Miembros del Grupo
Coordinador
Investigadores
Ricardo
Diez Valle
Marc
García Moure
Sonia
Tejada Solís
Ignacio
Íñigo Marco
Colaboradores
Iker
Ausejo Mauleón
Líneas de Investigación
- Búsquedas de marcadores diagnósticos, pronósticos de respuesta a terapias en exosomas de sangre periférica.
- Ensayos clínicos de nuevas terapias.
- Mejora de nuestro conocimiento de la respuesta a radioterapia.
- Nuevas terapias biológicas solas o en combinación con radioterapia.
Palabras Clave
- Biomarcadores
- Exosomas
- Genética molecular
- Inmunoterapia
- Metástasis cerebrales
- Radioterapia
- Terapias biológicas
- Tumores cerebrales
- Viroterapia
Publicaciones Científicas desde 2018
-
Autores: Gállego Pérez de Larraya, Jaime (Autor de correspondencia); García Moure, Marc; Alonso Roldán, Marta MaríaRevista: REVUE NEUROLOGIQUEISSN: 0035-3787 Vol.179 N° 5 2023 págs. 475 - 480ResumenDiffuse intrinsic pontine glioma (DIPG) is the most frequent brainstem glioma and the most lethal brain tumor in childhood. Despite transient benefit with radiotherapy, the prognosis of children with this disease remains dismal with severe neurological morbidity and median survival less than 12 months. Oncolytic immunovirotherapy is emerging as a potential therapeutic approach in neuro-oncology. The oncolytic adenovirus Delta-24-RGD has shown efficacy in adult patients with recurrent GBM. Our group has demonstrated that Delta-24-RGD has oncolytic activity and triggers immune response in preclinical models of DIPG, and has a synergistic effect with radiotherapy in animal models of this disease. In this scenario, we conducted a first-in-human phase 1 clinical trial to evaluate the safety and efficacy of intratumoral injection of Delta-24-RGD in pediatric patients with newly diagnosed DIPG prior to standard radiotherapy. The study confirmed the feasibility of this treatment with an acceptable safety profile and encouraging efficacy results. Correlative analyses showed a biological activity from Delta-24-RGD in DIPG. Further advanced trials are needed to validate these results. Meanwhile, plenty of opportunities to increase the potential contribution of oncolytic viruses in the management of devastating tumors with no current effective treatment such as DIPG need to be explored and exploited.
-
Autores: Foster, J. B. (Autor de correspondencia); Alonso Roldán, Marta María; Sayour, E.; et al.Revista: NEOPLASIAISSN: 1476-5586 Vol.42 2023 págs. 100909ResumenWhile immunotherapy for pediatric cancer has made great strides in recent decades, including the FDA approval of agents such as dinutuximab and tisgenlecleucel, these successes have rarely impacted children with pediatric central nervous system (CNS) tumors. As our understanding of the biological underpinnings of these tumors evolves, new immunotherapeutics are undergoing rapid clinical translation specifically designed for children with CNS tumors. Most recently, there have been notable clinical successes with oncolytic viruses, vaccines, adoptive cellular therapy, and immune checkpoint inhibition. In this article, the immunotherapy working group of the Pacific Pediatric Neuro-Oncology Consortium (PNOC) reviews the current and future state of immunotherapeutic CNS clinical trials with a focus on clinical trial development. Based on recent therapeutic trials, we discuss unique immunotherapy clinical trial challenges, including toxicity considerations, disease assessment, and correlative studies. Combinatorial strategies and future directions will be addressed. Through internationally collaborative efforts and consortia, we aim to direct this promising field of immuno-oncology to the next frontier of successful application against pediatric CNS tumors.
-
Autores: Jablonska, Paola Anna (Autor de correspondencia); Galán Gallego, Nuria; Barranco, J.; et al.Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 1661-6596 Vol.24 N° 18 2023 págs. 14219ResumenBrain radiation necrosis (RN) is a subacute or late adverse event following radiotherapy, involving an exacerbated inflammatory response of the brain tissue. The risk of symptomatic RN associated with stereotactic radiosurgery (SRS) as part of the treatment of brain metastases (BMs) has been a subject of recent investigation. The activation of the signal transducer and activator of transcription 3 (STAT3) was shown in reactive astrocytes (RA) associated with BMs. Given that the pathophysiological mechanisms behind RN are not fully understood, we sought to investigate the role of STAT3 among other inflammatory markers in RN development. A mouse model of RN using clinical LINAC-based SRS was designed to induce brain necrosis with the administration of 50 Gy in a single fraction to the left hemisphere using a circular collimator of 5 mm diameter. Immunohistochemistry and multiplex staining for CD4, CD8, CD68, GFAP, and STAT3 were performed. For validation, eleven patients with BMs treated with SRS who developed symptomatic RN and required surgery were identified to perform staining for CD68, GFAP, and STAT3. In the mouse model, the RN and perinecrotic areas showed significantly higher staining for F4/80+ and GFAP+ cells, with a high infiltration of CD4 and CD8 T-lymphocytes, when compared to the non-irradiated cerebral hemisphere. A high number of GFAP+pSTAT3+ and F4/80+pSTAT3+ cells was found in the RN areas and the rest of the irradiated hemisphere. The analysis of human brain specimens showed that astrocytes and microglia were actively phosphorylating STAT3 in the areas of RN and gliosis. Phosphorylated STAT3 is highly expressed in the microglia and RA pertaining to the areas of brain RN. Targeting STAT3 via inhibition represents a promising strategy to ameliorate symptomatic RN in BM patients undergoing SRS.
-
Autores: Vicente Ruiz, Miriam; Aristu Mendioroz, José Javier; Hontanilla Calatayud, Bernardo Carlos (Autor de correspondencia)Revista: JOURNAL OF RADIOTHERAPY IN PRACTICEISSN: 1460-3969 Vol.22 2023 págs. e47ResumenIntroduction: The management of extracranial arterio-venous malformations (AVMs) is complex and often requires a multidisciplinary approach. Currently, treatment includes surgical resection and embolotherapy. Methods: We present the case of a foot AVM that was managed with adjuvant radiotherapy after previous surgery and embolotherapy had been attempted, and we discuss the role of radiotherapy in the management of extracranial AVMs. Results: The malformation was successfully eradicated with complete obliteration of the nidus and no recurrence. Conclusions: The addition of radiotherapy in the management of extracranial arterio-venous malformations offers promising results using similar doses to those used in brain AVMs.
