nach oben

Angiogenesis

Erschienen in:

01.12.2007 | Review Paper

Angiogenesis as a therapeutic target in arthritis: learning the lessons of the colorectal cancer experience

verfasst von: Tak Loon Khong, Helene Larsen, Yvonne Raatz, Ewa Paleolog

Erschienen in: Angiogenesis | Ausgabe 4/2007

Einloggen, um Zugang zu erhalten

Abstract

The idea of a therapeutic modality aimed at ‘starving’ a tissue of blood vessels, and consequentially of oxygen and nutrients, was born from the concept that blood vessel formation (angiogenesis) is central to the progression and maintenance of diseases which involve tissue expansion/invasion. In the first instance, solid malignancies were the target for anti-angiogenic treatments, with colorectal cancer being the first disease for which an angiogenesis inhibitor—anti-vascular endothelial growth factor antibody bevacizumab—was approved in 2004.

Our understanding of the pathogenesis of rheumatoid arthritis (RA) has lead to many parallels being drawn between this chronic inflammatory disease and solid tumours, in that both involve tissue expansion, invasion, expression of cytokines and growth factors and areas of hypoxia/hypoperfusion. As a result, angiogenesis blockade has been touted as a possible treatment for RA. The lessons learnt during the progression of eventually successful therapies such as bevacizumab should undoubtedly guide us in the future development of comparable treatments for RA.

Paleolog EM, Miotla JM (1998) Angiogenesis in arthritis: role in disease pathogenesis and as a potential therapeutic target. Angiogenesis 2(4):295–307PubMed

Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186PubMedCrossRef

Folkman J, Merler E, Abernathy C, Williams G (1971) Isolation of a tumor factor responsible for angiogenesis. J Exp Med 133(2):275–288PubMed

Lobb RR, Key ME, Alderman EM, Fett JW (1985) Partial purification and characterization of a vascular permeability factor secreted by a human colon adenocarcinoma cell line. Int J Cancer 36(4):473–478PubMed

Senger DR, Perruzzi CA, Feder J, Dvorak HF (1986) A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res 46(11):5629–5632PubMed

Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935):1306–1309PubMed

Ertel AN (1989) Flexor tendon ruptures in rheumatoid arthritis. Hand Clin 5(2):177–190PubMed

Williamson SC, Feldon P (1995) Extensor tendon ruptures in rheumatoid arthritis. Hand Clin 11(3):449–459PubMed

Walsh DA (1999) Angiogenesis and arthritis. Rheumatology (Oxford) 38(2):103–112

10.

Koch AE (2003) Angiogenesis as a target in rheumatoid arthritis. Ann Rheum Dis 62(Suppl 2):ii60–ii67PubMed

11.

Schumacher HR Jr, Bautista BB, Krauser RE, Mathur AK, Gall EP (1994) Histological appearance of the synovium in early rheumatoid arthritis. Semin Arthritis Rheum 23(6 Suppl 2):3–10PubMed

12.

FitzGerald O, Bresnihan B (1995) Synovial membrane cellularity and vascularity. Ann Rheum Dis 54(6):511–515PubMed

13.

Hirohata S, Sakakibara J (1999) Angioneogenesis as a possible elusive triggering factor in rheumatoid arthritis. Lancet 353(9161):1331PubMed

14.

Rooney M, Condell D, Quinlan W, Daly L, Whelan A, Feighery C et al (1988) Analysis of the histologic variation of synovitis in rheumatoid arthritis. Arthritis Rheum 31(8):956–963PubMed

15.

Ceponis A, Konttinen YT, MacKevicius Z, Solovieva SA, Hukkanen M, Tamulaitiene M et al (1996) Aberrant vascularity and von Willebrand factor distribution in inflamed synovial membrane. J Rheumatol 23(11):1880–1886PubMed

16.

Walsh DA, Wade M, Mapp PI, Blake DR (1998) Focally regulated endothelial proliferation and cell death in human synovium. Am J Pathol 152(3):691–702PubMed

17.

Sivakumar B, Harry LE, Paleolog EM (2004) Modulating angiogenesis: more vs. less. Jama 292(8):972–977PubMed

18.

Sivakumar B, Paleolog EM (2005) Immunotherapy of rheumatoid arthritis: past, present and future. Curr Opin Drug Discov Devel 8(2):169–176PubMed

19.

Bainbridge J, Sivakumar B, Paleolog E (2006) Angiogenesis as a therapeutic target in arthritis: lessons from oncology. Curr Pharm Des 12(21):2631–2644PubMed

20.

Taylor PC, Paleolog EM (2006) Is the vasculature a potential therapeutic target in arthritis? Curr Rheumatol Rev 2(2):151–158

21.

Sano H, Engleka K, Mathern P, Hla T, Crofford LJ, Remmers EF et al (1993) Coexpression of phosphotyrosine-containing proteins, platelet-derived growth factor-B, and fibroblast growth factor-1 in situ in synovial tissues of patients with rheumatoid arthritis and Lewis rats with adjuvant or streptococcal cell wall arthritis. J Clin Invest 91(2):553–565PubMed

22.

