A5051545190- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Radiopharmaceutical Chemistry and Applications
- Immunotherapy and Immune Responses
- Synthesis and Biological Evaluation
- Synthesis and Characterization of Heterocyclic Compounds
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer Immunotherapy and Biomarkers
- Synthesis and biological activity
- Phenothiazines and Benzothiazines Synthesis and Activities
- T-cell and B-cell Immunology
- S100 Proteins and Annexins
- Nanoplatforms for cancer theranostics
- Quinazolinone synthesis and applications
- Obesity, Physical Activity, Diet
- Virus-based gene therapy research
- Toxin Mechanisms and Immunotoxins
- Adipose Tissue and Metabolism
- interferon and immune responses
- Synthesis and Reactions of Organic Compounds
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Synthesis and Reactivity of Heterocycles
University of Nebraska Medical Center
2019-2025
Navarre Institute of Health Research
2016-2024
Universidad de Navarra
2013-2024
Centro de Investigación Biomédica en Red de Cáncer
2017-2024
Clinica Universidad de Navarra
2009-2024
National Institute of Public Health
2024
Bipar
2021
Hospital Virgen de la Concha
2011-2014
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2013
Bristol-Myers Squibb (Germany)
2013
Combined PD-1 and CTLA-4-targeted immunotherapy with nivolumab ipilimumab is effective against melanoma, renal cell carcinoma non-small-cell lung cancer1–3. However, this comes at the cost of frequent, serious immune-related adverse events, necessitating a reduction in recommended dose that given to patients4. In mice, co-treatment surrogate anti-PD-1 anti-CTLA-4 monoclonal antibodies transplantable cancer models, but also exacerbates autoimmune colitis. Here we show treating mice clinically...
Abstract Thirteen N,N ‐diazolylmethanes, including derivatives of pyrazole, imidazole, 1,2,4‐triazole, benzimidazole and indazole were prepared by reaction azoles with methylene chloride under phase transfer catalysis conditions. The relative amounts isomeric mixtures obtained ‘asymmetric’ or equimolar are compared literature results on monoalkylation azoles. Proton carbon‐13 nmr spectra the N,N' ‐diazolylmethanes discussed.
Abstract Agonist monoclonal antibodies (mAb) to the immune costimulatory molecule CD137, also known as 4-1BB, are presently in clinical trials for cancer treatment on basis of their effects primed T cells and perhaps other system. Here we provide evidence that CD137 is selectively expressed surface tumor endothelial cells. Hypoxia upregulated murine Treatment tumor-bearing immunocompromised Rag−/− mice with agonist mAb did not elicit any measurable antiangiogenic effects. In contrast,...
Background The immune response to cancer is often conceptualized with the immunity cycle. An essential step in this interpretation that antigens released by dying tumors are presented dendritic cells naive or memory T tumor-draining lymph nodes. Whether tumor cell death resulting from cytotoxicity, as mediated natural killer (NK) lymphocytes, actually immunogenic currently remains unknown. Methods In study, were killed antigen-specific T-cell receptor (TCR) transgenic CD8 activated NK cells....
Abstract Neutrophil extracellular traps (NETs) are webs of nuclear DNA extruded by dying neutrophils infiltrating tissue. NETs constitute a defence mechanism to entrap and kill fungi bacteria. Tumours induce the formation advantage malignancy via variety mechanisms shown in mouse models. Here, we investigated presence human solid tumours their association with IL‐8 (CXCL8) protein expression CD8 + T‐cell density tumour microenvironment. Multiplex immunofluorescence panels were developed...
Interleukin-8 (CXCL8) produced in the tumor microenvironment correlates with poor response to checkpoint inhibitors and is known chemoattract activate immunosuppressive myeloid leukocytes. In human cancer, IL8 mRNA levels correlate IL1B TNF transcripts. Both cytokines induced IL-8 functional expression from a broad variety of cancer cell lines, primary colon carcinoma organoids, fresh explants. Although absent mouse genome, similar murine axis which TNFα IL-1β upregulate CXCL1 CXCL2 cells...
