腺病毒介导碱性成纤维细胞生长因子对人脐静脉内皮细胞生物学行为的影响及血管瘤动物模型建立的初步研究
|
摘要
目的: bFGF基因以腺病毒为载体体外转染HUVEC,改变其生物学行为,并在裸鼠体内发挥促血管生成作用,旨在构建血管瘤动物模型。方法:应用同源重组的方法构建携带bFGF基因的腺病毒载体,体外转染HUVEC。检测bFGF和VEGF蛋白、mRNA表达变化。观察bFGF基因转染的HUVEC细胞增殖能力的变化,及在裸鼠体内促血管生成作用。结果:构建了携带bFGF基因的腺病毒载体,并成功在HUVEC表达,同时上调VEGF表达。过量表达bFGF和VEGF的HUVEC细胞增殖能力增强,并在裸鼠体内促进血管增生。结论:通过基因工程的方法可以获得高表达bFGF的HUVEC细胞,该基因可引起细胞生物学行为发生改变,在裸鼠体内可以诱导血管瘤样病变形成,为建立真正的血管瘤动物模型奠定基础。
Objective: bFGF gene transfect HUVEC mediated by adenovirus in vitro. The biological behavior of HUVEC was changed after transfection and bFGF transfected HUVEC (bFGF-T-HUVEC) induced highly angiogenesis when injected in nude mice, aiming to construct a hemangioma animal model. Methods: The adenovirus vector harboring human bFGF cDNA was constructed by homologous recombination technique and transfect HUVEC in vitro. Detect protein and mRNA expression of bFGF and VEGF before and after transfection. Investigate proliferative ability of bFGF transfected HUVEC in vitro and its effect on angiogenesis in nude mice. Results: Construct an adenovirus vector harboring bFGF gene. bFGF gene was expressed successfully and upreguated VEGF expression in HUVEC. HUVEC with bFGF and VEGF overexpressed showed enhanced proliferative ability and trigger highly angiogenesis in nude mice. Conclusions: HUVEC with bFGF overexpressed can be obtained by gene engineer. The transfected HUVEC shows changed biological behavior and resembles hemangioma-like lesions in nude mice, providing the basis for constructing a truly hemangioma animal model.
Objective: bFGF gene transfect HUVEC mediated by adenovirus in vitro. The biological behavior of HUVEC was changed after transfection and bFGF transfected HUVEC (bFGF-T-HUVEC) induced highly angiogenesis when injected in nude mice, aiming to construct a hemangioma animal model. Methods: The adenovirus vector harboring human bFGF cDNA was constructed by homologous recombination technique and transfect HUVEC in vitro. Detect protein and mRNA expression of bFGF and VEGF before and after transfection. Investigate proliferative ability of bFGF transfected HUVEC in vitro and its effect on angiogenesis in nude mice. Results: Construct an adenovirus vector harboring bFGF gene. bFGF gene was expressed successfully and upreguated VEGF expression in HUVEC. HUVEC with bFGF and VEGF overexpressed showed enhanced proliferative ability and trigger highly angiogenesis in nude mice. Conclusions: HUVEC with bFGF overexpressed can be obtained by gene engineer. The transfected HUVEC shows changed biological behavior and resembles hemangioma-like lesions in nude mice, providing the basis for constructing a truly hemangioma animal model.
引文
1 Mulliken JB.GlowackiJ Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristic, Plast Reconstr Surg. 1982, 69(3):412-422.
2 Stephen JM, Vincent RH, Kathy H, et al. Plastic surgery,2nd edition [M]. (volume 5 ). Philadelphia, PA,USA: Saunders Elsevier, 2006: 19-20.
3 Williams EF 3rd, Hochman M, Rodgers BJ. A psychological profile of children with hemaniomas and their families. Arch Facial Plast Srug. 2003,5(3):229-234
4 Ritter EJ. The chicken comb and wattle as an experimental model for the therapy of hemangiomas. Preliminary laser studies. Life Sci.1966;5(20):1903一10.
5 Liekens S, Verbeken E, Vandeputte M, et al. A novel animal model for hemangiomas: inhibition of hemangioma development by the angiogenesis inhibitor TNP-470.Cancer Res. 1999, 59(10):2376一83.
6 徐骎,张志原,陈万涛,等. 转基因小鼠血管瘤动物模型建立. 中华口腔医学杂志.2003, 38(5):355-7.
7 Peng Q, Liu W, Tang Y, et al. The establishment of the hemangioma model in nude mouse. J Pendiatr Surg, 2005, 40(7):1167-72.
8 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med, 1995, 1(1): 27–31.
9 Frischer JS, Huang J, Serur A. et al Biomolecular markers and involutionof hemangiomas. Pediatr Surg, 2004, 39(3):400-4.
10 Francesco Sola, Anna Gualandris, Mirella Belleri, et al.Endothelial cells overexpressing basic fibroblast growth factor (FGF-2) induce vascular tumors in immunodeficient mice. Angiogenesis, 1997; 1(1): 102-116.
11 Sandra Liekens, Johan Neyts, Erik De Clercq, et al. Inhibition of Fibroblast Growth Factor-2-induced Vascular Tumor Formation by the Acyclic Nucleoside Phosphonate Cidofovir[J]. Cancer Research,2001, 61(1), 5057-5064.
12 George T. Stavri, FRCS, Ian C, et al. Basic Fibroblast Growth Factor Upregulates the Expression of Vascular Endothelial Growth Factor in Vascular Smooth Muscle Cells. Circulation. 1995,92(1):11-14.
