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dc.contributor.author
Mateu-Jimenez, Mercè
dc.contributor.author
Fermoselle, Clara
dc.contributor.author
Rojo, Federico
dc.contributor.author
Mateu, Javier
dc.contributor.author
Peña, Raúl
dc.contributor.author
Urtreger, Alejandro Jorge
dc.contributor.author
Diament, Miriam
dc.contributor.author
Bal, Elisa Dora
dc.contributor.author
Pijuan, Lara
dc.contributor.author
Herreros, Antonio
dc.contributor.author
Barreiro, Esther
dc.date.available
2018-06-08T20:01:09Z
dc.date.issued
2016-11
dc.identifier.citation
Mateu-Jimenez, Mercè; Fermoselle, Clara; Rojo, Federico; Mateu, Javier; Peña, Raúl; et al.; Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology; Bentham Science Publishers; Current Pharmaceutical Design; 22; 34; 11-2016; 5300-5310
dc.identifier.issn
1381-6128
dc.identifier.uri
http://hdl.handle.net/11336/47973
dc.description.abstract
Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-KB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking. We hypothesized that antioxidants and NF-KB, MAPK, and proteasome inhibitors may exert an antitumoral response through attenuation of several key biological mechanisms that promote tumorigenesis and cancer cell growth. Body and tumor weights, oxidative stress, antioxidants, inflammation, NF-KB p65 expression, fibulins, apoptosis, autophagy, tumor and stroma histology were evaluated in the subcutaneous tumor of LC (LP07) adenocarcinoma) BALB/c mice, with and without concomitant treatment with NF-KB (sulfasalazine), MEK (U0126), and proteasome (bortezomib) inhibitors, and N-acetyl cysteine (NAC). Compared to LC control mice, in subcutaneous tumors, the four pharmacological agents reduced oxidative stress markers and tumor proliferation (ki-67). Inflammation and NF-KB p65 expression were attenuated by NF-KB and MAPK inhibitors, and the latter also enhanced apoptotic markers. Catalase was induced by the three inhibitors, while bortezomib also promoted superoxide dismutase expression. NF-KB and MEK inhibitors significantly reduced tumor burden through several biological mechanisms that favored tumor degradation and attenuated tumor proliferation. These two pharmacological agents may enhance the anti-tumor activity of selectively targeted therapeutic strategies for LC. Proteasomal inhibition using bortezomib rather promotes tumor degradation, while treatment with antioxidants cannot be recommended. This experimental model supports the use of adjuvant drugs for the improvement of LC treatment.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Bentham Science Publishers
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Non-Small Cell Lung Cancer
dc.subject
Mapk
dc.subject
Nf-Kb
dc.subject.classification
Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-06T19:39:39Z
dc.journal.volume
22
dc.journal.number
34
dc.journal.pagination
5300-5310
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Oak Park
dc.description.fil
Fil: Mateu-Jimenez, Mercè. Barcelona Biomedical Research Park; España
dc.description.fil
Fil: Fermoselle, Clara. Barcelona Biomedical Research Park; España
dc.description.fil
Fil: Rojo, Federico. Fundación Jiménez Díaz; España
dc.description.fil
Fil: Mateu, Javier. Hospital del Mar; España
dc.description.fil
Fil: Peña, Raúl. Hospital del Mar; España
dc.description.fil
Fil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Diament, Miriam. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.description.fil
Fil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
dc.description.fil
Fil: Pijuan, Lara. Hospital del Mar; España
dc.description.fil
Fil: Herreros, Antonio. Hospital del Mar; España
dc.description.fil
Fil: Barreiro, Esther. Barcelona Biomedical Research Park; España
dc.journal.title
Current Pharmaceutical Design
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.2174/1381612822666160623065523
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/143505/article
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