hpa 62.5%, MMP-975.0%; specificity, respectively:CL 66.7%, Hpa 63.0%, MMP-963.0%.
4. Detection of liquid silicon substrate enzyme levels to determine the nature of the test performance of ovarian cancer is generally better than ELISA, especially in benign and malignant tumors when judging the specificity was significantly higher than ELISA.
5. Liquid chip technology and the ELISA assay test ovarian cancer metastasis have almost the same performance.
Conclusions:Liquid Biochip can be used to detect multi tumor marker, and can increase the diagnosis sensitivity.
The Meta Analysis of Relationship Between Several Stroma enzymes and Invasion and Metastasis in Ovarian Cancer
Objective:To explore the relationship of the value of stroma enzymes in ovarian and the ovarian cancer.
Methods:We have searched CBMdisc database, EMBASE database and MEDLINE database, and found 16 papers between January 2005 and December 2009 complied with the standard. The survival results have been obtained through the study of the heterogeneity and fixed effects and random effects models. Statistical methods have been used by utilizing RevMan 4.2.10 software.
Results:
1. MMP-9 expression in the study, included 7 studies, OR= 11.43, Or 95CI is 6.78,19.27, P <0.00001. Matrix metalloproteinases in malignant and non-malignant ovarian tumor tissues and contents are significantly different; studies are homogeneous.
2. Hpa expression in the study, included 6 studies, OR= 8.62, Or 95%CI is 4.57,15.28, P <0.00001. Heparanase in malignant and non-malignant ovarian tumor tissues and contents are significantly different; study are homogeneous.
3. CL expression in the study, included 3 studies, OR= 2.70, Or 95CI is 0.26,27.97, P=0.41. Cathepsin in malignant and non-malignant ovarian tumor tissues and contents are significantly different; study are heterogeneity.
Conclusions:The Meta analysis result has showed that the expression of stroma enzymes in much higher in ovarian cancer than that in normal ovarian tissue. Because the evidence-based medicine method has only several distribute examples, the effect of the expression of stroma enzymes in ovarian cancer is not very convincing. It needs more examples to research and study. Anyway, stroma enzymes have the possibility to be the new maker of ovarian cancer.
血清MMP-9、Hpa、CL的检测对卵巢癌浸润转移判断的临床价值目的：探讨卵巢肿瘤患者外周血基质酶类的表达及与其临床病理的相关性。方法：采用ELISA酶联免疫吸附法检测了217例卵巢恶性肿瘤、101例卵巢良性肿瘤及101例正常对照的血清中几种基质酶含量的表达,将结果与临床及病理资料进行统计学分析。
结果：恶性卵巢肿瘤患者血中基质酶含量的表达均显著高于良性组及正常对照组,差异有显著性(P<0.05)；在恶性卵巢肿瘤患者血清中,基质酶类的表达与病理类型无关,与临床分期、组织分化程度有关；CL表达与腹腔转移有关,Hpa表达与远处转移有关,MMP-9表达与腹腔转移有关。相关分析显示血清CL与CA125的相关系数为0.051,P=0.434。P>0.05,二者无明显相关性。血清Hpa与CA125的相关系数为0.183,P=0.005。两者呈正相关,即Hpa含量越高患者,CA125含量也越高；血清mmp9与CA125的相关系数为0.131,P=0.044,两者呈正相关,即MMP-9含量越高患者,CA125含量也越高。
结论：基质酶类的表达与卵巢恶性肿瘤的发生,发展有关,并与恶性肿瘤的浸润转移有关。认为几种基质酶类有望在临床上成为判断侵袭、转移的指标之一。
血清基质酶类含量联合检测判断卵巢恶性肿瘤浸润转移诊断模型的建立及验证
目的：构建了三种酶类联合诊断卵巢癌浸润转移诊断模型并对模型进行验证。
方法：采用SAS8.0软件包进行统计学分析。模型建立方法采用logistic回归。以250例血清样本三种酶类含量来建立回归模型,168例血清样本三种酶类含量用于验证所得到模型,并与CA125检测结果进行对比。
结果：最终所建诊断模型为：
Logit(P)=14.90-43.24xCL-33.12xhl-43.80xml+71.08x(CLxhl)+55.83x(CLxml)
1.模型对于肿瘤性质判断的灵敏度为86.4%,特异度为82.1%,ROC曲线下面积为0.935,P值为0.000,灵敏度及特异度均高于任一种标志物单一检测,故本模型用于判断卵巢恶性肿瘤有显著意义。
2.模型对于肿瘤浸润转移判断的灵敏度为70.4%,特异度为63.9%,ROC曲线下面积为0.732, P值为0.000,灵敏度及特异度均高,故本模型用于判断卵巢恶性肿瘤浸润转移有显著意义。
结论：本研究所建模型具有较好的诊断效能,在判断肿瘤性质及进展程度时的灵敏度特异度均较高。本实验尽可能收集多的血清样本,但样本量毕竟有限。如能更加大量增加样本量,对模型进行调试及完善,使其更加接近肿瘤实际演进情况,则以诊断模型协助诊断恶性肿瘤有望成为新的辅助诊断模式。
液态芯片检测血清MMP-9、Hpa、CL的临床验证试验
目的：探讨液态芯片卵巢肿瘤患者外周血基质酶类的表达及与其临床病理的相关性。
方法：运用流式荧光法检测了96例卵巢恶性肿瘤、79例卵巢良性肿瘤及55例正常对照的血清中几种基质酶含量的表达,将结果与临床及病理资料进行统计学分析。
结果：
1.恶性卵巢肿瘤患者血中基质酶含量的表达均显著高于良性组及正常对照组,差异有显著性(P<0.05)；在恶性卵巢肿瘤患者血清中,基质酶类的表达与病理类型无关。
2.液态芯片法检测基质酶对于判断卵巢肿瘤性质的判断灵敏度分别为：CL84.3%,Hpa 72.3%,MMP-973.5%；特异度分别为：CL76.0%,Hpa 84.0%,MMP-988.0%。
3.液态芯片法检测基质酶对于判断卵巢肿瘤转移的判断灵敏度分别为：CL867.9%,Hpa 62.5%,MMP-975.0%；特异度分别为：CL66.7%,Hpa 63.0%,MMP-963.0%。
4.液态芯片法检测基质酶含量,判断卵巢恶性肿瘤性质的检验效能总体上优于ELISA法,尤其在判断肿瘤良恶性时的特异度明显高于ELISA法。
5.液态芯片法与ELISA法检测卵巢恶性肿瘤转移与否的检验效能相差不多。
结论：液态芯片是可同时、快速、准确检测多种肿瘤标志物的综合技术,其灵敏度和特异度均高,有望用于肿瘤标志物检测。
基质酶类在卵巢恶性肿瘤组织中表达的Meta分析
目的：评价基质酶类在卵巢组织中的含量对肿瘤性质的判断。
方法：检索CBMdisc光盘数据库、EMBASE数据库MEDLINE数据库,确定纳入标准,筛选符合纳入标准的2000年1月至2009年12月公开国内外发表的文献16篇。通过各研究间的异质性分析及固定效应、随机效应两种模型的综合分析得出生存结果,统计学方法采用Cochrane协作网提供的软件包RevMan 4.2.10。
结果：在MMP-9表达的研究中,纳入的7个研究,OR=11.43,OR95%C1为6.78,19.27,P<0.00001。基质金属蛋白酶在恶性及非恶性卵巢肿瘤组织中含量有统计学差异；研究间无异质性。
2.在Hpa表达的研究中,纳入的6个研究,OR=8.62,OR95%CI为4.57,15.28,P<0.00001。乙酰肝素酶在恶性及非恶性卵巢肿瘤组织中含量有统计学差异；研究间无异质性。
3.在CL表达的研究中,纳入的3个研究,OR=2.70,OR95%CI为0.26,27.97,P=0.41。组织蛋白酶在恶性及非恶性卵巢肿瘤组织中含量无统计学差异；研究间存在异质性。
结论：Meta分析的结果说明恶性组基质蛋白酶及乙酰肝素酶的表达显著高于非恶性组,组织蛋白酶未见差异。由于目前的循证医学证据均是一些分散的小样本病例,基质酶类在恶性卵巢中的表达作用,尚需要大规模多中心的研究。根据现有研究结果,基质酶类有望成为最新的卵巢肿瘤标志物。
Mortality of ovarian cancer is the highest in gynecological malignancies. Despite the platinum-based chemotherapy and cytoreductive surgery has played a positive role in ovarian cancer management,70% of patients still displays at advanced stage in first diagnosis with newly method due to lacking of effective early diagnosis. The relapse and resistance after surgery and chemotherapy cause the 5-year survival rate has still remained about 30%. Matrix metalloproteinases is known to play an important role in cancer cell invasion by mediating the degradation of extracellular matrix (ECM). In this study, firstly, we sought to explore the relationship between MMP-9, Hpa, CL expressions and clinic-pathologic pattern in ovarian cancer. Secondly, It is also to explore the role of MMP-9, Hpa,CL in invasion and metastatic of ovarian cancer. Thirdly, we also construct and validate an ovarian cancer metastasis diagnosis model which is comprehensive judged by MMP-9, Hpa and CL. Finally, we have made a META analysis of the stroma enzymes expression of relevant researches which have been published in the tissue, and analysis the issues in dispute with evidence-based medicine method.
The Detection of MMP-9, Hpa and CL on Tumor Invasion and Metastasis and Its Clinical Significance
Objective:To explore the matrix enzyme on peripheral blood expression and its relationship with the clinic and pathological characteristics in ovarian carcinomas.
Methods:Serum levels of CA125, MMP-9,Hpa and CL in patients with 217 cases of ovarian cancers, 101cases of benign tumors and 101 healthy women as controls were determined by enzyme linked immunosorbent assay(ELISA). Statistical method was used to analyze the clinical and pathological characterization by the analysis of the result.
Results:The serum levels of stroma enzymes in ovarian cancers was significantly higher than that in the benign tumors and the control group(p<0.05); The serum expression of stroma enzymes was not associated with pathology types, but associated with pathological types, clinical stage and degree of differentiation. The expression of CL, MMP-9 is associated with peritoneal metastasis. The expression of Hpa is associated with distant metastasis. Correlation analysis showed the relationship between the serum levels of the CL and CA125 is 0.051 and P=0.434, P>0.05, no significant correlation between these two stroma enzymes. Correlation analysis showed the relationship between the serum levels of the Hpa and CA125 is direct correlation, and r=0.183, P=0.005. Correlation analysis showed the relationship between the serum levels of the MMP-9 and CA125 is direct correlation, and r=0.131, P=0.044.
Conclusion:The results showed that serum expression levels of These stroma enzymes was correlated with carcinogenesis and progress of ovarian cancer and was expected to become as indicators for judging invasion and metastasis.
The Establish and Validation of the combined Mathematical Diagnosis Model of serum levels of Stroma enzymes of Ovarian Cancer
Objective:To establish the combined diagnosis model of serum levels of stroma enzymes of ovarian cancer and validate the model's effectiveness.
Methods:The statistical analysis method (SAS 8.0 software) is used to analyze the mathematical model. The establish method of the diagnosis model is logistic Regresion by using 250 matrix enzyme cases.168 cases was used to validate the model's effectiveness. The comparison result was made between the new model and CA125.
Results:The established mathematical diagnosis model is: Logit(P)=14.90-43.24xCL-33.12xhl-43.80xml+71.08x(CLxhl)+55.83x(CLxml)
1. Model to judge the nature of the sensitivity of the tumor is 86.4%, specificity is 82.1%, ROC area under the curve is 0.935, P= 0.000. Sensitivity and specificity are higher than any other markers which were detected, so this model is used to determine ovarian cancer are significant.
2. Model to judge tumor invasion and metastasis's sensitivity is 70.4%, specificity is 63.9%, ROC area under the curve is 0.732, P= 0.000, sensitivity and specificity are high, so this model is used to judge the invasion and metastasis of ovarian cancer is significant.
Conclusion:The model in this study has good diagnostic performance. The sensitivity and specificity of progressing in determining the nature and extent of tumor are high. In this study, many of serum samples collected as much as possible, but the sample size is limited. If a more substantial increase in sample size, debuging and improving the model so that it closer to the actual tumor evolution. It is expected to become as indicators for judging invasion and metastasis.
Clinical Value of Liquid Biochip in detection MMP-9, Hpa and CL's value of serum
Objective:To explore the matrix enzyme on peripheral blood liquid biochip expression and its relationship with the clinic and pathological characteristics in ovarian carcinomas.
Methods:Serum levels of CA125, MMP-9,Hpa and CL in patients with 96 cases of ovarian cancers,79cases of benign tumors and 55 healthy women as controls were determined by flow fluorescence assay. Statistical method was used to analyze the clinical and pathological characterization by the analysis of the result.
Results:
1. Patients with malignant ovarian tumor expression levels of matrix enzymes were significantly higher than benign group and control group, the difference is significant (P<0.05); in serum of patients with malignant ovarian tumors, the expression of matrix enzymes and pathological types has no relationship.
2. liquid silicon substrate enzyme assay for determining the quality of judging the sensitivity of ovarian cancer are:CL 84.3%, Hpa 72.3%, MMP-973.5%; specificity, respectively:CL 76.0%, Hpa 84.0%, MMP-988.0%.
3. Liquid silicon substrate enzyme assay for the judgement to judge the sensitivity of ovarian tumor metastasis are:CL 867.9%, Hpa 62.5%, MMP-975.0%; specificity, respectively:CL 66.7%, Hpa 63.0%, MMP-963.0%.
4. Detection of liquid silicon substrate enzyme levels to determine the nature of the test performance of ovarian cancer is generally better than ELISA, especially in benign and malignant tumors when judging the specificity was significantly higher than ELISA.
5. Liquid chip technology and the ELISA assay test ovarian cancer metastasis have almost the same performance.
Conclusions:Liquid Biochip can be used to detect multi tumor marker, and can increase the diagnosis sensitivity.
The Meta Analysis of Relationship Between Several Stroma enzymes and Invasion and Metastasis in Ovarian Cancer
Objective:To explore the relationship of the value of stroma enzymes in ovarian and the ovarian cancer.
Methods:We have searched CBMdisc database, EMBASE database and MEDLINE database, and found 16 papers between January 2005 and December 2009 complied with the standard. The survival results have been obtained through the study of the heterogeneity and fixed effects and random effects models. Statistical methods have been used by utilizing RevMan 4.2.10 software.
Results:
1. MMP-9 expression in the study, included 7 studies, OR= 11.43, Or 95CI is 6.78,19.27, P <0.00001. Matrix metalloproteinases in malignant and non-malignant ovarian tumor tissues and contents are significantly different; studies are homogeneous.
2. Hpa expression in the study, included 6 studies, OR= 8.62, Or 95%CI is 4.57,15.28, P <0.00001. Heparanase in malignant and non-malignant ovarian tumor tissues and contents are significantly different; study are homogeneous.
3. CL expression in the study, included 3 studies, OR= 2.70, Or 95CI is 0.26,27.97, P=0.41. Cathepsin in malignant and non-malignant ovarian tumor tissues and contents are significantly different; study are heterogeneity.
Conclusions:The Meta analysis result has showed that the expression of stroma enzymes in much higher in ovarian cancer than that in normal ovarian tissue. Because the evidence-based medicine method has only several distribute examples, the effect of the expression of stroma enzymes in ovarian cancer is not very convincing. It needs more examples to research and study. Anyway, stroma enzymes have the possibility to be the new maker of ovarian cancer.
引文
[1]. Berkenblit A,Cannistra SA.Advances in the management of epithelial ovarian cancer[J]. Reprod Med,2005,50(6):426-438.
[2].Armstrong DK. Relapsed ovarian cancer:challenges and management strategies for a chronic disease[J].Oncologist,2002,7 Suppl 5:20-28.
