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Antiangiogenic Strategies in Pancreatic Cancer

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Pancreatic Cancer

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References

  1. Warshaw AL, Fernandez-del Castillo C. Pancreatic carcinoma N Engl J Med. 1992;326:455–465.

    CAS  PubMed  Google Scholar 

  2. Evans DB, Abbruzzese JL, Rich TR. Cancer of the pancreas. In: de Vita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia: JB Lippincott; 1997:1054–1087.

    Google Scholar 

  3. Wanebo HJ, Vezeridis MP. Pancreatic carcinoma in perspective: a continuing challenge. Cancer. 1996;78:580–591.

    CAS  PubMed  Google Scholar 

  4. Landis SH, Murray T, Bolden S, et al. Cancer statistics. CA Cancer J Clin. 1999;49:8–31.

    CAS  PubMed  Google Scholar 

  5. Fernandez E, La Vecchia C, Porta M, et al. Trends in pancreatic cancer mortality in Europe, 1955–1989. Int J Cancer. 1994;57:786–792.

    CAS  PubMed  Google Scholar 

  6. Burris HA III, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-a randomized trial. J Clin Oncol. 1997:2403–2413.

    Google Scholar 

  7. Almohuera C, Shibata D, Forrester K, et al. Most human carcinomas of the exocrine pancreas contain mutant k-ras genes. Cell. 1988;53:549–554.

    Google Scholar 

  8. Pellegata N, Sessa F, Renault B, et al. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res. 1994;54:1556–1560.

    CAS  PubMed  Google Scholar 

  9. Caldas C, Hanh S, da Costa L, et al. Frequent somatic mutations and homozygous deletions of o16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet. 1994;8:27–31.

    Article  CAS  PubMed  Google Scholar 

  10. Hanh SA, Schutte M, Hoque A, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996;271:350–353.

    Google Scholar 

  11. Grau AM, Zhang L, Wang W, et al. Inducation of p21waf1 expression and growth inhibition by transforming growth factor-b is mediated by the tumor suppressor gene DPC-4 in human pancreatic adenocarcinoma cells. Cancer Res. 1997;57:3929–3934.

    CAS  PubMed  Google Scholar 

  12. Sinicrope FA, Evans DB, Leach SD, et al. Bcl-2 and p53 expression in resectable pancreatic adenocarcinomas—association with clinical outcome. Clin Cancer Res. 1996;2:2015–2022.

    CAS  PubMed  Google Scholar 

  13. Korc M, Chaqndrasekar B, Yamanke Y, et al. Overexpression of epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the level of epidermal growth factor and transforming factor alpha. J Clin Invest. 1993;90:1352–1360.

    Google Scholar 

  14. Yamanaka Y, Friess H, Kobrin MS, et al. Overexpression of HER2/neu oncogene in human pancreatic carcinoma. Hum Pathol. 1993;24:1127–1134.

    Article  CAS  PubMed  Google Scholar 

  15. Bergmann U, Funatomi H, Yokoyama M, et al. Insulinlike growth factor I overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles. Cancer Res. 1995;55:2007–2011.

    CAS  PubMed  Google Scholar 

  16. Wagner M, Lopez ME, Cahn M, et al. Suppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo. Gastroenterology. 1998;114:798–807.

    Article  CAS  PubMed  Google Scholar 

  17. Friess H, Kleeff J, Korc M, et al. Molecular aspects of pancreatic cancer and future perspectives. Dig Surg. 1999;16:281–290.

    Article  CAS  PubMed  Google Scholar 

  18. Yamanaka Y, Friess H, Kobrin MS, et al. Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res. 1993;13:565–570.

    CAS  PubMed  Google Scholar 

  19. Kobrin MS, Funatomi H, Friess H, et al. Induction and expression of heparin-binding EGF-like growth factor in human pancreatic cancer. Biochem Biophys Res Commun. 1994;202:1705–1709.

