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1,151 results on '"Velasco, Guillermo"'

1. Retrospective study assessing the role of the androgen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy

Author

Osorio, Lucia, Grazioso, Tatiana P., de Velasco, Guillermo, Etxaniz, Olatz, Pérez-Gracia, Jose Luis, Pinto, Álvaro, Durán, Ignacio, Grande, Enrique, Garcia, Pablo Borrega, Lázaro, Martín, Rodriguez, Laura, Villalobos, Maria Laura, García, Lourdes, Cuellar, Andrés, Solís-Hernández, María Pilar, Pernaut, Cristina, Rodríguez-Moreno, Juan Francisco, Rodriguez-Antona, Cristina, and García-Donas, Jesús

Published
2024
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2. Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors.

Author

El Zarif, Talal, Nassar, Amin, Pond, Gregory, Zhuang, Tony, Master, Viraj, Nazha, Bassel, Niglio, Scot, Simon, Nicholas, Hahn, Andrew, Pettaway, Curtis, Tu, Shi-Ming, Abdel-Wahab, Noha, Velev, Maud, Flippot, Ronan, Buti, Sebastiano, Maruzzo, Marco, Mittra, Arjun, Gheeya, Jinesh, Yang, Yuanquan, Rodriguez, Pablo, Castellano, Daniel, de Velasco, Guillermo, Roviello, Giandomenico, Antonuzzo, Lorenzo, McKay, Rana, Vincenzi, Bruno, Cortellini, Alessio, Hui, Gavin, Drakaki, Alexandra, Glover, Michael, Khaki, Ali, El-Am, Edward, Adra, Nabil, Mouhieddine, Tarek, Patel, Vaibhav, Piedra, Aida, Gernone, Angela, Davis, Nancy, Matthews, Harrison, Harrison, Michael, Kanesvaran, Ravindran, Giudice, Giulia, Barata, Pedro, Farolfi, Alberto, Lee, Jae, Milowsky, Matthew, Stahlfeld, Charlotte, Appleman, Leonard, Kim, Joseph, Freeman, Dory, Choueiri, Toni, Spiess, Philippe, Necchi, Andrea, Apolo, Andrea, and Sonpavde, Guru

Subjects
Male, Humans, Middle Aged, Aged, Nivolumab, Immune Checkpoint Inhibitors, Penile Neoplasms, Antineoplastic Agents, Immunological, Retrospective Studies, Carcinoma, Squamous Cell, Antineoplastic Combined Chemotherapy Protocols
Abstract

BACKGROUND: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors. METHODS: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons. RESULTS: Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher. CONCLUSIONS: Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.

Published
2023

4. Case–control study assessing the impact of COVID19 in advanced kidney cancer patients treated with antiangiogenics or immunotherapy: the COVID-REN study

Author

García-Donas, Jesús, de Velasco, Guillermo, Madurga, Rodrigo, Chamorro, Jesús, Rosero, Diana, Etxaniz, Olatz, Pérez-Gracia, Jose Luis, Pinto, Álvaro, Cacho, Diego, Barba, María, Borrega, Pablo, Lázaro, Martín, Rodriguez, Laura, Villalobos, Laura, García, Lourdes, Cuellar, Andrés, Solís-Hernández, María Pilar, González, Amalia, Pernaut, Cristina, and Rodríguez-Moreno, Juan Francisco

Published
2024
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8. Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study

Author

Romero-Laorden, Nuria, Lorente, David, de Velasco, Guillermo, Lozano, Rebeca, Herrera, Bernardo, Puente, Javier, López, Pedro P., Medina, Ana, Almagro, Elena, Gonzalez-Billalabeitia, Enrique, Villla-Guzman, Jose Carlos, González-del-Alba, Aránzazu, Borrega, Pablo, Laínez, Nuria, Fernández-Freire, Ana, Hernández, Amaia, Rodriguez-Vida, Alejo, Chirivella, Isabel, Fernandez-Parra, Eva, López-Campos, Fernando, Isabel Pacheco, Maria, Morales-Barrera, Rafael, Fernández, Ovidio, Villatoro, Rosa, Luque, Raquel, Hernando, Susana, Castellano, Daniel C., Castro, Elena, and Olmos, David

