Oncohematology and Genetics

Molecular Pathology of Sarcomas and other Tumors

Enrique  de Álava Casado
Enrique de Álava Casado
IBiS
Campus Hospital Universitario Virgen del Rocío
Avda. Manuel Siurot, s/n.
41013 · Sevilla

Laboratory: 203

Enrique  de Álava Casado

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  1. Group members
  2. Research areas
  3. Publications

Group: Molecular Pathology of Sarcomas and other Tumors

Directory
Group members  Molecular Pathology of Sarcomas and other Tumors
  • Aguado Domínguez, Elena.Investigadora Postdoctoral
  • Biscuola, Michele.Dr. En Biología
  • de Álava Casado, Enrique .Investigador Responsable. Doctor en Medicina
  • Delgado Bellido, Daniel.Doctorado en Biomedicina.
  • Delgado García, Mercedes.Doctora. en Biología
  • Díaz Martín, Juan.Doctor en Biología
  • Hernández Barrera, Mª José .Técnico Sup. Lab. Anatomía Patológica (FP2)
  • Jordán Pérez, Mª del Carmen.Técnico Anatomía Patológica
  • Lobo Selma, Laura.Graduada en Biomedicina
  • Olmedo Pelayo , José Joaquín.Investigador en Formación. Plan Propio US. Ldo. en Biomedicina
  • Perez, Marco.Degree in Biology. Technician.
  • Robles Frías, Mª José .Doctora en Medicina.
  • Romero Pérez, Laura.Doctora en Biología.
  • Salguero Aranda, Carmen.Dra. Biotecnología.
  • Vargas Padilla, María Victoria.Técnico.

Research areas

Ewing Sarcoma (ES) is a malignant bone and soft-tissue tumor mainly affecting children and young adults. Advances in terms of  multimodal therapies in patients presenting localized disease, lead to a surprising overall survival of 70% at 5-year diagnostic. Despite this, patients presenting multifocal/metastatic or refractory disease present disappointing overall survival rates of around 20% .

From a molecular point of view, ES is characterized by the presence of reciprocal chromosomal translocations, given rise to fusion genes which in turn are translated into chimerical proteins (mostly involving EWSR1-ETS members). These functional chimerical proteins represent the major oncogenic event in ES. They typically involve the EWSR1 gene and a member of the ETS family, mostly FLI1, in about 85% of the cases. This aberrant transcription factor deregulates the transcription of target genes such as IGF1/IGF1R related genes, among many others.

 Despite the evident role of the ES fusion protein, recent evidence has demonstrated that other secondary alterations also play an enormous part in terms of tumor development, progression and even clinical prognostic.

The main research line of our group is based on the definition and characterization of these secondary alterations and how they may affect ES biology. Our goal is to establish new therapeutic targets as well as biomarkers of response to treatment based on preclinical studies focused on alternative/novel therapies.

 Detailed Objectives

 Discovery and validation of molecular mechanisms of tumor initiation and progression in sarcomas, namely in Ewing Sarcoma, our model of study.

 Translate these molecular mechanisms to the clinic in the form of biomarkers either of response to treatment or therapeutic monitoring.

 Establish stable collaborations with academic/ pharmaceutical groups interested in our research

 Research Lines:

 1.     Discovery and validation of molecular mechanisms of tumor initiation and progression in Ewing Sarcoma.

 The mechanisms of tumor initiation of Ewing Sarcoma remain unclear until this day. Despite this, the mesenchymal stem cell has been postulated as the most probable cell of origin of this tumor entity. Our group, developed an Ewing sarcoma cell line where the EWSR1-FLI1 stable interference led to a decrease of the intrinsic tumor characteristics followed by an increase of mesenchymal stem cells characteristics, namely differentiation capacity and phenotype. This study revealed a new target of the chimerical protein, TOPK1. Also, the in vivo implantation of the interfered tumor cells resulted in the production of smaller tumors in comparison to the parental cell line. (Herrero-Martín D et al, Br J Cancer. 2009 Jul 7;101(1):80-90.)

More recently, in collaboration with other European groups and within the Europoan Project EuroBONET, we have studied the phenotype of Mesenchymal stem cells derived from Ewing Sarcoma patients in comparison to Ewing Sarcoma cells and Ewing Sarcoma samples. We observed that Ewing Sarcoma patients are similar to other mesenchymal stem cells and show no differential phenotype. However, Ewing sarcoma cells present some phenotypic features of mesenchymal stem cells.

Also, the detailed study of CD99 expression in a large set of mesenchymal stem cells revealed that the inhibition of this receptor showed no impairment on this cell type survival. (Amaral AT et al, PLoS One, 2014, )

2. Discovery, functional validation and further clinical translation of new therapeutic targets from genomic, integrative proteomic studies in Ewing Sarcoma.

