Experience with Sunitinib in metastatic renal cell carcinoma (mRCC) patients: pooled analysis from 3 Spanish observational prospective studies

[Abstract] Background: A pivotal, randomized, phase III trial demonstrated a statistically significant superiority of sunitinib over interferon-α in metastatic renal cell carcinoma (mRCC) patients. Objective: To evaluate the effectiveness and safety of sunitinib in patients with advanced or mRCC in routine clinical practice. Methods: Retrospective pooled analysis of clinical data from three observational and prospective studies carried out between 2007 and 2011 in 33 Spanish hospitals. Tumor response, Progression-free survival (PFS) and overall survival (OS), and main sunitinib-related toxicities were registered. Results: 224 patients were analyzed. Median PFS 10.6 months (95% CI: 9.02–12.25), median OS 21.9 months (95% CI: 17.2–26.6). Objective response rate (ORR) 43.8% (95% CI: 36.8–50.7). Median time to PR was 3.8 months (95% CI: 3.86–5.99) and to CR 8.2 months (95% CI: 4.75–9.77). The most common ≥ grade-3 AEs were asthenia/fatigue (18.7%), hand-foot syndrome (6.2%), hypertension (5.8%) and neutropenia (4.8%). Hand-foot syndrome, diarrhea and mucositis were confirmed as independent predictors for PFS and/or OS in a multivariate analysis (p < 0.05) Conclusions: Outcomes with sunitinib in daily clinical practice resemble those obtained in clinical trials. Long-term benefit with sunitinib is possible in advanced RCC patients but the appropriate management of toxicities is mandatory to enable patients to remain on treatment

Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma

Background: several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Patients and methods: multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. Results: 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Conclusions: certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers of sunitinib response

Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma

Background: Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Patients and methods: Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)=22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. Results: 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Conclusions: Certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR- 628-5p could be potentially used as biomarkers of sunitinib response

Cruise Summary Report - MEDWAVES survey. MEDiterranean out flow WAter and Vulnerable EcosystemS (MEDWAVES)

The MEDWAVES (MEDiterranean out flow WAter and Vulnerable EcosystemS) cruise targeted areas under the potential influence of the MOW within the Mediterranean and Atlantic realms. These include seamounts where Cold-water corals (CWCs) have been reported but that are still poorly known, and which may act as essential “stepping stones” connecting fauna of seamounts in the Mediterranean with those of the continental shelf of Portugal, the Azores and the Mid-Atlantic Ridge. During MEDWAVES sampling has been conducted in two of the case studies of ATLAS: Case study 7 (Gulf of Cádiz-Strait of Gibraltar-Alboran Sea) and Case study 8 (Azores). The initially targeted areas in the Atlantic were: the Gazul Mud volcano, in the Gulf of Cádiz (GoC) area, included in the case study 7, and the Atlantic seamounts Ormonde (Portuguese shelf) and Formigas (by Azores), both part of the case study 8. In the Mediterranean the targeted areas were The Guadiaro submarine canyon and the Seco de los Olivos (also known as Chella Bank) seamount. Unfortunately it was not possible to sample in Guadiaro due to time constraints originated by adverse meteorological conditions which obligate us to reduce the time at sea focusing only in 4 of the 5 initially planned areas. MEDWAVES was structured in two legs; the first leg took place from the 21st September (departure from Cádiz harbour in Spain) to the 13th October 2016 (arrival in Ponta Delgada, São Miguel, Azores, Portugal took place the 8th of October due to the meteorological conditions that obligated to conclude the first leg earlier as planned). during the Leg 1 sampling was carried out in Gazul, Ormonde and Formigas. The second leg started the 14th October (departure from Ponta Delgada) and finished the 26th October (arrival in Málaga harbour, Spain). MEDWAVES had a total of 30 effective sampling days, being 6 days not operative due to the adverse meteorological conditions experienced during the first leg which forced us to stay in Ponta Delgada from the 08th to the 13th October. During MEDWAVES the daily routine followed a similar scheme, depending of course on the weather and sea conditions. The main activity during the day, starting early in the morning (around 08:00 AM, once the night activities were finished), was the ROV deployment. Generally a single ROV dive of around 8 hours was performed, however in several occasions two dives were carried out in the same day (see General station list, Appendix II). After the ROV (and sometimes between two dives) the Box Corer and/or Van Veen Grab and/or Multicore was deployed. After these activities, during the night CTD-Rosette deployments and MB was conducted. Accordingly to this schema the scientific personnel worked in the day or in the night watch. A total of 215 sampling stations have been covered in MEDWAVES, using the following sampling gears: Multibeam echosounder, CTD-Rosette, LADCP, Box Corer, Van Veen Grab, Multicorer and a Remotely Operated Vehicle (ROV). Table 1 sumamrised the number of sampling stations conducted with each gear in each sampling zone. Additionally MB surveys have been conducted during the transits between area

La ciudad como experiencia de conocimiento: nuevas metodologías de aprendizaje, iniciación a la investigación y extensión universitaria a partir de la historia urbana

Memoria que recoge las actividades desarolladas en el proyecto de Innovación docente 327 de 2020 con título La ciudad como experiencia de conocimiento: nuevas metodologías de aprendizaje, iniciación a la investigación y extensión universitaria a partir de la historia urbana y dirigido por Rubén Pallol Trigueros

La ciudad como experiencia de conocimiento: nuevas metodologías de aprendizaje, iniciación a la investigación y extensión universitaria a partir de la historia urbana

El proyecto de innovación docente "La ciudad como experiencia de conocimiento: nuevas metodologías de aprendizaje, iniciación a la investigación y extensión universitaria a partir de la historia urbana" es una iniciativa de varios profesores, investigadores y estudiantes de los grados de Historia e Historia del Arte, que pretende aprovechar todas las posibilidades que proporciona el estudio de la ciudad en el proceso de enseñanza y aprendizaje, la iniciación a la investigación, el fomento de la interdisciplinariedad y el desarrollo de actividades de extensión universitaria

La ciudad como experiencia de conocimiento: Nuevas metodologías de aprendizaje, iniciación de la investigación y extensión universitaria a partir de la historia urbana

Depto. de GeografíaDepto. de Historia Moderna y ContemporáneaDepto. de Historia del ArteFac. de Geografía e HistoriaFALSEsubmitte

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research