American Journal of Obstetrics & Gynecology
Volume 198, Issue 4 , Pages 477.e1-477.e10 , April 2008

Impact of vessel maturation on antiangiogenic therapy in ovarian cancer

This research was presented at the 26th Annual Scientific Meeting of the American Gynecological and Obstetrical Society, Chicago, IL, Sept. 26-29, 2007.

  • Chunhua Lu, MD, PhD

      Affiliations

    • Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • Premal H. Thaker, MD

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO
  • ,
  • Yvonne G. Lin, MD

      Affiliations

    • Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • Whitney Spannuth, MD

      Affiliations

    • Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • Charles N. Landen, MD

      Affiliations

    • Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • William M. Merritt, MD

      Affiliations

    • Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • Nicholas B. Jennings, BS

      Affiliations

    • Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • Robert R. Langley, PhD

      Affiliations

    • Department of Cancer Biology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • David M. Gershenson, MD

      Affiliations

    • Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • George D. Yancopoulos, MD, PhD

      Affiliations

    • Regeneron Pharmaceuticals, Tarrytown, NY.
  • ,
  • Lee M. Ellis, MD

      Affiliations

    • Department of Cancer Biology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
    • Department of Surgical Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • Robert B. Jaffe, MD

      Affiliations

    • Center for Reproductive Sciences, University of California, San Francisco, CA
  • ,
  • Robert L. Coleman, MD

      Affiliations

    • Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
  • ,
  • Anil K. Sood, MD

      Affiliations

    • Department of Gynecologic Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
    • Department of Cancer Biology, the University of Texas M. D. Anderson Cancer Center, Houston, TX
    • Corresponding Author InformationReprints: Anil K. Sood, MD, Professor, Departments of Gynecologic Oncology and Cancer Biology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1362, Houston, TX 77030.

Received 14 April 2007 ,Accepted 21 December 2007.