-
Autores: Nassiri, F.; Patil, V.; Yefet, L. S.; et al.Título: Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trialRevista: NATURE MEDICINEISSN: 1078-8956 Vol.29 N° 6 2023 págs. 1370 - 1378ResumenImmune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2-20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1-69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7-13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05-0.87). A total of 56.2% (95% CI 41.1-70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406).
-
Autores: Hoang-Xuan, K. (Autor de correspondencia); Deckert, M.; Ferreri, A. J. M.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.25 N° 1 2023 págs. 37 - 53ResumenThe management of primary central nervous system (PCNSL) is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the limited number of controlled studies available. In 2021, given recent advances and the publication of practice-changing randomized trials, the European Association of Neuro-Oncology (EANO) created a multidisciplinary task force to update the previously published evidence-based guidelines for immunocompetent adult patients with PCNSL and added a section on immunosuppressed patients. The guideline provides consensus considerations and recommendations for the treatment of PCNSL, including intraocular manifestations and specific management of the elderly. The main changes from the previous guideline include strengthened evidence for the consolidation with ASCT in first-line treatment, prospectively assessed chemotherapy combinations for both young and elderly patients, clarification of the role of rituximab even though the data remain inconclusive, of the role of new agents, and the incorporation of immunosuppressed patients and primary ocular lymphoma. The guideline should aid the clinicians in everyday practice and decision making and serve as a basis for future research in the field.
-
Autores: Nussbaumer, G.; Benesch, M.; Grabovska, Y.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.25 N° Supl. 1 2023
-
Autores: Ausejo Mauleón, Iker; Laspidea Ustés, Virginia; De la Nava Martin, Daniel; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.25 N° Supl. 1 2023 págs. NOAD073.051
-
Autores: Ciani, L.; Laternser, S.; Kritzer, B.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.25 N° Supl. 1 2023 págs. NOAD073.069
-
Autores: Laspidea Ustés, Virginia; Ausejo Mauleón, Iker; De la Nava Martin, Daniel; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.25 N° Supl. 1 2023 págs. NOAD073.057
-
Autores: García Moure, Marc (Autor de correspondencia); Tallón-Cobos, A. C.; Alonso Roldán, Marta María (Autor de correspondencia)Revista: MOLECULAR THERAPY ONCOLYTICSISSN: 2372-7705 Vol.27 2022 págs. 124 - 125
-
Autores: Idoate Gastearena, Miguel Ángel (Autor de correspondencia); Aquerreta Beola, Jesús Dámaso; Lamo de Espinosa Vázquez de Sola, José María; et al.Revista: DIAGNOSTICSISSN: 2075-4418 Vol.12 N° 2 2022 págs. 450ResumenOsteosarcoma is a primary malignant bone tumor usually arising at the metaphysis of long bones, particularly around the knee. The physis has been regarded as a barrier capable of blocking tumor extension, thus allowing it to preserve their epiphysis and therefore improve functional results. With the objective of clarifying how effective the physis is as a barrier to tumor spread, a large series of skeletally immature patients with osteosarcoma were reviewed. From 452 metaphyseal osteosarcomas a selection of 282 cases in which the tumor was close or crossing the physis were carried out. This sub-sample was split into two groups according to the surgical treatment (epiphyseal preservation or not). The specimens obtained by resection were studied, and the physeal and metaphyseal areas were studied by multiple sections. Immunostaining against VEGF of physis was obtained in selected cases. In about half of the patients affected by metaphyseal malignant bone tumors, the growth plate and epiphysis were not compromised by the tumor. Three sequential invasive growth patterns of an osteosarcoma in its relationship with the physis could be distinguished. An intense angiogenesis and osteoclastic reaction could be observed in the growth plate in the free zone between the tumor and the physis. The local recurrence incidence was lower in the epiphyseal preservation treated patients than it was in the conventional treatment (8% vs. 12%). Most local recurrences appeared in the first 2 years. The overall survival of patients treated with epiphyseal preservation was better than that of the patients treated without preserving the epiphysis (73% vs. 59%; p = 0.03) at a mean follow-up of 18 years. We have described an angiogenic and osteoclastic reaction in the base of the growth plate in the proximity of the advance front of the tumor, which could facilitate the osteosarcoma invasion. It is also shown that the preoperative imaging method for examination is a valid approach for the decision to carry out epiphyseal preservation. Finally, we concluded that epiphyseal preservation combined with protective chemotherapy is an excellent clinical approach for selected patients with metaphyseal osteosarcoma.
-
Autores: Cohen, A. D.; Parekh, S.; Santomasso, B. D.; et al.Revista: BLOOD CANCER JOURNALISSN: 2044-5385 Vol.12 N° 2 2022 págs. 32ResumenChimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade >= 2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to <1% across the cilta-cel program, supporting its favorable benefit-risk profile for treatment of MM.
-
Autores: Laspidea Ustés, Virginia; Puigdelloses Vallcorba, Montserrat; Labiano Almiñana, Sara; et al.Revista: JCI INSIGHTISSN: 2379-3708 Vol.7 N° 7 2022 págs. e154812ResumenDiffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8(+) T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed immunological memory against these tumors. In addition, Delta-24-ACT was safe and caused no local or systemic toxicity. Mechanistic studies showed that Delta-24-ACT modulated the tumor-immune content, not only increasing the number, but also improving the functionality of immune cells. All of these data highlight the safety and potential therapeutic benefit of Delta-24-ACT the treatment of patients with DIPG.
-
Autores: Damanskiene, E. (Autor de correspondencia); Balnyte, I.; Valanciute, A.; et al.Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 1422-0067 Vol.23 N° 4 2022 págs. 2001ResumenIt is necessary to elucidate the individual effects of temozolomide (TMZ) on carcinogenesis and tumor resistance to chemotherapy mechanisms. The study aimed to investigate the TMZ 50 and 100 mu M dose effect difference between PBT24 and SF8628 cell line high-grade pediatric glioblastoma (phGBM) xenografts in a chicken chorioallantoic membrane (CAM) model, on PCNA and EZH2 immunohistochemical expression in the tumor and on the expression of NKCC1, KCC2, E- and N-cadherin genes in TMZ-treated and control cell groups in vitro. TMZ at a 100 mu g dose reduced the incidence of PBT24 xenograft invasion into the CAM, CAM thickening and the number of blood vessels in the CAM (p < 0.05), but did not affect the SF8628 tumor in the CAM model. The TMZ impact on PBT24 and SF8628 tumor PCNA expression was similarly significantly effective but did not alter EZH2 expression in the studied tumors. The TMZ at 50 mu M caused significantly increased RNA expression of the NKCC1 gene in both studied cell types compared with controls (p < 0.05). The expression of the KCC2 gene was increased in PBT24 TMZ-treated cells (p < 0.05), and no TMZ effect was found in SF8628-treated cells. The study supports the suggestion that individual sensitivity to TMZ should be assessed when starting treatment.