[3].Harries M, Gore M. Part Ⅱ:chemotherapy for epithelial ovarian cancer treatment of recurrent disease[J]. Lancet Oncol,2002,3 (9):537-545.
[4].Paget S. The distribution of secondary growths in cancer of the breast [J]. Lancet, 1889,1:571-573.
[5]. Fidler IJ.The pathogenesis of cancer metastasis:the "seed and soil" hypothesis revisited[J]. Nature Reviews Cancer,2003,3:453-458。
[6].Fidler IJ.Critical factors in the biology of human cancer metastasis:twenty-eight GH.A. Clowes Memorial Award lecture[J]. Cancer Res,1990,50:6130-6138.
[7].Fidler IJ.Critical determinants of matastasis[J].Nature,2003,423:593-595.
[8].李红梅,方伟岗,何春生等.不同转移能力的人前列腺癌细胞亚系中p38和cJun氨基末端激酶激活机制[J].中华病理学杂志,2001,30(3)：194-197.
[9]. Todd R, Wong DT. Oncogenes. Anticancer Res.1999,19(6A):4729-4746.
[10]. Vogelstein B, Kinzler KW. The Genetic Basis Of Human Cancer[M]. New York: McGraw-Hill, Health Professions Division,1998,205-340.
[11]. Scambia G, Masciullo V, Benedetti Panici p, et al. Prognostic singnificance of ras/p21 alterations in human ovarian cancer[J].Br J Cancer,1997,75 (10):1547-1553.
[12]. Garrett Ap, Lee KR, Colitti CR, et al. k-ras mutation may be earlyevent in mucinous ovarian tumorigenesis [J]. Int J Gynecol pathol,2001,20(3):244-251.
[13]. CuatrecasasM, Erill N, Musulen E, et al. K-ras mutations in nonmucinous ovarian epithelial tumors:a molecular analysis and clinicopathologic study of 144 patients [J]. Cancer,1998,82 (6):1088-1095.
[14]. Yamashita K, Kuba T, Shinoda H, et al.Detection of k-ras pointnmutations in the supernatants of peritoneal and pleural effusions for diagnosis complementary to cytologic examination [J]. Am J ClinPathol,1998,109(6):704-711.
[15]. Bernhard EJ, Stanbridge EJ, Gupta S, et al. Direct evidence for thecontribution of activated N-ras and K-ras oncogenes to increasedintrinsic radiation resistance in human tumor cell lines [J]. CancerRas,2000,60(23):6597-6600.
[16]. Funato T, Ishii T, Kambe M,et al.Anti-k-ras ribozyme inducesgrowth inhibition and increased chemosensitivity in human colon cancer cells [J]. Gancer Gene Ther, 2000,7 (3):495-500.
[17]. Rutter JL,Chatterjee N,Wacholders S,et al.The Her2 I655V polymorphism and breast cancer risk in Ashkenazim [J].Epidemiology,2003,14:694-700.
[18]. Hattori M, Sakamoto H, Satoh K, et al.DNA demethylase is expressed in ovarian cancers and the expression correlates with demethylation of CpG sites in the promoter region of c-erbB-2 and survivin genes[J]. Cancer Lett,2001,169(2):155-164.
[19]. Baker VV, Borst MP, Dixon D, et al. C-Myc amplification in ovarian cancer. Gynecol oncol,1990,38:340-342.
[20]. Schlotter CM,Vogt U,Bosse U,et al.C-Myc not Her2/Neu can predict recurrence and mortality of paients with node-negative breast cancer [J]. Breast cancer Res,2003,5:R30-36.
[21]. Plisiecka-Halasa J, Karpinska G, Szymanska T, et al. P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens[J]. Ann Oncol 2003:14(7):1078-1085.
[22]. Spentzos D, Levine DA, Ramoni MF, Joseph M, Gu X, Boyd J, et al. Gene expression signature with independent prognostic significance in epithelial ovarian cancer[J]. Clin Oncol 2004:22(23):4700-4710.
[23]. Harris H, Miller OJ,Klein G et al. Suppression of malignancy by cell fuion[J].Nature,1969,223:363-368.
[24]. Ryan KM, Phillips AC, Vousden KH. Regulation and function of the p53 tumor suppressor protein [J].Current Opinion in Cell Biology,2001,13:2973-2983.
[25].詹启敏.分子肿瘤学[M].人民卫生出版社.2005年第一版.
[26]. Berchuck A, Kohler MF, Marks JR, et al. The p53 tumor suppressor gene frequently is altered in gynecologic cancers[J]. Am J Obstet Gynecol,1994,170 (1):246-253.
[27]. Sui L, Dong Y, Ohno M, et al. Inverse expression of Cdk4 and p16 in epithelial ovarian tumors[J]. Gynecol Oncol,2000,79(2):230-237.
[28].王刚,任杰平,王世阆,等.人卵巢浆液性囊腺癌中p16蛋白表达及其临床意义[J],中华临床杂志,2001,1(2)：1-3.
[29].苏荣健,姚阳,时亮,等.卵巢癌p16基因的纯合性缺失、突变及表达异常的研究[J].中国医科大学学报2002,3(6)：428-432.
[30]. Wang Min,Wei jun,Zhang Jialin. Replacement of the p16 gene in human ovarian cancer cells.Chinese Medical Journal,2001,114 (8):857-859.
[31]. Yamada KM,Araki M.Tumor suppressor PTEN:modulator of cell signaling[J] Journal of Cell Science,2002,114,(8):2375-2382.
[32]. Che Y, Yao Q, Dai S, et al. Analysis of PTEN mutation in epithelial ovarian cancer [J]. Prog Obstet Genecol,2002,11(1):18-20.
[33]. Catasus L, Bussaglia E, Rodrguez I,et al. Molecular genetic alterations in endometrioid carcinomas of the ovary:similar frequency of beta-catenin abnormalities but lower rate of microsatellite instability and PTEN alterations than in uterine endometrioid carcinomas[J]. Hum Pathol,2004,35 (11):1360-1368.
[34]. Chen R, Zheng H, Yang X, et al. Relationship between the mutation and mRNA expression of PTEN gene and pathobiological behavior of ovarian cancer[J]. Chin Clin Tumor,2004,31(7):365-367.
[35]. Gomes CP, Andrade LA(?) PTEN and p53 expression in primary ovarian carcinomas:immunohistochemical study and discussion of pathogenetic mechanisms [J]. Int J GynecolCancer,2006,16(Suppl1):254-258.
[36]. Hashiguchi Y, Tsuda H, Inoue T, et al. PTEN expression in clear cell adenocarcinoma of the ovary[J]. Gynecol Oncol,2006,101(1):71-75.
[37]. Dinulescu DM, Ince TA, Quade BJ, et al. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer [J]. Nat Med,2005,11(1):24-26.
[38]. Lee JS, Choi YD, Choi C, et al. Expression of PTEN in ovarian epithelial tumors and its relation to tumor behavior and growth[J].Anal Quant Cytol Histol,2005, 27(4):202-210.
[39]. Nicolson GL,Nawa AToh Y,Taniquchi S.Tumor metastasis-associated human MTA1 gene and its MTA1 protein product:role in epithelial cancer invasion,proliferation and nuclear regulationg[J]. Clin Exp Metastasis,2003 V20N1:19-24.
[40]. Van de Vijver MJ,He YD,Van't Veer LJ,et al.A gene-expession signature as a predictor of survival in breast cancer[J].N.Engl.J.Med,2002,3(47):1999-2009
[41]. Yoshida BA, Sokoloff MM, Welch DR, et al. Metastasis2 suppressor genes:a review and perspective on an emerging field[J]. Natl Cancer Inst,2000, 92(21):1717-1730.
[42]. Nakayama T, Ohtsuru A, Nakao K, et al. Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase,a homologue of the nm23 gene product [J]. J Natl Cancer Inst,1992,84 (17):1349-1354.
[43]. Shimada M, Taguchi K, Hasegawa H, et al. Nm232H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma[J]. Liver 1998,18 (5):337-342.
[44]. Schindl M, Birner P, Breitenecker G, et al. Downregulation of KAI1 metastasis suppressor protein is associated with a dismal prognosis in epithelial ovarian cancer[J]. Gynecol Oncol,2001,83 (2):244-248.
[45]. Uzawa K, Ono K, Suzuki H, et al. High prevalence of decreased expression of KAI1 metastasis suppressor in human oral carcinogenesis[J]. Clin Cancer Res, 2002,8(3):828-835.
[46]. Su JS, Arima K, Hasegawa M, et al. Decreased expression of KAI1metastasis suppressor gene is a recurrence predictor in primary pTa and pT1 urothelial bladder carcinoma[J]. Int J Urol,2004,11 (2):74-82.
[47]. Sun HC, Tang ZY, Zhou G, et al. KAI1 gene expression in hepatocellular carcinoma and its relationship with intrahepatic metastases [J]. J Exp Clin Cancer Res, 1998,17(3):307-311.
[48]. Stroop CJM,Weber W,Gerwig GJ.et al. Characterization of the carbohydrate chains of the secreted forms of the human epidermal growth factor receptor[J].Glycobiology,2000,10:901-917.
[49]. Mckallip R,Li R,Landisch S, Tumor gangliosides inhibit the tumor-specific immune response. [J]. Immumology,1999,163:3718-3726
[50].王兴旺,谢弘.AFP研究[J].中华医学杂志,1998,7(8)：723-724.
[51].周柔丽.细胞外基质及与细胞间的相互作用.宋今丹主编.医学细胞分子生物学.北京：人民卫生出版社,2003,62-86.
[52]. Bidart JM, Thuillier F, Augereau C. et al. Kinetics of Serum Tomur Marker Concentrations and Usefulness in Clinical Monitoring[J].Clinical Chemistry,1999, 4(5):1695-1707
[53]. Dong L, Cui H, Li XP, et al. Clinical value of serum CA19-9, CA125 and CP2 in mucinous ovarian tumor:a retrospective study of 273 patients[J]. Zhonghua Fu Chan Ke Za Zhi 2008,1,43(1):5-8.
[54]. Yin BW, Lyoyd KO.Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16[J]. Boil Chem 2001,7,20; 276(29):27371-5.
[55]. Kumar P, Rehani MM, Kumar L, et al.Tumor marker CA-125 as an evaluator and response indicator in ovarian cancer:its quantitative correlation with tumor volume[J].Med Sci Monit 2005,11(2):CR84-9.
[56].彭莉,张桂霞,朱传金.CEA、CA125在卵巢癌预后检测和复发诊断中的价值分析[J].肿瘤基础与临床,2006,10,19(5)：381-382.
[57]. Dong Y, Kaushal A, Bui L, et al. Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas[J]. Clin Cancer Res.2001,8(7):2363-71.
[58].陈文彬,潘祥林,主编.诊断学.第6版.北京：人民卫生出版社.2004,457.
[59]. Roberts JD,Olden K.et al. The role of Protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer[J]. Cancer detection and prevention 1998,22(5):455-462.
[60]. Thurin M,Kieber-Emmons T. SA-Lea and tumor metastasis:the old prediction and recent findings[J].Hybrid Hybridomics,2002,21(2):111-116.
[61]. Zacharski LR,Loynes JT. The heparins and cancer. Curr Opin Pulm Med, 2002,8(5):379-382.
[62]. Varki A,Varki NM. P-selectin,carcinoma metastasis and heparin:novel mechanistic connection with therapeutic implications[J]. Braz J Med Biol Res,2001,34(6):711-717.
[63].周柔丽.细胞黏附分子与细胞外基质.张乃蘅、童坦君主编.医学分子生物学, 北京：北京医科大学出版社,1999,282-307.
[64]. Okegawa T,Li YM,Pong RC, et al.Cell adhesion proteins as tumor suppressors[J].J-Ural,2002,167(4):1836-1843.
[65]. Conacci-Sorrell M,Zhurinsky J,Ben-Ze'ev A.The cadherin-catenin adhesion system in signaling and cancer[J]. Clin Invest.2002;109(8):987-991.
[66]. Davidson B, Gotlieb WH, Ber-Baruch G, et al. E-Cadherin complex protein Expression and survival in ovarian carcinoma[J]. Gynecol Oncol.2000,78(3): 362-371.
[67]. Beavon IR.The E-cadherin-catentia complex in tumour metastasis:structure, function and regulation [J].Eur J Cancer,2000,3(6):1607-1617.
[68]. Li G.Dynamics of intercellular communication during melanoma development [J].M Mol T oday,2000,6(4):163
[69]. Kim M, Carman C V, Springer TA, et al. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins[J]. Science.2003,301 (5640):1720-1725.
[70]. Calderwood DA,Huttenlocher A, Kiosses WB, et al. Increased filamin binding to beta-integrin cytoplasmic domains inhibits cell migration [J]. Net Cell Biol 2001,3:1060-1068.
[71]. Felding-Habermann B. Integrin adhesion receptors in tumor metastasis. Clin Exp Metastasis,2003,20(3):203-213.
[72]. Davidson B, Goldberg I, Reich R, et al. AlphaV-and betal-integrin subunits are commonly expressed in malignant effusions from ovarian carcinoma patients[J]. Gynecol Oncol.2003;90(2):248-257.
[73]. Buerkle MA,Pahernik SA,Sutter A, et al.Inbibition of the alpha-nu integerins with a cyclie RGD peptie impairs angiogenesis,growth and metastasis of solid tumor in vivo[J].Br J Cancer,2002,86(5):788-795.
[74]. Borsig L, Wong R, Hynes RO, et al. Synergistic effects of L-and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis[J]. Proc Nail AcM Sci USA.2002,99(4):2193-2198.
[75]. Borsig L, Wong R, Feramisco J. et al. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis[J]. Proc Natl Acad Sci USA.2001,98(6):3352-3357.
[76].钱思源,王黎娜,刘惠喜.P-选择素在卵巢癌中表达的意义.武警医学,2001, 12(9)：520.
[77].周同,王玲玲,陈金联,等.P选择素在几种肿瘤中表达的临床意义[J].上海免疫学杂志,2000,20(4)：236.
[78].周柔丽.糖类复合物及细胞黏附分子与肿瘤转移.吴秉铨,方伟岗主编.肿瘤转移机制及其阻断.杭州：浙江科学技术出版社,2005,92-93.
[79]. Zieglschmid V, Hollmann C, Bocher O. Detection of disseminated tumor cells in periphereal blood[J]. Crit Rev Clin lab Sci,2005,42(2):155-196.
[80]. Hong SC, Song JY, Lee JK, et al. Significance of CD44v6 expression in gynecologic malignancies[J].J Obstet Gynaecol Res,2006,32(4):379-386.
[81].李莉.CD44v6与肿瘤浸润、转移及预后[J].福建医科大学学报,2000,34(3)：315-317.
[82]. Darai E,Scoazec J Y. Expression of cadherins and CD44 proteins inovarian tumors physiopathology and diagnosis interest. Eur J Obstet Gynecol Reprod Biol,1999,86:131-133.
[83].Fidler IJ:The organ microenvironment andcancer metastasis. Differentiation 2002,70:498-505.
[84]. Ficorella C, Cannita K, Ricevuto E, et al. P16 hypermethylation contributes to the characterization of gene inactivation profiles in primary gastric cancer[J]. Oncol Report.2003,10(1):169-173.
[85].马怡红,吴秉权,柳剑英等.三种鼠不同结构p53 minigene瞬时转染H1299细胞对其生长的影响.中国肺癌杂志,2001,4(2)：94-98.
[86].吴晓,郑杰,付坚等.血管内皮生长因子反义基因转染对高转移人巨细胞肺癌细胞系生物学行为的影响.中华病理学杂志,2000,29(5)：363-366.
[87]. Kohn EC, Liotta LA. Local invasion and metastasis.in Satterfield(eds):Oncology, Williams&Wilhines,1991:131-137.
[88]. Fata JE, Ho AT, Leco KJ, et al. Cellular turnover and extracellular matrix remodeling in female reproductive tissues:functions of metalloproteinases and their inhibitors[J].Cell Mol Life Sci.2000,20,57(1):77-95.
