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dc.contributor.author
Real, Nilda E.
dc.contributor.author
Castro, Gisela Natalia
dc.contributor.author
Cuello Carrión, Fernando Darío
dc.contributor.author
Perinetti, Claudia
dc.contributor.author
Röhrich, Hanna
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Cayado Gutiérrez, Niubys de Los Milagros
dc.contributor.author
Guerrero Gimenez, Martin Eduardo
dc.contributor.author
Ciocca, Daniel Ramon
dc.date.available
2018-06-22T20:55:07Z
dc.date.issued
2017-11
dc.identifier.citation
Real, Nilda E.; Castro, Gisela Natalia; Cuello Carrión, Fernando Darío; Perinetti, Claudia; Röhrich, Hanna; et al.; Molecular markers of DNA damage and repair in cervical cancer patients treated with cisplatin neoadjuvant chemotherapy: an exploratory study; Springer; Cell Stress & Chaperones; 22; 6; 11-2017; 811-822
dc.identifier.issn
1355-8145
dc.identifier.uri
http://hdl.handle.net/11336/49801
dc.description.abstract
Neoadjuvant (or induction) chemotherapy can be used for cervical cancer patients with locally advanced disease; this treatment is followed by radical surgery and/or radiation therapy. Cisplatin is considered to be the most active platinum agent drug for this cancer, with a response rate of 20%. In order to understand how the cisplatin treatment affects the stress response, in this work, we performed an exploratory study to analyze a number of stress proteins before and after cisplatin neoadjuvant chemotherapy. The study involved 14 patients; the pre- and post-chemotherapy paired biopsies were examined by hematoxylin and eosin staining and by immunohistochemistry. The proteins evaluated were p53, P16/INK4A, MSH2, nuclear protein transcriptional regulator 1 (NUPR1), and HSPB1 (total: HSPB1/t and phosphorylated: HSPB1/p). These proteins were selected because there is previous evidence of their relationship with drug resistance. The formation of platinum-DNA adducts was also studied. There was a great variation in the expression levels of the mentioned proteins in the pre-chemotherapy biopsies. After chemotherapy, p53 was not significantly affected by cisplatin, as well as P16/INK4A and MSH2 while nuclear NUPR1 content tended to decrease (p = 0.056). Cytoplasmic HSPB1/t expression levels decreased significantly following cisplatin therapy while nuclear HSPB1/t and HSPB1/p tended to increase. Since the most significant changes following chemotherapy appeared in the HSPB1 expression levels, the changes were confirmed by Western blot. The platinum-DNA adducts were observed in HeLa cell in apoptosis; however, in the tumor samples, the platinum-DNA adducts were observed in morphologically healthy tumor cells; these cells displayed nuclear HSPB1/p. Further mechanistic studies should be performed to reveal how HSPB1/p is related with drug resistance. When the correlations of the markers with the response to neoadjuvant chemotherapy were examined, only high pre-chemotherapy levels of cytoplasmic HSPB1/p correlated with a poor clinical and pathological response to neoadjuvant cisplatin chemotherapy (p = 0.056) suggesting that this marker could be useful opening its study in a larger number of cases.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Cervical Cancer
dc.subject
Cisplatin
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Dna Damage
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Heat Shock Proteins
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Hspb1
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Molecular Markers
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Neoadjuvant Chemotherapy
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Medicina Critica y de Emergencia
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Molecular markers of DNA damage and repair in cervical cancer patients treated with cisplatin neoadjuvant chemotherapy: an exploratory study
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-18T19:10:22Z
dc.journal.volume
22
dc.journal.number
6
dc.journal.pagination
811-822
dc.journal.pais
Alemania
dc.journal.ciudad
Berlin
dc.description.fil
Fil: Real, Nilda E.. Hospital Diego Paroissien; Argentina
dc.description.fil
Fil: Castro, Gisela Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.description.fil
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.description.fil
Fil: Perinetti, Claudia. Hospital Diego Paroissien; Argentina
dc.description.fil
Fil: Röhrich, Hanna. Freie Universitaet Berlin; Alemania
dc.description.fil
Fil: Cayado Gutiérrez, Niubys de Los Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.description.fil
Fil: Guerrero Gimenez, Martin Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.description.fil
Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.journal.title
Cell Stress & Chaperones
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12192-017-0811-z
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s12192-017-0811-z


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