-
Autores: Paricio Martínez, José Joaquín (Autor de correspondencia); Panadero Meseguer, Pablo; Baptista Jardín, Peter Michael; et al.Revista: REVISTA ESPAÑOLA DE PATOLOGIAISSN: 1988-561X Vol.55 N° 3 2022 págs. 192 - 196ResumenA 54-year-old female patient presented with a left nasal obstruction. On physical examination a pink delimited mass in the left nostril was observed. A cranial computed tomography scan revealed an expansive mass in the upper anterior third of the left nasal fossa, partially obstructing it. Endoscopic resection of the mass was performed. Histopathology revealed an atypical mesenchymal proliferation formed by cells disposed in disorganized and interconnected long bundles. Tumor cells had abundant eosinophilic cytoplasm and an oval, vesicular and hyperchromatic nucleus. Frequent mitotic figures were observed, many of them atypical. Necrosis was not observed. Immunohistochemistry showed tumor cells to be positive for calponin, muscle specific actin, caldesmon and smooth muscle specific myosin. Ki-67 index proliferation was 30%. A diagnosis of leiomyosarcoma of the nasal fossa was established.
-
Autores: Arbizu Lostao, Javier; Gállego Pérez de Larraya, Jaime; Hilario, A.; et al.Revista: REVISTA ESPAÑOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULARISSN: 2253-654X Vol.41 N° 4 2022 págs. 247 - 257ResumenAutoimmune encephalitis are brain inflammatory processes that are classified into two main groups according to the underlying pathogenic mechanism: antibodies to intracellular antigens (paraneoplastic) and antibodies to extracellular or neuronal surface antigens. The clinical manifestations of autoimmune encephalitis are very varied and non-specific. Complementary tests included in its clinical diagnosis include determination of antibodies in serum or cerebrospinal fluid and magnetic resonance imaging (MRI). MRI may show characteristic patterns such as mesial temporal involvement, although in some cases it may be normal or non-specific. 18F-Fluorodeoxyglucose PET/CT (18F-FDG PET/CT) imaging may be helpful in cases of paraneoplastic autoimmune encephalitis to find the primary tumor. In autoimmune encephalitis mediated by antibodies to extracellular antigens, 18F-FDG PET/CT shows distinctive patterns that can aid clinical diagnosis. This continuing education aims to present in a clear and easy-to-understand way, the clinical features of autoimmune encephalitis, the difficulties in clinical diagnosis and the patterns seen on MRI and 18F-FDG PET/CT.
-
Autores: Nguyen, T. T.; Shin, D. H.; Sohoni, S.; et al.Revista: JOURNAL FOR IMMUNOTHERAPY OF CANCERISSN: 2051-1426 Vol.10 N° 7 2022 págs. e004935ResumenBackground Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms underlying the immunosuppressive tumor microenvironment optimizes viroimmunotherapy. Methods We used RNA-seq analyses to analyze the transcriptome, and validated the results using Q-PCR, flow cytometry, and immunofluorescence. Viral activity was analyzed by replication assays and viral titration. Kyn and Trp metabolite levels were quantified using liquid chromatography-mass spectrometry. Aryl hydrocarbon receptor (AhR) activation was analyzed by examination of promoter activity. Therapeutic efficacy was assessed by tumor histopathology and survival in syngeneic murine models of gliomas, including Indoleamine 2,3-dioxygenase (IDO)-/- mice. Flow cytometry was used for immunophenotyping and quantification of cell populations. Immune activation was examined in co-cultures of immune and cancer cells. T-cell depletion was used to identify the role played by specific cell populations. Rechallenge experiments were performed to identify the development of anti-tumor memory. Results Bulk RNA-seq analyses showed the activation of the immunosuppressive IDO-kynurenine-AhR circuitry in response to Delta-24-RGDOX infection of tumors. To overcome the effect of this pivotal pathway, we combined Delta-24-RGDOX with clinically relevant IDO inhibitors. The combination therapy increased the frequency of CD8(+) T cells and decreased the rate of myeloid-derived suppressor cell and immunosupressive Treg tumor populations in animal models of solid tumors. Functional studies demonstrated that IDO-blockade-dependent activation of immune cells against tumor antigens could be reversed by the oncometabolite kynurenine. The concurrent targeting of the effectors and suppressors of the tumor immune landscape significantly prolonged the survival in animal models of orthotopic gliomas. Conclusions Our data identified for the first time the in vivo role of IDO-dependent immunosuppressive pathways in the resistance of solid tumors to oncolytic adenoviruses. Specifically, the IDO-Kyn-AhR activity was responsible for the resurface of local immunosuppression and resistance to therapy, which was ablated through IDO inhibition. Our data indicate that combined molecular and immune therapy may improve outcomes in human gliomas and other cancers treated with virotherapy.
-
Autores: Persson, M. L.; Douglas, A. M.; Alvaro, F.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° 9 2022 págs. 1408 - 1422ResumenDiffuse midline glioma (DMG), including those of the brainstem (diffuse intrinsic pontine glioma), are pediatric tumors of the central nervous system (CNS). Recognized as the most lethal of all childhood cancers, palliative radiotherapy remains the only proven treatment option, however, even for those that respond, survival is only temporarily extended. DMG harbor an immunologically cold tumor microenvironment (TME) with few infiltrating immune cells. The mechanisms underpinning the cold TME are not well understood. Low expression levels of immune checkpoint proteins, including PD-1, PD-L1, and CTLA-4, are recurring features of DMG and likely contribute to the lack of response to immune checkpoint inhibitors (ICIs). The unique epigenetic signatures (including stem cell-like methylation patterns), a low tumor mutational burden, and recurring somatic mutations (H3K27M, TP53, ACVR1, MYC, and PIK3CA), possibly play a role in the reduced efficacy of traditional immunotherapies. Therefore, to circumvent the lack of efficacy thus far seen for the use of ICIs, adoptive cell transfer (including chimeric antigen receptor T cells) and the use of oncolytic viruses, are currently being evaluated for the treatment of DMG. It remains an absolute imperative that we improve our understanding of DMG's intrinsic and TME features if patients are to realize the potential benefits offered by these sophisticated treatments. Herein, we summarize the limitations of immunotherapeutic approaches, highlight the emerging safety and clinical efficacy shown for sophisticated cell-based therapies, as well as the evolving knowledge underpinning the DMG-immune axis, to guide the development of immunotherapies that we hope will improve outcomes.
-
Autores: Idoate Gastearena, Miguel Ángel (Autor de correspondencia); López Janeiro, Álvaro; Lecumberri Aznarez, A.; et al.Revista: BIOMEDICINESISSN: 2227-9059 Vol.10 N° 7 2022 págs. 1753ResumenObjectives: Immunostimulatory therapies using immune checkpoint blockers show clinical activity in a subset of glioblastoma (GBM) patients. Several inhibitory mechanisms play a relevant role in the immune response to GBM. With the objective of analyzing the tumor immune microenvironment and its clinical significance, we quantified several relevant immune biomarkers. Design: We studied 76 primary (non-recurrent) GBMs with sufficient clinical follow-up, including a subgroup of patients treated with a dendritic cell vaccine. The IDH-mutation, EGFR-amplification, and MGMT methylation statuses were determined. Several relevant immune biomarkers, including CD163, CD8, PD1, and PDL1, were quantified in representative selected areas by digital image analysis and semiquantitative evaluation. The percentage of each immune expression was calculated with respect to the total number of tumor cells. Results: All GBMs were wild-type IDH, with a subgroup of classical GBMs according to the EGFR amplification (44%). Morphologically, CD163 immunostained microglia and intratumor clusters of macrophages were observed. A significant direct correlation was found between the expression of CD8 and the mechanisms of lymphocyte immunosuppression, in such a way that higher values of CD8 were directly associated with higher values of CD163 (p < 0.001), PDL1 (0.026), and PD1 (0.007). In a multivariate analysis, high expressions of CD8+ (HR = 2.05, 95%CI (1.02-4.13), p = 0.034) and CD163+ cells (HR 2.50, 95%CI (1.29-4.85), p = 0.007), were associated with shorter survival durations. The expression of immune biomarkers was higher in the non-classical (non-EGFR amplified tumors) GBMs. Other relevant prognostic factors were age, receipt of the dendritic cell vaccine, and MGMT methylation status. Conclusions: In accordance with the inverse correlation between CD8 and survival and the direct correlation between effector cells and CD163 macrophages and immune-checkpoint expression, we postulate that CD8 infiltration could be placed in a state of anergy or lymphocytic inefficient activity. Furthermore, the significant inverse correlation between CD163 tissue concentration and survival explains the relevance of this type of immune cell when creating a strong immunosuppressive environment. This information may potentially be used to support the selection of patients for immunotherapy.
-
Autores: Le Rhun, E. (Autor de correspondencia); Devos, P.; Winklhofer, S.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° 10 2022 págs. 1726 - 1735ResumenBackground Validation of the 2016 RANO MRI scorecard for leptomeningeal metastasis failed for multiple reasons. Accordingly, this joint EORTC Brain Tumor Group and RANO effort sought to prospectively validate a revised MRI scorecard for response assessment in leptomeningeal metastasis. Methods Coded paired cerebrospinal MRI of 20 patients with leptomeningeal metastases from solid cancers at baseline and follow-up after treatment and instructions for assessment were provided via the EORTC imaging platform. The Kappa coefficient was used to evaluate the interobserver pairwise agreement. Results Thirty-five raters participated, including 9 neuroradiologists, 17 neurologists, 4 radiation oncologists, 3 neurosurgeons, and 2 medical oncologists. Among single leptomeningeal metastases-related imaging findings at baseline, the best median concordance was noted for hydrocephalus (Kappa = 0.63), and the worst median concordance for spinal linear enhancing disease (Kappa = 0.46). The median concordance of raters for the overall response assessment was moderate (Kappa = 0.44). Notably, the interobserver agreement for the presence of parenchymal brain metastases at baseline was fair (Kappa = 0.29) and virtually absent for their response to treatment. 394 of 700 ratings (20 patients x 35 raters, 56%) were fully completed. In 308 of 394 fully completed ratings (78%), the overall response assessment perfectly matched the summary interpretation of the single ratings as proposed in the scorecard instructions. Conclusion This study confirms the principle utility of the new scorecard, but also indicates the need for training of MRI assessment with a dedicated reviewer panel in clinical trials. Electronic case report forms with "blocking options" may be required to enforce completeness and quality of scoring.
-
Autores: Persson, M.; Jackson, E.; Duchatel, R.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 2022 págs. 272 - 272
-
Autores: Ausejo Mauleón, Iker; Labiano Almiñana, Sara; De la Nava Martin, Daniel; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° Supl. 1 2022 págs. 22 - 23
-
Autores: Shin, D. H.; Jiang, H.; Gillard, A.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° SUPPL 7 2022 págs. 139 - 140
-
Autores: Jiang, H.; Shin, D. H.; Yi, Y. H.; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.82 N° 12 2022
-
Autores: De la Nava Martin, Daniel; Marco Sanz, Javier; Laspidea Ustés, Virginia; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.82 N° 12 Supl. 2022 págs. 2000
-
Autores: Ausejo Mauleón, Iker; Labiano Almiñana, Sara; Laspidea Ustés, Virginia; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° Supl. 7 2022 págs. 222
-
Autores: Illade, L.; Garrido, C.; Cruz, O.; et al.Revista: PEDIATRIC BLOOD AND CANCERISSN: 1545-5009 Vol.69 N° SUPPL 5 2022 págs. S295 - S296
-
Autores: Jiang, H.; Shin, D. H.; Yi, Y. H.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° SUPPL 7 2022 págs. 231 - 231
-
Autores: Van Wieren, A. C.; Sahoni, S.; Nguyen, T.; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.82 N° 12 2022
-
Autores: Shin, D. H.; Jiang, H.; Kim, D.; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.82 N° 12 2022
-
Autores: Lohmann, P.; Smits, M.; Razis, E.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° Supl. 7 2022 págs. 168
-
Autores: Nguyen, T.; Shin, D. H.; Kim, D.; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° SUPPL 7 2022 págs. 223 - 223
-
Autores: Gillard, A.; Shin, D. H.; Laspidea Ustés, Virginia; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° SUPPL 7 2022 págs. 133 - 133
-
Autores: Nguyen, T. T.; Shin, D. H.; Sohoni, S.; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.82 N° 12 2022
-
Autores: Labiano Almiñana, Sara; Marco Sanz, Javier; Laspidea Ustés, Virginia; et al.Título: Targeting antigen presenting cells to improve virotherapy efficacy in diffuse midline gliomasRevista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.24 N° Supl. 1 2022 págs. i85
-
Autores: Laspidea Ustés, Virginia; Labiano Almiñana, Sara; Gupta, S.; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.82 N° 12 Supl. 2022
-
Autores: Herrador Cañete, Guillermo; Zalacain Díez, Marta; Labiano Almiñana, Sara; et al.Título: Auto-replicative vectors expressing galectin-3 inhibitors new tools to fight pediatric osteosarcomaRevista: MOLECULAR THERAPYISSN: 1525-0016 Vol.30 N° 4 2022 págs. 416 - 417
-
Autores: Luna, J. (Autor de correspondencia); Bobo, A.; Cabrera-Rodríguez, J. J. ; et al.Revista: WORLD JOURNAL OF CLINICAL ONCOLOGYISSN: 2218-4333 Vol.12 N° 8 2021 págs. 581 - 608ResumenMalignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis and rising incidence. Palliative care is common in MPM as radical treatment with curative intent is often not possible due to metastasis or extensive locoregional involvement. Numerous therapeutic advances have been made in recent years, including the use of less aggressive surgical techniques associated with lower morbidity and mortality (e.g., pleurectomy/decortication), technological advancements in the field of radiotherapy (intensity-modulated radiotherapy, image-guided radiotherapy, stereotactic body radiotherapy, proton therapy), and developments in systemic therapies (chemotherapy and immunotherapy). These improvements have had as yet only a modest effect on local control and survival. Advances in the management of MPM and standardization of care are hampered by the evidence to date, limited by high heterogeneity among studies and small sample sizes. In this clinical guideline prepared by the oncological group for the study of lung cancer of the Spanish Society of Radiation Oncology, we review clinical, histologic, and therapeutic aspects of MPM, with a particular focus on all aspects relating to radiotherapy, including the current evidence base, associations with chemotherapy and surgery, treatment volumes and planning, technological advances, and reradiation.
-
Autores: Shin, D. H.; Nguyen, T.; Ozpolat, B.; et al.Revista: JOURNAL FOR IMMUNOTHERAPY OF CANCERISSN: 2051-1426 Vol.9 N° 4 2021 págs. e002086ResumenCancer virotherapy is a paradigm-shifting treatment modality based on virus-mediated oncolysis and subsequent antitumor immune responses. Clinical trials of currently available virotherapies showed that robust antitumor immunity characterizes the remarkable and long-term responses observed in a subset of patients. These data suggest that future therapies should incorporate strategies to maximize the immunotherapeutic potential of oncolytic viruses. In this review, we highlight the recent evidence that the antiviral immunity of the patients may limit the immunotherapeutic potential of oncolytic viruses and summarize the most relevant approaches to strategically redirect the immune response away from the viruses and toward tumors to heighten the clinical impact of viro-immunotherapy platforms.
-
Autores: Fueyo, J.; Gómez-Manzano, C.; Lang, F. F.; et al.Revista: LANCET ONCOLOGYISSN: 1470-2045 Vol.22 N° 8 2021 págs. 1049 - 1051
-
Autores: Ross, J. L.; Chen, Z.; Herting, C. J.; et al.Título: Platelet-derived growth factor beta is a potent inflammatory driver in paediatric high-grade gliomaRevista: BRAINISSN: 0006-8950 Vol.144 2021 págs. 53 - 69ResumenPaediatric high-grade gliomas (HGGs) account for the most brain tumour-related deaths in children and have a median survival of 12-15 months. One promising avenue of research is the development of novel therapies targeting the properties of non-neoplastic cell-types within the tumour such as tumour associated macrophages (TAMs). TAMs are immunosuppressive and promote tumour malignancy in adult HGG; however, in paediatric medulloblastoma, TAMs exhibit anti-tumour properties. Much is known about TAMs in adult HGG, yet little is known about them in the paediatric setting. This raises the question of whether paediatric HGGs possess a distinct constituency of TAMs because of their unique genetic landscapes. Using human paediatric HGG tissue samples and murine models of paediatric HGG, we demonstrate diffuse midline gliomas possess a greater inflammatory gene expression profile compared to hemispheric paediatric HGGs. We also show despite possessing sparse T-cell infiltration, human paediatric HGGs possess high infiltration of IBA1+ TAMs. CD31, PDGFR beta, and PDGFB all strongly correlate with IBA1+ TAM infiltration. To investigate the TAM population, we used the RCAS/tv-a system to recapitulate paediatric HGG in newborn immunocompetent mice. Tumours are induced in Nestin-positive brain cells by PDGFA or PDGFB overexpression with Cdkn2a or Tp53 co-mutations. Tumours driven by PDGFB have a significantly lower median survival compared to PDGFA-driven tumours and have increased TAM infiltration. NanoString and quantitative PCR analysis indicates PDGFB-driven tumours have a highly inflammatory microenvironment characterized by high chemokine expression. In vitro bone marrow-derived monocyte and microglial cultures demonstrate bone marrow-derived monocytes are most responsible for the production of inflammatory signals in the tumour microenvironment in response to PDGFB stimulation. Lastly, using knockout mice deficient for individual chemokines, we demonstrate the feasibility of reducing TAM infiltration and prolonging survival in both PDGFA and PDGFB-driven tumours. We identify CCL3 as a potential key chemokine in these processes in both humans and mice. Together, these studies provide evidence for the potent inflammatory effects PDGFB has in paediatric HGGs.
-
Autores: Urdiciain Ezpeleta, Alejandro; Erausquin, E.; Zelaya, M. V.; et al.Revista: BIOLOGYISSN: 2079-7737 Vol.10 N° 6 2021 págs. 467ResumenSimple Summary Glioblastoma multiforme (GBM) is the most common as well as the most aggressive malignant brain tumor, with an overall survival of almost 15 months. Histone deacetylase 6 (HDAC6), an enzyme related to the deacetylation of alpha-tubulin, is overexpressed in GBM. The aim of our research was to study the effects of HDAC6 silencing in GBM cells. We first confirmed the overexpression of HDAC6 in GBM tissue (n = 40) against control brain (n = 10). Treatment with siHDAC6 diminished viability, clonogenic potential, and migration ability in GBM-derived cell lines. HDAC6 inhibition also reverted the mesenchymal phenotype, inhibited the Sonic Hedgehog pathway, restored primary cilium structure, and decreased autophagy. Thus, we confirm that HDAC6 is a good therapeutic target for GBM treatment. Glioblastoma multiforme, the most common type of malignant brain tumor as well as the most aggressive one, lacks an effective therapy. Glioblastoma presents overexpression of mesenchymal markers Snail, Slug, and N-Cadherin and of the autophagic marker p62. Glioblastoma cell lines also present increased autophagy, overexpression of mesenchymal markers, Shh pathway activation, and lack of primary cilia. In this study, we aimed to evaluate the role of HDAC6 in the pathogenesis of glioblastoma, as HDAC6 is the most overexpressed of all HDACs isoforms in this tumor.