[89]. Marneros AG, Olsen BR. The role of collagen-drived proteolytic fragments in angiogenesis[J].Matrix Biol,2001,20(5-6):337-345.
[90]. Yam HF,Chew EC,Chen HB. et al. The 67-KD Laminin-receptor in high and low metastatic melanoma cell line[J].Oncoligy Repot 1997,7(4):115-118.
[91].吴珊,郑杰,由江峰等.层粘连蛋白受体单克隆抗体的置备及其对肿瘤细胞的影响[J].中华病理学杂志,1993,22(4)：207-210.
[92]. Hoekstra R, Eskens FA, Verweij J. Matrix metalloproteinase inhibitions:current developments and future perspective[J].Oncolodist,2001,6:415-427.
[93]. Joyce E. Rundhaug. Matrix metalloproteinase,angiogenesis, and cancer[J]. Clim Cancer Res,2003,9:551-554
[94]. Hofmann UB,Westphal JR,Van Krasts AA, et al. Expression of integrin alpha (v)beta(3)correlates with activation of membrane-type matrix metalloproteinase-I (MT-MMP) and matrix metalloproteinase-2(MMP-2)in human melanoma cells in vitro and in vivo[J]. Int J Cancer,2000.87:12-19.
[95]. Deryugina EI,Bourdon MA,Jungwirth K. et al.Functional activation of integrin alpha V beta 3 in tumor cells espressing membrane-type 1 matrix metalloproteinase [J]. Int J Cancer,2000,86:15-23.
[96]. Fang J,Shing Y,Wiederschain D, et al.Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model[J].Proc Natl Acad Sci USA,2000,97.3884-3889.
[97]. Zhang A, Meng L, Wang Q, et al. Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2[J]. Oncol Rep. 2006;15(4):831-836.
[98]. Aparna A K,Mavis F, et al. The Clinical Relevance of Stromal Matrix Metalloproteinase Expression in Ovarian Cancer [J]. Clin Cancer Res 2006; 12(6) 1707-1714.
[99]. Sakata K, Shigemasa K, Nagai N, et al. Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary[J]. Int J Oncol,2000,17(6):673-6811.
[100]. Wang FQ, So J, Reierstad S, et al. Matrilysin (MMP-7) promotes invasion of ovarian cancer cells by activation of progelatinase[J]. Int J Cancer.2005,11(1):19-31.
[101]. Wang FQ,So J,Reielstad S, et al.Vascular endothelial growth factor-regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases[J]. Int J Cancer.2006,118:879-888.
[102]. Furuya M, Ishikura H,Kawarada Y. Tissue-type inhibitor matrix metalloproteinase expression in human ovarian cancer cells[J]. Gynecol OncoI.2000, 78(9):106-112.
[103]. Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function[J].Biochim Biophys Acta.,2000,1477(12):267-2831.
[104]. Zucker S,Mirza H.Conner CE, et al.Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cell conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation[J].Int J Cancer.1998,7(5):780-786.
[105]. Wojtowicz Praga S.Clincal potential of matrix metalloprotease inhibitors[J]. Drug RD,1999,6(1):117-129.
[106]. Wojtukiewicz M, Sierko E, Zacharski LR, et al. Occurrence of components of fibrinolytic pathways in situ in laryngeal cancer[J].Semin Thromb Hemost, 2003,29(3):317-320.
[107]. Ajani AE, Waksman R. Thrombolytic therapy in patients with submassive pulmonary embolism[J]. N Engl J Med,2003,348(4):357-359.
[108]. Sun Z, Zhang PX, Wang P, et al. Amino-terminal fragment of urokinase-type plasminogen activator inhibits its plasminogen activation [J]. Thromb Res,2002,106(2):105-111.
[109]. Mignati P, Rifkin DB.Nonenzymatic interactions between proteinases and the cell surface:novel roles in normal and malignant cell physiology[J]. Adv Cancer Res, 2000,8(7):103-157.
[110]. Liang OD,Chavakis T, kanse SM, et al.Ligand binding regions in the receptor for urokinase-type plasminogen activator[J]. Biol Chem,2001,276(31):28946-28953.
[111]. Podor TJ, Shaughnessy SG, Blackburn MN, et al. New insights into the size and stoichiometry of the plasminogen activator inhibitor type-1, vitronectin complex [J] Biol Chem,2000,275(33):25402-25410.
[112]. Blouse GE, Perron MJ, Thompson JH, et al. A concerted structural transition in theplasminogen activator inhibitor-1 mechanism of inhibition[J]. Biochemistry 2002,41(40):1997-2009.
[113]. Jankova L, Harrop SJ, Saunders DN, et al.Crystal structure of the complex of plasminogenactivator inhibitor 2 with a peptide mimicking the reactive center loop[J]. Bio Chem,2001,276(46):43374-43382.
[114]. Zhou H M, NicholsA, Meda P, et al. Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis[J]. EMBO J,2000,19 (17): 4817-4826.
[115]. Kerr JS,Slee AM,Mousa SA.The alpha v integrin antagonists as novel anticancer agents an update[J].Exper Opin Investing Drugs,2002,11(12):1765.
[116].凌丹,李力,纤溶酶原激活因子及其抑制因子与卵巢癌浸润转移[J],国外医学妇产科学分册,2004,31(3)：543-548.
[117]. Liu S, Bugge T H, Leppla SH. Targeting of tumor by cell surface urokinase plasminogen activator2dependent anthrax toxin [J]. J Biol Chem,2001,276 (2): 17976-17984.
[118]. Konecny G, UntchM, Pihan A, et al. Association of urokinase type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer[J]. Clin Cancer Res,2001,7 (6):1743-1749.
[119].舒晓燕,熊俊.尿激酶型纤溶酶原激活剂mRNA在卵巢癌组织中的表达及意义[J].中国现代医学杂志,2004,14(20)：57-58.
[120]. Borgfeldt C, Hansson SR, Gustavsson B, et al. Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasninogen activator(uPA),its receptor(uPAR) and its inhibitor(PAI-1) [J]. Int J Cancer,2001,92(4):497-502.
[121]. Boss E A, Massuger LF, Thomas CM, et al. Clnical value of components of the plasminogen activation system in ovarian cyst fluid[J]. Anticancer Res,2002,22 (1A):2752-282.
[122]. Liu J, Zhao Q, Zhao B, et al. A new format of single chain tri-specific antibody with diminished molecular size efficiently induces ovarian tumor cell killing.[J].Biotechnol Lett.2005,27(22):1821-1827.
[123]. Lecaille F, Kaleta J, Bromme D, et al. Human and parasitic papain2like cysteine proteases:their role in physiology and pathology and recent developments in inhibitor design [J]. Chem Rev,2002,102:4459-4488.
[124]. Halangk, Lerch MM, Brandt-Ned elev B, et al. Role of cathepsin B in intracelhlar trypsinogen activation and the onset of acute pancreatitis[J].Clin Invest. 2000,106(6):773-781.
[125]. Frohlich E, Schlagenhauf B, Mohrle M, et al. Activity, expression, and transcription rate ofthe cathepsins B,D,H,and L in cutaneous malignant melanoma[J]. Cancer.2001,91(5):972-982.
[126]. Roshy S, Sloane B F, Moin K. Pericellular cathepsin B and malignant progression [J]. Cancer Metastasis Rev,2003,223 (22):271-286.
[127]. Pogorski I, Sloane B F. Cathepsin B and its role(s) in cancer progression[J]. Biochem Soc Symp,2003,70(10):263-276.
[128]. Downs LS Jr, Lima PH, Bliss RL, et al.. Cathepsins B and D activity and activity ratios in normal ovaries, benign ovarian neoplasms, and epithelial ovarian cancer[J]. Soc Gynecol Investig.2005; 12(7):539-544.
[129]. Liu J, Guo Q, Chen B, et al. Cathepsin B and its interacting proteins, bikunin and TSRC1, correlate with TNF-induced apoptosis of ovarian cancer cells OV-90[J]. FEBS Lett,2006,580(1):245-250.
[130]. Niedergethmann M, Wostbrock B, Sturm JW, et al Prognostic impact of cysteine proteases cathepsinB and cathepsinL in pancreatic adenocarcinoma [J]. Pancreas,2004,29(3):204-211.
[131]. Nishida Y, Kohno K, Kawamata T, et al.. Increased cathepsin L levels in serum in some patients with ovarian cancer:comparison with CA125 and CA72-4[J]. Gynecol Oncol.1995 3;56(3):357-361.
[132]. Krueger S, Kellner U, Buehling F, et al. Cathepsin Lantisense oligonucleotides in a human osteosarcoma cell line:effects on the invasivphenotype[J]. Cancer Gene Ther,2001,8(7):522.-528
[133]. Nishikawa H, Ozaki Y, Nakanishi T, et al.. The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer[J].Gynecol Oncol.2004 Mar;92(3):881-6.
[134]. Mohamed MM, Sloane BF Cysteine cathepsins:multifunctional enzymes in cancer[J]. Nat Rev Cancer.2006,6(10):764-775.
[135]. Mohanam S,Jasti SL, Kondraganti SR, et al.Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells[J].Oncogene.2001,20(28):3665-3673.
[136]. Miyake H, Hara I, Eto H. Serum level of cathepsin B and its density in men with prostate cancer as novel markers of disease progression[J]. Anticancer Res,2004, 24(4):2573-2577.
[137]. Yu B, Li SY, An P, et al. Expression of cathepsin B and its clinical importance in colorectal cancer[J]. Zhonghua Wei Chang Wai KeZa Zhi,2005,8(6):507-509.
[138]. Wang M, Tang J,Liu S,et al. Expression of cathepsinB and microvascular density increases with higher grade of astrocytomas[J].JNeurooncol,2005,71(1):3-7.
[139]. Krueger S, Kellner U, Buehling F, et al Cathepsin L antisense oligonucleotides in a human osteosarcoma cell line:effects on the invasive phenotype [J]. Cancer Gene Ther,2001,8(7):522-528.
[140]. Levicar N, Dewey RA, Daley E, et al.Selective suppression of cathepsin L by antisense cDNA impairs human brain tumor cell invasion invitro and promotesapoptosis[J].CancerGeneTher.2003,10(2):141-151.
[141].曹新广,郭长青,李继昌,等.原位杂交法检测组织蛋白酶L在大肠癌中的表达[J].肿瘤基础与临床,2007,20(1)：9-11.
[142]. Vlodavsky I, Friedmann Y, Elkin M, et al. Mammalian heparanase:gene cloning, expression an d function in tumor progression and metastasis [J].Nat Med, 1999,5(7):793-802.
[143]. McKenzie E,Young K.Biochemical characterization of the active heterodimer form of human heparanase (Hpa) protein expressed in insect cell [J].Boochem J,2003,373(Pt2):423-466.
[144]. Dong J,Kukula AK,Toyoshima M, et al.Genomic organization and chromosome localization of the newly identified human heparanase gene [J].Gene,2000,25(3):171-179.
[145].李燕杰,乙酰肝素酶的结构功能及调控[J],生物技术通讯,2003,4,2-14.
[146]. Bame KJ.Heparanase:endoglycosidases that degrade heparin sulfate proteoglycans. Glycobiology 2001;11(11):91R-98R.
[147]. Ihrcke NS, Reissner KJ, Reissner KJ, et al.Regulation of platelet heparanase during inflammation:role of pH and proteinases[J]. Journal of Cellular Physiology. 1998,175:255-267.
[148]. Vlodavsky I,Friedman Y. Molecular properties and involvement of heparanase in cancer metastasis and mlgiogenesis[J].J Clin Invest.2001,10(8):341-355.
[149]. Pillarisetti S. lipoprotein modulation of subendothelial heparan sulfate proteoglycans (perlecan) and atherogenicity [J]. Trends Cardiovasc Med,2000,10 (2):60-65.
[150].黄庆,田辉,李林等,乙酰肝素酶与肿瘤关系的研究进展,现代诊断与治疗,2006,5,17(3)：160-163.
[151]. Vlodavsky I, Zcharia E, Goldshmidt O, et al..Involvement of heparanase in tumor progression and normal differentiation[J].Pathoph3 siol Haemost Thromb, 2003,3[Suppll]:59-61.
[152]. Hollingsworth HC,Kohn EC,Steinberg SM, et al. Tumor angiogenesis in advanced stage ovarian carcinomas[J].Am J Pathol,1995,147(1):33-41
[153]. Liotta LA, An attractive force in metastasis [J]. Nature,2001,40(1):24-29.
[154]. Folkman J.Tumor angiogenesis:therapeutic implication[J]. N Engl J Med,1971,185:1182-1186.
[155]. Folkman J. Role of angiogenesis in tumor growth and metastasis [J]. Semin Oncol,2002,6 Suppl 16:15-18.
[156]. Mesiano S, Ferrara N, Jaffe RB. Role of vascular endothelial growth factor in ovarian cancer. Inhibition of ascites formation by immunoneutralization[J]. Am J Pathol.1998,153:1249-1256.
[157]. Ferrara N. Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis:therapeutic implications [J]. Semin Oncol,2002,29:10-14.
[158]. Kuwata T, Kitagawa M, Takemura T, et al. Proliferative activity and P53 over-expression of ovarian epithelia tumors[J]. Gen Diagn Pathor,1995; 14(2): 131-139.
[159]. Nam JS, Ino Y, Sakamoto M, et al. Src family kinase inhibitor PP2 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis[J].Clin Cancer Res.2002,8(7):2430-2436.
[160]. Miotti S, Tomassetti A, Facetti I, et al. Simultaneous expression of caveolin-1 and E-cadherin in ovarian carcinoma cells stabilizes adherens junctions through inhibition of src-related kinases[J].Am J Pathol.2005,167(5):1411-1427.
[161]. Lee BC, Cha K, Avraham S, et al. Microarray analysis of differentially expressed genes associated with human ovarian cancer[J]. Int J Oncol.2004, 24(4):847-851.
[162]. Henic E, Sixt M, Hansson S, et al. EGF-stimulated migration in ovarian cancer cells is associated with decreased internalization, increased surface expression, and increased shedding of the urokinase plasminogen activator receptor[J].Gynecol Oncol. 2006,101(1):28-39.
[163]. Shen MR, Lin AC, Hsu YM, etal. Insulin-like growth factor 1 stimulates KC1 cotransport, which is necessary for invasion and proliferation of cervical cancer and ovarian cancer cells[J]. Biol Chem.2004,279(38):40017-40025.
[164]. Ueoka Y, Kato K, Wake N. Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via ras mediated pathway[J]. Mol Cell Endocrinol. 2003,202(1-2):81-88.
[165]. Antoni Castells, Anil K. Rustgi. Tumor Invasion and Metastasis.
[166]. Li AJ, Madden AC, Cass I, et al. The prognostic significance of thrombocytosis in epithelial ovarian carcinoma[J]. Gynecol Oncol.2004,92(1):211-214.
[167]. Rashidi B, Gamagami R,Sasson A, et al.An Orthotopic mouse model of remetastasis of human colon cancer liver metastasis[J].Clin Cancer Res,2000, 6(6):2556-2561.
[168]. Ono K,Ishihara M,Ishikawa K, et al Non-anticoagulant heparin carrying polystyrene(NAC-HCPS) affects angiofenesis and inhibits subcutaneous induced tumor growth and metastasis to the lung [J].Br J Cancer,2002,86(110):1803-1812.
[169]. Witte MH, Bernas MJ, Martin CP, et al. Lymphangiogenesis and lymphangiodysplasia:from molecular to clinical lymphology[J]. Microsc Res Tech, 2001; 55(2):122-145.
[170].高进,章静波.肿瘤侵袭和转移的形态学基础[A].高进,章静波主编.癌的侵袭与转移基础与临床[M].北京：科学出版社.2003,10-11.
[171].陈邸瑕,杨湛中.广泛根治术治疗原发性卵巢癌初步报告[J].中华妇产科杂志,1992,27(13)：165-166.