 Pre-clinical in vitro and in vivo studies described the protein HSP90 (Heat Shock Protein 90) as a biomarker of response to treatment with anti-IGF1R (Insulin-like growth factor receptor 1) inhibitors (namely ADW). Integrative proteomic analysis revealed that ES cell lines resistant to treatment with ADW, expressed higher levels of HSP90. This fact was later validated by RNA interference and in vivo studies in xenograft models. Also, Histopathological analysis of Ewing sarcoma samples demonstrated that in fact, in patients, the differential expression of HSP90 was a marker of worst response to treatment. (Martins AS et al, Cancer Res. 2008 Aug 1;68(15):6260-70.)

[T1] 

More recently, in a multicentre retrospective study, we demonstrated through CGH arrays the prognostic value of a particular secondary alteration. The gain of chromosome long arm (1qG) was present in approximately 30% of a total of 67 tumor samples. Furthermore, we performed a transcriptomic study with 38 tumor samples and finally established the 1qG fingerprint. This fingerprint was characterized by the differential expression of 74 genes located on 1q. Cases presenting this 1qG fingerprint were correlated with cell cycle deregulation, relapse and worst survival. Some genes with described over expression resulting from this 1qG in these cases were CDT2 and PARP1. (Mackintosh C et al, Oncogene. 2012 Mar 8;31(10):1287-98)

 Design and development of diagnostic tools which will allow the selection of patients for specific treatments, with particular emphasis to FISH and molecular signatures related with the over expression of 1q located genes.

 Retrospective Studies showed the clinical relevance of secondary alterations in Ewing Sarcoma, namely, alterations of copy number (CNAs), 1q and 8q Gains, 16q losses, among others. The next objective is to establish in prospective studies the prognostic value of CNAs in Ewing Sarcoma patients, through the development of FISH probes (for the evaluation of 1qG and 16q losses) and genes such as CDT2 and PARP1.

 Preclinical evaluation of experimental/commercial drugs on Ewing Sarcoma cell lines (previously validated in the European Project EuroBonet) and in xenograft models.

 a)     Taking together that CDT2 belongs to a subtype of complexes with  ubiquitin ligase activity (known as Cullin-RING ligases, CRL) and that these complexes con be inhibited with a potent specific new drug (MLN4924) we decided to study the effectiveness of MLN4924 in Ewing Sarcoma cell lines. Our results showed a high sensitivity of Ewing Sarcoma cell lines, with a dose dependent mechanism of response. At concentrations lower than the IC50 of proliferation (concentration needed to achieve the death of 50% of the cell population), we observed moderate apoptosis, with a delay in the G2-phase mostly due to the accumulation of WEE1. On the other hand, at concentrations higher than the IC50 of proliferation we observed a delay in the S-phase and high apoptotic index. More importantly, an efficient antitumoral effect was observed in our in vivo model. (Mackintosh C et al, Oncogene. 2013 Mar 14; 32(11):1441-51.)

 b)    PARP proteins are crucial for cell survival and are involved in several mechanisms such as DNA damage repair, cell cycle, apoptosis induction, angiogenesis and tumor formation and tumor progression. This fact evidently renders PARP proteins as interesting therapeutic targets. Although studies in other solid tumors suggested that PARP inhibitors were mostly active in tumors with deficiencies/mutations in DNA repair mechanisms, and that in Ewing Sarcoma these have not been described, the use of PARP inhibitors in combination with other chemotherapeutic agents (Temozolamide and radiotherapy) has shown great results in recent in vitro / in vivo studies. In our lab, we are focused in studying possible drug combinations of PARP inhibitors and other DNA-related agents in in vitro and in vivo models in Ewing Sarcoma.

 c)     Another key mechanism related to malignancy is the over expression of the IGF1-IGF1R axis in Ewing Sarcoma. Initially, we studied the effects of small molecules (ADW), which by competition of IGF1 exert an antagonistic action, blocking IGF1R activation. This tyrosine kynase inhibitor is an important regulator of cell proliferation in Ewing Sarcoma. ADW demonstrated an efficient anti-tumoral activity in comparison to traditional chemotherapeutic agents such as Vincristine or Doxorubicin. Interestingly, resistance to anti-IGF1R therapies has been related to the IGF2/IR dependency as well as with HSP90 over expression. So, more recently, and within the European project EuroSARC, we have studied the effects of a dual inhibitor of IGF1R/IR in Ewing Sarcoma cell lines, Linsitinb. In fact, we combined Linsitinib with DNA damage inducing agent, Trabectedin, and observed high levels of synergism.

