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5
BIOSIS Evolutions
Vol. 8 Issue 4 2001
Ovid: Bibliographic Records
Accession Number: PREV200100169091
Author/Editor/Inventor: Li S [a]. Zhang X. Xia X. Zhou L. Breau R. Suen J. Hanna E.
Institution: [a] Department of Otolaryngology/Head and Neck Surgery, University of
Arkansas School of Medicine, 4001 W Capital Avenue, Little Rock, AR, 72205
USA.
Country: USA.
Title: Intramuscular electroporation delivery of IFN-alpha gene therapy for inhibition of
tumor growth located at a distant site.
Source: Gene Therapy. [ print] 8(5). March, 2001. 400-407.
Year of Publication: 2001
Publication Type: Article.
ISSN: 0969-7128
Concept Codes:
Genetics and Cytogenetics/General [03502]
Genetics and Cytogenetics/Animal [03506]
Pathology, General and Miscellaneous/Therapy (1971- ) [12512]
Muscle/Physiology and Biochemistry [17504]
Neoplasms and Neoplastic Agents/Pathology; Clinical Aspects; Systemic Effects
[24004]
Neoplasms and Neoplastic Agents/Therapeutic Agents; Therapy [24008]
Biosystematic Codes: Muridae [86375]
Languages: English.
Summary Language: English.
Abstract: Although electroporation has been shown in recent years to be a powerful
method for delivering genes to muscle, no gene therapy via electro-injection has
been studied for the treatment of tumors. In an immunocompetent tumor-bearing
murine model, we have found that delivery of a low dose of reporter gene DNA (10
mug) to muscle via electroporation under specific pulse conditions (two 25-ms
pulses of 375 V/cm) increased the level of gene expression by two logs of
magnitude. Moreover, administration of 10 mug of interferon (IFN)-alpha DNA
plasmid using these parameters once a week for 3 weeks increased the survival
time and reduced squamous cell carcinoma (SCC) growth at a distant site in the
C3H/HeJ-immunocompetent mouse. IFN-alpha gene therapy delivered to muscle
using electroporation demonstrated statistically significant (P < 0.05) therapeutic
efficacy for treating SCC located at a distant site, compared with interleukin (IL)-2
or endostatin gene, also delivered by electro-injection. The increased therapeutic
efficacy was associated with a high level and extended duration of IFN-alpha
expression in muscle and serum. We also discovered that the high level of IFN-
alpha expression correlated with increased expression levels of the antiangiogenic
genes IP-10 and Mig in local tumor tissue, which may have led to the reduction of
blood vessels observed at the local tumor site. Delivery of increasing doses (10-
100 mug) of IFN-alpha plasmid DNA by injection alone did not increase antitumor
activity, whereas electroporation delivery of increasing doses (10-40 mug) of IFN-
alpha plasmid DNA did increase the survival time. Our data clearly demonstrate the
potential utility of electroporation for delivery of gene therapy to muscle for the
treatment of residual or disseminated tumors.
Major Concepts: Molecular Genetics (Biochemistry and Molecular Biophysics).
Methods and Techniques. Tumor Biology.
Super Taxa: Muridae: Rodentia, Mammalia, Vertebrata, Chordata, Animalia.
Organisms: mouse (Muridae): immunocompetent, strain-C3H/HeJ.
Taxa Notes: Animals; Chordates; Mammals; Nonhuman Mammals; Nonhuman
Vertebrates; Rodents; Vertebrates.
Parts, Structures & Systems of Organisms: muscle: muscular system.
Diseases: squamous cell carcinoma: neoplastic disease.
Methods & Equipment: cancer gene therapy: gene transfer method, therapeutic
method; electroporation: gene expression/vector techniques, genetic method,
intramuscular administration.
Miscellaneous Descriptors: tumor growth: inhibition.
Update Code: 200116. BIOSIS Update: 20010327.
Copyright (c) 2000-2001 Ovid Technologies, Inc.
Version: rel4.3.0, SourceID: 1.5031.1.381
Sample Record from BIOSIS Previews
Sample Record from Medline
Ovid: Bibliographic Records
Unique Identifier: 21214787
PubMed Identifier: 11313817
Authors: Li S. Zhang X. Xia X. Zhou L. Breau R. Suen J. Hanna E.
Institution: Department of Otolaryngology/Head and Neck Surgery, University of
Arkansas School of Medicine, 4001 W Capital Avenue, Little Rock, AR 72205,
USA.
Title: Intramuscular electroporation delivery of IFN-alpha gene therapy for inhibition of
tumor growth located at a distant site.
Source: Gene Therapy. 8(5):400-7, 2001 Mar.
NLM Journal Code: cce, 9421525
Journal Subset: Index Medicus
Country of Publication: England
MeSH Subject Headings:
Animal
Carcinoma, Squamous Cell / bs [Blood Supply]
Carcinoma, Squamous Cell / pa [Pathology]
*Carcinoma, Squamous Cell / th [Therapy]
Chemokines, CXC / me [Metabolism]
*Electroporation / mt [Methods]
Female
Gene Expression
*Gene Therapy / mt [Methods]
Genes, Reporter
Injections, Intramuscular
*Interferon-alpha / ge [Genetics]
Interferon-alpha / me [Metabolism]
Interleukin-12 / ge [Genetics]
Interleukin-2 / ge [Genetics]
Mice
Mice, Inbred C3H
Neovascularization, Pathologic / pc [Prevention & Control]
Support, Non-U.S. Gov't
Survival Rate
Abstract: Although electroporation has been shown in recent years to be a powerful
method for delivering genes to muscle, no gene therapy via electro-injection has
been studied for the treatment of tumors. In an immunocompetent tumor-bearing
murine model, we have found that delivery of a low dose of reporter gene DNA
(10 microg) to muscle via electroporation under specific pulse conditions (two 25-
ms pulses of 375 V/cm) increased the level of gene expression by two logs of
magnitude. Moreover, administration of 10 microg of interferon (IFN)-alpha DNA
plasmid using these parameters once a week for 3 weeks increased the survival
time and reduced squamous cell carcinoma (SCC) growth at a distant site in the
C3H/HeJ-immunocompetent mouse. IFN-alpha gene therapy delivered to muscle
using electroporation demonstrated statistically significant (P < 0.05) therapeutic
efficacy for treating SCC located at a distant site, compared with interleukin (IL)-2
or endostatin gene, also delivered by electro-injection. The increased therapeutic
efficacy was associated with a high level and extended duration of IFN-alpha
expression in muscle and serum. We also discovered that the high level of IFN-
alpha expression correlated with increased expression levels of the antiangiogenic
genes IP-10 and Mig in local tumor tissue, which may have led to the reduction of
blood vessels observed at the local tumor site. Delivery of increasing doses (10-
100 microg) of IFN-alpha plasmid DNA by injection alone did not increase
antitumor activity, whereas electroporation delivery of increasing doses (10-40
microg) of IFN-alpha plasmid DNA did increase the survival time. Our data clearly
demonstrate the potential utility of electroporation for delivery of gene therapy to
muscle for the treatment of residual or disseminated tumors.
Registry Numbers: 0 (CXC chemokine IP-10). 0 (Chemokines, CXC). 0 (Interferon-
alpha). 0 (Interleukin-12). 0 (Interleukin-2). 0 (humig).
ISSN: 0969-7128
Publication Type: Journal Article.
Language: English
Entry Month: 20010614. Entry Week: 20010614.
Copyright (c) 2000-2001 Ovid Technologies, Inc.
Version: rel4.3.0, SourceID: 1.5031.1.381
