Grupos Investigadores

Miembros del Grupo

Investigadores
Marc
García Moure
Anna
González Neira
Lucía
Marrodán Fernández
Naiara
Martínez Velez
Antonio
Pérez Martínez
Marta
Zalacain Díez
Ignacio
Íñigo Marco
Colaboradores
Virginia
Laspidea Ustés

Líneas de Investigación

  • Caracterización genética de los tumores infantiles
  • Modelos animales de sarcoma
  • Terapias avanzadas en tumores infantiles/sarcomas
  • Tumores sólidos infantiles

Palabras Clave

  • Cáncer infantil
  • Modelos animales
  • Sarcomas infantiles
  • Terapias avanzadas

Publicaciones Científicas desde 2018

  • Autores: Antoñanzas Pérez, Javier; Querol Cisneros, Elena; Alkorta Aranburu, Gorka; et al.
    Revista: INTERNATIONAL JOURNAL OF DERMATOLOGY
    ISSN: 0011-9059 Vol.62 N° 3 2023 págs. e176 - e178
  • Autores: Gómez-Vecino, A.; Corchado-Cobos, R.; Blanco-Gómez, A.; et al.
    Revista: CELLS
    ISSN: 2073-4409 Vol.12 N° 15 2023 págs. 1956
    Resumen
    Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.
  • Autores: San Julián Aranguren, Miguel (Autor de correspondencia); Gómez Alvarez, Jorge; Idoate Gastearena, Miguel Ángel; et al.
    Revista: BONE & JOINT JOURNAL
    ISSN: 2049-4394 Vol.105-B N° 1 2023 págs. 11 - 16
    Resumen
    Paediatric bone sarcomas are a dual challenge for orthopaedic surgeons in terms of tumour resection and reconstruction, as it is important to minimize functional and growth problems without compromising survival rates. Canadell's technique consists of a Type I epiphysiolysis performed using continuous distraction by an external fixator prior to resection. It was designed to achieve a safe margin due to the ability of the physeal cartilage to be a barrier to tumour spread in some situations, avoiding the need for articular reconstruction, and preserving the growth capacity most of the times. Despite initial doubts raised in the scientific community, this technique is now widely used in many countries for the treatment of metaphyseal paediatric bone sarcomas. This annotation highlights the importance of Canadell's work and reviews the experience of applying it to bone sarcoma patients over the last 40 years.
  • Autores: García-Peláez, J.; Barbosa-Matos, R.; Lobo, S.; et al.
    Revista: LANCET ONCOLOGY
    ISSN: 1470-2045 Vol.24 N° 1 2023 págs. 91 - 106
    Resumen
    Background Truncating pathogenic or likely pathogenic variants of CDH1 cause hereditary diffuse gastric cancer (HDGC), a tumour risk syndrome that predisposes carrier individuals to diffuse gastric and lobular breast cancer. Rare CDH1 missense variants are often classified as variants of unknown significance. We conducted a genotypephenotype analysis in families carrying rare CDH1 variants, comparing cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV; analysed jointly) or missense variants of unknown significance, assessing the frequency of families with lobular breast cancer among PV/LPV carrier families, and testing the performance of lobular breast cancer-expanded criteria for CDH1 testing. Methods This genotype-first study used retrospective diagnostic and clinical data from 854 carriers of 398 rare CDH1 variants and 1021 relatives, irrespective of HDGC clinical criteria, from 29 institutions in ten member-countries of the European Reference Network on Tumour Risk Syndromes (ERN GENTURIS). Data were collected from Oct 1, 2018, to Sept 20, 2022. Variants were classified by molecular type and clinical actionability with the American College of Medical Genetics and Association for Molecular Pathology CDH1 guidelines (version 2). Families were categorised by whether they fulfilled the 2015 and 2020 HDGC clinical criteria. Genotype-phenotype associations were analysed by Student's t test, Kruskal-Wallis, chi (2), and multivariable logistic regression models. Performance of HDGC clinical criteria sets were assessed with an equivalence test and Youden index, and the areas under the receiver operating characteristic curves were compared by Z test. Findings From 1971 phenotypes (contributed by 854 probands and 1021 relatives aged 1-93 years), 460 had gastric and breast cancer histology available. CDH1 truncating PV/LPVs occurred in 176 (21%) of 854 families and missense variants of unknown significance in 169 (20%) families. Multivariable logistic regression comparing phenotypes occurring in families carrying PV/LPVs or missense variants of unknown significance showed that lobular breast cancer had the greatest positive association with the presence of PV/LPVs (odds ratio 12.39 [95% CI 2.66-57.74], p=0.0014), followed by diffuse gastric cancer (8.00 [2.18-29.39], p=0.0017) and gastric cancer (7.81 [2.03-29.96], p=0.0027). 136 (77%) of 176 families carrying PV/LPVs fulfilled the 2015 HDGC criteria. Of the remaining 40 (23%) families, who did not fulfil the 2015 criteria, 11 fulfilled the 2020 HDGC criteria, and 18 had lobular breast cancer only or lobular breast cancer and gastric cancer, but did not meet the 2020 criteria. No specific CDH1 variant was found to predispose individuals specifically to lobular breast cancer, although 12 (7%) of 176 PV/LPV carrier families had lobular breast cancer only. Addition of three new lobular breast cancer-centred criteria improved testing sensitivity while retaining high specificity. The probability of finding CDH1 PV/LPVs in patients fulfilling the lobular breast cancer-expanded criteria, compared with the 2020 criteria, increased significantly (AUC 0.92 vs 0.88; Z score 3.54; p=0.0004). Interpretation CDH1 PV/ LPVs were positively associated with HDGC-related phenotypes (lobular breast cancer, diffuse gastric cancer, and gastric cancer), and no evidence for a positive association with these phenotypes was found for CDH1 missense variants of unknown significance. CDH1 PV/LPVs occurred often in families with lobular breast cancer who did not fulfil the 2020 HDGC criteria, supporting the expansion of lobular breast cancer-centred criteria.
  • Autores: Alba Pavon, P.; Alaña, L.; Gutiérrez Jimeno, Miriam; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN: 2045-2322 Vol.13 N° 1 2023 págs. 2959
    Resumen
    Genetic predisposition is an important risk factor for cancer in children and adolescents but detailed associations of individual genetic mutations to childhood cancer are still under intense investigation. Among pediatric cancers, sarcomas can arise in the setting of cancer predisposition syndromes. The association of sarcomas with these syndromes is often missed, due to the rarity and heterogeneity of sarcomas and the limited search of cancer genetic syndromes. This study included 43 pediatric and young adult patients with different sarcoma subtypes. Tumor profiling was undertaken using the Oncomine Childhood Cancer Research Assay (Thermo Fisher Scientific). Sequencing results were reviewed for potential germline alterations in clinically relevant genes associated with cancer predisposition syndromes. Jongmans¿ criteria were taken into consideration for the patient selection. Fifteen patients were selected as having potential pathogenic germline variants due to tumor sequencing that identified variants in the following genes: CDKN2A, NF1, NF2, RB1, SMARCA4, SMARCB1 and TP53. The variants found in NF1 and CDKN2A in two different patients were detected in the germline, confirming the diagnosis of a cancer predisposition syndrome. We have shown that the results of somatic testing can be used to identify those at risk of an underlying cancer predisposition syndrome.
  • Autores: De la Nava Martin, Daniel; Mert Selvi, K.; Alonso Roldán, Marta María (Autor de correspondencia)
    Revista: FRONTIERS IN IMMUNOLOGY
    ISSN: 1664-3224 Vol.13 2022 págs. 866892
    Resumen
    Immunotherapy has seen tremendous strides in the last decade, acquiring a prominent position at the forefront of cancer treatment since it has been proven to be efficacious for a wide variety of tumors. Nevertheless, while immunotherapy has changed the paradigm of adult tumor treatment, this progress has not yet been translated to the pediatric solid tumor population. For this reason, alternative curative therapies are urgently needed for the most aggressive pediatric tumors. In recent years, oncolytic virotherapy has consolidated as a feasible strategy for cancer treatment, not only for its tumor-specific effects and safety profile but also for its capacity to trigger an antitumor immune response. This review will summarize the current status of immunovirotherapy to treat cancer, focusing on pediatric solid malignancies. We will revisit previous basic, translational, and clinical research and discuss advances in overcoming the existing barriers and limitations to translate this promising therapeutic as an every-day cancer treatment for the pediatric and young adult populations.
  • Autores: Martínez Velez, Naiara; Laspidea Ustés, Virginia; Zalacain Díez, Marta; et al.
    Revista: MOLECULAR CANCER THERAPEUTICS
    ISSN: 1535-7163 Vol.21 N° 3 2022 págs. 471 - 480
    Resumen
    Osteosarcoma is an aggressive bone tumor occurring primarily in pediatric patients. Despite years of intensive research, the outcomes of patients with metastatic disease or those who do not respond to therapy have remained poor and have not changed in the last 30 years. Oncolytic virotherapy is becoming a reality to treat local and metastatic tumors while maintaining a favorable safety profile. Delta-24-ACT is a replicative oncolytic adenovirus engineered to selectively target cancer cells and to potentiate immune responses through expression of the immune costimulatory ligand 4-1BB. This work aimed to assess the antisarcoma effect of Delta-24-ACr. MIS and replication assays were used to quantify the antitumor effects of Delta-24-ACT in vitro in osteosarcoma human and murine cell lines. Evaluation of the in vivo antitumor effect and immune response to Delta-24-ACI was performed in immunocompetent mice bearing the orthotopic K7M2 cell line. Immunophenotyping of the tumor microenvironment was characterized by immunohistochemistry and flow cytomcny. In vitro, Delta-24-ACT killed osteosarcoma cells and triggered the production of danger signals. In vivo, local treatment with Delta-24-ACT led to antitumor effects against both the primary tumor and spontaneous metastases in a murine osteosarcoma model. Viral treatment was safe, with no noted toxicity. Delta-24-ACT significantly increased the median survival time of treated mice. Collectively, our data identify Delta24-ACT administration as an effective and safe therapeutic strategy for patients with local and metastatic osteosarcoma. These results support clinical translation of this viral immunothcrapy approach.
