乳腺癌超声光散射断层成像与预后及病理学对照研究
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摘要
目的
探讨乳腺癌超声光散射断层成像与预后的相关性。
资料与方法
2007年10月至2010年2月,经手术证实、进行腋窝淋巴结评价、术后进行系统治疗、影像学资料完备、定期随诊的原发性乳腺癌195例(207个病灶)。术前进行常规超声检查,记录病灶超声特点,并用超声定位光散射断层成像系统测量病灶的总血红蛋白浓度,生成光吸收图。术后查阅患者门诊及住院病历,并进行电话随访,记录患者临床特点、术后治疗及复查情况。分析乳腺癌超声光散射断层成像总血红蛋白浓度(THC)与预后的相关性
结果
1.THC与病灶的大小密切相关,最大径>2cm者THC明显高于≤2cm者(P=0.000)；THC与乳腺癌病理类型密切相关(P=0.041),非特殊类型浸润性乳腺癌THC明显高于特殊类型浸润性乳腺癌；THC与乳腺癌pTNM分期有关,Ⅰ期病灶THC明显低于Ⅱ期和Ⅲ期(P值分别为0.002和0.001),Ⅱ期和Ⅲ期之间THC无明显统计学差异(P=0.369)。
2.THC与患者预后明显相关,术后有复发或转移的乳腺癌THC值明显高于术后无复发、转移者(P=0.023)。
3.THC与术后复发或转移时间呈负相关,但是差异未达统计学显著性(相关系数r=-0.254,P=0.241)。
4.THC与转移部位之间无统计学相关性(P=0.139)。
结论
1.THC与病灶大小、病理类型、pTNM分期、术后有无复发或转移有相关性。
2.THC与术后复发或转移的时间、部位无明显相关性。
目的
1.分析转移组和未转移组THC值高低产生的病理学基础。
2.探讨总血红蛋白浓度(THC)与血管生成因子(HIF-1α、OPN、VEGF)、微血管密度(MVD)及血管生成拟态的关系。
资料与方法
对2007年10月至2010年2月间195例术前进行超声光散射断层成像的原发性乳腺进行随访,其中术后发生复发或转移者23例,将所有发生复发或转移的病例按照pTNM分期进行1：2配对,共计69例。对69例患者石蜡包埋的组织切片进行缺氧诱导因子-1α(HIF-1α)、骨桥蛋白(OPN)、血管内皮细胞生长因子(VEGF)、CD34染色及血管生成拟态染色(CD34和PAS双重染色),并对染色切片进行评价,分析其与THC的相关性。
结果
1.转移组THC与HIF-1α相关,未转移组THC与HIF-1α无相关性。
2.THC与VEGF、OPN无统计学相关性
3.THC与MVD、MVD+VM呈直线相关,VM对乳腺癌总体血供影响不大。
结论
1.转移组THC与HIF-1α相关,未转移组THC与HIF-1α无相关性,两组THC高低均与VEGF和OPN无明显相关性。
2.THC与MVD、MVD+VM之和呈直线相关,VM对总体血供影响不大。
Objective
To probe the correlation between the ultrasound-guided diffused optical tomography(DOT) of breast cancer and prognosis.
Materials and methods
195patients (207lesions) from October2007to February2010with primary breast cancer, verified by pathology, evaluated with axillary lymph nodes, treated systematicly, with detailed imaging examination data and follow-up, were enrolled in the research. Every patients took routine preoperative ultrasonography and were recorded with all ultrasound characters. Then Ultrasound localization of light scattering tomography was used to measure the total hemoglobin concentration within lesions and generated the optical absorption map.We checked all patients'medical records and clinic medical records and recorded their clinical characters, therapy projects and the results of follow-up. Then we probe the correlation between the ultrasound-guided diffused optical tomography(DOT) of breast cancer and prognosis.
Results
1. The THC of breast cancer and size of lesion were closely related, The THC of lesions lager than2cm was obviously higher than those smaller than2cm(P=0.000); The THC of breast cancer was closely related with the pathology type (P=0.041), The THC of non-special type of invasive breast cancer was obviously higher than that of special type of invasive breast cancer;The THC of breast cancer was closely related with the pathology TNM stage;The THC of I stage was obviously lower than that of II and III stage(P=0.002,0.001, respectively), there was no correlation between the THC of II and III stage(P=0.369).
2. The THC of breast cancer was closely related with the prognosis, and the THC of patients with recurrences or metastasis after operation was obviously higher than those without recurrences or metastasis(P=0.023).
3. The THC of breast cancer was negatively correlated with the time of recurrences or metastasis, but there was no statistical significance(r=-0.254, P=0.241).
4. There was no statistical significance between THC and metastatic locations after operation(P=0.139).
Conclusion
1. There was correlation between the THC of breast caner and the size, pathology type, pTNM stage and recurrences or metastasis after operation.
2. The THC of breast cancer was negatively correlated with the time of recurrences or metastasis
Objective
1. To analyse the pathology mechanism of the total hemoglobin concentration of the metastastic and non-metastasic groups.
2. To analyze correlation of the THC and HIF-1α、OPN、VEGF、MVD and VM.
Materials and methods
To follow-up the195patients with primary breast cancer diagnosed from October2007to February2010, we found23patients to relapse or metastasize after operation. All these cases were matched with the non-metastastic cases according to the proportion of1:2, and there were69cases. We carried out immumohistochemical staining of HIF-1a, OPN, VEGF, CD34and double staining of CD34and PAS, then we graded all the section stained and analyzed the correlation of the angiogenesis factor and THC.
Results
1.THC of the metastastic group was closely related with HIF-1α and THC of the non-metastastic group was not related with HIF-1α.
2.There was no relation between THC and VEGF. OPN.
3. THC was rectilinearly correlated with MVD and MVD+VM. VM contributed little to the blood supply of the breast cancer.
Conclusion
1. THC of the metastastic group was closely related with HIF-1α and THC of the non-metastastic group was not related with HIF-1α. THC of both group was not related with VEGF and OPN.
