Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
607
result(s) for
"Quesada, Alfonso"
Sort by:
Evolution of Conifer Diterpene Synthases: Diterpene Resin Acid Biosynthesis in Lodgepole Pine and Jack Pine Involves Monofunctional and Bifunctional Diterpene Synthases
Diterpene resin acids (DRAs) are major components of pine (Pinus spp.) oleoresin. They play critical roles in conifer defense against insects and pathogens and as a renewable resource for industrial bioproducts. The core structures of DRAs are formed in secondary (i.e. specialized) metabolism via cycloisomerization of geranylgeranyl diphosphate (GGPP) by diterpene synthases (diTPSs). Previously described gymnosperm diTPSs of DRA biosynthesis are bifunctional enzymes that catalyze the initial bicyclization of GGPP followed by rearrangement of a (+)-copalyl diphosphate intermediate at two discrete class II and class I active sites. In contrast, similar diterpenes of gibberellin primary (i.e. general) metabolism are produced by the consecutive activity of two monofunctional class II and class I diTPSs. Using high-throughput transcriptome sequencing, we discovered 11 diTPS from jack pine (Pinus banksiana) and lodgepole pine (Pinus contorta). Three of these were orthologous to known conifer bifunctional levopimaradiene/abietadiene synthases. Surprisingly, two sets of orthologous PbdiTPSs and PcdiTPSs were monofunctional class I enzymes that lacked functional class II active sites and converted (+)-copalyl diphosphate, but not GGPP, into isopimaradiene and pimaradiene as major products. Diterpene profiles and transcriptome sequences of lodgepole pine and jack pine are consistent with roles for these diTPSs in DRA biosynthesis. The monofunctional class I diTPSs of DRA biosynthesis form a new clade within the gymnosperm-specific TPS-d3 subfamily that evolved from bifunctional diTPS rather than monofunctional enzymes (TPS-c and TPS-e) of gibberellin metabolism. Homology modeling suggested alterations in the class I active site that may have contributed to their functional specialization relative to other conifer diTPSs.
Journal Article
263 Real world experience with PARPi maintenance use in ovarian cancer
Introduction/BackgroundSurvival of ovarian carcinoma has improved in recent years due to determination of the homologous recombination deficit (HRD), and the use of first-line maintenance with PARP inhibitors (PARPi).The aim of our study was to do a real world study in patients treated in our Center.MethodologyA cross-sectional longitudinal observational study was designed in a cohort of 100 patients diagnosed with ovarian cancer during the period 2018 to 2022. HRD was determined by Myriad myChoice test. The variables to be studied were: somatic mutation, and germline if positive by NGS, type of mutation, age at diagnosis, histology, stage, primary or interval surgery after neoadjuvant chemotherapy, response, PARPi, progression free survival (PFS), and allergy to chemotherapy.ResultsThe mean age at diagnosis of ovarian carcinoma was 62 years, with a predominance of 50% stage IIIC, and 80% of serous histology grade 3. 32% were HRD positive, with BRCA1 in 55%, BRCA2 in 10%, and the remaining 35% others of the RAD51C, BRIP1.68% of cases received neoadjuvant chemotherapy, and only 50% were candidates for interval surgery. Primary surgery was performed in 32% of patients. Results: CR 38.4%, PR 53.5%. SD: 2% and progression 6.1%. Allergic reaction to chemotherapy occurred in 22% of the total.38% of patients received PARPi as first-line maintenance.In the group of patients who progressed to first line (49% of our series), PFS was higher in those with somatic line pathogenic variants, presenting a median of 18 months versus 10 months, (p=0.015).ConclusionThe results of our case series are compatible with those published in the literature, highlighting the increase in PFS in HRD+ patients who have received maintenance with PARPi. We found an increase of allergic reactions in patients carrying pathogenic germline variants, probably due to splicing-related mechanisms. These data should be cross-checked with other future studies.Abstract #263 Figure 1Stage/Progression. PFS/HRD[Figure omitted. See PDF]DisclosuresNo