  • Autores: Bosma, S. E.; van der Heijden, L.; Sierrasesúmaga Ariznavarreta, Luis; et al.
    Revista: CANCERS
    ISSN: 2072-6694 Vol.14 N° 6 2022 págs. 1456
    Resumen
    Simple Summary Younger age has been associated with better overall survival in Ewing sarcoma, especially under the age of 10. Our study aimed at describing long-term outcomes of a cohort of 60 patients aged 0-10 with Ewing sarcoma, treated with chemotherapy, surgery and/or radiotherapy. Overall survival of these youngest patients with ES was very good. After 10 years, 81% of patients were still alive, 89% did not have a local recurrence and 81% did not have distant metastasis (in lungs and/or bone). Limb salvage surgery was achieved in >90% of patients. Wide resection margin was the only factor significantly associated with better survival, but age < 6 years, smaller tumors, no metastases at diagnosis and treatment after 2000 also seemed to result in better overall survival. (1) Background: Younger age has been associated with better overall survival (OS) in Ewing sarcoma (ES), especially under the age of 10. The favorable survival in younger patients underlines the need for minimizing treatment burden and late sequelae. Our study aimed at describing clinical characteristics, treatment and outcome of a cohort of ES patients aged 0-10. (2) Methods: In this retrospective multicenter study, all consecutive ES patients aged 0-10, treated in four sarcoma centers in the Netherlands (n = 33) and one in Spain (n = 27) between 1982 and 2008, with a minimum follow-up of 10 years, were included. OS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were calculated. Potential factors of influence on OS (risk and protective factors) were analyzed. (3) Results: 60 patients with median follow-up 13.03 years were included. All patients were treated with chemotherapy in combination with local treatment, being surgery alone in 30 (50%) patients, radiotherapy (RT) alone in 12 (20%) patients or surgery plus RT in 18 (30%) patients (12 pre- and 6 postoperative). Limb salvage was achieved in 93% of patients. The 10-OS, -LRFS and -DMFS are 81% (95% CI: 71-91%), 89% (95% CI: 85-93%) and 81% (95% CI: 71-91%), respectively. Six patients developed LR, of which two developed subsequent DM; all had axial ES (pelvis, spine or chest wall), and these patients all died. Ten patients developed DM; eight died due to progressive disease, and two are currently in remission, both with pulmonary metastasis only. Negative or wide resection margin was significantly associated with better OS. Age < 6 years, tumor volume < 200 mL, absence of metastatic disease and treatment after 2000 showed trends towards better OS. Two patients developed secondary malignancy; both had chemotherapy combined with definitive RT for local treatment. (4) Conclusions: Overall survival of these youngest patients with ES was very good. Limb salvage surgery was achieved in >90% of patients. Wide resection margin was the only factor significantly associated with better survival.
  • Autores: Gutiérrez Jimeno, Miriam; Panizo Morgado, Elena; Calvo Imirizaldu, Marta; et al.
    Revista: FRONTIERS IN PEDIATRICS
    ISSN: 2296-2360 Vol.10 2022 págs. 875510
    Resumen
    We report the case of a 7-month-old female patient who developed acute megakaryoblastic leukemia 6 months after the appearance of skull bone lesions. Initial evaluation and diagnosis of this patient were challenging and only achieved thanks to genomic analysis by NGS (next generation sequencing). It is unusual for the initial manifestation of acute megakaryoblastic leukemia to be a skull bone lesion. Extramedullary acute myeloid leukemia (eAML), also known as myeloid sarcoma (MS), often occurs simultaneously with acute myeloid leukemia (AML), although it may precede AML. Genomic analysis based on a NGS panel (Oncomine Childhood Cancer Research Assay) detected a RBM15::MKL1 fusion, a consequence of a t (1;22)(p13;q13) translocation, establishing the diagnosis of acute megakaryoblastic leukemia and enabling disease follow-up by qPCR. A diagnosis of eAML is built up from various findings in radiological, histological, immunophenotypic and genomic studies; when the tumor appears de novo, diagnosis is more complicated. We emphasize the importance of a multidisciplinary team in the initial approach to rare tumors and the use of genomic studies to contribute to the knowledge of these neoplasms, risk stratification and treatment planning.
  • Autores: Herrador Cañete, Guillermo; Zalacain Díez, Marta; Labiano Almiñana, Sara; et al.
    Revista: MOLECULAR THERAPY ONCOLYTICS
    ISSN: 2372-7705 Vol.26 2022 págs. 246 - 264
    Resumen
    The outcomes of metastatic and nonresponder pediatric osteosarcoma patients are very poor and have not improved in the last 30 years. These tumors harbor a highly immunosuppressive environment, making existing immunotherapies ineffective. Here, we evaluated the use of Semliki Forest virus (SFV) vectors expressing galectin-3 (Gal3) inhibitors as therapeutic tools, since both the inhibition of Gal3, which is involved in immunosuppression and metastasis, and virotherapy based on SFV have been demonstrated to reduce tumor progression in different tumor models. In vitro, inhibitors based on the Gal3 amino-terminal domain alone (Gal3-N) or fused to a Gal3 peptide inhibitor (Gal3-N-C12) were able to block the binding of Gal3 to the surface of activated T cells. In vivo, SFV expressing Gal3-N-C12 induced strong antitumor responses in orthotopic K7M2 and MOS-J osteosarcoma tumors, leading to complete regressions in 47% and 30% of mice, respectively. Pulmonary metastases were also reduced in K7M2 tumor-bearing mice after treatment with SFV-Gal3-N-C12. Both the antitumor and antimetastatic responses were dependent on modulation of the immune system, primarily including an increase in tumor-infiltrating lymphocytes and a reduction in the immunosuppressive environment inside tumors. Our results demonstrated that SFV-Gal3-N-C12 could constitute a potential therapeutic agent for osteosarcoma patients expressing Gal3.
  • Autores: Damanskiene, E.; Balnyte, I.; Valanciute, A.; et al.
    Revista: BIOMEDICINES
    ISSN: 2227-9059 Vol.10 N° 5 2022 págs. 968
    Resumen
    Valproic acid (VPA) is a histone deacetylase inhibitor with sex-specific immunomodulatory and anticancer effects. This study aimed to investigate the effect of 0.5 and 0.75 mM VPA on NKCC1 (SLC12A2), KCC2 (SLC12A5) and SLC5A8 (SLC5A8) co-transporter gene expressions in pediatric PBT24 (boy's) and SF8628 (girl's) glioblastoma cells. The SLC12A2, SLC12A5 and SLC5A8 RNA expressions were determined by the RT-PCR method. The SLC12A2 and SLC5A8 expressions did not differ between the PBT24 and SF8628 controls. The SLC12A5 expression in the PBT24 control was significantly higher than in the SF8628 control. VPA treatment significantly increased the expression of SLC12A2 in PBT24 but did not affect SF8628 cells. VPA increased the SLC12A5 expression in PBT24 and SF8628 cells. The SLC12A5 expression of the PBT24-treated cells was significantly higher than in corresponding SF8628 groups. Both VPA doses increased the SLC5A8 expression in PBT24 and SF8628 cells, but the expression was significantly higher in the PBT24-treated, compared to the respective SF8628 groups. The SLC5A8 expression in PBT24-treated cells was 10-fold higher than in SF8628 cells. The distinct effects of VPA on the expression of SLC12A2, SLC12A5 and SLC5A8 in PBT24 and SF8628 glioblastoma cells suggest differences in tumor cell biology that may be gender-related.
  • Autores: Hurkmans, E. G. E.; Koenderink, J. B.; an den Heuvel, J. J. M. W.; et al.
    Revista: FRONTIERS IN PHARMACOLOGY
    ISSN: 1663-9812 Vol.13 2022 págs. 1042989
    Resumen
    Background: Despite (neo) adjuvant chemotherapy with cisplatin, doxorubicin and methotrexate, some patients with primary osteosarcoma progress during first-line systemic treatment and have a poor prognosis. In this study, we investigated whether patients with early disease progression (EDP), are characterized by a distinctive pharmacogenetic profile. Methods and Findings: Germline DNA from 287 Dutch high-grade osteosarcoma patients was genotyped using the DMET Plus array (containing 1,936 genetic markers in 231 drug metabolism and transporter genes). Associations between genetic variants and EDP were assessed using logistic regression models and associated variants (p < 0.05) were validated in independent cohorts of 146 (Spain and United Kingdom) and 28 patients (Australia). In the association analyses, EDP was significantly associated with an SLC7A8 locus and was independently validated (meta-analysis validation cohorts: OR 0.19 [0.06-0.55], p = 0.002). The functional relevance of the top hits was explored by immunohistochemistry staining and an in vitro transport models. SLC7A8 encodes for the L-type amino acid transporter 2 (LAT2). Transport assays in HEK293 cells overexpressing LAT2 showed that doxorubicin, but not cisplatin and methotrexate, is a substrate for LAT2 (p < 0.0001). Finally, SLC7A8 mRNA expression analysis and LAT2 immunohistochemistry of osteosarcoma tissue showed that the lack of LAT2 expression is a prognostic factor of poor prognosis and reduced overall survival in patients without metastases (p = 0.0099 and p = 0.14, resp.). Conclusion: This study identified a novel locus in SLC7A8 to be associated with EDP in osteosarcoma. Functional studies indicate LAT2-mediates uptake of doxorubicin, which could give new opportunities to personalize treatment of osteosarcoma patients.