Published
2024
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12. Tailored immunotherapy approach with nivolumab with or without nivolumab plus ipilimumab as immunotherapeutic boost in patients with metastatic renal cell carcinoma (TITAN-RCC): a multicentre, single-arm, phase 2 trial

Author

Barone, Carlo, Castellano, Daniel, Chevreau, Christine, Gajate Borau, Pablo, Gopalakrishnan, Srinavasan, Grande, Enrique, Hamid, Abdel, Heinzelbecker, Julia, Janssen, Martin, Kopecký, Jindřich, Kubala, Eugen, Loidl, Wolfgang, Lorch, Anja, Melichar, Bohuslav, Lainez Milagro, Nuria, Niegisch, Günter, Ohlmann, Carsten, Sacré, Anne, Sarwar, Naveed, Schinzari, Giovanni, Schrijvers, Dirk, Tartas, Sophie, Wirth, Manfred, Wolter, Pascal, Zemanova, Milanda, Grimm, Marc-Oliver, Esteban, Emilio, Barthélémy, Philippe, Schmidinger, Manuela, Busch, Jonas, Valderrama, Begoña P, Charnley, Natalie, Schmitz, Marc, Schumacher, Ulrike, Leucht, Katharina, Foller, Susan, Baretton, Gustavo, Duran, Ignacio, de Velasco, Guillermo, Priou, Frank, Maroto, Pablo, and Albiges, Laurence

Published
2023
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13. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial

Author

Pal, Sumanta Kumar, Albiges, Laurence, Tomczak, Piotr, Suárez, Cristina, Voss, Martin H, de Velasco, Guillermo, Chahoud, Jad, Mochalova, Anastasia, Procopio, Giuseppe, Mahammedi, Hakim, Zengerling, Friedemann, Kim, Chan, Osawa, Takahiro, Angel, Martín, Gupta, Suyasha, Khan, Omara, Bergthold, Guillaume, Liu, Bo, Kalaitzidou, Melania, Huseni, Mahrukh, Scheffold, Christian, Powles, Thomas, and Choueiri, Toni K

Published
2023
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14. Long-term Clinical Outcomes of a Spanish Cohort of Metastatic Renal Cell Carcinoma Patients with a Complete Response to Sunitinib

Author

de Velasco, Guillermo, Alonso-Gordoa, Teresa, Rodríguez-Vida, Alejo, Anguera, Georgia, Campayo, Marc, Pinto, Álvaro, Ortega, Esther Martínez, Gallardo, Enrique, Núñez, Natalia Fernández, García-Carbonero, Iciar, Reig, Oscar, Méndez-Vidal, María José, Fernández-Calvo, Ovidio, Cassinello, Natalia Vidal, Torregrosa, Dolores, López-Martín, Ana, Rosero, Adriana, Valiente, Patricia G., de España, Carmen Garcías, Climent, Miguel A., Santasusana, Montserrat Domenech, Sánchez, Ángel Rodríguez, González, Isabel Chirivella, Afonso, Ruth, García del Muro, Xavier, Casinello, Javier, Fernández-Parra, Eva M., García Sánchez, Lourdes, Afonso, Javier, Polo, Susana Hernando, and Asensio, Úrsula

Published
2023
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15. Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status

Author

Carril-Ajuria, Lucía, Colomba, Emeline, Romero-Ferreiro, Carmen, Cerbone, Luigi, Ratta, Raffaele, Barthelemy, Philippe, Vindry, Clarisse, Fléchon, Aude, Cherifi, François, Boughalem, Elouen, Linassier, Claude, Fornarini, Giuseppe, Rebuzzi, Sara E., Gross-Goupil, Marine, Saldana, Carolina, Martin-Soberón, Maricruz, de Velasco, Guillermo, Manneh, Ray, Pernaut, Cristina, Sanchez de Torre, Ana, Flippot, Ronan, Escudier, Bernard, and Albiges, Laurence

Published
2023
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18. Systemic treatments in favorable and very favorable risk metastatic renal cell carcinoma (mRCC): Real world evidence from the International mRCC Database Consortium (IMDC).

