The effects of vandetanib on paclitaxel tumor distribution and antitumor activity in a xenograft model of human ovarian carcinoma.
This study was designed to determine the effects of vandetanib, a small-molecule receptor tyrosine kinase inhibitor of vascular endothelial growth factor and epidermal growth factor receptor, on paclitaxel (PTX) tumor distribution and antitumor activity in xenograft models of human ovarian carcinoma...
| मुख्य लेखकों: | , , , , , , , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
2009
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| _version_ | 1826296880463609856 |
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| author | Cesca, M Frapolli, R Berndt, A Scarlato, V Richter, P Kosmehl, H D'Incalci, M Ryan, A Giavazzi, R |
| author_facet | Cesca, M Frapolli, R Berndt, A Scarlato, V Richter, P Kosmehl, H D'Incalci, M Ryan, A Giavazzi, R |
| author_sort | Cesca, M |
| collection | OXFORD |
| description | This study was designed to determine the effects of vandetanib, a small-molecule receptor tyrosine kinase inhibitor of vascular endothelial growth factor and epidermal growth factor receptor, on paclitaxel (PTX) tumor distribution and antitumor activity in xenograft models of human ovarian carcinoma. Nude mice bearing A2780-1A9 xenografts received daily (5, 10, or 15 days) doses of vandetanib (50 mg/kg per os), combined with PTX (20 mg/kg intravenously). Morphologic and functional modifications associated with the tumor vasculature (CD31 and alpha-smooth muscle actin staining and Hoechst 33342 perfusion) and PTX concentrations in plasma and tumor tissues were analyzed. Activity was evaluated as inhibition of tumor growth subcutaneously and spreading into the peritoneal cavity. Vandetanib treatment produced no significant change in tumor vessel density, although a reduced number of large vessels, an increased percentage of mature vessels, and diminished tumor perfusion were evident. Pretreatment with vandetanib led to decreased tumor PTX levels within 1 hour of PTX injection, although 24 hours later, tumor PTX levels were comparable with controls. In efficacy studies, the combination of vandetanib plus PTX improved antitumor activity compared with vandetanib or PTX alone, with greater effects being obtained when PTX was administered before vandetanib. The combination of PTX plus vandetanib reduced tumor burden in the peritoneal cavity of mice and significantly increased their survival. Analysis of vascular changes and PTX tumor uptake in vandetanib-treated tumors may help to guide the scheduling of vandetanib plus PTX combinations and may have implications for the design of clinical trials with these drugs. |
| first_indexed | 2024-03-07T04:23:08Z |
| format | Journal article |
| id | oxford-uuid:cbb3d005-6d06-4fb0-88f3-1fbc7777db3d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:23:08Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:cbb3d005-6d06-4fb0-88f3-1fbc7777db3d2022-03-27T07:16:44ZThe effects of vandetanib on paclitaxel tumor distribution and antitumor activity in a xenograft model of human ovarian carcinoma.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cbb3d005-6d06-4fb0-88f3-1fbc7777db3dEnglishSymplectic Elements at Oxford2009Cesca, MFrapolli, RBerndt, AScarlato, VRichter, PKosmehl, HD'Incalci, MRyan, AGiavazzi, RThis study was designed to determine the effects of vandetanib, a small-molecule receptor tyrosine kinase inhibitor of vascular endothelial growth factor and epidermal growth factor receptor, on paclitaxel (PTX) tumor distribution and antitumor activity in xenograft models of human ovarian carcinoma. Nude mice bearing A2780-1A9 xenografts received daily (5, 10, or 15 days) doses of vandetanib (50 mg/kg per os), combined with PTX (20 mg/kg intravenously). Morphologic and functional modifications associated with the tumor vasculature (CD31 and alpha-smooth muscle actin staining and Hoechst 33342 perfusion) and PTX concentrations in plasma and tumor tissues were analyzed. Activity was evaluated as inhibition of tumor growth subcutaneously and spreading into the peritoneal cavity. Vandetanib treatment produced no significant change in tumor vessel density, although a reduced number of large vessels, an increased percentage of mature vessels, and diminished tumor perfusion were evident. Pretreatment with vandetanib led to decreased tumor PTX levels within 1 hour of PTX injection, although 24 hours later, tumor PTX levels were comparable with controls. In efficacy studies, the combination of vandetanib plus PTX improved antitumor activity compared with vandetanib or PTX alone, with greater effects being obtained when PTX was administered before vandetanib. The combination of PTX plus vandetanib reduced tumor burden in the peritoneal cavity of mice and significantly increased their survival. Analysis of vascular changes and PTX tumor uptake in vandetanib-treated tumors may help to guide the scheduling of vandetanib plus PTX combinations and may have implications for the design of clinical trials with these drugs. |
| spellingShingle | Cesca, M Frapolli, R Berndt, A Scarlato, V Richter, P Kosmehl, H D'Incalci, M Ryan, A Giavazzi, R The effects of vandetanib on paclitaxel tumor distribution and antitumor activity in a xenograft model of human ovarian carcinoma. |
| title | The effects of vandetanib on paclitaxel tumor distribution and antitumor activity in a xenograft model of human ovarian carcinoma. |
| title_full | The effects of vandetanib on paclitaxel tumor distribution and antitumor activity in a xenograft model of human ovarian carcinoma. |
| title_fullStr | The effects of vandetanib on paclitaxel tumor distribution and antitumor activity in a xenograft model of human ovarian carcinoma. |
| title_full_unstemmed | The effects of vandetanib on paclitaxel tumor distribution and antitumor activity in a xenograft model of human ovarian carcinoma. |
| title_short | The effects of vandetanib on paclitaxel tumor distribution and antitumor activity in a xenograft model of human ovarian carcinoma. |
| title_sort | effects of vandetanib on paclitaxel tumor distribution and antitumor activity in a xenograft model of human ovarian carcinoma |
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