2. THC was rectilinearly correlated with MVD and MVD+VM. VM contributed little to the blood supply of the breast cancer.
探讨乳腺癌超声光散射断层成像与预后的相关性。
资料与方法
2007年10月至2010年2月,经手术证实、进行腋窝淋巴结评价、术后进行系统治疗、影像学资料完备、定期随诊的原发性乳腺癌195例(207个病灶)。术前进行常规超声检查,记录病灶超声特点,并用超声定位光散射断层成像系统测量病灶的总血红蛋白浓度,生成光吸收图。术后查阅患者门诊及住院病历,并进行电话随访,记录患者临床特点、术后治疗及复查情况。分析乳腺癌超声光散射断层成像总血红蛋白浓度(THC)与预后的相关性
结果
1.THC与病灶的大小密切相关,最大径>2cm者THC明显高于≤2cm者(P=0.000)；THC与乳腺癌病理类型密切相关(P=0.041),非特殊类型浸润性乳腺癌THC明显高于特殊类型浸润性乳腺癌；THC与乳腺癌pTNM分期有关,Ⅰ期病灶THC明显低于Ⅱ期和Ⅲ期(P值分别为0.002和0.001),Ⅱ期和Ⅲ期之间THC无明显统计学差异(P=0.369)。
2.THC与患者预后明显相关,术后有复发或转移的乳腺癌THC值明显高于术后无复发、转移者(P=0.023)。
3.THC与术后复发或转移时间呈负相关,但是差异未达统计学显著性(相关系数r=-0.254,P=0.241)。
4.THC与转移部位之间无统计学相关性(P=0.139)。
结论
1.THC与病灶大小、病理类型、pTNM分期、术后有无复发或转移有相关性。
2.THC与术后复发或转移的时间、部位无明显相关性。
目的
1.分析转移组和未转移组THC值高低产生的病理学基础。
2.探讨总血红蛋白浓度(THC)与血管生成因子(HIF-1α、OPN、VEGF)、微血管密度(MVD)及血管生成拟态的关系。
资料与方法
对2007年10月至2010年2月间195例术前进行超声光散射断层成像的原发性乳腺进行随访,其中术后发生复发或转移者23例,将所有发生复发或转移的病例按照pTNM分期进行1：2配对,共计69例。对69例患者石蜡包埋的组织切片进行缺氧诱导因子-1α(HIF-1α)、骨桥蛋白(OPN)、血管内皮细胞生长因子(VEGF)、CD34染色及血管生成拟态染色(CD34和PAS双重染色),并对染色切片进行评价,分析其与THC的相关性。
结果
1.转移组THC与HIF-1α相关,未转移组THC与HIF-1α无相关性。
2.THC与VEGF、OPN无统计学相关性
3.THC与MVD、MVD+VM呈直线相关,VM对乳腺癌总体血供影响不大。
结论
1.转移组THC与HIF-1α相关,未转移组THC与HIF-1α无相关性,两组THC高低均与VEGF和OPN无明显相关性。
2.THC与MVD、MVD+VM之和呈直线相关,VM对总体血供影响不大。
Objective
To probe the correlation between the ultrasound-guided diffused optical tomography(DOT) of breast cancer and prognosis.
Materials and methods
195patients (207lesions) from October2007to February2010with primary breast cancer, verified by pathology, evaluated with axillary lymph nodes, treated systematicly, with detailed imaging examination data and follow-up, were enrolled in the research. Every patients took routine preoperative ultrasonography and were recorded with all ultrasound characters. Then Ultrasound localization of light scattering tomography was used to measure the total hemoglobin concentration within lesions and generated the optical absorption map.We checked all patients'medical records and clinic medical records and recorded their clinical characters, therapy projects and the results of follow-up. Then we probe the correlation between the ultrasound-guided diffused optical tomography(DOT) of breast cancer and prognosis.
Results
1. The THC of breast cancer and size of lesion were closely related, The THC of lesions lager than2cm was obviously higher than those smaller than2cm(P=0.000); The THC of breast cancer was closely related with the pathology type (P=0.041), The THC of non-special type of invasive breast cancer was obviously higher than that of special type of invasive breast cancer;The THC of breast cancer was closely related with the pathology TNM stage;The THC of I stage was obviously lower than that of II and III stage(P=0.002,0.001, respectively), there was no correlation between the THC of II and III stage(P=0.369).
2. The THC of breast cancer was closely related with the prognosis, and the THC of patients with recurrences or metastasis after operation was obviously higher than those without recurrences or metastasis(P=0.023).
3. The THC of breast cancer was negatively correlated with the time of recurrences or metastasis, but there was no statistical significance(r=-0.254, P=0.241).
4. There was no statistical significance between THC and metastatic locations after operation(P=0.139).
Conclusion
1. There was correlation between the THC of breast caner and the size, pathology type, pTNM stage and recurrences or metastasis after operation.
2. The THC of breast cancer was negatively correlated with the time of recurrences or metastasis
Objective
1. To analyse the pathology mechanism of the total hemoglobin concentration of the metastastic and non-metastasic groups.
2. To analyze correlation of the THC and HIF-1α、OPN、VEGF、MVD and VM.
Materials and methods
To follow-up the195patients with primary breast cancer diagnosed from October2007to February2010, we found23patients to relapse or metastasize after operation. All these cases were matched with the non-metastastic cases according to the proportion of1:2, and there were69cases. We carried out immumohistochemical staining of HIF-1a, OPN, VEGF, CD34and double staining of CD34and PAS, then we graded all the section stained and analyzed the correlation of the angiogenesis factor and THC.
Results
1.THC of the metastastic group was closely related with HIF-1α and THC of the non-metastastic group was not related with HIF-1α.
2.There was no relation between THC and VEGF. OPN.
