Effect of molecular therapeutics on liver regeneration in a murine model

George Van Buren, Anthony D. Yang, Nikolaos A. Dallas, Michael J. Gray, Sherry J. Lim, Ling Xia, Fan Fan, Ray Somcio, Yan Wu, Daniel J. Hicklin, Lee M. Ellis

Research output: Contribution to journalArticle

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Abstract

Purpose: Unresectable metastatic colorectal cancer (CRC) can be rendered resectable with systemic chemotherapy in approximately 20% of cases. Most patients with metastatic CRC receive chemotherapy with the addition of targeted therapy with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) antibodies. We sought to determine whether anti-VEGF receptor (VEGFR) or anti-EGFR therapy would impair liver regeneration after partial hepatectomy (PH) in mice. Materials and Methods: Mice underwent either 66% PH or sham laparotomy. In the first experiment, mice in the PH group were randomly assigned to receive daily intraperitoneal injections of monoclonal antibodies (MoABs) to murine VEGFR-2 or nonspecific MoABs (control). In the second experiment, mice in the PH group were randomly assigned to receive intraperitoneal injections of antimurine EGFR or nonspecific (control) MoABs. In both experiments, therapy was initiated the day before surgery and continued until the mice were killed on day 5. Livers were collected and processed. Results: Anti-VEGFR-2 therapy slightly impaired liver regeneration and hepatic cell proliferation compared with control. Hematoxylin and eosin staining showed no differences in liver morphology. CD105 staining showed decreased levels of activated endothelium in livers in the VEGFR-2 MoAB group. VEGFR-2 MoAB therapy decreased the levels of the cell cycle regulators cyclin D1 and cyclin D3 and the regenerative cytokine interleukin-6. Anti-EGFR therapy had no effect on liver regeneration or cellular proliferation. Conclusion: Anti-VEGFR-2 therapy slightly impaired liver regeneration in this murine model, whereas anti-EGFR therapy had no effect on liver regeneration.

Original languageEnglish (US)
Pages (from-to)1836-1842
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number11
DOIs
StatePublished - 2008
Externally publishedYes

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Liver Regeneration
Therapeutic Uses
Vascular Endothelial Growth Factor Receptor
Epidermal Growth Factor Receptor
Hepatectomy
Monoclonal Antibodies
Therapeutics
Intraperitoneal Injections
Colorectal Neoplasms
Liver
Cell Proliferation
Cyclin D3
Staining and Labeling
Drug Therapy
Cyclin D1
Hematoxylin
Eosine Yellowish-(YS)
Ambulatory Surgical Procedures
Laparotomy
Vascular Endothelial Growth Factor A

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Van Buren, G., Yang, A. D., Dallas, N. A., Gray, M. J., Lim, S. J., Xia, L., ... Ellis, L. M. (2008). Effect of molecular therapeutics on liver regeneration in a murine model. Journal of Clinical Oncology, 26(11), 1836-1842. https://doi.org/10.1200/JCO.2007.11.6566

Effect of molecular therapeutics on liver regeneration in a murine model. / Van Buren, George; Yang, Anthony D.; Dallas, Nikolaos A.; Gray, Michael J.; Lim, Sherry J.; Xia, Ling; Fan, Fan; Somcio, Ray; Wu, Yan; Hicklin, Daniel J.; Ellis, Lee M.

In: Journal of Clinical Oncology, Vol. 26, No. 11, 2008, p. 1836-1842.

Research output: Contribution to journalArticle

Van Buren, G, Yang, AD, Dallas, NA, Gray, MJ, Lim, SJ, Xia, L, Fan, F, Somcio, R, Wu, Y, Hicklin, DJ & Ellis, LM 2008, 'Effect of molecular therapeutics on liver regeneration in a murine model', Journal of Clinical Oncology, vol. 26, no. 11, pp. 1836-1842. https://doi.org/10.1200/JCO.2007.11.6566
Van Buren, George ; Yang, Anthony D. ; Dallas, Nikolaos A. ; Gray, Michael J. ; Lim, Sherry J. ; Xia, Ling ; Fan, Fan ; Somcio, Ray ; Wu, Yan ; Hicklin, Daniel J. ; Ellis, Lee M. / Effect of molecular therapeutics on liver regeneration in a murine model. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 11. pp. 1836-1842.
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AU - Dallas, Nikolaos A.

AU - Gray, Michael J.

AU - Lim, Sherry J.

AU - Xia, Ling

AU - Fan, Fan

AU - Somcio, Ray

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AU - Hicklin, Daniel J.

AU - Ellis, Lee M.

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N2 - Purpose: Unresectable metastatic colorectal cancer (CRC) can be rendered resectable with systemic chemotherapy in approximately 20% of cases. Most patients with metastatic CRC receive chemotherapy with the addition of targeted therapy with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) antibodies. We sought to determine whether anti-VEGF receptor (VEGFR) or anti-EGFR therapy would impair liver regeneration after partial hepatectomy (PH) in mice. Materials and Methods: Mice underwent either 66% PH or sham laparotomy. In the first experiment, mice in the PH group were randomly assigned to receive daily intraperitoneal injections of monoclonal antibodies (MoABs) to murine VEGFR-2 or nonspecific MoABs (control). In the second experiment, mice in the PH group were randomly assigned to receive intraperitoneal injections of antimurine EGFR or nonspecific (control) MoABs. In both experiments, therapy was initiated the day before surgery and continued until the mice were killed on day 5. Livers were collected and processed. Results: Anti-VEGFR-2 therapy slightly impaired liver regeneration and hepatic cell proliferation compared with control. Hematoxylin and eosin staining showed no differences in liver morphology. CD105 staining showed decreased levels of activated endothelium in livers in the VEGFR-2 MoAB group. VEGFR-2 MoAB therapy decreased the levels of the cell cycle regulators cyclin D1 and cyclin D3 and the regenerative cytokine interleukin-6. Anti-EGFR therapy had no effect on liver regeneration or cellular proliferation. Conclusion: Anti-VEGFR-2 therapy slightly impaired liver regeneration in this murine model, whereas anti-EGFR therapy had no effect on liver regeneration.

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