登录    
  
首页 > 期刊论文 > 论文摘要
肿瘤血管正常化与肿瘤治疗
         
Tumor blood vessel normalization and antitumor therapy

摘    要
传统的抗血管生成疗法的目的在于阻断有助于肿瘤生长和转移的营养通道。虽然这类药物已在临床上应用多年,但其治疗效果仍存在争议,并可能会进一步增加化疗药物耐药性的产生。造成这一现象的原因可能是由于促血管生长因子的过度表达和释放,使得肿瘤组织血管呈现出一种结构和功能异常的状态。基于此,有学者提出了肿瘤血管的正常化理论。诸多研究显示,肿瘤血管正常化可以作为抗肿瘤治疗的补充疗法。本文着重讨论肿瘤血管正常化的分子机制、临床优势以及仍待解决的问题,以便为肿瘤研究工作者及正在研发肿瘤血管抑制剂的制药企业提供有益的参考。
标    签 肿瘤   新生血管化,病理性   肿瘤辅助治疗   血管正常化   Neoplasms   Neovascularization, pathologic   Neoadjuvant therapy   Blood vessel normalization  
 
Abstract
Traditional anti-angiogenesis strategies attempt to limit the blood supply to tumor and hence inhibit tumor growth. Although such therapeutic strategies have been used in clinical practice for many years, their effects are still controversial because they may lead to drug resistance. As a result of excessive production of angiogenic molecules, the tumor vessels become abnormal in structure and function. Based on these findings, some researchers have proposed a theory of normalization of tumor blood vessels. The evidence from preclinical and initial clinical trials revealed that normalization of tumor blood vessels could be considered as a complementary therapy to treat tumor. In this article, the mechanisms, benefits, and possible clinical translation of vessel normalization for tumor, which may provide some beneficial references for investigators and pharmaceutical companies involved in this research area, were discussed.

中图分类号 R730.5   DOI 10.3781/j.issn.1000-7431.2013.07.015

 
  购买该论文  中国光学期刊网论文下载说明
      


所属栏目 综述

基金项目 国家自然科学基金资助项目(编号:81173174);国家科技支撑计划(编号:2008BAI51B02)

收稿日期 2013/3/22

修改稿日期 2013/4/26

网络出版日期

作者单位点击查看


引用该论文: WANG Si-liang,SHENG Xiao-bo,WEI Zhong-hong,YANG Zhao-cong,CHEN Chen,CHEN Wen-xing,WANG Ai-yun,ZHENG Shi-zhong,LU Yin. Tumor blood vessel normalization and antitumor therapy[J]. Tumor, 2013, 33(7): 653~657
汪思亮,盛晓波,韦忠红,杨召聪,陈晨,陈文星,王爱云,郑仕中,陆茵. 肿瘤血管正常化与肿瘤治疗[J]. 肿瘤, 2013, 33(7): 653~657


论文评价
共有人对该论文发表了看法,其中:
人认为该论文很差
人认为该论文较差
人认为该论文一般
人认为该论文较好
人认为该论文很好
分享论文
分享到新浪微博 分享到腾讯微博 分享到人人网 分享到 Google Reader 分享到百度搜藏分享到Twitter

参考文献
【1】CARMELIET P, JAIN R K. Molecular mechanisms andc linical applications of angiogenesis[J]. Nature, 2011,473(7347):298-307.
 
【2】JAIN R K. Molecular regulation of vessel maturation[J].Nat Med, 2003, 9(6):685-693.
 
【3】HOLLEB A I, FOLKMAN J. Tumor angiogenesis[J]. CACancer J Clin, 1972, 22(4):226-229.
 
【4】NAGY J A, CHANG S H, SHIH S C, et al. Heterogeneity ofthe tumor vasculature[J]. Semin Thromb Hemost, 2010,36(3):321-331.
 
【5】FOLKMAN J. Tumor angiogenesis:therapeuticimplications[J]. N Engl J Med, 1971, 285(21):1182-1186.
 
【6】虞永峰, 庄兰妹, 陆舜. 抗肿瘤血管生成:肺癌治疗新希望——2006年ASCO新进展[J]. 肿瘤, 2006, (7):592-595.
 
【7】CARMELIET P, JAIN R K. Principles and mechanisms ofvessel normalization for cancer and other angiogenicdiseases[J]. Nat Rev Drug Discov, 2011, 10(6):417-427.
 
