Publications by authors named "Silvia Pineda"

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 different tumorigenesis pathways playing decisive roles at different stages of tumor development, resulting in distinct tumor microenvironment containing both innate and adaptive immune cells (T and B lymphocytes). We aim to characterize the MIBC tumor microenvironment by analyzing the tumor-infiltrating B and T cell repertoire according to the taxonomic molecular subtypes.

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The evident genetic, pathological, and clinical heterogeneity of Alzheimer's disease (AD) poses challenges for traditional drug development. We conducted a computational drug repurposing screen for drugs to treat apolipoprotein (apo) E4-related AD. We first established apoE-genotype-dependent transcriptomic signatures of AD by analyzing publicly-available human brain database.

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Tumor-infiltrating B cells can play an important role in anti-tumor responses but their presence is not well understood. In this study, we extracted the B cell receptor repertoires from 9522 tumor and adjacent non-tumor samples across 28 tumor types in the Cancer Genome Atlas project and performed diversity and network analysis. We identified differences in diversity and network statistics across tumor types and subtypes and observed a trend towards increased clonality in primary tumors compared to adjacent non-tumor tissues.

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Preterm labor (PTL) is the leading cause of neonatal morbidity and mortality worldwide. Whereas many studies have investigated the maternal immune responses that cause PTL, fetal immune cell activation has recently been raised as an important contributor to the pathogenesis of PTL. In this study, we analyzed lymphocyte receptor repertoires in maternal and cord blood from 14 term and 10 preterm deliveries, hypothesizing that the high prevalence of infection in patients with PTL may result in specific changes in the T cell and B cell repertoires.

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Background: Infiltrating B and T cells have been observed in several tumor tissues, including pancreatic ductal adenocarcinoma (PDAC). The majority known PDAC risk factors point to a chronic inflammatory process leading to different forms of immunological infiltration. Understanding pancreatic tumor infiltration may lead to improved knowledge of this devastating disease.

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Introduction: Peripheral blood (PB) molecular patterns characterizing the different effector immune pathways driving distinct kidney rejection types remain to be fully elucidated. We hypothesized that transcriptome analysis using RNA sequencing (RNAseq) in samples of kidney transplant patients would enable the identification of unique protein-coding and noncoding genes that may be able to segregate different rejection phenotypes.

Methods: We evaluated 37 biopsy-paired PB samples from the discovery cohort, with stable (STA), antibody-mediated rejection (AMR), and T cell-mediated rejection (TCMR) by RNAseq.

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Background: Platinum-based neoadjuvant chemotherapy (NAC) increases the survival of patients with organ-confined urothelial bladder cancer (UBC). In retrospective studies, patients with basal/squamous (BASQ)-like tumors present with more advanced disease and have worse prognosis. Transcriptomics-defined tumor subtypes are associated with response to NAC.

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Studying immune repertoire in the context of organ transplant provides important information on how adaptive immunity may contribute and modulate graft rejection. Here we characterize the peripheral blood immune repertoire of individuals before and after kidney transplant using B cell receptor sequencing in a longitudinal clinical study. Individuals who develop rejection after transplantation have a more diverse immune repertoire before transplant, suggesting a predisposition for post-transplant rejection risk.

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Omics data integration is already a reality. However, few omics-based algorithms show enough predictive ability to be implemented into clinics or public health domains. Clinical/epidemiological data tend to explain most of the variation of health-related traits, and its joint modeling with omics data is crucial to increase the algorithm's predictive ability.

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Article Synopsis
  • The study focuses on analyzing CD8+ cytotoxic lymphocytes in bladder cancer, particularly in non-muscle invasive bladder cancer (NMIBC), to understand their role in the immune response against tumors.
  • A standardized method was developed for estimating CD8+ cell counts using tissue samples from a large cohort, revealing significant spatial heterogeneity in immune cell infiltration between different tumor stages.
  • The findings indicate that CD8+ infiltration varies with tumor stage but does not correlate with patient prognosis, highlighting the need for careful study design in future research.
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Transplant rejection is the critical clinical end-point limiting indefinite survival after histocompatibility antigen (HLA) mismatched organ transplantation. The predominant cause of late graft loss is antibody-mediated rejection (AMR), a process whereby injury to the organ is caused by donor-specific antibodies, which bind to HLA and non-HLA (nHLA) antigens. AMR is incompletely diagnosed as donor/recipient (D/R) matching is only limited to the HLA locus and critical nHLA immunogenic antigens remain to be identified.

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Integrative analyses of several omics data are emerging. The data are usually generated from the same source material (i.e.

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Primary and secondary prevention can highly benefit a personalized medicine approach through the accurate discrimination of individuals at high risk of developing a specific disease from those at moderate and low risk. To this end precise risk prediction models need to be built. This endeavor requires a precise characterization of the individual exposome, genome, and phenome.

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Omics data integration is becoming necessary to investigate the genomic mechanisms involved in complex diseases. During the integration process, many challenges arise such as data heterogeneity, the smaller number of individuals in comparison to the number of parameters, multicollinearity, and interpretation and validation of results due to their complexity and lack of knowledge about biological processes. To overcome some of these issues, innovative statistical approaches are being developed.

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Objectives: Different types of '-omics' data are becoming available in the post-genome era; still a single -omics assessment provides limited insights to understand the biological mechanism of complex diseases. Genomics, epigenomics and transcriptomics data provide insight into the molecular dysregulation of neoplastic diseases, among them urothelial bladder cancer (UBC). Here, we propose a detailed analytical framework necessary to achieve an adequate integration of the three sets of -omics data to ultimately identify previously hidden genetic mechanisms in UBC.

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Article Synopsis
  • * The study analyzed 184 SNPs from 18 genes in over 2,000 participants, comparing newly diagnosed bladder cancer patients with matched controls, using various genetic testing methods.
  • * Although some SNPs appeared significant in initial tests, corrections for multiple comparisons showed no strong associations, and only one SNP (rs6567355 in SERPINB5) showed a potential link that needs further investigation.
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Introduction: Gene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D1 has been linked to both worse and better clinical outcome. CCND1 amplification and protein overexpression have also been associated with resistance to treatment with tamoxifen or even to a potentially detrimental effect of tamoxifen.

Methods: To clarify these challenging and partly contrasting treatment predictive and prognostic links for cyclin D1 we analysed a large cohort of postmenopausal breast cancer patients randomised to receive either adjuvant anastrozole or tamoxifen, as part of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

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Purpose: We recently reported that the mRNA-based, 21-gene Genomic Health recurrence score (GHI-RS) provided additional prognostic information regarding distant recurrence beyond that obtained from classical clinicopathologic factors (age, nodal status, tumor size, grade, endocrine treatment) in women with early breast cancer, confirming earlier reports. The aim of this article is to determine how much of this information is contained in standard immunohistochemical (IHC) markers.

Patients And Methods: The primary cohort comprised 1,125 estrogen receptor-positive (ER-positive) patients from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial who did not receive adjuvant chemotherapy, had the GHI-RS computed, and had adequate tissue for the four IHC measurements: ER, progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67.

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Objective: To estimate the yellow fever (YF) vaccine coverage for the endemic and non-endemic areas of Bolivia and to determine whether selected districts had acceptable levels of coverage (>70%).

Methods: We conducted two surveys of 600 individuals (25 x 12 clusters) to estimate coverage in the endemic and non-endemic areas. We assessed 11 districts using lot quality assurance sampling (LQAS).

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