<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Moura, David S</style></author><author><style face="normal" font="default" size="100%">Mondaza-Hernandez, Jose L</style></author><author><style face="normal" font="default" size="100%">Sanchez-Bustos, Paloma</style></author><author><style face="normal" font="default" size="100%">Peña-Chilet, Maria</style></author><author><style face="normal" font="default" size="100%">Cordero-Varela, Juan A</style></author><author><style face="normal" font="default" size="100%">Lopez-Alvarez, Maria</style></author><author><style face="normal" font="default" size="100%">Carrillo-Garcia, Jaime</style></author><author><style face="normal" font="default" size="100%">Martin-Ruiz, Marta</style></author><author><style face="normal" font="default" size="100%">Romero-Gonzalez, Pablo</style></author><author><style face="normal" font="default" size="100%">Renshaw-Calderon, Marta</style></author><author><style face="normal" font="default" size="100%">Ramos, Rafael</style></author><author><style face="normal" font="default" size="100%">Marcilla, David</style></author><author><style face="normal" font="default" size="100%">Alvarez-Alegret, Ramiro</style></author><author><style face="normal" font="default" size="100%">Agra-Pujol, Carolina</style></author><author><style face="normal" font="default" size="100%">Izquierdo, Francisco</style></author><author><style face="normal" font="default" size="100%">Ortega-Medina, Luis</style></author><author><style face="normal" font="default" size="100%">Martin-Davila, Francisco</style></author><author><style face="normal" font="default" size="100%">Hernandez-Leon, Carmen Nieves</style></author><author><style face="normal" font="default" size="100%">Romagosa, Cleofe</style></author><author><style face="normal" font="default" size="100%">Salgado, Maria Angeles Vaz</style></author><author><style face="normal" font="default" size="100%">Lavernia, Javier</style></author><author><style face="normal" font="default" size="100%">Bagué, Silvia</style></author><author><style face="normal" font="default" size="100%">Mayodormo-Aranda, Empar</style></author><author><style face="normal" font="default" size="100%">Alvarez, Rosa</style></author><author><style face="normal" font="default" size="100%">Valverde, Claudia</style></author><author><style face="normal" font="default" size="100%">Martinez-Trufero, Javier</style></author><author><style face="normal" font="default" size="100%">Castilla-Ramirez, Carolina</style></author><author><style face="normal" font="default" size="100%">Gutierrez, Antonio</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Hindi, Nadia</style></author><author><style face="normal" font="default" size="100%">Garcia-Foncillas, Jesus</style></author><author><style face="normal" font="default" size="100%">Martin-Broto, Javier</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.</style></title><secondary-title><style face="normal" font="default" size="100%">Cell Mol Life Sci</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Cell Mol Life Sci</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antineoplastic Agents, Alkylating</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Resistance, Neoplasm</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation, Neoplastic</style></keyword><keyword><style  face="normal" font="default" size="100%">HMGA1a Protein</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Leiomyosarcoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Prognosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Sarcoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">TOR Serine-Threonine Kinases</style></keyword><keyword><style  face="normal" font="default" size="100%">Trabectedin</style></keyword><keyword><style  face="normal" font="default" size="100%">Xenograft Model Antitumor Assays</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024 May 17</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">81</style></volume><pages><style face="normal" font="default" size="100%">219</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Moura, David S</style></author><author><style face="normal" font="default" size="100%">Peña-Chilet, Maria</style></author><author><style face="normal" font="default" size="100%">Cordero Varela, Juan Antonio</style></author><author><style face="normal" font="default" size="100%">Alvarez-Alegret, Ramiro</style></author><author><style face="normal" font="default" size="100%">Agra-Pujol, Carolina</style></author><author><style face="normal" font="default" size="100%">Izquierdo, Francisco</style></author><author><style face="normal" font="default" size="100%">Ramos, Rafael</style></author><author><style face="normal" font="default" size="100%">Ortega-Medina, Luis</style></author><author><style face="normal" font="default" size="100%">Martin-Davila, Francisco</style></author><author><style face="normal" font="default" size="100%">Castilla-Ramirez, Carolina</style></author><author><style face="normal" font="default" size="100%">Hernandez-Leon, Carmen Nieves</style></author><author><style face="normal" font="default" size="100%">Romagosa, Cleofe</style></author><author><style face="normal" font="default" size="100%">Vaz Salgado, Maria Angeles</style></author><author><style face="normal" font="default" size="100%">Lavernia, Javier</style></author><author><style face="normal" font="default" size="100%">Bagué, Silvia</style></author><author><style face="normal" font="default" size="100%">Mayodormo-Aranda, Empar</style></author><author><style face="normal" font="default" size="100%">Vicioso, Luis</style></author><author><style face="normal" font="default" size="100%">Hernández Barceló, Jose Emilio</style></author><author><style face="normal" font="default" size="100%">Rubio-Casadevall, Jordi</style></author><author><style face="normal" font="default" size="100%">de Juan, Ana</style></author><author><style face="normal" font="default" size="100%">Fiaño-Valverde, Maria Concepcion</style></author><author><style face="normal" font="default" size="100%">Hindi, Nadia</style></author><author><style face="normal" font="default" size="100%">Lopez-Alvarez, Maria</style></author><author><style face="normal" font="default" size="100%">Lacerenza, Serena</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Gutierrez, Antonio</style></author><author><style face="normal" font="default" size="100%">Alvarez, Rosa</style></author><author><style face="normal" font="default" size="100%">Valverde, Claudia</style></author><author><style face="normal" font="default" size="100%">Martinez-Trufero, Javier</style></author><author><style face="normal" font="default" size="100%">Martin-Broto, Javier</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin.</style></title><secondary-title><style face="normal" font="default" size="100%">Mol Oncol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Mol Oncol</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2021 12</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">15</style></volume><pages><style face="normal" font="default" size="100%">3691-3705</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Predictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">12</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/33983674?dopt=Abstract</style></custom1></record></records></xml>