食管癌螺旋CT征象与MVD、VEGF及MMP-7表达间关系的研究
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摘要
背景和目的：食管癌是消化道常见恶性肿瘤之一。螺旋CT(Spiral CT，SCT或称Helical CT，HCT)的应用为食管癌的诊断提供了更多的信息，被认为是食管癌患者的一种有效检查方法。肿瘤影像学特征都有其病理学基础，并由肿瘤的生物学特性决定。研究表明肿瘤生长依赖于肿瘤血管生成。肿瘤内微血管密度(microvessel density，MVD)可定量反映肿瘤血管生成状态，是目前评价肿瘤血管生成的“金标准”。肿瘤血管生成依赖于多种相关因子的诱导和调节，血管内皮生长因子(vascular endothelial growth factor，VEGF)被认为是促进血管生成的主要因子之一，在肿瘤的血管生成及浸润、转移中发挥促进作用，对判断预后具有重要的临床意义。基质金属蛋白酶家族(matrix metalloproteinases，MMPs)是降解细胞外基质的主要酶类之一。其中基质金属蛋白酶-7(MMP-7，Matrilysin)是MMPs中唯一由上皮性肿瘤细胞特异性表达的酶，在消化道肿瘤的发展中起重要作用。将SCT征象通过病理与肿瘤的生物学特性对照分析，探讨影像学与分子生物学之间的内在联系是近年来研究的热点之一。本研究的目的是探讨食管癌的SCT征象与MVD和VEGF、MMP-7表达间的关系。
材料与方法：46例食管癌病人术前行SCT增强扫描。扫描前10分钟肌肉注射盐酸山莨菪碱15mg，口服温开水800-1200毫升。扫描范围包括下颈部、
郑州大学20叫年硕士毕业论文
食管癌螺旋Cl，征象与MVD、VEGF及MMP一7表达间关系的研究
纵隔及上腹部。直接行增强扫描，用高压注射器从肘静脉注入对比剂欧乃派
克或优维显looml(300mgl/ml)，注射速度3ml/s，于对比剂注射开始后405扫
描，扫描时嘱患者大口吞咽空气，以便扩张食管，期间闭气一次。参照食管
造影片或食管镜检，病变部位准直smm，其它部位扫描准直10mm，螺距均为
1，重建厚度smm。术后标本全部经10%福尔马林固定，常规脱水后石蜡包埋，
采用免疫组织化学Sp(streptavidin peroxidase)法检测肿瘤组织中MvD、vEeF
和MMP一7的表达。实验数据经SPSS统计软件包进行统计学处理。MVD以
均数，标准差表示，计量资料的比较采用t检验，计数资料的比较采用扩检
验，相关分析采用spearman等级相关分析，一致性检验采用肋即a分析。
取以=0.05为显著性检验水准。
结果:1.46例食管癌患者的SCT增强扫描诊断结果与手术病理对照，
对邻近结构有无受侵判断准确率为89.13%(41/46)，对有无淋巴结转移判断准
确率为86.%%(40/46)。SCT诊断邻近结构有无受侵及淋巴结有无转移的结果与
手术病理对照一致性好(肋即a值分别为0.726、0.721，尸<0.001)。
2.46例食管癌中，MVD变化范围从17.33到41.67，值为29.89士5.36。
在SCT征象上邻近结构侵犯阳性组和阴性组，MVD分别为32.92士3.47和
28.82士5.54，两组比较差异有统计学意义(t=2.389，尸二0.021)。在SCT征象上
淋巴结转移阳性组和阴性组，MVD分别为32.67士3.92和28.41士5.49，两
组比较差异具有统计学意义(t=2.734，p=0.009)。
3.在46例食管癌中，VEGF阳性表达18例，阳性率为39.13%。在
SCT征象上邻近结构侵犯阳性组和阴性组，VEGF的阳性表达率分别为
75 .00%(9/xZ)和26.47%(9/34)，两组比较差异有统计学意义(xZ=6.551，
尸二0.009)。在scT征象上淋巴结转移阳性组和阴性组，vEGF的阳性表达率
分别为62.50%(10/16)和26.67%(8/30)，两组比较差异具有统计学意义
(xZ=5 .625，尸=0.015)。
4.在46例食管癌中，MMP一7阳性表达28例，阳性率为60.87%。在SCT
征象上邻近结构有、无侵犯组，MMP一7的阳性表达率分别为91 .67(n/ 12)和
郑州大学2004年硕士毕业论文
食管癌螺旋C」，征象与MVD、VEGF及MMP一7表达间关系的研究
50.00%(17/34)，差异有统计学意义(xZ=4.534，尸=0.025)。在淋巴结转移有、无
组，MMP一7的阳性表达率分别为87.50%(14/16)和46.67%(14/30)，差异有统
计学意义(xZ=5.691，尸=0.017)。
5.VEGF阳性组的MVD为33.02士3.87，显著高于VEGF阴性组的
27.88士5.27(t=3.558，p=0.001)。而MMp一7阳性组的 MVD为31.93士4.29，
阴性组的MVD为26.72士5.42，差异有显著性(t二3.620，p=0.001)
6.VEGF、MMp一7在食管癌中的表达有相关性(r、=0.369，p=0.012)。
结论:1.SCI，增强扫描是食管癌治疗前一项颇有价值的诊断技术。
2.MvD与食管癌SCT征象上的邻近结构侵犯及淋巴结转移相关，提示
血管生成可能对食管癌浸润和转移起促进作用。
3.vEGF、MMP一7高表达与食管癌SCT征象上的邻近结构侵犯及淋巴
结转移相关，提示它们可能对食管癌进展起促进作用。
4.vEGF和MMP一7可能是食管癌血管生成的重要调控因子，它们都可
促进肿瘤血管生成。
5.食管癌中VEGF表达与MMP一7表达相关，提示VEGF与MMP一7在
食管癌的发展及血管生成中发挥协同作用。
6.食管癌SCT表现与MvD、vEGF及MMP一7表达相结合，有助于判
定邻近结构侵犯、淋巴结和/或远隔器官转移状况及估计预后，为临床选择治
疗方案提供有价值的理论依据。