[172]. Rose PG, Piver MS, Tsukada Y, Latus. Metastatic patterns in histologic variants of ovarian cancer. An autopsy study[J]. Cancer 1989; 64(7):1508-1513.
[173]. Di Te F, Baiocchi G. Value of lymph node assessment in ovarian cancer:Status of the art at the end of the second millennium [J]. Int J gynecol Cancer,2000,10(6):435-442.
[174]. Pereira A, Magrina JF, Rey V, et al. Pelvic and aortic lymph node metastasis in epithelial ovarian cancer[J]. Gynecol Oncol.2007 Jun; 105(3):604-608.
[175]. Di Re F,Baiocchi G, Fontanelli R, et al. Systematic pelvic and paraaortic lymphadenectomy for advanced ovarian cancer. prognostic significance of node metastases[J]. Gynecol Oncol,1996,6(2):360-365
[176]. Parazzini F, Valsecchi G, Bolis G, etc. Pelvic and paraotic lymph nodal status in advanced ovarian cancer and survival[J].Gynecol Oncol,1999,74(1):7-11.
[177]. Shaaban A, Rezvani M. Ovarian cancer:detection and radiologic staging [J]. Clin Obstet Gynecol.2009;52(1):73-93.
[178].连利娟.卵巢上皮性癌与交界性瘤的临床[A].见：连利娟主编.林巧稚妇科肿瘤学[M].第四版.北京：人民卫生出版社.2006,553-554.
[179].郎景和,沈铿,向阳.临床妇科肿瘤学[M].北京：人民卫生出版社,2003.290-296.
[180]. Ali Ayhan, Murat Gultekin, Cagatay Taskiran, et al. Routine Appendectomy in Epithelial Ovarian Carcinoma:Is It Necessary? [J].Obstetrics & Gynecology.2005, 105:719-724.
[181]. Aviram R, Gassner G, M arkovitch O, et al. Volumes of normal ovaries, ovaries with benign lesions, and ovaries with cancer in menopausal women:is there an optimal cut-off value to predict malignancy[J]. Clin Ultrasound,2008,36(1):1-5.
[182].林黎娟.卵巢恶性肿瘤的CT表现[J].中国辐射卫生.2008,17(1)：90.
[183].吴珊珊,万云,刘波等,卵巢肿瘤的MRI诊断与鉴别诊断[J].现代临床医学生物工程学杂志.2006,12(2)：119-122.
[184]. Barranger E, Petegnief Y, Petegnief Y. Laparoscopic resection of occult metastasis using the combination of FDG-positron emission tomography/computed tomography image fusion with intraoperative probe guidance in a woman with recurrent ovarian cancer[J]. Gynecol Oncol.2005,9(6):241-244.
[185]. Harpreet K. Pannu, Robert E. Bristow, Christian Cohade, et al.PET-CT in Recurrent Ovarian Cancer:Initial Observations[J]. Radiographics.2004,24(4): 209-223.
[186].赵军,管一晖,左传涛等,18F-FDG PET／CT在探测卵巢癌术后复发和转移中的价值[J].中国肿瘤.2007,3.
[187]. Kirchhoff C, Habben I, Ivell R, et al. A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors[J].Biol Reprod,1999,45 (2):350-370.
[188]. Bingle L, Singleton V, Bingle CD. The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms[J].Oncogene,2002,21(17):2768-2799.
[189].Schummer M,Ng WV,Bumgarner RE, et al.Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas[J].Gene,1999,238(2):375-385.
[190]. Hellstrom I, Raycraft J,Hayden-Ledbetter M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma [J].Cancer Res,2003,63 (13):36-95.
[191]. Moore RG, Brown AK, Miller MC,et al.The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass [J].Gynecol Oncol,2008,108(2):402-408.
[192]. Drapkin R, Von Horsten HH, LIN Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas[J].Cancer Res.2005,65 (6):2162-2169.
[193]. Morice P, Dubernard G, Rey A,et al. Results of interval debulking surgery compared with primary debulking surgery in advanced stage ovarian cancer [J]. Am Coll Surg.2003,197(6):955-963.
[194]. Dowdy SC,Constantinou CL,Hartmann LC,et al.Longterm follow-up of women with ovarian cancer after positive second-look lararotomy[J].Gynecol Oncol,2003,9(1):563-568.
[195].缪智辉,殷平,王玉梅,张际菲.卵巢癌患者大网膜切除的临床病理分析 [J].中国肿瘤临床.2001.28.114-119.
[196]. Parker R T.Cancer of the ovary survival study based upon operation therapy chemotherapy and radiotherapy[J].Am J Obstet Gynecol,1970,18(8):87-89.
[197]. Yokoyanma Y,Sakamoto T,Sato S, et al.Evaluation of cytoreductive surgery with pelvic and paraaortic lymphadenectomy and intermittent cisplatin-based combination chemotherapy for improvement of long-term survival in ovarian cancer[J].Eur J Gynaecol Oncol,1999,2(95-6):361-366.
[198]. Di Re F,Baiocchi G.Fontanelli R, et al.Systemtic pelvie and paraaortic lymphadenectomy for advanced ovarian cancer:prognostic significance of node metastases.Gynecol Oncol,1996:62(3):360-365.
[199].张亦文,刘新民,孙玉蓉.妇科手术同时切除阑尾的探讨[J].中国实用妇科与产科杂志,2001,17(3)：165-169.
[200].李力.卵巢癌阑尾切除临床分析[J].临床外科杂志,2001,10(1),219-229.
[201].赵晶,刘新民.卵巢恶性肿瘤手术同时切除阑尾53例分析[J].现代妇产科进展,1996,5(1)：38-40.
[202]. Rose PG, Reade FR, Fisher A, et al. Appendectomy in primary and secondary staging operations for ovarian malignancy[J]. Obstetrics & Gynecology, 1991,77(6):116-118.
[203]. Fontanclli R, Paladini D, Raspagliesi F, et al. The role of appendectory in surgical procedures for ovarian cancer[J]. Gynecol Oncol,1992,4(6):42-43.
[204]. Magtibay PM, Adams PB, Silverman MB, et al. Splenectomy as part of cytoreduction surgery in ovarian cancer [J]. Gynecol Oncol,2006,102(2):369-374.
[205].于爱军,杨悦,脾脏切除在晚期上皮性卵巢癌肿瘤细胞减灭术中的意义[J].肿瘤学杂志,2007,13(3)：208-211.
[206]. Eisenhauer EL, Abu-Rustum NR, Sonoda Y, et al. The addition of extensive upper abdominal surgery to achieve optimal cytoreduction improves survival in patients with stages Ⅲc-Ⅳ epithelial ovarian cancer [J]. Gynecol Oncol,2006, 103(3):1083-1090.
[207].杨来春,段涛,朱关珍.铁林迪妇科手术学[M].济南：山东科学技术出版社,2003.1453-1463.
[208].张师前,智绪亭,李家福.晚期卵巢癌理想肿瘤细胞减灭术可行性研究[J].中 国现代手术学杂志,2004,8(6)：345-347.
[209].王世阆等.卵巢疾病,北京：人民卫生出版社[M],2004.1：237.
[210]. Neijt JP,Engelholm SA,Tuxen MK, et al.Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carbopiatin in advanced ovarian cancer[J]. Clin Oncol,2000 sep,18(17):3084-3092
[211]. Trope C,Hogberg T, Kaem J, et al.Long-term results from a phase II study of single agent paclitaxel(Taxol) in previously platinum treated patients with advanced ovarian cancer:the Nordic experience[J].Ann On col,1998 Del,9(12):1301-1307
[212]. Mirakhur B,Pareh Hk,Simpkins H, et al.Expression of the cisplatin resistance phenotype in a human ovarian carcinoma cell line segregates with chromosonmes 11 and 16[J].Cancer Res,1996,56(10):2256-2262.
[213]. Underthill CR,Parnis FX,Highiey MS, et al.Multicenter phae II study of gemcitabine in previously untreated patients with advanced epithelial ovarian cancer[J].Anticancer Drugs,2001 sep,12(8):647-52.
[214]. Hansen SW,Tuxen MK,Sessa S, et al.Gemcitabine in the treatment of ovarian cancer[J],Ann Oncol,1999,10(suppl 1):51-53.
[215]. Ivsrael VP,Garcia AA,Romar K, et al.Phase II study of liposomal doxorubicin in advanced gynecologic cancer[J]. Gynecol Oncol,2000,7(8):143-147.
[216]. Mayerhofer K, Bodner-Adler B, Bodner k, et al. Paclitaxel/carboplatin as first-line chemotherapy in advanced ovarian cancer:efficacy and adverse effects with special consideraration of peripheral neuotoxicity[J].Anticancer Res,2000 Sep-Oct,20(5c):4047-4050.
[217].陈丽,宋磊,李秀丽,泰素、泰索蒂联合铂类化疗在晚期卵巢癌治疗作用[J].中国现代医学与临床,2007,6(6):53-56.
[218]. NeijtlP, Engelholm SA, TuxenMK, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and Carboplatin in advanced ovarian cancer[J]. J Clin Oncol,2000,18(17):3084-3092.
[219]. OzolsRF,BtmdyBN,GreerBE, et al.Phase III trial of calboplatin and paclitaxel compared with cisplatin and paclitaxd in patients with optimally resected stage III ovarian Cancer:a Gynecology Oncoloy Group study [J].Clin Oncol,2003,21(17): 3194-3200.
[220]. Yen MS,Juang CM,Lai CR, et al.Intraperitoneal cisplatin-based chemotherapy VS intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer[J],Inr J Gynecol Obster,2001,72(1):55-60.
[221].彭小萍,李孟达,介入治疗在妇科恶性肿瘤治疗中的应用价值[J],新医学,2004,2,35(2)：69-71.
[222].于钦德,陈传凤,马进强.30例晚期卵巢癌术前介入化疗疗效分析[J],肿瘤防治杂志,2001,10,8(5)：549-554.
[223]. Ziller C,Lincet H,Muller CD,et al.The cyclin-dependent kinase inhibitor p21 (Cipl/wafl) enhances the cytotoxicity of ganciclovir in HSV-TK transfected ovarian carcinoma cells [J]. Cancer Lett,2004;212(1):43-52.
[224]. Szary J,Kalita K,Przybyszewska M,et al.KDR promoyer can transcriptionally target cytosine deaminase suicide gene to cancer cells of nonendothelial origin [J].Anticancer Res,2001;21(5):3471-3475.
[225]. Kamazawa S, Kigawa J, Kanamori Y,et al. Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer[J].Gynecol Oncol.2002;86(2):171-176.
[226]. Zhang T,Guan M,Jin HY, et al.Reversal of multidrug resistance by small interfering double-stranded RNAs in ovarian cancer cells[J].Gynecol Oncol,2005,97(2):501-507
[227]. Wright JD,Second AA,Numnum TM,et al.A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer[J].Int J Gynecol Cancer,2007,2(8):151-159.
[228]. Chura JC,Van Iseghem K,Downs LS,et al. Bevacizumab plus cyclophosphamid in heavily pretreated patients with recurrent ovarian cancer[J].Gynecol Oncol,2007,10(3):401-407.
[229]. Downs LS Jr, Judson PL, Argenta PA,et al. A prospective randomized trial of thalidomide with topotecan compared with topotecan alone in women with recurrent epithelial ovarian carcinoma[J]. Cancer.2008 Jan 15;112(2):331-339.
[230]. Chan JK, Manuel MR, Ciaravino G, et al. Safety and efficacy of thalidomide in recurrent epithelial ovarian and peritoneal carcinoma[J]. Gynecol Oncol. 2006;103(3):919-923.
[231]. Machida S, Saga Y, Takei Y,et al. Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU-68)[J]. Int J Cancer. 2005,114(2):224-229.
[232]. Naumova E, Ubezio P, Garofalo A,et al. The vascular targeting property of paclitaxel is enhanced by SU6668, a receptor tyrosine kinase inhibitor, causing apoptosis of endothelial cells and inhibition of angiogenesis[J]. Clin Cancer Res. 2006,12(6):1839-1849.
[233].康玉,徐丛剑,刘惜时,等.DC融合瘤苗治疗大鼠腹腔播散性卵巢癌[J].现代妇产科进展,2005,14(4)：266-269.
[234]. Banchereau J,Palucka A K.Dendritic cells as therapeutic vaccines gainstcancer[J].NatRevImmunol,2005,(5):296-306.
[235]. Mobus VJ, Baum RP, Bolle M,et al. Immune responses to murine monoclonal antibody-B43.13 correlate with prolonged survival of women with recurrent ovarian cancer[J]. Am J Obstet Gynecol.2003;189(1):28-36.
[236]. Guo MG, Jiang MH, Yang Q, et al. Gene therapy for ovarian cancers by adenovirus-mediated complete antibody gene[J].Zhonghua Yi Xue Za Zhi.2004,84(1 4):1147-51.
[237]. Yang JZ, Zhang Z, Ma L, et al. Biologic properties of an anti-human ovarian carcinoma/anti-human CD3 single chain bispecific antibody [J]. Ai Zheng. 2005,24(7):787-91.
[238]. Liu J, Zhao Q, Zhao B, et al. Anew format of single chain tri-specific antibody with diminished molecular size efficiently induces ovarian tumor cell killing[J].Biotechnol Lett.2005,27(22):1821-1827.
[1]. Shaaban A, Rezvani M. Ovarian cancer:detection and radiologic staging, Clin Obstet Gynecol.2009;52(1):73-93.
[2]. Fata JE, Ho AT, Leco KJ,et al. Cellular turnover and extracellular matrix remodeling in female reproductive tissues:functions of metalloproteinases and their inhibitors, Cell Mol Life Sci.2000,20;57(1):77-95.
[3]. Shield K, Ackland ML, Ahmed N, et al. Multicellular spheroids in ovarian cancer metastases:Biology and pathology, Gynecol Oncol.2009;113(1):143-8.
[4].Manenti L, Paganoni P, Floriani I,Expression levels of vascular endothelial growth factor, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 and 2 in the plasma of patients with ovarian carcinoma. Eur J Cancer.2003, 39(13):1948-1956.
[5]. Karihtala P, Maenpaa J, Turpeenniemi-Hujanen T,et,.al.Front-line bevacizumab in serous epithelial ovarian cancer:biomarker analysis of the FINAVAST trial.Anticancer Res.2010,30(3):1001-1006.
[6]. Shinyo Y., Kodama J., Hongo A., et al. Heparanase expression is an independent prognostic factor in patients with invasive cervical cancer, [J]Annals of Oncology 2003,14 (6):1505-1510
[7]. Siewinski M, Saleh Y, Gryboc M,et al. Determination of cysteine peptidases-like activity and their inhibitors in the serum of patients with ovarian cancer treated by conventional chemotherapy and vitamin E. J Exp Ther Oncol.2004 Oct;4(3):189-93.
[8]. Yurkovetsky Z, Skates S, Lomakin A,et al. Development of a multimarker assay for early detection of ovarian cancer, J Clin Oncol.2010;28(13):2159-2166.
[9].王素梅,李力,张玮等.血清组织蛋白酶L在卵巢癌诊断及检测中的临床意义.J.中国肿瘤临床.2008,35(3)：167-168.
[10]. Sakata K, Shigemasa K, Nagai N, etc. Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary. Int J Oncol,2000,17:673-6811.
[11].王中显,刘少扬,江大琼,等.组织蛋白酶在卵巢癌中的表达及意义.肿 瘤,2006,26(6)：559-562.
[12].毛敬,辛晓燕,刘玉等,卵巢癌uPA及HPA的表达与肿瘤转移的相关性研究,现代肿瘤医学,2006,3,14(3)：329-331.