  • Autores: Gargallo, P. (Autor de correspondencia); Bautista, F.; Juan-Ribelles, A.; et al.
    Revista: CLINICAL AND TRANSLATIONAL ONCOLOGY
    ISSN: 1699-048X Vol.24 N° 5 2022 págs. 809 - 815
    Resumen
    The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed. Next generation sequencing-based (NGS) gene panels are the technology used in the majority of centers and financial limitations are the main reason for not incorporating these studies into routine care. Nowadays, the application of precision medicine in pediatric oncology is a reality in a great number of Spanish centers. However, its implementation is uneven and lacks standardization of protocols; therefore, national coordination to overcome the inequalities is required. Collaborative work within the Personalized Medicine Group of SEHOP is an adequate framework for encouraging a step forward in the effort to move precision medicine into the national healthcare system.
  • Autores: Gállego Pérez de Larraya, Jaime; García Moure, Marc; Labiano Almiñana, Sara; et al.
    Revista: NEW ENGLAND JOURNAL OF MEDICINE
    ISSN: 0028-4793 Vol.386 N° 26 2022 págs. 2471 - 2481
    Resumen
    Background: Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. Oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, but data regarding oncolytic viral therapy in patients with DIPG are lacking. Methods: We conducted a single-center, dose-escalation study of DNX-2401, an oncolytic adenovirus that selectively replicates in tumor cells, in patients with newly diagnosed DIPG. The patients received a single virus infusion through a catheter placed in the cerebellar peduncle, followed by radiotherapy. The primary objective was to assess the safety and adverse-event profile of DNX-2401. The secondary objectives were to evaluate the effect of DNX-2401 on overall survival and quality of life, to determine the percentage of patients who have an objective response, and to collect tumor-biopsy and peripheral-blood samples for correlative studies of the molecular features of DIPG and antitumor immune responses. Results: A total of 12 patients, 3 to 18 years of age, with newly diagnosed DIPG received 1×1010 (the first 4 patients) or 5×1010 (the subsequent 8 patients) viral particles of DNX-2401, and 11 received subsequent radiotherapy. Adverse events among the patients included headache, nausea, vomiting, and fatigue. Hemiparesis and tetraparesis developed in 1 patient each. Over a median follow-up of 17.8 months (range, 5.9 to 33.5), a reduction in tumor size, as assessed on magnetic resonance imaging, was reported in 9 patients, a partial response in 3 patients, and stable disease in 8 patients. The median survival was 17.8 months. Two patients were alive at the time of preparation of the current report, 1 of whom was free of tumor progression at 38 months. Examination of a tumor sample obtained during autopsy from 1 patient and peripheral-blood studies revealed alteration of the tumor microenvironment and T-cell repertoire. Conclusions: Intratumoral infusion of oncolytic virus DNX-2401 followed by radiotherapy in pediatric patients with DIPG resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events. (Funded by the European Research Council under the European Union's Horizon 2020 Research and Innovation Program and others; EudraCT number, 2016-001577-33; ClinicalTrials.gov number, NCT03178032.).
  • Autores: Hurkmans, E. G. E.; Groothuismink, J. M. G.; Vos, H. I.; et al.
    Revista: EUROPEAN JOURNAL OF HUMAN GENETICS
    ISSN: 1018-4813 Vol.30 N° Supl. 1 2022 págs. 515
  • Autores: Panizo Morgado, Elena; Lassaletta Atienza, Alvaro; Díaz-Villapalos, M.; et al.
    Revista: PEDIATRIC BLOOD AND CANCER
    ISSN: 1545-5009 Vol.69 N° Suppl. 5 2022 págs. S515 - S515
  • Autores: Van der Heijden, L.; Bosma, S.; Sierrasesúmaga Ariznavarreta, Luis; et al.
    Revista: PEDIATRIC BLOOD AND CANCER
    ISSN: 1545-5009 Vol.69 2022
  • Autores: Alba-Pavón, P.; Alana, L.; Gutiérrez Jimeno, Miriam; et al.
    Revista: PEDIATRIC BLOOD AND CANCER
    ISSN: 1545-5009 Vol.69 N° Supl. 5 2022 págs. S237 - S238
  • Autores: Nussbaumer, G.; Benesch, M.; Gielen, G. H.; et al.
    Revista: NEURO-ONCOLOGY
    ISSN: 1522-8517 Vol.24 N° Supl. 1 2022 págs. 72 - 73
  • Autores: Van-der-Heijden, L. (Autor de correspondencia); Farfalli, G. L.; Balaco, I.; et al.
    Revista: JOURNAL OF CHILDREN'S ORTHOPAEDICS
    ISSN: 1863-2521 Vol.15 N° 4 2021 págs. 322 - 330
    Resumen
    Purpose: The main challenge in reconstruction after malignant bone tumour resection in young children remains how and when growth-plates can be preserved and which options remain if impossible. Methods: We describe different strategies to assure best possible long-term function for young children undergoing resection of malignant bone tumours. Results: Different resources are available to treat children with malignant bones tumours: a) preoperative planning simulates scenarios for tumour resection and limb reconstruction, facilitating decision-making for surgical and reconstructive techniques in individual patients; b) allograft reconstruction offers bone-stock preservation for future needs. Most allografts are intact at long-term follow-up, but limb-length inequalities and corrective/revision surgery are common in young patients; c) free vascularized fibula can be used as stand-alone reconstruction, vascularized augmentation of structural allograft or devitalized autograft. Longitudinal growth and joint remodelling potential can be preserved, if transferred with vascularized proximal physis; d) epiphysiolysis before resection with continuous physeal distraction provides safe resection margins and maintains growth-plate and epiphysis; e) 3D printing may facilitate joint salvage by reconstruction with patient-specific instruments. Very short stems can be created for fixation in (epi-)metaphysis, preserving native joints; f) growing endoprosthesis can provide for remaining growth after resection of epi-metaphyseal tumours. At ten-year follow-up, limb survival was 89%, but multiple surgeries are often required; g) rotationplasty and amputation should be considered if limb salvage is impossible and/or would result in decreased function and quality of life. Conclusion: Several biological and technological reconstruction options must be merged and used to yield best outcomes when treating young children with malignant bone tumours. Level of evidence: Level V Expert opinion.
  • Autores: Agullo Pérez, A. D. (Autor de correspondencia); Resano Abarzuza, M. A.; Córdoba Iturriagagoitia, A.; et al.
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN: 1137-6627 Vol.44 N° 2 2021 págs. 163 - 176
    Resumen
    Background. Cutaneous, superficial and or suprafascial leiomyoma are divided into three variants: piloleiomyomas (PL), angioleiomyomas (AL) and genital leiomyomas (GL) that include the vulvar, scrotal and areolar forms. This study set out to establish the clinical and histological characteristics and incidence of each variant, and any likely associations with internal neoplasms. Methods. A review was carried out of 255 cases of cutaneous leiomyomas diagnosed between 1982 and 2018 at the Pathology departments of three hospitals (Navarra and Alicante). Demographic, clinical, histological and immunohistochemical variables were described and compared. Results. The incidence of PL in Navarra was 4.3 cases per million inhabitants a year, with another 20 cases of AL and 1.4 cases of GL. Cutaneous forms make up approximately 3.5% of the total leiomyomas. The population with PL suffered more frequently from breast cancer (OR = 4.8; CI 95%: 1.3-17.4; p = 0.006). Nipple leiomyomas are small, accompanied by localised pain, and are predominantly fascicular or solid, with very infrequent effect on the subcutaneous cellular tissue and scarce atypia. This makes for a contrast with the other GLs, which are medium sized and infrequently painful, predominantly nodular, and frequent effect on the subcutaneous tissue and atypia. Conclusions. The information provided here about the clinical and histological characteristics of the different varieties of leiomyomas indicate that there is a need to reconsider the classification of nipple leiomyomas outside the group of GLs. An association between PL and breast carcinoma was detected, which needs to be confirmed in future studies so as to determine if this leiomyoma is a risk marker for breast cancer.
  • Autores: Payo Ollero, Jesús (Autor de correspondencia); Moreno Figaredo, Victoria; Llombart Blanco, Rafael; et al.
    Revista: FOOT AND ANKLE SURGERY
    ISSN: 1268-7731 Vol.27 N° 5 2021 págs. 592
  • Autores: Pan, C. ; Humbatova, A.; Zheng, L.; et al.
    Revista: BRITISH JOURNAL OF DERMATOLOGY
    ISSN: 0007-0963 Vol.185 N° 2 2021 págs. 439 - 441
  • Autores: Gutiérrez Jimeno, Miriam; Alba-Pavón, P.; Astigarraga, I.; et al.
    Revista: CANCERS
    ISSN: 2072-6694 Vol.13 N° 21 2021 págs. 5436
    Resumen
    Simple Summary: Clinical management of sarcomas is complex because they are rare and heterogeneous tumors. Management requires a coordinated multidisciplinary approach, especially in children. Genomic characterization of this complex group of tumors contributes to the identification of prognostic biomarkers and to the continued expansion of therapeutic options. In this article, we present the positive experience of two Spanish hospitals in the use of genomic analysis in the overall clinical management of sarcomas in children and young adults. We describe on a case-by-case basis how genomic analysis has contributed to both diagnosis and treatment.Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing's sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.
  • Autores: Gambera, S.; Patiño García, Ana; Alfranca, A.; et al.