【8】VAN CUTSEM E, LAMBRECHTS D, PRENEN H, et al.Lessons from the adjuvant bevacizumab trial on coloncancer:what next?[J]. J Clin Oncol, 2011, 29(1):1-4.
 
【9】CRAWFORD Y, FERRARA N. VEGF inhibition:insights frompreclinical and clinical studies[J]. Cell Tissue Res, 2009,335(1):261-269.
 
【10】FERRARA N. Pathways mediating VEGF-independenttumor angiogenesis[J]. Cytokine Growth Factor Rev,2010, 21(1):21-26.
 
【11】SHANG B, CAO Z, ZHOU Q. Progress in tumor vascularnormalization for anticancer therapy:challenges andperspectives[J]. Front Med, 2012, 6(1):67-78.
 
【12】SATO Y. Persistent vascular normalization as analternative goal of anti-angiogenic cancer therapy[J].Cancer Sci, 2011, 102(7):1253-1256.
 
【13】JAIN R K. Normalizing tumor vasculature with antiangiogenic therapy:a new paradigm for combinationtherapy[J]. Nat Med, 2001, 7(9):987-989.
 
【14】GOEL S, DUDA D G, XU L, et al. Normalization of thevasculature for treatment of cancer and other diseases[J].Physiol Rev, 2011, 91(3):1071-1121.
 
【15】JAIN R K. Normalization of tumor vasculature:anemerging concept in antiangiogenic therapy[J]. Science,2005, 307(5706):58-62.
 
【16】TONG R T, BOUCHER Y, KOZIN S V, et al. Vascularnormalization by vascular endothelial growth factorreceptor 2 blockade induces a pressure gradient acrossthe vasculature and improves drug penetration intumors[J]. Cancer Res, 2004, 64(11):3731-3736.
 
【17】WINKLER F, KOZIN S V, TONG R T, et al. Kinetics ofvascular normalization by VEGFR2 blockade governsbrain tumor response to radiation:role of oxygenation,angiopoietin-1, and matrix metalloproteinases[J]. CancerCell, 2004, 6(6):553-563.
 
【18】CARMELIET P. Angiogenesis in life, disease andmedicine[J]. Nature, 2005, 438(7070):932-936.
 
【19】MAZZONE M, DETTORI D, LEITE DE OLIVEIRA R,et al. Heterozygous deficiency of PHD2 restores tumoroxygenation and inhibits metastasis via endothelialnormalization[J]. Cell, 2009, 136(5):839-851.
 
【20】HAMZAH J, JUGOLD M, KIESSLING F, et al. Vascularnormalization in Rgs5-deficient tumours promotesimmune destruction[J]. Nature, 2008, 453(7193):410-414.
 
【21】FUKUMURA D, DUDA D G, MUNN L L, et al. Tumormicrovasculature and microenvironment:novel insightsthrough intravital imaging in pre-clinical models[J].Microcirculation, 2010, 17(3):206-225.
 
【22】JAIN R K, STYLIANOPOULOS T. Delivering nanomedicine tosolid tumors[J]. Nat Rev Clin Oncol, 2010, 7(11):653-664.
 
【23】BALUK P, HASHIZUME H, McDONALD D M. Cellularabnormalities of blood vessels as targets in cancer[J].Curr Opin Genet Dev, 2005, 15(1):102-111.
 
【24】PÀEZ-RIBES M, ALLEN E, HUDOCK J, et al. Antiangiogenic therapy elicits malignant progression of tumors toincreased local invasion and distant metastasis[J]. CancerCell, 2009, 15(3):220-231.
 
【25】BERGERS G, HANAHAN D. Modes of resistance to antiangiogenic therapy[J]. Nat Rev Cancer, 2008, 8(8):592-603.
 
【26】EBOS J M, LEE C R, CRUZ-MUNOZ W, et al. Acceleratedmetastasis after short-term treatment with a potent inhibitorof tumor angiogenesis[J]. Cancer Cell, 2009, 15(3):232-239.
 
【27】OZAWA M G, YAO V J, CHANTHERY Y H, et al. Angiogenesiswith pericyte abnormalities in a transgenic model ofprostate carcinoma[J]. Cancer, 2005, 104(10):2104-2115.
 