Journal Article
2022-RA-449-ESGO Clinical-molecular correlations of endometrial cancer. Retrospective study
Introduction/BackgroundEndometrial cancer (EC) is the most common gynecological tumor in developed countries, with more than 75% diagnosed at early stages. It is associated in 20–30% with microsatellite instability (MSI) due to mutations in the MMR genes, which can be sporadic (80–90%) or hereditary (10–20%) such as Lynch syndrome (LS).Objective: To establish the clinical-molecular profile of endometrial carcinoma and its implication for treatment.MethodologyRetrospective cross-sectional observational study. 162 patients diagnosed with EC during the period 2010–2020 and treated in Medical Oncology Service at the HUNSC were studied.Study variables: age, histology grade and type, stage, hormone receptors (HR), MSI, LS, overall survival. SPSS 25 was used for statistical analysis.Abstract 2022-RA-449-ESGO Figure 1ResultsThe median age was 64,51 years. The most frequent stages at diagnosis were IA (25.3%) and IB (24.7%). Histologically, endometrioid adenocarcinoma accounted for 51.2% and grade 3 for 41.4% of cases. Patients with LS were mainly diagnosed at stage III, being endometrioid or serous adenocarcinomas, and mainly grade 3 (60%). Overall survival was longer in the HR+ group (40.5 months). MSI-H was observed in 36.1% of the sample and the dMMR distribution: MLH1 (27.9%) and PMS2 (24.6%), MSH2 (16.4%), MSH6 (13.1%). Ten patients were diagnosed with LS.Abstract 2022-RA-449-ESGO Figure 2ConclusionOur EC and LS results are comparable to those published for other settings. There is a significant association between HR+ and longer overall survival. The percentage of dMMR/MSI-H is higher than reported in other studies. Further studies with a larger sample would be needed.
Journal Article
Publicidad en abierto: el rol de las revistas diamante para una investigación transparente y accesible
En los últimos años, la ciencia abierta se ha consolidado como un nuevo paradigma que promueve la transparencia, el acceso libre al conocimiento y la participación ciudadana, especialmente en investigaciones financiadas con fondos públicos. Las revistas diamante representan un modelo editorial alineado con estos valores: sin ánimo de lucro, sin costes para autores ni lectores, y con gestión comunitaria. En el ámbito de la publicidad, este modelo supone una oportunidad para hacer la investigación más inclusiva, ética y accesible, fortaleciendo el vínculo entre academia, industria y sociedad. Questiones Publicitarias se presenta como un ejemplo de este compromiso transformador. En els darrers anys, la ciència oberta s’ha consolidat com un nou paradigma que promou la transparència, l’accés lliure al coneixement i la participació ciutadana, especialment en investigacions finançades amb fons públics. Les revistes diamant representen un model editorial alineat amb aquests valors: sense ànim de lucre, sense costos per a autores ni lectores, i amb una gestió comunitària. En l’àmbit de la publicitat, aquest model suposa una oportunitat per fer la recerca més inclusiva, ètica i accessible, enfortint el vincle entre acadèmia, indústria In recent years, open science has emerged as a new paradigm promoting transparency, free access to knowledge, and public engagement, especially in research funded with public resources. Diamond journals embody this approach through non-profit, community-driven publishing models with no fees for authors or readers. In the field of advertising, this model offers a unique opportunity to make research more inclusive, ethical, and accessible, strengthening the connection between academia, industry, and society. Questiones Publicitarias stands as a living example of this transformative commitment.
Journal Article
SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer
BackgroundMinimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse.MethodsWe obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group.ResultsMean age was 48.3 years (range; 23–83) while the mean BMI was 25.7 kg/m2 (range; 15–49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52).ConclusionsMinimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.
