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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chen, Wei Ancukiewicz, Marek Liao, Shan Goel, Shom Liu, Jieqiong Xu, Lei Naxerova, Kamila Diop-frimpong, Benjamin Boucher, Yves Jain, Rakesh K. |
| Description | Author Affiliation: Liu J ( Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.); |
| Abstract | Although the role of TGF-ß in tumor progression has been studied extensively, its impact on drug delivery in tumors remains far from understood. In this study, we examined the effect of TGF-ß blockade on the delivery and efficacy of conventional therapeutics and nanotherapeutics in orthotopic mammary carcinoma mouse models. We used both genetic (overexpression of sTßRII, a soluble TGF-ß type II receptor) and pharmacologic (1D11, a TGF-ß neutralizing antibody) approaches to block TGF-ß signaling. In two orthotopic mammary carcinoma models (human MDA-MB-231 and murine 4T1 cell lines), TGF-ß blockade significantly decreased tumor growth and metastasis. TGF-ß blockade also increased the recruitment and incorporation of perivascular cells into tumor blood vessels and increased the fraction of perfused vessels. Moreover, TGF-ß blockade normalized the tumor interstitial matrix by decreasing collagen I content. As a result of this vessel and interstitial matrix normalization, TGF-ß blockade improved the intratumoral penetration of both a low-molecular-weight conventional chemotherapeutic drug and a nanotherapeutic agent, leading to better control of tumor growth. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 41 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antineoplastic Combined Chemotherapy Protocols Therapeutic Use Breast Neoplasms Drug Therapy Doxorubicin Transforming Growth Factor Beta Antagonists & Inhibitors Xenograft Model Antitumor Assays Animals Antibiotics, Antineoplastic Administration & Dosage Pharmacokinetics Antibodies, Neutralizing Immunology Apoptosis Drug Effects Blotting, Western Metabolism Pathology Cell Line, Tumor Cell Proliferation Collagen Type I Lung Neoplasms Prevention & Control Mice Mice, Nude Protein-Serine-Threonine Kinases Genetics Receptors, Transforming Growth Factor Beta Signal Transduction Tissue Distribution Tumor Burden Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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