食管鳞癌中uPA、P-选择素、nm23、p27的表达及其与浸润转移关系的研究
|
摘要
[背景和目的]：食管癌是我国常见的恶性肿瘤之一，严重威胁着人们的生命健康。食管癌的发生发展是一个多因素参与和多阶段演变的结果，其浸润、转移而导致的肿瘤扩散是引起病人死亡的重要因素。研究表明，肿瘤的浸润转移是由肿瘤细胞分泌的蛋白酶降解细胞外基质而启动。其中纤溶酶原被激活与肿瘤浸润转移的关系最为密切，另外，细胞粘附分子也起着重要作用。迄今为止，有关食管癌中uPA、P-选择素、p27活性的检测及其与临床病理因素关系的研究报道极少，uPA、P-选择素、nm23、p27在食管鳞癌浸润、转移中相互关系的相关报道更为罕见。探讨联合检测uPA、P-选择素、nm23、p27在食管癌浸润转移中的意义进而通过抑制uPA、P-选择素的活性和增加nm23、p27的活性为食管癌的靶向治疗提供理论依据。
[材料与方法]：收集河南省安阳市肿瘤医院2003年8-9月份手术切除标本54例，病理证实全部为鳞状细胞癌，其中Ⅰ级15例，Ⅱ级30例，Ⅲ级9例，发生淋巴结转移的有21例。每例均在癌灶、(?)癌旁(?)组织及远端正常粘膜处分别取材。运用原位杂交和免疫组织化学方法对54例食管鳞癌组织、22例癌旁不典型增生组织及54例正常粘膜中uPA和P-选择素的mRNA及蛋白的表达、nm23 mRNA的表达和p27蛋白的表达进行了系统检测及观察。统计学采用x~2检验对资料进行分析，以α=0.05为显著性检验水准。
[结果]
郑州大学2(X)4硕士毕业论文
食管鳞癌中uPA、P一选择素、nm23、p27的表达及其与浸润转移关系的研究
1.54例食管鳞癌组织中uPA mRNA阳性表达主要位于细胞胞浆内，在组织学分级、
大小、浸润深度和有无转移的不同组别间的表达其差异具有显著性(P<0.05);
uPA蛋白阳性表达位于胞浆，其表达在不同浸润深度，有无转移的肿瘤之间有显
著差异性(P<0.05)。
2.食管鳞癌、癌旁不典型增生、正常食管粘膜组织中uPA mRNA阳性表达率分别
是70.4%(38/54)、40.9%(9/22)、1 1.1%(6/54)，三组间两两比较差异均有显著
，胜(P<0 .05)。
3.食管鳞癌、癌旁不典型增生、正常食管粘膜组织中uPA蛋白阳性表达率分别是
66.7%(36/54)、36.4%(8/22)、14.8%(8/54)，三组f’ed两两比较差异均有显著性
(P(0 .05)。
4.54例食管鳞癌组织中P一选择素mRNA阳性表达主要位于细胞胞浆，其表达与组
织学分级、浸润深度、淋巴结转移有关，差异具有显著性(P<0 .05);P一选择素
蛋白的阳性表达位于细胞胞浆及胞膜上，其表达与浸润深度，淋巴结转移有关，
差异具有显著性(P(0.05)。
5.食管鳞癌、癌旁不典型增生、正常食管组织中P一选择素mRNA的阳性表达率分
别为59.3%(32/54)、31.8%(7/22)、9.3%(5/54)，三组间两两比较差异均有显
著性(P(0.05)。
6.食管鳞癌、癌旁不典型增生、正常食管组织中P一选择素蛋白的阳性表达率分
别为66.7%(36/54)、40.9%(9/22)、14.8%(8/54)，三组间两两比较差异均有显
著性(P(0.05)。
7.食管鳞癌、癌旁不典型增生、正常食管组织中nm23 mRNA的阳性表达率分别为
35.2%(19/54)、63.6%(14/22)、85.2%(46/54)，三组间两两比较差异均有显著
性(P<0 .05)。nm23 mRNA的表达位于细胞胞浆，其表达与浸润深度、淋巴结转
移有关，差异具有显著性(P<0.05)。
8.食管鳞癌、癌旁不典型增生、正常食管组织中p27蛋白的阳性表达率分别为
31.5%(17/54)、59.1%(13/22)、81.5%(44/54)，三组间两两比较差异均有显著性
(P<0.05)。P27蛋白的表达位于细胞胞核内，胞浆和胞膜亦可见着色。其表达
与浸润深度、淋巴结转移有关，具差异有显著性差异(P(0 .05)。
9.uPA mRNA表达与蛋白表达之间差异无显著性(P>0 .05);P一选择素mRNA表达
郑州大学2以孙硕士毕业论文
食管鳞癌中uPA、P选择素、nm23、p27的表达及其与浸润转移关系的研究
与蛋白表达之间有显著性差异(P<0.05)。
10.uPA mRNA的表达与P一选择素mRNA的表达具有相关性(P<0.05);uPA蛋白的
表达与P一选择素蛋白的表达无相关性(P> .05)。
11.nm23 mRNA与uPA mRNA的表达和P一选择素mRNA的表达均具有相关性
(P<0.05);与uPA蛋白的表达和P一选择素蛋白的表达均无相关性(P>.05)。
12.p27蛋白的表达与uPA mRNA和蛋白的表达、P一选择素mRNA和蛋白的表达以
及nm23 mRNA的表达之间均无相关性(P)0.05)。
13.uPA、P一选择素、nm23和p27中2个或2个以上基因表达异常的病例与基因
表达阴性或只有一个基因表达异常者相比，在癌浸润深度、淋巴结转移、肿瘤大
小、大体类型、组织学分级方面差异显著(P<0 .05或P<0.01)。
〔结论〕
1.在食管鳞癌的发生过程中，uPA、P一选择素的活性在正常食管组织中呈现低表
达，随着病变的加重，uPA及P一选择素活性依次显著增高，提示uPA及P一选择
素参与了食管癌的发生、发展，uPA及P一选择素的激活是食管癌的早期事件。uPA
及P一选择素有望成为食管癌的病情监测及早期诊断的生物学指标。
2.nm23及p27的活性在正常食管组织呈现高表达，随着病变的加重，nm23及p27
的活性显著降低，提示 nm23及p27参与了食管癌的发生发展，nm23及p27的失
活是食管癌的早期事件。
3.uPA mRNA的表达与食管鳞癌组织学分级、肿瘤大小、浸润深度和淋巴结转移
有关;uPA蛋白的表
[Background and objective]:The esophageal carcinoma is an one of the most familiar malignant tumor of our countries, it threatens seriously people life health. Cancerous occurrence in oesophagus development is tumor proliferation that the result that a many factors participates to turn into with many stages, its gradually, transfer but cause is an important factor to cause patient die. The research expresses that tumor start up invasion and metastasis because proteinase which is excreted by tumor cell separate Extracelluar Matrix. The connection of plasminogen's activation and tumor's invasion and metastasis is the most closely. Moreover, Cell adhesion molecules is also important to tumor's invasion and metastasis. Up to the present, there are very few studies of the correlation of uPA,P-selectin,p27 to the characters of clinical pathology of esophageal carcinoma, the study of the correlation of uPA, P- selectin, nm23, p27 in the esophageal squamous cell carcinoma is even more few. It provide a theoretic fou
ndation for that unite examine uPA, P- selectin, nm23, p27 to find the meaning in invasion and metastasis of esophageal squamous cell carcinoma, in addition, it also tell us that restrain activation of uPA or P- selectin and increase activation of nm23, p27 is likely to a new therapy method of esophageal carcinoma.
[ Materials and methods]: 54 cases of esophageal carcinoma were collected in tumor hospital of Anyang City Henan province. All tissues were identified by pathologist, it is entirely squamous carcinoma. 15 cases are I rank,30 cases are II rank, 9 cases are III rank. 21 example appeared the lymph node metastasis, each all in the site of cancer, cancer beside and far normal mucoma cut a piece of tissue. In situ hybridization and immunohistochemistry was used to analyze the expression of uPA, P- selectin, nm23 and p27 in normal esophageal mucoma, esophageal squamous cell carcinoma and atypical hyperplasia. Data were performed with SPSS 10.0 software. Chi-square test was used and statistically significant level was considered as "alpha equals 0.05".
[Results]
1. The positive staining of uPA mRNA in 54 cases esophageal squamous cell carcinoma was located at cytoplasm of neoplasm, it's expression had significant difference in histology classification, tumor size, invasion depth and lymph node metastasis group ( P<0.05 ) ; The positive staining of uPA protein in 54 cases esophageal squamous cell carcinoma was located at cytoplasm of neoplasm, it's expression had significant difference in invasion depth and lymph node metastasis group ( P<0.05 ) .
2. The rates of uPA mRNA positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 70.4%(38/54), 40.9%(9/22), 11.1% (6/54) , each other compared in three group had all significant difference (P<0.05 ) .
3. The rates of uPA protein positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 66.7% (36/54), 36.4%(8/22), 14.8%(8/54) , each other compared in three group had all significant difference ( P<0.05 ) .
4. The positive staining of P- selectin mRNA in 54 cases esophageal squamous cell carcinoma was located at cytoplasm of neoplasm, it's expression had significant difference in histology classification, invasion depth and lymph node metastasis group
(P<0.05) ; The positive staining of P- selectin protein in 54 cases esophageal
squamous cell carcinoma was located at cytoplasm and cytomembrane of neoplasm, it's expression had significant difference in invasion depth and lymph node metastasis group ( P<0.05 ) .
5. The rates of P- selectin mRNA positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 59.3% (32/54)
31.8% (7/22), 9.3% ( 5/54) , each other compared in three group had all significant difference ( P<0.05 ) .
6. The rates of P- selectin protein positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 66.7% (36/54). 40.9
[材料与方法]：收集河南省安阳市肿瘤医院2003年8-9月份手术切除标本54例，病理证实全部为鳞状细胞癌，其中Ⅰ级15例，Ⅱ级30例，Ⅲ级9例，发生淋巴结转移的有21例。每例均在癌灶、(?)癌旁(?)组织及远端正常粘膜处分别取材。运用原位杂交和免疫组织化学方法对54例食管鳞癌组织、22例癌旁不典型增生组织及54例正常粘膜中uPA和P-选择素的mRNA及蛋白的表达、nm23 mRNA的表达和p27蛋白的表达进行了系统检测及观察。统计学采用x~2检验对资料进行分析，以α=0.05为显著性检验水准。
[结果]
郑州大学2(X)4硕士毕业论文
食管鳞癌中uPA、P一选择素、nm23、p27的表达及其与浸润转移关系的研究
1.54例食管鳞癌组织中uPA mRNA阳性表达主要位于细胞胞浆内，在组织学分级、
大小、浸润深度和有无转移的不同组别间的表达其差异具有显著性(P<0.05);
uPA蛋白阳性表达位于胞浆，其表达在不同浸润深度，有无转移的肿瘤之间有显
著差异性(P<0.05)。
2.食管鳞癌、癌旁不典型增生、正常食管粘膜组织中uPA mRNA阳性表达率分别
是70.4%(38/54)、40.9%(9/22)、1 1.1%(6/54)，三组间两两比较差异均有显著
，胜(P<0 .05)。
3.食管鳞癌、癌旁不典型增生、正常食管粘膜组织中uPA蛋白阳性表达率分别是
66.7%(36/54)、36.4%(8/22)、14.8%(8/54)，三组f’ed两两比较差异均有显著性
(P(0 .05)。
4.54例食管鳞癌组织中P一选择素mRNA阳性表达主要位于细胞胞浆，其表达与组
织学分级、浸润深度、淋巴结转移有关，差异具有显著性(P<0 .05);P一选择素
蛋白的阳性表达位于细胞胞浆及胞膜上，其表达与浸润深度，淋巴结转移有关，
差异具有显著性(P(0.05)。
5.食管鳞癌、癌旁不典型增生、正常食管组织中P一选择素mRNA的阳性表达率分
别为59.3%(32/54)、31.8%(7/22)、9.3%(5/54)，三组间两两比较差异均有显
著性(P(0.05)。
6.食管鳞癌、癌旁不典型增生、正常食管组织中P一选择素蛋白的阳性表达率分
别为66.7%(36/54)、40.9%(9/22)、14.8%(8/54)，三组间两两比较差异均有显
著性(P(0.05)。
7.食管鳞癌、癌旁不典型增生、正常食管组织中nm23 mRNA的阳性表达率分别为
35.2%(19/54)、63.6%(14/22)、85.2%(46/54)，三组间两两比较差异均有显著
性(P<0 .05)。nm23 mRNA的表达位于细胞胞浆，其表达与浸润深度、淋巴结转
移有关，差异具有显著性(P<0.05)。
8.食管鳞癌、癌旁不典型增生、正常食管组织中p27蛋白的阳性表达率分别为
31.5%(17/54)、59.1%(13/22)、81.5%(44/54)，三组间两两比较差异均有显著性
(P<0.05)。P27蛋白的表达位于细胞胞核内，胞浆和胞膜亦可见着色。其表达
与浸润深度、淋巴结转移有关，具差异有显著性差异(P(0 .05)。
9.uPA mRNA表达与蛋白表达之间差异无显著性(P>0 .05);P一选择素mRNA表达
郑州大学2以孙硕士毕业论文
食管鳞癌中uPA、P选择素、nm23、p27的表达及其与浸润转移关系的研究
与蛋白表达之间有显著性差异(P<0.05)。
10.uPA mRNA的表达与P一选择素mRNA的表达具有相关性(P<0.05);uPA蛋白的
表达与P一选择素蛋白的表达无相关性(P> .05)。
11.nm23 mRNA与uPA mRNA的表达和P一选择素mRNA的表达均具有相关性
(P<0.05);与uPA蛋白的表达和P一选择素蛋白的表达均无相关性(P>.05)。
12.p27蛋白的表达与uPA mRNA和蛋白的表达、P一选择素mRNA和蛋白的表达以
及nm23 mRNA的表达之间均无相关性(P)0.05)。