13 Graziano Seghezzi, Sundeep Patel, Christine J Ren, et al. Fibroblast Growth Factor-2 (FGF-2) Induces Vascular Endothelial Growth Factor (VEGF) Expression in the Endothelial Cells of Forming Capillaries: An Autocrine Mechanism Contributing to Angiogenesis. Cell Biol, 1998, 141(7); 1659-1673.
14 Soker S, Machado, Atala A. Systems for therapeutic angiogenesis in tissue engineering. World J Urol, 2001;18(1):10-19
1 Lafage-pochital M, Galland F, Simonetti J, et al. The human basic fibroblast growth gene is located on the long arm of chromosome 4 at bands q26-27. Oncogene research, 1990, 5(3):242-244.
2 Abraham JA, Whang JL, Tumolo A, et al. Human basic fibroblast growth factor : nucleotide sequence and genomic organization. EMBO J, 1986,5(10):2523-2528
3 Gunzburg WH, Salmons B. Virus vector design in gene therapy. Mol Med Today. 1995, 1(9): 410-417.
4Walther W, Stein U. Viral vectors for gene transfers review of their use in the treatment of Human diseases. Drugs, 2000,60(2):249-271
5 Miller DG, Adam MA, Miller AD, et al. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol, 1990,10:4239-4242
6 Danos O, Mullligan RC. Safe and efficient generation of recombinant retroviruses withamphotropic and ecotropic host ranges. Proc Natl Acad Sci USA. 1988,85:6460-6464
7 Friedman T, Yee JK. Pseudotyped retroviral vectors for studies of human gene therapy. Nature Med. 1995, 1:275-277
8 Evoy D, Hirschowitz EA, Noama HA, et al. In vivo adenoviral2 mediated gene transfer in treatment of pancreatic cancer. J Surg Res. 1997,69(1):226-231.
9 Dong Y, Wen P, Manome Y, et al. In vivo replication deficient adenovirus vector2 mediated transfection of the cytosine deaming gene sensitizes glioma cells to 52 fluorocytosine. Hum Gene Ther. 1996,7(6):713-720.
10 孙晗笑,陆大祥,刘飞鹏主编.转基因技术理论与应用.郑州:河南医科大学出版社,2000,39-40.
11 Stephan A, Kelly K. Adenoviral gene therapy. The oncologist. 2002,7: 46-59.
12 孙树权主编. 基因工程原理与方法,北京:人民军医出版社,2001,113.
13 Wang Y, Hunag S. Adenovirus technology for gene manipulation and functional studies. Drug Discovery Today. 2000,5:10-16
14 Flint J, Shenk T. Viral transactivating protein. Annu Rev Genet. 1997,31;177-212
15 Ng P, Parks RJ,Cummungs DT, et al . An enhanced system tor construction of adenoviral vectars by the two-palsmM resue method. Hum Gene Ther. 2000;11:693-699
16 Elahi SM, Oualikene W, Naghdi L, et al. Adenovirus-based libraries: efficient generation of recombinant adenoviruses by positive selection with the adenovirus protease. Gene-Ther.2002; 9(18): 1238-46
1 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med,1995, 1: 27–31
2 Stavin J, Fibroblast growth factors: at the heart of angiogenesis. Cell Biology Inter. 1995, 19(5):431-439.
3 张启旭,周刚,陆佳韵,等. 碱性成纤维生长因子真核表达载体的构建及表达[J]. 中国修复重建外科, 2004,18(5),435-450.
4 Sandra Liekens, Johan Neyts, Erik De Clercq, et al. Inhibition of Fibroblast Growth Factor-2-induced Vascular Tumor Formation by the Acyclic Nucleoside Phosphonate Cidofovir[J]. Cancer Research,2001, 61(1), 5057-5064.
5 Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics [J]. Plast Reconstr Surg, 1982, 69(3):412-422
6 Stephen JM, Vincent RH, Kathy H, et al. Plastic surgery,2nd edition [M]. (volume 5 ). Philadelphia, PA,USA: Saunders Elsevier, 2006: 19-20
7 Folkman JB, Mulliken J, Ezekowitz RAB: Angiogenesis and hemangiomas. In Oldham K, Colombani P, Foglio R, eds: Surgery of infangts and children : Scientific Principles and practice. Philadelphia, Lippincott-Raven. 1997, 569-579
8 Chang J, Most D, Bresnick S, et al. Proliferative hemangiomas: analysis of cytokine gene expression and angiogenesis. Plast Resconstr Surg, 1999,103(1):1-9.
9 Tan, Swee T. M.B.B.S., F.R.A.C.S,et al. Cellular and Extracellular Markers of Hemangioma. Plast Resconstr Surg, 2000, 106(3): 529-538.
10 Chang J, Most D, Bresnick S, et al. Successful treatment of infantile hemangiomas with interfereron-alpha-2b. J Pediatr Hematol Oncol 1997, 19:237-244.
11 张莉、林晓曦、祁佐良等,尿碱性成纤维细胞生长因子用于鉴别血管瘤和血管畸形的作用,2006,44(3):186-188.
12 Stavin J. Fibroblast growth factors: at the heart of angiogenesis. Cell Biology Inter. 1995, 19(5):431-439.
13 Distler J.H., Hirth A, Kurowska. Angiogenic and angiostatic factors in the molecular control of angiogenesis. QJ Nucl Med. 2003,47(3):149-61.