    Revista: CANCERS
    ISSN: 2072-6694 Vol.13 N° 9 2021 págs. 2003
    Resumen
    Osteosarcoma (OS) is a highly aggressive tumor characterized by malignant cells producing pathologic bone; the disease presents a natural tendency to metastasize. Genetic studies indicate that the OS genome is extremely complex, presenting signs of macro-evolution, and linear and branched patterns of clonal development. However, those studies were based on the phylogenetic reconstruction of next-generation sequencing (NGS) data, which present important limitations. Thus, testing clonal evolution in experimental models could be useful for validating this hypothesis. In the present study, lentiviral LeGO-vectors were employed to generate colorimetric red, green, blue (RGB)-marking in murine, canine, and human OS. With this strategy, we studied tumor heterogeneity and the clonal dynamics occurring in vivo in immunodeficient NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ (NSG) mice. Based on colorimetric label, tumor clonal composition was analyzed by confocal microscopy, flow cytometry, and different types of supervised and unsupervised clonal analyses. With this approach, we observed a consistent reduction in the clonal composition of RGB-marked tumors and identified evident clonal selection at the first passage in immunodeficient mice. Furthermore, we also demonstrated that OS could follow a neutral model of growth, where the disease is defined by the coexistence of different tumor sub-clones. Our study demonstrates the importance of rigorous testing of the selective forces in commonly used experimental models.
  • Autores: Rubio-San Simón, A.; Hladun Alvaro, R.; Juan Ribelles, A.; et al.
    Revista: CLINICAL AND TRANSLATIONAL ONCOLOGY
    ISSN: 1699-048X Vol.23 2021 págs. 2489 - 2496
    Resumen
    Purpose Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. Methods Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. Results Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. Conclusions The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barrie
  • Autores: Henarejos-Castillo, I.; Aleman, A.; Martínez-Montoro, B.; et al.
    Revista: JOURNAL OF PERSONALIZED MEDICINE
    ISSN: 2075-4426 Vol.11 N° 7 2021 págs. 609
    Resumen
    Ovarian failure (OF) is a common cause of infertility usually diagnosed as idiopathic, with genetic causes accounting for 10-25% of cases. Whole-exome sequencing (WES) may enable identifying contributing genes and variant profiles to stratify the population into subtypes of OF. This study sought to identify a blood-based gene variant profile using accumulation of rare variants to promote precision medicine in fertility preservation programs. A case-control (n = 118, n = 32, respectively) WES study was performed in which only non-synonymous rare variants <5% minor allele frequency (MAF; in the IGSR) and coverage >= 100x were considered. A profile of 66 variants of uncertain significance was used for training an unsupervised machine learning model to separate cases from controls (97.2% sensitivity, 99.2% specificity) and stratify the population into two subtypes of OF (A and B) (93.31% sensitivity, 96.67% specificity). Model testing within the IGSR female population predicted 0.5% of women as subtype A and 2.4% as subtype B. This is the first study linking OF to the accumulation of rare variants and generates a new potential taxonomy supporting application of this approach for precision medicine in fertility preservation.
  • Autores: Zalacain Díez, Marta; Buñuales Aramendía, María; Marrodán Fernández, Lucía; et al.
    Revista: MOLECULAR THERAPY ONCOLYTICS
    ISSN: 2372-7705 Vol.20 2021 págs. 23 - 33
    Resumen
    Osteosarcoma is the most frequent and aggressive bone tumor in children and adolescents, with a long-term survival rate of 30%. Interleukin-12 (IL-12) is a potent cytokine that bridges innate and adaptive immunity, triggers antiangiogenic responses, and achieves potent antitumor effects. In this work, we evaluated the antisarcoma effect of a high-capacity adenoviral vector encoding mouse IL-12. This vector harbored a mifepristone-inducible system for controlled expression of IL-12 (High-Capacity adenoviral vector enconding the EF1alpha promoter [HCA-EFZP]-IL-12). We found that local administration of the vector resulted in a reduction in the tumor burden, extended overall survival, and tumor eradication. Moreover, long-term survivors exhibited immunological memory when rechallenged with the same tumor cells. Treatment with HCA-EFZP-IL-12 also resulted in a significant decrease in lung metastasis. Immunohistochemical analyses showed profound remodeling of the osteosarcoma microenvironment with decreases in angiogenesis and macrophage and myeloid cell numbers. In summary, our data underscore the potential therapeutic value of IL-12 in the context of a drug-inducible system that allows controlled expression of this cytokine, which can trigger a potent antitumor immune response in primary and metastatic pediatric osteosarcoma.
  • Autores: Nguyen, T. T.; Shin, D. H.; Jiang, H.; et al.
    Revista: CANCER RESEARCH
    ISSN: 0008-5472 Vol.81 N° 13 Supl. S 2021
  • Autores: Gupta, S.; Laspidea Ustés, Virginia; Fueyo, J.; et al.
    Revista: CANCER RESEARCH
    ISSN: 0008-5472 Vol.81 N° 13 Supl. S 2021
  • Autores: Pelaez, J.; Monteiro, R.; Lobo, S.; et al.
    Revista: MEDICINE (BALTIMORE)
    ISSN: 0025-7974 Vol.100 N° 4 2021 págs. OP4
  • Autores: Alana-Rodrigo, L.; Alba-Pavon, P.; Villate-Bejarano, O.; et al.
    Revista: PEDIATRIC BLOOD AND CANCER
    ISSN: 1545-5009 Vol.68 N° Supl. 5 2021 págs. S288
  • Autores: Zuazo, M.; Arasanz, H.; Chocarro, L.; et al.
    Revista: ANNALS OF ONCOLOGY
    ISSN: 0923-7534 Vol.32 N° Supl. 5 2021 págs. S1028 - S1028
  • Autores: Ausejo Mauleón, Iker; Labiano Almiñana, Sara; Laspidea Ustés, Virginia; et al.
    Revista: NEURO-ONCOLOGY
    ISSN: 1522-8517 Vol.23 N° Supl. 1 2021 págs. 28
  • Autores: Lassaletta Atienza, Alvaro; Panizo Morgado, Elena; Vázquez, F.; et al.
    Revista: RADIOTHERAPY AND ONCOLOGY
    ISSN: 0167-8140 Vol.161 N° Supplement 1 2021 págs. S875 - S876
  • Autores: Herrador Cañete, Guillermo; Zalacain Díez, Marta; De la Nava Martin, Daniel; et al.
    Revista: HUMAN GENE THERAPY
    ISSN: 1043-0342 Vol.32 N° 19-20 2021 págs. A127
  • Autores: Ricobaraza Abarquero, Ana; González Aparicio, Manuela; Mora Jiménez, Lucía; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.21 N° 10 2020 págs. 3643
    Resumen
    The adaptation of adenoviruses as gene delivery tools has resulted in the development of high-capacity adenoviral vectors (HC-AdVs), also known, helper-dependent or "gutless". Compared with earlier generations (E1/E3-deleted vectors), HC-AdVs retain relevant features such as genetic stability, remarkable efficacy of in vivo transduction, and production at high titers. More importantly, the lack of viral coding sequences in the genomes of HC-AdVs extends the cloning capacity up to 37 Kb, and allows long-term episomal persistence of transgenes in non-dividing cells. These properties open a wide repertoire of therapeutic opportunities in the fields of gene supplementation and gene correction, which have been explored at the preclinical level over the past two decades. During this time, production methods have been optimized to obtain the yield, purity, and reliability required for clinical implementation. Better understanding of inflammatory responses and the implementation of methods to control them have increased the safety of these vectors. We will review the most significant achievements that are turning an interesting research tool into a sound vector platform, which could contribute to overcome current limitations in the gene therapy field.
  • Autores: Mirones, I.; Moreno, L.; Patiño García, Ana; et al.
    Revista: ANALES DE PEDIATRIA
    ISSN: 1695-4033 Vol.93 N° 1 2020 págs. 59.e1 - 59.e10
    Resumen
    Despite being a rare disease, cancer is the first cause of mortality due to disease during the paediatric age in the developed countries. The current, great increase in new treatments, such as immunotherapy, constitutes a new clinical and regulatory paradigm. Cellular immunotherapy is one of these types of immunotherapy. In particular, the advanced therapy drugs with chimeric antigen receptors in the T-lymphocytes (CAR-T), and particularly the CAR-T19 cells, has opened up a new scenario in the approach to haematology tumours like acute lymphoblastic leukaemia and the B-Cell lymphomas. The approval of tisagenlecleucel and axicabtagene ciloleucel by the regulatory authorities has led to the setting up of the National Plan for Advanced Therapies-CAR-T drugs in Spain. There is evidence of, not only the advantage of identifying the centres most suitable for their administration, but also the need for these to undergo a profound change in order that their healthcare activity is extended, in some cases, to the ability for the in-house manufacture of these types of therapies. The hospitals specialised in paediatric haematology-oncology thus have the challenge of progressing towards a healthcare model that integrates cellular immunotherapy, having the appropriate capacity to manage all aspects relative to their use, manufacture, and administration of these new treatments.
  • Autores: Paternain Nuin, Alberto (Autor de correspondencia); García Velloso, María José; Rosales Castillo, Juan Jose; et al.
