Abstract |
The endothelin-1 antagonist, Atrasentan (ABT-627) was used to modify perfusion in the human tumor xenograft model, HT29, growing in nude mice. Atrasentan produced a significant increase in perfusion, as measured in vivo by Gd-DTPA DCE-MRI. Changes in tumor hypoxia were assessed by comparing the binding of two hypoxia tracers, pimonidazole and EF5 given before and after Atrasentan administration. In vehicle-treated controls, the distribution of EF5 and pimonidazole was very similar. However, Atrasentan treatment was associated with decreased uptake of the second hypoxia tracer (EF5), relative to the first ( pimonidazole). Although Atrasentan had no independent effect on the growth of HT29 tumors, Atrasentan combined with 20 Gy radiation led to a modest but significant increase in tumor growth delay compared to radiation alone.
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Authors | Kwang Mo Yang, James Russell, Mihaela E Lupu, Hyungjoon Cho, Xiao-Feng Li, Jason A Koutcher, C Clifton Ling |
Journal | Cancer biology & therapy
(Cancer Biol Ther)
Vol. 8
Issue 20
Pg. 1940-6
(Oct 2009)
ISSN: 1555-8576 [Electronic] United States |
PMID | 19717985
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Hydrocarbons, Fluorinated
- Nitroimidazoles
- Pyrrolidines
- Radiation-Sensitizing Agents
- Etanidazole
- 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide
- pimonidazole
- Gadolinium DTPA
- Atrasentan
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Topics |
- Adenocarcinoma
(metabolism, pathology, therapy)
- Animals
- Atrasentan
- Colonic Neoplasms
(metabolism, pathology, therapy)
- Combined Modality Therapy
- Etanidazole
(analogs & derivatives, pharmacokinetics)
- Gadolinium DTPA
- HT29 Cells
- Humans
- Hydrocarbons, Fluorinated
(pharmacokinetics)
- Hypoxia
- Magnetic Resonance Imaging
(methods)
- Male
- Mice
- Mice, Nude
- Nitroimidazoles
(pharmacokinetics)
- Perfusion
- Pyrrolidines
(pharmacology)
- Radiation-Sensitizing Agents
(pharmacokinetics)
- Radiotherapy
(methods)
- Treatment Outcome
- Xenograft Model Antitumor Assays
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