1 Cao Y, Liu Q. Therapeutic targets of multiple angiogenic factors for the treatment of cancer and metastasis. Adv Cancer Res. 2007,97:203-224.
2 Tan, Swee T. M.B.B.S., F.R.A.C.S,et al. Cellular and Extracellular Markers of Hemangioma. Plast Resconstr Surg, 2000,106(3): 529-538.
3 Dyduch G, Okon K, Mierzynski W. Benign vascular proliferations--an immunohistochemical and comparative study. Pol-J-Pathol. 2004; 55(2): 59-64.
4 George T. Stavri, FRCS, Ian C, et al. Basic Fibroblast Growth Factor Upregulates the Expression of Vascular Endothelial Growth Factor in Vascular Smooth Muscle Cells. Circulation. 1995,92(1):11-14
5 Graziano Seghezzi, Sundeep Patel, Christine J Ren, et al. Fibroblast Growth Factor-2 (FGF-2) Induces Vascular Endothelial Growth Factor (VEGF) Expression in the Endothelial Cells of Forming Capillaries: An Autocrine Mechanism Contributing to Angiogenesis. Cell Biol, 1998, 141(7); 1659-1673.
6 Ribatti D, Gualandris A, Belleri M, et al. Alterations of blood vessel development by endothelial cells overexpressing fibroblast growth factor-2. J Pathol. 1999, 189(4):590-599.
7 Ribatti Domenico, Nico Beatrice, Morbidelli Lucia. Cell-mediated delivery of fibroblast growth factor-2 and vascular endothelial growth factor onto the chick chorioallantoic membrane: endothelial fenestration and angiogenesis. Vascular research,2001,38(4):389-397.
8 B. Garmy-Susini, E. Delmas, P. Gourdy, et al. Role of Fibroblast Growth Factor-2 Isoforms in the Effect of Estradiol on Endothelial Cell Migration and Proliferation. Circulation research 2004,94(10),1301-1309.
9 Nicosia RF, Lin YJ, Hazelton D et al. Endogenous regulation of angiogenesis in the rat aorta model. Role of vascular endothelial growth factor. Am J Pathol, 1997; 151(5):1379 -1386.
10 HouckK A,L eungD W,R owlandA M eta l. Dual regulation of vascular endothelialgrowth factor bioavailability by genetic and proteolytic mechanisms J Biol Chem,1992;267(36):26031-26037.
11 Maeda K, Chung Y, Ogawa Y et al. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer. 1996 ,77(5):858-63.
12 Rabie AB, Lu M. Basic fibroblast growth factor up-regulates the expression of vascular endothelial growth factor during healing of allogeneic bone graft. Arch Oral Biol 2004, 49(12):1025—33.
13 Seghezzi G, Patel S, Ren C, et al. Fibroblast growth factor (VEGF) expression in the endothelial cells of forming capillaries: An autocrine mechanism contribution to angiogenesis. J Cell Biol, 1998, 141(7):1659-1673.
14 Pieter Koowijk, Monique G M, Van Erch, et al. Cooperative effect of tubular structures of human microvascular endothelial cells in a fibrin matrix: role of urkinase activity. J Cell Bio, 1996, 132(6):1177-1186.
15 Goldman C K, Kim J, Wong W L, et al. Editorial angiogenesis in three-dimensional cultures. Mol Cell Bio, 1993, 4:121-134.
16 Jung-Sun Lee1, Jonghoe Byun,Jung-Min Kim et al. Cardiac expression profiles of the naked DNA vectors encoding vascular endothelial growth factor and basic fibroblast growth. Expreimental and molecular medicine, 2005, 37(5): 447-456.
17 Soker S, Machado, Atala A. Systems for therapeutic angiogenesis in tissue engineering. World J Urol, 2001, 18(1):10-19.
18 Hartmut Kuhna, Jana Konrada, Silke Holtzb et al .Enhanced expression of VEGF following bFGF inhibition in non-small cell lung cancer cell lines. Lung Cancer , 2006, 54:149—153.
1 Frischer JS, Huang J, Serur A. et al Biomolecular markers and involutionof hemangiomas. Pediatr Surg, 2004, 39(3):400-4.
2 Tan ST, Velickovic M. Ruger BM, et al. Cellular and extracellular markers o hemangioma. Plast Reconstr Surg, 2000, 106(3):529-538.
3 Lamszus K, Lengler U, Schmidt N O, et al. Vascular endothelial growth factor, hepatocyte grow and their relation to antigenesis and malignancy. Neurosurgery, 2000, 46(4):938 -947.
4 Nilesh M. Pandya b, Naranjan S. et al. Angiogenesis—a new target for future therapy. Vascular Pharmacology. 2006, 44(5):265–274.
5 Ritter EJ. The chiken comb and wattle as an experimental model for the therapy of hemangiomas. Preliminary laser studies. Life Sci.1966, 5(20):1903-10.
6 Groot D, Rao J, Johnston P, et al. Algorithm for using a long pulsed Nd: YAG laser in the treatment of deep cutaneous vascular lesions. Dermatol Surg, 2003, 29(1):35-42
7 陈光,赵敏,王琪,等,平阳霉素治疗血管瘤的实验研究. 现代口腔医学杂志,1999,13(4):290-291.
8 Sato N, Sato T, Takahashi S, et al. Establishment of murine endothelial cell lines that develop angiosarcomas in vivo: brief demonstration of a proposed animal model for Kaposi's sarcoma. Cancer Res.1 986, 46(1):362-6.
