血管抑素与内皮抑素作用下抗血管生成治疗对肿瘤微血管网与微环境影响的模拟研究

吴洁; 丁祖荣; 蔡彦; 许世雄; 赵改平; 龙泉

doi:10.3879/j.issn.1000-0887.2011.04.005

血管抑素与内皮抑素作用下抗血管生成治疗对肿瘤微血管网与微环境影响的模拟研究

doi: 10.3879/j.issn.1000-0887.2011.04.005

上海交通大学船舶海洋与建筑工程学院,上海 200240;
复旦大学力学与工程科学系,上海 200433;
上海理工大学医疗器械与食品学院,上海 200093;

基金项目: 国家自然科学基金资助项目(10772051);中国博士后基金资助项目(20100470702)

详细信息

作者简介:
吴洁(1982- ),女,上海人,博士(联系人.Tel:+86-21-34204313;E-mail:janny-wujie@yahoo.com.cn).

中图分类号: R318.01; TB115
计量
- 文章访问数: 1253
- HTML全文浏览量: 92
- PDF下载量: 861
- 被引次数: 0
出版历程
- 收稿日期: 2010-05-10
- 修回日期: 2011-02-23
- 刊出日期: 2011-04-15

Simulation of Tumor Microvasculature and Microenvironment Response to Anti-Angiogenic Treatment by Angiostatin and Endostatin

School of Naval Architecture, Ocean and Civil Engineering, Shanghai Jiaotong University, Shanghai 200240, P. R. China;
Department of Mechanics and Engineering Science, Fudan University, Shanghai 200433, P. R. China;
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, P. R. China;
Brunel Institute for Bioengineering, Brunel University, London UB8 3PH, UK

摘要

摘要: 基于对血管抑素和内皮抑素作用下肿瘤抗血管生成及血液动力学的数学建模与数值模拟，研究抗血管生成治疗对肿瘤微血管网的影响及对微环境流动的改善作用．研究表明，抗血管生成治疗后:1）新生血管的生长与分叉受到抑制，血管化程度降低；2）血液灌注量减少,间质高压得到缓解,渗入宿主组织的间质液减少,负向跨壁流量大幅下降．
- 实体肿瘤 /
- 抗血管生成 /
- 微环境正常化 /
- 数值模拟
Abstract: The effects of anti-angiogenesis treatment by angiostain and endostatin on normalization of tumor microvasculature and microenvironment was investigated,based on mathematical modeling and numerical simulation of tumor anti-angiogenesis and tumor haemodynamics.The results show that,after antiangiogenesis treatment:1) the proliferation,growth and branching of neo-vessels is effectively inhibited,the extent of vascularization in tumors is accordingly reduced;2) the overall blood perfusion inside tumor is declined;the plateau of tumor interstitial fluid pressure is relieved;the interstitial fluid oozing out from the tumor periphery into the surrounding normal tissue is reduced;the intravasations across vasculature is remarkably decreased.
- solid tumor /
- anti-angiogenesis /
- microenvironment normalization /
- numerical simulation

HTML全文

参考文献(20)