    Revista: EUROPEAN JOURNAL OF RADIOLOGY
    ISSN: 0720-048X Vol.133 2020 págs. 109403
    Resumen
    Objectives: To analyze the feasibility of DWI-MRI and ADC to evaluate treatment response in patients with multiple myeloma (MM). To correlate the variations of ADC and SUVmax in F-18-FDG PET-CT. Methods: 27 patients with MM that had a whole-body MRI and F-18-FDG PET-CT performed at baseline and after treatment were retrospectively recruited between February 2018 and May 2020. Three target bone lesions were selected for each patient and their ADC, SUVmax and Deauville score were measured in every study. Correlation between ADC and SUVmax of the lesions was evaluated, as well as changes in mean ADC, SUVmax, and Deauville score between studies. Patients were classified as responder or non-responder according to the IMWG, MRI (MY-RADS) and PET-CT (IMPeTUs) response criteria. Agreement between the MRI and PET-CT criteria with the IMWG criteria was evaluated. Results: The correlation between the ADC and SUVmax of all the target lesions was strong, negative and significant (r=-0.603; p < 0.001). After treatment, mean ADC in lesions from responders was significantly higher than in non-responders (1585.51 x 10(-6) mm(2)/s vs 698.17 x 10(-6) mm(2)/s; p < 0.001). SUVmax of the same lesions was significantly lower in responders than in non-responders (2.05 vs 5.33; p < 0.001). There was a very strong or strong agreement of the IMWG response criteria with both MRI (kappa = 0.852; p < 0.001) and PET (kappa = 0.767; p < 0.001) criteria. Conclusion: DWI-MRI and ADC may be used to assess treatment response in MM patients, showing a good correlation with F-18-FDG PET-CT and the IMWG response criteria.
  • Autores: Mirabello, L.; Zhu, B.; koster, R.; et al.
    Revista: JAMA ONCOLOGY
    ISSN: 2374-2437 Vol.6 N° 5 2020 págs. 724 - 734
    Resumen
    This next-generation exome sequencing study investigates the frequency of pathogenic or likely pathogenic germline genetic variants in known cancer-susceptibility genes among patients with osteosarcoma. Importance Osteosarcoma, the most common malignant bone tumor in children and adolescents, occurs in a high number of cancer predisposition syndromes that are defined by highly penetrant germline mutations. The germline genetic susceptibility to osteosarcoma outside of familial cancer syndromes remains unclear. Objective To investigate the germline genetic architecture of 1244 patients with osteosarcoma. Design, Setting, and Participants Whole-exome sequencing (n = 1104) or targeted sequencing (n = 140) of the DNA of 1244 patients with osteosarcoma from 10 participating international centers or studies was conducted from April 21, 2014, to September 1, 2017. The results were compared with the DNA of 1062 individuals without cancer assembled internally from 4 participating studies who underwent comparable whole-exome sequencing and 27 & x202f;173 individuals of non-Finnish European ancestry who were identified through the Exome Aggregation Consortium (ExAC) database. In the analysis, 238 high-interest cancer-susceptibility genes were assessed followed by testing of the mutational burden across 736 additional candidate genes. Principal component analyses were used to identify 732 European patients with osteosarcoma and 994 European individuals without cancer, with outliers removed for patient-control group comparisons. Patients were subsequently compared with individuals in the ExAC group. All data were analyzed from June 1, 2017, to July 1, 2019. Main Outcomes and Measures The frequency of rare pathogenic or likely pathogenic genetic variants. Results Among 1244 patients with osteosarcoma (mean [SD] age at diagnosis, 16 [8.9] years [range, 2-80 years]; 684 patients [55.0%] were male), an analysis restricted to individuals with European ancestry indicated a significantly higher pathogenic or likely pathogenic variant burden in 238 high-interest cancer-susceptibility genes among patients with osteosarcoma compared with the control group (732 vs 994, respectively; P = 1.3 x 10(-18)). A pathogenic or likely pathogenic cancer-susceptibility gene variant was identified in 281 of 1004 patients with osteosarcoma (28.0%), of which nearly three-quarters had a variant that mapped to an autosomal-dominant gene or a known osteosarcoma-associated cancer predisposition syndrome gene. The frequency of a pathogenic or likely pathogenic cancer-susceptibility gene variant was 128 of 1062 individuals (12.1%) in the control group and 2527 of 27 & x202f;173 individuals (9.3%) in the ExAC group. A higher than expected frequency of pathogenic or likely pathogenic variants was observed in genes not previously linked to osteosarcoma (eg, CDKN2A, MEN1, VHL, POT1, APC, MSH2, and ATRX) and in the Li-Fraumeni syndrome-associated gene, TP53. Conclusions and Relevance In this study, approximately one-fourth of patients with osteosarcoma unselected for family history had a highly penetrant germline mutation requiring additional follow-up analysis and possible genetic counseling with cascade testing. Question What is the frequency of pathogenic or likely pathogenic germline genetic variants in known cancer-susceptibility genes in a large population of patients with osteosarcoma who were unselected for family history? Findings In this next-generation exome sequencing study of 1244 patients with osteosarcoma, 28.0% of patients in the discovery set carried a rare pathogenic or likely pathogenic germline variant in a cancer-susceptibility gene compared with 12.1% of individuals without cancer who were comparably sequenced and 9.3% of individuals of non-Finnish European ancestry identified through the Exome Aggregation Consortium database. Meaning A higher than expected frequency of patients with osteosarcoma carrying a pathogenic or likely pathogenic germline variant suggests germline genetic testing may be warranted for individuals with osteosarcoma.
  • Autores: Gutiérrez-Jimeno, M.; Panizo-Morgado, E.; Tamayo Uria, Ibon; et al.
    Revista: NPJ GENOMIC MEDICINE
    ISSN: 2056-7944 Vol.5 N° 1 2020 págs. 51
    Resumen
    Rothmund-Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted.
  • Autores: Paternain Nuin, Alberto (Autor de correspondencia); García Velloso, María José; Rosales Castillo, Juan Jose; et al.
    Revista: EUROPEAN JOURNAL OF RADIOLOGY
    ISSN: 0720-048X Vol.133 2020 págs. 109403
    Resumen
    Objectives: To analyze the feasibility of DWI-MRI and ADC to evaluate treatment response in patients with multiple myeloma (MM). To correlate the variations of ADC and SUVmax in 18F-FDG PET-CT. Methods: 27 patients with MM that had a whole-body MRI and 18F-FDG PET-CT performed at baseline and after treatment were retrospectively recruited between February 2018 and May 2020. Three target bone lesions were selected for each patient and their ADC, SUVmax and Deauville score were measured in every study. Correlation between ADC and SUVmax of the lesions was evaluated, as well as changes in mean ADC, SUVmax, and Deauville score between studies. Patients were classified as responder or non-responder according to the IMWG, MRI (MY-RADS) and PET-CT (IMPeTUs) response criteria. Agreement between the MRI and PET-CT criteria with the IMWG criteria was evaluated. Results: The correlation between the ADC and SUVmax of all the target lesions was strong, negative and significant (r=-0.603; p < 0.001). After treatment, mean ADC in lesions from responders was significantly higher than in non-responders (1585.51 × 10-6 mm2/s vs 698.17 × 10-6 mm2/s; p < 0.001). SUVmax of the same lesions was significantly lower in responders than in non-responders (2.05 vs 5.33; p < 0.001). There was a very strong or strong agreement of the IMWG response criteria with both MRI (¿ = 0.852; p < 0.001) and PET (¿ = 0.767; p < 0.001) criteria. Conclusion: DWI-MRI and ADC may be used to assess treatment response in MM patients, showing a good correlation with 18F-FDG PET-CT and the IMWG response criteria.
  • Autores: Lin, S. H. ; Sampson, J. N. ; Grunewald, T. G. P. ; et al.
    Revista: PLOS ONE
    ISSN: 1932-6203 Vol.15 N° 9 2020 págs. e0237792
    Resumen
    Background Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor. Methods We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry). Results We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively; P-value < 5x10(-8)) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84x10(-8)). Conclusions These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk. Impact Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci.
  • Autores: García Moure, Marc; González Huarriz, María Soledad; Laspidea Ustés, Virginia; et al.
    Revista: NEURO-ONCOLOGY
    ISSN: 1522-8517 Vol.22 N° Suppl. 2 2020 págs. 100 - 100
  • Autores: Petrilli, L. L.; Paolini, A.; Galardi, A.; et al.
    Revista: NEURO-ONCOLOGY
    ISSN: 1522-8517 Vol.22 N° Supl. 3 2020 págs. 347
  • Autores: Laspidea Ustés, Virginia; Puigdelloses Vallcorba, Montserrat; Martínez Velez, Naiara; et al.
    Revista: NEURO-ONCOLOGY
    ISSN: 1522-8517 Vol.22 2020 págs. 107 - 107
  • Autores: Castillo, I. H.; Aleman, A.; Martinez-Montoro, B.; et al.
    Revista: HUMAN REPRODUCTION
    ISSN: 0268-1161 Vol.35 N° Supl. 1 2020 págs. I364
  • Autores: García-Peláez, J.; Monteiro, R.; Sousa, L.; et al.
    Revista: EUROPEAN JOURNAL OF HUMAN GENETICS
    ISSN: 1018-4813 Vol.28 N° Suppl. 1 2020 págs. 61 - 63
  • Autores: Mulder, F. I. (Autor de correspondencia); Candeloro, M.; Kamphuisen, P. W.; et al.
    Revista: HAEMATOLOGICA
    ISSN: 0390-6078 Vol.104 N° 6 2019 págs. 1277 - 1287
    Resumen
    We aimed to evaluate the performance of the Khorana score in predicting venous thromboembolic events in ambulatory cancer patients. Embase and MEDLINE were searched from January 2008 to June 2018 for studies which evaluated the Khorana score. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Additional data on the 6-month incidence of venous thromboembolism were sought by contacting corresponding authors. The incidence in each Khorana score risk group was estimated with random effects meta-analysis. A total of 45 articles and eight abstracts were included, comprising 55 cohorts enrolling 34,555 ambulatory cancer patients. For 27,849 patients (81%), 6-month follow-up data were obtained. Overall, 19% of patients had a Khorana score of 0 points, 64% a score of 1 or 2 points, and 17% a score of 3 or more points. The incidence of venous thromboembolism in the first six months was 5.0% (95% CI: 3.9-6.5) in patients with a low-risk Khorana score (0 points), 6.6% (95% CI: 5.6-7.7) in those with an intermediate-risk Khorana score (1 or 2 points), and 11.0% (95% CI: 8.8-13.8) in those with a high-risk Khorana score (3 points or higher). Of the patients with venous thromboembolism in the first six months, 23.4% (95% CI: 18.4-29.4) had been classified as high risk according to the Khorana score. In conclusion, the Khorana score can be used to select ambulatory cancer patients at high risk of venous thromboembolism for thromboprophylaxis; however, most events occur outside this high-risk group.