9 Bautch VL, Toda S, Hassell JA, et al. Endothelial cell tumors develop in transgenic mice carrying polyoma virus middle T oncogene. Cell. 1987, 51(4):529一37.
10 Taraboletti G, Belotti D, Dejana E, et al. Endothelial cell migration and invasiveness are induced by a soluble factor produced by murine endothelioma cells transformed by polyoma virus middle T oncogene. Cancer Res. 1993, 53(16):3812-6.
11 徐骎,张志原,陈万涛,等.转基因小鼠血管瘤动物模型建立.中华口腔医学杂志. 2003,38(5):355-7.
12 Liekens S, Verbeken E, Vandeputte M, et al. A novel animal model for hemangiomas: inhibition of hemangioma development by the angiogenesis inhibitor T NP-470. Cancer Res. 1999, 59(10):2376一83.
13 Dubois Stringfellow N, Kolpack Martindale L, et al. Mice with hemangiomas induced by transgenic endothelial cells. A model for the Kasabach一Merritt syndrome. Am J Pathol.1994, 144(4):796-806.
14 Yu Y, Varughese J, Brown LF, et al. Increased tie2 expression, enhanced response to angiopoietin-1,and dysregulated an giopoietin-2 expression in hemangioma- derived endothelial cells. A m JP athol. 2001, 159(6):2271一80.
15 郭军,吴汉江. 多种药物对体外培养的血管内皮细胞损伤作用比较的研究.华西口腔医学杂志. 2000, 18(5):310-3.
16 Peng Q, Liu W, Tang Y, et al. The establishment of the hemangioma model in mude mouse. J Pediatr Surg. 2005, 40(7):1167-1172.
17 Francesco Sola,1 Anna Gualandris, Mirella Belleri, et al. Endothelial cells overexpressing basic fibroblast growth factor (FGF-2) induce vascular tumors in immunodeficient mice. Angiogenesis, 1997, 1(1): 102-116.
18 Sandra Liekens, Johan Neyts, Erik De Clercq, et al. Inhibition of Fibroblast Growth Factor-2-induced Vascular Tumor Formation by the Acyclic Nucleoside Phosphonate Cidofovir[J]. Cancer Research,2001, 61(1): 5057-5064.
[1] Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics [J]. Plast Reconstr Surg, 1982, 69(3):412-422.
[2] Stephen JM, Vincent RH, Kathy H, et al. Plastic surgery,2nd edition [M]. (volume 5 ). Philadelphia, PA,USA: Saunders Elsevier, 2006: 19-20.
[3] Smolinski,Kara N, Yan,et al. Hemangiomas of infancy:clinical and biological characteristics [J].Clinical pediatrics, 2005,44(9):747-766.
[4] Ceisler EJ, Santos L, Blei F. Periocular hemangiomas: what every physician should know [J]. Pediatr Dermatol, 2004, 21(1):1-9. [ 5 ] Bouchard S, Yazbeck S, Lallier M. Perineal hemangioma, anorectal malformation, and genital anomaly: a new association? [J]. J Pediatr Surg, 1999, 34(7):1133-1135.
[6] Allen RM, Sandquist MA, Piatt JH Jr, et al. Ultrasonographic screening in infants with isolated spinal strawberry nevi [J]. J Neurosurg, 2003,98(3 Suppl):247-250.
[7] Sie KC, Tampakopoulou DA. Hemangiomas and vascular malformations of the airway [J]. Otolaryngol Clin North Am, 2000, 33(1):209-220.
[8] Azizkhan RG. Laser surgery: new applications for pediatric skin and airway lesions [J]. Curr Opin Pediatr, 2003, 15(3):243-247.
[9] Metry DW, Hawrot A, Altman C, et al. Association of solitary, segmental hemangiomas of the skin with visceral hemangiomatosis [J]. Arch Dermatol, 2004, 140(5):591-596.
[10] Haqqstrom AM, Lammer EJ, Schneider RA, et al. Patterns of infantile hemangiomas : new clues to hemangioma pathogenesis and embryonic facial development [J]. Pediatrics, 2006,117(3):698-703.
[11] Metry D. Update on hemangiomas of infancy[J].Current Opinion Pediatrics,2004,16(4):373-377
[12] Waner M. North PE, Scherer KA, et al. The nonrandom distribution of facial hemangiomas [J] . Arch Dermatol, 2003, 139(7):869-875.
[13] Ilona J, Anita N, Haggstrom, et al. Infantile hemangiomas: current knowledge, future directions. Proceedings of a research workshop on infantile hemangiomas [J]. Pediatric dermatology, 2005, 22(5):383-406.
[14] Brook I. Microbiology of infected hemangiomas in children [J]. Pediatr Dermatol, 2004, 21(2):113-116.
[15] Kim HJ, Colombo M, Frieden IJ. Ulcerated hemangiomas: clinical characteristics and response to therapy [J]. J Am Acad Dermatol, 2001,44(6):962-972.
[16] Poetke M, Frommeld T, Berlien HP. PHACE syndrome: new views on diagnostic criteria [J]. Eur J Pediatr Surg, 2002,12(6):366-374.
[17] Metry DW, Dowd CF, Barkovich AJ, et al. The many faces of PHACE syndrome [J]. J Pediatr, 2001,139(1):117-123.
[18] Leung AK, Rafaat M. Benign neonatal hemangiomatosis [J]. Pediatr Dermatol, 2003, 20(2):161-163.