[13]. Kodama J, Shinyo Y, Hashen G. etc. Heparanase messenger RNA expression in epithelial ovarian tumor. Int J Mol Med.2003 12(6):961-964
[14]. Kleiner DE, Stetler-Stevenson WG. Matrix metcloproteinases and metastasis. Cancer Chemother Pharmacol.1999,43 [Supp]:42-51.
[17]. Wang M, Tang J,Liu S,et al. Expression of cathepsinB and microvascular density increases with higher grade of astrocytomas[J].J Neuro oncol,2005,71(1):3-7.
[18]. He X, Brenchley PE,Janyson GC, et al.Hypoxia increases heparanase dependent tumor cell invasion, which can be inhibited by antiheparanase antibodies,Cancer Res,2004,64(11):3928-3933
[19]. Ricciardelli C, Rodgers RJ. Extracellular matrix of ovarian tumors, Semin Reprod Med.2006;24(4):270-282.
[1]. Yurkovetsky Z,Skates S,Lomakin A,et al. Development of a multimarker assay for early detection of ovarian cancer[J]. Clin Oncol.2010;28(13):2159-2166.
[2]. Mittlboeck, M. and M. Schemper, Explained variation for logistic regression. Statistics in Medicine,1996.15(19):p.1987-1997.
[3]. Nolen B, Velikokhatnaya L, Marrangoni A, et al. Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol Oncol.2010;117(3):440-5
[4]. Fredriksson S, Horecka J, Brustugun OT,et al。 Multiplexed proximity ligation assays to profile putative plasma biomarkers relevant to pancreatic and ovarian cancer Clin Chem.2008,54(3):582-9.
[5]. Yurkovetsky ZR, Linkov FY, E Malehorn D,et al.Multiple biomarker panels for early detection of ovarian cancer, Future Oncol.2006,2(6):733-41.
[6]. Yurkovetsky Z, Ta'asan S, Skates S,et al. Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin. Gynecol Oncol.2007,107(1):58-65.
[7]. Kohandel M, Sivaloganathan S, Oza A.et al. Mathematical modeling of ovarian cancer treatments:sequencing of surgery and chemotherapy. J Theor Biol.2006, 7;242(1):62-8.
[8]. Bendrik C, Karlsson L, Dabrosin C, et al. Increased endostatin generation and decreased angiogenesis via MMP-9 by tamoxifen in hormone dependent ovarian cancer. Cancer Lett.2010 292(1):32-40.
[9]. Obayashi Y, Yabushita H, Kanyama K,et al. Role of serum-derived hyaluronan-associated protein-hyaluronan complex in ovarian cancer. Oncol Rep. 2008May;19(5):1245-51.
[10]. Maatta M, Talvensaari-Mattila A, Turpeenniemi-Hujanen T,et al Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in differential diagnosis between low malignant potential (LMP) and malignant ovarian tumours Anticancer Res.2007;27(4C):2753-8
[1]. Dunbar SA, Vander Zee CA, Oliver KG, et al. Quantitative multi plexed detection of bacterial pathogens:DNA an d protein applications Of the Luminex Lab MAP system[J].Microbiol Methods,2003,53 (2):245-252.
[2].陈允硕.肿瘤标志物的临床应用价值[J].中华检验医学杂志,2000,23(1)：522
[3].Kayaba H. Tumor markers:essential diagnostic tools for radiologists. Nippon Igaku Hoshasen Gakkhi,2003,63(4):133
[4].孔宪涛.肿瘤标志物应用进展与评价.实用肿瘤杂志,2002,17(5)：289
[5].Alley WR, Madera M, Mechref Y,et al Chip-based Reversed-phase Liquid Chromatography-Mass Spectrometry of Permethylated N-Linked Glycans:A Potential Methodology for Cancer-biomarker Discovery, Anal Chem.2010 21(5):235-241
[6]. Zhao J, Qiu W, Simeone DM, et al.N-linked glycosylation profiling of pancreatic cancer serum using capillary liquid phase separation coupled with mass spectrometric analysis, J Proteome Res.2007;6(3):1126-1138.
[7]. Peter-Katalinic J. Methods in enzymology:O-glycosylation of proteins. Methods Enzymol.2005;405 (2):139-171.
[1]. Weir HK. Than MJ. Hankey BF. et al. Annual report to the nation on the status of cancer,1975-2000. featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst,2003.95(17):1276-1299
[2]. David AG, David A. The U. S. Preventive services task force:putting evidence. based medicine to work. Clin Obstet Gynecol,1998,41 (21):332-342
[3].张鸣明,李幼平,等.Cochrane协作网及Coehrae图书馆[M].北京：科学出版社.2002,1
[4]. Glass GV. Primary secondary and meta analysis of research [J]. EducationResearch,1976,6:
[5].孙丽君.基质金属蛋白酶-9与卵巢上皮性癌血管生成关系的研究[J].中国医药,2007,2(8)：506-507
[6].巫静娴,赵涌,贾世军等.CD147与基质金属蛋白酶-2,3,9在卵巢癌中的表达及临床病理意义[J].重庆医科大学学报,2007,32(11)：1165-1168
[7].张立晶,谭文华,杨庆华.基质金属蛋白酶-9与层粘连蛋白受体在卵巢上皮性肿瘤中的表达及意义[J].中国优生与遗传杂志,2007,15(5)：31-32
[8].李道成,梁立治,邓高丕.MMP-9在上皮性卵巢癌组织中的表达及临床意义[J].实用癌症杂志,2008,1(23)：1-2
[9].孙淑娥,田立粮,于红丽.MMP-9、 PCNA在卵巢上皮性肿瘤中的表达及临床意义[J].中国妇幼保健,2008,7(23)：975-977
[10].夏庆安,吴瑜,姜丽等.MMP-9在上皮性卵巢肿瘤中的表达和微血管密度与临床病理的关系[J].现代预防医学,2008,15(6)：1180-1181
[11].闫慧,谭文华.血管内皮生长因子与MMP-9在上皮性卵巢癌中的表达及临床意义[J].黑龙江医学,2008,32(2)：89-91
[12].刘玉,辛晓燕,韩良辅等.乙酰肝素酶、层粘连蛋白及其受体的表达以及在卵巢癌中转移的作用[J].细胞与分子免疫学杂志,2003,19(5)：459-461.
[13].韩静,杨鹰,阎萍.乙酰肝素酶在卵巢组织中的表达及其临床意义[J].第三军医大学学报,2006,10,28(20)：2054-2056.
[14].毛敬,辛晓燕,刘玉等.卵巢癌upa及Hpa的表达与肿瘤转移的相关性研究[J]. 现代肿瘤医学,2006,3,14(3)：329-331.
[15].苍亚芹,马致南.乙酰肝素酶在卵巢癌中表达的临床意义[J].黑龙江医学,2007,31(5)：324.
[16].李翠,王福玲.卵巢癌中乙酰肝素酶蛋白的表达及临床意义[J].中国现代药物应用,2008,5,2(10)：5-7.
[17].De Moura JP, Nicolau SM, Stavale JN. et al. Heparanse-2 expression in normal epithelium and in bengin and malignant ovarian tumors[J]. Int J Gynecol Cancer,2009, 12,19(9):1494-1500
[18].Losch A, Schindl M, Kohlberger P. et al. Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density [J]. Gynecol Oncol,2004,2,92(2):545-552.
[19].王中显,刘少扬,江大琼.组织蛋白酶B在卵巢癌中的表达及意义[J].肿瘤,2006,6,26(6)：229-562.
[20].王素梅,李力,张玮等.组织蛋白酶B及其组织抑制剂在卵巢恶性肿瘤组织中表达及其意义的研究[J].中国肿瘤防治杂志,2008,3,15(5)：363-366.
[21].Sillanpaa S, Anttila M, Voutilainen K. et al. Prognostic significance of matrix metallo-proteinase-9 (MMP-9) in epithelial ovarian cancer[J]. Gynecologic Oncology, 2007, (104):296-303
[22].Aparna A. K, Mavis F,Lynn M.G. et al. The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer [J]. Clin Cancer Res 2006,12(6):1707-1714
[2].Armstrong DK. Relapsed ovarian cancer:challenges and management strategies for a chronic disease[J].Oncologist,2002,7 Suppl 5:20-28.
[3].Harries M, Gore M. Part Ⅱ:chemotherapy for epithelial ovarian cancer treatment of recurrent disease[J]. Lancet Oncol,2002,3 (9):537-545.
[4].Paget S. The distribution of secondary growths in cancer of the breast [J]. Lancet, 1889,1:571-573.
[5]. Fidler IJ.The pathogenesis of cancer metastasis:the "seed and soil" hypothesis revisited[J]. Nature Reviews Cancer,2003,3:453-458。
[6].Fidler IJ.Critical factors in the biology of human cancer metastasis:twenty-eight GH.A. Clowes Memorial Award lecture[J]. Cancer Res,1990,50:6130-6138.
[7].Fidler IJ.Critical determinants of matastasis[J].Nature,2003,423:593-595.
[8].李红梅,方伟岗,何春生等.不同转移能力的人前列腺癌细胞亚系中p38和cJun氨基末端激酶激活机制[J].中华病理学杂志,2001,30(3)：194-197.
[9]. Todd R, Wong DT. Oncogenes. Anticancer Res.1999,19(6A):4729-4746.
[10]. Vogelstein B, Kinzler KW. The Genetic Basis Of Human Cancer[M]. New York: McGraw-Hill, Health Professions Division,1998,205-340.
[11]. Scambia G, Masciullo V, Benedetti Panici p, et al. Prognostic singnificance of ras/p21 alterations in human ovarian cancer[J].Br J Cancer,1997,75 (10):1547-1553.
[12]. Garrett Ap, Lee KR, Colitti CR, et al. k-ras mutation may be earlyevent in mucinous ovarian tumorigenesis [J]. Int J Gynecol pathol,2001,20(3):244-251.
[13]. CuatrecasasM, Erill N, Musulen E, et al. K-ras mutations in nonmucinous ovarian epithelial tumors:a molecular analysis and clinicopathologic study of 144 patients [J]. Cancer,1998,82 (6):1088-1095.
[14]. Yamashita K, Kuba T, Shinoda H, et al.Detection of k-ras pointnmutations in the supernatants of peritoneal and pleural effusions for diagnosis complementary to cytologic examination [J]. Am J ClinPathol,1998,109(6):704-711.
[15]. Bernhard EJ, Stanbridge EJ, Gupta S, et al. Direct evidence for thecontribution of activated N-ras and K-ras oncogenes to increasedintrinsic radiation resistance in human tumor cell lines [J]. CancerRas,2000,60(23):6597-6600.
[16]. Funato T, Ishii T, Kambe M,et al.Anti-k-ras ribozyme inducesgrowth inhibition and increased chemosensitivity in human colon cancer cells [J]. Gancer Gene Ther, 2000,7 (3):495-500.
[17]. Rutter JL,Chatterjee N,Wacholders S,et al.The Her2 I655V polymorphism and breast cancer risk in Ashkenazim [J].Epidemiology,2003,14:694-700.
[18]. Hattori M, Sakamoto H, Satoh K, et al.DNA demethylase is expressed in ovarian cancers and the expression correlates with demethylation of CpG sites in the promoter region of c-erbB-2 and survivin genes[J]. Cancer Lett,2001,169(2):155-164.
[19]. Baker VV, Borst MP, Dixon D, et al. C-Myc amplification in ovarian cancer. Gynecol oncol,1990,38:340-342.
[20]. Schlotter CM,Vogt U,Bosse U,et al.C-Myc not Her2/Neu can predict recurrence and mortality of paients with node-negative breast cancer [J]. Breast cancer Res,2003,5:R30-36.
[21]. Plisiecka-Halasa J, Karpinska G, Szymanska T, et al. P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens[J]. Ann Oncol 2003:14(7):1078-1085.
[22]. Spentzos D, Levine DA, Ramoni MF, Joseph M, Gu X, Boyd J, et al. Gene expression signature with independent prognostic significance in epithelial ovarian cancer[J]. Clin Oncol 2004:22(23):4700-4710.
[23]. Harris H, Miller OJ,Klein G et al. Suppression of malignancy by cell fuion[J].Nature,1969,223:363-368.
[24]. Ryan KM, Phillips AC, Vousden KH. Regulation and function of the p53 tumor suppressor protein [J].Current Opinion in Cell Biology,2001,13:2973-2983.
[25].詹启敏.分子肿瘤学[M].人民卫生出版社.2005年第一版.
[26]. Berchuck A, Kohler MF, Marks JR, et al. The p53 tumor suppressor gene frequently is altered in gynecologic cancers[J]. Am J Obstet Gynecol,1994,170 (1):246-253.
[27]. Sui L, Dong Y, Ohno M, et al. Inverse expression of Cdk4 and p16 in epithelial ovarian tumors[J]. Gynecol Oncol,2000,79(2):230-237.
[28].王刚,任杰平,王世阆,等.人卵巢浆液性囊腺癌中p16蛋白表达及其临床意义[J],中华临床杂志,2001,1(2)：1-3.
[29].苏荣健,姚阳,时亮,等.卵巢癌p16基因的纯合性缺失、突变及表达异常的研究[J].中国医科大学学报2002,3(6)：428-432.
[30]. Wang Min,Wei jun,Zhang Jialin. Replacement of the p16 gene in human ovarian cancer cells.Chinese Medical Journal,2001,114 (8):857-859.
[31]. Yamada KM,Araki M.Tumor suppressor PTEN:modulator of cell signaling[J] Journal of Cell Science,2002,114,(8):2375-2382.
[32]. Che Y, Yao Q, Dai S, et al. Analysis of PTEN mutation in epithelial ovarian cancer [J]. Prog Obstet Genecol,2002,11(1):18-20.
[33]. Catasus L, Bussaglia E, Rodrguez I,et al. Molecular genetic alterations in endometrioid carcinomas of the ovary:similar frequency of beta-catenin abnormalities but lower rate of microsatellite instability and PTEN alterations than in uterine endometrioid carcinomas[J]. Hum Pathol,2004,35 (11):1360-1368.
[34]. Chen R, Zheng H, Yang X, et al. Relationship between the mutation and mRNA expression of PTEN gene and pathobiological behavior of ovarian cancer[J]. Chin Clin Tumor,2004,31(7):365-367.
[35]. Gomes CP, Andrade LA(?) PTEN and p53 expression in primary ovarian carcinomas:immunohistochemical study and discussion of pathogenetic mechanisms [J]. Int J GynecolCancer,2006,16(Suppl1):254-258.
[36]. Hashiguchi Y, Tsuda H, Inoue T, et al. PTEN expression in clear cell adenocarcinoma of the ovary[J]. Gynecol Oncol,2006,101(1):71-75.
[37]. Dinulescu DM, Ince TA, Quade BJ, et al. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer [J]. Nat Med,2005,11(1):24-26.
[38]. Lee JS, Choi YD, Choi C, et al. Expression of PTEN in ovarian epithelial tumors and its relation to tumor behavior and growth[J].Anal Quant Cytol Histol,2005, 27(4):202-210.
[39]. Nicolson GL,Nawa AToh Y,Taniquchi S.Tumor metastasis-associated human MTA1 gene and its MTA1 protein product:role in epithelial cancer invasion,proliferation and nuclear regulationg[J]. Clin Exp Metastasis,2003 V20N1:19-24.
[40]. Van de Vijver MJ,He YD,Van't Veer LJ,et al.A gene-expession signature as a predictor of survival in breast cancer[J].N.Engl.J.Med,2002,3(47):1999-2009
[41]. Yoshida BA, Sokoloff MM, Welch DR, et al. Metastasis2 suppressor genes:a review and perspective on an emerging field[J]. Natl Cancer Inst,2000, 92(21):1717-1730.
[42]. Nakayama T, Ohtsuru A, Nakao K, et al. Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase,a homologue of the nm23 gene product [J]. J Natl Cancer Inst,1992,84 (17):1349-1354.
[43]. Shimada M, Taguchi K, Hasegawa H, et al. Nm232H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma[J]. Liver 1998,18 (5):337-342.