13.uPA、P一选择素、nm23和p27中2个或2个以上基因表达异常的病例与基因
表达阴性或只有一个基因表达异常者相比，在癌浸润深度、淋巴结转移、肿瘤大
小、大体类型、组织学分级方面差异显著(P<0 .05或P<0.01)。
〔结论〕
1.在食管鳞癌的发生过程中，uPA、P一选择素的活性在正常食管组织中呈现低表
达，随着病变的加重，uPA及P一选择素活性依次显著增高，提示uPA及P一选择
素参与了食管癌的发生、发展，uPA及P一选择素的激活是食管癌的早期事件。uPA
及P一选择素有望成为食管癌的病情监测及早期诊断的生物学指标。
2.nm23及p27的活性在正常食管组织呈现高表达，随着病变的加重，nm23及p27
的活性显著降低，提示 nm23及p27参与了食管癌的发生发展，nm23及p27的失
活是食管癌的早期事件。
3.uPA mRNA的表达与食管鳞癌组织学分级、肿瘤大小、浸润深度和淋巴结转移
有关;uPA蛋白的表
[Background and objective]:The esophageal carcinoma is an one of the most familiar malignant tumor of our countries, it threatens seriously people life health. Cancerous occurrence in oesophagus development is tumor proliferation that the result that a many factors participates to turn into with many stages, its gradually, transfer but cause is an important factor to cause patient die. The research expresses that tumor start up invasion and metastasis because proteinase which is excreted by tumor cell separate Extracelluar Matrix. The connection of plasminogen's activation and tumor's invasion and metastasis is the most closely. Moreover, Cell adhesion molecules is also important to tumor's invasion and metastasis. Up to the present, there are very few studies of the correlation of uPA,P-selectin,p27 to the characters of clinical pathology of esophageal carcinoma, the study of the correlation of uPA, P- selectin, nm23, p27 in the esophageal squamous cell carcinoma is even more few. It provide a theoretic fou
ndation for that unite examine uPA, P- selectin, nm23, p27 to find the meaning in invasion and metastasis of esophageal squamous cell carcinoma, in addition, it also tell us that restrain activation of uPA or P- selectin and increase activation of nm23, p27 is likely to a new therapy method of esophageal carcinoma.
[ Materials and methods]: 54 cases of esophageal carcinoma were collected in tumor hospital of Anyang City Henan province. All tissues were identified by pathologist, it is entirely squamous carcinoma. 15 cases are I rank,30 cases are II rank, 9 cases are III rank. 21 example appeared the lymph node metastasis, each all in the site of cancer, cancer beside and far normal mucoma cut a piece of tissue. In situ hybridization and immunohistochemistry was used to analyze the expression of uPA, P- selectin, nm23 and p27 in normal esophageal mucoma, esophageal squamous cell carcinoma and atypical hyperplasia. Data were performed with SPSS 10.0 software. Chi-square test was used and statistically significant level was considered as "alpha equals 0.05".
[Results]
1. The positive staining of uPA mRNA in 54 cases esophageal squamous cell carcinoma was located at cytoplasm of neoplasm, it's expression had significant difference in histology classification, tumor size, invasion depth and lymph node metastasis group ( P<0.05 ) ; The positive staining of uPA protein in 54 cases esophageal squamous cell carcinoma was located at cytoplasm of neoplasm, it's expression had significant difference in invasion depth and lymph node metastasis group ( P<0.05 ) .
2. The rates of uPA mRNA positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 70.4%(38/54), 40.9%(9/22), 11.1% (6/54) , each other compared in three group had all significant difference (P<0.05 ) .
3. The rates of uPA protein positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 66.7% (36/54), 36.4%(8/22), 14.8%(8/54) , each other compared in three group had all significant difference ( P<0.05 ) .
4. The positive staining of P- selectin mRNA in 54 cases esophageal squamous cell carcinoma was located at cytoplasm of neoplasm, it's expression had significant difference in histology classification, invasion depth and lymph node metastasis group
(P<0.05) ; The positive staining of P- selectin protein in 54 cases esophageal
squamous cell carcinoma was located at cytoplasm and cytomembrane of neoplasm, it's expression had significant difference in invasion depth and lymph node metastasis group ( P<0.05 ) .
5. The rates of P- selectin mRNA positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 59.3% (32/54)
31.8% (7/22), 9.3% ( 5/54) , each other compared in three group had all significant difference ( P<0.05 ) .