Author

Zarba, Martin, primary, Ferrier, Evan, additional, Wells, Connor, additional, El Zarif, Talal, additional, Basappa, Naveen S., additional, Ebrahimi, Hedyeh, additional, McKay, Rana R., additional, Wood, Lori, additional, Beuselinck, Benoit, additional, Suárez, Cristina, additional, Takemura, Kosuke, additional, Lalani, Aly-Khan A., additional, Li, Haoran, additional, Spain, Lavinia Anne, additional, Templeton, Arnoud J., additional, Powles, Thomas, additional, Bjarnason, Georg A., additional, de Velasco, Guillermo, additional, CHOUEIRI, Toni K., additional, and Heng, Daniel Yick Chin, additional

Published
2024
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21. Cytotoxicity, Proapoptotic Activity and Drug-like Potential of Quercetin and Kaempferol in Glioblastoma Cells: Preclinical Insights.

Author

Kusaczuk, Magdalena, Tovar-Ambel, Elena, Martín-Cabrera, Paola, Lorente, Mar, Salvador-Tormo, Nélida, Mikłosz, Agnieszka, Chabowski, Adrian, Velasco, Guillermo, and Naumowicz, Monika

Subjects
CHORIOALLANTOIS, REACTIVE oxygen species, CYTOTOXINS, TUMOR growth, CENTRAL nervous system, QUERCETIN
Abstract

Despite the increasing understanding of the pathogenesis of glioblastoma (GBM), treatment options for this tumor remain limited. Recently, the therapeutic potential of natural compounds has attracted great interest. Thus, dietary flavonoids quercetin (QCT) and kaempferol (KMF) were investigated as potential cytostatic agents in GBM. Moreover, the physicochemical properties of QCT and KMF, determining their bioavailability and therapeutic efficiency, were evaluated. We proved that both polyphenols significantly reduced the viability of GBM cells. We also demonstrated that both QCT and KMF evoked the cytotoxic effect in T98G cells via induction of apoptotic cell death as shown by increased activity of caspase 3/7 and caspase 9 together with an overexpression of the cleaved form of PARP. Apoptosis was additionally accompanied by the activation of stress responses in QCT- and KMF-treated cells. Both polyphenols caused oxidative stress and endoplasmic reticulum (ER) stress, as demonstrated by the increased generation of reactive oxygen species (ROS), deregulated expressions of superoxide dismutases (SOD2 and Sod1 on protein and transcriptomic levels, respectively), as well as an overexpression of ERO1α, GRP78, p-JNK, and an up-regulation of Chop, Atf4 and Atf6α genes. The antitumor effect of QCT and KMF was also confirmed in vivo, showing reduced growth of tumor xenografts in the chick chorioallantoic membrane (CAM) experiment. Moreover, electrophoretic light scattering (ELS) was used to measure the zeta potential of cell membranes upon exposition to QCT and KMF. Additionally, on the basis of existing physicochemical data, the drug-likeness score of QCT and KMF was evaluated. Analyses showed that both compounds accomplish Lipinski's Rule of 5, and they both fit into the criteria of good central nervous system (CNS) drugs. Altogether, our data support the idea that QCT and KMF might be plausible candidates for evaluation as therapeutic agents in preclinical models of glioblastoma. [ABSTRACT FROM AUTHOR]

Published
2024
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22. A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily

Author

Korkut, Anil, Zaidi, Sobia, Kanchi, Rupa S, Rao, Shuyun, Gough, Nancy R, Schultz, Andre, Li, Xubin, Lorenzi, Philip L, Berger, Ashton C, Robertson, Gordon, Kwong, Lawrence N, Datto, Mike, Roszik, Jason, Ling, Shiyun, Ravikumar, Visweswaran, Manyam, Ganiraju, Rao, Arvind, Shelley, Simon, Liu, Yuexin, Ju, Zhenlin, Hansel, Donna, de Velasco, Guillermo, Pennathur, Arjun, Andersen, Jesper B, O'Rourke, Colm J, Ohshiro, Kazufumi, Jogunoori, Wilma, Nguyen, Bao-Ngoc, Li, Shulin, Osmanbeyoglu, Hatice U, Ajani, Jaffer A, Mani, Sendurai A, Houseman, Andres, Wiznerowicz, Maciej, Chen, Jian, Gu, Shoujun, Ma, Wencai, Zhang, Jiexin, Tong, Pan, Cherniack, Andrew D, Deng, Chuxia, Resar, Linda, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Li, Jun, Liang, Han, Liu, Wenbin, and Lu, Yiling