[19] Blei F, Orlow SJ, Geronemus R. Multimodal management of diffuse neonatal hemangiomatosis [J]. J Am Acad Dermatol, 1997,37(6):1019-1021.
[20] Boon LM, Enjolras O, Mulliken JB. Congenital hemangioma: evidence of accelerated involution [J]. J Pediatr, 1996,128(3):329-335. [ 21 ] Enjolras O, Mulliken JB, Boon LM, et al. Noninvoluting congenital hemangioma: a rare cutaneous vascular anomaly [J] . Plast Reconstr Surg, 2001,107(7):1647-1654.
[22] Berenguer B, Mulliken JB, Enjolras O, et al. Rapidly involuting congenital hemangioma: clinical and histopathologic features [J]. Pediatr Dev Pathol, 2003,6(6):495-510.
[23] North PE, Waner M, James CA, et al. Congenital nonprogressive hemangioma: a distinct clinicopathologic entity unlike infantile hemangioma [J]. Arch Dermatol, 2001,137(12):1607-1620.
[24] Mulliken JB, Enjolras O. Congenital hemangiomas and infantile hemangioma: missing links [J]. J Am Acad Dermatol, 2004,50(6):875-882.
[25] Enjolras O, Wassef M, Mazoyer E, et al. Infants with Kasabach-Merritt syndrome do not have "true" hemangiomas [J]. J Pediatr, 1997,130 (4):631-640. [ 26 ] Lyons LL, North PE, Mac-Moune Lai F, et al. Kaposiformhemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma [J]. Am J Surg Pathol, 2004, 28(5):559-68.
[27] Enjolras O, Mulliken JB. Wassef M, Residual lesions after Kasabach-Merrittnomenon in 41 patients [J] . J Am Acad Derm, 2000,42(2 pt1):225-235
2 Stephen JM, Vincent RH, Kathy H, et al. Plastic surgery,2nd edition [M]. (volume 5 ). Philadelphia, PA,USA: Saunders Elsevier, 2006: 19-20.
3 Williams EF 3rd, Hochman M, Rodgers BJ. A psychological profile of children with hemaniomas and their families. Arch Facial Plast Srug. 2003,5(3):229-234
4 Ritter EJ. The chicken comb and wattle as an experimental model for the therapy of hemangiomas. Preliminary laser studies. Life Sci.1966;5(20):1903一10.
5 Liekens S, Verbeken E, Vandeputte M, et al. A novel animal model for hemangiomas: inhibition of hemangioma development by the angiogenesis inhibitor TNP-470.Cancer Res. 1999, 59(10):2376一83.
6 徐骎,张志原,陈万涛,等. 转基因小鼠血管瘤动物模型建立. 中华口腔医学杂志.2003, 38(5):355-7.
7 Peng Q, Liu W, Tang Y, et al. The establishment of the hemangioma model in nude mouse. J Pendiatr Surg, 2005, 40(7):1167-72.
8 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med, 1995, 1(1): 27–31.
9 Frischer JS, Huang J, Serur A. et al Biomolecular markers and involutionof hemangiomas. Pediatr Surg, 2004, 39(3):400-4.
10 Francesco Sola, Anna Gualandris, Mirella Belleri, et al.Endothelial cells overexpressing basic fibroblast growth factor (FGF-2) induce vascular tumors in immunodeficient mice. Angiogenesis, 1997; 1(1): 102-116.
11 Sandra Liekens, Johan Neyts, Erik De Clercq, et al. Inhibition of Fibroblast Growth Factor-2-induced Vascular Tumor Formation by the Acyclic Nucleoside Phosphonate Cidofovir[J]. Cancer Research,2001, 61(1), 5057-5064.
12 George T. Stavri, FRCS, Ian C, et al. Basic Fibroblast Growth Factor Upregulates the Expression of Vascular Endothelial Growth Factor in Vascular Smooth Muscle Cells. Circulation. 1995,92(1):11-14.
13 Graziano Seghezzi, Sundeep Patel, Christine J Ren, et al. Fibroblast Growth Factor-2 (FGF-2) Induces Vascular Endothelial Growth Factor (VEGF) Expression in the Endothelial Cells of Forming Capillaries: An Autocrine Mechanism Contributing to Angiogenesis. Cell Biol, 1998, 141(7); 1659-1673.
14 Soker S, Machado, Atala A. Systems for therapeutic angiogenesis in tissue engineering. World J Urol, 2001;18(1):10-19
1 Lafage-pochital M, Galland F, Simonetti J, et al. The human basic fibroblast growth gene is located on the long arm of chromosome 4 at bands q26-27. Oncogene research, 1990, 5(3):242-244.
2 Abraham JA, Whang JL, Tumolo A, et al. Human basic fibroblast growth factor : nucleotide sequence and genomic organization. EMBO J, 1986,5(10):2523-2528
3 Gunzburg WH, Salmons B. Virus vector design in gene therapy. Mol Med Today. 1995, 1(9): 410-417.
4Walther W, Stein U. Viral vectors for gene transfers review of their use in the treatment of Human diseases. Drugs, 2000,60(2):249-271
5 Miller DG, Adam MA, Miller AD, et al. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol, 1990,10:4239-4242
6 Danos O, Mullligan RC. Safe and efficient generation of recombinant retroviruses withamphotropic and ecotropic host ranges. Proc Natl Acad Sci USA. 1988,85:6460-6464
7 Friedman T, Yee JK. Pseudotyped retroviral vectors for studies of human gene therapy. Nature Med. 1995, 1:275-277
8 Evoy D, Hirschowitz EA, Noama HA, et al. In vivo adenoviral2 mediated gene transfer in treatment of pancreatic cancer. J Surg Res. 1997,69(1):226-231.
