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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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August 2007 Volume 31 Issue 2

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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.

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August 2007 Volume 31 Issue 2

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Article

Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumour models

  • Authors:
    • Steven D. Shnyder
    • Patricia A. Cooper
    • Nicola J. Millington
    • G. Robert Pettit
    • Michael C. Bibby

  • View Affiliations / Copyright

    Affiliations: Institute of Cancer Therapeutics, University of Bradford, Bradford BD7 1DP, UK. s.d.shnyder@bradford.ac.uk
  • Pages: 353-360
    |
    Published online on: August 1, 2007
       https://doi.org/10.3892/ijo.31.2.353
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Abstract

Despite promising early data, the natural product dolastatin 10 has not been successful as a single agent in phase II clinical trials. Herein the mechanism of action and efficacy of a synthetic analogue, auristatin PYE, was investigated in 2 human colon adenocarcinoma models, DLD-1 and COLO 205. In vivo efficacy was assessed in subcutaneous xenografts following intravenous administration. Mechanistic studies investigated effects of auristatin PYE on microtubule disruption using immunocytochemistry, whilst cell cycle effects were studied using flow cytometry. Possible effects on tumour functional blood vasculature were assessed in tumour-bearing mice. Auristatin PYE was less potent in vitro than dolastatin 10, but was significantly more effective (p<0.01) in vivo against both tumours. Significant effects on tumour blood vasculature were seen, with optimal shutdown at 6-h post-treatment. Extensive necrosis became more evident over time after treatment. Auristatin PYE caused severe disruption of normal microtubule structure at concentrations and times comparable with the IC50 data, and also instigated a G2/M cell cycle block. Auristatin PYE was more effective in the DLD-1 and COLO 205 models than dolastatin 10, with anti-tumour effects mediated through vascular shutdown. These data suggest that auristatin PYE has good potential as an anti-cancer agent.

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Copy and paste a formatted citation
Spandidos Publications style
Shnyder SD, Cooper PA, Millington NJ, Pettit GR and Bibby MC: Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumour models. Int J Oncol 31: 353-360, 2007.
APA
Shnyder, S.D., Cooper, P.A., Millington, N.J., Pettit, G.R., & Bibby, M.C. (2007). Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumour models. International Journal of Oncology, 31, 353-360. https://doi.org/10.3892/ijo.31.2.353
MLA
Shnyder, S. D., Cooper, P. A., Millington, N. J., Pettit, G. R., Bibby, M. C."Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumour models". International Journal of Oncology 31.2 (2007): 353-360.
Chicago
Shnyder, S. D., Cooper, P. A., Millington, N. J., Pettit, G. R., Bibby, M. C."Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumour models". International Journal of Oncology 31, no. 2 (2007): 353-360. https://doi.org/10.3892/ijo.31.2.353
Copy and paste a formatted citation
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Spandidos Publications style
Shnyder SD, Cooper PA, Millington NJ, Pettit GR and Bibby MC: Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumour models. Int J Oncol 31: 353-360, 2007.
APA
Shnyder, S.D., Cooper, P.A., Millington, N.J., Pettit, G.R., & Bibby, M.C. (2007). Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumour models. International Journal of Oncology, 31, 353-360. https://doi.org/10.3892/ijo.31.2.353
MLA
Shnyder, S. D., Cooper, P. A., Millington, N. J., Pettit, G. R., Bibby, M. C."Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumour models". International Journal of Oncology 31.2 (2007): 353-360.
Chicago
Shnyder, S. D., Cooper, P. A., Millington, N. J., Pettit, G. R., Bibby, M. C."Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumour models". International Journal of Oncology 31, no. 2 (2007): 353-360. https://doi.org/10.3892/ijo.31.2.353
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