3. THC was rectilinearly correlated with MVD and MVD+VM. VM contributed little to the blood supply of the breast cancer.
Conclusion
1. THC of the metastastic group was closely related with HIF-1α and THC of the non-metastastic group was not related with HIF-1α. THC of both group was not related with VEGF and OPN.
2. THC was rectilinearly correlated with MVD and MVD+VM. VM contributed little to the blood supply of the breast cancer.
引文
1.国家癌症中心,卫生部疾病预防控制局.2011中国肿瘤登记年报[M].北京：军事医学科学出版社,2012：53-55.
2. Zhi W, Gu X, Qin J, et al. Solid breast lesions:Clinical experience with us-guided diffuse optical tomography combined with conventional us[J]. Radiology.2012;265(2):371-378.
3. Zhu Q, Kurtzma SH, Hegde P, et al. Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers[J]. Neoplasia. 2005; 7 (3):263-270.
4. Folkman J. Tumor angiogenesis:Therapeutic implications[J]. The New England journal of medicine.1971;285 (21):1182-1186.
5. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma[J]. The New England journal of medicine.1991;324:1-8.
6. Yang J, Mani SA, Donaher JL, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis[J]. Cell. 2004;117(17):927-939.
7. Hansen S, Grabau DA, Sorensen FB, et al. Vascular grading of angiogenesis: Prognostic significance in breast cancer [J]. British journal of cancer. 2000;82(2):339-347.
8. Zhu Q, Xiao M, You S, et al. Ultrasound-guided diffuse optical tomography (dot) of invasive breast carcinoma:Does tumour total haemoglobin concentration contribute to the prediction of axillary lymph node status[J]?European journal of radiology.2012;81:3185-3189.
9. Bolat F, Kayaselcuk F, Nursal TZ,et al. Microvessel density, vegf expression, and tumor-associated macrophages in breast tumors Correlations with prognostic parameters[J]. Journal of experimental & clinical cancer research:CR.2006;25(3):365-372.
10.孝梦甦,乳腺病变及其术后疤痕的超声定位光散射断层成像研究[D].北京：北京协和医学院,2010：
11. Choi JS, Kim MJ, Youk JH, et al. Us-guided optical tomography: Correlation with clinicopathologic variables in breast cancer[J]. Ultrasound in medicine & biology.2013;39(2):233-240.
12.单明,张建国.肿瘤淋巴转移机制的研究进展[J].解剖与临床.2008；13(1)：57-62.
13. Li C, Li R, Song H, et al. Significance of aeg-1 expression in correlation with vegf, microvessel density and clinicopathological characteristics in triple-negative breast cancer[J]. Journal of surgical oncology.2011;103(2):184-192.
14. Thielemann A, Kopczynski Z, Filas V, et al. The determination of vegf and mvd, among patients with primary breast cancer [J]. Pathology oncology research.2008;14(2):137-144.
15. Toikkanen S, Pylkkanen L, Joensuu H. Invasive lobular carcinoma of the breast has better short-and long-term survival than invasive ductal carcinoma[J].Br J Cancer.1997;76(9):1234-1240.
16. Colleoni M, Russo L, Dellapasqua S. Adjuvant therapies for special types of breast cancer[J]. Breast.2011;20 Suppl 3:S153-157.
17. Liotta LA, Kleinerman J, Saidel GM. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation[J]. Cancer research.1974;34(5):997-1004.
18. Heimann R.Ferguson D, Powers C, et al. Angiogenesis as a predictor of long-term survival for patients with node-negative breast cancer [J]. J Natl Cancer Inst.1996;88(23):1764-1769.
19. Ludovini V, Sidoni A, Pistola L, et al. Evaluation of the prognostic role of vascular endothelial growth factor and microvessel density in stages i and ii breast cancer patients[J].Breast cancer research and treatment.2003;81(2):159-168.
20. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis:A new significant and independent prognostic indicator in early-stage breast carcinoma[J]. Journal of the National Cancer Institute.1992;84(24):1875-1887.
21. L. A. Liotta, M. L. Stracke, E. Kohn, et al. New Directions in Cancer Treatment[J].Heidelberg:Springer Berlin Heidelberg,1989:381-398.
22.周力恒,殷文瑾,陆劲松,等.乳腺癌患者术后不同部位复发转移的风险分布[J].中国癌症杂志,2008,18(2)：124-127.
23.殷文瑾,周力恒,陆劲松,等.乳腺癌术后复发风险时间分布规律研究[J].实用肿瘤杂志,2007,22(6)：527-531.
1. Zhu Q, Xiao M, You S, et al. Ultrasound-guided diffuse optical tomography (dot) of invasive breast carcinoma:Does tumour total haemoglobin concentration contribute to the prediction of axillary lymph node status[J]?European journal of radiology.2012;81 (11):3185-3189.
2. Choi JS, Kim MJ, Youk JH, et al. Us-guided optical tomography: Correlation with clinicopathologic variables in breast cancer[J]. Ultrasound in medicine & biology.2013;39 (2):233-240.
3. You SS, Jiang YX, Zhu QL, et al. Us-guided diffused optical tomography:A promising functional imaging technique in breast lesions [J]. European radiology.2010;20 (2):309-317.
4. Zhi W, Gu X, Qin J, et al. Solid breast lesions:Clinical experience with us-guided diffuse optical tomography combined with conventional us[J]. Radiology.2012;265 (2):371-378.
5. Ludovini V, Sidoni A, Pistola L, et al. Evaluation of the prognostic role of vascular endothelial growth factor and microvessel density in stages i and ii breast cancer patients [J]. Breast cancer research and treatment.2003;81 (2):159-168.
6.孙宝存.肿瘤血管生成研究进展[R].长春,中华医学会,2005：
7. Chaudary N, Hill RP. Hypoxia and metastasis in breast cancer [J]. Breast disease.2006;26:55-64.
8. Liaw L, Lindner V, Schwartz SM, et al. Osteopontin and beta 3 integrin are coordinately expressed in regenerating endothelium in vivo and stimulate arg-gly-asp-dependent endothelial migration in vitro[J]. Circulation research.1995;77 (4):665-672.
