• 四川大學華西醫(yī)院普外科（成都610041）;

目的介紹內(nèi)源性血管生成抑制因子(內(nèi)皮抑素、血管抑素)在肝癌治療中的作用和意義。
方法復習相關(guān)文獻資料并作綜述性報道。
結(jié)果內(nèi)源性血管生成抑制因子通過抑制腫瘤血管的生長，有效地阻礙了肝癌的發(fā)展和轉(zhuǎn)移，可為臨床肝癌治療提供新的途徑。
結(jié)論應用內(nèi)源性血管生成抑制因子的研究,對肝癌的防治將有積極的意義。

引用本文： 鄧靖宇,何生. 內(nèi)源性血管生成抑制因子的研究進展及在肝癌中的應用前景. 中國普外基礎與臨床雜志, 2006, 13(2): 184-186. doi: 復制

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2. Yancopoulos GD, Davis S, Gale NW, et al. Vascularspecific growth factors and blood vessel formation [J]. Nature, 2000; 407(6801)∶242.
3. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis [J]. Cell, 1996; 86(3)∶353.
4. Iwasaki T, Hamano T, Ogata A, et al. Clinical significance of vascular endothelial growth factor and hepatocyte growth factor in multiple myeloma [J]. Br J Haematol, 2002; 116(4)∶796.
5. 侯恩存. 腫瘤血管生成與抗血管生成治療 [J]. 中國腫瘤臨床與康復， 2003； 10（2）∶179.
6. 過邦輔， 凌勵立. 血管生成和蛋白酶在腫瘤侵襲中的作用 [J]. 中國腫瘤， 1999； 8（4）∶177.
7. 王成偉， 寵琦， 張慶林. 血管生成與腫瘤的生長及轉(zhuǎn)移 [J]. 國外醫(yī)學·腫瘤學分冊， 2001； 28（2）∶118.
8. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease [J]. Nat Med, 1995; 1(1)∶27.
9. 駱成玉， 祝學光. 腫瘤血管生成對微轉(zhuǎn)移影響的研究進展 [J]. 中國普外基礎與臨床雜志， 2003； 10（5）∶516.
10. Thaloor D, Singh AK, Sidhu GS, et al. Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin [J]. Cell Growth Differ, 1998; 9(4)∶305.
11. Folkman J. What is the evidence that tumors are angiogenesis dependent? [J]. J Natl Cancer Inst, 1990; 82(1)∶4.
12. 顏春洪， 韓銳. 抗惡性腫瘤轉(zhuǎn)移藥研究進展 [A]. 見： 曹世龍主編.腫瘤學新理論與新技術(shù) [M]. 上海： 上?？萍冀逃霭嫔纾?1997∶462～484.
13. Claffey KP, Robinson GS. Regulation of VEGF/VPF expression in tumor cells: consequences for tumor growth and metastasis [J]. Cancer Metastasis Rev, 1996; 15(2)∶165.
14. Merwin RM, Algire GH. The role of graft and host vessels in the vascularization of grafts of normal and neoplastic tissue [J]. J Natl Cancer Inst, 1956; 17(1)∶23.
15. Taylor S, Folkman J. Protamine is an inhibitor of angiogenesis [J]. Nature, 1982; 297(5864)∶307.
16. 后信， 桑野信彥. か轉(zhuǎn)移阻止開發(fā)口一千 [J]. 日本癌癥治療， 1995； 30（5）∶713.
17. Saphir A. Angiogenesis: the unifying concept in cancer? [J]. J Natl Cancer Inst, 1997; 89(22)∶1658.
18. Burke PA, DeNardo SJ. Antiangiogenic agents and their promising potential in combined therapy [J]. Crit Rev Oncol Hematol, 2001; 39(1-2)∶155.
19. 王貴齊. 腫瘤與血管 [J]. 中國腫瘤臨床， 1995； 22（10）∶743.
20. Cao Y, Ji RW, Davidson D, et al. Kringle domains of human angiostatin. Characterization of the antiproliferative activity on endothelial cells [J]. J Biol Chem, 1996; 271(46)∶29461.
21. Cao Y, Chen A, An SS, et al. Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth [J]. J Biol Chem, 1997; 272(36)∶22924.
22. Luo J, Lin J, Paranya G, et al. Angiostatin upregulates Eselectin in proliferating endothelial cells [J]. Biochem Biophys Res Commun, 1998; 245(3)∶906.
23. Ito H, Rovira II, Bloom ML, et al. Endothelial progenitor cells as putative targets for angiostatin [J]. Cancer Res, 1999; 59(23)∶5875.