Subjects
Biological Sciences, Genetics, Cancer, Biotechnology, Human Genome, Cancer Genomics, 2.1 Biological and endogenous factors, Bone Morphogenetic Protein 5, DNA Methylation, Humans, MicroRNAs, Mutation Rate, Neoplasms, Receptor, Transforming Growth Factor-beta Type I, Signal Transduction, Smad Proteins, Transforming Growth Factor beta, Cancer Genome Atlas Research Network, DNA methylation, Pan-Cancer, TCGA, TGF-β, TGF-β pathway, The Cancer Genome Atlas, cancer, microRNA, mutation hotspot, transcription, Biochemistry and Cell Biology, Biochemistry and cell biology
Abstract

We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-β ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-β superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-β signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-β superfamily.

Published
2018

26. Clinical Effectiveness of Second-line Sunitinib Following Immuno-oncology Therapy in Patients with Metastatic Renal Cell Carcinoma: A Real-world Study

Author

Wells, J. Connor, Dudani, Shaan, Gan, Chun Loo, Stukalin, Igor, Azad, Arun A., Liow, Elizabeth, Donskov, Frede, Yuasa, Takeshi, Pal, Sumanta K., De Velasco, Guillermo, Hansen, Aaron R., Beuselinck, Benoit, Kollmannsberger, Christian K., Powles, Thomas, McGregor, Bradley A., Duh, Mei S., Huynh, Lynn, and Heng, Daniel Y.C.

Published
2021
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27. Efficacy of immune-checkpoint inhibitors (ICI) in the treatment of older adults with metastatic renal cell carcinoma (mRCC) – an International mRCC Database Consortium (IMDC) analysis

Author

Araujo, Daniel V., Wells, J. Connor, Hansen, Aaron R., Dizman, Nazli, Pal, Sumanta K., Beuselinck, Benoit, Donskov, Frede, Gan, Chun L., Yan, Flora, Tran, Ben, Kollmannsberger, Christian K., de Velasco, Guillermo, Yuasa, Takeshi, Reaume, M. Neil, Ernst, D. Scott, Powles, Thomas, Bjarnason, Georg A., Choueiri, Toni K., Heng, Daniel Y.C., and Dudani, Shaan

Published
2021
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29. Outcomes of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy After Immuno-oncology Checkpoint Inhibitors

Author

Graham, Jeffrey, Shah, Amishi Y., Wells, J. Connor, McKay, Rana R., Vaishampayan, Ulka, Hansen, Aaron, Donskov, Frede, Bjarnason, Georg A., Beuselinck, Benoit, De Velasco, Guillermo, Iafolla, Marco, Duh, Mei S., Huynh, Lynn, Chang, Rose, Zanotti, Giovanni, Ramaswamy, Krishnan, Choueiri, Toni K., Tannir, Nizar M., and Heng, Daniel Y.C.

Published
2021
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30. Loss of Tribbles pseudokinase-3 promotes Akt-driven tumorigenesis via FOXO inactivation

Author

Velasco, Guillermo, Salazar Roa, María, Lorente, M, Garcia-Taboada, E, Perez Gomez, E, Davila, D, Zuñiga, P, Flores Landeira, Juana María, Rodriguez, A, Hegedus, Z, Mosen-Ansorena, D, Aransay, AM, Hernandez-Tiedra, S, Lopez-Valero, I, Quintanilla, M, Sanchez, C, Iovanna, JL, Dusetti, N, Guzman, M, Francis, SE, Carracedo, A, Kiss-Toth, E, Velasco, G, Pérez Gómez, Eduardo, Velasco, Guillermo, Salazar Roa, María, Lorente, M, Garcia-Taboada, E, Perez Gomez, E, Davila, D, Zuñiga, P, Flores Landeira, Juana María, Rodriguez, A, Hegedus, Z, Mosen-Ansorena, D, Aransay, AM, Hernandez-Tiedra, S, Lopez-Valero, I, Quintanilla, M, Sanchez, C, Iovanna, JL, Dusetti, N, Guzman, M, Francis, SE, Carracedo, A, Kiss-Toth, E, Velasco, G, and Pérez Gómez, Eduardo