9. Augustin HG. Antiangiogenic tumour therapy:Will it work[J]?Trends in pharmacological sciences.1998;19 (6):216-222.
10. Zhang S, Zhang D, Sun B. Vasculogenic mimicry:Current status and future prospects[J]. Cancer letters.2007;254 (2):157-164.
11. Li C, Li R, Song H, et al. Significance of aeg-1 expression in correlation with vegf, microvessel density and clinicopathological characteristics in triple-negative breast cancer[J]. Journal of surgical oncology.2011;103 (2):184-192.
12. Wang-Rodriguez J, Urquidi V, Rivard A, et al. Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status [J]. Breast cancer research:BCR.2003;5 (5):R136-143.
13. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma[J]. The New England journal of medicine.1991;324 (1):1-8.
14. Bussolino F, Mantovani A, Persico G. Molecular mechanisms of blood vessel formation[J]. Trends in biochemical sciences.1997;22 (7):251-256.
15.程丽.乳腺癌抗血管生成研究进展[J].西南军医,2010,12(5)：936-938.
16. Kohn S, Nagy JA, Dvorak HF,et al. Pathways of macromolecular tracer transport across venules and small veins. Structural basis for the hyperpermeability of tumor blood vessels[J]. Laboratory investigation.1992;67 (5):596-607.
17. Gupta MK, Qin RY. Mechanism and its regulation of tumor-induced angiogenesis[J]. World journal of gastroenterology.2003;9 (6):1144-1155.
18. Thielemann A, Kopczynski Z, Filas V, et al. The determination of vegf and mvd, among patients with primary breast cancer [J]. Pathology oncology research.2008;14 (2):137-144.
19.李晓,黄迪南,侯敢.肿瘤血管生成调节因子的研究进展[J].生命科学.2007：19(2)：198-202.
20. Zhu Q, Kurtzma SH, Hegde P, et al. Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers[J].Neoplasia.2005;7 (3):263-270.
21. Zhu Q, Tannenbaum S, Hegde P, et al. Noninvasive monitoring of breast cancer during neoadjuvant chemotherapy using optical tomography with ultrasound localization[J]. Neoplasia.2008;10 (10):1028-1040.
22. Xiang L, Gilkes DM, Chaturvedi P, et al. Ganetespib blocks hif-1 activity and inhibits tumor growth, vascularization, stem cell maintenance, invasion, and metastasis in orthotopic mouse models of triple-negative breast cancer[J]. Journal of molecular medicine.2014;92 (2):151-164.
23. Fang J, Yan L, Shing Y, et al. Hif-lalpha-mediated up-regulation of vascular endothelial growth factor, independent of basic fibroblast growth factor, is important in the switch to the angiogenic phenotype during early tumorigenesis[J]. Cancer research.2001;61 (15):5731-5735.
24. Jiang BH, Semenza GL, Bauer C, et al. Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of o2 tension[J]. The American journal of physiology.1996;271 (4 Pt 1):C1172-1180.
25. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia:Role of the hif system[J]. Nature medicine.2003;9 (6):677-684.
26.王红磊,武力,阙燕,等.超声光散射断层成像(dot)与乳腺癌血管生成病理学的相关性[J].复旦学报(医学版),2012：39(3)：261-267.
27. Amini A, Masoumi Moghaddam S, Morris DL, et al.The critical role of vascular endothelial growth factor in tumor angiogenesis [J]. Current cancer drug targets.2012;12 (1):23-43.
28. Kim MJ, Kim JY, Youn JH, et al. Us-guided diffuse optical tomography for breast lesions:The reliability of clinical experience[J]. European radiology.2011:21 (7):1353-1363.
29. Kerbel RS.Tumor angiogenesis:Past,present and the near future[J].Carcinogenesis.2000;21 (3):505-515.
30. Zhu Q, Huang M, Chen N, et al. Ultrasound-guided optical tomographic imaging of malignant and benign breast lesions:Initial clinical results of 19 cases[J].Neoplasia.2003;5 (5):379-388.
31. Yamamoto Y, Ibusuki M, Okumura Y, et al. Hypoxia-inducible factor lalpha is closely linked to an aggressive phenotype in breast cancer [J]. Breast cancer research and treatment.2008; 110 (3):465-475.
32. Wang W, He YF, Sun QK, et al. Hypoxia-inducible factor lalpha in breast cancer prognosis[J]. Clinica chimica acta.2014;428:32-37.
33. Bolat F, Kayaselcuk F, Nursal TZ,et al.Microvessel density, vegf expression, and tumor-associated macrophages in breast tumors Correlations with prognostic parameters[J]. Journal of experimental & clinical cancer research.2006;25 (3):365-372.
34.许进,夏潮涌,周序珑,等.实体肿瘤组织微血管计数方法的探讨[J].中华病理学杂志,2005;34(2)：111-112.
35. Rudland PS, Platt-Higgins A, El-Tanani M, et al. Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer[J]. Cancer research.2002;62 (12):3417-3427.
36. Macri A, Versaci A, Lupo G, et al. Role of osteopontin in breast cancer patients[J].Tumori.2009;95 (1):48-52.
37.杨莉,魏玲,左文述.骨桥蛋白与乳腺癌的研究现状[J].中华肿瘤防治杂志,2011：18(14)：1133-1137.
38. Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro:Vasculogenic mimicry [J]. The American journal of pathology.1999;155 (3):739-752.
39. Liu T, Sun B, Zhao X, et al. Her2/neu expression correlates with vasculogenic mimicry in invasive breast carcinoma[J]. Journal of cellular and molecular medicine.2013;17 (1):116-122.
40. Shirakawa K, Kobayashi H, Heike Y, et al.Hemodynamics in vasculogenic mimicry and angiogenesis of inflammatory breast cancer xenograft[J]. Cancer research.2002;62 (2):560-566.