24. Standker L, Schrader M, Kanse SM, et al. Isolation and characterization of the circulating form of human endostatin [J]. FEBS Lett, 1997; 420(2-3)∶129.
25. Schuppan D, Cramer T, Bauer M, et al. Hepatocytes as a source of collagen type ⅩⅧ endostatin [J]. Lancet, 1998; 352(9131)∶879.
26. He ZY, Chen ZY, Qiu CP, et al. Cloning, expression and tamor suppression of human endostatin [J]. Acta Biochemica and Biophysica Sinica, 2000; 32(4)∶333.
27. Felbor U, Dreier L, Bryant RA, et al. Secreted cathepsin L generates endostatin from collagen ⅩⅧ [J]. EMBO J, 2000; 19(6)∶1187.
28. 王軒， 劉福坤， 黎介壽. 血管內(nèi)皮抑制素的研究進展 [J]. 臨床腫瘤學雜志， 2001； 6（3）∶287.
29. Dixelius J, Larsson H, Sasaki T, et al. Endostatininduced tyrosine kinase signaling through the Shb adaptor protein regulates endothelial cell apoptosis [J]. Blood, 2000; 95(11)∶3403.
30. Yamaguchi N, AnandApte B, Lee M, et al. Endostatin inhibits VEGFinduced endothelial cell migration and tumor growth independently of zinc binding [J]. EMBO J, 1999; 18(16)∶4414.
31. Dhanabal M, Volk R, Ramchandran R, et al. Cloning, expression, and in vitro activity of human endostatin [J]. Biochem Biophys Res Commun, 1999; 258(2)∶345.
32. Hohenester E, Sasaki T, Mann K, et al. Variable zinc coordination in endostatin [J]. J Mol Biol, 2000; 297(1)∶1.
33. Perletti G, Concari P, Giardini R, et al. Antitumor activity of endostatin against carcinogeninduced rat primary mammary tumors [J]. Cancer Res, 2000; 60(7)∶1793.
34. 孫惠川， 湯釗猷， 王魯. Endostatin抑制裸鼠移植性肝癌切除后的復發(fā)移植 [J]. 中華腫瘤雜志， 2000； 22（6）∶469.
35. Folkman J. Antiangiogenic gene therapy [J]. Proc Natl Acad Sci USA， 1998; 95(16)∶9064.
36. Teicher BA, Holden SA, Ara G, et al. Potentiation of cytotoxic cancer therapies by TNP470 alone and with other antiangiogenic agents [J]. Int J Cancer, 1994; 57(6)∶920.
  1. 1. Folkman J. Tumor angiogenesis: therapeutic implications [J]. N Engl J Med, 1971; 285(21)∶1182.
  2. 2. Yancopoulos GD, Davis S, Gale NW, et al. Vascularspecific growth factors and blood vessel formation [J]. Nature, 2000; 407(6801)∶242.
  3. 3. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis [J]. Cell, 1996; 86(3)∶353.
  4. 4. Iwasaki T, Hamano T, Ogata A, et al. Clinical significance of vascular endothelial growth factor and hepatocyte growth factor in multiple myeloma [J]. Br J Haematol, 2002; 116(4)∶796.
  5. 5. 侯恩存. 腫瘤血管生成與抗血管生成治療 [J]. 中國腫瘤臨床與康復， 2003； 10（2）∶179.
  6. 6. 過邦輔， 凌勵立. 血管生成和蛋白酶在腫瘤侵襲中的作用 [J]. 中國腫瘤， 1999； 8（4）∶177.
  7. 7. 王成偉， 寵琦， 張慶林. 血管生成與腫瘤的生長及轉(zhuǎn)移 [J]. 國外醫(yī)學·腫瘤學分冊， 2001； 28（2）∶118.
  8. 8. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease [J]. Nat Med, 1995; 1(1)∶27.
  9. 9. 駱成玉， 祝學光. 腫瘤血管生成對微轉(zhuǎn)移影響的研究進展 [J]. 中國普外基礎與臨床雜志， 2003； 10（5）∶516.
  10. 10. Thaloor D, Singh AK, Sidhu GS, et al. Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin [J]. Cell Growth Differ, 1998; 9(4)∶305.
  11. 11. Folkman J. What is the evidence that tumors are angiogenesis dependent? [J]. J Natl Cancer Inst, 1990; 82(1)∶4.
  12. 12. 顏春洪， 韓銳. 抗惡性腫瘤轉(zhuǎn)移藥研究進展 [A]. 見： 曹世龍主編.腫瘤學新理論與新技術(shù) [M]. 上海： 上?？萍冀逃霭嫔?， 1997∶462～484.