  • Autores: Martínez Velez, Naiara; García Moure, Marc; Marigil Sánchez, Miguel; et al.
    Revista: NATURE COMMUNICATIONS
    ISSN: 2041-1723 Vol.10 N° 1 2019 págs. 2235
    Resumen
    Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032).
  • Autores: Habel, N.; Stefanovska, B.; Carene, D. ; et al.
    Revista: BMC CANCER
    ISSN: 1471-2407 Vol.19 2019 págs. 62
    Resumen
    BACKGROUND: Osteosarcoma is the most prevalent primary bone malignancy in children and young adults. These tumors are highly metastatic, leading to poor outcome. We previously demonstrated that Cysteine-rich protein 61 (CYR61/CCN1) expression level is correlated to osteosarcoma aggressiveness in preclinical model and in patient tumor samples. The aim of the present study was to investigate the CYR61-induced intracellular mechanisms leading to the acquisition of an invasive phenotype by osteosarcoma cells. METHODS: Modified murine and human osteosarcoma cell lines were evaluated for cell adhesion, aggregation (spheroid), motility (wound healing assay), phenotypic markers expression (RT-qPCR, western blot). Cell-derived xenograft FFPE samples and patients samples (TMA) were assessed by IHC. RESULTS: CYR61 levels controlled the expression of markers related to an Epithelial-mesenchymal transition (EMT)-like process, allowing tumor cells to migrate acquiring a competent morphology, and to be able to invade the surrounding stroma. This phenotypic shift indeed correlated with tumor grade and aggressiveness in patient samples and with the metastatic dissemination potential in cell-derived xenograft models. Unlike EGFR or PDGFR, IGF1Rß levels correlated with CYR61 and N-cadherin levels, and with the aggressiveness of osteosarcoma and overall survival. The expression levels of IGF1Rß/IGF1 axis were controlled by CYR61, and anti-IGF1 neutralizing antibody prevented the CYR61-induced phenotypic shift, aggregation, and motility abilities. CONCLUSIONS: Taken together, our study provides new evidence that CYR61 acts as a key inducing factor in the metastatic progression of osteosarcoma by playing a critical role in primary tumor dissemination, with a process associated with IGF1/IGFR stimulation. This suggests that CYR61 may represent a potential pivotal target for therapeutic management of metastases spreading in osteosarcoma, in correlation with IGF1/IGFR pathway.
  • Autores: Martínez Velez, Naiara; Marigil Sánchez, Miguel; García Moure, Marc; et al.
    Revista: ACTA NEUROPATHOLOGICA
    ISSN: 1432-0533 Vol.7 2019 págs. 64
    Resumen
    Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has shown safety and clinical efficacy in adults with recurrent gliomas. In this work, we evaluated the feasibility, safety and therapeutic efficacy of Delta-24-RGD in combination with radiotherapy in pHGGs and DIPGs models. Our results showed that the combination of Delta-24-RGD with radiotherapy was feasible and resulted in a synergistic anti-glioma effect in vitro and in vivo in pHGG and DIPG models. Interestingly, Delta-24-RGD treatment led to the downregulation of relevant DNA damage repair proteins, further sensitizing tumors cells to the effect of radiotherapy. Additionally, Delta-24-RGD/radiotherapy treatment significantly increased the trafficking of immune cells (CD3, CD4+ and CD8+) to the tumor niche compared with single treatments. In summary, administration of the Delta-24-RGD/radiotherapy combination to pHGG and DIPG models is safe and significantly increases the overall survival of mice bearing these tumors. Our data offer a rationale for the combination Delta-24-RGD/radiotherapy as a therapeutic option for children with these tumors. SIGNIFICANCE: Delta-24-RGD/radiotherapy administration is safe and significantly increases the survival of treated mice. These positive data underscore the urge to translate this approach to the clinical treatment of children with pHGG and DIPGs.
  • Autores: García Moure, Marc; Martínez Velez, Naiara; González Huarriz, María Soledad; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN: 2045-2322 Vol.9 N° 1 2019 págs. 14368
    Resumen
    Last advances in the treatment of pediatric tumors has led to an increase of survival rates of children affected by primitive neuroectodermal tumors, however, still a significant amount of the patients do not overcome the disease. In addition, the survivors might suffer from severe side effects caused by the current standard treatments. Oncolytic virotherapy has emerged in the last years as a promising alternative for the treatment of solid tumors. In this work, we study the anti-tumor effect mediated by the oncolytic adenovirus VCN-01 in CNS-PNET models. VCN-01 is able to infect and replicate in PNET cell cultures, leading to a cytotoxicity and immunogenic cell death. In vivo, VCN-01 increased significantly the median survival of mice and led to long-term survivors in two orthotopic models of PNETs. In summary, these results underscore the therapeutic effect ofVCN-01 for rare pediatric cancers such as PNETs, and warrants further exploration on the use of this virus to treat them.
  • Autores: Zalacain Díez, Marta; Laspidea Ustés, Virginia; Martínez Velez, Naiara; et al.
    Revista: CANCER RESEARCH
    ISSN: 0008-5472 Vol.79 N° 13 2019
  • Autores: Alba-Pavon, P.; Astigarraga, I. ; Garcia-Obregon, S.; et al.
    Revista: PEDIATRIC BLOOD AND CANCER
    ISSN: 1545-5009 Vol.66 2019 págs. S347 - S348
  • Autores: Pelaez, J. G. ; Monteiro, A.; Sousa, L. ; et al.
    Revista: EUROPEAN JOURNAL OF HUMAN GENETICS
    ISSN: 1018-4813 Vol.27 N° Supl. 2 2019 págs. 1126 - 1128
  • Autores: Nguyen, T.; Avci, N. G.; Shin, D. H.; et al.
    Revista: CANCERS
    ISSN: 2072-6694 Vol.10 N° 6 2018 págs. E171
    Resumen
    With the progress of immunotherapy in cancer, oncolytic viruses (OVs) have attracted more and more attention during the past decade. Due to their cancer-selective and immunogenic properties, OVs are considered ideal candidates to be combined with immunotherapy to increase both specificity and efficacy in cancer treatment. OVs preferentially replicate in and lyse cancer cells, resulting in in situ autovaccination leading to adaptive anti-virus and anti-tumor immunity. The main challenge in OV approaches is how to redirect the host immunity from anti-virus to anti-tumor and optimize the clinical outcome of cancer patients. Here, we summarize the conceptual updates on oncolytic virotherapy and immunotherapy in cancer, and the development of strategies to enhance the virus-mediated anti-tumor immune response, including: (1) arm OVs with cytokines to modulate innate and adaptive immunity; (2) combining OVs with immune checkpoint inhibitors to release T cell inhibition; (3) combining OVs with immune co-stimulators to enhance T cell activation. Future studies need to be enforced on developing strategies to augment the systemic effect on metastasized tumors.
  • Autores: Koster, R.; Panagiotou, O.A.; Wheeler, W.A.; et al.
    Revista: INTERNATIONAL JOURNAL OF CANCER
    ISSN: 0020-7136 Vol.142 N° 8 2018 págs. 1594 - 1601
    Resumen
    Survival rates for osteosarcoma, the most common primary bone cancer, have changed little over the past three decades and are particularly low for patients with metastatic disease. We conducted a multi-institutional genome-wide association study (GWAS) to identify germline genetic variants associated with overall survival in 632 patients with osteosarcoma, including 523 patients of European ancestry and 109 from Brazil. We conducted a time-to-event analysis and estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models, with and without adjustment for metastatic disease. The results were combined across the European and Brazilian case sets using a random-effects meta-analysis. The strongest association after meta-analysis was for rs3765555 at 9p24.1, which was inversely associated with overall survival (HR¿=¿1.76; 95% CI 1.41-2.18, p¿=¿4.84 × 10-7 ). After imputation across this region, the combined analysis identified two SNPs that reached genome-wide significance. The strongest single association was with rs55933544 (HR¿=¿1.9; 95% CI 1.5-2.4; p¿=¿1.3 × 10-8 ), which localizes to the GLDC gene, adjacent to the IL33 gene and was consistent across both the European and Brazilian case sets. Using publicly available data, the risk allele was associated with lower expression of IL33 and low expression of IL33 was associated with poor survival in an independent set of patients with osteosarcoma. In conclusion, we have identified the GLDC/IL33 locus on chromosome 9p24.1 as associated with overall survival in patients with osteosarcoma. Further studies are needed to confirm this association and shed light on the biological underpinnings of this susceptibility locus.
  • Autores: Collantes Martínez, María; Martínez Velez, Naiara; Zalacain Díez, Marta; et al.
    Revista: BMC CANCER
    ISSN: 1471-2407 Vol.18 N° 1 2018 págs. 1193
    Resumen
    BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([18F] FDG) and sodium [18F] Fluoride (Na [18F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses. METHODS: Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [18F]FDG and Na [18F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (107 and 108 pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [18F] FDG PET studies. [18F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [18F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques. RESULTS: The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [18F] FDG uptake, with a sensitivity and specificity of 100%. The [18F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [18F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [18F] F uptake, significantly higher than 143B tumors (p < 0.01).