41.张旭,陈宣世,刘俊.乳腺癌血管生成拟态与mvd、mmp-2表达及预后的关系[J].现代医药卫生.2007；23(18)：2693-2694.
1.国家癌症中心,卫生部疾病预防控制局.2011中国肿瘤登记年报[M].北京：军事医学科学出版社,2012：53-55.
2. Folkman J. Tumor angiogenesis:Therapeutic implications[J]. The New England journal of medicine.1971;285(21):1182-1186.
3. Bussolino F, Mantovani A, Persico G.Molecular mechanisms of blood vessel formation[J]. Trends in biochemical sciences.1997;22 (7):251-256.
4.程丽.乳腺癌抗血管生成研究进展[J].西南军医,2010,12(5)：936-938.
5. Fang J, Yan L, Shing Y, et al. Hif-lalpha-mediated up-regulation of vascular endothelial growth factor, independent of basic fibroblast growth factor, is important in the switch to the angiogenic phenotype during early tumorigenesis[J]. Cancer research.2001;61 (15):5731-5735.
6. Rykala J, Przybylowska K, Majsterek I, et al. Angiogenesis markers quantification in breast cancer and their correlation with clinicopathological prognostic variables[J]. Pathol Oncol Res.2011; 17(4):809-17.
7. Liaw L, Lindner V, Schwartz SM, et al. Osteopontin and beta 3 integrin are coordinately expressed in regenerating endothelium in vivo and stimulate Arg-Gly-Asp-dependent endothelial migration in vitro[J].Circ Res.1995;77(4):665-72.
8.李晓,黄迪南,侯敢.肿瘤血管生成调节因子的研究进展[J].生命科学.2007：19(2)：198-202.
9. Li C, Li R, Song H, et al. Significance of aeg-1 expression in correlation with vegf, microvessel density and clinicopathological characteristics in triple-negative breast cancer[J]. Journal of surgical oncology.2011;103(2):184-192.
10. Uzzan B,Nicolas P, Cucherat M, et al. Microvessel density as a prognostic factor in women with breast cancer:A systematic review of the literature and meta-analysis[J]. Cancer research. 2004;64 (9):2941-2955.
11. Weidner N, Semple JP,Welch WR, et al. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma[J].The New England journal of medicine.1991;324(1):1-8.
12. da Silva BB, Lopes-Costa PV, dos Santos AR, et al. Comparison of three vascular endothelial markers in the evaluation of microvessel density in breast cancer[J]. European journal of gynaecological oncology.2009;30 (3):285-288.
13. Ludovini V, Sidoni A, Pistola L, et al. Evaluation of the prognostic role of vascular endothelial growth factor and microvessel density in stages i and ii breast cancer patients[J]. Breast cancer research and treatment.2003;81(2):159-168.
14. Bolat F, Kayaselcuk F, Nursal TZ, et al. Microvessel density, vegf expression, and tumor-associated macrophages in breast tumors: Correlations with prognostic parameters [J]. Journal of experimental & clinical cancer research.2006;25 (3):365-372.
15. Saponaro C, Malfettone A, Ranieri G, et al. VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer[J]. PLoS One.2013; 8(1):1-8.
16. Rykala J, Przybylowska K,Majsterek I, et al. Angiogenesis markers quantification in breast cancer and their correlation with clinicopathological prognostic variables[J]. Pathol Oncol Res.2011; 17 (4):809-17.
17. Zhou D, Cheng SQ, Ji HF, et al.Evaluation of protein pigment epithelium-derived factor (PEDF) and microvessel density (MVD) as prognostic indicators in breast cancer[J].J Cancer Res Clin Oncol.2010; 136(11):1719-27.
18. Weidner N, Folkman J, Pozza F,et al. Tumor angiogenesis:a new significant and independent prognostic indicator in early-stage breast carcinoma[J]. J Natl Cancer Inst.1992;84(24):1875-87.
19.朱庆莉,游珊珊,孝梦甦等.对比超声定位光散射断层成像与彩色多普勒血流显像检测乳腺癌血供[J].中国医学影像技术,2011,27(9)：1833-1837.
20.周永昌,郭万学.超声医学(第四版)[M].北京：科学技术文献出版社,2002：108-109.
21.钱小霞,司芩,钱晓莉等.乳腺癌超声造影特征分析[J].中华超声影像学杂志,2012,21(3)：217-219.
22. Zhu Q, Kurtzma SH, Hegde P, et al. Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers[J]. Neoplasia.2005; 7(3):263-270.
23. Choi JS, Kim MJ, Youk JH, et al. Us-guided optical tomography:Correlation with clinicopathologic variables in breast cancer[J]. Ultrasound in medicine & biology.2013;39:233-240.
24. Zhi W, Gu X, Qin J, et al. Solid breast lesions:Clinical experience with us-guided diffuse optical tomography combined with conventional us[J]. Radiology.2012;265 (2):371-378.
25. You SS, Jiang YX, Zhu QL, et al. Us-guided diffused optical tomography:A promising functional imaging technique in breast lesions [J]. European radiology.2010;20:309-317.
26.梁忠锃.抗血管生成治疗在乳腺癌中的研究进展[J].医学综述,2012,18(7)：1032-1034.
27. Loges S1, Roncal C, Carmeliet PDevelopment of targeted angiogenic medicine[J]. J Thromb Haemost.2009;7(1):21-33.
28.林燕,孙强,管珩,等.贝伐单抗在乳腺癌治疗中的应用[J].中国普通外科杂志,2011,20(11)：1255-1258.
29.胡燕,姚颐,张钧,等.表阿霉素联合索拉非尼对乳腺癌MCF-7细胞的生长周期及凋亡作用[J].医学信息,2013,(13)：453-453.
30.袁霞,张东生,袁中玉,等.恩度联合化疗在HER-2阴性乳腺癌肝转移中的临床应用——附5例报告[J].癌症进展,2007,5(6)：604-607.