Background and purpose: Esophageal carcinoma is one of the common malignant tumors in digestive tract. Considered as an effective method in examination of the esophageal carcinoma, Spiral CT (SCT) can provide with more important information of the tumor. Imaging features of all tumors are based on their pathological natures and are determined by their biological behaviors. Recent reports reveal that tumor angiogenesis is necessary for growth of all-solid tumors. Microvessel density (MVD) can mirror the status of tumor angiogenesis and is regarded as the gold standard to assess tumor angiogenesis. Tumor angiogenesis is regulated by many kinds of correlative factors. Vascular endothelial growth factor (VEGF) is considered as a potent angiogenesis-promoting factor that relates to tumor angiogenesis, infiltration, metastasis and prognosis. Matrix metalloproteinases (MMPs) is a main enzyme to degrade extracelluar matrix. Matrix metalloproteinase 7 (MMP-7) is the only MMP that can be expressed specifically by the
epithelial tumor cells, playing an important role in the development of digestive tract tumors. The inherent relationship between modern medical imaging and molecular biology can be found by comparing SCT features of tumor with its biological behaviors. The
purpose of this study is to evaluate the correlation between SCT features, MVD, the expressions of VEGF and MMP-7 in esophageal carcinoma.
Materials and methods: Spiral CT contrast-enhanced scans were performed in 46 patients with esophageal carcinoma before operation. About 10 minutes before the scanning, 15 mg 654-2 was injected intramuscularly. Then 800-1200ml lukewarm water was taken. Spiral CT examination was performed with a GE HiSpeed Advantage Rp22 Helical scanner. The field of scanning included lower neck, mediastinum and upper abdomen. 100ml contrast medium (Omnipaque or Ultravist 300mgI/ml) was injected via cubital vein with the speed of 3ml/s, and the scanning began at 40s after the start of injection. Patients were asked to swallow air during scanning and to hold their breathing for 1 time. The tumor location was defined according to the barium meal examination or esophageal endoscope. The collimation of the tumor location was 5mm, and other parts were 10mm, pitch 1:1, reconstruction depth 5mm. After operation, all the specimens were fixed in 10% neutral formalin and embedded in paraffin. Immunohistochemical streptavidin peroxidase conjugate method was used to analyze the MVD as well as the expressions of VEGF and MMP-7 in esophageal carcinoma. Statistical analysis was performed with SPSS 10.0 software, using Mest, Chi-square test, spearman test and Kappa test. Statistically significant level was considered as "alpha equals 0.05".