 Development of epigenetic studies based in the activity of the chimerical protein EWSR1/FLI1 in models of inducible ectopic expression. These studies include chromatin remodeling, non-coding RNAs and pre-clinical in vitro and in vivo studies with epigenetic-based drugs.

 Secondary genetic alterations and epigenetic alterations might help to explain the most aggressive forms of Ewing Sarcoma and reveal new promising therapeutic targets. In this study we propose the stratification of Ewing sarcoma patients according to their epigenetic profile. We are currently developing and validating diagnostic tools which will allow us to molecularly characterize Ewing Sarcoma patients through techniques which can be easily translated to the clinical reality. Finally, we plan to further study the targets found through in vivo and in vitro studies and according to their effectiveness applied them to future clinical trials in Ewing Sarcoma patients.

 

 

 

 

 


 [T1]En la versión en castellano, falta referencia a este trabajo.

International Journals
Perez-Martinez, A; Ferreras, C; Pascual, A; Gonzalez-Vicent, M; Alonso, L; Badell, I; Navarro, JMF; Regueiro, A; Plaza, M; Hurtado, JMP; Benito, A; Belendez, C; Couselo, JM; Fuster, JL; Diaz-Almiron, M; Bueno, D; Mozo, Y; Marsal, J; Lopez, AG; Sisinni, L; de Heredia, CD; Diaz, MA
Haploidentical transplantation in high-risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH)
AMERICAN JOURNAL OF HEMATOLOGY
Rodriguez-Nunez, P; Romero-Perez, L; Amaral, AT; Puerto-Camacho, P; Jordan, C; Marcilla, D; Grunewald, TGP; Alonso, J; de Alava, E; Diaz-Martin, J
Hippo pathway effectors YAP1/TAZ induce an EWS-FLI1-opposing gene signature and associate with disease progression in Ewing sarcoma
JOURNAL OF PATHOLOGY
Velasco, A; Tokat, F; Bonde, J; Trim, N; Bauer, E; Meeney, A; de Leng, W; Chong, G; Dalstein, V; Kis, LL; Lorentzen, JA; Tomic, S; Thwaites, K; Putzova, M; Birnbaum, A; Qazi, R; Primmer, V; Dockhorn-Dworniczak, B; Hernandez-Losa, J; Soares, FA; Gertler, AA; Kalman, M; Wong, C; Carraro, DM; Sousa, AC; Reis, RM; Fox, SB; Fassan, M; Brevet, M; Merkelbach-Bruse, S; Colling, R; Soilleux, E; Teo, RYW; D'Haene, N; Nolet, S; Ristimaki, A; Vaisanen, T; Chapusot, C; Soruri, A; Unger, T; Wecgowiec, J; Biscuola, M; Frattini, M; Long, AN; Campregher, PV; Matias-Guiu, X
Multi-center real-world comparison of the fully automated Idylla (TM) microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer
VIRCHOWS ARCHIV
Remon, J; Garcia-Campelo, R; de Alava, E; Vera, R; Rodriguez-Peralto, JL; Rodriguez-Lescure, A; Bellosillo, B; Garrido, P; Rojo, F; Alvarez-Alegret, R
Liquid biopsy in oncology: a consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology
CLINICAL & TRANSLATIONAL ONCOLOGY
Almacellas-Rabaiget, O; Monaco, P; Huertas-Martinez, J; Garcia-Monclus, S; Chicon-Bosch, M; Maqueda-Marcos, S; Fabra-Heredia, I; Herrero-Martin, D; Rello-Varona, S; de Alava, E; Lopez-Alemany, R; Giangrande, PH; Tirado, OM
LOXL2 promotes oncogenic progression in alveolar rhabdomyosarcoma independently of its catalytic activity
CANCER LETTERS
Rodriguez-Bano, J; Perez-Moreno, MA; Penalva, G; Garnacho-Montero, J; Pinto, C; Salcedo, I; Fernandez-Urrusuno, R; Neth, O; Gil-Navarro, MV; Perez-Milena, A; Sierra, R; Estella, A; Lupion, C; Irastorza, A; Marquez, JL; Pascual, A; Rojo-Martin, MD; Perez-Lozano, MJ; Valencia-Martin, R; Cisneros, JM
Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis
CLINICAL MICROBIOLOGY AND INFECTION