Abstract

This work was supported by grants from Spanish Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) (PS09/01401; PI12/02248, FR2009-0052 and IT2009-0053toGV), Comunidad de Madrid (S2011/BMD-2308toMG), Fundacion Mutua Madrilena (AP101042012 to GV) and Breast Cancer Campaign (2012NovSP033 to EKT and GV). Purchase of the TRIB3-deficient mice (LEXKO-1947) linewas fundedby theWellcomeTrust., Tribbles pseudokinase-3 (TRIB3) has been proposed to act as an inhibitor of AKT although the precise molecular basis of this activity and whether the loss of TRIB3 contributes to cancer initiation and progression remain to be clarified. In this study, by using a wide array of in vitro and in vivo approaches, including a Trib3 knockout mouse, we demonstrate that TRIB3 has a tumor- suppressing role. We also find that the mechanism by which TRIB3 loss enhances tumorigenesis relies on the dysregulation of the phosphorylation of AKT by the mTORC2 complex, which leads to an enhanced phosphorylation of AKT on Ser473 and the subsequent hyperphosphorylation and inactivation of the transcription factor FOXO3. These observations support the notion that loss of TRIB3 is associated with a more aggressive phenotype in various types of tumors by enhancing the activity of the mTORC2/AKT/FOXO axis, Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Químicas, TRUE, pub

Published
2024
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31. AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest

Author

Domenech, Elena, Maestre, Carolina, Esteban-Martínez, Lorena, Partida, David, Pascual, Rosa, Fernández-Miranda, Gonzalo, Seco, Esther, Campos-Olivas, Ramón, Pérez, Manuel, Megias, Diego, Allen, Katherine, Lopez, Miguel, K. Saha, Asish, Velasco, Guillermo, Rial, Eduardo, Mendez, Raúl, Boya, Patricia, Salazar Roa, María, Malumbres, Marcos, Domenech, Elena, Maestre, Carolina, Esteban-Martínez, Lorena, Partida, David, Pascual, Rosa, Fernández-Miranda, Gonzalo, Seco, Esther, Campos-Olivas, Ramón, Pérez, Manuel, Megias, Diego, Allen, Katherine, Lopez, Miguel, K. Saha, Asish, Velasco, Guillermo, Rial, Eduardo, Mendez, Raúl, Boya, Patricia, Salazar Roa, María, and Malumbres, Marcos

Abstract

E.D., C.M. and M.S.-R. were supported by the Spanish Fondo de Investigaciones Sanitarias (Madrid), MINECO (Juan de la Cierva programme) and Asociación Española contra el Cáncer (AECC), respectively. L.E.-M. is a recipient of a JAE predoctoral fellowship from the CSIC. A.K.S. was supported by USPHS grants RO1DK19514, RO1DK67509. G.V. was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) (PI12/02248), Fundació La Marató de TV3 (m12 20134031), and Fundación Mutua Madrileña (AP101042012). M.L. was supported by the European Community’s Seventh Framework Programme under grant agreement no. 281854—the ObERStress (European Research Council project). E.R. was financially supported by a MINECO grant (SAF 2010-20256). Work in the R.M. laboratory was supported by the Fundación Botín, Banco Santander and MINECO (BFU2011-30121, BFU2014-52125-REDT and Consolider RNAREG CSD2009-00080). Work in the P.B. laboratory is supported by a grant from the Spanish Ministry for Economy and Competitiveness (MINECO; SAF2012-36079). Work in the M.M. laboratory was supported by grants from the MINECO (SAF2012-38215), Consolider-Ingenio 2010 Programme (SAF2014-57791-REDC), Excellence Network CellSYS (BFU2014-52125-REDT), the OncoCycle Programme (S2010/BMD-2470) from the Comunidad de Madrid, Worldwide Cancer Research (WCR no. 15-0278), and the European Union Seventh Framework Programme (MitoSys project; HEALTH-F5-2010-241548)., Blocking mitotic progression has been proposed as an attractive therapeutic strategy to impair proliferation of tumour cells. However, how cells survive during prolonged mitotic arrest is not well understood. We show here that survival during mitotic arrest is affected by the special energetic requirements of mitotic cells. Prolonged mitotic arrest results in mitophagy-dependent loss of mitochondria, accompanied by reduced ATP levels and the activation of AMPK. Oxidative respiration is replaced by glycolysis owing to AMPK-dependent phosphorylation of PFKFB3 and increased production of this protein as a consequence of mitotic-specific translational activation of its mRNA. Induction of autophagy or inhibition of AMPK or PFKFB3 results in enhanced cell death in mitosis and improves the anti-tumoral efficiency of microtubule poisons in breast cancer cells. Thus, survival of mitotic-arrested cells is limited by their metabolic requirements, a feature with potential implications in cancer therapies aimed to impair mitosis or metabolism in tumour cells., Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Biológicas, TRUE, pub