【28】HOBBS S K, MONSKY W L, YUAN F, et al. Regulation oftransport pathways in tumor vessels:role of tumor typeand microenvironment[J]. Proc Nat Acad Sci U S A, 1998,95(8):4607-4612.
 
【29】JAIN R K. Lessons from multidisciplinary translationaltrials on anti-angiogenic therapy of cancer[J]. Nat RevCancer, 2008, 8(4):309-316.
 
【30】MAJMUNDAR A J, WONG W J, SIMON M C. Hypoxiainducible factors and the response to hypoxic stress[J].Mol Cell, 2010, 40(2):294-309.
 
【31】REY S, SEMENZA G L. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascularremodelling[J]. Cardiovasc Res, 2010, 86(2):236-242.
 
【32】DEJANA E, ORSENIGO F, LAMPUGNANI M G. Therole of adherens junctions and VE-cadherin in thecontrol of vascular permeability[J]. J Cell Sci, 2008,121(Pt13):2115-2122.
 
【33】ZHANG L Z, MEI J, QIAN Z K, et al. The role of VEcadherin in osteosarcoma cells[J]. Pathol Oncol Res,2010, 16(1):111-117.
 
【34】DíAZ-FLORES L, GUTIÉRREZ R, MADRID J F, et al.Pericytes. Morphofunction, interactions and pathologyin a quiescent and activated mesenchymal cell niche[J].Histol Histopathol, 2009, 24(7):909-969.
 
【35】VAN DE VEIRE S, STALMANS I, HEINDRYCKX F, et al.Further pharmacological and genetic evidence for theefficacy of PlGF inhibition in cancer and eye disease[J].Cell, 2010, 141(1):178-190.
 
【36】RAZA A, FRANKLIN M J, DUDEK A Z. Pericytes and vesselmaturation during tumor angiogenesis and metastasis[J].Am J Hematol, 2010, 85(8):593-598.
 
【37】MOELLER B J, RICHARDSON R A, DEWHIRST M W. Hypoxia andradiotherapy:opportunities for improved outcomes in cancertreatment[J]. Cancer Metastasis Rev, 2007, 26(2):241-248.
 
【38】DEWHIRST M W. Relationships between cycling hypoxia,HIF-1, angiogenesis and oxidative stress[J]. Radiat Res,2009, 172(6):653-665.
 
【39】EBLE J A, NILAND S. The extracellular matrix of bloodvessels[J]. Curr Pharm Des, 2009, 15(12):1385-1400.
 
【40】LUNT S J, CHAUDARY N, HILL R P. The tumormicroenvironment and metastatic disease[J]. Clin ExpeMetastasis, 2009, 26(1):19-34.
 
【41】HELLBERG C, OSTMAN A, HELDIN C H. PDGF andvessel maturation[J]. Recent Results Cancer Res, 2010,180:103-114.
 
【42】GAENGEL K, GENOVÉ G, ARMULIK A, et al. Endothelial-muralcell signaling in vascular development and angiogenesis[J].Arterioscler Thromb Vas Biol, 2009, 29(5):630-638.
 
【43】LIU J, LIAO S, HUANG Y, et al. PDGF-D improves drugdelivery and efficacy via vascular normalization,but promotes lymphatic metastasis by activatingCXCR4 in breast cancer[J]. Clin Cancer Res, 2011,17(11):3638-3648.
 
【44】NISANCIOGLU M H, MAHONEY W M Jr, KIMMEL D D, et al.Generation and characterization of rgs5 mutant mice[J].Mol Cell Biol, 2008, 28(7):2324-2331.
 
【45】KASHIWAGI S, TSUKADA K, XU L, et al. Perivascular nitricoxide gradients normalize tumor vasculature[J]. NatMed, 2008, 14(3):255-257.
 
【46】AUGUSTIN H G, KOH G Y, THURSTON G, et al. Control ofvascular morphogenesis and homeostasis through theangiopoietin-Tie system[J]. Nat Rev Mol Cell Biol, 2009,10(3):165-177.
 
【47】STOELTZING O, AHMAD S A, LIU W, et al. Angiopoietin-1inhibits vascular permeability, angiogenesis, and growthof hepatic colon cancer tumors[J]. Cancer Res, 2003,63(12):3370-3377.
 