Sano H, Forough R, Maier JA, Case JP, Jackson A, Engleka K et al (1990) Detection of high levels of heparin binding growth factor-1 (acidic fibroblast growth factor) in inflammatory arthritic joints. J Cell Biol 110(4):1417–1426PubMed

23.

Remmers EF, Sano H, Lafyatis R, Case JP, Kumkumian GK, Hla T et al (1991) Production of platelet derived growth factor B chain (PDGF-B/c-sis) mRNA and immunoreactive PDGF B-like polypeptide by rheumatoid synovium: coexpression with heparin binding acidic fibroblast growth factor-1. J Rheumatol 18(1):7–13PubMed

24.

Koch AE, Halloran MM, Hosaka S, Shah MR, Haskell CJ, Baker SK et al (1996) Hepatocyte growth factor. A cytokine mediating endothelial migration in inflammatory arthritis. Arthritis Rheum 39(9):1566–1575PubMed

25.

Feuerherm AJ, Borset M, Seidel C, Sundan A, Leistad L, Ostensen M et al (2001) Elevated levels of osteoprotegerin (OPG) and hepatocyte growth factor (HGF) in rheumatoid arthritis. Scand J Rheumatol 30(4):229–234PubMed

26.

Yukioka K, Inaba M, Furumitsu Y, Yukioka M, Nishino T, Goto H et al (1994) Levels of hepatocyte growth factor in synovial fluid and serum of patients with rheumatoid arthritis and release of hepatocyte growth factor by rheumatoid synovial fluid cells. J Rheumatol 21(12):2184–2189PubMed

27.

Kusada J, Otsuka T, Matsui N, Hirano T, Asai K, Kato T (1993) Immuno-reactive human epidermal growth factor (h-EGF) in rheumatoid synovial fluids. Nippon Seikeigeka Gakkai Zasshi 67(9):859–865PubMed

28.

Farahat MN, Yanni G, Poston R, Panayi GS (1993) Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis 52(12):870–875PubMed

29.

Scott BB, Zaratin PF, Colombo A, Hansbury MJ, Winkler JD, Jackson JR (2002) Constitutive expression of angiopoietin-1 and -2 and modulation of their expression by inflammatory cytokines in rheumatoid arthritis synovial fibroblasts. J Rheumatol 29(2):230–239PubMed

30.

Gravallese EM, Pettit AR, Lee R, Madore R, Manning C, Tsay A et al (2003) Angiopoietin-1 is expressed in the synovium of patients with rheumatoid arthritis and is induced by tumour necrosis factor alpha. Ann Rheum Dis 62(2):100–107PubMed

31.

DeBusk LM, Chen Y, Nishishita T, Chen J, Thomas JW, Lin PC (2003) Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alpha-induced angiogenesis in rheumatoid arthritis. Arthritis Rheum 48(9):2461–2471PubMed

32.

Shahrara S, Volin MV, Connors MA, Haines GK, Koch AE (2002) Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue. Arthritis Res 4(3):201–208PubMed

33.

Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. Faseb J 13(1):9–22PubMed

34.

Koch AE, Harlow LA, Haines GK, Amento EP, Unemori EN, Wong WL et al (1994) Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 152(8):4149–4156PubMed

35.

Lee SS, Joo YS, Kim WU, Min DJ, Min JK, Park SH et al (2001) Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol 19(3):321–324PubMed

36.

Fava RA, Olsen NJ, Spencer-Green G, Yeo KT, Yeo TK, Berse B et al (1994) Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J Exp Med 180(1):341–346PubMed

37.

Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M, Maini RN (1998) Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha and interleukin-1 in rheumatoid arthritis. Arthritis Rheum 41(7):1258–1265PubMed

38.

Harada M, Mitsuyama K, Yoshida H, Sakisaka S, Taniguchi E, Kawaguchi T et al (1998) Vascular endothelial growth factor in patients with rheumatoid arthritis. Scand J Rheumatol 27(5):377–380PubMed

39.

Kikuchi K, Kubo M, Kadono T, Yazawa N, Ihn H, Tamaki K (1998) Serum concentrations of vascular endothelial growth factor in collagen diseases. Br J Dermatol 139(6):1049–1051PubMed

40.

Sone H, Sakauchi M, Takahashi A, Suzuki H, Inoue N, Iida K et al (2001) Elevated levels of vascular endothelial growth factor in the sera of patients with rheumatoid arthritis correlation with disease activity. Life Sci 69(16):1861–1869PubMed

41.

Pufe T, Petersen W, Tillmann B, Mentlein R (2001) The splice variants VEGF121 and VEGF189 of the angiogenic peptide vascular endothelial growth factor are expressed in osteoarthritic cartilage. Arthritis Rheum 44(5):1082–1088PubMed

42.

Ballara SC, Taylor PC, Reusch P, Marmé D, Feldmann M, Maini RN et al (2001) Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum 44(9):2055–2064PubMed

43.

Latour F, Zabraniecki L, Dromer C, Brouchet A, Durroux R, Fournie B (2001) Does vascular endothelial growth factor in the rheumatoid synovium predict joint destruction? A clinical, radiological, and pathological study in 12 patients monitored for 10 years. Joint Bone Spine 68(6):493–498PubMed

44.