  13. 13. Claffey KP, Robinson GS. Regulation of VEGF/VPF expression in tumor cells: consequences for tumor growth and metastasis [J]. Cancer Metastasis Rev, 1996; 15(2)∶165.
  14. 14. Merwin RM, Algire GH. The role of graft and host vessels in the vascularization of grafts of normal and neoplastic tissue [J]. J Natl Cancer Inst, 1956; 17(1)∶23.
  15. 15. Taylor S, Folkman J. Protamine is an inhibitor of angiogenesis [J]. Nature, 1982; 297(5864)∶307.
  16. 16. 后信， 桑野信彥. か轉(zhuǎn)移阻止開發(fā)口一千 [J]. 日本癌癥治療， 1995； 30（5）∶713.
  17. 17. Saphir A. Angiogenesis: the unifying concept in cancer? [J]. J Natl Cancer Inst, 1997; 89(22)∶1658.
  18. 18. Burke PA, DeNardo SJ. Antiangiogenic agents and their promising potential in combined therapy [J]. Crit Rev Oncol Hematol, 2001; 39(1-2)∶155.
  19. 19. 王貴齊. 腫瘤與血管 [J]. 中國腫瘤臨床， 1995； 22（10）∶743.
  20. 20. Cao Y, Ji RW, Davidson D, et al. Kringle domains of human angiostatin. Characterization of the antiproliferative activity on endothelial cells [J]. J Biol Chem, 1996; 271(46)∶29461.
  21. 21. Cao Y, Chen A, An SS, et al. Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth [J]. J Biol Chem, 1997; 272(36)∶22924.
  22. 22. Luo J, Lin J, Paranya G, et al. Angiostatin upregulates Eselectin in proliferating endothelial cells [J]. Biochem Biophys Res Commun, 1998; 245(3)∶906.
  23. 23. Ito H, Rovira II, Bloom ML, et al. Endothelial progenitor cells as putative targets for angiostatin [J]. Cancer Res, 1999; 59(23)∶5875.
  24. 24. Standker L, Schrader M, Kanse SM, et al. Isolation and characterization of the circulating form of human endostatin [J]. FEBS Lett, 1997; 420(2-3)∶129.
  25. 25. Schuppan D, Cramer T, Bauer M, et al. Hepatocytes as a source of collagen type ⅩⅧ endostatin [J]. Lancet, 1998; 352(9131)∶879.
  26. 26. He ZY, Chen ZY, Qiu CP, et al. Cloning, expression and tamor suppression of human endostatin [J]. Acta Biochemica and Biophysica Sinica, 2000; 32(4)∶333.
  27. 27. Felbor U, Dreier L, Bryant RA, et al. Secreted cathepsin L generates endostatin from collagen ⅩⅧ [J]. EMBO J, 2000; 19(6)∶1187.
  28. 28. 王軒， 劉福坤， 黎介壽. 血管內(nèi)皮抑制素的研究進展 [J]. 臨床腫瘤學雜志， 2001； 6（3）∶287.
  29. 29. Dixelius J, Larsson H, Sasaki T, et al. Endostatininduced tyrosine kinase signaling through the Shb adaptor protein regulates endothelial cell apoptosis [J]. Blood, 2000; 95(11)∶3403.
  30. 30. Yamaguchi N, AnandApte B, Lee M, et al. Endostatin inhibits VEGFinduced endothelial cell migration and tumor growth independently of zinc binding [J]. EMBO J, 1999; 18(16)∶4414.
  31. 31. Dhanabal M, Volk R, Ramchandran R, et al. Cloning, expression, and in vitro activity of human endostatin [J]. Biochem Biophys Res Commun, 1999; 258(2)∶345.
  32. 32. Hohenester E, Sasaki T, Mann K, et al. Variable zinc coordination in endostatin [J]. J Mol Biol, 2000; 297(1)∶1.
  33. 33. Perletti G, Concari P, Giardini R, et al. Antitumor activity of endostatin against carcinogeninduced rat primary mammary tumors [J]. Cancer Res, 2000; 60(7)∶1793.
  34. 34. 孫惠川， 湯釗猷， 王魯. Endostatin抑制裸鼠移植性肝癌切除后的復發(fā)移植 [J]. 中華腫瘤雜志， 2000； 22（6）∶469.
  35. 35. Folkman J. Antiangiogenic gene therapy [J]. Proc Natl Acad Sci USA， 1998; 95(16)∶9064.
  36. 36. Teicher BA, Holden SA, Ara G, et al. Potentiation of cytotoxic cancer therapies by TNP470 alone and with other antiangiogenic agents [J]. Int J Cancer, 1994; 57(6)∶920.