Analysis of genetic and phenotypic interactions between DNA damage / genotoxicity pathways in heart tissue and heart damage caused by anthracyclines and taxanes

التفاصيل البيبلوغرافية
العنوان: Analysis of genetic and phenotypic interactions between DNA damage / genotoxicity pathways in heart tissue and heart damage caused by anthracyclines and taxanes
المؤلفون: Corchado Cobos, Roberto, Gómez-Vecino, Aurora, García-Macías, Carmen, Rodrigues Teixeira, Telmo, Isidoro-García, María, García Sánchez, Asunción, Galvis-Jiménez, Julie Milena, Ramos, Isabel, Blanco-Gómez, Adrián, Sánchez-Fernández, Pedro Luis, Pérez-Losada, J.
بيانات النشر: Sociedad Española de Bioquímica y Biología Molecular
سنة النشر: 2016
المجموعة: Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council)
الوصف: Resumen del póster presentado al XXXIX Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca del 5 al 8 de septiembre de 2016. ; [Introduction]: Anthracyclines are among the most widely used chemotherapeutic agents in the treatment of a variety of tumors. The identification of genetic and molecular factors responsible for the increased risk of CDA (cardiotoxicity due to anthracyclines) will contribute to a better understanding of their pathophysiology, which could lead to new approaches to predict, prevent and treat this serious complication of chemotherapy. [Working hypothesis]: Based on two premises: (i) anthracyclines have a pro-genotoxicity effect. Differences in anti-genotoxicity pathways and genetic variants could contribute to different susceptibility to CDA. (ii) The usefulness of a simplified model system to identify genetic determinants involved in the quantitative inheritance of complex traits. [Materials and methods]: We treated a cohort of mice carrying ERBB2 breast cancer with doxorubicin alone (N = 85) or in combination with docetaxel (N = 77). The cohort was generated by a backcross between two genetically homogeneous strains, C57BL/6 and FVB, with the latter carrying the MMTV- ErbB2 / Neu transgene. Histopathologic heart damage was assessed by quantification of histologic parameters using Ariol automated system. Cardiac level of some key anti-genotoxicity proteins: ATR total, pp53 (Ser15), P21 Total, Total MDM2, pHistone H2AX (Ser139), pCHK1 (Ser345) and pCHK2 (Thr68) were quantified. [Results]: We identified: (i) differences dependent on the genetic background in both cardiotoxicity and the levels of proteins implicated in the pathways protecting against genotoxicity; (ii) activation of anti-genotoxicity pathways were associated with chemotherapy cardiotoxicity; (iii) quantitative trait loci (QTLs) specific and common to cardiotoxicity and the levels of the pathways studied. [Conclusion]: We identified genetic determinants associated with anthracycline ...
نوع الوثيقة: still image
اللغة: English
العلاقة: Sí; XXXIX Congreso de la SEBBM (2016); http://hdl.handle.net/10261/169551Test
الإتاحة: http://hdl.handle.net/10261/169551Test
حقوق: none
رقم الانضمام: edsbas.E6D7D369
قاعدة البيانات: BASE