Document Detail


Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy.
MedLine Citation:
PMID:  23293085     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-01-06
Journal Detail:
Title:  Small (Weinheim an der Bergstrasse, Germany)     Volume:  9     ISSN:  1613-6829     ISO Abbreviation:  Small     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-17     Completed Date:  2013-12-09     Revised Date:  2014-03-27    
Medline Journal Info:
Nlm Unique ID:  101235338     Medline TA:  Small     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1799-808     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
Animals
Ataxia Telangiectasia Mutated Proteins / genetics*
Breast Neoplasms / immunology,  pathology,  therapy*
Cell Division
Cell Line, Tumor
Female
Genetic Therapy*
Genetic Vectors*
Humans
Immunity, Innate
Mice
Mice, Nude
RNA, Small Interfering / genetics*
Toxicity Tests, Subacute
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
U54 CA143837/CA/NCI NIH HHS; U54 CA151668/CA/NCI NIH HHS; U54CA143837/CA/NCI NIH HHS; U54CA151668/CA/NCI NIH HHS; UL1 TR000371/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; EC 2.7.11.1/ATM protein, human; EC 2.7.11.1/Ataxia Telangiectasia Mutated Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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