[44]. Schindl M, Birner P, Breitenecker G, et al. Downregulation of KAI1 metastasis suppressor protein is associated with a dismal prognosis in epithelial ovarian cancer[J]. Gynecol Oncol,2001,83 (2):244-248.
[45]. Uzawa K, Ono K, Suzuki H, et al. High prevalence of decreased expression of KAI1 metastasis suppressor in human oral carcinogenesis[J]. Clin Cancer Res, 2002,8(3):828-835.
[46]. Su JS, Arima K, Hasegawa M, et al. Decreased expression of KAI1metastasis suppressor gene is a recurrence predictor in primary pTa and pT1 urothelial bladder carcinoma[J]. Int J Urol,2004,11 (2):74-82.
[47]. Sun HC, Tang ZY, Zhou G, et al. KAI1 gene expression in hepatocellular carcinoma and its relationship with intrahepatic metastases [J]. J Exp Clin Cancer Res, 1998,17(3):307-311.
[48]. Stroop CJM,Weber W,Gerwig GJ.et al. Characterization of the carbohydrate chains of the secreted forms of the human epidermal growth factor receptor[J].Glycobiology,2000,10:901-917.
[49]. Mckallip R,Li R,Landisch S, Tumor gangliosides inhibit the tumor-specific immune response. [J]. Immumology,1999,163:3718-3726
[50].王兴旺,谢弘.AFP研究[J].中华医学杂志,1998,7(8)：723-724.
[51].周柔丽.细胞外基质及与细胞间的相互作用.宋今丹主编.医学细胞分子生物学.北京：人民卫生出版社,2003,62-86.
[52]. Bidart JM, Thuillier F, Augereau C. et al. Kinetics of Serum Tomur Marker Concentrations and Usefulness in Clinical Monitoring[J].Clinical Chemistry,1999, 4(5):1695-1707
[53]. Dong L, Cui H, Li XP, et al. Clinical value of serum CA19-9, CA125 and CP2 in mucinous ovarian tumor:a retrospective study of 273 patients[J]. Zhonghua Fu Chan Ke Za Zhi 2008,1,43(1):5-8.
[54]. Yin BW, Lyoyd KO.Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16[J]. Boil Chem 2001,7,20; 276(29):27371-5.
[55]. Kumar P, Rehani MM, Kumar L, et al.Tumor marker CA-125 as an evaluator and response indicator in ovarian cancer:its quantitative correlation with tumor volume[J].Med Sci Monit 2005,11(2):CR84-9.
[56].彭莉,张桂霞,朱传金.CEA、CA125在卵巢癌预后检测和复发诊断中的价值分析[J].肿瘤基础与临床,2006,10,19(5)：381-382.
[57]. Dong Y, Kaushal A, Bui L, et al. Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas[J]. Clin Cancer Res.2001,8(7):2363-71.
[58].陈文彬,潘祥林,主编.诊断学.第6版.北京：人民卫生出版社.2004,457.
[59]. Roberts JD,Olden K.et al. The role of Protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer[J]. Cancer detection and prevention 1998,22(5):455-462.
[60]. Thurin M,Kieber-Emmons T. SA-Lea and tumor metastasis:the old prediction and recent findings[J].Hybrid Hybridomics,2002,21(2):111-116.
[61]. Zacharski LR,Loynes JT. The heparins and cancer. Curr Opin Pulm Med, 2002,8(5):379-382.
[62]. Varki A,Varki NM. P-selectin,carcinoma metastasis and heparin:novel mechanistic connection with therapeutic implications[J]. Braz J Med Biol Res,2001,34(6):711-717.
[63].周柔丽.细胞黏附分子与细胞外基质.张乃蘅、童坦君主编.医学分子生物学, 北京：北京医科大学出版社,1999,282-307.
[64]. Okegawa T,Li YM,Pong RC, et al.Cell adhesion proteins as tumor suppressors[J].J-Ural,2002,167(4):1836-1843.
[65]. Conacci-Sorrell M,Zhurinsky J,Ben-Ze'ev A.The cadherin-catenin adhesion system in signaling and cancer[J]. Clin Invest.2002;109(8):987-991.
[66]. Davidson B, Gotlieb WH, Ber-Baruch G, et al. E-Cadherin complex protein Expression and survival in ovarian carcinoma[J]. Gynecol Oncol.2000,78(3): 362-371.
[67]. Beavon IR.The E-cadherin-catentia complex in tumour metastasis:structure, function and regulation [J].Eur J Cancer,2000,3(6):1607-1617.
[68]. Li G.Dynamics of intercellular communication during melanoma development [J].M Mol T oday,2000,6(4):163
[69]. Kim M, Carman C V, Springer TA, et al. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins[J]. Science.2003,301 (5640):1720-1725.
[70]. Calderwood DA,Huttenlocher A, Kiosses WB, et al. Increased filamin binding to beta-integrin cytoplasmic domains inhibits cell migration [J]. Net Cell Biol 2001,3:1060-1068.
[71]. Felding-Habermann B. Integrin adhesion receptors in tumor metastasis. Clin Exp Metastasis,2003,20(3):203-213.
[72]. Davidson B, Goldberg I, Reich R, et al. AlphaV-and betal-integrin subunits are commonly expressed in malignant effusions from ovarian carcinoma patients[J]. Gynecol Oncol.2003;90(2):248-257.
[73]. Buerkle MA,Pahernik SA,Sutter A, et al.Inbibition of the alpha-nu integerins with a cyclie RGD peptie impairs angiogenesis,growth and metastasis of solid tumor in vivo[J].Br J Cancer,2002,86(5):788-795.
[74]. Borsig L, Wong R, Hynes RO, et al. Synergistic effects of L-and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis[J]. Proc Nail AcM Sci USA.2002,99(4):2193-2198.
[75]. Borsig L, Wong R, Feramisco J. et al. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis[J]. Proc Natl Acad Sci USA.2001,98(6):3352-3357.
[76].钱思源,王黎娜,刘惠喜.P-选择素在卵巢癌中表达的意义.武警医学,2001, 12(9)：520.
[77].周同,王玲玲,陈金联,等.P选择素在几种肿瘤中表达的临床意义[J].上海免疫学杂志,2000,20(4)：236.
[78].周柔丽.糖类复合物及细胞黏附分子与肿瘤转移.吴秉铨,方伟岗主编.肿瘤转移机制及其阻断.杭州：浙江科学技术出版社,2005,92-93.
[79]. Zieglschmid V, Hollmann C, Bocher O. Detection of disseminated tumor cells in periphereal blood[J]. Crit Rev Clin lab Sci,2005,42(2):155-196.
[80]. Hong SC, Song JY, Lee JK, et al. Significance of CD44v6 expression in gynecologic malignancies[J].J Obstet Gynaecol Res,2006,32(4):379-386.
[81].李莉.CD44v6与肿瘤浸润、转移及预后[J].福建医科大学学报,2000,34(3)：315-317.
[82]. Darai E,Scoazec J Y. Expression of cadherins and CD44 proteins inovarian tumors physiopathology and diagnosis interest. Eur J Obstet Gynecol Reprod Biol,1999,86:131-133.
[83].Fidler IJ:The organ microenvironment andcancer metastasis. Differentiation 2002,70:498-505.
[84]. Ficorella C, Cannita K, Ricevuto E, et al. P16 hypermethylation contributes to the characterization of gene inactivation profiles in primary gastric cancer[J]. Oncol Report.2003,10(1):169-173.
[85].马怡红,吴秉权,柳剑英等.三种鼠不同结构p53 minigene瞬时转染H1299细胞对其生长的影响.中国肺癌杂志,2001,4(2)：94-98.
[86].吴晓,郑杰,付坚等.血管内皮生长因子反义基因转染对高转移人巨细胞肺癌细胞系生物学行为的影响.中华病理学杂志,2000,29(5)：363-366.
[87]. Kohn EC, Liotta LA. Local invasion and metastasis.in Satterfield(eds):Oncology, Williams&Wilhines,1991:131-137.
[88]. Fata JE, Ho AT, Leco KJ, et al. Cellular turnover and extracellular matrix remodeling in female reproductive tissues:functions of metalloproteinases and their inhibitors[J].Cell Mol Life Sci.2000,20,57(1):77-95.
[89]. Marneros AG, Olsen BR. The role of collagen-drived proteolytic fragments in angiogenesis[J].Matrix Biol,2001,20(5-6):337-345.
[90]. Yam HF,Chew EC,Chen HB. et al. The 67-KD Laminin-receptor in high and low metastatic melanoma cell line[J].Oncoligy Repot 1997,7(4):115-118.
[91].吴珊,郑杰,由江峰等.层粘连蛋白受体单克隆抗体的置备及其对肿瘤细胞的影响[J].中华病理学杂志,1993,22(4)：207-210.
[92]. Hoekstra R, Eskens FA, Verweij J. Matrix metalloproteinase inhibitions:current developments and future perspective[J].Oncolodist,2001,6:415-427.
[93]. Joyce E. Rundhaug. Matrix metalloproteinase,angiogenesis, and cancer[J]. Clim Cancer Res,2003,9:551-554
[94]. Hofmann UB,Westphal JR,Van Krasts AA, et al. Expression of integrin alpha (v)beta(3)correlates with activation of membrane-type matrix metalloproteinase-I (MT-MMP) and matrix metalloproteinase-2(MMP-2)in human melanoma cells in vitro and in vivo[J]. Int J Cancer,2000.87:12-19.
[95]. Deryugina EI,Bourdon MA,Jungwirth K. et al.Functional activation of integrin alpha V beta 3 in tumor cells espressing membrane-type 1 matrix metalloproteinase [J]. Int J Cancer,2000,86:15-23.
[96]. Fang J,Shing Y,Wiederschain D, et al.Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model[J].Proc Natl Acad Sci USA,2000,97.3884-3889.
[97]. Zhang A, Meng L, Wang Q, et al. Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2[J]. Oncol Rep. 2006;15(4):831-836.
[98]. Aparna A K,Mavis F, et al. The Clinical Relevance of Stromal Matrix Metalloproteinase Expression in Ovarian Cancer [J]. Clin Cancer Res 2006; 12(6) 1707-1714.
[99]. Sakata K, Shigemasa K, Nagai N, et al. Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary[J]. Int J Oncol,2000,17(6):673-6811.
[100]. Wang FQ, So J, Reierstad S, et al. Matrilysin (MMP-7) promotes invasion of ovarian cancer cells by activation of progelatinase[J]. Int J Cancer.2005,11(1):19-31.
[101]. Wang FQ,So J,Reielstad S, et al.Vascular endothelial growth factor-regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases[J]. Int J Cancer.2006,118:879-888.
[102]. Furuya M, Ishikura H,Kawarada Y. Tissue-type inhibitor matrix metalloproteinase expression in human ovarian cancer cells[J]. Gynecol OncoI.2000, 78(9):106-112.
[103]. Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function[J].Biochim Biophys Acta.,2000,1477(12):267-2831.
[104]. Zucker S,Mirza H.Conner CE, et al.Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cell conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation[J].Int J Cancer.1998,7(5):780-786.
[105]. Wojtowicz Praga S.Clincal potential of matrix metalloprotease inhibitors[J]. Drug RD,1999,6(1):117-129.
[106]. Wojtukiewicz M, Sierko E, Zacharski LR, et al. Occurrence of components of fibrinolytic pathways in situ in laryngeal cancer[J].Semin Thromb Hemost, 2003,29(3):317-320.
[107]. Ajani AE, Waksman R. Thrombolytic therapy in patients with submassive pulmonary embolism[J]. N Engl J Med,2003,348(4):357-359.
[108]. Sun Z, Zhang PX, Wang P, et al. Amino-terminal fragment of urokinase-type plasminogen activator inhibits its plasminogen activation [J]. Thromb Res,2002,106(2):105-111.
[109]. Mignati P, Rifkin DB.Nonenzymatic interactions between proteinases and the cell surface:novel roles in normal and malignant cell physiology[J]. Adv Cancer Res, 2000,8(7):103-157.
[110]. Liang OD,Chavakis T, kanse SM, et al.Ligand binding regions in the receptor for urokinase-type plasminogen activator[J]. Biol Chem,2001,276(31):28946-28953.
[111]. Podor TJ, Shaughnessy SG, Blackburn MN, et al. New insights into the size and stoichiometry of the plasminogen activator inhibitor type-1, vitronectin complex [J] Biol Chem,2000,275(33):25402-25410.
[112]. Blouse GE, Perron MJ, Thompson JH, et al. A concerted structural transition in theplasminogen activator inhibitor-1 mechanism of inhibition[J]. Biochemistry 2002,41(40):1997-2009.
[113]. Jankova L, Harrop SJ, Saunders DN, et al.Crystal structure of the complex of plasminogenactivator inhibitor 2 with a peptide mimicking the reactive center loop[J]. Bio Chem,2001,276(46):43374-43382.
[114]. Zhou H M, NicholsA, Meda P, et al. Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis[J]. EMBO J,2000,19 (17): 4817-4826.
[115]. Kerr JS,Slee AM,Mousa SA.The alpha v integrin antagonists as novel anticancer agents an update[J].Exper Opin Investing Drugs,2002,11(12):1765.
[116].凌丹,李力,纤溶酶原激活因子及其抑制因子与卵巢癌浸润转移[J],国外医学妇产科学分册,2004,31(3)：543-548.
[117]. Liu S, Bugge T H, Leppla SH. Targeting of tumor by cell surface urokinase plasminogen activator2dependent anthrax toxin [J]. J Biol Chem,2001,276 (2): 17976-17984.
[118]. Konecny G, UntchM, Pihan A, et al. Association of urokinase type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer[J]. Clin Cancer Res,2001,7 (6):1743-1749.
[119].舒晓燕,熊俊.尿激酶型纤溶酶原激活剂mRNA在卵巢癌组织中的表达及意义[J].中国现代医学杂志,2004,14(20)：57-58.
[120]. Borgfeldt C, Hansson SR, Gustavsson B, et al. Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasninogen activator(uPA),its receptor(uPAR) and its inhibitor(PAI-1) [J]. Int J Cancer,2001,92(4):497-502.
[121]. Boss E A, Massuger LF, Thomas CM, et al. Clnical value of components of the plasminogen activation system in ovarian cyst fluid[J]. Anticancer Res,2002,22 (1A):2752-282.
[122]. Liu J, Zhao Q, Zhao B, et al. A new format of single chain tri-specific antibody with diminished molecular size efficiently induces ovarian tumor cell killing.[J].Biotechnol Lett.2005,27(22):1821-1827.
[123]. Lecaille F, Kaleta J, Bromme D, et al. Human and parasitic papain2like cysteine proteases:their role in physiology and pathology and recent developments in inhibitor design [J]. Chem Rev,2002,102:4459-4488.
[124]. Halangk, Lerch MM, Brandt-Ned elev B, et al. Role of cathepsin B in intracelhlar trypsinogen activation and the onset of acute pancreatitis[J].Clin Invest. 2000,106(6):773-781.
[125]. Frohlich E, Schlagenhauf B, Mohrle M, et al. Activity, expression, and transcription rate ofthe cathepsins B,D,H,and L in cutaneous malignant melanoma[J]. Cancer.2001,91(5):972-982.
[126]. Roshy S, Sloane B F, Moin K. Pericellular cathepsin B and malignant progression [J]. Cancer Metastasis Rev,2003,223 (22):271-286.
[127]. Pogorski I, Sloane B F. Cathepsin B and its role(s) in cancer progression[J]. Biochem Soc Symp,2003,70(10):263-276.
[128]. Downs LS Jr, Lima PH, Bliss RL, et al.. Cathepsins B and D activity and activity ratios in normal ovaries, benign ovarian neoplasms, and epithelial ovarian cancer[J]. Soc Gynecol Investig.2005; 12(7):539-544.