Results: 1. Compared with operation and pathology, the accuracy of Spiral CT contrast-enhanced scan in judging adjacent-infiltration and lymph node metastasis in 46 patients was 89.13%(41 of 46) and 86.96%(40 of 46); The diagnostic outcome of Spiral CT in judging adjacent-infiltration and lymph node metastasis had good coincidence with operation and pathology(Kappa was 0.726 and 0.721, P < 0.001).
2. In 46 cases, microvessel densities ranged from 17.33 to 41.67 with a mean of 30.07(standard deviation, 4.63). In the adjacent-infiltration group and the non-adjacent-infiltration group in SCT features, the microvessel densities were 32.92 + 3.47 and 28.82 + 5.54 respectively and the difference was statistically significant(t=2.389, P=0.021). In the group with lymph node
metastasis and the group without lymph node metastasis in SCT features, the microvessel densities were 32.67 + 3.92 and 28.41 + 5.49 respectively and the difference was statistically significant(r=2.734, P=0.009).
3. In 46 cases, VEGF positive-expression was detected in 18 patients. The VEGF positive rate was 39.13%. In the adjacent-infiltration group and the non-adjacent-infiltration group in SCT features, the positive rates of VEGF protein were 75.00% (9 of 12) and 26.47% (9 of 34) respectively, which had statistically significa
材料与方法：46例食管癌病人术前行SCT增强扫描。扫描前10分钟肌肉注射盐酸山莨菪碱15mg，口服温开水800-1200毫升。扫描范围包括下颈部、
郑州大学20叫年硕士毕业论文
食管癌螺旋Cl，征象与MVD、VEGF及MMP一7表达间关系的研究
纵隔及上腹部。直接行增强扫描，用高压注射器从肘静脉注入对比剂欧乃派
克或优维显looml(300mgl/ml)，注射速度3ml/s，于对比剂注射开始后405扫
描，扫描时嘱患者大口吞咽空气，以便扩张食管，期间闭气一次。参照食管
造影片或食管镜检，病变部位准直smm，其它部位扫描准直10mm，螺距均为
1，重建厚度smm。术后标本全部经10%福尔马林固定，常规脱水后石蜡包埋，
采用免疫组织化学Sp(streptavidin peroxidase)法检测肿瘤组织中MvD、vEeF
和MMP一7的表达。实验数据经SPSS统计软件包进行统计学处理。MVD以
均数，标准差表示，计量资料的比较采用t检验，计数资料的比较采用扩检
验，相关分析采用spearman等级相关分析，一致性检验采用肋即a分析。
取以=0.05为显著性检验水准。
结果:1.46例食管癌患者的SCT增强扫描诊断结果与手术病理对照，
对邻近结构有无受侵判断准确率为89.13%(41/46)，对有无淋巴结转移判断准
确率为86.%%(40/46)。SCT诊断邻近结构有无受侵及淋巴结有无转移的结果与
手术病理对照一致性好(肋即a值分别为0.726、0.721，尸<0.001)。
2.46例食管癌中，MVD变化范围从17.33到41.67，值为29.89士5.36。
在SCT征象上邻近结构侵犯阳性组和阴性组，MVD分别为32.92士3.47和
28.82士5.54，两组比较差异有统计学意义(t=2.389，尸二0.021)。在SCT征象上
淋巴结转移阳性组和阴性组，MVD分别为32.67士3.92和28.41士5.49，两
组比较差异具有统计学意义(t=2.734，p=0.009)。
3.在46例食管癌中，VEGF阳性表达18例，阳性率为39.13%。在
SCT征象上邻近结构侵犯阳性组和阴性组，VEGF的阳性表达率分别为
75 .00%(9/xZ)和26.47%(9/34)，两组比较差异有统计学意义(xZ=6.551，
尸二0.009)。在scT征象上淋巴结转移阳性组和阴性组，vEGF的阳性表达率
分别为62.50%(10/16)和26.67%(8/30)，两组比较差异具有统计学意义
(xZ=5 .625，尸=0.015)。
4.在46例食管癌中，MMP一7阳性表达28例，阳性率为60.87%。在SCT
征象上邻近结构有、无侵犯组，MMP一7的阳性表达率分别为91 .67(n/ 12)和
郑州大学2004年硕士毕业论文
食管癌螺旋C」，征象与MVD、VEGF及MMP一7表达间关系的研究
50.00%(17/34)，差异有统计学意义(xZ=4.534，尸=0.025)。在淋巴结转移有、无
组，MMP一7的阳性表达率分别为87.50%(14/16)和46.67%(14/30)，差异有统
计学意义(xZ=5.691，尸=0.017)。
5.VEGF阳性组的MVD为33.02士3.87，显著高于VEGF阴性组的
27.88士5.27(t=3.558，p=0.001)。而MMp一7阳性组的 MVD为31.93士4.29，
阴性组的MVD为26.72士5.42，差异有显著性(t二3.620，p=0.001)
6.VEGF、MMp一7在食管癌中的表达有相关性(r、=0.369，p=0.012)。
结论:1.SCI，增强扫描是食管癌治疗前一项颇有价值的诊断技术。
2.MvD与食管癌SCT征象上的邻近结构侵犯及淋巴结转移相关，提示
血管生成可能对食管癌浸润和转移起促进作用。
3.vEGF、MMP一7高表达与食管癌SCT征象上的邻近结构侵犯及淋巴
