Publication Date:
2006-11-25
Description:
Clostridium novyi-NT is an anaerobic bacterium that can infect hypoxic regions within experimental tumors. Because C. novyi-NT lyses red blood cells, we hypothesized that its membrane-disrupting properties could be exploited to enhance the release of liposome-encapsulated drugs within tumors. Here, we show that treatment of mice bearing large, established tumors with C. novyi-NT plus a single dose of liposomal doxorubicin often led to eradication of the tumors. The bacterial factor responsible for the enhanced drug release was identified as a previously unrecognized protein termed liposomase. This protein could potentially be incorporated into diverse experimental approaches for the specific delivery of chemotherapeutic agents to tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheong, Ian -- Huang, Xin -- Bettegowda, Chetan -- Diaz, Luis A Jr -- Kinzler, Kenneth W -- Zhou, Shibin -- Vogelstein, Bert -- CA062924/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2006 Nov 24;314(5803):1308-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and the Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17124324" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Antineoplastic Agents/*administration & dosage/pharmacokinetics/therapeutic use
;
Bacterial Proteins/chemistry/genetics/*metabolism
;
Base Sequence
;
Camptothecin/administration & dosage/analogs &
;
derivatives/pharmacokinetics/therapeutic use
;
Cell Line, Tumor
;
Cloning, Molecular
;
Clostridium/*chemistry/genetics
;
Colorectal Neoplasms/*drug therapy
;
Doxorubicin/*administration & dosage/pharmacokinetics/therapeutic use
;
Drug Carriers
;
Humans
;
Lipase/chemistry/genetics/*metabolism
;
Lipid Bilayers/chemistry
;
Liposomes/chemistry/*metabolism
;
Mice
;
Molecular Sequence Data
;
Mutation
;
Neoplasm Transplantation
;
Protein Structure, Tertiary
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
