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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
August-2015 Volume 47 Issue 2

Full Size Image

Cover Legend PDF

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
August-2015 Volume 47 Issue 2

Full Size Image

Cover Legend PDF

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 Open Access

Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition

  • Authors:
    • L. Mavroeidis
    • H. Sheldon
    • E. Briasoulis
    • M. Marselos
    • P. Pappas
    • A. L. Harris
  • View Affiliations / Copyright

    Affiliations: Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK, Department of Hematology, School of Medicine, University of Ioannina, University Campus, 45110 Ioannina, Greece, Department of Pharmacology, School of Medicine, University of Ioannina, University Campus, 45110 Ioannina, Greece
    Copyright: © Mavroeidis et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 455-464
    |
    Published online on: June 19, 2015
       https://doi.org/10.3892/ijo.2015.3059
  • 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

Metronomic chemotherapy is the protracted, dense administration of low sub-toxic doses of chemotherapy, to inhibit tumor angiogenesis. Vinorelbine is an orally bioavailable vinca alkaloid shown to be useable for metronomic administration. In clinical trials, metronomic vinorelbine has been demonstrated to generate sustainable antitumor efficacy at low nanomolar (nM) concentrations with negligible toxicity. We sought to determine whether the clinically relevant metronomic concentration of vinorelbine is anti-angiogenic in vitro and whether hypoxia, often induced by anti-angiogenic therapy, modifies its effectiveness. We found that the metronomic concentration of 10 nM vinorelbine inhibited human umbilical vein endothelial cell (HUVEC) proliferation, migration, tube formation and sprouting. Severe hypoxia, did not affect the inhibitory effect of metronomic vinorelbine on migration, tube formation and sprouting. However, severe hypoxia reduced its anti-proliferative effect by decreasing its ability to induce G2/M block as it shifted the cell population to the G1 phase and decreased the fraction of the cells in the DNA synthesis S phase. Furthermore, the pro-apoptotic effects of 10 nM vinorelbine were also decreased. Metronomic vinorelbine decreased the Bcl-2/Bax ratio in normoxia whereas the ratio was reduced in severe hypoxia but unaltered by vinorelbine treatment. Akt signals to an anti-apoptotic pathway and we demonstrated that the Akt inhibitor V reversed the protective effect of severe hypoxia. Thus, we provide evidence for the anti-angiogenic basis of metronomic vinorelbine and we show that severe hypoxia mediates resistance to its anti-proliferative effect on endothelial cells. Akt warrants further investigation as a potential target to circumvent this hypoxic resistance.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Kerbel RS and Kamen BA: The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 4:423–436. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Pasquier E, Kavallaris M and André N: Metronomic chemotherapy: New rationale for new directions. Nat Rev Clin Oncol. 7:455–465. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Pasquier E, Honore S and Braguer D: Microtubule-targeting agents in angiogenesis: where do we stand? Drug Resist Update. 9:74–86. 2006. View Article : Google Scholar

4 

Briasoulis E, Pappas P, Puozzo C, Tolis C, Fountzilas G, Dafni U, Marselos M and Pavlidis N: Dose-ranging study of metronomic oral vinorelbine in patients with advanced refractory cancer. Clin Cancer Res. 15:6454–6461. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Briasoulis E, Aravantinos G, Kouvatseas G, Pappas P, Biziota E, Sainis I, Makatsoris T, Varthalitis I, Xanthakis I, Vassias A, et al: Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: A hellenic cooperative oncology group clinical translational study. BMC Cancer. 13:2632013. View Article : Google Scholar : PubMed/NCBI

6 

Bergers G and Hanahan D: Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 8:592–603. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Azam F, Mehta S and Harris AL: Mechanisms of resistance to antiangiogenesis therapy. Eur J Cancer. 46:1323–1332. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Loges S, Schmidt T and Carmeliet P: Mechanisms of resistance to anti-angiogenic therapy and development of third-generation anti-angiogenic drug candidates. Genes Cancer. 1:12–25. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Cosse JP and Michiels C: Tumour hypoxia affects the responsiveness of cancer cells to chemotherapy and promotes cancer progression. Anticancer Agents Med Chem. 8:790–797. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Huang L, Ao Q, Zhang Q, Yang X, Xing H, Li F, Chen G, Zhou J, Wang S, Xu G, et al: Hypoxia induced paclitaxel resistance in human ovarian cancers via hypoxia-inducible factor 1alpha. J Cancer Res Clin Oncol. 136:447–456. 2010. View Article : Google Scholar