    Article  CAS  PubMed  Google Scholar 

  20. Wagner M, Cao T, Lopez ME, et al. Expression of truncated EGF receptor is associated with inhibition of pancreatic cancer cell growth and enhanced sensitivity to cisplatin. Int J Cancer. 1996;68:782–787.

    Article  CAS  PubMed  Google Scholar 

  21. Liu N, Furukawa T, Kobari M, et al. Comparative phenotypic studies of duct epithelial cell lines derived from normal human pancreas and pancreatic carcinoma. Am J Pathol. 1998;153:263–269.

    CAS  PubMed  Google Scholar 

  22. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1989;82:4–6.

    Google Scholar 

  23. Folkman J. The role of angiogenesis in tumor growths. Semin Cancer Biol. 1992;3:65–71.

    CAS  PubMed  Google Scholar 

  24. Folkman J. How is blood vessel growth regulated in normal and neoplastic tissue? G.H.A. Clowes Memorial Award Lecture. Cancer Res. 1986;46:467–473.

    CAS  PubMed  Google Scholar 

  25. Liotta LA, Kleinerman J, Saidel GM. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res. 1974;34:997–1003.

    CAS  PubMed  Google Scholar 

  26. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis-correlation in invasive breast cancer. N Engl J Med. 1991;324:1–8.

    CAS  PubMed  Google Scholar 

  27. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992;84:1875–1887.

    CAS  PubMed  Google Scholar 

  28. Graham CH, Rivers J, Kerbel RS, et al. Extent of vascularization as a prognostic indicator in thin (<0.76 mm) malignant melanomas. Am J Pathol. 1994;145:510–514.

    CAS  PubMed  Google Scholar 

  29. Macchiarini P, Fontanini G, Hardin M, et al. Relation of neovascularization to metastasis of non-smallcell lung cancer. Lancet. 1992;340:145–146.

    Article  CAS  PubMed  Google Scholar 

  30. Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995;55:3964–3968.

    CAS  PubMed  Google Scholar 

  31. Takahashi Y, Tucker SL, Kitadai Y, et al. Vessel counts and VEGF expression as prognostic factors in node-negative colon cancer. Arch Surg. 1997;132:541–546.

    CAS  PubMed  Google Scholar 

  32. Weidner N. Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol. 1995;147:9–19.

    CAS  PubMed  Google Scholar 

  33. Houck KA, Ferrara N, Winer J, et al. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991;5:1806–1814.

    CAS  PubMed  Google Scholar 

  34. Bruns CJ, Harbison M, Kuniyasu H, et al. In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia. 1999;1:50–62.

    Article  CAS  PubMed  Google Scholar 

  35. O’Mahony CA, Seidel A, Albo D, et al. Angiostatin generation by human pancreatic cancer. J Surg Res. 1998;77:55–58.

    CAS  PubMed  Google Scholar 

  36. O’Mahony CA, Albo D, Tuszynski GP, et al. Transforming growth factor-beta 1 inhibits generation of angiostatin by human pancreatic cancer cells. Surgery. 1998;124:388–393.

    CAS  PubMed  Google Scholar 

  37. Kumar R, Kuniyasu H, Bucana CD, Wilson MR, Fidler IJ. Spatial and temporal expression of angiogenic molecules during tumor growth and progression. Oncol Res. 1998;10:301–311.

    CAS  PubMed  Google Scholar 

  38. Olofsson B, Jeltsch M, Eriksson U, et al. Current biology of VEGF-B and VEGF-C. Curr Opin Biotechnol. 1999;10:528–535.

    Article  CAS  PubMed  Google Scholar 

  39. Yonekura H, Sakurai S, Liu X, et al. Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes. Implication in autocrine and paracrine regulation of angiogenesis. J Biol Chem. 1999;274:35172–35178.

    Article  CAS  PubMed  Google Scholar 

  40. Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219:983–985.