9 Dong Y, Wen P, Manome Y, et al. In vivo replication deficient adenovirus vector2 mediated transfection of the cytosine deaming gene sensitizes glioma cells to 52 fluorocytosine. Hum Gene Ther. 1996,7(6):713-720.
10 孙晗笑,陆大祥,刘飞鹏主编.转基因技术理论与应用.郑州:河南医科大学出版社,2000,39-40.
11 Stephan A, Kelly K. Adenoviral gene therapy. The oncologist. 2002,7: 46-59.
12 孙树权主编. 基因工程原理与方法,北京:人民军医出版社,2001,113.
13 Wang Y, Hunag S. Adenovirus technology for gene manipulation and functional studies. Drug Discovery Today. 2000,5:10-16
14 Flint J, Shenk T. Viral transactivating protein. Annu Rev Genet. 1997,31;177-212
15 Ng P, Parks RJ,Cummungs DT, et al . An enhanced system tor construction of adenoviral vectars by the two-palsmM resue method. Hum Gene Ther. 2000;11:693-699
16 Elahi SM, Oualikene W, Naghdi L, et al. Adenovirus-based libraries: efficient generation of recombinant adenoviruses by positive selection with the adenovirus protease. Gene-Ther.2002; 9(18): 1238-46
1 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med,1995, 1: 27–31
2 Stavin J, Fibroblast growth factors: at the heart of angiogenesis. Cell Biology Inter. 1995, 19(5):431-439.
3 张启旭,周刚,陆佳韵,等. 碱性成纤维生长因子真核表达载体的构建及表达[J]. 中国修复重建外科, 2004,18(5),435-450.
4 Sandra Liekens, Johan Neyts, Erik De Clercq, et al. Inhibition of Fibroblast Growth Factor-2-induced Vascular Tumor Formation by the Acyclic Nucleoside Phosphonate Cidofovir[J]. Cancer Research,2001, 61(1), 5057-5064.
5 Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics [J]. Plast Reconstr Surg, 1982, 69(3):412-422
6 Stephen JM, Vincent RH, Kathy H, et al. Plastic surgery,2nd edition [M]. (volume 5 ). Philadelphia, PA,USA: Saunders Elsevier, 2006: 19-20
7 Folkman JB, Mulliken J, Ezekowitz RAB: Angiogenesis and hemangiomas. In Oldham K, Colombani P, Foglio R, eds: Surgery of infangts and children : Scientific Principles and practice. Philadelphia, Lippincott-Raven. 1997, 569-579
8 Chang J, Most D, Bresnick S, et al. Proliferative hemangiomas: analysis of cytokine gene expression and angiogenesis. Plast Resconstr Surg, 1999,103(1):1-9.
9 Tan, Swee T. M.B.B.S., F.R.A.C.S,et al. Cellular and Extracellular Markers of Hemangioma. Plast Resconstr Surg, 2000, 106(3): 529-538.
10 Chang J, Most D, Bresnick S, et al. Successful treatment of infantile hemangiomas with interfereron-alpha-2b. J Pediatr Hematol Oncol 1997, 19:237-244.
11 张莉、林晓曦、祁佐良等,尿碱性成纤维细胞生长因子用于鉴别血管瘤和血管畸形的作用,2006,44(3):186-188.
12 Stavin J. Fibroblast growth factors: at the heart of angiogenesis. Cell Biology Inter. 1995, 19(5):431-439.
13 Distler J.H., Hirth A, Kurowska. Angiogenic and angiostatic factors in the molecular control of angiogenesis. QJ Nucl Med. 2003,47(3):149-61.
1 Cao Y, Liu Q. Therapeutic targets of multiple angiogenic factors for the treatment of cancer and metastasis. Adv Cancer Res. 2007,97:203-224.
2 Tan, Swee T. M.B.B.S., F.R.A.C.S,et al. Cellular and Extracellular Markers of Hemangioma. Plast Resconstr Surg, 2000,106(3): 529-538.
3 Dyduch G, Okon K, Mierzynski W. Benign vascular proliferations--an immunohistochemical and comparative study. Pol-J-Pathol. 2004; 55(2): 59-64.
4 George T. Stavri, FRCS, Ian C, et al. Basic Fibroblast Growth Factor Upregulates the Expression of Vascular Endothelial Growth Factor in Vascular Smooth Muscle Cells. Circulation. 1995,92(1):11-14
5 Graziano Seghezzi, Sundeep Patel, Christine J Ren, et al. Fibroblast Growth Factor-2 (FGF-2) Induces Vascular Endothelial Growth Factor (VEGF) Expression in the Endothelial Cells of Forming Capillaries: An Autocrine Mechanism Contributing to Angiogenesis. Cell Biol, 1998, 141(7); 1659-1673.
6 Ribatti D, Gualandris A, Belleri M, et al. Alterations of blood vessel development by endothelial cells overexpressing fibroblast growth factor-2. J Pathol. 1999, 189(4):590-599.
7 Ribatti Domenico, Nico Beatrice, Morbidelli Lucia. Cell-mediated delivery of fibroblast growth factor-2 and vascular endothelial growth factor onto the chick chorioallantoic membrane: endothelial fenestration and angiogenesis. Vascular research,2001,38(4):389-397.