Castillo-Ecija, H; Monterrubio, C; Pascual-Pasto, G; Gomez-Gonzalez, S; Garcia-Dominguez, DJ; Hontecillas-Prieto, L; Resa-Pares, C; Burgueno, V; Paco, S; Olaciregui, NG; Vila-Ubach, M; Restrepo-Perdomo, C; Cuadrado-Vilanova, M; Balaguer-Lluna, L; Perez-Jaume, S; Castaneda, A; Santa-Maria, V; Roldan, M; Sunol, M; de Alava, E; Mora, J; Lavarino, C; Carcaboso, AM
Treatment-driven selection of chemoresistant Ewing sarcoma tumors with limited drug distribution
JOURNAL OF CONTROLLED RELEASE
Martin-Gutierrez, G; Penalva, G; de Pipaon, MRP; Aguilar, M; Gil-Navarro, MV; Perez-Blanco, JL; Perez-Moreno, MA; Amaya-Villar, R; Ferraadiz-Millon, C; Gascon, ML; Goycochea-Valdivia, WA; Jimenez-Mejias, ME; Navarro, MD; Lepe, JA; Alvarez-Marin, R; Neth, O; Guisado-Gil, AB; Infante-Dominguez, C; Molina, J; Cisneros, JM
Efficacy and safety of a comprehensive educational antimicrobial stewardship program focused on antifungal use
JOURNAL OF INFECTION
Martin-Broto, J; Cruz, J; Penel, N; Le Cesne, A; Hindi, N; Luna, P; Moura, DS; Bernabeu, D; de Alava, E; Lopez-Guerrero, JA; Dopazo, J; Pena-Chilet, M; Gutierrez, A; Collini, P; Karanian, M; Redondo, A; Lopez-Pousa, A; Grignani, G; Diaz-Martin, J; Marcilla, D; Fernandez-Serra, A; Gonzalez-Aguilera, C; Casali, PG; Blay, JY; Stacchiotti, S
Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial
LANCET ONCOLOGY
Garcia-Heredia, JM; Otero-Albiol, D; Perez, M; Perez-Castejon, E; Munoz-Galvan, S; Carnero, A
Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells
ONCOGENESIS
Perez, M; Garcia-Heredia, JM; Felipe-Abrio, B; Munoz-Galvan, S; Martin-Broto, J; Carnero, A
Sarcoma stratification by combined pH2AX and MAP17 (PDZK1IP1) levels for a better outcome on doxorubicin plus olaparib treatment
SIGNAL TRANSDUCTION AND TARGETED THERAPY
Gomez, VE; Garcia-Gutierrez, V; Corral, LL; Cadenas, IG; Martinez, AP; Malaver, FMJ; Caballero-Velazquez, T; Sierra, PGA; Alegria, MCV; Salinas, IPM; Cabrera, CC; Vicent, MG; Torres, NR; Porras, RP; Coll, CF; Orti, G; Ferreiras, DV; Llanza, RD; Moles, P; Velazquez-Kennedy, K; Mende, MJ; Barrigon, DC; Perez, E; Bofarull, RM; Gerosa, SS; Sierra, J; Poch, M; Ripa, MTZ; Perez, MDA; Angulo, BM; Ortega, IS; Caballer, JS; Gomez, JM; Tocino, IE; Perez-Simon, JA
Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study
BONE MARROW TRANSPLANTATION
Borras, N; Garcia-Martinez, I; Batlle, J; Perez-Rodriguez, A; Parra, R; Altisent, C; Lopez-Fernandez, MF; Pinto, JC; Batlle-Lopez, F; Cid, AR; Bonanad, S; Cabrera, N; Moret, A; Mingot-Castellano, ME; Navarro, N; Perez-Montes, R; Marcellini, S; Moreto, A; Herrero, S; Soto, I; Fernandez-Mosteirin, N; Jimenez-Yuste, V; Alonso, N; de Andres-Jacob, A; Fontanes, E; Campos, R; Paloma, MJ; Bermejo, N; Berrueco, R; Mateo, J; Arribalzaga, K; Marco, P; Palomo, A; Quismondo, NC; Inigo, B; Nieto, MD; Vidal, R; Martinez, MP; Aguinaco, R; Tenorio, M; Ferreiro, M; Garcia-Frade, J; Rodriguez-Huerta, AM; Cuesta, J; Rodriguez-Gonzalez, R; Garcia-Candel, F; Dobon, M; Aguilar, C; Corrales, I; Vidal, F
Unraveling the Influence of Common von Willebrand factor variants on von Willebrand Disease Phenotype: An Exploratory Study on the Molecular and Clinical Profile of von Willebrand Disease in Spain Cohort
THROMBOSIS AND HAEMOSTASIS
Olmedo-Pelayo, J; Rubio-Contreras, D; Gomez-Herreros, F
Canonical non-homologous end-joining promotes genome mutagenesis and translocations induced by transcription-associated DNA topoisomerase 2 activity
NUCLEIC ACIDS RESEARCH
Jimenez, DG; Rodriguez-Belvis, MV; Gonzalez, PF; Ortega, GD; Segarra, O; Benitez, EM; Tirado, DG; Romero, RG; Lopez, RV; Crehua-Gaudiza, E; Queralt, M; Perez, LMP; Martin, JJD
COVID-19 Gastrointestinal Manifestations Are Independent Predictors of PICU Admission in Hospitalized Pediatric Patients
PEDIATRIC INFECTIOUS DISEASE JOURNAL