31. Wang R, Zhou S, Li S. Cancer therapeutic agents targeting hypoxia-inducible factor-1[J]. Curr Med Chem.2011;18(21):3168-3189.
2. Zhi W, Gu X, Qin J, et al. Solid breast lesions:Clinical experience with us-guided diffuse optical tomography combined with conventional us[J]. Radiology.2012;265(2):371-378.
3. Zhu Q, Kurtzma SH, Hegde P, et al. Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers[J]. Neoplasia. 2005; 7 (3):263-270.
4. Folkman J. Tumor angiogenesis:Therapeutic implications[J]. The New England journal of medicine.1971;285 (21):1182-1186.
5. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma[J]. The New England journal of medicine.1991;324:1-8.
6. Yang J, Mani SA, Donaher JL, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis[J]. Cell. 2004;117(17):927-939.
7. Hansen S, Grabau DA, Sorensen FB, et al. Vascular grading of angiogenesis: Prognostic significance in breast cancer [J]. British journal of cancer. 2000;82(2):339-347.
8. Zhu Q, Xiao M, You S, et al. Ultrasound-guided diffuse optical tomography (dot) of invasive breast carcinoma:Does tumour total haemoglobin concentration contribute to the prediction of axillary lymph node status[J]?European journal of radiology.2012;81:3185-3189.
9. Bolat F, Kayaselcuk F, Nursal TZ,et al. Microvessel density, vegf expression, and tumor-associated macrophages in breast tumors Correlations with prognostic parameters[J]. Journal of experimental & clinical cancer research:CR.2006;25(3):365-372.
10.孝梦甦,乳腺病变及其术后疤痕的超声定位光散射断层成像研究[D].北京：北京协和医学院,2010：
11. Choi JS, Kim MJ, Youk JH, et al. Us-guided optical tomography: Correlation with clinicopathologic variables in breast cancer[J]. Ultrasound in medicine & biology.2013;39(2):233-240.
12.单明,张建国.肿瘤淋巴转移机制的研究进展[J].解剖与临床.2008；13(1)：57-62.
13. Li C, Li R, Song H, et al. Significance of aeg-1 expression in correlation with vegf, microvessel density and clinicopathological characteristics in triple-negative breast cancer[J]. Journal of surgical oncology.2011;103(2):184-192.
14. Thielemann A, Kopczynski Z, Filas V, et al. The determination of vegf and mvd, among patients with primary breast cancer [J]. Pathology oncology research.2008;14(2):137-144.
15. Toikkanen S, Pylkkanen L, Joensuu H. Invasive lobular carcinoma of the breast has better short-and long-term survival than invasive ductal carcinoma[J].Br J Cancer.1997;76(9):1234-1240.
16. Colleoni M, Russo L, Dellapasqua S. Adjuvant therapies for special types of breast cancer[J]. Breast.2011;20 Suppl 3:S153-157.
17. Liotta LA, Kleinerman J, Saidel GM. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation[J]. Cancer research.1974;34(5):997-1004.
18. Heimann R.Ferguson D, Powers C, et al. Angiogenesis as a predictor of long-term survival for patients with node-negative breast cancer [J]. J Natl Cancer Inst.1996;88(23):1764-1769.
19. Ludovini V, Sidoni A, Pistola L, et al. Evaluation of the prognostic role of vascular endothelial growth factor and microvessel density in stages i and ii breast cancer patients[J].Breast cancer research and treatment.2003;81(2):159-168.
20. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis:A new significant and independent prognostic indicator in early-stage breast carcinoma[J]. Journal of the National Cancer Institute.1992;84(24):1875-1887.
21. L. A. Liotta, M. L. Stracke, E. Kohn, et al. New Directions in Cancer Treatment[J].Heidelberg:Springer Berlin Heidelberg,1989:381-398.
22.周力恒,殷文瑾,陆劲松,等.乳腺癌患者术后不同部位复发转移的风险分布[J].中国癌症杂志,2008,18(2)：124-127.
23.殷文瑾,周力恒,陆劲松,等.乳腺癌术后复发风险时间分布规律研究[J].实用肿瘤杂志,2007,22(6)：527-531.
1. Zhu Q, Xiao M, You S, et al. Ultrasound-guided diffuse optical tomography (dot) of invasive breast carcinoma:Does tumour total haemoglobin concentration contribute to the prediction of axillary lymph node status[J]?European journal of radiology.2012;81 (11):3185-3189.
2. Choi JS, Kim MJ, Youk JH, et al. Us-guided optical tomography: Correlation with clinicopathologic variables in breast cancer[J]. Ultrasound in medicine & biology.2013;39 (2):233-240.
3. You SS, Jiang YX, Zhu QL, et al. Us-guided diffused optical tomography:A promising functional imaging technique in breast lesions [J]. European radiology.2010;20 (2):309-317.
4. Zhi W, Gu X, Qin J, et al. Solid breast lesions:Clinical experience with us-guided diffuse optical tomography combined with conventional us[J]. Radiology.2012;265 (2):371-378.
5. Ludovini V, Sidoni A, Pistola L, et al. Evaluation of the prognostic role of vascular endothelial growth factor and microvessel density in stages i and ii breast cancer patients [J]. Breast cancer research and treatment.2003;81 (2):159-168.
6.孙宝存.肿瘤血管生成研究进展[R].长春,中华医学会,2005：
7. Chaudary N, Hill RP. Hypoxia and metastasis in breast cancer [J]. Breast disease.2006;26:55-64.
8. Liaw L, Lindner V, Schwartz SM, et al. Osteopontin and beta 3 integrin are coordinately expressed in regenerating endothelium in vivo and stimulate arg-gly-asp-dependent endothelial migration in vitro[J]. Circulation research.1995;77 (4):665-672.