8 B. Garmy-Susini, E. Delmas, P. Gourdy, et al. Role of Fibroblast Growth Factor-2 Isoforms in the Effect of Estradiol on Endothelial Cell Migration and Proliferation. Circulation research 2004,94(10),1301-1309.
9 Nicosia RF, Lin YJ, Hazelton D et al. Endogenous regulation of angiogenesis in the rat aorta model. Role of vascular endothelial growth factor. Am J Pathol, 1997; 151(5):1379 -1386.
10 HouckK A,L eungD W,R owlandA M eta l. Dual regulation of vascular endothelialgrowth factor bioavailability by genetic and proteolytic mechanisms J Biol Chem,1992;267(36):26031-26037.
11 Maeda K, Chung Y, Ogawa Y et al. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer. 1996 ,77(5):858-63.
12 Rabie AB, Lu M. Basic fibroblast growth factor up-regulates the expression of vascular endothelial growth factor during healing of allogeneic bone graft. Arch Oral Biol 2004, 49(12):1025—33.
13 Seghezzi G, Patel S, Ren C, et al. Fibroblast growth factor (VEGF) expression in the endothelial cells of forming capillaries: An autocrine mechanism contribution to angiogenesis. J Cell Biol, 1998, 141(7):1659-1673.
14 Pieter Koowijk, Monique G M, Van Erch, et al. Cooperative effect of tubular structures of human microvascular endothelial cells in a fibrin matrix: role of urkinase activity. J Cell Bio, 1996, 132(6):1177-1186.
15 Goldman C K, Kim J, Wong W L, et al. Editorial angiogenesis in three-dimensional cultures. Mol Cell Bio, 1993, 4:121-134.
16 Jung-Sun Lee1, Jonghoe Byun,Jung-Min Kim et al. Cardiac expression profiles of the naked DNA vectors encoding vascular endothelial growth factor and basic fibroblast growth. Expreimental and molecular medicine, 2005, 37(5): 447-456.
17 Soker S, Machado, Atala A. Systems for therapeutic angiogenesis in tissue engineering. World J Urol, 2001, 18(1):10-19.
18 Hartmut Kuhna, Jana Konrada, Silke Holtzb et al .Enhanced expression of VEGF following bFGF inhibition in non-small cell lung cancer cell lines. Lung Cancer , 2006, 54:149—153.
1 Frischer JS, Huang J, Serur A. et al Biomolecular markers and involutionof hemangiomas. Pediatr Surg, 2004, 39(3):400-4.
2 Tan ST, Velickovic M. Ruger BM, et al. Cellular and extracellular markers o hemangioma. Plast Reconstr Surg, 2000, 106(3):529-538.
3 Lamszus K, Lengler U, Schmidt N O, et al. Vascular endothelial growth factor, hepatocyte grow and their relation to antigenesis and malignancy. Neurosurgery, 2000, 46(4):938 -947.
4 Nilesh M. Pandya b, Naranjan S. et al. Angiogenesis—a new target for future therapy. Vascular Pharmacology. 2006, 44(5):265–274.
5 Ritter EJ. The chiken comb and wattle as an experimental model for the therapy of hemangiomas. Preliminary laser studies. Life Sci.1966, 5(20):1903-10.
6 Groot D, Rao J, Johnston P, et al. Algorithm for using a long pulsed Nd: YAG laser in the treatment of deep cutaneous vascular lesions. Dermatol Surg, 2003, 29(1):35-42
7 陈光,赵敏,王琪,等,平阳霉素治疗血管瘤的实验研究. 现代口腔医学杂志,1999,13(4):290-291.
8 Sato N, Sato T, Takahashi S, et al. Establishment of murine endothelial cell lines that develop angiosarcomas in vivo: brief demonstration of a proposed animal model for Kaposi's sarcoma. Cancer Res.1 986, 46(1):362-6.
9 Bautch VL, Toda S, Hassell JA, et al. Endothelial cell tumors develop in transgenic mice carrying polyoma virus middle T oncogene. Cell. 1987, 51(4):529一37.
10 Taraboletti G, Belotti D, Dejana E, et al. Endothelial cell migration and invasiveness are induced by a soluble factor produced by murine endothelioma cells transformed by polyoma virus middle T oncogene. Cancer Res. 1993, 53(16):3812-6.
11 徐骎,张志原,陈万涛,等.转基因小鼠血管瘤动物模型建立.中华口腔医学杂志. 2003,38(5):355-7.
12 Liekens S, Verbeken E, Vandeputte M, et al. A novel animal model for hemangiomas: inhibition of hemangioma development by the angiogenesis inhibitor T NP-470. Cancer Res. 1999, 59(10):2376一83.
13 Dubois Stringfellow N, Kolpack Martindale L, et al. Mice with hemangiomas induced by transgenic endothelial cells. A model for the Kasabach一Merritt syndrome. Am J Pathol.1994, 144(4):796-806.
14 Yu Y, Varughese J, Brown LF, et al. Increased tie2 expression, enhanced response to angiopoietin-1,and dysregulated an giopoietin-2 expression in hemangioma- derived endothelial cells. A m JP athol. 2001, 159(6):2271一80.
15 郭军,吴汉江. 多种药物对体外培养的血管内皮细胞损伤作用比较的研究.华西口腔医学杂志. 2000, 18(5):310-3.
16 Peng Q, Liu W, Tang Y, et al. The establishment of the hemangioma model in mude mouse. J Pediatr Surg. 2005, 40(7):1167-1172.