Published
2024

32. Molecular characterization of chromophobe renal cell carcinoma reveals mTOR pathway alterations in patients with poor outcome

Author

Roldan-Romero, Juan María, Santos, María, Lanillos, Javier, Caleiras, Eduardo, Anguera, Georgia, Maroto, Pablo, García-Donas, Jesús, de Velasco, Guillermo, Martinez-Montes, Ángel Mario, Calsina, Bruna, Monteagudo, María, Letón, Rocío, Leandro-García, Luis Javier, Montero-Conde, Cristina, Cascón, Alberto, Robledo, Mercedes, and Rodriguez-Antona, Cristina

Published
2020
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33. AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity

Author

Maiani, Emiliano, Milletti, Giacomo, Nazio, Francesca, Holdgaard, Søs Grønbæk, Bartkova, Jirina, Rizza, Salvatore, Cianfanelli, Valentina, Lorente, Mar, Simoneschi, Daniele, Di Marco, Miriam, D’Acunzo, Pasquale, Di Leo, Luca, Rasmussen, Rikke, Montagna, Costanza, Raciti, Marilena, De Stefanis, Cristiano, Gabicagogeascoa, Estibaliz, Rona, Gergely, Salvador, Nélida, Pupo, Emanuela, Merchut-Maya, Joanna Maria, Daniel, Colin J., Carinci, Marianna, Cesarini, Valeriana, O’sullivan, Alfie, Jeong, Yeon-Tae, Bordi, Matteo, Russo, Francesco, Campello, Silvia, Gallo, Angela, Filomeni, Giuseppe, Lanzetti, Letizia, Sears, Rosalie C., Hamerlik, Petra, Bartolazzi, Armando, Hynds, Robert E., Pearce, David R., Swanton, Charles, Pagano, Michele, Velasco, Guillermo, Papaleo, Elena, De Zio, Daniela, Maya-Mendoza, Apolinar, Locatelli, Franco, Bartek, Jiri, and Cecconi, Francesco

Published
2021
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37. Phase II Trial of Palbociclib in Recurrent Retinoblastoma-Positive Anaplastic Oligodendroglioma: A Study from the Spanish Group for Research in Neuro-Oncology (GEINO)

Author

Sepúlveda-Sánchez, Juan Manuel, Gil-Gil, Miguel, Alonso-García, Miriam, Vaz Salgado, María Ángeles, Vicente, Elena, Mesía Barroso, Carlos, Rodríguez Sánchez, Ángel, Durán, Gema, De Las Peñas, Ramón, Muñoz-Langa, José, Velasco, Guillermo, Hernández-Laín, Aurelio, Hilario, Amaya, Navarro Martín, Miguel, Benavides, Manuel, Oleaga, Laura, Cantero Montenegro, Diana, Ruano, Yolanda, Sánchez-Gómez, Pilar, Martín-Soberón, María Cruz, Morales-Llombart, Robert, Pachón, Vanessa, and Pineda, Estela

