Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
March-April 2010 Volume 1 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-April 2010 Volume 1 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6

  • Authors:
    • Yoshiko Aoyagi
    • Hisae Iinuma
    • Atsushi Horiuchi
    • Ryu Shimada
    • Toshiaki Watanabe
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan
  • Pages: 253-259
    |
    Published online on: March 1, 2010
       https://doi.org/10.3892/ol_00000045
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

For individualized bevacizumab-based therapy, non-invasive biomarkers are necessary. This study assessed the predictive value of plasma vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-1 and sVEGFR-2 levels as biomarkers for clinical response and survival in advanced colorectal cancer (CRC) patients treated with bevacizumab and modified FOLFOX6 (mFOLFOX6). Forty-six unresectable advanced CRC patients and 20 healthy controls were included in this study. CRC patients were treated with bevacizumab and mFOLFOX6. Pretreatment plasma VEGF-A, sVEGFR-1 and sVEGFR-2 levels were measured using the multiplex immunoassay. Plasma VEGF-A, sVEGFR-1 and sVEGFR-2 levels were significantly higher in CRC patients than in the healthy subjects. The plasma sVEGFR-1 levels in the responder patients [complete response (CR)/partial response (PR)] and stable disease (SD) patients were significantly lower than those in the progressive disease (PD) patients (CR/PR vs. PD, p=0.025; SD vs. PD, p=0.032), while the plasma VEGF-A and sVEGFR-2 levels did not show any significant differences between the two groups of patients. Patients with higher sVEGFR-1 levels showed a significantly poorer progression-free survival (PFS) and overall survival (OS) than those with lower VEGFR-1 levels. In contrast, VEGF-A and sVEGFR-2 did not show any significant relationship between PFS and OS according to the status of each level. In the multivariate Cox proportional hazard regression analysis, sVEGFR-1 levels showed a significant relationship between PFS and OS. These results suggest that plasma sVEGFR-1 levels have a predictive value for clinical response and survival in advanced CRC patients treated with bevacizumab and mFOLFOX6. Larger scale studies are needed to further validate our results.
View Figures

Figure 1

Figure 2

View References

1 

Hicklin DJ and Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 23:1011–1027. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Hurwits H, Fehrenbacher L, Novotny W, et al: Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med. 350:2335–2342. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Iwasaki J and Nihira S: Anti-angiogenic therapy against gastrointestinal tract cancers. Jpn J Clin Oncol. 16:1–9. 2009.

4 

Yamaguchi K, Boku N, Kato K, Komatsu Y, Muro K and Hamamoto Y: Preliminary efficacy, safety and operability of bevacizumab plus capecitabine plus oxaliplatin (XELOX) as first-line therapy in Japanese patients with initially unresectable metastatic colorectal cancer. Ann Oncol. 19:viii1302008.

5 

Karapetis CS, Khambata FS, Jonker DJ, et al: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 359:1757–1765. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Willett CG, Boucher Y, Duda DG, et al: Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a Phase I trial and rectal cancer patients. J Clin Oncol. 22:8136–8139. 2005. View Article : Google Scholar

7 

Galizia G, Lieto E, Ferraraccio F, et al: Determination of molecular marker expression can predict clinical outcome in colon carcinoma. Clin Cancer Res. 10:3490–3499. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Takahashi Y, Kitadai Y, Bucana CD, Cleary KR and Ellis LM: Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity metastasis and proliferation of human colon cancer. Cancer Res. 55:3964–3968. 1995.PubMed/NCBI

9 

Werther K, Christensen IJ and Nielsen HJ: Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma. Br J Cancer. 86:417–423. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Broll R, Erdmann H, Duchrow M, et al: Vascular endothelial growth factor (VEGF) – a valuable serum tumor marker in patients with colorectal cancer? Eur J Surg Oncol. 27:37–42. 2001.

11 

Willett CG, Boucher Y, Duda DG, et al: Efficacy, safety and biomarkers of neoadjuvant bevacizumab, radiation therapy and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol. 18:3020–3026. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Denduluri N, Yang SX, Berman AW, Nguyen D, Liewehr DJ, Steinberg SM and Swalin SM: Circulating biomarkers of bevacizumab activity in patients. Cancer Biol Ther. 7:15–20. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Ferrara N and Alitalo K: Clinical application of angiogenic growth factors and their inhibitors. Nat Med. 5:1359–1364. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Shibuya M: Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Func. 26:25–35. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Kendall RL and Thomas KA: Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci USA. 90:10705–10709. 1993. View Article : Google Scholar : PubMed/NCBI

16 

Kendall RL, Wang G and Thomas KA: Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun. 226:324–328. 1996. View Article : Google Scholar : PubMed/NCBI

17 

Harris AL, Reusch P, Barlenon B, Hang C, Dobbs N and Marme D: Soluble Tie2 and Flt1 extracellular domains in serum of patients with renal cancer and response to antiangiogenic therapy. Clin cancer Res. 7:1992–1997. 2001.PubMed/NCBI