17 Francesco Sola,1 Anna Gualandris, Mirella Belleri, et al. Endothelial cells overexpressing basic fibroblast growth factor (FGF-2) induce vascular tumors in immunodeficient mice. Angiogenesis, 1997, 1(1): 102-116.
18 Sandra Liekens, Johan Neyts, Erik De Clercq, et al. Inhibition of Fibroblast Growth Factor-2-induced Vascular Tumor Formation by the Acyclic Nucleoside Phosphonate Cidofovir[J]. Cancer Research,2001, 61(1): 5057-5064.
[1] Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics [J]. Plast Reconstr Surg, 1982, 69(3):412-422.
[2] Stephen JM, Vincent RH, Kathy H, et al. Plastic surgery,2nd edition [M]. (volume 5 ). Philadelphia, PA,USA: Saunders Elsevier, 2006: 19-20.
[3] Smolinski,Kara N, Yan,et al. Hemangiomas of infancy:clinical and biological characteristics [J].Clinical pediatrics, 2005,44(9):747-766.
[4] Ceisler EJ, Santos L, Blei F. Periocular hemangiomas: what every physician should know [J]. Pediatr Dermatol, 2004, 21(1):1-9. [ 5 ] Bouchard S, Yazbeck S, Lallier M. Perineal hemangioma, anorectal malformation, and genital anomaly: a new association? [J]. J Pediatr Surg, 1999, 34(7):1133-1135.
[6] Allen RM, Sandquist MA, Piatt JH Jr, et al. Ultrasonographic screening in infants with isolated spinal strawberry nevi [J]. J Neurosurg, 2003,98(3 Suppl):247-250.
[7] Sie KC, Tampakopoulou DA. Hemangiomas and vascular malformations of the airway [J]. Otolaryngol Clin North Am, 2000, 33(1):209-220.
[8] Azizkhan RG. Laser surgery: new applications for pediatric skin and airway lesions [J]. Curr Opin Pediatr, 2003, 15(3):243-247.
[9] Metry DW, Hawrot A, Altman C, et al. Association of solitary, segmental hemangiomas of the skin with visceral hemangiomatosis [J]. Arch Dermatol, 2004, 140(5):591-596.
[10] Haqqstrom AM, Lammer EJ, Schneider RA, et al. Patterns of infantile hemangiomas : new clues to hemangioma pathogenesis and embryonic facial development [J]. Pediatrics, 2006,117(3):698-703.
[11] Metry D. Update on hemangiomas of infancy[J].Current Opinion Pediatrics,2004,16(4):373-377
[12] Waner M. North PE, Scherer KA, et al. The nonrandom distribution of facial hemangiomas [J] . Arch Dermatol, 2003, 139(7):869-875.
[13] Ilona J, Anita N, Haggstrom, et al. Infantile hemangiomas: current knowledge, future directions. Proceedings of a research workshop on infantile hemangiomas [J]. Pediatric dermatology, 2005, 22(5):383-406.
[14] Brook I. Microbiology of infected hemangiomas in children [J]. Pediatr Dermatol, 2004, 21(2):113-116.
[15] Kim HJ, Colombo M, Frieden IJ. Ulcerated hemangiomas: clinical characteristics and response to therapy [J]. J Am Acad Dermatol, 2001,44(6):962-972.
[16] Poetke M, Frommeld T, Berlien HP. PHACE syndrome: new views on diagnostic criteria [J]. Eur J Pediatr Surg, 2002,12(6):366-374.
[17] Metry DW, Dowd CF, Barkovich AJ, et al. The many faces of PHACE syndrome [J]. J Pediatr, 2001,139(1):117-123.
[18] Leung AK, Rafaat M. Benign neonatal hemangiomatosis [J]. Pediatr Dermatol, 2003, 20(2):161-163.
[19] Blei F, Orlow SJ, Geronemus R. Multimodal management of diffuse neonatal hemangiomatosis [J]. J Am Acad Dermatol, 1997,37(6):1019-1021.
[20] Boon LM, Enjolras O, Mulliken JB. Congenital hemangioma: evidence of accelerated involution [J]. J Pediatr, 1996,128(3):329-335. [ 21 ] Enjolras O, Mulliken JB, Boon LM, et al. Noninvoluting congenital hemangioma: a rare cutaneous vascular anomaly [J] . Plast Reconstr Surg, 2001,107(7):1647-1654.
[22] Berenguer B, Mulliken JB, Enjolras O, et al. Rapidly involuting congenital hemangioma: clinical and histopathologic features [J]. Pediatr Dev Pathol, 2003,6(6):495-510.
[23] North PE, Waner M, James CA, et al. Congenital nonprogressive hemangioma: a distinct clinicopathologic entity unlike infantile hemangioma [J]. Arch Dermatol, 2001,137(12):1607-1620.
[24] Mulliken JB, Enjolras O. Congenital hemangiomas and infantile hemangioma: missing links [J]. J Am Acad Dermatol, 2004,50(6):875-882.
[25] Enjolras O, Wassef M, Mazoyer E, et al. Infants with Kasabach-Merritt syndrome do not have "true" hemangiomas [J]. J Pediatr, 1997,130 (4):631-640. [ 26 ] Lyons LL, North PE, Mac-Moune Lai F, et al. Kaposiformhemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma [J]. Am J Surg Pathol, 2004, 28(5):559-68.
[27] Enjolras O, Mulliken JB. Wassef M, Residual lesions after Kasabach-Merrittnomenon in 41 patients [J] . J Am Acad Derm, 2000,42(2 pt1):225-235