6. The rates of P- selectin protein positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 66.7% (36/54). 40.9
引文
[1]Ribeiro U Jr, Posner MC, Safatle-Ribeiro AV, et al. Risk factors for squamous cell carcinoma of the oesophagus. Br J Surg. 1996;83(9):1174-85
[2]李连弟，鲁凤珠．全国恶性肿瘤死亡抽样调查报告．中国肿瘤，1996；5(1)：3-7
[3]Hart DA, Rehemtulla A. Plasminogen activators and their inhibitors: regulators of extracellular proteolysis and cell function. Comp Biochem Physiol B. 1988;90(4):691-708
[4]Reuning U, Magdolen V, Wilhelm O, et al. Multifunctional potential of the plasminogen activation system in tumor invasion and metastasis. Int J Oncol. 1998;13(5):893-906
[5]Andreasen PA, Egelund R, Petersen HH. The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci. 2000;57(1):25-40
[6]Matsuura N, Katsumoto Y, Takeda T, et al. Cell adhesion in cancer and immunology. Biotherapy. 1993;7(5):1552
[7]Okusa Y, Ichikura T, Mochizuki H. Prognostic impact of stromal cell-derived urokinase-type plasminogen activator in gastric carcinoma. Cancer. 1999;85(5):1033-8
[8]陈金联，周同．选择素与肿瘤转移研究进展．生命科学．1996；8(1)：31
[9]Nourse J, Firpo E, Flanagan WM, et al. Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. Nature. 1994;372(6506):570-3
[10]Peng D, Fan Z, Lu Y, et al. Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145.Cancer Res. 1996;56(16):3666-9
[11]Jin L, Qian X, Kulig E, et al. Transforming growth factor-beta, transforming growth factor-beta receptor Ⅱ, and p27Kip1 expression in nontumorous and neoplastic human pituitaries. Am J Pathol. 1997;151(2):509-19
[12]Yasui W, Kudo Y, Semba S, et al. Reduced expression of cyclin-dependent kinase inhibitor p27Kip1 is associated with advanced stage and invasiveness of gastric
carcinomas.Jpn J Cancer Res. 1997;88(7):625-9
[13]Tam P, Cavalla P, Piva R, et al. p27/KIP1 expression in mastocarcinoma and its possible prognostic role. Cancer Res, 1997;57(6):1259
[14]Thapar K, Kovacs K, Stefaneanu L, et al. Overexpression of the growth-hormone-releasing hormone gene in acromegaly-associated pituitary tumors. An event associated with neoplastic progression and aggressive behavior. Am J Pathol. 1997;151(3):769-84
[15]Takeuchi S, Koeffler HP, Hinton DR, et al. Mutation and expression analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in pituitary tumors. J Endocrinol. 1998;157(2):337-41
[16]Steeg PS, Cohn KH, Leone A. Tumor metastasis and nm23: current concepts. Cancer Cells. 1991;3(7):257-62
[17]Singh SP, Lipman J, Goldman H, et al. Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma. Cancer Res. 1998;58(8):1730-5
[18]Fero ML, Randel E, Gurley KE, et al. The murine gene p27Kip1 is haplo-insufficient for tumour suppression. Nature. 1998;396(6707):177-80
[19]Rao J, Eu K W, seow-chien F, et al. Down-regulation of p27 is a significant predictor of poor overall survival and may facilitate metastasis in colorectal carcinomas. Int. J Cancer. 2000;89(3):213-216
[20]Rajput B, Degen SF, Reich E, et al. Chromosomal locations of human tissue plasminogen activator and urokinase genes. Science. 1985;230(4726):672-4
[21]Pannell R, Gurewich V. Activation of plasminogen by single-chain urokinase or by two-chain urokinase--a demonstration that single-chain urokinase has a low catalytic activity (pro-urokinase). Blood. 1987,69(1):22-6
[22]Appella E, Robinson EA, Ullrich SJ, et al. The receptor-binding sequence of urokinase. A biological function for the growth-factor module of proteases.J Biol Chem. 1987;262(10):4437-40
[23]Patthy L Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules.Cell. 1985;41(3):657-63
[24]Bowen RM, Hoidal JR, Estensen RD. Urokinase-type plasrninogen activator in
alveolar macrophages and bronchoalveolar lavage fluid from normal and smoke-exposed hamsters and humans.J Lab Clin Med. 1985;106(6):667-73
[25]Roldan AL, Cubellis MV, Masucci MT, et al. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis.EMBO J. 1990;9(2):467-74
[26]Astedt B, Holmberg L. Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture.Nature. 1976;261(5561):595-7
[27]Vaheri A, Stephens RW, Salonen EM, et al. Plasminogen activation at the cell surface-matrix interface.Cell Differ Dev. 1990;32(3):255-62
[28]Duffy MJ, O'Grady P, Devaney D, et al. Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report.Cancer. 1988;62(3):531-3
[29]Foekens JA, Peters HA, Look MP, et al The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients.Cancer Res. 2000;60(3):636-43
[30]Cao Y, Veitonmaki N, Keough K, et al. Elevated levels of urine angiostatin and plasminogen/plasmin in cancer patients.Int J Mol Med. 2000;5(5):547-51
[31]Casslen B, Bossmar T, Lecander I, et al. Plasminogen activators and plasminogen activator inhibitors in blood and tumour fluids of patients with ovarian cancer.Eur J Cancer. 1994;(9):1302-9
[32]Farinati F, Herszenyi L, Plebani M, et al. Increased levels of cathepsin B and L, urokinase-type plasminogen activator and its inhibitor type-1 as an early event in gastric carcinogenesis.Carcinogenesis. 1996;17(12):2581-7
[33]Yamamoto M, Sawaya R, Mohanam S, et al. Expression and localization of urokinase-type plasminogen activator in human astrocytomas in vivo.Cancer Res. 1994;54(14):3656-61
[34]孙达春，刘文励．恶性肿瘤患者血液中尿激酶型纤溶酶原激活系统测定的临床意义．临床内科杂志．2000；3(2)：157-8
[35]郑起，汤钊猷，吴志全，等．尿激酶型纤溶酶原激活物及其特异受体和抑制物
与肝细胞癌浸润转移及预后．中华肿瘤杂志．1998；20(1)：57-59
[36]陈淑勤，黄培生，李一伟，等．尿激酶型纤溶原激活物在鼻咽癌的表达及临床意义．福建医科大学学报．2002；1：36-38
[37]肖继平，张广德，夏广华，等．乳腺癌中尿激酶型纤溶酶原激活物的过度表达．[J]实用癌症杂志．1999；14(4)：261-2