结转移相关，提示它们可能对食管癌进展起促进作用。
4.vEGF和MMP一7可能是食管癌血管生成的重要调控因子，它们都可
促进肿瘤血管生成。
5.食管癌中VEGF表达与MMP一7表达相关，提示VEGF与MMP一7在
食管癌的发展及血管生成中发挥协同作用。
6.食管癌SCT表现与MvD、vEGF及MMP一7表达相结合，有助于判
定邻近结构侵犯、淋巴结和/或远隔器官转移状况及估计预后，为临床选择治
疗方案提供有价值的理论依据。
Background and purpose: Esophageal carcinoma is one of the common malignant tumors in digestive tract. Considered as an effective method in examination of the esophageal carcinoma, Spiral CT (SCT) can provide with more important information of the tumor. Imaging features of all tumors are based on their pathological natures and are determined by their biological behaviors. Recent reports reveal that tumor angiogenesis is necessary for growth of all-solid tumors. Microvessel density (MVD) can mirror the status of tumor angiogenesis and is regarded as the gold standard to assess tumor angiogenesis. Tumor angiogenesis is regulated by many kinds of correlative factors. Vascular endothelial growth factor (VEGF) is considered as a potent angiogenesis-promoting factor that relates to tumor angiogenesis, infiltration, metastasis and prognosis. Matrix metalloproteinases (MMPs) is a main enzyme to degrade extracelluar matrix. Matrix metalloproteinase 7 (MMP-7) is the only MMP that can be expressed specifically by the
epithelial tumor cells, playing an important role in the development of digestive tract tumors. The inherent relationship between modern medical imaging and molecular biology can be found by comparing SCT features of tumor with its biological behaviors. The
purpose of this study is to evaluate the correlation between SCT features, MVD, the expressions of VEGF and MMP-7 in esophageal carcinoma.
Materials and methods: Spiral CT contrast-enhanced scans were performed in 46 patients with esophageal carcinoma before operation. About 10 minutes before the scanning, 15 mg 654-2 was injected intramuscularly. Then 800-1200ml lukewarm water was taken. Spiral CT examination was performed with a GE HiSpeed Advantage Rp22 Helical scanner. The field of scanning included lower neck, mediastinum and upper abdomen. 100ml contrast medium (Omnipaque or Ultravist 300mgI/ml) was injected via cubital vein with the speed of 3ml/s, and the scanning began at 40s after the start of injection. Patients were asked to swallow air during scanning and to hold their breathing for 1 time. The tumor location was defined according to the barium meal examination or esophageal endoscope. The collimation of the tumor location was 5mm, and other parts were 10mm, pitch 1:1, reconstruction depth 5mm. After operation, all the specimens were fixed in 10% neutral formalin and embedded in paraffin. Immunohistochemical streptavidin peroxidase conjugate method was used to analyze the MVD as well as the expressions of VEGF and MMP-7 in esophageal carcinoma. Statistical analysis was performed with SPSS 10.0 software, using Mest, Chi-square test, spearman test and Kappa test. Statistically significant level was considered as "alpha equals 0.05".