9. Augustin HG. Antiangiogenic tumour therapy:Will it work[J]?Trends in pharmacological sciences.1998;19 (6):216-222.
10. Zhang S, Zhang D, Sun B. Vasculogenic mimicry:Current status and future prospects[J]. Cancer letters.2007;254 (2):157-164.
11. Li C, Li R, Song H, et al. Significance of aeg-1 expression in correlation with vegf, microvessel density and clinicopathological characteristics in triple-negative breast cancer[J]. Journal of surgical oncology.2011;103 (2):184-192.
12. Wang-Rodriguez J, Urquidi V, Rivard A, et al. Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status [J]. Breast cancer research:BCR.2003;5 (5):R136-143.
13. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma[J]. The New England journal of medicine.1991;324 (1):1-8.
14. Bussolino F, Mantovani A, Persico G. Molecular mechanisms of blood vessel formation[J]. Trends in biochemical sciences.1997;22 (7):251-256.
15.程丽.乳腺癌抗血管生成研究进展[J].西南军医,2010,12(5)：936-938.
16. Kohn S, Nagy JA, Dvorak HF,et al. Pathways of macromolecular tracer transport across venules and small veins. Structural basis for the hyperpermeability of tumor blood vessels[J]. Laboratory investigation.1992;67 (5):596-607.
17. Gupta MK, Qin RY. Mechanism and its regulation of tumor-induced angiogenesis[J]. World journal of gastroenterology.2003;9 (6):1144-1155.
18. Thielemann A, Kopczynski Z, Filas V, et al. The determination of vegf and mvd, among patients with primary breast cancer [J]. Pathology oncology research.2008;14 (2):137-144.
19.李晓,黄迪南,侯敢.肿瘤血管生成调节因子的研究进展[J].生命科学.2007：19(2)：198-202.
20. Zhu Q, Kurtzma SH, Hegde P, et al. Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers[J].Neoplasia.2005;7 (3):263-270.
21. Zhu Q, Tannenbaum S, Hegde P, et al. Noninvasive monitoring of breast cancer during neoadjuvant chemotherapy using optical tomography with ultrasound localization[J]. Neoplasia.2008;10 (10):1028-1040.
22. Xiang L, Gilkes DM, Chaturvedi P, et al. Ganetespib blocks hif-1 activity and inhibits tumor growth, vascularization, stem cell maintenance, invasion, and metastasis in orthotopic mouse models of triple-negative breast cancer[J]. Journal of molecular medicine.2014;92 (2):151-164.
23. Fang J, Yan L, Shing Y, et al. Hif-lalpha-mediated up-regulation of vascular endothelial growth factor, independent of basic fibroblast growth factor, is important in the switch to the angiogenic phenotype during early tumorigenesis[J]. Cancer research.2001;61 (15):5731-5735.
24. Jiang BH, Semenza GL, Bauer C, et al. Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of o2 tension[J]. The American journal of physiology.1996;271 (4 Pt 1):C1172-1180.
25. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia:Role of the hif system[J]. Nature medicine.2003;9 (6):677-684.
26.王红磊,武力,阙燕,等.超声光散射断层成像(dot)与乳腺癌血管生成病理学的相关性[J].复旦学报(医学版),2012：39(3)：261-267.
27. Amini A, Masoumi Moghaddam S, Morris DL, et al.The critical role of vascular endothelial growth factor in tumor angiogenesis [J]. Current cancer drug targets.2012;12 (1):23-43.
28. Kim MJ, Kim JY, Youn JH, et al. Us-guided diffuse optical tomography for breast lesions:The reliability of clinical experience[J]. European radiology.2011:21 (7):1353-1363.
29. Kerbel RS.Tumor angiogenesis:Past,present and the near future[J].Carcinogenesis.2000;21 (3):505-515.
30. Zhu Q, Huang M, Chen N, et al. Ultrasound-guided optical tomographic imaging of malignant and benign breast lesions:Initial clinical results of 19 cases[J].Neoplasia.2003;5 (5):379-388.
31. Yamamoto Y, Ibusuki M, Okumura Y, et al. Hypoxia-inducible factor lalpha is closely linked to an aggressive phenotype in breast cancer [J]. Breast cancer research and treatment.2008; 110 (3):465-475.
32. Wang W, He YF, Sun QK, et al. Hypoxia-inducible factor lalpha in breast cancer prognosis[J]. Clinica chimica acta.2014;428:32-37.
33. Bolat F, Kayaselcuk F, Nursal TZ,et al.Microvessel density, vegf expression, and tumor-associated macrophages in breast tumors Correlations with prognostic parameters[J]. Journal of experimental & clinical cancer research.2006;25 (3):365-372.
34.许进,夏潮涌,周序珑,等.实体肿瘤组织微血管计数方法的探讨[J].中华病理学杂志,2005;34(2)：111-112.
35. Rudland PS, Platt-Higgins A, El-Tanani M, et al. Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer[J]. Cancer research.2002;62 (12):3417-3427.
36. Macri A, Versaci A, Lupo G, et al. Role of osteopontin in breast cancer patients[J].Tumori.2009;95 (1):48-52.
37.杨莉,魏玲,左文述.骨桥蛋白与乳腺癌的研究现状[J].中华肿瘤防治杂志,2011：18(14)：1133-1137.
38. Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro:Vasculogenic mimicry [J]. The American journal of pathology.1999;155 (3):739-752.
39. Liu T, Sun B, Zhao X, et al. Her2/neu expression correlates with vasculogenic mimicry in invasive breast carcinoma[J]. Journal of cellular and molecular medicine.2013;17 (1):116-122.
40. Shirakawa K, Kobayashi H, Heike Y, et al.Hemodynamics in vasculogenic mimicry and angiogenesis of inflammatory breast cancer xenograft[J]. Cancer research.2002;62 (2):560-566.
41.张旭,陈宣世,刘俊.乳腺癌血管生成拟态与mvd、mmp-2表达及预后的关系[J].现代医药卫生.2007；23(18)：2693-2694.