[38]杨进益，李韶，周荣祥，等．尿激酶型纤溶原激活物及其受体在膀胱移行细胞癌中表达的意义．中华泌尿外科杂志．2000；8：465-6
[39]孟春城，陈孝平，刘安重．肝细胞癌门静脉主干癌栓UPA和UPAR基因表达．肝胆外科杂志．2002；10(2)：148-50
[40]刘大林，陈国玉，夏建国，等．尿激酶型纤溶原激活物于胃癌侵袭及转移关系的研究．南京医科大学学报．2001；5(5)：393-5
[41]杨春花，谷志远，郝好杰，等．Northern印迹杂交检测胃癌组织中UPA和UPAR mRNA表达及其意义．军医进修学院学报．2000；1(1)：45-7
[42]陈卫昌，严辉，彭群新，等．胃癌患者血清UPA测定及临床意义．苏州医学院学报．2001；21(4)：440-2
[43]汤文浩，李国强，王凤臣，等．食管癌组织中纤溶成份的表达及其意义．中华消化杂志．2000；20(2)：85-8
[44]Johnston G I, Cook R G, Mcever R P. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation.Cell. 1989;56(6):1033-44
[45]Dunlop LC, Skinner MP, Bendall LJ, et al. Characterization of GMP-140 (P-selectin) as a circulating plasma protein.J Exp Med. 1992;175(4):1147-50
[46]Lip GY, Blann AD, Zarifis J, et al. Soluble adhesion molecule P-selectin and endothelial dysfunction in essential hypertension: implications for atherogenesis? A preliminary report.J Hypertens. 1995;13(5):1674-8
[47]Kim YJ, Borsig L, Varki NM, et al. P-selectin deficiency attenuates tumor growth and metastasis.Proc Natl Acad Sci U S A. 1998;95(16):9325-30
[48]Schadendorf D, Diehl S, Zuberbier T, et al. Quantitative detection of soluble adhesion molecules in sera of melanoma patients correlates with clinical stage.Dermatology. 1996;192(2):89-93
[49]黄耀庭，马天乐．CD62P在结直肠癌患者组织及血浆中的表达．胃肠病学．2000；3(2)：161-3
[50]刘剑勇，覃宇周，陈汉华，等．直肠癌患者手术前后血浆可溶性P-选择素的水平及意义．中国肝肠病杂志．2002；22(2)：14-6
[51]官成浓，徐军发，银正民．中晚期原发性肝癌患者血浆可溶性P-选择素的测定及临床意义．癌症．2000；19(3)：256-8
[52]官成浓，银正民，徐军发．血浆可溶性P-选择素的临床应用价值．实用癌症杂志．2001；16(3)：295-6
[53]周同，王玲玲，陈金联，等．P-选择素在几种恶性肿瘤中表达的临床意义．上海免疫学杂志．2000；20(4)：236-8
[54]陈金联，张月星，储榆德，等．粘附分子P-选择素单克隆抗体抑制胃癌转移的实验研究．中华医学杂志．1998；78(6)：437-9
[55]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)：520-2
[56]Steeg PS, Bevilacqua G, Kopper L, et al. Evidence for a novel gene associated with low tumor metastatic potential.J Natl Cancer Inst. 1988;80(3):200-4
[57]Rosengard AM, Krutzsch HC, Shearn A, et al. Reduced nm23/Awd protein in tumour metastasis and aberrant Drosophila development.Nature. 1989;342(6246): 177-80
[58]Urano T, Furukawa K, Shiku H. Expression of nm23/NDP kinase proteins on the cell surface.Oncogene. 1993;8(5):1371-6
[59]Leone A, Flatow U, VanHoutte K, et al. Transfection of human nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potential, colonization and enzymatic activity.Oncogene. 1993;8(9):2325-33
[60]Howlett AR, Petersen OW, Steeg PS, et al. A novel function for the nm23-H1 gene: overexpression in human breast carcinoma cells leads to the formation of basement membrane and growth arrest.J Natl Cancer Inst. 1994;86(24):1838-44
[61]Lee CS, Pirdas-Zivcic A. nm23-H1 protein immunoreactivity in cancers of the gallbladder, extrahepatic bile ducts and ampulla of Vater.Pathology. 1994;26(4):448-52
[62]邬剑华，王鲁，蔡端．胆囊癌c-erbB-2和nm23H-1产物的临床意义．肿瘤．1999；19(2)：115-7
[63]Berney CR, Yang JL, Fisher RJ, et al. Overexpression of nm23 protein assessed by color video image analysis in metastatic colorectal cancer: correlation with reduced patient survival.World J Surg. 1998;22(5):484-90
[64]Mori M, Mimori K, Tanaka S, et al. Prognostic factors of colon cancer from a molecular biology standpoint. Can to Kagaku Ryoho. 1996;23(8):982-6
[65]Urano T, Furukawa K, Shiku H. Expression of nm23/NDP kinase proteins on the cell surface.Oncogene. 1993;8(5):1371-6
[66]Nakamori S, Ishikawa O, Ohigashi H, et al. Clinicopathological features and prognostic significance of nucleoside diphosphate kinase/nm23 gene product in human pancreatic exocrine neoplasms.Int J Pancreatol. 1993;14(2):125-33
[67]Pulido-Cejudo G, Slack R, Hebert RL, et al. Effect of retinoic acid on Nm/23 nucleoside diphosphate kinase and components of cyclic adenosine monophosphate-dependent signalling in human neuroblastoma cell lines.Biochim Biophys Acta. 1995;1266(2):201-6
[68]Cohn KH, Ornstein DL, Wang F, et al. The significance of allelic deletions and aneuploidy in colorectal carcinoma. Results of a 5-year follow-up study.Cancer. 1997;79(2):233-44
[69]Wang CS, Lin KH, Hsu YC, et al. Distant metastasis of gastric cancer is associated with elevated expression of the antimetastatic nm23 gene.Cancer Lett. 1998;128(1):23-9
[70]Lin LI, Lee PH, Wu CM, et al. Significance of nm23 mRNA expression in human hepatocellular carcinoma.Anticancer Res. 1998;18(1):541-6
[71]Greco IM, Calvisi G, Ventura L, et al. An immunohistochemical analysis of nm23 gene product expression in uveal melanoma.Melanoma Res. 1997;7(3):231-6
[72]Kawakubo Y, Sato Y, Koh T, et al. Expression of nm23 protein in pulmonary adenocarcinomas: inverse lorrelation to tumor progression.Lung Cancer. 1997;17(1):103-13
[73]Bosnar N. Loss of heterozygosity of the nm23H_1 gene in human renal cell carcinomas. J Cancer Res Clin Oncol. 1997;123(9):485-8
[74]Sauer j, Furu I, Beraki K, et al. nm23 protein expression in fine needle aspirates from breast carcinoma: inverse correlation with cytologic grading, lymph node status and ploidy. Cancer, 1998;84(2):109-14
[75]Kanitakis J, Euvrard S, Bourchany D, et al. Expression of the nm23 metastasis-suppressor gene product in skin tumors.J Cutan Pathol. 1997;24(3):151-6
[76]Sarac E, Ayhan A, Ertoy D, et al. nm23 expression in carcinoma of the uterine cervix.Eur J Gynaecol Oncol. 1998;19(3):312-5
[77]Masaki T, Takanori A, Yasunori M, et al. Expression of nm23H_1 gene product in esophageal squamous cell carcinoma and its association with vessel in vasion and survival. Cancer.2001;1(1):3-8
