A5085024028- Bladder and Urothelial Cancer Treatments
- Urinary and Genital Oncology Studies
- Cancer Immunotherapy and Biomarkers
- Genetic Associations and Epidemiology
- Lung Cancer Diagnosis and Treatment
- Genetic and Kidney Cyst Diseases
- Genetic Syndromes and Imprinting
- Pituitary Gland Disorders and Treatments
- Atherosclerosis and Cardiovascular Diseases
- Liver physiology and pathology
- Liver Disease and Transplantation
- Lung Cancer Treatments and Mutations
- Genetic and phenotypic traits in livestock
- Advanced Causal Inference Techniques
- Renal and related cancers
- Chemokine receptors and signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Tissue Engineering and Regenerative Medicine
- Organ Transplantation Techniques and Outcomes
- Galectins and Cancer Biology
- Health, Education, and Cultural Studies
- Public Health in Brazil
- Epigenetics and DNA Methylation
- Urticaria and Related Conditions
- Respiratory Support and Mechanisms
St. Michael's Hospital
2024
Unity Health Toronto
2024
Spanish National Cancer Research Centre
2019-2023
Centro de Investigación Biomédica en Red de Cáncer
2021-2023
Institut Català d'Oncologia
2023
Hospital Universitario Puerta de Hierro Majadahonda
2023
Hospital Universitario La Paz
2023
Centro de Investigación del Cáncer
2023
Instituto Oncológico Dr. Rosell
2023
Hospital Clínico Universitario de Valladolid
2023
Approximately 20% of patients with non-small-cell lung cancer (NSCLC) receive a diagnosis stage III disease. There is no current consensus regarding the most appropriate treatment for these patients.In this open-label, phase 2 trial, we randomly assigned resectable IIIA or IIIB NSCLC to neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) alone (control group), followed by surgery. Patients in experimental group who had R0 resections received adjuvant 6 months. The...
8501 Background: Non-small cell lung cancer (NSCLC) is incurable in most patients with locally advanced stage IIIA disease. Previous results indicate that the use of neoadjuvant chemoimmunotherapy could increase percentage cured being a promising therapeutic option has to be tested randomized clinical trials. Methods: NADIM II (NCT03838159) an open-label, randomized, two-arm, phase II, multi-center trial. Patients resectable (per AJCC 7 th ed) NSCLC, ECOG PS 0-1, and no known EGFR/ALK...
Mendelian randomization (MR) uses genetic variants as instrumental variables to investigate the causal effect of a risk factor on an outcome. A collider is variable influenced by two or more other variables. Naive calculation MR estimates in strata population defined collider, such affected factor, can result bias. We propose approach that allows estimation while avoiding This constructs new variable, residual from regression instrument, and then calculates quantiles collider. Estimates...
Platinum-based neoadjuvant chemotherapy (NAC) increases the survival of patients with organ-confined urothelial bladder cancer (UBC). In retrospective studies, basal/squamous (BASQ)-like tumors present more advanced disease and have worse prognosis. Transcriptomics-defined tumor subtypes are associated response to NAC.
Many studies have reported biomarkers predictive of response to immune checkpoint inhibitors (ICI) based on retrospective analyses. However, few clinical trials tested their value prospectively. The DUTRENEO trial (EudraCT: 2017-002246-6) investigated whether an 18-gene Tumour Inflammation Signature (TIS) that can robustly identify patients who respond ICI in multiple tumour types could stratify with localized muscle-invasive bladder cancer (MIBC) receive neoadjuvant...
Introduction Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease with several taxonomic molecular subtypes showing different genetic, clinical, and epidemiological profiles. It has been suggested that MIBC-subtypes follow tumorigenesis pathways playing decisive roles at stages of tumor development, resulting in distinct microenvironment containing both innate adaptive immune cells (T B lymphocytes). We aim to characterize the MIBC by analyzing tumor-infiltrating T cell...
Abstract Atherosclerosis is a chronic inflammatory cardiovascular disease that responsible of high mortality worldwide. Evidence indicates maladaptive autoimmune responses in the arterial wall play critical roles process atherosclerosis. Cortistatin neuropeptide expressed vascular system and atherosclerotic plaques regulates calcification neointimal formation, inhibits inflammation different experimental models diseases. Its role disorders largely unexplored. The aim this study to...
Abstract Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts various vascular and cardioprotective functions regulates immune function inflammatory response at multiple levels. However, its role in cardiovascular disorders largely unknown. Myocarditis atherosclerosis are two autoimmune diseases cause important adverse circulatory events. In this study, we investigate the therapeutic effects of VIP well-established preclinical models experimental myocarditis atherosclerosis....
Background and Purpose Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) pulmonary fibrosis remain major causes of morbidity, mortality a healthcare burden in critically ill patient. There is an urgent need to identify factors causing susceptibility for the design new therapeutic agents. Here, we evaluate effectiveness immunomodulatory neuropeptide cortistatin regulate inflammation vivo . Experimental Approach ALI/ARDS were induced experimentally wild‐type...