18 

Toi M, Bando H, Ogawa T, Muta M, Horing C and Weich HA: Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer. Int J Cancer. 98:14–18. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Tas F, Duranyildiz D, Oguz H, Camlica H, Yasasever V and Topuz E: Circulating serum levels of angiogenic factors and vascular endothelial growth factor receptors 1 and 2 in melanoma patients. Melanoma Res. 16:405–411. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Yamaguchi T, Nando H, Mori T, et al: Overexpression of soluble vascular endothelial growth factor receptor 1 in colorectal cancer: association with progression and prognosis. Cancer Sci. 98:405–410. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Hu Q, Dey AL, Yang Y, et al: Soluble vascular endothelial growth factor receptor 1, and not receptor 2, is an independent prognostic factor in acute myeloid leukemia and myeloidysplastic syndromes. Cancer. 100:1884–1891. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Hormbrey E, Gillespie P, Turner K, Han C, Roberts A, McGrouther D and Harris AL: A critical review of vascular endothelial growth factor (VEGF) analysis in peripheral blood: is the current literature meaningful? Clin Exp Metastasis. 19:651–663. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Otrock ZK, Makarem JA and Shamseddine AI: Vascular endothelial growth factor family of ligands and receptors: review. Blood Cells Mol Dis. 38:258–268. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Poon RT, Fan ST and Wong J: Clinical implication of circulating angiogenic factors in cancer patients. J Clin Oncol. 19:1207–1225. 2001.PubMed/NCBI

25 

Burstein A, Chen Y-H and Parker LM: VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res. 14:7871–7877. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Holden SN, Ryan E, Kearns A, Holmgren E and Hurwitz H: Benefit from bevacizumab (BV) is independent of pretreatment plasma vascular endothelial growth factor-A (pl-VEGF) in patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol. 123:35552005.

27 

Olsson AK, Dimberg A, Kreuger J and Claesson-Welsh L: VEGF receptor signaling – in control of vascular function. Nat Rev Mol Cell Biol. 7:359–371. 2006.

28 

Herold MC, Steiner HH, Andl T, et al: Expression and functional significance of vascular endothelial growth factor receptors in human tumor cells. Lab Invest. 79:1573–1582. 1999.PubMed/NCBI

29 

Masood R, Cai J, Zheng T, Smith DL, Hinton DR and Gill PS: Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors. Blood. 98:1904–1913. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Holash J, Davis S, Papadopoulos N, et al: VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA. 99:11393–11398. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Wierzbowska A, Robak T, Wizesien-Kus A, Krawczynska A, Maranda EL and Urbanska-Rys H: Circulating VEGF and its soluble receptors sVEGFR-1 and sVEGFR-2 in patients with acute leukemia. Eur Cytokine Netw. 14:149–153. 2003.PubMed/NCBI

33 

AI-Moundhri M, Shukaili A, AI-Nabhani M, AI-Bahrani B, Burney IA, Rozovo A and Ganguly SS: Measurement of circulating levels of VEGF-A, -C and -D and their receptors, VEGFR-1 and -2 in gastric adenocarcinoma. World Gastroenterol. 14:3879–3883. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Ustuner Z, Saip P, Yasasever V, et al: Prognostic and predictive value of vascular endothelial growth factor and its soluble reseptor VEGFR-1 and VEGFR-2 levels in the sera of small cell lung cancer patients. Med Oncol. 25:394–399. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Aoyagi Y, Iinuma H, Horiuchi A, Shimada R and Watanabe T: Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6 . Oncol Lett 1: 253-259, 2010.
APA
Aoyagi, Y., Iinuma, H., Horiuchi, A., Shimada, R., & Watanabe, T. (2010). Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6 . Oncology Letters, 1, 253-259. https://doi.org/10.3892/ol_00000045
MLA
Aoyagi, Y., Iinuma, H., Horiuchi, A., Shimada, R., Watanabe, T."Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6 ". Oncology Letters 1.2 (2010): 253-259.
Chicago
Aoyagi, Y., Iinuma, H., Horiuchi, A., Shimada, R., Watanabe, T."Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6 ". Oncology Letters 1, no. 2 (2010): 253-259. https://doi.org/10.3892/ol_00000045
Copy and paste a formatted citation
x
Spandidos Publications style
Aoyagi Y, Iinuma H, Horiuchi A, Shimada R and Watanabe T: Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6 . Oncol Lett 1: 253-259, 2010.
APA
Aoyagi, Y., Iinuma, H., Horiuchi, A., Shimada, R., & Watanabe, T. (2010). Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6 . Oncology Letters, 1, 253-259. https://doi.org/10.3892/ol_00000045
MLA
Aoyagi, Y., Iinuma, H., Horiuchi, A., Shimada, R., Watanabe, T."Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6 ". Oncology Letters 1.2 (2010): 253-259.
Chicago
Aoyagi, Y., Iinuma, H., Horiuchi, A., Shimada, R., Watanabe, T."Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6 ". Oncology Letters 1, no. 2 (2010): 253-259. https://doi.org/10.3892/ol_00000045
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team