| Multistage Vectored siRNA Targeting Ataxia-Telangiectasia Mutated for Breast Cancer Therapy. | |
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MedLine Citation:
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PMID: 23293085 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The ataxia-telangiectasia mutated (ATM) protein plays a central role in DNA damage response and cell cycle checkpoints, and may be a promising target for cancer therapy if normal tissue toxicity could be avoided. The strategy presented here to target ATM for breast cancer therapy involves the use of liposomal-encapsulated, gene-specific ATM siRNA delivered with a well-characterized porous silicon-based multistage vector (MSV) delivery system (MSV/ATM). Biweekly treatment of MSV/ATM suppressed ATM expression in tumor tissues, and consequently inhibited growth of MDA-MB-231 orthotopic tumor in nude mice. At the therapeutic dosage, neither free liposomal ATM siRNA nor MSV/ATM triggered an acute immune response in BALB/c mice, including changes in serum cytokines, chemokines or colony-stimulating factors. Weekly treatments of mice with free liposomal ATM siRNA or MSV/ATM for 4 weeks did not cause significant changes in body weight, hematology, blood biochemistry, or major organ histology. These results indicate that MSV/ATM is biocompatible and efficacious in inhibiting tumor growth, and that further preclinical evaluation is warranted for the development of MSV/ATM as a potential therapeutic agent. |
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Authors:
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Rong Xu; Yi Huang; Junhua Mai; Guodong Zhang; Xiaojing Guo; Xiaojun Xia; Eugene J Koay; Guoting Qin; Donald R Erm; Qingpo Li; Xuewu Liu; Mauro Ferrari; Haifa Shen |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-6 |
Journal Detail:
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Title: Small (Weinheim an der Bergstrasse, Germany) Volume: - ISSN: 1613-6829 ISO Abbreviation: Small Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101235338 Medline TA: Small Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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