ORCID Profile
0000-0002-3856-9177
Current Organisation
Vall d´Hebron Institut d´Oncologia
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Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540537
Abstract: Key Resources Tables
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540516
Abstract: Supplementary Figure 6
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540522.V1
Abstract: Supplementary Figure 4
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540519
Abstract: Supplementary Figure 5
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540531
Abstract: Supplementary Figure 2
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540510
Abstract: Supplementary Tables
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540513
Abstract: Supplementary Figure 7
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.C.6549400.V1
Abstract: Abstract Mutations in i ARID1A /i rank among the most common molecular aberrations in human cancer. However, oncogenic consequences of i ARID1A /i mutation in human cells remain poorly defined due to lack of forward genetic models. Here, CRISPR/Cas9-mediated i ARID1A /i knockout (KO) in primary i TP53 sup −/− /sup /i human gastric organoids induced morphologic dysplasia, tumorigenicity, and mucinous differentiation. Genetic WNT/β-catenin activation rescued mucinous differentiation, but not hyperproliferation, suggesting alternative pathways of i ARID1A /i KO-mediated transformation. i ARID1A /i mutation induced transcriptional regulatory modules characteristic of microsatellite instability and Epstein–Barr virus–associated subtype human gastric cancer, including i FOXM1 /i -associated mitotic genes and i BIRC5/ /i survivin. Convergently, high-throughput compound screening indicated selective vulnerability of i ARID1A /i -deficient organoids to inhibition of BIRC5/survivin, functionally implicating this pathway as an essential mediator of i ARID1A /i KO-dependent early-stage gastric tumorigenesis. Overall, we define distinct pathways downstream of oncogenic i ARID1A /i mutation, with nonessential WNT-inhibited mucinous differentiation in parallel with essential transcriptional i FOXM1/BIRC5 /i -stimulated proliferation, illustrating the general utility of organoid-based forward genetic cancer analysis in human cells. Significance: We establish the first human forward genetic modeling of a commonly mutated tumor suppressor gene, i ARID1A /i . Our study integrates erse modalities including CRISPR/Cas9 genome editing, organoid culture, systems biology, and small-molecule screening to derive novel insights into early transformation mechanisms of i ARID1A /i -deficient gastric cancers. i See related commentary by Zafra and Dow, p. 1327 /i . i This article is highlighted in the In This Issue feature, p. 1307 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540534
Abstract: Supplementary Figure 1
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540510.V1
Abstract: Supplementary Tables
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540531.V1
Abstract: Supplementary Figure 2
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540537.V1
Abstract: Key Resources Tables
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540516.V1
Abstract: Supplementary Figure 6
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540519.V1
Abstract: Supplementary Figure 5
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.C.6549400
Abstract: Abstract Mutations in i ARID1A /i rank among the most common molecular aberrations in human cancer. However, oncogenic consequences of i ARID1A /i mutation in human cells remain poorly defined due to lack of forward genetic models. Here, CRISPR/Cas9-mediated i ARID1A /i knockout (KO) in primary i TP53 sup −/− /sup /i human gastric organoids induced morphologic dysplasia, tumorigenicity, and mucinous differentiation. Genetic WNT/β-catenin activation rescued mucinous differentiation, but not hyperproliferation, suggesting alternative pathways of i ARID1A /i KO-mediated transformation. i ARID1A /i mutation induced transcriptional regulatory modules characteristic of microsatellite instability and Epstein–Barr virus–associated subtype human gastric cancer, including i FOXM1 /i -associated mitotic genes and i BIRC5/ /i survivin. Convergently, high-throughput compound screening indicated selective vulnerability of i ARID1A /i -deficient organoids to inhibition of BIRC5/survivin, functionally implicating this pathway as an essential mediator of i ARID1A /i KO-dependent early-stage gastric tumorigenesis. Overall, we define distinct pathways downstream of oncogenic i ARID1A /i mutation, with nonessential WNT-inhibited mucinous differentiation in parallel with essential transcriptional i FOXM1/BIRC5 /i -stimulated proliferation, illustrating the general utility of organoid-based forward genetic cancer analysis in human cells. Significance: We establish the first human forward genetic modeling of a commonly mutated tumor suppressor gene, i ARID1A /i . Our study integrates erse modalities including CRISPR/Cas9 genome editing, organoid culture, systems biology, and small-molecule screening to derive novel insights into early transformation mechanisms of i ARID1A /i -deficient gastric cancers. i See related commentary by Zafra and Dow, p. 1327 /i . i This article is highlighted in the In This Issue feature, p. 1307 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 15-01-2021
