Abstract |
By attacking established tumor vasculature, vascular disrupting agents (VDAs) represent an alternative approach to the treatment of cancer. One such VDA, 5,6-dimethylxanthenone-4-acetic acid ( DMXAA), is scheduled for phase III trials for prostate and lung cancer in combination with conventional chemotherapies. In this work, we identify interferon-beta (IFN-beta) as a central mediator in the host's response to DMXAA. In mice bearing Lewis lung adenocarcinomas, a single intraperitoneal dose of DMXAA was shown to effect a highly significant reduction in tumor growth rate in wild-type mice that was not seen in IFN-beta-null mice. Moreover, intratumoral cytokine expression was shown to be dependent on host-derived IFN-beta, as DMXAA-treated IFN-beta-null mice demonstrated a lack of induction of not only IFN-beta but also the antiangiogenic cytokine, IP-10, in excised tumor tissue. These results support the conclusion that DMXAA derives its potent anticancer properties in part through elicitation of IFN-beta expression by host-derived elements.
|
Authors | Zachary J Roberts, Lai-Ming Ching, Stefanie N Vogel |
Journal | Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
(J Interferon Cytokine Res)
Vol. 28
Issue 3
Pg. 133-9
(Mar 2008)
ISSN: 1079-9907 [Print] United States |
PMID | 18338946
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antineoplastic Agents
- Chemokine CXCL10
- Xanthones
- vadimezan
- Interferon-beta
|
Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Blood Vessels
(metabolism)
- Carcinoma, Lewis Lung
(drug therapy, immunology)
- Chemokine CXCL10
(immunology, metabolism)
- Female
- Interferon-beta
(immunology, physiology)
- Lung Neoplasms
(drug therapy, immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Mutant Strains
- Xanthones
(pharmacology)
|