【48】NASARRE P, THOMAS M, KRUSE K, et al. Hostderived angiopoietin-2 affects early stages of tumordevelopment and vessel maturation but is dispensablefor later stages of tumor growth[J]. Cancer Res, 2009,69(4):1324-1333.
 
【49】QIAN B Z, POLLARD J W. Macrophage diversity enhancestumor progression and metastasis[J]. Cell, 2010,141(1):39-51.
 
【50】NIZET V, JOHNSON R S. Interdependence of hypoxic andinnate immune responses[J]. Nat Rev Immunol, 2009,9(9):609-617.
 
【51】ROLNY C, MAZZONE M, TUGUES S, et al. HRGinhibits tumor growth and metastasis by inducingmacrophage polarization and vessel normalizationthrough downregulation of PlGF[J]. Cancer Cell, 2011,19(1):31-44.
 
【52】GANSS R, RYSCHICH E, KLAR E, et al. Combination ofT-cell therapy and trigger of inflammation inducesremodeling of the vasculature and tumor eradication[J].Cancer Res, 2002, 62(5):1462-1470.
 
【53】WILLETT C G, DUDA D G, DI TOMASO E, et al. Efficacy,safety, and biomarkers of neoadjuvant bevacizumab,radiation therapy, and fluorouracil in rectal cancer:amultidisciplinary phaseⅡ study[J]. J Clin Oncol, 2009,27(18):3020-3026.
 
【54】BATCHELOR T T, DUDA D G, DI TOMASO E, et al. PhaseⅡ study of cediranib, an oral pan-vascular endothelialgrowth factor receptor tyrosine kinase inhibitor, inpatients with recurrent glioblastoma[J]. J Clin Oncol,2010, 28(17):2817-2823.
 
相关信息
   标题 相关频次
 瞬时受体通道TRPM8及其对前列腺癌的影响
 18
 川芎嗪抑制缺氧诱导的乳腺癌MDA-MB-435S细胞的侵袭及迁移
 12
 抑制肿瘤转移的新策略——靶向肿瘤细胞的外渗过程
 12
 转录因子叉头框Q1与肿瘤相关性的研究进展
 10
 NK细胞在肿瘤免疫治疗中的研究进展展
 7
 辣椒素抗肿瘤作用研究进展
 7
 临床前癌症模型的研究进展
 7
 PGC-1α与肿瘤代谢关系的研究进展
 6
 晚期糖基化终产物受体异常表达对肿瘤发生和侵袭转移的影响
 6
 乙酰辅酶A合成酶2在肿瘤能量代谢中的研究进展
 6
 肿瘤转移新靶点HOTAIR的研究进展
 6
 斑马鱼微肿瘤模型的建立及其在抗血管生成研究中的应用
 4
 携带溶瘤病毒的CIK细胞载体构建及其抗肝癌初步研究
 4
 组织因子途径抑制物-2对人肝癌裸鼠皮下移植瘤生长及血管生成的影响
 4
 K-Ras基因突变型结直肠癌治疗的研究进展
 3
 提高抗肿瘤血管生成治疗的方法
 3
 肿瘤相关基因STK33生物学特性的研究进展
 3
 CRISPR/Cas9基因编辑技术在肿瘤研究及治疗中的应用
 2
 EIF5A2基因在恶性肿瘤中的研究进展
 2
 MS4A基因家族与肿瘤的研究进展
 2
 SEPT 9基因与恶性肿瘤关系的研究进展
 2
 125I内放疗联合热疗和化疗治疗中晚期肿瘤的临床观察
 2
 18F-FDG PET/CT在同时性多原发癌中的应用
 2
 1-磷酸鞘氨醇对恶性肿瘤生物学行为调控的研究进展
 2
 3株肺癌细胞中9个肿瘤相关基因的启动子甲基化状态和部分基因表达的相关性(英文)
 2
 AMPK在肿瘤发生发展中的作用机制研究
 2
 Arresten抑制HUVEC细胞增殖和管腔形成的实验研究
 2
 Bcl-2与IP3R相互作用调控肿瘤细胞程序性死亡的研究进展
 2
 CD26/DPPⅣ与肿瘤相关的研究进展
 2
 CDK12与肿瘤相关性的研究进展
 2

  热点专题


关于我们  |   联系我们  |   广告投放  |   《肿瘤》杂志社版权所有 《肿瘤》杂志社   © 中国 上海 2014.3
沪ICP备15036656号-2