[78]Sarbia M, Porschen R, Borchard F, et al. Incidence and prognostic significance of vascular and neural invasion in squamous cell carcinomas of the esophagus.Int J Cancer. 1995;61(3):333-6
[79]Spirin KS, Simpson JF, Takeuchi S, et al. p27/Kip1 mutation found in breast cancer.Cancer Res. 1996;56(10):2400-4
[80]Kawamata N, Morosetti R, Miller CW, et al. Molecular analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in human malignancies.Cancer Res. 1995;55(11):2266-9
[81]Polyak K, Kato JY, Solomon MJ, et al p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.Genes. 1994;8(1):9-22
[82]Polyak K, Lee MH, Erdjument-Bromage H, et al. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.Cell. 1994;78(1):59-66
[83]Jellinek M, Castaneda M, Garvin PJ, et al Oxidation-reduction maintenance in organ preservation.Arch Surg. 1985;120(4):439-42
[84]Pietenpol JA, Bohlander SK, Sato Y, et al. Assignment of the human p27Kip1
gene to 12p13 and its analysis in leukemias.Cancer Res. 1995;55(6):1206-10
[85]Liotta LA. Tumor invasion and metastases--role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res. 1986;46(1):1-7
[86]Albelda SM._Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest. 1993;68(1):4-17
[87]Pottratz ST, Hall TD, Scribner WM,et al. P-selectin-mediated attachment of small cell lung carcinoma to endothelial cells. Am J Physiol. 1996;271(6):918-23
[88]Rochefort H, Capony F, Garcia M. Cathepsin D in breast cancer: from molecular and cellular biology to clinical applications. Cancer Cells. 1990;2(12):383-8
[89]Ossowski L, Reich E. Antibodies to plasminogen activator inhibit human tumor metastasis. Cell. 1983;35(25):611-9
[90]Ossowski L, Russo-Payne H, Wilson EL. Inhibition of urokinase-type plasminogen activator by antibodies: the effect on dissemination of a human tumor in the nude mouse.Cancer Res. 1991;51(1):274-81
[91]Testa JE, Quigley JP. The role of urokinase-type plasminogen activator in aggressive tumor cell behavior. Cancer Metastasis Rev. 1990;9(4):353-67
[92]李节．尿激酶型纤溶酶原激活物与肿瘤的关系．国外医学分子生物学分册．1994；16(1)：26-8
[93]Kawano K, Aoki I, Aoki N, et al. Human platelet activation by thrombolytic agents: effects of tissue-type plasminogen activator and urokinase on platelet surface P- selectin expression.Am Heart J. 1998;135(6):268-71
[94]Salerno M, Ouatas T, Palmieri D, et al. Inhibition of signal transduction by the nm23 metastasis suppressor: possible mechanisms.Clin Exp Metastasis. 2003;20(1):3-10
[95]Belev B, Aleric I, Vrbanec D, et al. nm23 gene product expression in invasive breast cancer--immunohistochemical analysis and clinicopathological correlation.Acta Oncol. 2002;41(4):355-61
[96]Kauffman EC, Robinson VL, Stadler WM, et al. Metastasis suppression: the evolving role of metastasis suppressor genes for regulating cancer cell growth at the secondary site.J Urol. 2003;169(3):1122-33
[2]李连弟，鲁凤珠．全国恶性肿瘤死亡抽样调查报告．中国肿瘤，1996；5(1)：3-7
[3]Hart DA, Rehemtulla A. Plasminogen activators and their inhibitors: regulators of extracellular proteolysis and cell function. Comp Biochem Physiol B. 1988;90(4):691-708
[4]Reuning U, Magdolen V, Wilhelm O, et al. Multifunctional potential of the plasminogen activation system in tumor invasion and metastasis. Int J Oncol. 1998;13(5):893-906
[5]Andreasen PA, Egelund R, Petersen HH. The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci. 2000;57(1):25-40
[6]Matsuura N, Katsumoto Y, Takeda T, et al. Cell adhesion in cancer and immunology. Biotherapy. 1993;7(5):1552
[7]Okusa Y, Ichikura T, Mochizuki H. Prognostic impact of stromal cell-derived urokinase-type plasminogen activator in gastric carcinoma. Cancer. 1999;85(5):1033-8
[8]陈金联，周同．选择素与肿瘤转移研究进展．生命科学．1996；8(1)：31
[9]Nourse J, Firpo E, Flanagan WM, et al. Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. Nature. 1994;372(6506):570-3
[10]Peng D, Fan Z, Lu Y, et al. Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145.Cancer Res. 1996;56(16):3666-9
[11]Jin L, Qian X, Kulig E, et al. Transforming growth factor-beta, transforming growth factor-beta receptor Ⅱ, and p27Kip1 expression in nontumorous and neoplastic human pituitaries. Am J Pathol. 1997;151(2):509-19
[12]Yasui W, Kudo Y, Semba S, et al. Reduced expression of cyclin-dependent kinase inhibitor p27Kip1 is associated with advanced stage and invasiveness of gastric
carcinomas.Jpn J Cancer Res. 1997;88(7):625-9
[13]Tam P, Cavalla P, Piva R, et al. p27/KIP1 expression in mastocarcinoma and its possible prognostic role. Cancer Res, 1997;57(6):1259
[14]Thapar K, Kovacs K, Stefaneanu L, et al. Overexpression of the growth-hormone-releasing hormone gene in acromegaly-associated pituitary tumors. An event associated with neoplastic progression and aggressive behavior. Am J Pathol. 1997;151(3):769-84
[15]Takeuchi S, Koeffler HP, Hinton DR, et al. Mutation and expression analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in pituitary tumors. J Endocrinol. 1998;157(2):337-41
[16]Steeg PS, Cohn KH, Leone A. Tumor metastasis and nm23: current concepts. Cancer Cells. 1991;3(7):257-62
[17]Singh SP, Lipman J, Goldman H, et al. Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma. Cancer Res. 1998;58(8):1730-5
[18]Fero ML, Randel E, Gurley KE, et al. The murine gene p27Kip1 is haplo-insufficient for tumour suppression. Nature. 1998;396(6707):177-80
[19]Rao J, Eu K W, seow-chien F, et al. Down-regulation of p27 is a significant predictor of poor overall survival and may facilitate metastasis in colorectal carcinomas. Int. J Cancer. 2000;89(3):213-216