1.国家癌症中心,卫生部疾病预防控制局.2011中国肿瘤登记年报[M].北京：军事医学科学出版社,2012：53-55.
2. Folkman J. Tumor angiogenesis:Therapeutic implications[J]. The New England journal of medicine.1971;285(21):1182-1186.
3. Bussolino F, Mantovani A, Persico G.Molecular mechanisms of blood vessel formation[J]. Trends in biochemical sciences.1997;22 (7):251-256.
4.程丽.乳腺癌抗血管生成研究进展[J].西南军医,2010,12(5)：936-938.
5. Fang J, Yan L, Shing Y, et al. Hif-lalpha-mediated up-regulation of vascular endothelial growth factor, independent of basic fibroblast growth factor, is important in the switch to the angiogenic phenotype during early tumorigenesis[J]. Cancer research.2001;61 (15):5731-5735.
6. Rykala J, Przybylowska K, Majsterek I, et al. Angiogenesis markers quantification in breast cancer and their correlation with clinicopathological prognostic variables[J]. Pathol Oncol Res.2011; 17(4):809-17.
7. Liaw L, Lindner V, Schwartz SM, et al. Osteopontin and beta 3 integrin are coordinately expressed in regenerating endothelium in vivo and stimulate Arg-Gly-Asp-dependent endothelial migration in vitro[J].Circ Res.1995;77(4):665-72.
8.李晓,黄迪南,侯敢.肿瘤血管生成调节因子的研究进展[J].生命科学.2007：19(2)：198-202.
9. Li C, Li R, Song H, et al. Significance of aeg-1 expression in correlation with vegf, microvessel density and clinicopathological characteristics in triple-negative breast cancer[J]. Journal of surgical oncology.2011;103(2):184-192.
10. Uzzan B,Nicolas P, Cucherat M, et al. Microvessel density as a prognostic factor in women with breast cancer:A systematic review of the literature and meta-analysis[J]. Cancer research. 2004;64 (9):2941-2955.
11. Weidner N, Semple JP,Welch WR, et al. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma[J].The New England journal of medicine.1991;324(1):1-8.
12. da Silva BB, Lopes-Costa PV, dos Santos AR, et al. Comparison of three vascular endothelial markers in the evaluation of microvessel density in breast cancer[J]. European journal of gynaecological oncology.2009;30 (3):285-288.
13. Ludovini V, Sidoni A, Pistola L, et al. Evaluation of the prognostic role of vascular endothelial growth factor and microvessel density in stages i and ii breast cancer patients[J]. Breast cancer research and treatment.2003;81(2):159-168.
14. Bolat F, Kayaselcuk F, Nursal TZ, et al. Microvessel density, vegf expression, and tumor-associated macrophages in breast tumors: Correlations with prognostic parameters [J]. Journal of experimental & clinical cancer research.2006;25 (3):365-372.
15. Saponaro C, Malfettone A, Ranieri G, et al. VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer[J]. PLoS One.2013; 8(1):1-8.
16. Rykala J, Przybylowska K,Majsterek I, et al. Angiogenesis markers quantification in breast cancer and their correlation with clinicopathological prognostic variables[J]. Pathol Oncol Res.2011; 17 (4):809-17.
17. Zhou D, Cheng SQ, Ji HF, et al.Evaluation of protein pigment epithelium-derived factor (PEDF) and microvessel density (MVD) as prognostic indicators in breast cancer[J].J Cancer Res Clin Oncol.2010; 136(11):1719-27.
18. Weidner N, Folkman J, Pozza F,et al. Tumor angiogenesis:a new significant and independent prognostic indicator in early-stage breast carcinoma[J]. J Natl Cancer Inst.1992;84(24):1875-87.
19.朱庆莉,游珊珊,孝梦甦等.对比超声定位光散射断层成像与彩色多普勒血流显像检测乳腺癌血供[J].中国医学影像技术,2011,27(9)：1833-1837.
20.周永昌,郭万学.超声医学(第四版)[M].北京：科学技术文献出版社,2002：108-109.
21.钱小霞,司芩,钱晓莉等.乳腺癌超声造影特征分析[J].中华超声影像学杂志,2012,21(3)：217-219.
22. Zhu Q, Kurtzma SH, Hegde P, et al. Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers[J]. Neoplasia.2005; 7(3):263-270.
23. Choi JS, Kim MJ, Youk JH, et al. Us-guided optical tomography:Correlation with clinicopathologic variables in breast cancer[J]. Ultrasound in medicine & biology.2013;39:233-240.
24. Zhi W, Gu X, Qin J, et al. Solid breast lesions:Clinical experience with us-guided diffuse optical tomography combined with conventional us[J]. Radiology.2012;265 (2):371-378.
25. You SS, Jiang YX, Zhu QL, et al. Us-guided diffused optical tomography:A promising functional imaging technique in breast lesions [J]. European radiology.2010;20:309-317.
26.梁忠锃.抗血管生成治疗在乳腺癌中的研究进展[J].医学综述,2012,18(7)：1032-1034.
27. Loges S1, Roncal C, Carmeliet PDevelopment of targeted angiogenic medicine[J]. J Thromb Haemost.2009;7(1):21-33.
28.林燕,孙强,管珩,等.贝伐单抗在乳腺癌治疗中的应用[J].中国普通外科杂志,2011,20(11)：1255-1258.
29.胡燕,姚颐,张钧,等.表阿霉素联合索拉非尼对乳腺癌MCF-7细胞的生长周期及凋亡作用[J].医学信息,2013,(13)：453-453.
30.袁霞,张东生,袁中玉,等.恩度联合化疗在HER-2阴性乳腺癌肝转移中的临床应用——附5例报告[J].癌症进展,2007,5(6)：604-607.
31. Wang R, Zhou S, Li S. Cancer therapeutic agents targeting hypoxia-inducible factor-1[J]. Curr Med Chem.2011;18(21):3168-3189.