Leskela, S; Romero, I; Cristobal, E; Perez-Mies, B; Rosa-Rosa, JM; Gutierrez-Pecharroman, A; Santon, A; Gonzalez, BO; Lopez-Reig, R; Hardisson, D; Vera-Sempere, F; Illueca, C; Vieites, B; Lopez-Guerrero, JA; Palacios, J; Poveda, A
The Frequency and Prognostic Significance of the Histologic Type in Early-stage Ovarian Carcinoma A Reclassification Study by the Spanish Group for Ovarian Cancer Research (GEICO)
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
Canizales, JT; Ferreras, C; Pascual, A; Alonso, L; Regueiro, A; Plaza, M; Hurtado, JMP; Benito, A; Couselo, JM; Fuster, JL; Diaz-Almiron, M; Bueno, D; Mozo, Y; Lopez, AG; Vicario, JL; Balas, A; Sisinni, L; de Heredia, CD; Perez-Martinez, A
Haploidentical transplantation in pediatric non-malignant diseases: A retrospective analysis on behalf of the Spanish Group for Hematopoietic Transplantation (GETH)
EUROPEAN JOURNAL OF HAEMATOLOGY
Sanchez-Molina, S; Figuerola-Bou, E; Blanco, E; Sanchez-Jimenez, M; Taboas, P; Gomez, S; Ballare, C; Garcia-Dominguez, DJ; Prada, E; Hontecillas-Prieto, L; Carcaboso, AM; Tirado, OM; Hernandez-Munoz, I; de Alava, E; Lavarino, C; Di Croce, L; Mora, J
RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
SCIENCE ADVANCES
Martin-Broto, J; Hindi, N; Grignani, G; Martinez-Trufero, J; Redondo, A; Valverde, C; Stacchiotti, S; Lopez-Pousa, A; D'Ambrosio, L; Gutierrez, A; Perez-Vega, H; Encinas-Tobajas, V; de Alava, E; Collini, P; Pena-Chilet, M; Dopazo, J; Carrasco-Garcia, I; Lopez-Alvarez, M; Moura, DS; Lopez-Martin, JA
Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial
JOURNAL FOR IMMUNOTHERAPY OF CANCER
de Miguel, PA; Enguix-Riego, MV; Cacicedo, J; Delgado, BD; Perez, M; Praena-Fernandez, JM; Cortes, LQ; Garcia, PB; del Campo, ER; Guerra, JLL
Prognostic value of the TGF beta 1 rs4803455 single nucleotide polymorphism in small cell lung cancer
TUMORI J
Delgado-Garcia, M; Weynand, B; Gomez-Izquierdo, L; Hernandez, MJ; Blanco, AM; Varela, M; Matias-Guiu, X; Nadal, E; Marquez-Lobo, B; Alarcao, A; de Alava, E; Biscuola, M
Clinical performance evaluation of the Idylla (TM) EGFR Mutation Test on formalin-fixed paraffin-embedded tissue of non-small cell lung cancer
BMC CANCER
Munoz-Galvan, S; Felipe-Abrio, B; Verdugo-Sivianes, EM; Perez, M; Jimenez-Garcia, MP; Suarez-Martinez, E; Estevez-Garcia, P; Carnero, A
Downregulation of MYPT1 increases tumor resistance in ovarian cancer by targeting the Hippo pathway and increasing the stemness
MOLECULAR CANCER
Suarez-Garcia, I; Moreno, C; Ruiz-Alguero, M; Perez-Elias, MJ; Navarro, M; Martinez, MD; Viciana, P; Perez-Martinez, L; Gorgolas, M; Amador, C; de Zarraga, MA; Jarrin, I
Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice: a multicentre cohort study
AIDS RESEARCH AND THERAPY
Lluch, A; Barrios, CH; Torrecillas, L; Ruiz-Borrego, M; Bines, J; Segalla, J; Guerrero-Zotano, A; Garcia-Saenz, JA; Torres, R; de la Haba, J; Garcia-Martinez, E; Gomez, HL; Llombart, A; Bofill, JS; Baena-Canada, JM; Barnadas, A; Calvo, L; Perez-Michel, L; Ramos, M; Fernandez, I; Rodriguez-Lescure, A; Cardenas, J; Vinholes, J; de Duenas, EM; Godes, MJ; Segui, MA; Anton, A; Lopez-Alvarez, P; Moncayo, J; Amorim, G; Villar, E; Reyes, S; Sampaio, C; Cardemil, B; Escudero, MJ; Bezares, S; Carrasco, E; Martin, M; Corona, J; Jara, C; Cardemil, B; Toro, R; Pimentel, C; Hernando, B; Vicente, E; Zagame, L; Gil, M; Estevez, LG; Rodriguez, C; de la Cruz, MA; Tello, JM; Campos, S; Lomas, M; Capdevile, D; Campos, M; Margeli, M; Andres, R; Tusquets, I; Ballesteros, A; Guerrero, A; Arguello, M; Rodriguez, JL; Munoz, M; Florian, J; Azevedo, S; Mondragon, R; Peralta, J; Palomo, AE; Barajas, LJ; Arcusa, A; Carranza, H; Garcia, C; Umbria, C; Ales, JE; Vega, JML; Romeo, M; Valero, J; Alonso, JL; Mathias, C; Gutierrez, F; Adrover, E; Nunez, P; Mendiola, C; Cassinello, J; de la Huerta, A
Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01)
JOURNAL OF CLINICAL ONCOLOGY
Garcia-Dominguez, DJ; Hontecillas-Prieto, L; Leon, EA; Sanchez-Molina, S; Rodriguez-Nunez, P; Moron, FJ; Hajji, N; Mackintosh, C; de Alava, E
An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis
PLOS ONE
Martin-Broto, J; Hindi, N; Aguiar, S; Badilla-Gonzalez, R; Castro-Oliden, V; Chacon, M; Correa-Generoso, R; de Alava, E; Donati, DM; Eriksson, M; Falla-Jimenez, M; German, G; Silva, MLG; Gouin, F; Gronchi, A; Haro-Varas, JC; Jimenez-Brenes, N; Kasper, B; de Mello, CAL; Maki, R; Martinez-Delgado, P; Martinez-Said, H; Martinez-Tlahuel, JL; Morales-Perez, JM; Munoz-Casares, FC; Nakagawa, SA; Ortiz-Cruz, EJ; Palmerini, E; Patel, S; Moura, DS; Stacchiotti, S; Sunyach, MP; Valverde, CM; Waisberg, F; Blay, JY
Sarcoma European and Latin American Network (SELNET) Recommendations on Prioritization in Sarcoma Care During the COVID-19 Pandemic
ONCOLOGIST
Urrutia, I; Delgado, J; Dominguez-Ortega, J; Mascaros, E; Perez, M; Resler, G; Plaza, V; Flor, X; Vega, JM; Martinez, GL; Fernandez, JP; Munoz, X; Roger, A; Navarro, EM; Gomez, E; Adrados, ACG; Perez, RG; Perez, JMH; Barcala, FJG; Rey, JG; Bobolea, ID; Garcia, SS; Saenz, JTG; Cebollera, P; Vina, AL; Moragon, EM; Valero, A; Campos, RD; Talavera, IG; Viteri, SA; Robaina, JCG; Arrondo, AP
Clinical Factors Associated With Overuse of Asthma Reliever Medication
JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY
Perez-Martinez, L; Romero, L; Munoz-Galvan, S; Verdugo-Sivianes, EM; Rubio-Mediavilla, S; Oteo, JA; Carnero, A; Blanco, JR
Implications of maraviroc and/or rapamycin in a mouse model of fragility
AGING-US
Herrador, BRG; Ariza, SR; Zamalloa, PL; Valbuena, AC; Paches, PJ; Monge, S; San Miguel, LG; Olaso, OP; Sagrado, TS; Castaneda, MP; Rodriguez, BS; Moros, MJS; Soria, FS; Gomez, MG; Martinez, CV; Sanz, CD; Dos Santos, RA; Lorusso, N; Ubago, AC; Pla, ED; Jimenez, CF; Vazquez, MG; Gracia, ADC; Boone, ALD; Ibanez, AF; Fernandez, BA; Duran, JG; Rovira, MC; Castell, MS; Moreno, MLR; Frances, AP; Raymundo, LV; Curiel-Olmo, S; Cuesta, MG; Jane, M; Martinez, A; Izquierdo, C; Perez, AIR; Marin, VR; Corrales, IL; Saavedra, RR; Perez, MJR; Hernandez, SG; Lopez, MG; Rodriguez, MDM; Sopena, CR; Arevalo, OLR; Guillem, SB; Cuevas, AT; Torvisco, MDLT; Salete, CA; Gonzalez, BM; Villar, AIG; Martinez, OP; Castillo, IL; Garduno, IR; Diaz, JS; Bueno, SJ; Perez, DC; Castro, LFH; Anes, AAG; Garcia-Fulgueiras, A; Chirlaque, MD; Barranco, MI; Cenoz, MG; Sayon-Orea, C; Casado, I; Amores, MO; Carollo, OM; Perez, ACI; Ochoa, EM; Zarate, MPM
COVID-19 outbreaks in a transmission control scenario: challenges posed by social and leisure activities, and for workers in vulnerable conditions, Spain, early summer 2020
EUROSURVEILLANCE
Hontecillas-Prieto, L; Flores-Campos, R; Silver, A; de Alava, E; Hajji, N; Garcia-Dominguez, DJ
Synergistic Enhancement of Cancer Therapy Using HDAC Inhibitors: Opportunity for Clinical Trials
FRONTIERS IN GENETICS
Lopez-Garcia, MA; Carretero-Barrio, I; Perez-Mies, B; Chiva, M; Castilla, C; Vieites, B; Palacios, J
Low Prevalence of HER2-Positive Breast Carcinomas among Screening Detected Breast Cancers
CANCERS
Pignata, L; Palumbo, O; Cerrato, F; Acurzio, B; de Alava, E; Roma, J; Gallego, S; Mora, J; Carella, M; Riccio, A; Verde, G
Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
CANCERS
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Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