[20]Rajput B, Degen SF, Reich E, et al. Chromosomal locations of human tissue plasminogen activator and urokinase genes. Science. 1985;230(4726):672-4
[21]Pannell R, Gurewich V. Activation of plasminogen by single-chain urokinase or by two-chain urokinase--a demonstration that single-chain urokinase has a low catalytic activity (pro-urokinase). Blood. 1987,69(1):22-6
[22]Appella E, Robinson EA, Ullrich SJ, et al. The receptor-binding sequence of urokinase. A biological function for the growth-factor module of proteases.J Biol Chem. 1987;262(10):4437-40
[23]Patthy L Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules.Cell. 1985;41(3):657-63
[24]Bowen RM, Hoidal JR, Estensen RD. Urokinase-type plasrninogen activator in
alveolar macrophages and bronchoalveolar lavage fluid from normal and smoke-exposed hamsters and humans.J Lab Clin Med. 1985;106(6):667-73
[25]Roldan AL, Cubellis MV, Masucci MT, et al. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis.EMBO J. 1990;9(2):467-74
[26]Astedt B, Holmberg L. Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture.Nature. 1976;261(5561):595-7
[27]Vaheri A, Stephens RW, Salonen EM, et al. Plasminogen activation at the cell surface-matrix interface.Cell Differ Dev. 1990;32(3):255-62
[28]Duffy MJ, O'Grady P, Devaney D, et al. Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report.Cancer. 1988;62(3):531-3
[29]Foekens JA, Peters HA, Look MP, et al The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients.Cancer Res. 2000;60(3):636-43
[30]Cao Y, Veitonmaki N, Keough K, et al. Elevated levels of urine angiostatin and plasminogen/plasmin in cancer patients.Int J Mol Med. 2000;5(5):547-51
[31]Casslen B, Bossmar T, Lecander I, et al. Plasminogen activators and plasminogen activator inhibitors in blood and tumour fluids of patients with ovarian cancer.Eur J Cancer. 1994;(9):1302-9
[32]Farinati F, Herszenyi L, Plebani M, et al. Increased levels of cathepsin B and L, urokinase-type plasminogen activator and its inhibitor type-1 as an early event in gastric carcinogenesis.Carcinogenesis. 1996;17(12):2581-7
[33]Yamamoto M, Sawaya R, Mohanam S, et al. Expression and localization of urokinase-type plasminogen activator in human astrocytomas in vivo.Cancer Res. 1994;54(14):3656-61
[34]孙达春，刘文励．恶性肿瘤患者血液中尿激酶型纤溶酶原激活系统测定的临床意义．临床内科杂志．2000；3(2)：157-8
[35]郑起，汤钊猷，吴志全，等．尿激酶型纤溶酶原激活物及其特异受体和抑制物
与肝细胞癌浸润转移及预后．中华肿瘤杂志．1998；20(1)：57-59
[36]陈淑勤，黄培生，李一伟，等．尿激酶型纤溶原激活物在鼻咽癌的表达及临床意义．福建医科大学学报．2002；1：36-38
[37]肖继平，张广德，夏广华，等．乳腺癌中尿激酶型纤溶酶原激活物的过度表达．[J]实用癌症杂志．1999；14(4)：261-2
[38]杨进益，李韶，周荣祥，等．尿激酶型纤溶原激活物及其受体在膀胱移行细胞癌中表达的意义．中华泌尿外科杂志．2000；8：465-6
[39]孟春城，陈孝平，刘安重．肝细胞癌门静脉主干癌栓UPA和UPAR基因表达．肝胆外科杂志．2002；10(2)：148-50
[40]刘大林，陈国玉，夏建国，等．尿激酶型纤溶原激活物于胃癌侵袭及转移关系的研究．南京医科大学学报．2001；5(5)：393-5
[41]杨春花，谷志远，郝好杰，等．Northern印迹杂交检测胃癌组织中UPA和UPAR mRNA表达及其意义．军医进修学院学报．2000；1(1)：45-7
[42]陈卫昌，严辉，彭群新，等．胃癌患者血清UPA测定及临床意义．苏州医学院学报．2001；21(4)：440-2
[43]汤文浩，李国强，王凤臣，等．食管癌组织中纤溶成份的表达及其意义．中华消化杂志．2000；20(2)：85-8
[44]Johnston G I, Cook R G, Mcever R P. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation.Cell. 1989;56(6):1033-44
[45]Dunlop LC, Skinner MP, Bendall LJ, et al. Characterization of GMP-140 (P-selectin) as a circulating plasma protein.J Exp Med. 1992;175(4):1147-50
[46]Lip GY, Blann AD, Zarifis J, et al. Soluble adhesion molecule P-selectin and endothelial dysfunction in essential hypertension: implications for atherogenesis? A preliminary report.J Hypertens. 1995;13(5):1674-8
[47]Kim YJ, Borsig L, Varki NM, et al. P-selectin deficiency attenuates tumor growth and metastasis.Proc Natl Acad Sci U S A. 1998;95(16):9325-30
[48]Schadendorf D, Diehl S, Zuberbier T, et al. Quantitative detection of soluble adhesion molecules in sera of melanoma patients correlates with clinical stage.Dermatology. 1996;192(2):89-93
[49]黄耀庭，马天乐．CD62P在结直肠癌患者组织及血浆中的表达．胃肠病学．2000；3(2)：161-3
[50]刘剑勇，覃宇周，陈汉华，等．直肠癌患者手术前后血浆可溶性P-选择素的水平及意义．中国肝肠病杂志．2002；22(2)：14-6
[51]官成浓，徐军发，银正民．中晚期原发性肝癌患者血浆可溶性P-选择素的测定及临床意义．癌症．2000；19(3)：256-8
[52]官成浓，银正民，徐军发．血浆可溶性P-选择素的临床应用价值．实用癌症杂志．2001；16(3)：295-6
[53]周同，王玲玲，陈金联，等．P-选择素在几种恶性肿瘤中表达的临床意义．上海免疫学杂志．2000；20(4)：236-8
[54]陈金联，张月星，储榆德，等．粘附分子P-选择素单克隆抗体抑制胃癌转移的实验研究．中华医学杂志．1998；78(6)：437-9
[55]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)：520-2
[56]Steeg PS, Bevilacqua G, Kopper L, et al. Evidence for a novel gene associated with low tumor metastatic potential.J Natl Cancer Inst. 1988;80(3):200-4
[57]Rosengard AM, Krutzsch HC, Shearn A, et al. Reduced nm23/Awd protein in tumour metastasis and aberrant Drosophila development.Nature. 1989;342(6246): 177-80
[58]Urano T, Furukawa K, Shiku H. Expression of nm23/NDP kinase proteins on the cell surface.Oncogene. 1993;8(5):1371-6
[59]Leone A, Flatow U, VanHoutte K, et al. Transfection of human nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potential, colonization and enzymatic activity.Oncogene. 1993;8(9):2325-33
[60]Howlett AR, Petersen OW, Steeg PS, et al. A novel function for the nm23-H1 gene: overexpression in human breast carcinoma cells leads to the formation of basement membrane and growth arrest.J Natl Cancer Inst. 1994;86(24):1838-44
[61]Lee CS, Pirdas-Zivcic A. nm23-H1 protein immunoreactivity in cancers of the gallbladder, extrahepatic bile ducts and ampulla of Vater.Pathology. 1994;26(4):448-52
[62]邬剑华，王鲁，蔡端．胆囊癌c-erbB-2和nm23H-1产物的临床意义．肿瘤．1999；19(2)：115-7
