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Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer

Pancreatic cancer is the eighth most common cause of death from cancer in the world, for which palliative treatments are not effective and frequently accompanied by severe side effects. We propose a DNA-based therapy for pancreatic cancer using a nonviral vector, expressing the diphtheria toxin A ch...

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Autores principales: Scaiewicz, V., Sorin, V., Fellig, Y., Birman, T., Mizrahi, A., Galula, J., Abu-lail, R., Shneider, T., Ohana, P., Buscail, L., Hochberg, A., Czerniak, A.
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967839/
https://www.ncbi.nlm.nih.gov/pubmed/21052499
http://dx.doi.org/10.1155/2010/178174
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author Scaiewicz, V.
Sorin, V.
Fellig, Y.
Birman, T.
Mizrahi, A.
Galula, J.
Abu-lail, R.
Shneider, T.
Ohana, P.
Buscail, L.
Hochberg, A.
Czerniak, A.
author_facet Scaiewicz, V.
Sorin, V.
Fellig, Y.
Birman, T.
Mizrahi, A.
Galula, J.
Abu-lail, R.
Shneider, T.
Ohana, P.
Buscail, L.
Hochberg, A.
Czerniak, A.
author_sort Scaiewicz, V.
collection PubMed
description Pancreatic cancer is the eighth most common cause of death from cancer in the world, for which palliative treatments are not effective and frequently accompanied by severe side effects. We propose a DNA-based therapy for pancreatic cancer using a nonviral vector, expressing the diphtheria toxin A chain under the control of the H19 gene regulatory sequences. The H19 gene is an oncofetal RNA expressed during embryo development and in several types of cancer. We tested the expression of H19 gene in patients, and found that 65% of human pancreatic tumors analyzed showed moderated to strong expression of the gene. In vitro experiments showed that the vector was effective in reducing Luciferase protein activity on pancreatic carcinoma cell lines. In vivo experiment results revealed tumor growth arrest in different animal models for pancreatic cancer. Differences in tumor size between control and treated groups reached a 75% in the heterotopic model (P = .037) and 50% in the orthotopic model (P = .007). In addition, no visible metastases were found in the treated group of the orthotopic model. These results indicate that the treatment with the vector DTA-H19 might be a viable new therapeutic option for patients with unresectable pancreatic cancer.
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spelling pubmed-29678392010-11-04 Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer Scaiewicz, V. Sorin, V. Fellig, Y. Birman, T. Mizrahi, A. Galula, J. Abu-lail, R. Shneider, T. Ohana, P. Buscail, L. Hochberg, A. Czerniak, A. J Oncol Research Article Pancreatic cancer is the eighth most common cause of death from cancer in the world, for which palliative treatments are not effective and frequently accompanied by severe side effects. We propose a DNA-based therapy for pancreatic cancer using a nonviral vector, expressing the diphtheria toxin A chain under the control of the H19 gene regulatory sequences. The H19 gene is an oncofetal RNA expressed during embryo development and in several types of cancer. We tested the expression of H19 gene in patients, and found that 65% of human pancreatic tumors analyzed showed moderated to strong expression of the gene. In vitro experiments showed that the vector was effective in reducing Luciferase protein activity on pancreatic carcinoma cell lines. In vivo experiment results revealed tumor growth arrest in different animal models for pancreatic cancer. Differences in tumor size between control and treated groups reached a 75% in the heterotopic model (P = .037) and 50% in the orthotopic model (P = .007). In addition, no visible metastases were found in the treated group of the orthotopic model. These results indicate that the treatment with the vector DTA-H19 might be a viable new therapeutic option for patients with unresectable pancreatic cancer. Hindawi Publishing Corporation 2010 2010-10-28 /pmc/articles/PMC2967839/ /pubmed/21052499 http://dx.doi.org/10.1155/2010/178174 Text en Copyright © 2010 V. Scaiewicz et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Scaiewicz, V.
Sorin, V.
Fellig, Y.
Birman, T.
Mizrahi, A.
Galula, J.
Abu-lail, R.
Shneider, T.
Ohana, P.
Buscail, L.
Hochberg, A.
Czerniak, A.
Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer
title Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer
title_full Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer
title_fullStr Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer
title_full_unstemmed Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer
title_short Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer
title_sort use of h19 gene regulatory sequences in dna-based therapy for pancreatic cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967839/
https://www.ncbi.nlm.nih.gov/pubmed/21052499
http://dx.doi.org/10.1155/2010/178174
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