Journal Article
2022-RA-1032-ESGO Evaluation of intraoperative HPV test as an early marker of residual disease after HSIL surgical treatment. a prospective multicenter study. Preliminary results
Introduction/BackgroundObjectiveTo evaluate if the intraoperative human papillomavirus (IOP-HPV) test has the same prognostic value as the HPV test performed 6 months after treatment of high-grade squamous intraepithelial Lesion (HSIL) to predict treatment failure.MethodologyDesignProspective multicenter cohort studySetting: 22 Referral Hospitals in Spain.Population: 1824 women treated for cervical HSIL by Loop Electrosurgical Excision between May 2020 and December 2021After LEEP an HPV test was performed immediately after excision using a Cobas (83%) or other genotyping test.Subsequently, pacients were followed with citology and HPV test, 6, 12 and 24 months after treatment.The IOP-HPV test was compared with HPV test 6 months after procedure and with surgical margins in order to detect residual disease.ResultsWe described results of the first 992 cases with the 6 month co-test performed. IOP HPV test was feasible (valid result 98,5%). IOP-HPV was positive in 40%, while only 25% at 6 month test. We observed association between the IOP and 6 month HPV test (ChiSquare p= 0.0001), IOP HPV positivity and abnormal citology at 6 months (p=0.063), and positive IOP HPV test and positive surgical margins.(p=0.0001)ConclusionPreliminary results show that IOP HPV test could be a satisfactory prognostic factor of cervical HSIL treatment result.
Journal Article
98 Real-world study of first-line metastatic cervical carcinoma: impact of PDL1 assessment and immunotherapy on progression-free survival
Introduction/BackgroundHistorically, first-line metastatic cervical carcinoma treatment relied on platinum-paclitaxel chemotherapy with or without Bevacizumab, yielding poor prognosis. This study aims to conduct a real-world analysis of the PDL1 effect assessment and the incorporation of immunotherapy (IT) into the standard regimen over the past two years.MethodologyA retrospective observational cohort study involving 56 patients with stage IV cervical carcinoma treated between 2010 and 2023. The cohort consists of 30 new patients with PDL1 determination and 26 old patients lacking PDL1 evaluation. The primary variable is Progression-Free Survival (PFS) in new cases concerning immunotherapy and PFS in old cases. Secondary variables include age at diagnosis, histology, grade (G), radiotherapy, bevacizumab, overall survival in old cases, and response rates.ResultsBoth groups exhibited no significant differences in mean age at diagnosis (53 years), squamous cell carcinoma histology (82.1%), G3 (62.5%), and radiotherapy rates (75–80%).A significant difference was observed in the Bevacizumab administration (p=0.023), with 28% of old cases receiving it compared to 59% of new cases. However, PFS was more favorable in old cases with bevacizumab, while new cases did not exhibit the same benefit. Median OS in old cases was 8 months.Among the new cases, 83.3% tested positive for PDL1. Statistically significant differences were noted (p<0,001; U Mann-Whitney Test) in median PFS, with the IT patient group demonstrating superior outcomes than without IT group: 12 [6–22,5] months versus 3 [2–12] months, respectively.IT resulted in a higher response rate (92%) in contrast to cases without IT (31.6%). Response types with IT included 42.9% complete response (CR), 50% partial response (PR) and 7.1% progression (P). In cases without IT, the responses included CR (15.8%), PR (15.8%), stable disease (SD, 28.9%), 39.5% P (p=0.001).ConclusionResults demonstrate a PFS increase in patients receiving immunotherapy regardless Bevacizumab addition, being consistent with the phase 3 KEYNOTE-826 results.DisclosuresNo.
Journal Article
SENECA study: staging endometrial cancer based on molecular classification
ObjectiveManagement of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I–II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification.MethodsThe SENECA study retrospectively reviewed data from 2139 women with stage I–II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens.ResultsAmong the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high–intermediate risk patients, and 22.51% for high-risk patients; p<0.001).ConclusionsOur study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.
Journal Article