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dc.contributor.author
Girouard, Julie
dc.contributor.author
Belgorosky, Denise
dc.contributor.author
Hamelin Morrissette , Jovane
dc.contributor.author
Boulanger, Valerie
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D'Orio, Ernesto
dc.contributor.author
Ramla, Djamel
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Perron, Robert
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Charpentier, Lucie
dc.contributor.author
Van Themsche, Celine
dc.contributor.author
Eijan, Ana Maria
dc.contributor.author
Bérubé, Gervais
dc.contributor.author
Reyes Moreno, Carlos
dc.date.available
2020-07-07T16:43:42Z
dc.date.issued
2019-12
dc.identifier.citation
Girouard, Julie; Belgorosky, Denise; Hamelin Morrissette , Jovane; Boulanger, Valerie; D'Orio, Ernesto; et al.; Molecular therapy with derivatives of amino benzoic acid inhibits tumor growth and metastasis in murine models of bladder cancer through inhibition of TNFα/NFΚB and iNOS/NO pathways; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 176; 12-2019; 1-15
dc.identifier.issn
0006-2952
dc.identifier.uri
http://hdl.handle.net/11336/109035
dc.description.abstract
Muscle-invasive bladder cancer (MIBC) is an aggressive form of urothelial bladder carcinoma (UBC) with poorer outcomes compared to the non-muscle invasive form (NMIBC). Higher recurrent rates and rapid progression after relapse in UBC is known to be linked with chronic inflammation. Here, the preclinical murine models of NMIBC (MB49) and MIBC (MB49-I) were used to assess the antitumor effects of DAB-1, an anti-inflammatory aminobenzoic acid derivative we have developed in order to target cancer-related inflammation. A subchronic toxicity study on cancer-free mice shown that DAB-1 treatment did not affect normal mouse development or normal function of vital organs. In mice bearing MB49-I tumors, whole body accumulation of the radioconjugate [ 131I]DAB-1 was higher than in control mice, the main sites of [131I]DAB-1 accumulation being the liver (34%), the intestines (21%), and the tumors (18%). In vivo molecular therapy of ectopic and orthotopic tumors indicated that treatment with DAB-1 efficiently inhibited tumor growth, metastasis formation, and mortality rate. The antitumor efficacy of DAB-1 was associated with strong decreased tumor cell proliferation and iNOS expression in tumor tissues and deactivation of macrophages from tumor-bearing mice. Mechanistic investigations revealed that DAB-1 efficiently inhibited i) TNFα/NFΚB and IL6/STAT3 signaling pathways activation; ii) TNFα-induced NO production by decreasing NFΚB transcriptional activation and functional iNOS expression; and iii) cellular proliferation with minimal or no effects on cell mortality or apoptosis. In conclusion, this study provides preclinical and biological/mechanistic data highlighting the potential of DAB-1 as a safe and efficient therapeutic agent for the treatment of patients with NMIBC and MIBC.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights
Atribución-NoComercial-CompartirIgual 2.5 Argentina (CC BY-NC-SA 2.5 AR)
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CANCER-RELATED INFLAMMATION
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BLADDER-CANCER
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TNFA
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NFKB
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INOS
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Biotecnología relacionada con la Salud
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Biotecnología de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Molecular therapy with derivatives of amino benzoic acid inhibits tumor growth and metastasis in murine models of bladder cancer through inhibition of TNFα/NFΚB and iNOS/NO pathways
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-07-01T17:11:28Z
dc.journal.volume
176
dc.journal.pagination
1-15
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Girouard, Julie. Université du Québec a Montreal; Canadá
dc.description.fil
Fil: Belgorosky, Denise. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
dc.description.fil
Fil: Hamelin Morrissette , Jovane. Université du Québec a Montreal; Canadá
dc.description.fil
Fil: Boulanger, Valerie. Université du Québec a Montreal; Canadá
dc.description.fil
Fil: D'Orio, Ernesto. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.description.fil
Fil: Ramla, Djamel. Université du Québec a Montreal; Canadá
dc.description.fil
Fil: Perron, Robert. Université du Québec a Montreal; Canadá
dc.description.fil
Fil: Charpentier, Lucie. Université du Québec a Montreal; Canadá
dc.description.fil
Fil: Van Themsche, Celine. Université du Québec a Montreal; Canadá
dc.description.fil
Fil: Eijan, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.description.fil
Fil: Bérubé, Gervais. Université du Québec a Montreal; Canadá
dc.description.fil
Fil: Reyes Moreno, Carlos. Université du Québec a Montreal; Canadá
dc.journal.title
Biochemical Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bcp.2019.113778
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0006295219304770?via%3Dihub
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