Immunostimulatory monoclonal antibodies (ISmAb) that unleash antitumor immune responses are showing efficacy in cancer clinical trials. Anti-B7-H1 (PD-L1) (mAb) block a critical inhibitory pathway T cells, whereas anti-CD137 and OX40 mAbs provide T-cell costimulation. A combination of these ISmAbs (anti-CD137 + anti-OX40 anti-B7-H1) was tested using transgenic mouse model multifocal rapidly progressing hepatocellular carcinoma, which c-myc drives transformation cytosolic ovalbumin (OVA) is...
The rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene has been widely associated with childhood obesity in several European cohorts. This association appears to be dependent on dietary macronutrients. Therefore, aim present study was evaluate whether fatty acid intake distribution could interact this FTO genetic variation a Spanish case–control children adolescents. A total 354 adolescents aged 6–18 years (49 % males) were genotyped for variant gene. Anthropometric...
Abstract CD137 (4-1BB; TNFSR9) is an activation-induced surface receptor that through costimulation effects provide antigen-primed T cells with augmented survival, proliferation and effector functions as well metabolic advantages. These immunobiological mechanisms are being utilised for cancer immunotherapy agonist CD137-binding crosslinking-inducing agents elicit intracellular signaling. In this study, side-by-side comparisons show provision of in-cis regard to the TCR-CD3-ligating cell...
In humans, IL-8 (CXCL8) is a key chemokine for chemotaxis of polymorphonuclear leukocytes and monocytes/macrophages when acting on CXCR1 CXCR2. CXCL8 activity neutrophils includes eliciting the extrusion neutrophil extracellular traps (NETs). this study, we show that concentrations induce NETosis surpass in at least one order magnitude those required to elicit chemoattraction human neutrophils. IL-8-induced was less dependent G-proteins than migration, while Ca+2 chelation similarly...
Rationale: The CEA-CD3 T cell bispecific antibody cibisatamab (CEA-TCB) is currently undergoing clinical trials. Here we study its performance against three-dimensional tumor organoids in cocultures with cells as compared to a higher affinity CEACAM5-CD3 (CEACAM5-TCB) using time-lapse confocal microscopy. Methods: Pre-labelled spheroids derived from colon cancer lines and primary four colorectal surgical specimens, which expressed different graded levels of CEA, were exposed lymphocytes....
Endogenous opioid peptides signal through delta-, kappa-, and mu-opioid receptors. Some of these such as endorphins enkephalins are present in the male reproductive tract, but presence corresponding receptors human sperm cells has not yet been reported.Our objective was to study expression localization on spermatozoa implication motility.The studied by RT-PCR, Western blot, immunofluorescence techniques. We evaluated effects activation each receptor specific agonist antagonist.Human express...
Abstract Purpose: Eradication of post-treatment residual myeloma cells is needed to prevent relapses, and immunostimulatory monoclonal antibodies (mAb) such as anti-CD137, CTLA-4, CD40, etc., which enhance the immune response against malignancies, represent a means achieving this purpose. This study explores anti-CD137 mAbs for multiple treatment in preclinical models disease because they safely augment tumor immunity are clinical trials other cancers. Experimental Design: The antitumor...
Abstract Objective To assess the association between consumption of sugar-sweetened carbonated beverages (SSCB) and obesity in children adolescents from Navarra (Spain). Design We used a matched case–control study design. The exposure, SSCB (1 serving: 200 ml), was measured with previously validated FFQ. Anthropometrical measures were taken using standardized protocols. outcome, obesity, defined as BMI above age- sex-specific 97th percentile according to Spanish reference charts. In analysis...
Background BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid that acting on toll-like receptor 3 (TLR3), melanoma differentiation-associated protein 5 (MDA5) and kinase RNA-activated (PKR) elicits rejection directly injected transplanted tumors, but has only modest efficacy against distant untreated tumors. Its clinical activity also been documented in early phase trials. The 5,6-dimethylxanthenone-4-acetic (DMXAA) stimulator interferon genes (STING) agonist shows comparable...