    CAS  PubMed  Google Scholar 

  41. Gerber HP, McMurtrey A, Kowalski J, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem. 1998;273:30336–30343.

    CAS  PubMed  Google Scholar 

  42. Gerber HP, Dixit V, Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem. 1998;273:13313–13316.

    CAS  PubMed  Google Scholar 

  43. Ishikawa F, Miyanzono K, Hellman U, et al. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth. Nature. 1989;338:557–562.

    Article  CAS  PubMed  Google Scholar 

  44. Badet J. Angiogenin, a potent mediator of angiogenesis. Biological, biochemical and structural properties. Pathol Biol (Paris). 1999;47:345–351.

    CAS  Google Scholar 

  45. Koch AE, Polverini PJ, Kunkel SL, et al. Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science. 1992;258:1798–1801.

    CAS  PubMed  Google Scholar 

  46. Kleeff J, Kusama T, Rossi DL, et al. Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer. Int J Cancer. 1999;81:650–657.

    Article  CAS  PubMed  Google Scholar 

  47. Jouan V, Canron X, Alemany M, et al. Inhibition of in vitro angiogenesis by platelet factor-4-derived peptides and mechanism of action. Blood. 1999;94:984–993.

    CAS  PubMed  Google Scholar 

  48. Kuniyasu H, Ellis LM, Evans DB, et al. Relative expression of e-cadherin and type iv collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma. Clin Cancer Res. 1999;5:25–33.

    CAS  PubMed  Google Scholar 

  49. Ikeda N, Adachi M, Taki T, et al. Prognostic significance of amgiogenesis in human pancreatic cancer. Br J Cancer. 1999;79:1553–1563.

    Article  CAS  PubMed  Google Scholar 

  50. Fujimoto K, Hosotani R, Wada M, et al. Expression of two angiogenic factors, vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relationship to angiogenesis. Eur J Cancer. 1998;34:1439–1447.

    Article  CAS  PubMed  Google Scholar 

  51. Ellis LM, Takahashi Y, Fenoglio CJ, et al. Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma. Eur J Cancer. 1998;34:337–340.

    CAS  PubMed  Google Scholar 

  52. Yamazaki K, Nagao T, Yamaguchi T, et al. Expression of basic fibroblast growth factor (FGF-2)-associated with tumor proliferation in human pancreatic carcinoma. Virchows Arch. 1997;431:95–101.

    Article  CAS  PubMed  Google Scholar 

  53. Shimoyama S, Gansauge F, Gansauge S, et al. Increased angiogenin expression in pancreatic cancer is related to cancer aggressiveness. Cancer Res. 1996;56:2703–2706.

    CAS  PubMed  Google Scholar 

  54. Kuehn R, Lelkes PL, Bloechle C, et al. Angiogenesis, angiogenic growth factors, and cell adhesion molecules are upregulated in chronic pancreatic diseases: angiogenesis in chronic pancreatitis and in pancreatic cancer. Pancreas. 1999;18:96–103.

    Article  CAS  PubMed  Google Scholar 

  55. Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999;284:1994–1998.

    Article  CAS  PubMed  Google Scholar 

  56. Maisonpierre PC, Surri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997;277:55–60.

    Article  CAS  PubMed  Google Scholar 

  57. Papapetropoulos A, Garcia-Cardena G, Dengler TJ, et al. Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival, and interaction with other angiogenic factors. Lab Invest. 1999;79:213–223.

    CAS  PubMed  Google Scholar 

  58. Neufeld G, Cohen T, Gengrinovitch S, et al. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999;13:9–22.

    CAS  PubMed  Google Scholar 

  59. Dibbens JA, Miller DL, Damert A, et al. Hypoxic regulation of vascular endothelial growth factor mRNA stability requires the cooperation of multiple RNA elements. Mol Biol Cell. 1999;10:907–919.

    CAS  PubMed  Google Scholar 

  60. Gerber HP, Condorelli F, Park J, et al. Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem. 1997;272:23659–23667.

