Molecular markers of DNA damage and repair in cervical cancer patients treated with cisplatin neoadjuvant chemotherapy: an exploratory study

Autor: Claudia Perinetti, Niubys Cayado-Gutiérrez, Gisela N. Castro, F. Darío Cuello-Carrión, Nilda E Real, Hanna Röhrich, Martin E. Guerrero-Gimenez, Daniel R. Ciocca
Rok vydání: 2017
Předmět:
0301 basic medicine
HEAT SHOCK PROTEINS
DNA Repair
medicine.medical_treatment
H&E stain
HSP27 Heat-Shock Proteins
Uterine Cervical Neoplasms
Drug resistance
Medicina Clínica
Biochemistry
NEOADJUVANT CHEMOTHERAPY
DNA Adducts
0302 clinical medicine
Neoadjuvant therapy
Heat-Shock Proteins
HSPB1
Middle Aged
Neoadjuvant Therapy
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
Immunohistochemistry
Female
Medicina Critica y de Emergencia
medicine.drug
Adult
CIENCIAS MÉDICAS Y DE LA SALUD
animal structures
MOLECULAR MARKERS
Biology
DNA DAMAGE
03 medical and health sciences
CISPLATIN
medicine
Biomarkers
Tumor
Humans
Aged
Cisplatin
Chemotherapy
Original Paper
Cancer
Cell Biology
CERVICAL CANCER
medicine.disease
Radiation therapy
030104 developmental biology
Drug Resistance
Neoplasm
Cancer research
Tumor Suppressor Protein p53
DNA Damage
HeLa Cells
Molecular Chaperones
Zdroj: Cell stresschaperones. 22(6)
ISSN: 1466-1268
Popis: 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. Fil: Real, Nilda E.. Hospital Diego Paroissien; Argentina 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 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 Fil: Perinetti, Claudia. Hospital Diego Paroissien; Argentina Fil: Röhrich, Hanna. Freie Universitaet Berlin; Alemania 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 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 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
Databáze: OpenAIRE
Externí odkaz: