Tumores sólidos pediátricos

Autores: De la Nava Martin, Daniel; Mert Selvi, K.; Alonso Roldán, Marta María (Autor de correspondencia)

Título: Immunovirotherapy for pediatric solid tumors: a promising treatment that is becoming a reality

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.

Título: Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune memory

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.

Título: What do we know about survival in skeletally premature children aged 0 to 10 years with Ewing sarcoma? A multicenter 10-year follow-up study in 60 patients

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.

Título: Case report: the value of genomic analysis in a case of megakaryoblastic leukemia with atypical initial manifestation

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.

Título: Galectin-3 inhibition boosts the therapeutic efficacy of Semliki Forest virus in pediatric osteosarcoma

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.

Título: Different effects of valproic acid on SLC12A2, SLC12A5 and SLC5A8 gene expression in pediatric glioblastoma cells as an approach to personalised therapy

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: Gargallo, P. (Autor de correspondencia); Bautista, F.; Juan-Ribelles, A.; et al.

Título: Current status of precision medicine in pediatric oncology in Spain: a consensus report by the Spanish Society of Paediatric Haematology and Oncology (SEHOP)

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.

Título: Oncolytic DNX-2401 virus for pediatric diffuse intrinsic pontine glioma

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.

Título: Pharmacogenetics of chemotherapy response in osteosarcoma: a genetic variant in SLC7A8 is associated with progressive disease

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.

Título: Two-year experience of a new proton facility in Madrid treating pediatric cancer patients during the Covid pandemic

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.

Título: / #58 What do we know about survival in skeletally premature children aged 0 to 10 years with ewing sarcoma? Multicenter 10-year follow-up study in 60 patients

Revista: PEDIATRIC BLOOD AND CANCER

ISSN: 1545-5009 Vol.69 2022
Autores: Nussbaumer, G.; Benesch, M.; Gielen, G. H.; et al.

Título: Gliomatosis cerebri in children: a collaborative report from the European Society for Pediatric Oncology (SIOPE)

Revista: NEURO-ONCOLOGY

ISSN: 1522-8517 Vol.24 N° Supl. 1 2022 págs. 72 - 73
Autores: Agulló-Pérez, A. D. (Autor de correspondencia); Resano-Abárzuza, M. A.; Córdoba-Iturriagagoitia, A.; et al.

Título: Cutaneous leiomyomas: a clinicpathological and epidemiological review

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: Agullo Pérez, A. D. (Autor de correspondencia); Resano Abarzuza, M. A.; Córdoba Iturriagagoitia, A.; et al.

Título: Leiomiomas cutáneos: revisión clinicopatológica y epidemiológica

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: Van-der-Heijden, L. (Autor de correspondencia); Farfalli, G. L.; Balaco, I.; et al.

Título: Biology and technology in the surgical treatment of malignant bone tumours in children and adolescents, with a special note on the very young

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: Payo Ollero, Jesús (Autor de correspondencia); Moreno Figaredo, Victoria; Llombart Blanco, Rafael; et al.

Título: Response to letter to the Editor by Correa DG, Canella C and Costa FM. Foot Ankle Surg. 2021 26:S1268-7731(21)00086-2. DOI: 10.1016/j.fas.2021.04.008

Revista: FOOT AND ANKLE SURGERY

ISSN: 1268-7731 Vol.27 N° 5 2021 págs. 592
Autores: Pan, C. ; Humbatova, A.; Zheng, L.; et al.

Título: Additional causal SNRPE mutations in hereditary hypotrichosis simplex

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.

Título: Clinical value of NGS genomic studies for clinical management of pediatric and young adult bone sarcomas

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.

Título: RGB-marking to identify patterns of selection and neutral evolution in human osteosarcoma models

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.

Título: The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP)

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.

Título: Machine learning-based approach highlights the use of genomic variant profile for precision medicine in ovarian failure

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.

Título: Local administration of IL-12 with an HC vector results in local and metastatic tumor control in pediatric osteosarcoma

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: Pelaez, J.; Monteiro, R.; Lobo, S.; et al.

Título: Genotype-phenotype associations provide a rational to identify potentially actionable vus

Revista: MEDICINE (BALTIMORE)

ISSN: 0025-7974 Vol.100 N° 4 2021 págs. OP4
Autores: Nguyen, T. T.; Shin, D. H.; Jiang, H.; et al.

Título: Inhibition of the IDO-Kyn-AhR cascade optimizes virotherapy in glioblastoma and depends on CD4 T-cell activation

Revista: CANCER RESEARCH

ISSN: 0008-5472 Vol.81 N° 13 Supl. S 2021
Autores: Gupta, S.; Laspidea Ustés, Virginia; Fueyo, J.; et al.

Título: Armed oncolytic virus for treatment of pediatric diffuse intrinsic pontine glioma

Revista: CANCER RESEARCH

ISSN: 0008-5472 Vol.81 N° 13 Supl. S 2021
Autores: Alana-Rodrigo, L.; Alba-Pavon, P.; Villate-Bejarano, O.; et al.

Título: Usefulness of next generation sequencing in the diagnosis and therapeutic management of pediatric central nervous system tumors

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.

Título: Comparison of different hyperprogressive disease criteria in non-small cell lung cancer patients treated with immunotherapy and correlation with somatic mutations in driver genes

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.

Título: Microenvironment modulation by TIM-3 blockade improves the outcome of preclinical DIPG models

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.

Título: Proton versus photon craniospinal irradiation in Pediatric patients with high-risk medulloblastoma

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.

Título: Expression of galectin-3 inhibitors from a self-replicating RNA vector can inhibit the growth of pediatric osteosarcoma

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.

Título: High-capacity adenoviral vectors: expanding the scope of gene therapy

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.

Título: Inmunoterapia con células CAR-T en hematooncología pediátrica

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.

Título: The utility of ADC value in diffusion-weighted whole-body MRI in the follow-up of patients with multiple myeloma. Correlation study with F-18-FDG PET-CT

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.

Título: Frequency of pathogenic germline variants in cancer-susceptibility genes in patients with osteosarcoma

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.

Título: Somatic and germline analysis of a familial Rothmund-Thomson syndrome in two siblings with osteosarcoma

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.

Título: The utility of ADC value in diffusion-weighted whole-body MRI in the follow-up of patients with multiple myeloma. Correlation study with 18F-FDG PET-CT

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.

Título: Low-frequency variation near common germline susceptibility loci are associated with risk of Ewing sarcoma

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.

Título: Characterization of the oncolytic adenovirus DELTA-24-RGD as therapeutic agent for the treatment of the pediatric embryonal brain tumors AT/RT and CNS-PNET

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.

Título: Identification of novel subgroup-specific miRNA exosomal biomarkers in pediatric high-grade gliomas

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.

Título: Oncolytic adenovirus delta-24-rgd engineered to express 4-1bbl as a therapeutic approach for dipg

Revista: NEURO-ONCOLOGY

ISSN: 1522-8517 Vol.22 2020 págs. 107 - 107
Autores: Castillo, I. H.; Aleman, A.; Martinez-Montoro, B.; et al.

Título: Clinical exome sequencing from peripheral blood reveals novel gene variants to prevent ovarian failure

Revista: HUMAN REPRODUCTION

ISSN: 0268-1161 Vol.35 N° Supl. 1 2020 págs. I364
Autores: García-Peláez, J.; Monteiro, R.; Sousa, L.; et al.

Título: The first genotype-phenotype study on European carriers of CDH1 germline mutations

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.

Título: The Khorana score for prediction of venous thromboembolism in cancer patients: a systematic review and meta-analysis

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.

Título: The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models

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.

Título: CYR61 triggers osteosarcoma metastatic spreading via an IGF1R-dependent EMT-like process

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.

Título: Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models

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.

Título: The oncolytic adenovirus VCN-01 promotes anti-tumor effect in primitive neuroectodermal tumor models

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.

Título: High-capacity adenoviral vectors with controlled expression of interleukin 12 as a new strategy against pediatric osteosarcoma

Revista: CANCER RESEARCH

ISSN: 0008-5472 Vol.79 N° 13 2019
Autores: Alba-Pavon, P.; Astigarraga, I. ; Garcia-Obregon, S.; et al.

Título: Identification of Gardner Syndrome Among Paediatric Fibroblastic and Myofibroblastic Tumours: A Study of 7 Cases

Revista: PEDIATRIC BLOOD AND CANCER

ISSN: 1545-5009 Vol.66 2019 págs. S347 - S348
Autores: Pelaez, J. G. ; Monteiro, A.; Sousa, L. ; et al.

Título: European Landscape of CDH1 germline mutations: a new tool to understand hereditary diffuse gastric cancer (HDGC)

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.

Título: Tune Up In Situ autovaccination against solid tumors with oncolytic viruses

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.

Título: Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients

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.

Título: Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [18F]FDG and sodium [18F]fluoride PET

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.

Título: Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility.

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.

Título: Variants in the 14q32 miRNA cluster are associated with osteosarcoma risk in the Spanish population.

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.

Título: Oncolytic viruses as therapeutic tools for pediatric brain tumors.

Revista: CANCERS

ISSN: 2072-6694 Vol.10 N° 7 2018 págs. E226.
Autores: Ruiz-Pinto, S.; Pita, G.; Martín, M.; et al.

Título: Exome array analysis identifies ETFB as a novel susceptibility gene for anthracycline-induced cardiotoxicity in cancer patients.

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.

Título: Multiple new susceptibility loci identified in genome-wide association study of Ewing sarcoma

Revista: CANCER RESEARCH

ISSN: 0008-5472 Vol.78 N° 13 2018
Autores: Machiela, M. J. ; Grunewald, T. G. P.; Surdez, D.; et al.

Título: Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility

Revista: CANCER RESEARCH

ISSN: 0008-5472 Vol.78 N° 19 2018
Autores: Koster, R.; Panagiotou, O. A.; Wheeler, W. A. ; et al.

Título: Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients

Revista: CANCER RESEARCH

ISSN: 0008-5472 Vol.78 N° 13 Supl. 2018

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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: 29-02-2024

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: 31-12-2022

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€

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