CANCERS
Salguero-Aranda, C; Amaral, AT; Olmedo-Pelayo, J; Diaz-Martin, J; de Alava, E
Breakthrough Technologies Reshape the Ewing Sarcoma Molecular Landscape
CELLS
Guerra-Castellano, A; Marquez, I; Perez-Mejias, G; Diaz-Quintana, A; De la Rosa, MA; Diaz-Moreno, I
Post-Translational Modifications of Cytochrome c in Cell Life and Disease
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Alvarez-Alegret R; Rojo Todo F; Garrido P; Bellosillo B; Rodriguez-Lescure A; Rodriguez-Peralto JL; Vera R; de Alava E; Garcia-Campelo R; Remon J
Biopsia liquida en oncologia: Consenso de la Sociedad Espanola de Oncologia Medica (SEOM) y la Sociedad Espanola de Anatomia Patologica (SEAP)
Revista espanola de patologia
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Pazopanib for treatment of advanced malignant and dedifferentiated solitary fibrous tumour: a multicentre, single-arm, phase 2 trial.
Lancet Oncol
María del Valle Enguix-Riego, Jon Cacicedo Fernández de Bobadilla, Blas David Delgado León, Jose María Nieto-Guerrero Gómez, Daniel Herrero Rivera, Marco Perez, Juan Manuel Praena-Fernández, Gerardo Sanchez Carmona, Eleonor Rivin del Campo, María José Ortiz Gordillo, Jose Luis Lopez Guerra.
The single nucleotide variant rs2868371 associates with the risk of mortality in non-small cell lung cancer patients: a multicenter prospective validation.
Radiotherapy & Oncology
Sandra Muñoz-Galván, Antonio Lucena-Cacace, Marco Perez, Daniel Otero-Albiol, Julian Gomez-Cambronero and Amancio Carnero.
Tumor cell-secreted PLD increases tumor stemness by senescence-mediated communication with microenvironment.
Oncogene
Martin-Broto J, Stacchiotti S, Lopez-Pousa A, Redondo A, Bernabeu D, de Alava E, Casali PG, Italiano A, Gutierrez A, Moura DS, Peña-Chilet M, Diaz-Martin J, Biscuola M, Taron M, Collini P, Ranchere-Vince D, Garcia Del Muro X, Grignani G, Dumont S, Martinez-Trufero J, Palmerini E, Hindi N, Sebio A, Dopazo J, Dei Tos AP, LeCesne A, Blay JY, Cruz J
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Pazopanib for treatment of advanced extraskeletal myxoid chondrosarcoma: a multicentre, single-arm, phase 2 trial.
Lancet Oncol.
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Preclinical Efficacy of Endoglin-Targeting Antibody-Drug Conjugates for the Treatment of Ewing Sarcoma.
Clin Cancer Res
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Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma.
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What's in a name? Molecular subclassification of sarcomas creates fresh challenges.
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Computer-Assisted Definition of the Inflammatory Infiltrates in Patients With Different Categories of Banff Kidney Allograft Rejection.
Front Immunol
Koelsche C, Kriegsmann M, Kommoss FKF, Stichel D, Kriegsmann K, Vokuhl C, Grünewald TGP, Romero-Pérez L, Kirchner T, de Alava E, Diaz-Martin J, Hartmann W, Baumhoer D, Antonescu CR, Szuhai K, Flucke U, Dirksen U, Pfister SM, Jones DTW, Mechtersheimer G, von Deimling A
DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma.
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A child with chronic cough and weight loss.
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Lung cancer treatments efficacy in tumors with high MAP17 (PDZK1IP1) expression levels.
J Exp Clin Cancer Res
Díaz-Martín J, Biscuola M, Benoit J, Marcilla D, Civantos G, de Álava E.
What's in a name? Molecular subclassification of sarcomas creates fresh challenges.
J Pathol
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Supplementary data for the biological age linked to oxidative stress modifies breast cancer aggressiveness.
