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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
dc.contributor.author 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
dc.subject DNA DAMAGE
dc.subject HEAT SHOCK PROTEINS
dc.subject HSPB1
dc.subject MOLECULAR MARKERS
dc.subject NEOADJUVANT CHEMOTHERAPY
dc.subject.classification Medicina Critica y de Emergencia
dc.subject.classification Medicina Clínica
dc.subject.classification 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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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)