[129]. Liu J, Guo Q, Chen B, et al. Cathepsin B and its interacting proteins, bikunin and TSRC1, correlate with TNF-induced apoptosis of ovarian cancer cells OV-90[J]. FEBS Lett,2006,580(1):245-250.
[130]. Niedergethmann M, Wostbrock B, Sturm JW, et al Prognostic impact of cysteine proteases cathepsinB and cathepsinL in pancreatic adenocarcinoma [J]. Pancreas,2004,29(3):204-211.
[131]. Nishida Y, Kohno K, Kawamata T, et al.. Increased cathepsin L levels in serum in some patients with ovarian cancer:comparison with CA125 and CA72-4[J]. Gynecol Oncol.1995 3;56(3):357-361.
[132]. Krueger S, Kellner U, Buehling F, et al. Cathepsin Lantisense oligonucleotides in a human osteosarcoma cell line:effects on the invasivphenotype[J]. Cancer Gene Ther,2001,8(7):522.-528
[133]. Nishikawa H, Ozaki Y, Nakanishi T, et al.. The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer[J].Gynecol Oncol.2004 Mar;92(3):881-6.
[134]. Mohamed MM, Sloane BF Cysteine cathepsins:multifunctional enzymes in cancer[J]. Nat Rev Cancer.2006,6(10):764-775.
[135]. Mohanam S,Jasti SL, Kondraganti SR, et al.Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells[J].Oncogene.2001,20(28):3665-3673.
[136]. Miyake H, Hara I, Eto H. Serum level of cathepsin B and its density in men with prostate cancer as novel markers of disease progression[J]. Anticancer Res,2004, 24(4):2573-2577.
[137]. Yu B, Li SY, An P, et al. Expression of cathepsin B and its clinical importance in colorectal cancer[J]. Zhonghua Wei Chang Wai KeZa Zhi,2005,8(6):507-509.
[138]. Wang M, Tang J,Liu S,et al. Expression of cathepsinB and microvascular density increases with higher grade of astrocytomas[J].JNeurooncol,2005,71(1):3-7.
[139]. Krueger S, Kellner U, Buehling F, et al Cathepsin L antisense oligonucleotides in a human osteosarcoma cell line:effects on the invasive phenotype [J]. Cancer Gene Ther,2001,8(7):522-528.
[140]. Levicar N, Dewey RA, Daley E, et al.Selective suppression of cathepsin L by antisense cDNA impairs human brain tumor cell invasion invitro and promotesapoptosis[J].CancerGeneTher.2003,10(2):141-151.
[141].曹新广,郭长青,李继昌,等.原位杂交法检测组织蛋白酶L在大肠癌中的表达[J].肿瘤基础与临床,2007,20(1)：9-11.
[142]. Vlodavsky I, Friedmann Y, Elkin M, et al. Mammalian heparanase:gene cloning, expression an d function in tumor progression and metastasis [J].Nat Med, 1999,5(7):793-802.
[143]. McKenzie E,Young K.Biochemical characterization of the active heterodimer form of human heparanase (Hpa) protein expressed in insect cell [J].Boochem J,2003,373(Pt2):423-466.
[144]. Dong J,Kukula AK,Toyoshima M, et al.Genomic organization and chromosome localization of the newly identified human heparanase gene [J].Gene,2000,25(3):171-179.
[145].李燕杰,乙酰肝素酶的结构功能及调控[J],生物技术通讯,2003,4,2-14.
[146]. Bame KJ.Heparanase:endoglycosidases that degrade heparin sulfate proteoglycans. Glycobiology 2001;11(11):91R-98R.
[147]. Ihrcke NS, Reissner KJ, Reissner KJ, et al.Regulation of platelet heparanase during inflammation:role of pH and proteinases[J]. Journal of Cellular Physiology. 1998,175:255-267.
[148]. Vlodavsky I,Friedman Y. Molecular properties and involvement of heparanase in cancer metastasis and mlgiogenesis[J].J Clin Invest.2001,10(8):341-355.
[149]. Pillarisetti S. lipoprotein modulation of subendothelial heparan sulfate proteoglycans (perlecan) and atherogenicity [J]. Trends Cardiovasc Med,2000,10 (2):60-65.
[150].黄庆,田辉,李林等,乙酰肝素酶与肿瘤关系的研究进展,现代诊断与治疗,2006,5,17(3)：160-163.
[151]. Vlodavsky I, Zcharia E, Goldshmidt O, et al..Involvement of heparanase in tumor progression and normal differentiation[J].Pathoph3 siol Haemost Thromb, 2003,3[Suppll]:59-61.
[152]. Hollingsworth HC,Kohn EC,Steinberg SM, et al. Tumor angiogenesis in advanced stage ovarian carcinomas[J].Am J Pathol,1995,147(1):33-41
[153]. Liotta LA, An attractive force in metastasis [J]. Nature,2001,40(1):24-29.
[154]. Folkman J.Tumor angiogenesis:therapeutic implication[J]. N Engl J Med,1971,185:1182-1186.
[155]. Folkman J. Role of angiogenesis in tumor growth and metastasis [J]. Semin Oncol,2002,6 Suppl 16:15-18.
[156]. Mesiano S, Ferrara N, Jaffe RB. Role of vascular endothelial growth factor in ovarian cancer. Inhibition of ascites formation by immunoneutralization[J]. Am J Pathol.1998,153:1249-1256.
[157]. Ferrara N. Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis:therapeutic implications [J]. Semin Oncol,2002,29:10-14.
[158]. Kuwata T, Kitagawa M, Takemura T, et al. Proliferative activity and P53 over-expression of ovarian epithelia tumors[J]. Gen Diagn Pathor,1995; 14(2): 131-139.
[159]. Nam JS, Ino Y, Sakamoto M, et al. Src family kinase inhibitor PP2 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis[J].Clin Cancer Res.2002,8(7):2430-2436.
[160]. Miotti S, Tomassetti A, Facetti I, et al. Simultaneous expression of caveolin-1 and E-cadherin in ovarian carcinoma cells stabilizes adherens junctions through inhibition of src-related kinases[J].Am J Pathol.2005,167(5):1411-1427.
[161]. Lee BC, Cha K, Avraham S, et al. Microarray analysis of differentially expressed genes associated with human ovarian cancer[J]. Int J Oncol.2004, 24(4):847-851.
[162]. Henic E, Sixt M, Hansson S, et al. EGF-stimulated migration in ovarian cancer cells is associated with decreased internalization, increased surface expression, and increased shedding of the urokinase plasminogen activator receptor[J].Gynecol Oncol. 2006,101(1):28-39.
[163]. Shen MR, Lin AC, Hsu YM, etal. Insulin-like growth factor 1 stimulates KC1 cotransport, which is necessary for invasion and proliferation of cervical cancer and ovarian cancer cells[J]. Biol Chem.2004,279(38):40017-40025.
[164]. Ueoka Y, Kato K, Wake N. Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via ras mediated pathway[J]. Mol Cell Endocrinol. 2003,202(1-2):81-88.
[165]. Antoni Castells, Anil K. Rustgi. Tumor Invasion and Metastasis.
[166]. Li AJ, Madden AC, Cass I, et al. The prognostic significance of thrombocytosis in epithelial ovarian carcinoma[J]. Gynecol Oncol.2004,92(1):211-214.
[167]. Rashidi B, Gamagami R,Sasson A, et al.An Orthotopic mouse model of remetastasis of human colon cancer liver metastasis[J].Clin Cancer Res,2000, 6(6):2556-2561.
[168]. Ono K,Ishihara M,Ishikawa K, et al Non-anticoagulant heparin carrying polystyrene(NAC-HCPS) affects angiofenesis and inhibits subcutaneous induced tumor growth and metastasis to the lung [J].Br J Cancer,2002,86(110):1803-1812.
[169]. Witte MH, Bernas MJ, Martin CP, et al. Lymphangiogenesis and lymphangiodysplasia:from molecular to clinical lymphology[J]. Microsc Res Tech, 2001; 55(2):122-145.
[170].高进,章静波.肿瘤侵袭和转移的形态学基础[A].高进,章静波主编.癌的侵袭与转移基础与临床[M].北京：科学出版社.2003,10-11.
[171].陈邸瑕,杨湛中.广泛根治术治疗原发性卵巢癌初步报告[J].中华妇产科杂志,1992,27(13)：165-166.
[172]. Rose PG, Piver MS, Tsukada Y, Latus. Metastatic patterns in histologic variants of ovarian cancer. An autopsy study[J]. Cancer 1989; 64(7):1508-1513.
[173]. Di Te F, Baiocchi G. Value of lymph node assessment in ovarian cancer:Status of the art at the end of the second millennium [J]. Int J gynecol Cancer,2000,10(6):435-442.
[174]. Pereira A, Magrina JF, Rey V, et al. Pelvic and aortic lymph node metastasis in epithelial ovarian cancer[J]. Gynecol Oncol.2007 Jun; 105(3):604-608.
[175]. Di Re F,Baiocchi G, Fontanelli R, et al. Systematic pelvic and paraaortic lymphadenectomy for advanced ovarian cancer. prognostic significance of node metastases[J]. Gynecol Oncol,1996,6(2):360-365
[176]. Parazzini F, Valsecchi G, Bolis G, etc. Pelvic and paraotic lymph nodal status in advanced ovarian cancer and survival[J].Gynecol Oncol,1999,74(1):7-11.
[177]. Shaaban A, Rezvani M. Ovarian cancer:detection and radiologic staging [J]. Clin Obstet Gynecol.2009;52(1):73-93.
[178].连利娟.卵巢上皮性癌与交界性瘤的临床[A].见：连利娟主编.林巧稚妇科肿瘤学[M].第四版.北京：人民卫生出版社.2006,553-554.
[179].郎景和,沈铿,向阳.临床妇科肿瘤学[M].北京：人民卫生出版社,2003.290-296.
[180]. Ali Ayhan, Murat Gultekin, Cagatay Taskiran, et al. Routine Appendectomy in Epithelial Ovarian Carcinoma:Is It Necessary? [J].Obstetrics & Gynecology.2005, 105:719-724.
[181]. Aviram R, Gassner G, M arkovitch O, et al. Volumes of normal ovaries, ovaries with benign lesions, and ovaries with cancer in menopausal women:is there an optimal cut-off value to predict malignancy[J]. Clin Ultrasound,2008,36(1):1-5.
[182].林黎娟.卵巢恶性肿瘤的CT表现[J].中国辐射卫生.2008,17(1)：90.
[183].吴珊珊,万云,刘波等,卵巢肿瘤的MRI诊断与鉴别诊断[J].现代临床医学生物工程学杂志.2006,12(2)：119-122.
[184]. Barranger E, Petegnief Y, Petegnief Y. Laparoscopic resection of occult metastasis using the combination of FDG-positron emission tomography/computed tomography image fusion with intraoperative probe guidance in a woman with recurrent ovarian cancer[J]. Gynecol Oncol.2005,9(6):241-244.
[185]. Harpreet K. Pannu, Robert E. Bristow, Christian Cohade, et al.PET-CT in Recurrent Ovarian Cancer:Initial Observations[J]. Radiographics.2004,24(4): 209-223.
[186].赵军,管一晖,左传涛等,18F-FDG PET／CT在探测卵巢癌术后复发和转移中的价值[J].中国肿瘤.2007,3.
[187]. Kirchhoff C, Habben I, Ivell R, et al. A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors[J].Biol Reprod,1999,45 (2):350-370.
[188]. Bingle L, Singleton V, Bingle CD. The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms[J].Oncogene,2002,21(17):2768-2799.
[189].Schummer M,Ng WV,Bumgarner RE, et al.Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas[J].Gene,1999,238(2):375-385.
[190]. Hellstrom I, Raycraft J,Hayden-Ledbetter M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma [J].Cancer Res,2003,63 (13):36-95.
[191]. Moore RG, Brown AK, Miller MC,et al.The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass [J].Gynecol Oncol,2008,108(2):402-408.
[192]. Drapkin R, Von Horsten HH, LIN Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas[J].Cancer Res.2005,65 (6):2162-2169.
[193]. Morice P, Dubernard G, Rey A,et al. Results of interval debulking surgery compared with primary debulking surgery in advanced stage ovarian cancer [J]. Am Coll Surg.2003,197(6):955-963.
[194]. Dowdy SC,Constantinou CL,Hartmann LC,et al.Longterm follow-up of women with ovarian cancer after positive second-look lararotomy[J].Gynecol Oncol,2003,9(1):563-568.
[195].缪智辉,殷平,王玉梅,张际菲.卵巢癌患者大网膜切除的临床病理分析 [J].中国肿瘤临床.2001.28.114-119.
[196]. Parker R T.Cancer of the ovary survival study based upon operation therapy chemotherapy and radiotherapy[J].Am J Obstet Gynecol,1970,18(8):87-89.
[197]. Yokoyanma Y,Sakamoto T,Sato S, et al.Evaluation of cytoreductive surgery with pelvic and paraaortic lymphadenectomy and intermittent cisplatin-based combination chemotherapy for improvement of long-term survival in ovarian cancer[J].Eur J Gynaecol Oncol,1999,2(95-6):361-366.
[198]. Di Re F,Baiocchi G.Fontanelli R, et al.Systemtic pelvie and paraaortic lymphadenectomy for advanced ovarian cancer:prognostic significance of node metastases.Gynecol Oncol,1996:62(3):360-365.
[199].张亦文,刘新民,孙玉蓉.妇科手术同时切除阑尾的探讨[J].中国实用妇科与产科杂志,2001,17(3)：165-169.
[200].李力.卵巢癌阑尾切除临床分析[J].临床外科杂志,2001,10(1),219-229.
[201].赵晶,刘新民.卵巢恶性肿瘤手术同时切除阑尾53例分析[J].现代妇产科进展,1996,5(1)：38-40.
[202]. Rose PG, Reade FR, Fisher A, et al. Appendectomy in primary and secondary staging operations for ovarian malignancy[J]. Obstetrics & Gynecology, 1991,77(6):116-118.
[203]. Fontanclli R, Paladini D, Raspagliesi F, et al. The role of appendectory in surgical procedures for ovarian cancer[J]. Gynecol Oncol,1992,4(6):42-43.
[204]. Magtibay PM, Adams PB, Silverman MB, et al. Splenectomy as part of cytoreduction surgery in ovarian cancer [J]. Gynecol Oncol,2006,102(2):369-374.
[205].于爱军,杨悦,脾脏切除在晚期上皮性卵巢癌肿瘤细胞减灭术中的意义[J].肿瘤学杂志,2007,13(3)：208-211.
[206]. Eisenhauer EL, Abu-Rustum NR, Sonoda Y, et al. The addition of extensive upper abdominal surgery to achieve optimal cytoreduction improves survival in patients with stages Ⅲc-Ⅳ epithelial ovarian cancer [J]. Gynecol Oncol,2006, 103(3):1083-1090.
[207].杨来春,段涛,朱关珍.铁林迪妇科手术学[M].济南：山东科学技术出版社,2003.1453-1463.
[208].张师前,智绪亭,李家福.晚期卵巢癌理想肿瘤细胞减灭术可行性研究[J].中 国现代手术学杂志,2004,8(6)：345-347.
[209].王世阆等.卵巢疾病,北京：人民卫生出版社[M],2004.1：237.
[210]. Neijt JP,Engelholm SA,Tuxen MK, et al.Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carbopiatin in advanced ovarian cancer[J]. Clin Oncol,2000 sep,18(17):3084-3092
[211]. Trope C,Hogberg T, Kaem J, et al.Long-term results from a phase II study of single agent paclitaxel(Taxol) in previously platinum treated patients with advanced ovarian cancer:the Nordic experience[J].Ann On col,1998 Del,9(12):1301-1307
[212]. Mirakhur B,Pareh Hk,Simpkins H, et al.Expression of the cisplatin resistance phenotype in a human ovarian carcinoma cell line segregates with chromosonmes 11 and 16[J].Cancer Res,1996,56(10):2256-2262.