Data Brief
Puerto-Camacho P, Amaral AT, Lamhamedi-Cherradi SE, Menegaz BA, Castillo-Ecija H, Ordóñez JL, Domínguez S, Jordan-Perez C, Diaz-Martin J, Romero-Pérez L, Lopez-Alvarez M, Civantos-Jubera G, Robles-Frías MJ, Biscuola M, Ferrer C, Mora J, Cuglievan B, Schadler K, Seifert O, Kontermann R, Pfizenmaier K, Simón L, Fabre M, Carcaboso ÁM, Ludwig JA, de Álava E.
Preclinical Efficacy of Endoglin-Targeting Antibody-Drug Conjugates for the Treatment of Ewing Sarcoma.
Clin Cancer Res
García-Domínguez DJ, Hontecillas-Prieto L, Rodríguez-Núñez P, Pascual-Pasto G, Vila-Ubach M, García-Mejías R, Robles MJ, Tirado OM, Mora J, Carcaboso AM, de Álava E.
The combination of epigenetic drugs SAHA and HCI-2509 synergistically inhibits EWS-FLI1 and tumor growth in Ewing sarcoma
Oncotarget
Grünewald TGP, Cidre-Aranaz F, Surdez D, Tomazou EM, de Álava E, Kovar H, Sorensen PH, Delattre O, Dirksen U.
Ewing sarcoma.
Nat Rev Dis Primers
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The biological age linked to oxidative stress modifies breast cancer aggressiveness
Free Radic Biol Med
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The bitter side of epigenetics: variability and resistance to chemotherapy.
Epigenomics.
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Mod Pathol
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EphA2 receptor is a key player in the metastatic onset of Ewing sarcoma
Int J Cancer
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Identification of the cellular components involved in de novo immune hepatitis: a quantitative immunohistochemical analysis.
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Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up.
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Espinosa M, Roldán-Romero JM, Durán I, de Álava E, Apellaniz-Ruiz M, Cascón A, Garrigós C, Robledo M, Rodríguez-Antona C.
Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation.
BMC Cancer.
García-Domínguez DJ, Hontecillas-Prieto L, Rodríguez-Núñez P, Pascual-Pasto G, Vila-Ubach M, García-Mejías R, Robles MJ, Tirado OM, Mora J, Carcaboso AM, de Álava E.
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Oncotarget.
García-Monclús S, López-Alemany R, Almacellas-Rabaiget O, Herrero-Martín D, Huertas-Martínez J, Lagares-Tena L, Alba-Pavón P, Hontecillas-Prieto L, Mora J, de Álava E, Rello-Varona S, Giangrande PH, Tirado OM.
EphA2 receptor is a key player in the metastatic onset of Ewing sarcoma.
Int J Cancer.
Garrido P, Aldaz A, Vera R, Calleja MA, de Álava E, Martín M, Matías-Guiu X, Palacios J.
Proposal for the creation of a national strategy for precision medicine in cancer: a position statement of SEOM, SEAP, and SEFH.
Clin Transl Oncol
Grünewald TGP, Cidre-Aranaz F, Surdez D, Tomazou EM, de Álava E, Kovar H, Sorensen PH, Delattre O, Dirksen U.
Ewing sarcoma.
Nat Rev Dis Primers.
Hajji N, García-Domínguez DJ, Hontecillas-Prieto L, O'Neill K, de Álava E, Syed N.
The bitter side of epigenetics: variability and resistance to chemotherapy.
Epigenomics.
Moreno Ortega M, Moreno García MDM, Pérez Borrego E, Gaboli M.
[A child with chronic cough and weight loss].
An Pediatr (Barc).
Sáez-Freire MDM, Blanco-Gómez A, Castillo-Lluva S, Gómez-Vecino A, Galvis-Jiménez JM, Martín-Seisdedos C, Isidoro-García M, Hontecillas-Prieto L, García-Cenador MB, García-Criado FJ, Patino-Alonso MC, Galindo-Villardón P, Mao JH, Prieto C, Castellanos-Martín A, Kaderali L, Pérez-Losada J.
The biological age linked to oxidative stress modifies breast cancer aggressiveness
Free Radic Biol Med.