Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: A single dose of FAK siRNA- DOPC was highly effective in reducing in vivo FAK expression for up to 4 days as assayed by Western blot and immunohistochemical analysis. Therapy experiments were started 1 week after injection of the ovarian cancer cells. Treatment with FAK siRNA- DOPC (150 mug/kg twice weekly) reduced mean tumor weight by 44% to 72% in the three cell lines compared with the control group (Ps < 0.05 for HeyA8, A2780-CP20, and SKOV3ip1). When FAK siRNA- DOPC was combined with docetaxel, there was even greater reduction in mean tumor weight in all models (all Ps < 0.05). Similar results were observed in combination with cisplatin. Treatment with FAK siRNA- DOPC plus docetaxel resulted in decreased microvessel density, decreased expression of vascular endothelial growth factor and matrix metalloproteinase-9, and increased apoptosis of tumor-associated endothelial cells and tumor cells. CONCLUSIONS:
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Authors | Jyotsnabaran Halder, Aparna A Kamat, Charles N Landen Jr, Liz Y Han, Susan K Lutgendorf, Yvonne G Lin, William M Merritt, Nicholas B Jennings, Arturo Chavez-Reyes, Robert L Coleman, David M Gershenson, Rosemarie Schmandt, Steven W Cole, Gabriel Lopez-Berestein, Anil K Sood |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 12
Issue 16
Pg. 4916-24
(Aug 15 2006)
ISSN: 1078-0432 [Print] United States |
PMID | 16914580
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Liposomes
- Phosphatidylcholines
- RNA, Small Interfering
- Focal Adhesion Protein-Tyrosine Kinases
- 1,2-oleoylphosphatidylcholine
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Topics |
- Animals
- Apoptosis
(drug effects)
- Cell Proliferation
(drug effects)
- Down-Regulation
- Female
- Focal Adhesion Protein-Tyrosine Kinases
(antagonists & inhibitors, genetics)
- Humans
- Liposomes
(administration & dosage)
- Mice
- Mice, Nude
- Neovascularization, Pathologic
(therapy)
- Ovarian Neoplasms
(blood supply, enzymology, genetics, therapy)
- Phosphatidylcholines
(administration & dosage)
- RNA, Small Interfering
(administration & dosage, genetics)
- Xenograft Model Antitumor Assays
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