Clavel G, Bessis N, Lemeiter D, Fardellone P, Mejjad O, Menard JF et al (2007) Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very early arthritis and their association with inflammation and joint destruction. Clin Immunol 124(2):158–164PubMed

45.

Nakahara H, Song J, Sugimoto M, Hagihara K, Kishimoto T, Yoshizaki K et al (2003) Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthritis Rheum 48(6):1521–1529PubMed

46.

Klimiuk PA, Sierakowski S, Domyslawska I, Fiedorczyk M, Chwiecko J (2004) Reduction of soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor levels in serum of rheumatoid arthritis patients following multiple intravenous infusions of infliximab. Arch Immunol Ther Exp (Warsz) 52(1):36–42

47.

Aggarwal A, Panda S, Misra R (2004) Effect of etanercept on matrix metalloproteinases and angiogenic vascular endothelial growth factor: a time kinetic study. Ann Rheum Dis 63(7):891–892PubMed

48.

Macias I, Garcia-Perez S, Ruiz-Tudela M, Medina F, Chozas N, Giron-Gonzalez JA (2005) Modification of pro- and antiinflammatory cytokines and vascular-related molecules by tumor necrosis factor-a blockade in patients with rheumatoid arthritis. J Rheumatol 32(11):2102–2108PubMed

49.

Nagashima M, Wauke K, Hirano D, Ishigami S, Aono H, Takai M et al (2000) Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial growth factor and basic fibroblast growth factor in cultured synoviocytes and patients with rheumatoid arthritis. Rheumatology (Oxford) 39(11):1255–1262

50.

Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S, Ciolkiewicz M (2006) A study on vascular endothelial growth factor and endothelin-1 in patients with extra-articular involvement of rheumatoid arthritis. Clin Rheumatol 25(3):314–319PubMed

51.

Ikeda M, Hosoda Y, Hirose S, Okada Y, Ikeda E (2000) Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis. J Pathol 191(4):426–433PubMed

52.

Giatromanolaki A, Sivridis E, Athanassou N, Zois E, Thorpe PE, Brekken RA et al (2001) The angiogenic pathway “vascular endothelial growth factor/flk-1(KDR)-receptor” in rheumatoid arthritis and osteoarthritis. J Pathol 194(1):101–108PubMed

53.

Lund-Olesen K (1970) Oxygen tension in synovial fluids. Arthritis Rheum 13(6):769–776PubMed

54.

Etherington PJ, Winlove P, Taylor P, Paleolog E, Miotla JM (2002) VEGF release is associated with reduced oxygen tensions in experimental inflammatory arthritis. Clin Exp Rheumatol 20(6):799–805PubMed

55.

Sivakumar B (2006) Hypoxia-driven angiogensis is a key feature of tendon disease in rheumatoid arthritis. Vascul Pharmacol 45(3):e123

56.

Hitchon C, Wong K, Ma G, Reed J, Lyttle D, El-Gabalawy H (2002) Hypoxia-induced production of stromal cell-derived factor 1 (CXCL12) and vascular endothelial growth factor by synovial fibroblasts. Arthritis Rheum 46(10):2587–2597PubMed

57.

Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ et al (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292(5516):468–472PubMed

58.

Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M et al (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O₂ sensing. Science 292(5516):464–468PubMed

59.

Wiesener MS, Turley H, Allen WE, Willam C, Eckardt KU, Talks KL et al (1998) Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1alpha. Blood 92(7):2260–2268PubMed

60.

Jiang BH, Semenza GL, Bauer C, Marti HH (1996) Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O₂ tension. Am J Physiol 271(4 Pt 1):C1172–C1180PubMed

61.

Zhou J, Schmid T, Brune B (2003) Tumor necrosis factor-alpha causes accumulation of a ubiquitinated form of hypoxia inducible factor-1alpha through a nuclear factor-kappaB-dependent pathway. Mol Biol Cell 14(6):2216–2225PubMed

62.

Scharte M, Han X, Bertges DJ, Fink MP, Delude RL (2003) Cytokines induce HIF-1 DNA binding and the expression of HIF-1-dependent genes in cultured rat enterocytes. Am J Physiol Gastrointest Liver Physiol 284(3):G373–G384PubMed

63.

Hellwig-Burgel T, Rutkowski K, Metzen E, Fandrey J, Jelkmann W (1999) Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of hypoxia-inducible factor-1. Blood 94(5):1561–1567PubMed

64.

Albina JE, Mastrofrancesco B, Vessella JA, Louis CA, Henry WL Jr, Reichner JS (2001) HIF-1 expression in healing wounds: HIF-1alpha induction in primary inflammatory cells by TNF-alpha. Am J Physiol Cell Physiol 281(6):C1971–C1977PubMed

65.

Bilton RL, Booker GW (2003) The subtle side to hypoxia inducible factor (HIFalpha) regulation. Eur J Biochem 270(5):791–798PubMed

66.

Jung Y, Isaacs JS, Lee S, Trepel J, Liu ZG, Neckers L (2003) Hypoxia-inducible factor induction by tumour necrosis factor in normoxic cells requires receptor-interacting protein-dependent nuclear factor kappa B activation. Biochem J 370(Pt 3):1011–1017PubMed

67.