[213]. Underthill CR,Parnis FX,Highiey MS, et al.Multicenter phae II study of gemcitabine in previously untreated patients with advanced epithelial ovarian cancer[J].Anticancer Drugs,2001 sep,12(8):647-52.
[214]. Hansen SW,Tuxen MK,Sessa S, et al.Gemcitabine in the treatment of ovarian cancer[J],Ann Oncol,1999,10(suppl 1):51-53.
[215]. Ivsrael VP,Garcia AA,Romar K, et al.Phase II study of liposomal doxorubicin in advanced gynecologic cancer[J]. Gynecol Oncol,2000,7(8):143-147.
[216]. Mayerhofer K, Bodner-Adler B, Bodner k, et al. Paclitaxel/carboplatin as first-line chemotherapy in advanced ovarian cancer:efficacy and adverse effects with special consideraration of peripheral neuotoxicity[J].Anticancer Res,2000 Sep-Oct,20(5c):4047-4050.
[217].陈丽,宋磊,李秀丽,泰素、泰索蒂联合铂类化疗在晚期卵巢癌治疗作用[J].中国现代医学与临床,2007,6(6):53-56.
[218]. NeijtlP, Engelholm SA, TuxenMK, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and Carboplatin in advanced ovarian cancer[J]. J Clin Oncol,2000,18(17):3084-3092.
[219]. OzolsRF,BtmdyBN,GreerBE, et al.Phase III trial of calboplatin and paclitaxel compared with cisplatin and paclitaxd in patients with optimally resected stage III ovarian Cancer:a Gynecology Oncoloy Group study [J].Clin Oncol,2003,21(17): 3194-3200.
[220]. Yen MS,Juang CM,Lai CR, et al.Intraperitoneal cisplatin-based chemotherapy VS intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer[J],Inr J Gynecol Obster,2001,72(1):55-60.
[221].彭小萍,李孟达,介入治疗在妇科恶性肿瘤治疗中的应用价值[J],新医学,2004,2,35(2)：69-71.
[222].于钦德,陈传凤,马进强.30例晚期卵巢癌术前介入化疗疗效分析[J],肿瘤防治杂志,2001,10,8(5)：549-554.
[223]. Ziller C,Lincet H,Muller CD,et al.The cyclin-dependent kinase inhibitor p21 (Cipl/wafl) enhances the cytotoxicity of ganciclovir in HSV-TK transfected ovarian carcinoma cells [J]. Cancer Lett,2004;212(1):43-52.
[224]. Szary J,Kalita K,Przybyszewska M,et al.KDR promoyer can transcriptionally target cytosine deaminase suicide gene to cancer cells of nonendothelial origin [J].Anticancer Res,2001;21(5):3471-3475.
[225]. Kamazawa S, Kigawa J, Kanamori Y,et al. Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer[J].Gynecol Oncol.2002;86(2):171-176.
[226]. Zhang T,Guan M,Jin HY, et al.Reversal of multidrug resistance by small interfering double-stranded RNAs in ovarian cancer cells[J].Gynecol Oncol,2005,97(2):501-507
[227]. Wright JD,Second AA,Numnum TM,et al.A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer[J].Int J Gynecol Cancer,2007,2(8):151-159.
[228]. Chura JC,Van Iseghem K,Downs LS,et al. Bevacizumab plus cyclophosphamid in heavily pretreated patients with recurrent ovarian cancer[J].Gynecol Oncol,2007,10(3):401-407.
[229]. Downs LS Jr, Judson PL, Argenta PA,et al. A prospective randomized trial of thalidomide with topotecan compared with topotecan alone in women with recurrent epithelial ovarian carcinoma[J]. Cancer.2008 Jan 15;112(2):331-339.
[230]. Chan JK, Manuel MR, Ciaravino G, et al. Safety and efficacy of thalidomide in recurrent epithelial ovarian and peritoneal carcinoma[J]. Gynecol Oncol. 2006;103(3):919-923.
[231]. Machida S, Saga Y, Takei Y,et al. Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU-68)[J]. Int J Cancer. 2005,114(2):224-229.
[232]. Naumova E, Ubezio P, Garofalo A,et al. The vascular targeting property of paclitaxel is enhanced by SU6668, a receptor tyrosine kinase inhibitor, causing apoptosis of endothelial cells and inhibition of angiogenesis[J]. Clin Cancer Res. 2006,12(6):1839-1849.
[233].康玉,徐丛剑,刘惜时,等.DC融合瘤苗治疗大鼠腹腔播散性卵巢癌[J].现代妇产科进展,2005,14(4)：266-269.
[234]. Banchereau J,Palucka A K.Dendritic cells as therapeutic vaccines gainstcancer[J].NatRevImmunol,2005,(5):296-306.
[235]. Mobus VJ, Baum RP, Bolle M,et al. Immune responses to murine monoclonal antibody-B43.13 correlate with prolonged survival of women with recurrent ovarian cancer[J]. Am J Obstet Gynecol.2003;189(1):28-36.
[236]. Guo MG, Jiang MH, Yang Q, et al. Gene therapy for ovarian cancers by adenovirus-mediated complete antibody gene[J].Zhonghua Yi Xue Za Zhi.2004,84(1 4):1147-51.
[237]. Yang JZ, Zhang Z, Ma L, et al. Biologic properties of an anti-human ovarian carcinoma/anti-human CD3 single chain bispecific antibody [J]. Ai Zheng. 2005,24(7):787-91.
[238]. Liu J, Zhao Q, Zhao B, et al. Anew format of single chain tri-specific antibody with diminished molecular size efficiently induces ovarian tumor cell killing[J].Biotechnol Lett.2005,27(22):1821-1827.
[1]. Shaaban A, Rezvani M. Ovarian cancer:detection and radiologic staging, Clin Obstet Gynecol.2009;52(1):73-93.
[2]. Fata JE, Ho AT, Leco KJ,et al. Cellular turnover and extracellular matrix remodeling in female reproductive tissues:functions of metalloproteinases and their inhibitors, Cell Mol Life Sci.2000,20;57(1):77-95.
[3]. Shield K, Ackland ML, Ahmed N, et al. Multicellular spheroids in ovarian cancer metastases:Biology and pathology, Gynecol Oncol.2009;113(1):143-8.
[4].Manenti L, Paganoni P, Floriani I,Expression levels of vascular endothelial growth factor, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 and 2 in the plasma of patients with ovarian carcinoma. Eur J Cancer.2003, 39(13):1948-1956.
[5]. Karihtala P, Maenpaa J, Turpeenniemi-Hujanen T,et,.al.Front-line bevacizumab in serous epithelial ovarian cancer:biomarker analysis of the FINAVAST trial.Anticancer Res.2010,30(3):1001-1006.
[6]. Shinyo Y., Kodama J., Hongo A., et al. Heparanase expression is an independent prognostic factor in patients with invasive cervical cancer, [J]Annals of Oncology 2003,14 (6):1505-1510
[7]. Siewinski M, Saleh Y, Gryboc M,et al. Determination of cysteine peptidases-like activity and their inhibitors in the serum of patients with ovarian cancer treated by conventional chemotherapy and vitamin E. J Exp Ther Oncol.2004 Oct;4(3):189-93.
[8]. Yurkovetsky Z, Skates S, Lomakin A,et al. Development of a multimarker assay for early detection of ovarian cancer, J Clin Oncol.2010;28(13):2159-2166.
[9].王素梅,李力,张玮等.血清组织蛋白酶L在卵巢癌诊断及检测中的临床意义.J.中国肿瘤临床.2008,35(3)：167-168.
[10]. Sakata K, Shigemasa K, Nagai N, etc. Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary. Int J Oncol,2000,17:673-6811.
[11].王中显,刘少扬,江大琼,等.组织蛋白酶在卵巢癌中的表达及意义.肿 瘤,2006,26(6)：559-562.
[12].毛敬,辛晓燕,刘玉等,卵巢癌uPA及HPA的表达与肿瘤转移的相关性研究,现代肿瘤医学,2006,3,14(3)：329-331.
[13]. Kodama J, Shinyo Y, Hashen G. etc. Heparanase messenger RNA expression in epithelial ovarian tumor. Int J Mol Med.2003 12(6):961-964
[14]. Kleiner DE, Stetler-Stevenson WG. Matrix metcloproteinases and metastasis. Cancer Chemother Pharmacol.1999,43 [Supp]:42-51.
[17]. Wang M, Tang J,Liu S,et al. Expression of cathepsinB and microvascular density increases with higher grade of astrocytomas[J].J Neuro oncol,2005,71(1):3-7.
[18]. He X, Brenchley PE,Janyson GC, et al.Hypoxia increases heparanase dependent tumor cell invasion, which can be inhibited by antiheparanase antibodies,Cancer Res,2004,64(11):3928-3933
[19]. Ricciardelli C, Rodgers RJ. Extracellular matrix of ovarian tumors, Semin Reprod Med.2006;24(4):270-282.
[1]. Yurkovetsky Z,Skates S,Lomakin A,et al. Development of a multimarker assay for early detection of ovarian cancer[J]. Clin Oncol.2010;28(13):2159-2166.
[2]. Mittlboeck, M. and M. Schemper, Explained variation for logistic regression. Statistics in Medicine,1996.15(19):p.1987-1997.
[3]. Nolen B, Velikokhatnaya L, Marrangoni A, et al. Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol Oncol.2010;117(3):440-5
[4]. Fredriksson S, Horecka J, Brustugun OT,et al。 Multiplexed proximity ligation assays to profile putative plasma biomarkers relevant to pancreatic and ovarian cancer Clin Chem.2008,54(3):582-9.
[5]. Yurkovetsky ZR, Linkov FY, E Malehorn D,et al.Multiple biomarker panels for early detection of ovarian cancer, Future Oncol.2006,2(6):733-41.
[6]. Yurkovetsky Z, Ta'asan S, Skates S,et al. Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin. Gynecol Oncol.2007,107(1):58-65.
[7]. Kohandel M, Sivaloganathan S, Oza A.et al. Mathematical modeling of ovarian cancer treatments:sequencing of surgery and chemotherapy. J Theor Biol.2006, 7;242(1):62-8.
[8]. Bendrik C, Karlsson L, Dabrosin C, et al. Increased endostatin generation and decreased angiogenesis via MMP-9 by tamoxifen in hormone dependent ovarian cancer. Cancer Lett.2010 292(1):32-40.
[9]. Obayashi Y, Yabushita H, Kanyama K,et al. Role of serum-derived hyaluronan-associated protein-hyaluronan complex in ovarian cancer. Oncol Rep. 2008May;19(5):1245-51.
[10]. Maatta M, Talvensaari-Mattila A, Turpeenniemi-Hujanen T,et al Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in differential diagnosis between low malignant potential (LMP) and malignant ovarian tumours Anticancer Res.2007;27(4C):2753-8
[1]. Dunbar SA, Vander Zee CA, Oliver KG, et al. Quantitative multi plexed detection of bacterial pathogens:DNA an d protein applications Of the Luminex Lab MAP system[J].Microbiol Methods,2003,53 (2):245-252.
[2].陈允硕.肿瘤标志物的临床应用价值[J].中华检验医学杂志,2000,23(1)：522
[3].Kayaba H. Tumor markers:essential diagnostic tools for radiologists. Nippon Igaku Hoshasen Gakkhi,2003,63(4):133
[4].孔宪涛.肿瘤标志物应用进展与评价.实用肿瘤杂志,2002,17(5)：289
[5].Alley WR, Madera M, Mechref Y,et al Chip-based Reversed-phase Liquid Chromatography-Mass Spectrometry of Permethylated N-Linked Glycans:A Potential Methodology for Cancer-biomarker Discovery, Anal Chem.2010 21(5):235-241
[6]. Zhao J, Qiu W, Simeone DM, et al.N-linked glycosylation profiling of pancreatic cancer serum using capillary liquid phase separation coupled with mass spectrometric analysis, J Proteome Res.2007;6(3):1126-1138.
[7]. Peter-Katalinic J. Methods in enzymology:O-glycosylation of proteins. Methods Enzymol.2005;405 (2):139-171.
[1]. Weir HK. Than MJ. Hankey BF. et al. Annual report to the nation on the status of cancer,1975-2000. featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst,2003.95(17):1276-1299
[2]. David AG, David A. The U. S. Preventive services task force:putting evidence. based medicine to work. Clin Obstet Gynecol,1998,41 (21):332-342
[3].张鸣明,李幼平,等.Cochrane协作网及Coehrae图书馆[M].北京：科学出版社.2002,1
[4]. Glass GV. Primary secondary and meta analysis of research [J]. EducationResearch,1976,6:
[5].孙丽君.基质金属蛋白酶-9与卵巢上皮性癌血管生成关系的研究[J].中国医药,2007,2(8)：506-507
[6].巫静娴,赵涌,贾世军等.CD147与基质金属蛋白酶-2,3,9在卵巢癌中的表达及临床病理意义[J].重庆医科大学学报,2007,32(11)：1165-1168
[7].张立晶,谭文华,杨庆华.基质金属蛋白酶-9与层粘连蛋白受体在卵巢上皮性肿瘤中的表达及意义[J].中国优生与遗传杂志,2007,15(5)：31-32
[8].李道成,梁立治,邓高丕.MMP-9在上皮性卵巢癌组织中的表达及临床意义[J].实用癌症杂志,2008,1(23)：1-2
[9].孙淑娥,田立粮,于红丽.MMP-9、 PCNA在卵巢上皮性肿瘤中的表达及临床意义[J].中国妇幼保健,2008,7(23)：975-977
[10].夏庆安,吴瑜,姜丽等.MMP-9在上皮性卵巢肿瘤中的表达和微血管密度与临床病理的关系[J].现代预防医学,2008,15(6)：1180-1181
[11].闫慧,谭文华.血管内皮生长因子与MMP-9在上皮性卵巢癌中的表达及临床意义[J].黑龙江医学,2008,32(2)：89-91
[12].刘玉,辛晓燕,韩良辅等.乙酰肝素酶、层粘连蛋白及其受体的表达以及在卵巢癌中转移的作用[J].细胞与分子免疫学杂志,2003,19(5)：459-461.
[13].韩静,杨鹰,阎萍.乙酰肝素酶在卵巢组织中的表达及其临床意义[J].第三军医大学学报,2006,10,28(20)：2054-2056.
[14].毛敬,辛晓燕,刘玉等.卵巢癌upa及Hpa的表达与肿瘤转移的相关性研究[J]. 现代肿瘤医学,2006,3,14(3)：329-331.
[15].苍亚芹,马致南.乙酰肝素酶在卵巢癌中表达的临床意义[J].黑龙江医学,2007,31(5)：324.
[16].李翠,王福玲.卵巢癌中乙酰肝素酶蛋白的表达及临床意义[J].中国现代药物应用,2008,5,2(10)：5-7.
[17].De Moura JP, Nicolau SM, Stavale JN. et al. Heparanse-2 expression in normal epithelium and in bengin and malignant ovarian tumors[J]. Int J Gynecol Cancer,2009, 12,19(9):1494-1500
[18].Losch A, Schindl M, Kohlberger P. et al. Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density [J]. Gynecol Oncol,2004,2,92(2):545-552.
[19].王中显,刘少扬,江大琼.组织蛋白酶B在卵巢癌中的表达及意义[J].肿瘤,2006,6,26(6)：229-562.
[20].王素梅,李力,张玮等.组织蛋白酶B及其组织抑制剂在卵巢恶性肿瘤组织中表达及其意义的研究[J].中国肿瘤防治杂志,2008,3,15(5)：363-366.
[21].Sillanpaa S, Anttila M, Voutilainen K. et al. Prognostic significance of matrix metallo-proteinase-9 (MMP-9) in epithelial ovarian cancer[J]. Gynecologic Oncology, 2007, (104):296-303
[22].Aparna A. K, Mavis F,Lynn M.G. et al. The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer [J]. Clin Cancer Res 2006,12(6):1707-1714