11 

Raz S, Sheban D, Gonen N, Stark M, Berman B and Assaraf YG: Severe hypoxia induces complete antifolate resistance in carcinoma cells due to cell cycle arrest. Cell Death Dis. 5:e10672014. View Article : Google Scholar : PubMed/NCBI

12 

Sersa G, Krzic M, Sentjurc M, Ivanusa T, Beravs K, Cemazar M, Auersperg M and Swartz HM: Reduced tumor oxygenation by treatment with vinblastine. Cancer Res. 61:4266–4271. 2001.PubMed/NCBI

13 

Zhao D, Jiang L, Hahn EW and Mason RP: Tumor physiologic response to combretastatin A4 phosphate assessed by MRI. Int J Radiat Oncol Biol Phys. 62:872–880. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, Bohlen P and Kerbel RS: Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest. 105:R15–R24. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Song G, Ouyang G and Bao S: The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 9:59–71. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Rovini A, Savry A, Braguer D and Carré M: Microtubule-targeted agents: When mitochondria become essential to chemotherapy. Biochim Biophys Acta. 1807.679–688. 2011.

17 

Kennedy SG, Kandel ES, Cross TK and Hay N: Akt/protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol Cell Biol. 19:5800–5810. 1999.PubMed/NCBI

18 

Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, Senac I and Puozzo C: Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors. Ann Oncol. 12:1643–1649. 2001. View Article : Google Scholar

19 

Potente M, Gerhardt H and Carmeliet P: Basic and therapeutic aspects of angiogenesis. Cell. 146:873–887. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Gascoigne KE and Taylor SS: How do anti-mitotic drugs kill cancer cells? J Cell Sci. 122:2579–2585. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Gardner LB, Li Q, Park MS, Flanagan WM, Semenza GL and Dang CV: Hypoxia inhibits G1/S transition through regulation of p27 expression. J Biol Chem. 276:7919–7926. 2001. View Article : Google Scholar

22 

Chipuk JE and Green DR: How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol. 18:157–164. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Bourgarel-Rey V, Savry A, Hua G, Carré M, Bressin C, Chacon C, Imbert J, Braguer D and Barra Y: Transcriptional down-regulation of Bcl-2 by vinorelbine: Identification of a novel binding site of p53 on Bcl-2 promoter. Biochem Pharmacol. 78:1148–1156. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Bertolini F, Paul S, Mancuso P, Monestiroli S, Gobbi A, Shaked Y and Kerbel RS: Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res. 63:4342–4346. 2003.PubMed/NCBI

25 

Pasquier E, Tuset MP, Street J, Sinnappan S, MacKenzie KL, Braguer D, Andre N and Kavallaris M: Concentration- and schedule-dependent effects of chemotherapy on the angiogenic potential and drug sensitivity of vascular endothelial cells. Angiogenesis. 16:373–386. 2013. View Article : Google Scholar :

26 

Schwartz EL: Antivascular actions of microtubule-binding drugs. Clin Cancer Res. 15:2594–2601. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Pourroy B, Honoré S, Pasquier E, Bourgarel-Rey V, Kruczynski A, Briand C and Braguer D: Antiangiogenic concentrations of vinflunine increase the interphase microtubule dynamics and decrease the motility of endothelial cells. Cancer Res. 66:3256–3263. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Wang J, Lou P, Lesniewski R and Henkin J: Paclitaxel at ultra low concentrations inhibits angiogenesis without affecting cellular microtubule assembly. Anticancer Drugs. 14:13–19. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Calvani M, Rapisarda A, Uranchimeg B, Shoemaker RH and Melillo G: Hypoxic induction of an HIF-1alpha-dependent bFGF autocrine loop drives angiogenesis in human endothelial cells. Blood. 107:2705–2712. 2006. View Article : Google Scholar