Berse B, Hunt JA, Diegel RJ, Morganelli P, Yeo K, Brown F et al (1999) Hypoxia augments cytokine (transforming growth factor-beta (TGF-beta) and IL-1)-induced vascular endothelial growth factor secretion by human synovial fibroblasts. Clin Exp Immunol 115(1):176–182PubMed

68.

Hollander AP, Corke KP, Freemont AJ, Lewis CE (2001) Expression of hypoxia-inducible factor 1alpha by macrophages in the rheumatoid synovium: implications for targeting of therapeutic genes to the inflamed joint. Arthritis Rheum 44(7):1540–1544PubMed

69.

Peters CL, Morris CJ, Mapp PI, Blake DR, Lewis CE, Winrow VR (2004) The transcription factors hypoxia-inducible factor 1alpha and Ets-1 colocalize in the hypoxic synovium of inflamed joints in adjuvant-induced arthritis. Arthritis Rheum 50(1):291–296PubMed

70.

Giatromanolaki A, Sivridis E, Maltezos E, Athanassou N, Papazoglou D, Gatter KC et al (2003) Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 5(4):R193–R201PubMed

71.

Richman AI, Su EY, Ho G Jr (1981) Reciprocal relationship of synovial fluid volume and oxygen tension. Arthritis Rheum 24(5):701–705PubMed

72.

Lee YA, Kim JY, Hong SJ, Lee SH, Yoo MC, Kim KS et al (2007). Synovial proliferation differentially affects hypoxia in the joint cavities of rheumatoid arthritis and osteoarthritis patients. Clin Rheumatol, doi: 10.1007/s10067-007-0605-2

73.

Qu Z, Huang XN, Ahmadi P, Andresevic J, Planck SR, Hart CE et al (1995) Expression of basic fibroblast growth factor in synovial tissue from patients with rheumatoid arthritis and degenerative joint disease. Lab Invest 73(3):339–346PubMed

74.

Salvador G, Sanmarti R, Gil-Torregrosa B, Garcia-Peiro A, Rodriguez-Cros JR, Canete JD (2006) Synovial vascular patterns and angiogenic factors expression in synovial tissue and serum of patients with rheumatoid arthritis. Rheumatology (Oxford) 45(8):966–971

75.

Dooley S, Herlitzka I, Hanselmann R, Ermis A, Henn W, Remberger K et al (1996) Constitutive expression of c-fos and c-jun, overexpression of ets-2, and reduced expression of metastasis suppressor gene nm23-H1 in rheumatoid arthritis. Ann Rheum Dis 55(5):298–304PubMed

76.

Trabandt A, Aicher WK, Gay RE, Sukhatme VP, Nilson-Hamilton M, Hamilton RT et al (1990) Expression of the collagenolytic and Ras-induced cysteine proteinase cathepsin L and proliferation-associated oncogenes in synovial cells of MRL/I mice and patients with rheumatoid arthritis. Matrix 10(6):349–361PubMed

77.

Lacey D, Sampey A, Mitchell R, Bucala R, Santos L, Leech M et al (2003) Control of fibroblast-like synoviocyte proliferation by macrophage migration inhibitory factor. Arthritis Rheum 48(1):103–109PubMed

78.

Lee MS, Yoo SA, Cho CS, Suh PG, Kim WU, Ryu SH (2006) Serum amyloid A binding to formyl peptide receptor-like 1 induces synovial hyperplasia and angiogenesis. J Immunol 177(8):5585–5594PubMed

79.

Kim WU, Kang SS, Yoo SA, Hong KH, Bae DG, Lee MS et al (2006) Interaction of vascular endothelial growth factor 165 with neuropilin-1 protects rheumatoid synoviocytes from apoptotic death by regulating Bcl-2 expression and Bax translocation. J Immunol 177(8):5727–5735PubMed

80.

Miagkov AV, Kovalenko DV, Brown CE, Didsbury JR, Cogswell JP, Stimpson SA et al (1998) NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc Natl Acad Sci USA 95(23):13859–13864PubMed

81.

Schedel J, Gay RE, Kuenzler P, Seemayer C, Simmen B, Michel BA et al (2002) FLICE-inhibitory protein expression in synovial fibroblasts and at sites of cartilage and bone erosion in rheumatoid arthritis. Arthritis Rheum 46(6):1512–1518PubMed

82.

Meinecke I, Cinski A, Baier A, Peters MA, Dankbar B, Wille A et al (2007) Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts. Proc Natl Acad Sci USA 104(12):5073–5078PubMed

83.

Seemayer CA, Kuchen S, Kuenzler P, Rihoskova V, Rethage J, Aicher WK et al (2003) Cartilage destruction mediated by synovial fibroblasts does not depend on proliferation in rheumatoid arthritis. Am J Pathol 162(5):1549–1557PubMed

84.

Mohr W, Beneke G, Mohing W (1975) Proliferation of synovial lining cells and fibroblasts. Ann Rheum Dis 34(3):219–224PubMed

85.

Baier A, Meineckel I, Gay S, Pap T (2003) Apoptosis in rheumatoid arthritis. Curr Opin Rheumatol 15(3):274–279PubMed

86.

Ho QT, Kuo CJ (2007) Vascular endothelial growth factor: biology and therapeutic applications. Int J Biochem Cell Biol 39(7–8):1349–1357PubMed

87.

Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967PubMed

88.

Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M et al (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85(3):221–228PubMed

89.

Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. Embo J 18(14):3964–3972PubMed

90.

Murayama T, Tepper OM, Silver M, Ma H, Losordo DW, Isner JM et al (2002) Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol 30(8):967–972PubMed

91.

Hattori K, Dias S, Heissig B, Hackett NR, Lyden D, Tateno M et al (2001) Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 193(9):1005–1014PubMed

92.

Ruger B, Giurea A, Wanivenhaus AH, Zehetgruber H, Hollemann D, Yanagida G et al (2004) Endothelial precursor cells in the synovial tissue of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum 50(7):2157–2166PubMed

93.

Grisar J, Aletaha D, Steiner CW, Kapral T, Steiner S, Seidinger D et al (2005) Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation 111(2):204–211PubMed

94.

Herbrig K, Haensel S, Oelschlaegel U, Pistrosch F, Foerster S, Passauer J (2005) Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells. Ann Rheum Dis 65(2):157–163PubMed

95.

Hirohata S, Yanagida T, Nampei A, Kunugiza Y, Hashimoto H, Tomita T et al (2004) Enhanced generation of endothelial cells from CD34+ cells of the bone marrow in rheumatoid arthritis: possible role in synovial neovascularization. Arthritis Rheum 50(12):3888–3896PubMed

96.

Ablin JN, Boguslavski V, Aloush V, Elkayam O, Paran D, Caspi D et al (2006) Effect of anti-TNFalpha treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis. Life Sci 79(25):2364–2369PubMed

97.

Van Doornum S, McColl G, Wicks IP (2002) Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum 46(4):862–873PubMed

98.

Van Doornum S, Brand C, King B, Sundararajan V (2006) Increased case fatality rates following a first acute cardiovascular event in patients with rheumatoid arthritis. Arthritis Rheum 54(7):2061–2068PubMed

99.

Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H et al (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89(1):E1–E7PubMed

100.

Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA et al (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348(7):593–600PubMed

101.

Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U et al (2005) Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 111(22):2981–2987PubMed

102.

Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A et al (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353(10):999–1007PubMed

103.

Grisar JC, Aletaha D, Steiner CW, Kapral T, Steiner S, Saemann M et al (2007) Endothelial progenitor cells in active rheumatoid arthritis: Effects of TNF and of glucocorticoid therapy. Ann Rheum Dis, doi: 10.1136/ard.2006.066605

104.

Seeger FH, Haendeler J, Walter DH, Rochwalsky U, Reinhold J, Urbich C et al (2005) p38 mitogen-activated protein kinase downregulates endothelial progenitor cells. Circulation 111(9):1184–1191PubMed

105.

Taylor PC, Sivakumar B (2005) Hypoxia and angiogenesis in rheumatoid arthritis. Curr Opin Rheumatol 17(3):293–298PubMed

106.

Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18(3):581–592PubMed

107.

Statistics OfN. Mortality Statistics: Cause. England and Wales 2005. London TSO 2006

108.

Campbell NC, Elliott AM, Sharp L, Ritchie LD, Cassidy J, Little J (2001) Rural and urban differences in stage at diagnosis of colorectal and lung cancers. Br J Cancer 84(7):910–914PubMed

109.

Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676PubMed

110.

Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ (1995) Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol 147(1):33–41PubMed

111.

Kuwai T, Kitadai Y, Tanaka S, Onogawa S, Matsutani N, Kaio E et al (2003) Expression of hypoxia-inducible factor-1alpha is associated with tumor vascularization in human colorectal carcinoma. Int J Cancer 105(2):176–181PubMed

112.

Konerding MA, Malkusch W, Klapthor B, van Ackern C, Fait E, Hill SA et al (1999) Evidence for characteristic vascular patterns in solid tumours: quantitative studies using corrosion casts. Br J Cancer 80(5–6):724–732PubMed

113.

Denekamp J (1990) Vascular attack as a therapeutic strategy for cancer. Cancer Metastasis Rev 9(3):267–282PubMed

114.

Wouters BG, Weppler SA, Koritzinsky M, Landuyt W, Nuyts S, Theys J et al (2002) Hypoxia as a target for combined modality treatments. Eur J Cancer 38(2):240–257PubMed

115.

Goethals L, Debucquoy A, Perneel C, Geboes K, Ectors N, De Schutter H et al (2006) Hypoxia in human colorectal adenocarcinoma: comparison between extrinsic and potential intrinsic hypoxia markers. Int J Radiat Oncol Biol Phys 65(1):246–254PubMed

116.

Zakarija A, Soff G (2005) Update on angiogenesis inhibitors. Curr Opin Oncol 17(6):578–583PubMed

117.

Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L et al (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57(20):4593–4599PubMed

118.

Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7(9):987–989PubMed

119.

Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10(2):145–147PubMed

120.

Koukourakis MI, Mavanis I, Kouklakis G, Pitiakoudis M, Minopoulos G, Manolas C et al (2007) Early antivascular effects of bevacizumab anti-VEGF monoclonal antibody on colorectal carcinomas assessed with functional CT imaging. Am J Clin Oncol 30(3):315–318PubMed

121.