Results: 1. Compared with operation and pathology, the accuracy of Spiral CT contrast-enhanced scan in judging adjacent-infiltration and lymph node metastasis in 46 patients was 89.13%(41 of 46) and 86.96%(40 of 46); The diagnostic outcome of Spiral CT in judging adjacent-infiltration and lymph node metastasis had good coincidence with operation and pathology(Kappa was 0.726 and 0.721, P < 0.001).
2. In 46 cases, microvessel densities ranged from 17.33 to 41.67 with a mean of 30.07(standard deviation, 4.63). In the adjacent-infiltration group and the non-adjacent-infiltration group in SCT features, the microvessel densities were 32.92 + 3.47 and 28.82 + 5.54 respectively and the difference was statistically significant(t=2.389, P=0.021). In the group with lymph node
metastasis and the group without lymph node metastasis in SCT features, the microvessel densities were 32.67 + 3.92 and 28.41 + 5.49 respectively and the difference was statistically significant(r=2.734, P=0.009).
3. In 46 cases, VEGF positive-expression was detected in 18 patients. The VEGF positive rate was 39.13%. In the adjacent-infiltration group and the non-adjacent-infiltration group in SCT features, the positive rates of VEGF protein were 75.00% (9 of 12) and 26.47% (9 of 34) respectively, which had statistically significa
引文
1．李连弟，鲁凤珠，张思维，等．中国恶性肿瘤死亡率20年变化趋势和近期预测分析．中华肿瘤杂志，1997，19：3-9．
2．张惠茅，杨海山．螺旋CT扫描在食管癌检查中的临床应用．临床放射学杂志，2001，20：433-435．
3．赵心明，孙伟，蒋力明，等．螺旋CT及其多平面重建技术对判定食管癌侵犯周围结构的价值．中国医学影像技术，2003，19：558-560．
4. Wu LF, Wang BZ, Feng JL, et, al. Preoperative TN staging of esophageal cancer: comparison of miniprobe ultrasonography, spiral CT and MRI. World J Gastroenterol, 2003, 9:219-224.
5. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med, 1971, 285:1182-1186.
6. Takahashi R, Tanaka S, Kitadai Y, et al. Expression of vascular endothelial growth factor and angiogenesis in gastrointestinal stromal tumor of the stomach. Oncology, 2003, 64:266-274.
7. Qi SY. Expression of vascular endothelial growth factor and microvessel density in ovarian tumor. Ai Zheng, 2003, 22:320-323.
8. Shou Y, Hirano T, Gong Y, et al. Influence of angiogenetic factors and matrix metalloproteinases upon tumor progression in non-small-cell lung cancer. Br J Cancer, 2001, 85:1706-1712.
9. Matrisin LM. Metalloproteinase and their inhibitor in matrix remolding. Trends Genet, 1990, 6:121-125.
10. Mori M, Barnard GF, Mimori K, et al. Over expression of matrix metalloproteinase-7 mRNA in human colon carcinomas. Cancer, 1995, 75:1516-1519.
11. Picus D, Balfe DM, Koehler RE, et al. CT in the staging of esophageal carcinoma. Radiology, 1983, 146:433-438.
12. Takashima S, Takenchi N, Shiozak H, et al. carcinoma of the esophagus: CT vs MR imaging in determining resectability. AJR, 1991, 156:297-302.
13．李文华，杨仁杰，赵廷常，主编．食管影像学．北京：人民卫生山版社，2002，181-193．
14．顾雅佳，王玖华，相加庆，等．CT观察胸段食管癌气管食管沟淋巴结转移的临床意义探讨．中华放射学杂志，2002，36：139-141．
15. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent
prognostic indicator in early-stage breast carcinoma. J Natl Inst, 1992, 84:1875-1877.
16. Maeda K, Chung YS, Ogawa Y, et al. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer, 1996, 77:858-863.
17．赵卫平，许敬尧，祝佳，等．食管鳞癌中基质金属蛋白酶-7的表达及意义．临床消化病杂志，2002，14：173-175．
18．李刚，刘曙正，戴涤新，等．河南省1996-2000年恶性肿瘤死亡状况分析．肿瘤防治杂志，2003，10：339-340．
19. Li H, Yao SC. Surgical treatment for carcinoma of the oesophagus in Chinese language publications. Br J Surg, 1997,84:855-857.
