Document Detail


Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain.
MedLine Citation:
PMID:  22666539     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therapeutic use. By placing an essential gene under a hypoxia conditioned promoter, SalmonellaTyphimurium strain SL7207 was engineered to survive only in anaerobic conditions (strain YB1) without otherwise affecting its functions. In breast tumor bearing nude mice, YB1 grew within the tumor, retarding its growth, while being rapidly eliminated from normal tissues. YB1 provides a safe bacterial vector for anti-tumor therapies without compromising the other functions or tumor fitness of the bacterium as attenuation methods normally do.
Authors:
Bin Yu; Mei Yang; Lei Shi; Yandan Yao; Qinqin Jiang; Xuefei Li; Lei-Han Tang; Bo-Jian Zheng; Kwok-Yung Yuen; David K Smith; Erwei Song; Jian-Dong Huang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-01
Journal Detail:
Title:  Scientific reports     Volume:  2     ISSN:  2045-2322     ISO Abbreviation:  Sci Rep     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-05     Completed Date:  2013-02-25     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101563288     Medline TA:  Sci Rep     Country:  England    
Other Details:
Languages:  eng     Pagination:  436     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia
Bacteria, Anaerobic / genetics,  pathogenicity,  physiology*
Bacterial Vaccines / pharmacology
Biological Therapy / methods
Breast Neoplasms / microbiology,  pathology,  therapy
Cell Line, Tumor
Female
Genetic Engineering / methods
Host-Pathogen Interactions*
Humans
Mice
Mice, Nude
Neoplasms / microbiology*,  pathology,  therapy
Salmonella typhimurium / genetics,  pathogenicity,  physiology*
Tumor Burden / drug effects
Virulence / genetics
Xenograft Model Antitumor Assays / methods
Chemical
Reg. No./Substance:
0/Bacterial Vaccines; 0/VNP 20009
Comments/Corrections

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


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