Yao K, Gietema JA, Shida S, Selvakumaran M, Fonrose X, Haas NB et al (2005) In vitro hypoxia-conditioned colon cancer cell lines derived from HCT116 and HT29 exhibit altered apoptosis susceptibility and a more angiogenic profile in vivo. Br J Cancer 93(12):1356–1363PubMed

122.

Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G et al (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21(1):60–65PubMed

123.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342PubMed

124.

Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S (2005) Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol 23(16):3706–3712PubMed

125.

Giantonio BJ, Levy DE, O’Dwyer P J, Meropol NJ, Catalano PJ, Benson AB 3rd (2006) A phase II study of high-dose bevacizumab in combination with irinotecan, 5-fluorouracil, leucovorin, as initial therapy for advanced colorectal cancer: results from the Eastern Cooperative Oncology Group study E2200. Ann Oncol 17(9):1399–1403PubMed

126.

Wood JM, Bold G, Buchdunger E, Cozens R, Ferrari S, Frei J et al (2000) PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 60(8):2178–2189PubMed

127.

Hecht J, Trarbach T, Jaeger E, Hainsworth J, Wolff R, Lloyd K et al (2005) A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/ 5-fluorouracil. J Clin Oncol 2005 ASCO Annual Meeting Proceedings 23(16S, Part I of II (June 1 Supplement)):3

128.

Koehne C, Bajetta E, Lin E, Van Cutsem E, Hecht J, Douillard J et al (2006) Results of an interim analysis of a multinational randomized, double-blind, phase III study in patients (pts) with previously treated metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo (CONFIRM 2). J Clin Oncol, 2006 ASCO Annual Meeting Proceedings Part I 24(No. 18S (June 20 Supplement), 2006):3508

129.

Major P, Trarbach T, Lenz H, Kerr D, Pendergrass K, Douillard J et al (2006) A meta-analysis of two randomized, double-blind, placebo-controlled, phase III studies in patients (pts) with metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK/ZK to determine clinical benefit on progression-free survival (PFS) in high LDH pts. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings Part I 24(No. 18S (June 20 Supplement)):3529

130.

Jost LM, Gschwind HP, Jalava T, Wang Y, Guenther C, Souppart C et al (2006) Metabolism and disposition of vatalanib (PTK787/ZK-222584) in cancer patients. Drug Metab Dispos 34(11):1817–1828PubMed

131.

Malemud CJ (2007) Growth hormone, VEGF and FGF: involvement in rheumatoid arthritis. Clin Chim Acta 375(1–2):10–19PubMed

132.

Berry S, Cunningham D, Michael M, Dibartolomeo M, Rivera F, Kretzschmar A et al (2006) Preliminary safety of bevacizumab with first-line Folfox, Capox, Folfiri and capecitabine for mCRC-First B.E.A.Trial. J Clin Oncol, ASCO Annual Meeting Proceedings Part I 24(No. 18S (June 20 Supplement)):3534

133.

Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J et al (2005) Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91(3):173–180PubMed

134.

Tabruyn SP, Griffioen AW (2007) Molecular pathways of angiogenesis inhibition. Biochem Biophys Res Commun 355(1):1–5PubMed

135.

Williams RO (2007) Collagen-induced arthritis in mice: a major role for tumor necrosis factor-alpha. Methods Mol Biol (Clifton, NJ 361:265–284

136.

Holmdahl R, Jansson L, Larsson E, Rubin K, Klareskog L (1986) Homologous type II collagen induces chronic and progressive arthritis in mice. Arthritis Rheum 29(1):106–113PubMed

137.

Malfait AM, Williams RO, Malik AS, Maini RN, Feldmann M (2001) Chronic relapsing homologous collagen-induced arthritis in DBA/1 mice as a model for testing disease-modifying and remission-inducing therapies. Arthritis Rheum 44(5):1215–1224PubMed

138.

Williams RO, Ghrayeb J, Feldmann M, Maini RN (1995) Successful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4. Immunology 84(3):433–439PubMed

139.

Williams RO, Marinova-Mutafchieva L, Feldmann M, Maini RN (2000) Evaluation of TNF-alpha and IL-1 blockade in collagen-induced arthritis and comparison with combined anti-TNF-alpha/anti-CD4 therapy. J Immunol 165(12):7240–7245PubMed

140.

Williams RO, Mason LJ, Feldmann M, Maini RN (1994) Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis. Proc Natl Acad Sci USA 91(7):2762–2766PubMed

141.

Lu J, Kasama T, Kobayashi K, Yoda Y, Shiozawa F, Hanyuda M et al (2000) Vascular endothelial growth factor expression and regulation of murine collagen-induced arthritis. J Immunol 164(11):5922–5927PubMed

142.

Sone H, Kawakami Y, Sakauchi M, Nakamura Y, Takahashi A, Shimano H et al (2001) Neutralization of vascular endothelial growth factor prevents collagen-induced arthritis and ameliorates established disease in mice. Biochem Biophys Res Commun 281(2):562–568PubMed

143.

Miotla J, Maciewicz R, Kendrew J, Feldmann M, Paleolog E (2000) Treatment with soluble VEGF receptor reduces disease severity in murine collagen-induced arthritis. Lab Invest 80(8):1195–1205PubMedCrossRef

144.