    CAS  PubMed  Google Scholar 

  61. Shi Q, Abbruzzese JL, Huang S, et al. Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic. Clin Cancer Res. 1999;5:3711–3721.

    CAS  PubMed  Google Scholar 

  62. Wojta J, Kaun C, Breuss JM, et al. Hepatocyte growth factor increases expression of vascular endothelial growth factor and plasminogen activator inhibitor-1 in human keratinocytes and the vascular endothelial growth factor receptor flk-1 in human endothelial cells. Lab Invest. 1999;79:427–438.

    CAS  PubMed  Google Scholar 

  63. Akagi Y, Liu W, Zebrowski B, et al. Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-I. Cancer Res. 1998;58:4008–4014.

    CAS  PubMed  Google Scholar 

  64. Zelzer E, Levy Y, Kahana C, et al. Insulin induces transcription of target genes through the hypoxia-inducible factor HIF-1alpha/ARNT. EMBO J. 1998;17:5085–5094.

    Article  CAS  PubMed  Google Scholar 

  65. Chin L, Tam A, Pomerantz J, et al. Essential role for oncogenic Ras in tumour maintenance. Nature. 1999;400:468–472.

    Article  CAS  PubMed  Google Scholar 

  66. Ellis LM, Staley CA, Liu W, et al. Down-regulation of vascular endothelial growth factor in a human colon carcinoma cell line transfected with an antisense expression vector specific for c-src. J Biol Chem. 1998;273:1052–1057.

    CAS  PubMed  Google Scholar 

  67. Gnarra JR, Zhou S, Merrill MJ, et al. Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. Proc Natl Acad Sci U S A. 1996;93:10589–10594.

    Article  CAS  PubMed  Google Scholar 

  68. Ravi R, Mookerjee B, Bhujwalla ZM, et al. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev. 2000;14:34–44.

    CAS  PubMed  Google Scholar 

  69. Maeda T, Matsumura S, Hiranuma H, et al. Expression of vascular endothelial growth factor in human oral squamous cell carcinoma: its association with tumour progression and p53 gene status. J Clin Pathol. 1998;51:771–775.

    CAS  PubMed  Google Scholar 

  70. Bouvet M, Ellis LM, Nishizaki M, et al. Adenovirusmediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human colon cancer. Cancer Res. 1998;58:2288–2292.

    CAS  PubMed  Google Scholar 

  71. Teicher BA, Sotomayor EA, Huang ZD. Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease. Cancer Res. 1992;52:6702–6704.

    CAS  PubMed  Google Scholar 

  72. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27–31.

    Article  CAS  PubMed  Google Scholar 

  73. Witte L, Hicklin DJ, Pytowski B, et al. Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy. Cancer Metastasis Rev. 1998;17:155–161.

    Article  CAS  PubMed  Google Scholar 

  74. Bruns C, Harbison MT, Davis DW, et al. EGF-R blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by anti-angiogenic mechanisms. Clin Cancer Res. 2000;6:1936–1948.

    CAS  PubMed  Google Scholar 

  75. Bruns CJ, Solorzano CC, Harbison MT, et al. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res. 2000;60:2926–2935.

    CAS  PubMed  Google Scholar 

  76. Shishido T, Yasoshima T, Denno R, et al. Inhibition of liver metastasis of human pancreatic carcinoma by angiogenesis inhibitor TNP-470 in combination with cisplatin. Jpn J Cancer. 1998;89:936–939.

    Google Scholar 

  77. Folkman J. Angiogenesis research from laboratory to clinic. Forum (Genova). 1999;9(suppl):59–62.

    CAS  Google Scholar 

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Bruns, C.J., Ellis, L.M., Radinsky, R. (2002). Antiangiogenic Strategies in Pancreatic Cancer. In: Evans, D.B., Pisters, P.W.T., Abbruzzese, J.L. (eds) Pancreatic Cancer. M. D. Anderson Solid Tumor Oncology Series. Springer, New York, NY. https://doi.org/10.1007/0-387-21600-6_34

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