30 

Ngan VK, Bellman K, Hill BT, Wilson L and Jordan MA: Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine. Mol Pharmacol. 60:225–232. 2001.PubMed/NCBI

31 

Estève MA, Carré M, Bourgarel-Rey V, Kruczynski A, Raspaglio G, Ferlini C and Braguer D: Bcl-2 down-regulation and tubulin subtype composition are involved in resistance of ovarian cancer cells to vinflunine. Mol Cancer Ther. 5:2824–2833. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Savry A, Carre M, Berges R, Rovini A, Pobel I, Chacon C, Braguer D and Bourgarel-Rey V: Bcl-2-enhanced efficacy of microtubule-targeting chemotherapy through Bim overexpression: Implications for cancer treatment. Neoplasia. 15:49–60. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Zhou H, Li XM, Meinkoth J and Pittman RN: Akt regulates cell survival and apoptosis at a postmitochondrial level. J Cell Biol. 151:483–494. 2000. View Article : Google Scholar : PubMed/NCBI

34 

Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y and Greenberg ME: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:231–241. 1997. View Article : Google Scholar : PubMed/NCBI

35 

Majewski N, Nogueira V, Bhaskar P, Coy PE, Skeen JE, Gottlob K, Chandel NS, Thompson CB, Robey RB and Hay N: Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell. 16:819–830. 2004. View Article : Google Scholar : PubMed/NCBI

36 

Pastorino JG, Hoek JB and Shulga N: Activation of glycogen synthase kinase 3beta disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity. Cancer Res. 65:10545–10554. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Chiara F, Castellaro D, Marin O, Petronilli V, Brusilow WS, Juhaszova M, Sollott SJ, Forte M, Bernardi P and Rasola A: Hexokinase II detachment from mitochondria triggers apoptosis through the permeability transition pore independent of voltage-dependent anion channels. PloS One. 3:e18522008. View Article : Google Scholar : PubMed/NCBI

38 

Brenner C and Grimm S: The permeability transition pore complex in cancer cell death. Oncogene. 25:4744–4756. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Mavroeidis L, Sheldon H, Briasoulis E, Marselos M, Pappas P and Harris AL: Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition. Int J Oncol 47: 455-464, 2015.
APA
Mavroeidis, L., Sheldon, H., Briasoulis, E., Marselos, M., Pappas, P., & Harris, A.L. (2015). Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition. International Journal of Oncology, 47, 455-464. https://doi.org/10.3892/ijo.2015.3059
MLA
Mavroeidis, L., Sheldon, H., Briasoulis, E., Marselos, M., Pappas, P., Harris, A. L."Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition". International Journal of Oncology 47.2 (2015): 455-464.
Chicago
Mavroeidis, L., Sheldon, H., Briasoulis, E., Marselos, M., Pappas, P., Harris, A. L."Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition". International Journal of Oncology 47, no. 2 (2015): 455-464. https://doi.org/10.3892/ijo.2015.3059
Copy and paste a formatted citation
x
Spandidos Publications style
Mavroeidis L, Sheldon H, Briasoulis E, Marselos M, Pappas P and Harris AL: Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition. Int J Oncol 47: 455-464, 2015.
APA
Mavroeidis, L., Sheldon, H., Briasoulis, E., Marselos, M., Pappas, P., & Harris, A.L. (2015). Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition. International Journal of Oncology, 47, 455-464. https://doi.org/10.3892/ijo.2015.3059
MLA
Mavroeidis, L., Sheldon, H., Briasoulis, E., Marselos, M., Pappas, P., Harris, A. L."Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition". International Journal of Oncology 47.2 (2015): 455-464.
Chicago
Mavroeidis, L., Sheldon, H., Briasoulis, E., Marselos, M., Pappas, P., Harris, A. L."Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition". International Journal of Oncology 47, no. 2 (2015): 455-464. https://doi.org/10.3892/ijo.2015.3059
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