Published
2020
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38. Mapping immune correlates and surfaceome genes in BRAF mutated colorectal cancers

Author

Instituto de Salud Carlos III, Fundación CRIS contra el Cáncer, Diputación de Albacete, National Research, Development and Innovation Office (Hungary), National Innovation Office (Hungary), European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Cabañas Morafraile, Esther [0000-0003-0929-6058], Saiz-Ladera, Cristina [0000-0001-8094-5992], Nieto-Jiménez, Cristina [0000-0002-3463-1439], Győrffy, Balázs [0000-0002-5772-3766], Velasco, Guillermo [0000-0002-1994-2386], Pérez-Segura, Pedro [0000-0001-5049-7199], Ocaña, Alberto [0000-0002-1067-9630], Cabañas Morafraile, Esther, Saiz-Ladera, Cristina, Nieto-Jiménez, Cristina, Győrffy, Balázs, Nagy, Adám, Velasco, Guillermo, Pérez-Segura, Pedro, Ocaña, Alberto, Instituto de Salud Carlos III, Fundación CRIS contra el Cáncer, Diputación de Albacete, National Research, Development and Innovation Office (Hungary), National Innovation Office (Hungary), European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Cabañas Morafraile, Esther [0000-0003-0929-6058], Saiz-Ladera, Cristina [0000-0001-8094-5992], Nieto-Jiménez, Cristina [0000-0002-3463-1439], Győrffy, Balázs [0000-0002-5772-3766], Velasco, Guillermo [0000-0002-1994-2386], Pérez-Segura, Pedro [0000-0001-5049-7199], Ocaña, Alberto [0000-0002-1067-9630], Cabañas Morafraile, Esther, Saiz-Ladera, Cristina, Nieto-Jiménez, Cristina, Győrffy, Balázs, Nagy, Adám, Velasco, Guillermo, Pérez-Segura, Pedro, and Ocaña, Alberto

Abstract

Despite the impressive results obtained with immunotherapy in several cancer types, a significant fraction of patients remains unresponsive to these treatments. In colorectal cancer (CRC), B-RafV600 mutations have been identified in 8-15% of the patients. In this work we interrogated a public dataset to explore the surfaceome of these tumors and found that several genes, such as GP2, CLDN18, AQP5, TM4SF4, NTSR1, VNN1, and CD109, were upregulated. By performing gene set enrichment analysis, we also identified a striking upregulation of genes (CD74, LAG3, HLA-DQB1, HLA-DRB5, HLA-DMA, HLA-DMB, HLA-DPB1, HLA-DRA, HLA-DOA, FCGR2B, HLA-DQA1, HLA-DRB1, and HLA-DPA1) associated with antigen processing and presentation via MHC class II. Likewise, we found a strong correlation between PD1 and PD(L)1 expression and the presence of genes encoding for proteins involved in antigen presentation such as CD74, HLA-DPA1, and LAG3. Furthermore, a similar association was observed for the presence of dendritic cells and macrophages. Finally, a low but positive relationship was observed between tumor mutational burden and neoantigen load. Our findings support the idea that a therapeutic strategy based on the targeting of PD(L)1 together with other receptors also involved in immuno-modulation, such as LAG3, could help to improve current treatments against BRAF-mutated CRC tumors.

Published
2023

39. Autophagy in malignant transformation and cancer progression

Author

Galluzzi, Lorenzo, Pietrocola, Federico, Bravo-San Pedro, José Manuel, Amaravadi, Ravi K, Baehrecke, Eric H, Cecconi, Francesco, Codogno, Patrice, Debnath, Jayanta, Gewirtz, David A, Karantza, Vassiliki, Kimmelman, Alec, Kumar, Sharad, Levine, Beth, Maiuri, Maria Chiara, Martin, Seamus J, Penninger, Josef, Piacentini, Mauro, Rubinsztein, David C, Simon, Hans-Uwe, Simonsen, Anne, Thorburn, Andrew M, Velasco, Guillermo, Ryan, Kevin M, and Kroemer, Guido

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Brain Disorders, Rare Diseases, Brain Cancer, Aetiology, 2.1 Biological and endogenous factors, Animals, Autophagy, Cell Transformation, Neoplastic, Humans, Neoplasms, Tumor Escape, Tumor Suppressor Proteins, adaptive stress responses, Beclin 1, inflammation, KRAS, mitophagy, Biological Sciences, Information and Computing Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.