20. Ferrare N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat, 1995, 36:127-137.
21. Kraft A, Weindel K, Ohs A, et al. Vascular endothelial growth factor in the sera and effuions of patients with malignant and non malignant disease. Cancer, 1999, 85:178-187.
22．吴静，樊代明．肿瘤血管生成与肿瘤血管抑制治疗．世界华人消化杂志，2001，9：316-321．
23．肖扬，焦炳华．肿瘤新生血管产生机制的研究进展．国外医学外科学分册，1999，26：264-267．
24. Weidner N. Current pathology methods for measuring intratumoral microvessel density within Brest carcinoma and other solid tumors. Breast cancer Res Treat, 1995, 36:169-180.
25. Inoue K, Ozeki Y, Suganuma T, et al. Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma-association with angiogenesis and tumor progression. Cancer, 1997, 79: 206-213.
26. Kitadai Y, Haruma K, Tokutomi T, et al. Significance of vessel count and vascular endothelial growth factor in human esophageal carcinoma. Clin Cancer Res, 1998, 4:2195-2200.
27. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigensis. Cell, 1996, 86:353-364.
28. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun, 1989, 161:851-858.
29. Vincenti V, Cassano L, Rocchi M, et al. Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation, 1996, 93:1493-1495.
30. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr rev, 1997, 18:4-25.
31. Kato H, Yoshikawa M, Miyazaki T, et al. Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) in esophageal squamous cell carcinoma. Anticancer Res, 2002, 22:3977-3984.
32. Kitadai Y, Amioka T, Haruma K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinoma. Int J Cancer, 2001, 93:662-666.
33．孙玲，邹雄．血管内皮生长因子在肿瘤中的表达及其临床意义．肿瘤防治杂志，2001，8：194-196．
34. Saito H, Tsujitani S, Ikeguchi M, et al. Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. Br J Cancer, 1998, 78:1573-1577.
35. Ogata Y, Fujita H, Yamaha H, et al. Expression of vascular endothelial growth factor as a prognostic factor in node-positive squamous cell carcinoma in the thoracic esophagus: long-term follow-up study. World J Surg, 2003, 27:584-589.
36. Shimada H, Takeda A, Nabeya Y, et al. Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma. Cancer, 2001, 92:663-669.
37．许运龙，汪毅．食管癌血清和尿液中血管内皮生长因子水平的变化及意义．中华肿瘤杂志，2001，23：393-394．
38. Knox JD, Boreham DR, Walker JA, et al. Mapping of the metalloproteinase gene matrilysin (MMP-7) to human chromosome 11q21-q22. Cytogenet Cell Genet, 1996, 72:179-182.
39. Giambernardi TA, Grant GM, Taylor GP, et al. Overview of matrix metalloproteinase express in cultured human cells. Matrix Biol, 1998, 16:483-496.
40. Burke B, Giannoudis A, Corke KP, et al. Hypoxia-induced gene express in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy. Am J Pathol, 2003, 163:1233-1243.
41. Busiek DF, Baragi V, Nehring LC, et al. Matrilysin expression by human mononuclear phagocytes and its regulation by cytokines and hormones. J Immunol, 1995, 154:6484-6491.
42. Itoh F, Yamamoto H, Hinode Y, et al. Enhanced secretion and activation of matrilysin during
malignant conversion of human colorectal epithelium and its relationship with invasive potential of colon cancer cells. Cancer, 1996, 77:1717-1721.
43. Yamashita K, Mori M, Shiraishi T, et al. Clinical significance of matrix metalloproteinase-7 expression in oesophageal carcinoma. Clin Cancer Res, 2000, 6:1169-1174.
44. Yamamoto H, Adachi Y, Itoh F, et al. Association of matrilysin express with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Cancer Res, 1999 59:3313-3316.
45. Noe V, Fingleton B, Jacobs KS, et al. Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sic, 2001, 114:111-118.
46. Mitsiades N, Yu WH, Poulaki V, et al. Matrix metalloproteinase-7 mediated cleavage of Fas ligant protects tumor cells from chemotherapeutic drug cytotoxicity. Cancer Res, 2001, 61:577-581.
47. Nishizuka I, Ichikawa Y, Ishikawa T, et al. Matrilysin stimulates DNA synthesis of cultured vascular endothelial cells and induces angiogenesis in vivo. Cancer Lett, 2001, 173:175-182.
