<?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%">López López, Daniel</style></author><author><style face="normal" font="default" size="100%">di Lernia, Davide</style></author><author><style face="normal" font="default" size="100%">Martin-Ruiz, Marta</style></author><author><style face="normal" font="default" size="100%">Lopez-Alvarez, Maria</style></author><author><style face="normal" font="default" size="100%">Ramos, Rafael</style></author><author><style face="normal" font="default" size="100%">Merino, Jose</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Lopez-Guerrero, Jose</style></author><author><style face="normal" font="default" size="100%">Mondaza-Hernandez, Jose L</style></author><author><style face="normal" font="default" size="100%">Romero, Pablo</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%">Shared germline genomic variants in two patients with double primary gastrointestinal stromal tumours (GISTs).</style></title><secondary-title><style face="normal" font="default" size="100%">J Med Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J Med Genet</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">DNA Copy Number Variations</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gastrointestinal Neoplasms</style></keyword><keyword><style  face="normal" font="default" size="100%">Gastrointestinal Stromal Tumors</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Germ-Line Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</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%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Proto-Oncogene Proteins c-kit</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptor, Platelet-Derived Growth Factor alpha</style></keyword><keyword><style  face="normal" font="default" size="100%">Whole Genome Sequencing</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 Sep 24</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">61</style></volume><pages><style face="normal" font="default" size="100%">927-934</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;Gastrointestinal stromal tumours (GISTs) are prevalent mesenchymal tumours of the gastrointestinal tract, commonly exhibiting structural variations in  and  genes. While the mutational profiling of somatic tumours is well described, the genes behind the susceptibility to develop GIST are not yet fully discovered. This study explores the genomic landscape of two primary GIST cases, aiming to identify shared germline pathogenic variants and shed light on potential key players in tumourigenesis.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Two patients with distinct genotypically and phenotypically GISTs underwent germline whole genome sequencing. CNV and single nucleotide variant (SNV) analyses were performed.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Both patients harbouring low-risk GISTs with different mutations ( and ) shared homozygous germline pathogenic deletions in both  and  genes. CNV analysis revealed additional shared pathogenic deletions in other genes such as . No particular pathogenic SNV shared by both patients was detected.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;Our study provides new insights into germline variants that can be associated with the development of GISTs, namely,  and  deep deletions. Further functional validation is warranted to elucidate the precise contributions of identified germline mutations in GIST development.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">10</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><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%">Hindi, Nadia</style></author><author><style face="normal" font="default" size="100%">Grignani, Giovanni</style></author><author><style face="normal" font="default" size="100%">Martinez-Trufero, Javier</style></author><author><style face="normal" font="default" size="100%">Redondo, Andres</style></author><author><style face="normal" font="default" size="100%">Valverde, Claudia</style></author><author><style face="normal" font="default" size="100%">Stacchiotti, Silvia</style></author><author><style face="normal" font="default" size="100%">Lopez-Pousa, Antonio</style></author><author><style face="normal" font="default" size="100%">D'Ambrosio, Lorenzo</style></author><author><style face="normal" font="default" size="100%">Gutierrez, Antonio</style></author><author><style face="normal" font="default" size="100%">Perez-Vega, Herminia</style></author><author><style face="normal" font="default" size="100%">Encinas-Tobajas, Victor</style></author><author><style face="normal" font="default" size="100%">de Alava, Enrique</style></author><author><style face="normal" font="default" size="100%">Collini, Paola</style></author><author><style face="normal" font="default" size="100%">Peña-Chilet, Maria</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Carrasco-Garcia, Irene</style></author><author><style face="normal" font="default" size="100%">Lopez-Alvarez, Maria</style></author><author><style face="normal" font="default" size="100%">Moura, David S</style></author><author><style face="normal" font="default" size="100%">Lopez-Martin, Jose A</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial.</style></title><secondary-title><style face="normal" font="default" size="100%">J Immunother Cancer</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J Immunother Cancer</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Antineoplastic Agents, Immunological</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</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%">Nivolumab</style></keyword><keyword><style  face="normal" font="default" size="100%">Sarcoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Sunitinib</style></keyword><keyword><style  face="normal" font="default" size="100%">Young Adult</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 11</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">8</style></volume><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;Sarcomas exhibit low expression of factors related to immune response, which could explain the modest activity of PD-1 inhibitors. A potential strategy to convert a cold into an inflamed microenvironment lies on a combination therapy. As tumor angiogenesis promotes immunosuppression, we designed a phase Ib/II trial to test the double inhibition of angiogenesis (sunitinib) and PD-1/PD-L1 axis (nivolumab).&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;This single-arm, phase Ib/II trial enrolled adult patients with selected subtypes of sarcoma. Phase Ib established two dose levels: level 0 with sunitinib 37.5 mg daily from day 1, plus nivolumab 3 mg/kg intravenously on day 15, and then every 2 weeks; and level -1 with sunitinib 37.5 mg on the first 14 days (induction) and then 25 mg per day plus nivolumab on the same schedule. The primary endpoint was to determine the recommended dose for phase II (phase I) and the 6-month progression-free survival rate, according to Response Evaluation Criteria in Solid Tumors 1.1 (phase II).&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;From May 2017 to April 2019, 68 patients were enrolled: 16 in phase Ib and 52 in phase II. The recommended dose of sunitinib for phase II was 37.5 mg as induction and then 25 mg in combination with nivolumab. After a median follow-up of 17 months (4-26), the 6-month progression-free survival rate was 48% (95% CI 41% to 55%). The most common grade 3-4 adverse events included transaminitis (17.3%) and neutropenia (11.5%).&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Sunitinib plus nivolumab is an active scheme with manageable toxicity in the treatment of selected patients with advanced soft tissue sarcoma, with almost half of patients free of progression at 6 months. NCT03277924.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/33203665?dopt=Abstract</style></custom1></record></records></xml>