DOI: 10.1158/2159-8290.CD-20-1109
Abstract: We establish the first human forward genetic modeling of a commonly mutated tumor suppressor gene, ARID1A. Our study integrates erse modalities including CRISPR/Cas9 genome editing, organoid culture, systems biology, and small-molecule screening to derive novel insights into early transformation mechanisms of ARID1A-deficient gastric cancers. See related commentary by Zafra and Dow, p. 1327. This article is highlighted in the In This Issue feature, p. 1307
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.JINF.2010.11.003
Abstract: To develop an artificial neural network to predict significant fibrosis (F≥2) (ANN-SF) in HIV/Hepatitis C (HCV) coinfected patients using clinical data derived from peripheral blood. Patients were randomly ided into an estimation group (217 cases) used to generate the ANN and a test group (145 cases) used to confirm its power to predict F≥2. Liver fibrosis was estimated according to the METAVIR score. The values of the area under the receiver operating characteristic curve (AUC-ROC) of the ANN-SF were 0.868 in the estimation set and 0.846 in the test set. In the estimation set, with a cut-off value of 0.75 to predict the presence of F≥2, the ANN-SF provided Se, Sp, PPV and NPV of 53.8%, 94.9%, 92.8% and 62.8% respectively. In the test set, with a cut-off value of 0.75 to predict the presence of F≥2, the ANN-SF provided Se, Sp, PPV and NPV of 43.5%, 96.7%, 94.9% and 54.7% respectively. The ANN-SF accurately predicted significant fibrosis and outperformed other simple non-invasive indices for HIV/HCV coinfected patients. Our data suggest that ANN may be a helpful tool for guiding therapeutic decisions in clinical practice concerning HIV/HCV coinfection.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540525.V1
Abstract: Supplementary Figure 3
Publisher: Bentham Science Publishers Ltd.
Date: 04-2013
DOI: 10.2174/1568026611313050004
Abstract: Advances done in "-Omics" technologies in the last 20 years have made available to the researches huge amounts of data spanning a wide variety of biological processes from gene sequences to the metabolites present in a cell at a particular time. The management, analysis and representation of these data have been facilitated by mean of the advances made by biomedical informatics in areas such as data architecture and integration systems. However, despite the efforts done by biologists in this area, research in drug design adds a new level of information by incorporating data related with small molecules, which increases the complexity of these integration systems. Current knowledge in molecular biology has shown that it is possible to use comprehensive and integrative approaches to understand the biological processes from a systems perspective and that pathological processes can be mapped into biological networks. Therefore, current strategies for drug design are focusing on how to interact with or modify those networks to achieve the desired effects on what is called systems chemical biology. In this review several approaches for data integration in systems chemical biology will be analysed and described. Furthermore, because of the increasing relevance of the development and use of nanomaterials and their expected impact in the near future, the requirements of integration systems that incorporate these new data types associated with nanomaterials will also be analysed.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540525
Abstract: Supplementary Figure 3
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540522
Abstract: Supplementary Figure 4
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540534.V1
Abstract: Supplementary Figure 1
Publisher: American Association for the Advancement of Science (AAAS)
Date: 26-10-2018
Abstract: The Cancer Genome Atlas (TCGA) provides a high-quality resource of molecular data on a large variety of human cancers. Corces et al. used a recently modified assay to profile chromatin accessibility to determine the accessible chromatin landscape in 410 TCGA s les from 23 cancer types (see the Perspective by Taipale). When the data were integrated with other omics data available for the same tumor s les, inherited risk loci for cancer predisposition were revealed, transcription factors and enhancers driving molecular subtypes of cancer with patient survival differences were identified, and noncoding mutations associated with clinical prognosis were discovered. Science , this issue p. eaav1898 see also p. 401
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540513.V1
Abstract: Supplementary Figure 7
Publisher: Springer Science and Business Media LLC
Date: 17-06-2019
DOI: 10.1038/S41467-019-09799-2
Abstract: The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for % of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
Publisher: Elsevier BV
Date: 04-2018
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jose A. Seoane.