48. Huachuan Z, Xiaohan L, Jinmin S, et al. Expression of matrix metalloproteinase-7 involving in growth, invasion, metastasis and angiogenesis of gastric cancer. Chin Med Sci J, 2003, 18:80-86.
49. Takahashi Y, Ellis LM, Mai M. The angiogenic switch of human colon cancer occurs simultaneous to initiation of invasion. Oncol Rep, 2003, 10:9-13.
50. Rak J, Mitsuhashi Y, Bakyo L, et al. Mutant ras oncogene up-regulate VEGF/VPF expression: implication for induction and inhibition of tumor angiogenesis. Cancer Res, 1995, 55:4575-4580.
2．张惠茅，杨海山．螺旋CT扫描在食管癌检查中的临床应用．临床放射学杂志，2001，20：433-435．
3．赵心明，孙伟，蒋力明，等．螺旋CT及其多平面重建技术对判定食管癌侵犯周围结构的价值．中国医学影像技术，2003，19：558-560．
4. Wu LF, Wang BZ, Feng JL, et, al. Preoperative TN staging of esophageal cancer: comparison of miniprobe ultrasonography, spiral CT and MRI. World J Gastroenterol, 2003, 9:219-224.
5. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med, 1971, 285:1182-1186.
6. Takahashi R, Tanaka S, Kitadai Y, et al. Expression of vascular endothelial growth factor and angiogenesis in gastrointestinal stromal tumor of the stomach. Oncology, 2003, 64:266-274.
7. Qi SY. Expression of vascular endothelial growth factor and microvessel density in ovarian tumor. Ai Zheng, 2003, 22:320-323.
8. Shou Y, Hirano T, Gong Y, et al. Influence of angiogenetic factors and matrix metalloproteinases upon tumor progression in non-small-cell lung cancer. Br J Cancer, 2001, 85:1706-1712.
9. Matrisin LM. Metalloproteinase and their inhibitor in matrix remolding. Trends Genet, 1990, 6:121-125.
10. Mori M, Barnard GF, Mimori K, et al. Over expression of matrix metalloproteinase-7 mRNA in human colon carcinomas. Cancer, 1995, 75:1516-1519.
11. Picus D, Balfe DM, Koehler RE, et al. CT in the staging of esophageal carcinoma. Radiology, 1983, 146:433-438.
12. Takashima S, Takenchi N, Shiozak H, et al. carcinoma of the esophagus: CT vs MR imaging in determining resectability. AJR, 1991, 156:297-302.
13．李文华，杨仁杰，赵廷常，主编．食管影像学．北京：人民卫生山版社，2002，181-193．
14．顾雅佳，王玖华，相加庆，等．CT观察胸段食管癌气管食管沟淋巴结转移的临床意义探讨．中华放射学杂志，2002，36：139-141．
15. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent
prognostic indicator in early-stage breast carcinoma. J Natl Inst, 1992, 84:1875-1877.
16. Maeda K, Chung YS, Ogawa Y, et al. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer, 1996, 77:858-863.
17．赵卫平，许敬尧，祝佳，等．食管鳞癌中基质金属蛋白酶-7的表达及意义．临床消化病杂志，2002，14：173-175．
18．李刚，刘曙正，戴涤新，等．河南省1996-2000年恶性肿瘤死亡状况分析．肿瘤防治杂志，2003，10：339-340．
19. Li H, Yao SC. Surgical treatment for carcinoma of the oesophagus in Chinese language publications. Br J Surg, 1997,84:855-857.
20. Ferrare N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat, 1995, 36:127-137.
21. Kraft A, Weindel K, Ohs A, et al. Vascular endothelial growth factor in the sera and effuions of patients with malignant and non malignant disease. Cancer, 1999, 85:178-187.
22．吴静，樊代明．肿瘤血管生成与肿瘤血管抑制治疗．世界华人消化杂志，2001，9：316-321．
23．肖扬，焦炳华．肿瘤新生血管产生机制的研究进展．国外医学外科学分册，1999，26：264-267．
24. Weidner N. Current pathology methods for measuring intratumoral microvessel density within Brest carcinoma and other solid tumors. Breast cancer Res Treat, 1995, 36:169-180.