Afuwape AO, Feldmann M, Paleolog EM (2003) Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) abrogates disease activity in murine collagen-induced arthritis. Gene Ther 10(23):1950–1960PubMed

145.

de Bandt M, Ben Mahdi MH, Ollivier V, Grossin M, Dupuis M, Gaudry M et al (2003) Blockade of vascular endothelial growth factor receptor I (VEGF-RI), but not VEGF-RII, suppresses joint destruction in the K/BxN model of rheumatoid arthritis. J Immunol 171(9):4853–4859PubMed

146.

Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F et al (2002) Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 8(8):831–840PubMed

147.

Grosios K, Wood J, Esser R, Raychaudhuri A, Dawson J (2004) Angiogenesis inhibition by the novel VEGF receptor tyrosine kinase inhibitor, PTK787/ZK222584, causes significant anti-arthritic effects in models of rheumatoid arthritis. Inflamm Res 53(4):133–142PubMed

148.

Clauss M, Weich H, Breier G, Knies U, Rockl W, Waltenberger J et al (1996) The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis. J Biol Chem 271(30):17629–17634PubMed

149.

Sawano A, Iwai S, Sakurai Y, Ito M, Shitara K, Nakahata T et al (2001) Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans. Blood 97(3):785–791PubMed

150.

Murakami M, Iwai S, Hiratsuka S, Yamauchi M, Nakamura K, Iwakura Y et al (2006) Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocytes/macrophages. Blood 108(6):1849–1856PubMed

151.

Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M et al (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573):435–439PubMed

152.

Mould AW, Tonks ID, Cahill MM, Pettit AR, Thomas R, Hayward NK et al (2003) Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis. Arthritis Rheum 48(9):2660–2669PubMed

153.

Autiero M, Luttun A, Tjwa M, Carmeliet P (2003) Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. J Thromb Haemost 1(7):1356–1370PubMed

154.

Tjwa M, Luttun A, Autiero M, Carmeliet P (2003) VEGF and PlGF: two pleiotropic growth factors with distinct roles in development and homeostasis. Cell Tissue Res 314(1):5–14PubMed

155.

Autiero M, Waltenberger J, Communi D, Kranz A, Moons L, Lambrechts D et al (2003) Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med 9(7):936–943PubMed

156.

Oosthuyse B, Moons L, Storkebaum E, Beck H, Nuyens D, Brusselmans K et al (2001) Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet 28(2):131–138PubMed

157.

Bottomley MJ, Webb NJ, Watson CJ, Holt L, Bukhari M, Denton J et al (2000) Placenta growth factor (PlGF) induces vascular endothelial growth factor (VEGF) secretion from mononuclear cells and is co-expressed with VEGF in synovial fluid. Clin Exp Immunol 119(1):182–188PubMed

158.

Date K, Matsumoto K, Shimura H, Tanaka M, Nakamura T (1997) HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor. FEBS Lett 420(1):1–6PubMed

159.

Kuba K, Matsumoto K, Date K, Shimura H, Tanaka M, Nakamura T (2000) HGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice. Cancer Res 60(23):6737–6743PubMed

160.

Nakabayashi M, Morishita R, Nakagami H, Kuba K, Matsumoto K, Nakamura T et al (2003) HGF/NK4 inhibited VEGF-induced angiogenesis in in vitro cultured endothelial cells and in vivo rabbit model. Diabetologia 46(1):115–123PubMed

161.

Matsumoto K, Nakamura T (2005) Mechanisms and significance of bifunctional NK4 in cancer treatment. Biochem Biophys Res Commun 333(2):316–327PubMed

162.

Kim JM, Ho SH, Park EJ, Hahn W, Cho H, Jeong JG et al (2002) Angiostatin gene transfer as an effective treatment strategy in murine collagen-induced arthritis. Arthritis Rheum 46(3):793–801PubMed

163.

Kato K, Miyake K, Igarashi T, Yoshino S, Shimada T (2005) Human immunodeficiency virus vector-mediated intra-articular expression of angiostatin inhibits progression of collagen-induced arthritis in mice. Rheumatol Int 25(7):522–529PubMed

164.

Takahashi H, Kato K, Miyake K, Hirai Y, Yoshino S, Shimada T (2005) Adeno-associated virus vector-mediated anti-angiogenic gene therapy for collagen-induced arthritis in mice. Clin Exp Rheumatol 23(4):455–461PubMed

165.

Sumariwalla P, Cao Y, Wu H, Feldmann M, Paleolog E (2003) The angiogenesis inhibitor protease-activated kringles 1–5 reduces the severity of murine collagen-induced arthritis. Arthritis Res Ther 5:R32–R39PubMed

166.

Matsuno H, Yudoh K, Uzuki M, Nakazawa F, Sawai T, Yamaguchi N et al (2002) Treatment with the angiogenesis inhibitor endostatin: a novel therapy in rheumatoid arthritis. J Rheumatol 29(5):890–895PubMed

167.

Yin G, Liu W, An P, Li P, Ding I, Planelles V et al (2002) Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis. Mol Ther 5(5 Pt 1):547–554PubMed

168.

