<?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%">Martin-Broto, Javier</style></author><author><style face="normal" font="default" size="100%">Cruz, Josefina</style></author><author><style face="normal" font="default" size="100%">Penel, Nicolas</style></author><author><style face="normal" font="default" size="100%">Le Cesne, Axel</style></author><author><style face="normal" font="default" size="100%">Hindi, Nadia</style></author><author><style face="normal" font="default" size="100%">Luna, Pablo</style></author><author><style face="normal" font="default" size="100%">Moura, David S</style></author><author><style face="normal" font="default" size="100%">Bernabeu, Daniel</style></author><author><style face="normal" font="default" size="100%">de Alava, Enrique</style></author><author><style face="normal" font="default" size="100%">Lopez-Guerrero, Jose Antonio</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Peña-Chilet, Maria</style></author><author><style face="normal" font="default" size="100%">Gutierrez, Antonio</style></author><author><style face="normal" font="default" size="100%">Collini, Paola</style></author><author><style face="normal" font="default" size="100%">Karanian, Marie</style></author><author><style face="normal" font="default" size="100%">Redondo, Andres</style></author><author><style face="normal" font="default" size="100%">Lopez-Pousa, Antonio</style></author><author><style face="normal" font="default" size="100%">Grignani, Giovanni</style></author><author><style face="normal" font="default" size="100%">Diaz-Martin, Juan</style></author><author><style face="normal" font="default" size="100%">Marcilla, David</style></author><author><style face="normal" font="default" size="100%">Fernandez-Serra, Antonio</style></author><author><style face="normal" font="default" size="100%">Gonzalez-Aguilera, Cristina</style></author><author><style face="normal" font="default" size="100%">Casali, Paolo G</style></author><author><style face="normal" font="default" size="100%">Blay, Jean-Yves</style></author><author><style face="normal" font="default" size="100%">Stacchiotti, Silvia</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial.</style></title><secondary-title><style face="normal" font="default" size="100%">Lancet Oncol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Lancet Oncol</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Follow-Up Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Indazoles</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Neoplasm Metastasis</style></keyword><keyword><style  face="normal" font="default" size="100%">Prognosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Prospective Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Kinase Inhibitors</style></keyword><keyword><style  face="normal" font="default" size="100%">Pyrimidines</style></keyword><keyword><style  face="normal" font="default" size="100%">Response Evaluation Criteria in Solid Tumors</style></keyword><keyword><style  face="normal" font="default" size="100%">Solitary Fibrous Tumors</style></keyword><keyword><style  face="normal" font="default" size="100%">Sulfonamides</style></keyword><keyword><style  face="normal" font="default" size="100%">Survival Rate</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 03</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">21</style></volume><pages><style face="normal" font="default" size="100%">456-466</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Solitary fibrous tumour is an ultra-rare sarcoma, which encompasses different clinicopathological subgroups. The dedifferentiated subgroup shows an aggressive course with resistance to pazopanib, whereas in the malignant subgroup, pazopanib shows higher activity than in previous studies with chemotherapy. We designed a trial to test pazopanib activity in two different cohorts of solitary fibrous tumour: the malignant-dedifferentiated cohort, which was previously published, and the typical cohort, which is presented here.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;In this single-arm, phase 2 trial, adult patients (aged ≥18 years) diagnosed with confirmed metastatic or unresectable typical solitary fibrous tumour of any location, who had progressed in the previous 6 months (by Choi criteria or Response Evaluation Criteria in Solid Tumors [RECIST]) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were enrolled at 11 tertiary hospitals in Italy, France, and Spain. Patients received pazopanib 800 mg once daily, taken orally, until progression, unacceptable toxicity, withdrawal of consent, non-compliance, or a delay in pazopanib administration of longer than 3 weeks. The primary endpoint was proportion of patients achieving an overall response measured by Choi criteria in patients who received at least 1 month of treatment with at least one radiological assessment. All patients who received at least one dose of the study drug were included in the safety analyses. This study is registered in ClinicalTrials.gov, NCT02066285, and with the European Clinical Trials Database, EudraCT 2013-005456-15.&lt;/p&gt;&lt;p&gt;&lt;b&gt;FINDINGS: &lt;/b&gt;From June 26, 2014, to Dec 13, 2018, of 40 patients who were assessed, 34 patients were enrolled and 31 patients were included in the response analysis. Median follow-up was 18 months (IQR 14-34), and 18 (58%) of 31 patients had a partial response, 12 (39%) had stable disease, and one (3%) showed progressive disease according to Choi criteria and central review. The proportion of overall response based on Choi criteria was 58% (95% CI 34-69). There were no deaths caused by toxicity, and the most frequent adverse events were diarrhoea (18 [53%] of 34 patients), fatigue (17 [50%]), and hypertension (17 [50%]).&lt;/p&gt;&lt;p&gt;&lt;b&gt;INTERPRETATION: &lt;/b&gt;To our knowledge, this is the first prospective trial of pazopanib for advanced typical solitary fibrous tumour. The manageable toxicity and activity shown by pazopanib in this cohort suggest that this drug could be considered as first-line treatment for advanced typical solitary fibrous tumour.&lt;/p&gt;&lt;p&gt;&lt;b&gt;FUNDING: &lt;/b&gt;Spanish Group for Research on Sarcomas (GEIS), Italian Sarcoma Group (ISG), French Sarcoma Group (FSG), GlaxoSmithKline, and Novartis.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/32066540?dopt=Abstract</style></custom1></record></records></xml>