  • Autores: Machiela, MJ.; Grünewald, TGP.; Surdez, D.; et al.
    Revista: NATURE COMMUNICATIONS
    ISSN: 2041-1723 Vol.9 N° 1 2018 págs. 3184
    Resumen
    Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1-FLI1 fusion. We performed a genome-wide association study of 733 EWS cases and 1346 unaffected individuals of European ancestry. Our study replicates previously reported susceptibility loci at 1p36.22, 10q21.3 and 15q15.1, and identifies new loci at 6p25.1, 20p11.22 and 20p11.23. Effect estimates exhibit odds ratios in excess of 1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS cases in familial cancer syndromes. Expression quantitative trait locus (eQTL) analyses identify candidate genes at 6p25.1 (RREB1) and 20p11.23 (KIZ). The 20p11.22 locus is near NKX2-2, a highly overexpressed gene in EWS. Interestingly, most loci reside near GGAA repeat sequences and may disrupt binding of the EWSR1-FLI1 fusion protein. The high locus to case discovery ratio from 733 EWS cases suggests a genetic architecture in which moderate risk SNPs constitute a significant fraction of risk.
  • Autores: Martín-Guerrero, I.; Bilbao-Aldaiturriaga, N.; Gutiérrez-Camino, A.; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN: 2045-2322 Vol.8 N° 1 2018 págs. 15414
    Resumen
    Association studies in osteosarcoma risk found significant results in intergenic regions, suggesting that regions which do not codify for proteins could play an important role. The deregulation of microRNAs (miRNAs) has been already associated with osteosarcoma. Consequently, genetic variants affecting miRNA function could be associated with risk. This study aimed to evaluate the involvement of all genetic variants in pre-miRNAs described so far in relationship to the risk of osteosarcoma. We analyzed a total of 213 genetic variants in 206 pre-miRNAs in two cohorts of osteosarcoma patients (n¿=¿100) and their corresponding controls (n¿=¿256) from Spanish and Slovenian populations, using Goldengate Veracode technology (Illumina). Four polymorphisms in pre-miRNAs at 14q32 miRNA cluster were associated with osteosarcoma risk in the Spanish population (rs12894467, rs61992671, rs58834075 and rs12879262). Pathway enrichment analysis including target genes of these miRNAs pointed out the WNT signaling pathways overrepresented. Moreover, different single nucleotide polymorphism (SNP) effects between the two populations included were observed, suggesting the existence of population differences. In conclusion, 14q32 miRNA cluster seems to be a hotspot for osteosarcoma susceptibility in the Spanish population, but not in the Slovenian, which supports the idea of the existence of population differences in developing this disease.
  • Autores: Varela Guruceaga, Maider; Tejada Solís, Sonia; García Moure, Marc; et al.
    Revista: CANCERS
    ISSN: 2072-6694 Vol.10 N° 7 2018 págs. E226.
  • Autores: Ruiz-Pinto, S.; Pita, G.; Martín, M.; et al.
    Revista: BREAST CANCER RESEARCH AND TREATMENT
    ISSN: 0167-6806 Vol.167 N° 1 2018 págs. 249 - 256
    Resumen
    PURPOSE: Anthracyclines are widely used chemotherapeutic drugs that can cause progressive and irreversible cardiac damage and fatal heart failure. Several genetic variants associated with anthracycline-induced cardiotoxicity (AIC) have been identified, but they explain only a small proportion of the interindividual differences in AIC susceptibility. METHODS: In this study, we evaluated the association of low-frequency variants with risk of chronic AIC using the Illumina HumanExome BeadChip array in a discovery cohort of 61 anthracycline-treated breast cancer patients with replication in a second independent cohort of 83 anthracycline-treated pediatric cancer patients, using gene-based tests (SKAT-O). RESULTS: The most significant associated gene in the discovery cohort was ETFB (electron transfer flavoprotein beta subunit) involved in mitochondrial ß-oxidation and ATP production (P = 4.16 × 10-4) and this association was replicated in an independent set of anthracycline-treated cancer patients (P = 2.81 × 10-3). Within ETFB, we found that the missense variant rs79338777 (p.Pro52Leu; c.155C > T) made the greatest contribution to the observed gene association and it was associated with increased risk of chronic AIC in the two cohorts separately and when combined (OR 9.00, P = 1.95 × 10-4, 95% CI 2.83-28.6). CONCLUSIONS: We identified and replicated a novel gene, ETFB, strongly associated with chronic AIC independently of age at tumor onset and related to anthracycline-mediated mitochondrial dysfunction. Although experimental verification and further studies in larger patient cohorts are required to confirm our finding, we demonstrated that exome array data analysis represents a valuable strategy to identify novel genes contributing to the susceptibility to chronic AIC.
  • Autores: Machiela, M. J.; Grunewald, T. G.; Surdez, D.; et al.
    Revista: CANCER RESEARCH
    ISSN: 0008-5472 Vol.78 N° 13 2018
  • Autores: Machiela, M. J. ; Grunewald, T. G. P.; Surdez, D.; et al.
    Revista: CANCER RESEARCH
    ISSN: 0008-5472 Vol.78 N° 19 2018
  • Autores: Koster, R.; Panagiotou, O. A.; Wheeler, W. A. ; et al.
    Revista: CANCER RESEARCH
    ISSN: 0008-5472 Vol.78 N° 13 Supl. 2018

Proyectos desde 2018

  • Título: MEdicina PERsonalizada para el TRatamiento de la OBEsidad: Integración de datos ómicos, dietéticos y de estilo de vida para la optimización de la nutrición personalizada del paciente con obesidad
    Código de expediente: 0011-1383-2022-000015 (PC098 MEPERTROBE)
    Investigador principal: JAVIER GOMEZ AMBROSI, JAVIER GOMEZ AMBROSI.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2022 GN Proyectos Colaborativos
    Fecha de inicio: 01-09-2022
    Fecha fin: 30-11-2024
    Importe concedido: 280.995,26€
    Otros fondos: -
  • Título: GRANATE - GRUPO DE RADIOTERAPIA AVANZADA DE NAVARRA ¿ TERAPIA Y EFICACIA
    Código de expediente: 0011-1411-2022-000066
    Investigador principal: ANA PATIÑO GARCIA.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2022 GN PROYECTOS ESTRATEGICOS DE I+D 2022-2025
    Fecha de inicio: 01-06-2022
    Fecha fin: 31-12-2024
    Importe concedido: 536.739,00€
    Otros fondos: -
  • Título: Tumor Immune Microenvironment (TIME) targeted therapy in pediatric brain cancer
    Código de expediente: PCI2021-122084-2B
    Investigador principal: MARTA MARIA ALONSO ROLDAN.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2021 AEI Proyectos de Colaboración Internacional - 2
    Fecha de inicio: 01-02-2022
    Fecha fin: 31-01-2024
    Importe concedido: 160.932,00€
    Otros fondos: -
  • Título: Inmunoviroterapia contra el osteosarcoma pediátrico: análisis preclínico de las estrategias basadas en el virus Delta-24-RGDOX.
    Código de expediente: PI21/00940
    Investigador principal: ANA PATIÑO GARCIA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2021 AES Proyectos de investigación
    Fecha de inicio: 01-01-2022
    Fecha fin: 31-12-2024
    Importe concedido: 171.820,00€
    Otros fondos: Fondos FEDER
  • Título: SEHOP-PENCIL study- Personalised Medicine for Cancer in Children in Spain Estrategia nacional para la implementación de la medicina personalizada en niños y adolescentes con cáncer A Spanish nation-wide strategy to implement personalised medicine in child
    Código de expediente: PMP21/00087
    Investigador principal: ANA PATIÑO GARCIA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2021 AES Medicina Personalizada
    Fecha de inicio: 01-01-2022
    Fecha fin: 31-12-2025
    Importe concedido: 200.420,00€
    Otros fondos: -
  • Título: Plasma extracellular vesicles (EVs): the key for precision medicine in Glioblastoma
    Código de expediente: AC20/00094
    Investigador principal: JAIME GALLEGO PEREZ DE LARRAYA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2020 AES Programación Conjunta Internacional
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2023
    Importe concedido: 38.720,00€
    Otros fondos: -
  • Título: Ayuda para contratación Juan de la Cierva Formación 2018
    Código de expediente: FJC2018-037394-I
    Investigador principal: MARTA MARIA ALONSO ROLDAN.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2018 AEI - MCIU JUAN DE LA CIERVA FORMACIÓN
    Fecha de inicio: 01-04-2020
    Fecha fin: 31-03-2022
    Importe concedido: 50.000,00€
    Otros fondos: Fondos FEDER
  • Título: Ensayo clínico fase I con el adenovirus oncolítico DNX-2440 para el tratamiento de tumores cerebrales pediátricos recurrentes.
    Código de expediente: PI19/01896
    Investigador principal: MARTA MARIA ALONSO ROLDAN.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2019 AES Proyectos de investigación
    Fecha de inicio: 01-01-2020
    Fecha fin: 30-06-2024
    Importe concedido: 189.970,00€
    Otros fondos: Fondos FEDER
  • Título: Papel del RNU6 aislado de exosomas circulantes como marcador diagnóstico y de seguimiento en pacientes con glioblastoma
    Código de expediente: PI19/01440
    Investigador principal: JAIME GALLEGO PEREZ DE LARRAYA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2019 AES Proyectos de investigación
    Fecha de inicio: 01-01-2020
    Fecha fin: 31-12-2023
    Importe concedido: 96.800,00€
    Otros fondos: Fondos FEDER
  • Título: Inmunoviroterapia contra el osteosarcoma infantil.