Kurosaka D, Yoshida K, Yasuda J, Yokoyama T, Kingetsu I, Yamaguchi N et al (2003) Inhibition of arthritis by systemic administration of endostatin in passive murine collagen induced arthritis. Ann Rheum Dis 62(7):677–679PubMed

169.

Yue L, Shen YX, Feng LJ, Chen FH, Yao HW, Liu LH et al (2007) Blockage of the formation of new blood vessels by recombinant human endostatin contributes to the regression of rat adjuvant arthritis. Eur J Pharmacol 567(1–2):166–170PubMed

170.

de Bandt M, Grossin M, Weber AJ, Chopin M, Elbim C, Pla M et al (2000) Suppression of arthritis and protection from bone destruction by treatment with TNP-470/AGM-1470 in a transgenic mouse model of rheumatoid arthritis. Arthritis Rheum 43(9):2056–2063PubMed

171.

Arsenault AL, Lhotak S, Hunter WL, Banquerigo ML, Brahn E (1998) Taxol involution of collagen-induced arthritis: ultrastructural correlation with the inhibition of synovitis and neovascularization. Clin Immunol Immunopathol 86(3):280–289PubMed

172.

Peacock DJ, Banquerigo ML, Brahn E (1992) Angiogenesis inhibition suppresses collagen arthritis. J Exp Med 175(4):1135–1138PubMed

173.

Peacock DJ, Banquerigo ML, Brahn E (1995) A novel angiogenesis inhibitor suppresses rat adjuvant arthritis. Cell Immunol 160(2):178–184PubMed

174.

Oliver SJ, Banquerigo ML, Brahn E (1994) Suppression of collagen-induced arthritis using an angiogenesis inhibitor, AGM-1470, and a microtubule stabilizer, taxol. Cell Immunol 157(1):291–299PubMed

175.

Oliver SJ, Cheng TP, Banquerigo ML, Brahn E (1995) Suppression of collagen-induced arthritis by an angiogenesis inhibitor, AGM-1470, in combination with cyclosporin: reduction of vascular endothelial growth factor (VEGF). Cell Immunol 166(2):196–206PubMed

176.

Nagashima M, Tanaka H, Takahashi H, Tachihara A, Tanaka K, Ishiwata T et al (2002) Study of the mechanism involved in angiogenesis and synovial cell proliferation in human synovial tissues of patients with rheumatoid arthritis using SCID mice. Lab Invest 82(8):981–988PubMed

177.

Bernier SG, Lazarus DD, Clark E, Doyle B, Labenski MT, Thompson CD et al (2004) A methionine aminopeptidase-2 inhibitor, PPI-2458, for the treatment of rheumatoid arthritis. Proc Natl Acad Sci USA 101(29):10768–10773PubMed

178.

Bernier SG, Taghizadeh N, Thompson CD, Westlin WF, Hannig G (2005) Methionine aminopeptidases type I and type II are essential to control cell proliferation. J Cell Biochem 95(6):1191–1203PubMed

179.

Fotsis T, Zhang Y, Pepper MS, Adlercreutz H, Montesano R, Nawroth PP et al (1994) The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 368(6468):237–239PubMed

180.

Ireson CR, Chander SK, Purohit A, Perera S, Newman SP, Parish D et al (2004) Pharmacokinetics and efficacy of 2-methoxyoestradiol and 2-methoxyoestradiol-bis-sulphamate in vivo in rodents. Br J Cancer 90(4):932–937PubMed

181.

Holmdahl R, Jansson L, Meyerson B, Klareskog L (1987) Oestrogen induced suppression of collagen arthritis: I. Long term oestradiol treatment of DBA/1 mice reduces severity and incidence of arthritis and decreases the anti type II collagen immune response. Clin Exp Immunol 70(2):372–378PubMed

182.

Josefsson E, Tarkowski A (1997) Suppression of type II collagen-induced arthritis by the endogenous estrogen metabolite 2-methoxyestradiol. Arthritis Rheum 40(1):154–163PubMed

Titel: Angiogenesis as a therapeutic target in arthritis: learning the lessons of the colorectal cancer experience
verfasst von: Tak Loon Khong
Helene Larsen
Yvonne Raatz
Ewa Paleolog
Publikationsdatum: 01.12.2007
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 4/2007
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-007-9081-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

24.04.2024 | DGIM 2024 | Kongressbericht | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Angiogenesis as a therapeutic target in arthritis: learning the lessons of the colorectal cancer experience

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Thrombophiliescreening – Wenn, dann richtig und nur bei therapeutischer Konsequenz

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Update Innere Medizin

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2007

Hedgehog signaling in the murine melanoma microenvironment

Thymosin β4 and angiogenesis: modes of action and therapeutic potential

Caveolin-1 polarization in transmigrating endothelial cells requires binding to intermediate filaments

Anti-angiogenic effects of imatinib target smooth muscle cells but not endothelial cells

Angiogenic response of endothelial cells seeded dispersed versus on beads in fibrin gels

Aortic rings stimulate inflammatory angiogenesis in a subcutaneous implant in vivo model

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Thrombophiliescreening – Wenn, dann richtig und nur bei therapeutischer Konsequenz

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Update Innere Medizin