References 

  1. Klagsbrun M, D’Amore PA. Vascular endothelial growth factor and its receptors. Cytokine Growth Factor Rev. 1996;7:259–270
  2. Thaker PH, Han LY, Kamat AA, et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 2006;12:939–944
  3. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–676
  4. Alon T, Hemo I, Itin A, Pe’er J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med. 1995;1:1024–1028
  5. Carmeliet P, Moons L, Luttun A, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001;7:575–583
  6. Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029–1039
  7. Cooper BC, Ritchie JM, Broghammer CL, et al. Preoperative serum vascular endothelial growth factor levels: significance in ovarian cancer. Clin Cancer Res. 2002;8:3193–3197
  8. Hefler LA, Zeillinger R, Grimm C, et al. Preoperative serum vascular endothelial growth factor as a prognostic parameter in ovarian cancer. Gynecol Oncol. 2006;103:512–517
  9. Li L, Wang L, Zhang W, et al. Correlation of serum VEGF levels with clinical stage, therapy efficacy, tumor metastasis and patient survival in ovarian cancer. Anticancer Res. 2004;24:1973–1979
  10. Paley PJ, Staskus KA, Gebhard K, et al. Vascular endothelial growth factor expression in early stage ovarian carcinoma. Cancer. 1997;80:98–106
  11. Frumovitz M, Sood AK. Vascular endothelial growth factor (VEGF) pathway as a therapeutic target in gynecologic malignancies. Gynecol Oncol. 2007;104:768–778
  12. Burger R, Sill M, Monk B, Greer B, Sorosky J. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007;25:5165–5171
  13. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–2342
  14. Jain RK, Duda DG, Clark JW, Loeffler JS. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol. 2006;3:24–40
  15. Lu C, Sood A. Role of pericytes in angiogenesis. In:  Teicher BA,  Ellis LM editor. Angiogenesis agents in cancer therapy. 2nd ed.. Totowa (NJ): Humana Press, Inc; 2008;p. 117–132
  16. Cuevas P, Gutierrez-Diaz JA, Reimers D, Dujovny M, Diaz FG, Ausman JI. Pericyte endothelial gap junctions in human cerebral capillaries. Anat Embryol. 1984;170:155–159(Berl)
  17. Matsusaka T. Tridimensional views of the relationship of pericytes to endothelial cells of capillaries in the human choroid and retina. J Electron Microsc. 1975;24:13–18(Tokyo)
  18. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407:249–257
  19. Hellstrom M, Gerhardt H, Kalen M, et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol. 2001;153:543–553
  20. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003;111:1287–1295
  21. Lu C, Kamat A, Lin YG, et al. Dual targeting of endothelial cells and pericytes in antivascular therapy for ovarian carcinoma. Clin Cancer Res. 2007;13:4209–4217
  22. Lindahl P, Johansson BR, Leveen P, Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science. 1997;277:242–245
  23. Lindblom P, Gerhardt H, Liebner S, et al. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev. 2003;17:1835–1840
  24. Pietras K, Hanahan D. A multi-targeted, metronomic, and maximum-tolerated dose “chemo-switch” regimen is anti-angiogenic, producing objective responses and survival benefit in a mouse model of cancer. J Clin Oncol. 2005;23:939–952
  25. Apte SM, Fan D, Killion JJ, Fidler IJ. Targeting the platelet-derived growth factor receptor in antivascular therapy for human ovarian carcinoma. Clin Cancer Res. 2004;10:897–908
  26. Betsholtz C, Karlsson L, Lindahl P. Developmental roles of platelet-derived growth factors. Bioessays. 2001;23:494–507
  27. Leveen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E, Betsholtz C. Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. Genes Dev. 1994;8:1875–1887
  28. Thaker PH, Yazici S, Nilsson MB, et al. Antivascular therapy for orthotopic human ovarian carcinoma through blockade of the vascular endothelial growth factor and epidermal growth factor receptors. Clin Cancer Res. 2005;11:4923–4933
  29. Langley RR, Ramirez KM, Tsan RZ, Van Arsdall M, Nilsson MB, Fidler IJ. Tissue-specific microvascular endothelial cell lines from H-2K(b)-tsA58 mice for studies of angiogenesis and metastasis. Cancer Res. 2003;63:2971–2976
  30. Sood AK, Coffin JE, Schneider GB, et al. Biological significance of focal adhesion kinase in ovarian cancer: role in migration and invasion. Am J Pathol. 2004;165:1087–1095
  31. Sood AK, Bhatty R, Kamat AA, et al. Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res. 2006;12:369–375
  32. Sood AK, Seftor EA, Fletcher MS, et al. Molecular determinants of ovarian cancer plasticity. Am J Pathol. 2001;158:1279–1288
  33. Cancer facts and figures 2007. Atlanta (GA): American Cancer Society; 2007;
  34. Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003;21:3194–3200
  35. Markman M, Walker JL. Intraperitoneal chemotherapy of ovarian cancer: a review, with a focus on practical aspects of treatment. J Clin Oncol. 2006;24:988–994
  36. Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest. 1999;103:159–165
  37. Reinmuth N, Liu W, Jung YD, et al. Induction of VEGF in perivascular cells defines a potential paracrine mechanism for endothelial cell survival. FASEB J. 2001;15:1239–1241

 This research was funded by the Specialized Programs of Research Excellence in ovarian cancer, University of Texas M. D. Anderson Cancer Center (P50CA083639); the Marcus Foundation; National Institutes of Health grants CA109298 and CA110793; and a Program Project Development Grant from the Ovarian Cancer Research Fund (A. K. S.).

 Cite this article as: Lu C, Thaker PH, Lin YG, et al. Impact of vessel maturation on antiangiogenic therapy in ovarian cancer. Am J Obstet Gynecol 2008;198:477.e1-477.e10.

PII: S0002-9378(07)02340-X

doi: 10.1016/j.ajog.2007.12.028

American Journal of Obstetrics & Gynecology
Volume 198, Issue 4 , Pages 477.e1-477.e10 , April 2008