    Código de expediente: PI18/00614
    Investigador principal: ANA PATIÑO GARCIA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: AES2018 PI
    Fecha de inicio: 01-01-2019
    Fecha fin: 31-12-2021
    Importe concedido: 93.170,00€
    Otros fondos: Fondos FEDER
  • Título: Desarrollo y validación de paneles génicos en niños y adolescentes con cáncer: herramientas clínicas de diagnóstico, predicción y asesoramiento genético.
    Código de expediente: 54/2018
    Investigador principal: ANA PATIÑO GARCIA.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2018 PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 01-01-2019
    Fecha fin: 31-12-2020
    Importe concedido: 49.352,25€
    Otros fondos: Fondos FEDER
  • Título: Implantación del diagnóstico de la epilepsia y la migraña en Navarra (Geneurona)
    Código de expediente: 0011-1411-2018-000053
    Investigador principal: MARIA CRUZ RODRIGUEZ OROZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2018 GN PROYECTOS ESTRATEGICOS DE I+D 2018-2020
    Fecha de inicio: 01-04-2018
    Fecha fin: 30-11-2020
    Importe concedido: 18.481,69€
    Otros fondos: -
  • Título: PT17/0015/0018 PLATAFORMA BIOBANCO 2017 TF
    Código de expediente: PT17/0015/0018
    Investigador principal: MARIA ANTONIA FORTUÑO CEBAMANOS.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2017 - PLATAFORMAS DE APOYO A LA INVESTIGACIÓN EN CIENCIAS Y TECNOLOGÍAS DE LA SALUD
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2021
    Importe concedido: 85.800,00€
    Otros fondos: Fondos FEDER
  • Título: Personalización genómica de la población navarra para la prevención del fallo ovárico precoz
    Código de expediente: 0011-1365-2017-000215
    Investigador principal: GORKA ALKORTA ARANBURU.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2017 GN I+D
    Fecha de inicio: 01-06-2017
    Fecha fin: 30-04-2019
    Importe concedido: 153.704,12€
    Otros fondos: -
  • Título: Tecnología de secuenciación de nueva generación (NGS) para optimizar la eficacia del diagnóstico y tratamiento en pacientes con tumores de alta mortalidad (DIANA: Diagnostico biomédico e Innovación Abierta en Navarra)
    Código de expediente: 0011-1411-2017-000030
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2017 GN ESTRATEGICOS
    Fecha de inicio: 01-04-2017
    Fecha fin: 30-11-2019
    Importe concedido: 37.315,72€
    Otros fondos: -
  • Título: Modulando el sistema inmune con adenovirus oncolíticos como estrategia para los tumores difusos de tronco (DIPGs).
    Código de expediente: PI16/00066
    Investigador principal: MARTA MARIA ALONSO ROLDAN.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2016 AES PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2019
    Importe concedido: 86.515,00€
    Otros fondos: Fondos FEDER
  • Título: Utilidad de un perfil de ARN pequeño no codificante aislado en exosomas circulantes como marcador diagnóstico y de seguimiento en pacientes con glioblastoma multiforme
    Código de expediente: 42/2015
    Investigador principal: JAIME GALLEGO PEREZ DE LARRAYA.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2015 GN SALUD
    Fecha de inicio: 06-12-2015
    Fecha fin: 05-12-2018
    Importe concedido: 50.682,00€
    Otros fondos: -
  • Título: Remodeling the tumor microenvironment with biological therapies as treatment for Diffuse Intrinsic Pontine Gliomas
    Código de expediente:
    Investigador principal: MARTA MARIA ALONSO ROLDAN
    Financiador: MICHAEL MOSIER DEFEAT DIPG FOUNDATION
    Convocatoria: Research Grant
    Fecha de inicio: 01-07-2021
    Fecha fin: 30-06-2024
    Importe concedido: 589.305,00€
    Otros fondos: -
  • Título: Viroimmunotherapeutic strategies to heat up DIPG microenviroment. A comprehensive approach to unleash anti-tumor immune response
    Código de expediente:
    Investigador principal: MARC GARCIA MOURE
    Financiador: MICHAEL MOSIER DEFEAT DIPG FOUNDATION
    Convocatoria: DEFEAT DIPG CHADTOUGH GRANTS
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2022
    Importe concedido: 150.000,00€
    Otros fondos: -
  • Título: ViroPedTher - Oncolytic viruses for the treatment of pediatric brain tumors: An integrated clinical and labapproach
    Código de expediente:
    Investigador principal: MARTA MARIA ALONSO ROLDAN
    Financiador: COMISIÓN EUROPEA
    Convocatoria: H2020-ERC-2018-COG
    Fecha de inicio: 01-03-2019
    Fecha fin: 01-09-2024
    Importe concedido: 2.000.000,00€
    Otros fondos: -
  • Título: Immuno-modulation mediated by virotherapy in osteosarcoma
    Código de expediente:
    Investigador principal: NAIARA MARTINEZ VELEZ
    Financiador: AACR - American Association Cancer Research
    Convocatoria: 2018 AACR - American
    Fecha de inicio: 01-07-2018
    Fecha fin: 30-06-2020
    Importe concedido: 93.113,00€
    Otros fondos: -
  • Título: Inmunomodulación del microambiente tumoral para el tratamiento del glioma difuso de línea media
    Investigador principal: SARA LABIANO ALMIÑANA, JAIME GALLEGO PEREZ DE LARRAYA
    Financiador: FUNDACIÓN BLANCA MORELL
    Convocatoria: 2021 FD BLANCA MORELL - Proyectos de Investigación en Gliomas
    Fecha de inicio: 10-02-2022
    Fecha fin: 09-02-2025
    Importe concedido: 194.352,00€
  • Título: Combinatorial biotherapies for the treatment of pediatric diffuse midline glioma
    Investigador principal: MARTA MARIA ALONSO ROLDAN
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: 2021 AECC Proyectos Generales
    Fecha de inicio: 01-12-2021
    Fecha fin: 30-11-2024
    Importe concedido: 300.000,00€
  • Título: Estudio de los mecanismos implicados en el déficit neurocognitivo en supervivientes de un tumor cerebral infantil y desarrollo de estrategias terapéuticas que minimicen las secuelas neurológicas a largo plazo.
    Investigador principal: SARA LABIANO ALMIÑANA
    Financiador: FUNDACION ALICIA KOPLOWITZ
    Convocatoria: 2021 FD Alicia Koplowitz - Proyectos de investigación
    Fecha de inicio: 01-11-2021
    Fecha fin: 31-10-2023
    Importe concedido: 45.000,00€
  • Título: Niños Contra el Cáncer (3 Convenio FDBLC)
    Investigador principal: MARTA MARIA ALONSO ROLDAN, ANA PATIÑO GARCIA
    Financiador: FUNDACIÓN BANCARIA LA CAIXA
    Convocatoria: 2021 FD La Caixa Niños contra el cáncer
    Fecha de inicio: 28-09-2021
    Fecha fin: 31-12-2022
    Importe concedido: 100.000,00€
  • Título: Terapias avanzadas para tumores sólidos pediátricos
    Investigador principal: MARTA MARIA ALONSO ROLDAN, ANA PATIÑO GARCIA, JAIME GALLEGO PEREZ DE LARRAYA
    Financiador: FUNDACIÓN ADEY
    Convocatoria: 2021 FD ADEY Proyectos
    Fecha de inicio: 01-04-2021
    Fecha fin: 03-04-2024
    Importe concedido: 120.000,00€
  • Título: Plasma extracellular vesicles (EVs): the key for precision medicine in Glioblastoma
    Investigador principal: JAIME GALLEGO PEREZ DE LARRAYA
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: 2020 AECC ERA Permed
    Fecha de inicio: 01-12-2020
    Fecha fin: 30-11-2023
    Importe concedido: 41.295,00€
  • Título: Targeting calcium channels against primary and resistant glioblastoma
    Investigador principal: MARTA MARIA ALONSO ROLDAN
    Financiador: FUNDACIO "LA MARATO DE TV3"
    Convocatoria: 2019 FD LA MARATÓ PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 31-07-2020
    Fecha fin: 30-07-2023
    Importe concedido: 117.500,00€
  • Título: Inmunovirus para el tratamiento del Osteosarcoma.
    Investigador principal: MARTA MARIA ALONSO ROLDAN
    Financiador: Asociación Pablo Ugarte
    Convocatoria: 2018 APU PI
    Fecha de inicio: 05-02-2018
    Fecha fin: 31-12-2024
    Importe concedido: 112.300,00€
  • Título: Terapia Génica para el Síndrome de Dravet
    Investigador principal: MIGUEL VALENCIA USTARROZ
    Financiador: FUNDACION INOCENTE INOCENTE
    Convocatoria: FUNDACION INOCENTE INOCENTE 2017
    Fecha de inicio: 19-10-2017
    Fecha fin: 31-01-2019
    Importe concedido: 29.755,00€
  • Título: Niños contra el cáncer - Inmunoterapia basada en el uso de células dendríticas en tumores sólidos avanzados de niños y adolescentes
    Investigador principal: MARTA MARIA ALONSO ROLDAN, ANA PATIÑO GARCIA
    Financiador: FUNDACIÓN BANCARIA LA CAIXA
    Convocatoria: 2017 CAIXA NCC
    Fecha de inicio: 26-09-2017
    Fecha fin: 27-09-2021
    Importe concedido: 400.000,00€
  • Título: Optimización de la quimioterapia en sarcomas óseos pediátricos mediante el uso de nanopartículas lipídicas
    Investigador principal: MARIA JOSE BLANCO PRIETO
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: 2014 AECC Cancer Infantil
    Fecha de inicio: 01-10-2014
    Fecha fin: 30-09-2019
    Importe concedido: 150.000,00€