[63]Berney CR, Yang JL, Fisher RJ, et al. Overexpression of nm23 protein assessed by color video image analysis in metastatic colorectal cancer: correlation with reduced patient survival.World J Surg. 1998;22(5):484-90
[64]Mori M, Mimori K, Tanaka S, et al. Prognostic factors of colon cancer from a molecular biology standpoint. Can to Kagaku Ryoho. 1996;23(8):982-6
[65]Urano T, Furukawa K, Shiku H. Expression of nm23/NDP kinase proteins on the cell surface.Oncogene. 1993;8(5):1371-6
[66]Nakamori S, Ishikawa O, Ohigashi H, et al. Clinicopathological features and prognostic significance of nucleoside diphosphate kinase/nm23 gene product in human pancreatic exocrine neoplasms.Int J Pancreatol. 1993;14(2):125-33
[67]Pulido-Cejudo G, Slack R, Hebert RL, et al. Effect of retinoic acid on Nm/23 nucleoside diphosphate kinase and components of cyclic adenosine monophosphate-dependent signalling in human neuroblastoma cell lines.Biochim Biophys Acta. 1995;1266(2):201-6
[68]Cohn KH, Ornstein DL, Wang F, et al. The significance of allelic deletions and aneuploidy in colorectal carcinoma. Results of a 5-year follow-up study.Cancer. 1997;79(2):233-44
[69]Wang CS, Lin KH, Hsu YC, et al. Distant metastasis of gastric cancer is associated with elevated expression of the antimetastatic nm23 gene.Cancer Lett. 1998;128(1):23-9
[70]Lin LI, Lee PH, Wu CM, et al. Significance of nm23 mRNA expression in human hepatocellular carcinoma.Anticancer Res. 1998;18(1):541-6
[71]Greco IM, Calvisi G, Ventura L, et al. An immunohistochemical analysis of nm23 gene product expression in uveal melanoma.Melanoma Res. 1997;7(3):231-6
[72]Kawakubo Y, Sato Y, Koh T, et al. Expression of nm23 protein in pulmonary adenocarcinomas: inverse lorrelation to tumor progression.Lung Cancer. 1997;17(1):103-13
[73]Bosnar N. Loss of heterozygosity of the nm23H_1 gene in human renal cell carcinomas. J Cancer Res Clin Oncol. 1997;123(9):485-8
[74]Sauer j, Furu I, Beraki K, et al. nm23 protein expression in fine needle aspirates from breast carcinoma: inverse correlation with cytologic grading, lymph node status and ploidy. Cancer, 1998;84(2):109-14
[75]Kanitakis J, Euvrard S, Bourchany D, et al. Expression of the nm23 metastasis-suppressor gene product in skin tumors.J Cutan Pathol. 1997;24(3):151-6
[76]Sarac E, Ayhan A, Ertoy D, et al. nm23 expression in carcinoma of the uterine cervix.Eur J Gynaecol Oncol. 1998;19(3):312-5
[77]Masaki T, Takanori A, Yasunori M, et al. Expression of nm23H_1 gene product in esophageal squamous cell carcinoma and its association with vessel in vasion and survival. Cancer.2001;1(1):3-8
[78]Sarbia M, Porschen R, Borchard F, et al. Incidence and prognostic significance of vascular and neural invasion in squamous cell carcinomas of the esophagus.Int J Cancer. 1995;61(3):333-6
[79]Spirin KS, Simpson JF, Takeuchi S, et al. p27/Kip1 mutation found in breast cancer.Cancer Res. 1996;56(10):2400-4
[80]Kawamata N, Morosetti R, Miller CW, et al. Molecular analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in human malignancies.Cancer Res. 1995;55(11):2266-9
[81]Polyak K, Kato JY, Solomon MJ, et al p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.Genes. 1994;8(1):9-22
[82]Polyak K, Lee MH, Erdjument-Bromage H, et al. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.Cell. 1994;78(1):59-66
[83]Jellinek M, Castaneda M, Garvin PJ, et al Oxidation-reduction maintenance in organ preservation.Arch Surg. 1985;120(4):439-42
[84]Pietenpol JA, Bohlander SK, Sato Y, et al. Assignment of the human p27Kip1
gene to 12p13 and its analysis in leukemias.Cancer Res. 1995;55(6):1206-10
[85]Liotta LA. Tumor invasion and metastases--role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res. 1986;46(1):1-7
[86]Albelda SM._Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest. 1993;68(1):4-17
[87]Pottratz ST, Hall TD, Scribner WM,et al. P-selectin-mediated attachment of small cell lung carcinoma to endothelial cells. Am J Physiol. 1996;271(6):918-23
[88]Rochefort H, Capony F, Garcia M. Cathepsin D in breast cancer: from molecular and cellular biology to clinical applications. Cancer Cells. 1990;2(12):383-8
[89]Ossowski L, Reich E. Antibodies to plasminogen activator inhibit human tumor metastasis. Cell. 1983;35(25):611-9
[90]Ossowski L, Russo-Payne H, Wilson EL. Inhibition of urokinase-type plasminogen activator by antibodies: the effect on dissemination of a human tumor in the nude mouse.Cancer Res. 1991;51(1):274-81
[91]Testa JE, Quigley JP. The role of urokinase-type plasminogen activator in aggressive tumor cell behavior. Cancer Metastasis Rev. 1990;9(4):353-67
[92]李节．尿激酶型纤溶酶原激活物与肿瘤的关系．国外医学分子生物学分册．1994；16(1)：26-8
[93]Kawano K, Aoki I, Aoki N, et al. Human platelet activation by thrombolytic agents: effects of tissue-type plasminogen activator and urokinase on platelet surface P- selectin expression.Am Heart J. 1998;135(6):268-71
[94]Salerno M, Ouatas T, Palmieri D, et al. Inhibition of signal transduction by the nm23 metastasis suppressor: possible mechanisms.Clin Exp Metastasis. 2003;20(1):3-10
[95]Belev B, Aleric I, Vrbanec D, et al. nm23 gene product expression in invasive breast cancer--immunohistochemical analysis and clinicopathological correlation.Acta Oncol. 2002;41(4):355-61
[96]Kauffman EC, Robinson VL, Stadler WM, et al. Metastasis suppression: the evolving role of metastasis suppressor genes for regulating cancer cell growth at the secondary site.J Urol. 2003;169(3):1122-33