Abstract Mesenchymal stromal stem/cells (MSC) therapies are clinically used in a wide range of disorders based on their robust HLA-independent immunosuppressive and anti-inflammatory properties. However, the mechanisms underlying MSC therapeutic activity remain elusive as demonstrated by unpredictable efficacy infusions reported multiple clinical trials. A seminal recent study showed that infused MSCs actively induced to undergo apoptosis recipient cytotoxic T cells, mechanism triggers vivo...
Polycystic kidney disease (PKD) is characterized by extensive cyst formation and progressive fibrosis. However, the molecular mechanisms whereby loss/loss-of-function of Polycystin 1 or 2 (PC1/2) provokes fibrosis are largely unknown. The small GTPase RhoA has been recently implicated in
Neuropathic pain is one of the most severe forms chronic caused by direct injury somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and development analgesics with novel modes action critical. identification endogenous anti-nociceptive factors has emerged as an attractive strategy designing new pharmacological approaches to treat neuropathic pain. Cortistatin a neuropeptide potent anti-inflammatory activity, recently...
Liver fibrosis induced by chronic hepatic injury remains a major cause of morbidity and mortality worldwide. Identification susceptibility/prognosis factors new therapeutic tools for treating fibrotic disorders are urgent medical needs. Cortistatin is neuropeptide with potent anti-inflammatory anti-fibrotic activities in lung that binds to receptors expressed liver fibroblasts stellate cells. We evaluated the capacity cortistatin regulate fibrosis.We experimentally mice CCl4 exposure bile...
Abstract The application of causal mediation analysis (CMA) considering the effect a third variable is increasing in epidemiological studies; however, this requires fitting strong assumptions on confounding bias. To address limitation, we propose an extension CMA combining it with Mendelian randomization (MRinCMA). We applied new approach to analyse obesity and diabetes pancreatic cancer, each factor as potential mediator. check performance MRinCMA under several conditions/scenarios, used...
Abstract Polycystic kidney disease (PKD) is characterized by extensive cyst formation and progressive fibrosis. However, the molecular mechanisms whereby loss/loss-of-function of Polycystin 1 or 2 (PC1/2) provokes fibrosis are largely unknown. The small GTPase RhoA has been recently implicated in cystogenesis , we have shown that RhoA/cytoskeleton/myocardin-related transcription factor (MRTF) pathway a key mediator epithelium-induced fibrogenesis. Therefore, hypothesized MRTF activated PC1/2...
Background and objective Neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care in muscle-invasive bladder cancer (MIBC). Pathological response has been associated with longer survival, but no currently available clinicopathological variables can identify patients likely to respond, highlighting need for predictive biomarkers. We sought a signature NAC integrating clinical score, taxonomic subtype, gene expression. Material methods From 1994 2014, pre-treatment tumor...
Background and Purpose: Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) pulmonary fibrosis remain major causes of morbidity, mortality healthcare burden in the critically ill patient. There is an urgent medical need for identifying factors susceptibility prognosis designing new therapeutic tools treating these disorders. Here, we evaluate capacity immunomodulatory neuropeptide cortistatin to regulate inflammation vivo. Experimental Approach: ALI/ARDS were induced...
Scleroderma, or systemic sclerosis, is a complex connective tissue disorder characterized by autoimmunity, vasculopathy, and progressive fibrosis of the skin internal organs. Because its aetiology unknown, identification genes/factors involved in disease severity, differential clinical forms, associated complications critical for understanding pathogenesis designing novel treatments. Neuroendocrine mediators emerge as potential candidates. We investigated role played neuropeptide cortistatin...
ABSTRACT Platinum-based neoadjuvant chemotherapy (NAC) increases the survival of patients with organ-confined urothelial bladder cancer (UBC). Because not all benefit from treatment, NAC has been widely applied in clinical setting. There is strong evidence, based on retrospective studies, that Basal/Squamous (BASQ)-like tumours present more advanced disease and have worse prognosis; global transcriptomics can identify tumour subtypes associated response to NAC. We aimed investigate whether...
Abstract Background Mendelian randomization (MR) uses genetic variants as instrumental variables to investigate the causal effect of a risk factor on an outcome. A collider is variable influenced by two or more other variables. Naive calculation MR estimates in strata population defined affected can result bias. Methods We propose approach that allows estimation while avoiding This constructs new variable, residual collider, from regression instrument, and then calculates quantiles collider....
Liver fibrosis induced by chronic hepatic injury remains as a major cause of morbidity and mortality worldwide. Identification susceptibility/prognosis factors new therapeutic tools for treating fibrotic disorders various etiologies are urgent medical needs. Cortistatin is neuropeptide with potent anti-inflammatory anti-fibrotic activities in lung that binds to receptors expressed liver fibroblasts stellate cells. Here, we evaluated the capacity cortistatin regulate fibrosis. We initially...