-
Autores: Urdiciain Ezpeleta, Alejandro; Bermúdez-Lekerika, P.; Meléndez, B.; et al.Revista: GLIOMAISSN: 2589-6113 Vol.4 N° 2 2021 págs. 27 - 33ResumenBackground and Aim: Glioblastoma is the most lethal brain tumor. No effective curative treatment is available yet, and it is treated by surgery, temozolomide (TMZ), and radiotherapy, with an average overall survival of around 15 months. Inhibitors of histone deacetylases (HDACs) are being explored against a variety of tumors, including glioblastoma. Specific inhibitors of HDAC6, such as tubastatin A (Tub A), may potentially be beneficial as HDAC6 has been demonstrated to be the most expressed HDACs in glioblastoma. Our aim was to test whether Tub A could reverse the malignant phenotype of U87MG cells via the inhibition of HDAC6. Materials and Methods: U87MG cells were treated with cyclopamine (Cyp), TMZ, and Tub A. Two double treatments were performed as well (Cyp + Tub A and TMZ + Tub A). Colony formation, wound healing, Caspase¿Glo 3/7, quantitative reverse transcription¿polymerase chain reaction, luciferase assay, and Western blot assays were conducted to determine clonogenic and migration capacity, apoptosis, activation of the Sonic Hedgehog pathway, acetylation of ¿¿tubulin and epithelial-to-mesenchymal transition, and autophagic flux of U87MG glioblastoma cells, respectively. Results: Tub A treatment caused a reversal of the U87MG malignant phenotype by reducing its clonogenic and migratory cellular potential, and inducing apoptosis.
-
Autores: de la Rosa Fernández-Pacheco, Francisco Javier; Urdiciain Ezpeleta, Alejandro; Zelaya, M. V.; et al.Revista: INTERNATIONAL JOURNAL OF ONCOLOGYISSN: 1019-6439 Vol.58 N° 3 2021 págs. 312 - 330ResumenGlioblastoma is the most malignant brain tumor and presents high resistance to chemotherapy and radiotherapy. Surgery, radiotherapy and chemotherapy with temozolomide are the only treatments against this tumor. New targeted therapies, including epigenetic modulators such as 3-deazane-planocin A (DZ-Nep; an EZH2 inhibitor) and panobinostat (a histone deacetylase inhibitor) are being tested in vitro, together with temozolomide. The present study combined APR-246 with DZ-Nep, panobinostat and teomozolomide in order to explore the possibility of restoring p53 function in mutated cases of glioblastoma. Following the Chou-Talalay method it was demonstrated that APR-246 acts in an additive manner together with the other compounds, reducing clonogenicity and inducing apoptosis in glioblastoma cells independently of p53 status.
-
Autores: Puigdelloses Vallcorba, Montserrat; García Moure, Marc; Labiano Almiñana, Sara; et al.Revista: JOURNAL FOR IMMUNOTHERAPY OF CANCERISSN: 2051-1426 Vol.9 N° 7 2021 págs. e002644ResumenBackground Glioblastoma (GBM) is a devastating primary brain tumor with a highly immunosuppressive tumor microenvironment, and treatment with oncolytic viruses (OVs) has emerged as a promising strategy for these tumors. Our group constructed a new OV named Delta-24-ACT, which was based on the Delta-24-RGD platform armed with 4-1BB ligand (4-1BBL). In this study, we evaluated the antitumor effect of Delta-24-ACT alone or in combination with an immune checkpoint inhibitor (ICI) in preclinical models of glioma. Methods The in vitro effect of Delta-24-ACT was characterized through analyses of its infectivity, replication and cytotoxicity by flow cytometry, immunofluorescence (IF) and MTS assays, respectively. The antitumor effect and therapeutic mechanism were evaluated in vivo using several immunocompetent murine glioma models. The tumor microenvironment was studied by flow cytometry, immunohistochemistry and IF. Results Delta-24-ACT was able to infect and exert a cytotoxic effect on murine and human glioma cell lines. Moreover, Delta-24-ACT expressed functional 4-1BBL that was able to costimulate T lymphocytes in vitro and in vivo. Delta-24-ACT elicited a more potent antitumor effect in GBM murine models than Delta-24-RGD, as demonstrated by significant increases in median survival and the percentage of long-term survivors. Furthermore, Delta-24-ACT modulated the tumor microenvironment, which led to lymphocyte infiltration and alteration of their immune phenotype, as ...
-
Autores: García Moure, Marc (Autor de correspondencia); Gonzalez-Huarriz, M.; Labiano Almiñana, Sara; et al.Revista: CLINICAL CANCER RESEARCHISSN: 1078-0432 Vol.27 N° 6 2021 págs. 1807 - 1820ResumenPurpose: Atypical teratoid/rhabdoid tumors (AT/RT) and central nervous system primitive neuroectodermal tumors (CNS-PNET) are pediatric brain tumors with poor survival and life-long negative side effects. Here, the aim was to characterize the efficacy and safety of the oncolytic adenovirus, Delta-24-RGD, which selectively replicates in and kills tumor cells. Experimental Design: Delta-24-RGD determinants for infection and replication were evaluated in patient expression datasets. Viral replication and cytotoxicity were assessed in vitro in a battery of CNS-PNET and AT/RT cell lines. In vivo, efficacy was determined in different orthotopic mouse models, including early and established tumor models, a disseminated AT/RT lesion model, and immunocompetent humanized mouse models (hCD34(+)-NSG-SGM3). Results: Delta-24-RGD infected and replicated efficiently in all the cell lines tested. In addition, the virus induced dose-dependent cytotoxicity [IC50 value below 1 plaque-forming unit (PFU)/cell] and the release of immunogenic markers. In vivo, a single intratumoral Delta-24-RGD injection (10(7) or 10(8) PFU) significantly increased survival and led to long-term survival in AT/RT and PNET models. Delta-24-RGD hindered the dissemination of AT/RTs and increased survival, leading to 70% of long-term survivors. Of relevance, viral administration to established tumor masses (30 days after engraftment) showed therapeutic benefit. In humanized immunocompetent models, Delta-24-RGD significantly extended the survival of mice bearing AT/RTs or PNETs (ranging from 11 to 27 days) and did not display any toxicity associated with inflammation. Immunophenotyping of Delta-24-RGD-treated tumors revealed increased CD8(+) T-cell infiltration. Conclusions: Delta-24-RGD is a feasible therapeutic option for AT/RTs and CNS-PNETs. This work constitutes the basis for potential translation to the clinical setting.
-
Autores: Rodríguez Garijo, Nuria; Bielsa, I.; Mascaro, J. M.; et al.Revista: JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGYISSN: 0926-9959 Vol.35 N° 4 2021 págs. 988 - 994ResumenBackground Confusion exists regarding interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic and granulomatous dermatitis (PNGD). Objective To determine whether IGD and PNGD are two different entities, or whether they must be considered as two subtypes of the same reactive pattern, and thus whether the unification of the nomenclature is necessary. Methods Observational retrospective multicentre study of patients with IGD and PNGD evaluated between 1999 and 2019 and review of their clinical and histological features. Results We identified 52 patients (38 women and 14 men). Clinical and histological findings of IGD were observed in 88.4% of cases. The most common cutaneous lesions were plaques/macules (IGD) or annular plaques and papules/nodules (PNGD), located mostly on the limbs and trunk. The rope sign was developed in two patients with IGD that associated autoimmune disorders. Similar associated comorbidities (75%) were found in both entities, mainly autoimmune diseases (53.8%). In IGD, the infiltrate was predominantly lympho-histiocytic. Neutrophilic infiltrates, karyorrhexis and skin lesions with limited clinical course were mainly associated with PNGD biopsies. In biopsies with a limited recurrent course, a predominant lymphocytic inflammatory infiltrate was found. Collagen degeneration was present in 75.9% of cases. The floating sign was observed only in IGD type patients (63%). Overlapping histological findings were found in one fourth of cases, especia
-
Autores: Stakisaitis, D. (Autor de correspondencia); Damanskiene, E.; Curkunaviciute, R.; et al.Revista: DOSE-RESPONSEISSN: 1559-3258 Vol.19 N° 1 2021 págs. 1559325821990166ResumenThe study's aim was to investigate the effectiveness of sodium dichloroacetate (NaDCA) or magnesium dichloroacetate (MgDCA) on adult U87 MG and pediatric PBT24 cell lines glioblastoma (GB) xenografts in a chicken chorioallantoic membrane (CAM) model. The study groups were: treated with 10 mM, 5 mM of NaDCA, and 5 mM, 2.5 mM of MgDCA, and controls. The U87 MG and PBT24 xenografts growth, frequency of tumor invasion into CAM, CAM thickening, and the number of blood vessels in CAM differed depending on the dichloroacetate salt treatment. NaDCA impact on U87 MG and PBT24 tumor on proliferating cell nunclear antigen (PCNA) and enhancer of zeste homolog 2 (EZH2) expression in the tumor was different, depending on the NaDCA dose. The 5 mM MgDCA impact was more potent and had similar effects on U87 MG and PBT24 tumors, and its impact was also reflected in changes in PCNA and EZH2 expression in tumor cells. The U87 MG and PBT24 tumor response variations to treatment with different NaDCA concentration on tumor growth or a contrast between NaDCA and MgDCA effectiveness may reflect some differences in U87 MG and PBT24 cell biology.
-
Autores: Laspidea Ustés, Virginia; Gupta, S.; Puigdelloses Vallcorba, Montserrat; et al.Revista: NEURO-ONCOLOGYISSN: 1522-8517 Vol.23 N° Supl. 1 2021 págs. 28
-
Autores: Diez Valle, Ricardo; Stummer, W.Libro: Fluorescence-guided neurosurgery. Neuro-oncology and cerebrovascular applicationsISSN: 978-1626237148 2018 págs. 13 - 20
Proyectos desde 2018
-
Título: GRANATE - GRUPO DE RADIOTERAPIA AVANZADA DE NAVARRA ¿ TERAPIA Y EFICACIACódigo de expediente: 0011-1411-2022-000066Investigador principal: ANA PATIÑO GARCIA.Financiador: GOBIERNO DE NAVARRAConvocatoria: 2022 GN PROYECTOS ESTRATEGICOS DE I+D 2022-2025Fecha de inicio: 01-06-2022Fecha fin: 31-12-2024Importe concedido: 536.739,00€Otros fondos: -
-
Título: Tumor Immune Microenvironment (TIME) targeted therapy in pediatric brain cancerCódigo de expediente: PCI2021-122084-2BInvestigador principal: MARTA MARIA ALONSO ROLDAN.Financiador: MINISTERIO DE CIENCIA E INNOVACIÓNConvocatoria: 2021 AEI Proyectos de Colaboración Internacional - 2Fecha de inicio: 01-02-2022Fecha fin: 31-01-2024Importe 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: PI21/00940Investigador principal: ANA PATIÑO GARCIA.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2021 AES Proyectos de investigaciónFecha de inicio: 01-01-2022Fecha fin: 31-12-2024Importe concedido: 171.820,00€Otros fondos: Fondos FEDER
-
Título: Identificación de biomarcadores para la detección de radionecrosis en pacientes tratados con radioterapia estereopática y desarrollo experimental de nuevas terapias para su prevención.Código de expediente: PI20/01531Investigador principal: JOSE JAVIER ARISTU MENDIOROZ.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2020 AES Proyectos de investigaciónFecha de inicio: 01-01-2021Fecha fin: 31-12-2023Importe concedido: 123.420,00€Otros fondos: Fondos FEDER
-
Título: Plasma extracellular vesicles (EVs): the key for precision medicine in GlioblastomaCódigo de expediente: AC20/00094Investigador principal: JAIME GALLEGO PEREZ DE LARRAYA.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2020 AES Programación Conjunta InternacionalFecha de inicio: 01-01-2021Fecha fin: 31-12-2023Importe concedido: 38.720,00€Otros fondos: -
-