Published
2015

44. POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1.

Author

Martínez‐López, Angélica, García‐Casas, Ana, Infante, Guiomar, González‐Fernández, Mónica, Salvador, Nélida, Lorente, Mar, Mendiburu‐Eliçabe, Marina, Gonzalez‐Moreno, Santiago, Villarejo‐Campos, Pedro, Velasco, Guillermo, Malliri, Angeliki, and Castillo‐Lluva, Sonia

Abstract

The small GTPase Rac1 (Ras‐related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial‐mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1‐SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1‐SUMO1. POTEE activates Rac1 in the invadopodium by recruiting TRIO‐GEF (triple functional domain protein), and it induces tumor cell proliferation and metastasis in vitro and in vivo. We found that the co‐localization of POTEE with Rac1 is correlated with more aggressive breast cancer subtypes. Given its role in tumor dissemination, the leading cause of cancer‐related deaths, POTEE could represent a potential therapeutic target for these types of cancer. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study

Author

Romero-Laorden, Nuria, primary, Lorente, David, additional, de Velasco, Guillermo, additional, Lozano, Rebeca, additional, Herrera, Bernardo, additional, Puente, Javier, additional, López, Pedro P., additional, Medina, Ana, additional, Almagro, Elena, additional, Gonzalez-Billalabeitia, Enrique, additional, Villla-Guzman, Jose Carlos, additional, González-del-Alba, Aránzazu, additional, Borrega, Pablo, additional, Laínez, Nuria, additional, Fernández-Freire, Ana, additional, Hernández, Amaia, additional, Rodriguez-Vida, Alejo, additional, Chirivella, Isabel, additional, Fernandez-Parra, Eva, additional, López-Campos, Fernando, additional, Isabel Pacheco, Maria, additional, Morales-Barrera, Rafael, additional, Fernández, Ovidio, additional, Villatoro, Rosa, additional, Luque, Raquel, additional, Hernando, Susana, additional, Castellano, Daniel C., additional, Castro, Elena, additional, and Olmos, David, additional

Published
2023
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46. Tailored immunotherapy approach with nivolumab with or without nivolumab plus ipilimumab as immunotherapeutic boost in patients with metastatic renal cell carcinoma (TITAN-RCC): a multicentre, single-arm, phase 2 trial

Author

Grimm, Marc-Oliver, primary, Esteban, Emilio, additional, Barthélémy, Philippe, additional, Schmidinger, Manuela, additional, Busch, Jonas, additional, Valderrama, Begoña P, additional, Charnley, Natalie, additional, Schmitz, Marc, additional, Schumacher, Ulrike, additional, Leucht, Katharina, additional, Foller, Susan, additional, Baretton, Gustavo, additional, Duran, Ignacio, additional, de Velasco, Guillermo, additional, Priou, Frank, additional, Maroto, Pablo, additional, Albiges, Laurence, additional, Barone, Carlo, additional, Castellano, Daniel, additional, Chevreau, Christine, additional, Gajate Borau, Pablo, additional, Gopalakrishnan, Srinavasan, additional, Grande, Enrique, additional, Hamid, Abdel, additional, Heinzelbecker, Julia, additional, Janssen, Martin, additional, Kopecký, Jindřich, additional, Kubala, Eugen, additional, Loidl, Wolfgang, additional, Lorch, Anja, additional, Melichar, Bohuslav, additional, Lainez Milagro, Nuria, additional, Niegisch, Günter, additional, Ohlmann, Carsten, additional, Sacré, Anne, additional, Sarwar, Naveed, additional, Schinzari, Giovanni, additional, Schrijvers, Dirk, additional, Tartas, Sophie, additional, Wirth, Manfred, additional, Wolter, Pascal, additional, and Zemanova, Milanda, additional

Published
2023
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