[1]	Jain R K, Tong R T, Munn L L. Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: insights from a mathematical model[J]. Cancer Res, 2007, 67(6): 2729-2735. doi: 10.1158/0008-5472.CAN-06-4102
[2]	Fukumura D, Jain R K. Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization[J]. Microvas Res, 2007, 74(2): 72-84. doi: 10.1016/j.mvr.2007.05.003
[3]	Huber P E, Bischof M, Jenne J, Heiland S, Peschke P, Saffrich R, Grne H J, Debus J, Lipson K E, Abdollahi A. Trimodal cancer treatment: beneficial effects of combined antiangiogenesis, radiation, and chemotherapy[J]. Cancer Res, 2005, 65(9): 3643-3655. doi: 10.1158/0008-5472.CAN-04-1668
[4]	Tong R T, Boucher Y, Kozin S V, Winkler F, Hicklin D J, Jain R K. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors[J]. Cancer Res, 2004, 64(11): 3731-3736. doi: 10.1158/0008-5472.CAN-04-0074
[5]	Willett C G, Boucher Y, di Tomaso E, Duda D G, Munn L L, Tong R T, Chung D C, Sahani D V, Kalva S P, Kozin S V, Mino M, Cohen K S, Scadden D T, Hartford A C, Fischman A J, Clark J W, Ryan D P, Zhu A X, Blaszkowsky L S, Chen H X, Shellito P C, Lauwers G Y, Jain R K. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer[J]. Nat Med, 2004, 10(2): 145-147. doi: 10.1038/nm988
[6]	Willett C G, Boucher Y, Duda D G, di Tomaso E, Munn L L, Tong R T, Kozin S V, Petit L, Jain R K, Chung D C, Sahani D V, Kalva S P, Cohen K S, Scadden D T, Fischman A J, Clark J W, Ryan D P, Zhu A X, Blaszkowsky L S, Shellito P C, Mino-Kenudson M, Lauwers G Y. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for Bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients[J]. J Clin Oncol, 2005, 23(31): 8136-8139. doi: 10.1200/JCO.2005.02.5635
[7]	O’Reilly M S, Holmgren L, Shing Y, Chen C, Rosenthal R A, Moses M, Lane W S, Cao Y, Sage E H, Folkman J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma[J]. Cell, 1994, 79(2): 315-328. doi: 10.1016/0092-8674(94)90200-3
[8]	O’Reilly M S, Boehm T, Shing Y, Fukai N, Vasios G, Lane W S, Flynn E, Birkhead J R, Olsen B R, Folkman J. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth[J]. Cell, 1997, 88(2): 277-285. doi: 10.1016/S0092-8674(00)81848-6
[9]	Tee D, DiStefano Ⅲ J. Simulation of tumor-induced angiogenesis and its response to anti-angiogenic drug treatment: mode of drug delivery and clearance rate dependencies[J]. J Cancer Res Clin Oncol, 2004, 130(1): 15-24. doi: 10.1007/s00432-003-0491-1
[10]	赵改平, 高昊, 吴洁, 许世雄，Collins M W, LONG Quan, Knig C S, Padhani A R.抗血管生成因子Angiostatin与Endostatin作用下肿瘤血管生成的二维数值模拟[J]. 医用生物力学, 2006, 21(4): 272-279. (ZHAO Gai-ping, GAO Hao, WU Jie, XU Shi-xiong, Collins M W, LONG Quan, Knig C S, Padhani A R. 2D numerical simulation of effect anti-angiogenic factors Angiostatin and Endostatin on tumor-induced angiogenesis[J]. J Med Biomech, 2006, 21(4): 272-279. (in Chinese))
[11]	Anderson A R A, Chaplain M A J. Continuous and discrete mathematical models of tumor-induced angiogenesis[J]. Bull Math Biol, 1998, 60(5): 857-900. doi: 10.1006/bulm.1998.0042
[12]	Wu J, Xu S X, Long Q, Collins M W, Knig C S, Zhao G, Jiang Y, Padhani A R. Coupled modeling of blood perfusion in intravascular, interstitial spaces in tumor microvasculature[J]. J Biomech, 2008, 41(5): 996-1004. doi: 10.1016/j.jbiomech.2007.12.008
[13]	Wu J, Long Q, Xu S X, Padhani A R.Study of tumor blood perfusion and its variation due to vascular normalization by anti-angiogenic therapy based on 3D angiogenic microvasculature[J]. J Biomech, 2009, 42(6): 712-721. doi: 10.1016/j.jbiomech.2009.01.009
[14]	Baxter L T, Jain R K. Transport of fluid and macromolecules in tumors—Ⅱ: role of heterogeneous perfusion and lymphatics[J]. Microvas Res, 1990, 40(2): 246-263. doi: 10.1016/0026-2862(90)90023-K
[15]	万若. 淋巴回流的动力[J]. 生物学教育, 1993, 9: 32. (WAN Ruo. Dynamics of lymphatic return[J]. Biology Teaching, 1993, 9: 32. (in Chinese))
[16]	Netti P A, Roberge S, Boucher Y, Baxter L T, Jain R K. Effect of transvascular fluid exchange on pressure-flow relationship in tumors: a proposed mechanism for tumor blood flow heterogeneity[J]. Microvas Res, 1996, 52(1): 27-46. doi: 10.1006/mvre.1996.0041
[17]	Pries A R, Secomb T W, Gessner T, Sperandio M B, Gross J F, Gaehtgens P. Resistance to blood flow in microvessels in vivo[J]. Circulation Res, 1994, 75(5): 904-915. doi: 10.1161/01.RES.75.5.904
[18]	Pries A R, Secomb T W. Microvascular blood viscosity in vivo and the endothelial surface layer[J]. Am J Physiol Heart Circ Physiol, 2005, 289(6): H2657-H2664.
[19]	Eriksson K, Magnusson P, Dixelius J, Claesson-Welsh L, Cross M J. Angiostatin and endostatin inhibit endothelial cell migration in response to FGF and VEGF without interfering with specific intracellular signal transduction pathways[J]. FEBS Letters, 2003, 536(1/3): 19-24. doi: 10.1016/S0014-5793(03)00003-6
[20]	Herbst R S, Mullani N A, Davis D W, Hess K R, McConkey D J, Charnsangavej C, O'Reilly M S, Kim H W, Baker C, Roach J, Ellis L M, Rashid A, Pluda J, Bucana C, Madden T L, Tran H T, Abbruzzese J L. Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin[J]. J Clin Oncol, 2002, 20(18): 3804-3814. doi: 10.1200/JCO.2002.05.102

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 1253
HTML全文浏览量: 92
PDF下载量: 861
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

血管抑素与内皮抑素作用下抗血管生成治疗对肿瘤微血管网与微环境影响的模拟研究

doi: 10.3879/j.issn.1000-0887.2011.04.005

作者简介:
吴洁(1982- ),女,上海人,博士(联系人.Tel:+86-21-34204313;E-mail:janny-wujie@yahoo.com.cn).

计量

Simulation of Tumor Microvasculature and Microenvironment Response to Anti-Angiogenic Treatment by Angiostatin and Endostatin

计量

目录

留言板

血管抑素与内皮抑素作用下抗血管生成治疗对肿瘤微血管网与微环境影响的模拟研究

doi: 10.3879/j.issn.1000-0887.2011.04.005

作者简介: 吴洁(1982- ),女,上海人,博士(联系人.Tel:+86-21-34204313;E-mail:janny-wujie@yahoo.com.cn).

计量

出版历程

Simulation of Tumor Microvasculature and Microenvironment Response to Anti-Angiogenic Treatment by Angiostatin and Endostatin

计量

出版历程

目录

作者简介:
吴洁(1982- ),女,上海人,博士(联系人.Tel:+86-21-34204313;E-mail:janny-wujie@yahoo.com.cn).