Título: Ayuda para contratación Juan de la Cierva Formación 2018Código de expediente: FJC2018-037394-IInvestigador principal: MARTA MARIA ALONSO ROLDAN.Financiador: MINISTERIO DE CIENCIA E INNOVACIÓNConvocatoria: 2018 AEI - MCIU JUAN DE LA CIERVA FORMACIÓNFecha de inicio: 01-04-2020Fecha fin: 31-03-2022Importe 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: PI19/01896Investigador principal: MARTA MARIA ALONSO ROLDAN.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2019 AES Proyectos de investigaciónFecha de inicio: 01-01-2020Fecha fin: 30-06-2024Importe 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 glioblastomaCódigo de expediente: PI19/01440Investigador principal: JAIME GALLEGO PEREZ DE LARRAYA.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2019 AES Proyectos de investigaciónFecha de inicio: 01-01-2020Fecha fin: 31-12-2023Importe concedido: 96.800,00€Otros fondos: Fondos FEDER
-
Título: Desarrollo de técnicas de mapeado de la reactividad cerebrovascular. Aplicaciones en la cirugía de tumores cerebrales.Código de expediente: PI18/00084Investigador principal: MARIA ASUNCION FERNANDEZ SEARA.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: AES2018 PIFecha de inicio: 01-01-2019Fecha fin: 30-06-2023Importe concedido: 62.920,00€Otros fondos: Fondos FEDER
-
Título: Implantes Crónicos con aplicación en NeurocienciasCódigo de expediente: 0011-1383-2018-000011Investigador principal: MIGUEL VALENCIA USTARROZ.Financiador: GOBIERNO DE NAVARRAConvocatoria: 2018 - GN INDUSTRIA PROYECTOS CENTROS TECNOLOGICOS Y ORGANISMOS DE INVESTIGACIONFecha de inicio: 01-02-2018Fecha fin: 30-11-2018Importe concedido: 151.269,06€Otros fondos: -
-
Título: Modulando el sistema inmune con adenovirus oncolíticos como estrategia para los tumores difusos de tronco (DIPGs).Código de expediente: PI16/00066Investigador principal: MARTA MARIA ALONSO ROLDAN.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2016 AES PROYECTOS DE INVESTIGACIÓNFecha de inicio: 01-01-2017Fecha fin: 31-12-2019Importe 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 multiformeCódigo de expediente: 42/2015Investigador principal: JAIME GALLEGO PEREZ DE LARRAYA.Financiador: GOBIERNO DE NAVARRAConvocatoria: 2015 GN SALUDFecha de inicio: 06-12-2015Fecha fin: 05-12-2018Importe concedido: 50.682,00€Otros fondos: -
-
Título: Oncolytic Immunotherapy for Diffuse Intrinsic Pontine GliomasCódigo de expediente:Investigador principal: MARTA MARIA ALONSO ROLDANFinanciador: National Institute of HealthConvocatoria: DOD -USA-DEFENCE-2017Fecha de inicio: 01-08-2017Fecha fin: 31-07-2020Importe concedido: 544.625,00€Otros fondos: -
-
Título: Combinatorial biotherapies for the treatment of pediatric diffuse midline gliomaInvestigador principal: MARTA MARIA ALONSO ROLDANFinanciador: ASOCIACION ESPAÑOLA CONTRA EL CANCERConvocatoria: 2021 AECC Proyectos GeneralesFecha de inicio: 01-12-2021Fecha fin: 30-11-2024Importe 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 ALMIÑANAFinanciador: FUNDACION ALICIA KOPLOWITZConvocatoria: 2021 FD Alicia Koplowitz - Proyectos de investigaciónFecha de inicio: 01-11-2021Fecha fin: 31-10-2023Importe concedido: 45.000,00€
-
Título: Niños Contra el Cáncer (3 Convenio FDBLC)Investigador principal: MARTA MARIA ALONSO ROLDAN, ANA PATIÑO GARCIAFinanciador: FUNDACIÓN BANCARIA LA CAIXAConvocatoria: 2021 FD La Caixa Niños contra el cáncerFecha de inicio: 28-09-2021Fecha fin: 31-12-2022Importe concedido: 100.000,00€
-
Título: Terapias avanzadas para tumores sólidos pediátricosInvestigador principal: MARTA MARIA ALONSO ROLDAN, ANA PATIÑO GARCIA, JAIME GALLEGO PEREZ DE LARRAYAFinanciador: FUNDACIÓN ADEYConvocatoria: 2021 FD ADEY ProyectosFecha de inicio: 01-04-2021Fecha fin: 03-04-2024Importe concedido: 120.000,00€
-
Título: Plasma extracellular vesicles (EVs): the key for precision medicine in GlioblastomaInvestigador principal: JAIME GALLEGO PEREZ DE LARRAYAFinanciador: ASOCIACION ESPAÑOLA CONTRA EL CANCERConvocatoria: 2020 AECC ERA PermedFecha de inicio: 01-12-2020Fecha fin: 30-11-2023Importe concedido: 41.295,00€
-
Título: Targeting calcium channels against primary and resistant glioblastomaInvestigador principal: MARTA MARIA ALONSO ROLDANFinanciador: FUNDACIO "LA MARATO DE TV3"Convocatoria: 2019 FD LA MARATÓ PROYECTOS DE INVESTIGACIÓNFecha de inicio: 31-07-2020Fecha fin: 30-07-2023Importe concedido: 117.500,00€
-
Título: Moduladores epigenéticos y promotores del cilio primario como nuevos agentes terapéuticos contra el glioblastomaInvestigador principal: FRANCISCO JAVIER SAEZ CASTRESANAFinanciador: UNIVERSIDAD DE NAVARRAConvocatoria: 2020 Convocatoria PIUNA, 2019 Convocatoria PIUNA, 2018 Convocatoria PIUNAFecha de inicio: 01-09-2018Fecha fin: 31-08-2021Importe concedido: 35.000,00€
-
Título: Inmunovirus para el tratamiento del Osteosarcoma.Investigador principal: MARTA MARIA ALONSO ROLDANFinanciador: Asociación Pablo UgarteConvocatoria: 2018 APU PIFecha de inicio: 05-02-2018Fecha fin: 31-12-2024Importe concedido: 112.300,00€
-
Título: Niños contra el cáncer - Inmunoterapia basada en el uso de células dendríticas en tumores sólidos avanzados de niños y adolescentesInvestigador principal: MARTA MARIA ALONSO ROLDAN, ANA PATIÑO GARCIAFinanciador: FUNDACIÓN BANCARIA LA CAIXAConvocatoria: 2017 CAIXA NCCFecha de inicio: 26-09-2017Fecha fin: 27-09-2021Importe concedido: 400.000,00€
-
Título: Estudio de moduladores de toxicidad de la proteína alfa-sinucleína: modificaciones post-traduccionales y respuesta al malplegamiento de proteínasInvestigador principal: MONTSERRAT ARRASATE IRAGUIFinanciador: FUNDACION TATIANA PEREZ DE GUZMAN EL BUENOConvocatoria: 2014 - FUND. TATIANA PROYECTOS I+DFecha de inicio: 15-12-2014Fecha fin: 14-04-2018Importe concedido: 82.500,00€