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Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences

BACKGROUND: Ovarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulato...

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Autores principales: Mizrahi, Aya, Czerniak, Abraham, Levy, Tally, Amiur, Smadar, Gallula, Jennifer, Matouk, Imad, Abu-lail, Rasha, Sorin, Vladimir, Birman, Tatiana, de Groot, Nathan, Hochberg, Abraham, Ohana, Patricia
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734756/
https://www.ncbi.nlm.nih.gov/pubmed/19656414
http://dx.doi.org/10.1186/1479-5876-7-69
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author Mizrahi, Aya
Czerniak, Abraham
Levy, Tally
Amiur, Smadar
Gallula, Jennifer
Matouk, Imad
Abu-lail, Rasha
Sorin, Vladimir
Birman, Tatiana
de Groot, Nathan
Hochberg, Abraham
Ohana, Patricia
author_facet Mizrahi, Aya
Czerniak, Abraham
Levy, Tally
Amiur, Smadar
Gallula, Jennifer
Matouk, Imad
Abu-lail, Rasha
Sorin, Vladimir
Birman, Tatiana
de Groot, Nathan
Hochberg, Abraham
Ohana, Patricia
author_sort Mizrahi, Aya
collection PubMed
description BACKGROUND: Ovarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer), while existing at a nearly undetectable level in the surrounding normal tissue. METHODS: H19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH) using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer. RESULTS: H19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth. CONCLUSION: These observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure.
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spelling pubmed-27347562009-08-29 Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences Mizrahi, Aya Czerniak, Abraham Levy, Tally Amiur, Smadar Gallula, Jennifer Matouk, Imad Abu-lail, Rasha Sorin, Vladimir Birman, Tatiana de Groot, Nathan Hochberg, Abraham Ohana, Patricia J Transl Med Research BACKGROUND: Ovarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer), while existing at a nearly undetectable level in the surrounding normal tissue. METHODS: H19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH) using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer. RESULTS: H19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth. CONCLUSION: These observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure. BioMed Central 2009-08-06 /pmc/articles/PMC2734756/ /pubmed/19656414 http://dx.doi.org/10.1186/1479-5876-7-69 Text en Copyright © 2009 Mizrahi et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Mizrahi, Aya
Czerniak, Abraham
Levy, Tally
Amiur, Smadar
Gallula, Jennifer
Matouk, Imad
Abu-lail, Rasha
Sorin, Vladimir
Birman, Tatiana
de Groot, Nathan
Hochberg, Abraham
Ohana, Patricia
Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences
title Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences
title_full Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences
title_fullStr Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences
title_full_unstemmed Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences
title_short Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences
title_sort development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of h19 regulatory sequences
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734756/
https://www.ncbi.nlm.nih.gov/pubmed/19656414
http://dx.doi.org/10.1186/1479-5876-7-69
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