25. Inoue K, Ozeki Y, Suganuma T, et al. Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma-association with angiogenesis and tumor progression. Cancer, 1997, 79: 206-213.
26. Kitadai Y, Haruma K, Tokutomi T, et al. Significance of vessel count and vascular endothelial growth factor in human esophageal carcinoma. Clin Cancer Res, 1998, 4:2195-2200.
27. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigensis. Cell, 1996, 86:353-364.
28. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun, 1989, 161:851-858.
29. Vincenti V, Cassano L, Rocchi M, et al. Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation, 1996, 93:1493-1495.
30. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr rev, 1997, 18:4-25.
31. Kato H, Yoshikawa M, Miyazaki T, et al. Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) in esophageal squamous cell carcinoma. Anticancer Res, 2002, 22:3977-3984.
32. Kitadai Y, Amioka T, Haruma K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinoma. Int J Cancer, 2001, 93:662-666.
33．孙玲，邹雄．血管内皮生长因子在肿瘤中的表达及其临床意义．肿瘤防治杂志，2001，8：194-196．
34. Saito H, Tsujitani S, Ikeguchi M, et al. Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. Br J Cancer, 1998, 78:1573-1577.
35. Ogata Y, Fujita H, Yamaha H, et al. Expression of vascular endothelial growth factor as a prognostic factor in node-positive squamous cell carcinoma in the thoracic esophagus: long-term follow-up study. World J Surg, 2003, 27:584-589.
36. Shimada H, Takeda A, Nabeya Y, et al. Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma. Cancer, 2001, 92:663-669.
37．许运龙，汪毅．食管癌血清和尿液中血管内皮生长因子水平的变化及意义．中华肿瘤杂志，2001，23：393-394．
38. Knox JD, Boreham DR, Walker JA, et al. Mapping of the metalloproteinase gene matrilysin (MMP-7) to human chromosome 11q21-q22. Cytogenet Cell Genet, 1996, 72:179-182.
39. Giambernardi TA, Grant GM, Taylor GP, et al. Overview of matrix metalloproteinase express in cultured human cells. Matrix Biol, 1998, 16:483-496.
40. Burke B, Giannoudis A, Corke KP, et al. Hypoxia-induced gene express in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy. Am J Pathol, 2003, 163:1233-1243.
41. Busiek DF, Baragi V, Nehring LC, et al. Matrilysin expression by human mononuclear phagocytes and its regulation by cytokines and hormones. J Immunol, 1995, 154:6484-6491.
42. Itoh F, Yamamoto H, Hinode Y, et al. Enhanced secretion and activation of matrilysin during
malignant conversion of human colorectal epithelium and its relationship with invasive potential of colon cancer cells. Cancer, 1996, 77:1717-1721.
43. Yamashita K, Mori M, Shiraishi T, et al. Clinical significance of matrix metalloproteinase-7 expression in oesophageal carcinoma. Clin Cancer Res, 2000, 6:1169-1174.
44. Yamamoto H, Adachi Y, Itoh F, et al. Association of matrilysin express with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Cancer Res, 1999 59:3313-3316.
45. Noe V, Fingleton B, Jacobs KS, et al. Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sic, 2001, 114:111-118.
46. Mitsiades N, Yu WH, Poulaki V, et al. Matrix metalloproteinase-7 mediated cleavage of Fas ligant protects tumor cells from chemotherapeutic drug cytotoxicity. Cancer Res, 2001, 61:577-581.
47. Nishizuka I, Ichikawa Y, Ishikawa T, et al. Matrilysin stimulates DNA synthesis of cultured vascular endothelial cells and induces angiogenesis in vivo. Cancer Lett, 2001, 173:175-182.
48. Huachuan Z, Xiaohan L, Jinmin S, et al. Expression of matrix metalloproteinase-7 involving in growth, invasion, metastasis and angiogenesis of gastric cancer. Chin Med Sci J, 2003, 18:80-86.
49. Takahashi Y, Ellis LM, Mai M. The angiogenic switch of human colon cancer occurs simultaneous to initiation of invasion. Oncol Rep, 2003, 10:9-13.
50. Rak J, Mitsuhashi Y, Bakyo L, et al. Mutant ras oncogene up-regulate VEGF/VPF expression: implication for induction and inhibition of tumor angiogenesis. Cancer Res, 1995, 55:4575-4580.