12022 results for "division 2 coins fc 26 Visit Buyfc26coins.com Kupiłem(a) duży pakiet monet FC 26 i dostałem(a) dodatkowy rabat. Świetnie!.fXzt"

in 12.02 milliseconds.

• Patient-derived organoids from gastrointestinal cancers

  Patient-derived organoids model treatment response of metastatic gastrointestinal cancers (80 targeted exome capture samples and 2 whole-genome sequencing samples)

  Dataset EGAD00001003926

• Epstein-Barr Virus status drives morphological and molecular intra-tumour heterogeneity in gastric cancer: insights from a case report and literature review

  This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion. Immunohistochemical and molecular studies confirmed that, despite the differing morphologies and immunophenotypes, both components were clonally related, with especially the EBV-negative area showing more complex DNA aberrations, reminiscent of Chromosomally instable (CIN) lesions. This case describes clonally related EBV-positive and negative components within a single gastric cancer, contributing to a better understanding of EBV role in tumour heterogeneity and progression and highlighting the impact of EBV loss on tumour behaviour.

  Study EGAS50000000706

• A Comprehensive Genetic Study of Classical Hodgkin Lymphoma Using Circulating Tumour DNA

  This study on classical Hodgkin lymphoma (cHL) used advanced methods to analyse circulating tumour DNA (ctDNA) in 297 cases, offering insights into its genetic landscape and linking it to disease pathophysiology and clinical progression. Key findings include the identification of whole genome duplication as a predictor of poor chemotherapy response. Additionally, a highly recurrent somatic expression quantitative trait locus of the BCL6 gene was discovered, implicating regulatory mutations in cHL pathophysiology and highlighting BCL6 as both a vulnerability and therapeutic target. Consensus clustering identified two cHL subtypes distinguished by the underlying mechanisms of genetic instability, rather than by specific genetic mutations or EBV infection. The study also linked the number and clonality of neoantigens with tumour microenvironment and response to checkpoint blockade. Finally, our results suggested ctDNA analysis as a tool to distinguish ambiguous PET/CT-positive lesions persisting after treatment, aiming to reduce unnecessary medical interventions.

  Study EGAS50000000873

• Whole-Genome Sequencing of a Healthy Aging Cohort.

  Studies of long-lived individuals have revealed few genetic mechanisms for protection against age-associated disease. Therefore, we pursued genome sequencing of a related phenotype-healthy aging-to understand the genetics of disease-free aging without medical intervention. In contrast with studies of exceptional longevity, usually focused on centenarians, healthy aging is not associated with known longevity variants, but is associated with reduced genetic susceptibility to Alzheimer and coronary artery disease. Additionally, healthy aging is not associated with a decreased rate of rare pathogenic variants, potentially indicating the presence of disease-resistance factors. In keeping with this possibility, we identify suggestive common and rare variant genetic associations implying that protection against cognitive decline is a genetic component of healthy aging. These findings, based on a relatively small cohort, require independent replication. Overall, our results suggest healthy aging is an overlapping but distinct phenotype from exceptional longevity that may be enriched with disease-protective genetic factors.

  Study EGAS00001002306

• Myelodysplastic cells in patients re-program mesenchymal stromal cells to establish a transplantable stem cell-niche disease unit.

  Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms with defects in hematopoietic stem/progenitor cells (HSPCs) and possibly the HSPC niche. Here we show that patient-derived mesenchymal stromal cells (MDS MSCs) display a disturbed differentiation program and are essential for the propagation of MDS-initiating lin-CD34+CD38- stem cells in orthotopic xenografts. Overproduction of niche factors such as N-Cadherin, IGFBP2, VEGFA and LIF is associated with the ability of MDS MSCs to enhance MDS expansion. These factors represent putative therapeutic targets to disrupt critical hematopoietic-stromal interactions in MDS. Finally, healthy MSCs adopt "MDS-MSC like" molecular features when exposed to hematopoietic MDS cells, indicative of an instructive remodeling of their microenvironment. This patient-derived xenograft model therefore provides functional and molecular evidence that MDS is a complex disease involving both the hematopoietic and stromal compartments. The resulting deregulated expression of niche factors may well also be a feature of other hematopoietic malignancies.

  Study EGAS00001000716

• Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

  RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations in this enzyme have not been previously linked to any pathology in humans, a testament to its indispensable role in cell biology. Based on a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II1, are sufficient to hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors reveal dysregulation of key meningeal identity genes, including WNT6 and ZIC1/ZIC42,3. In addition to POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA and SMO4-8, we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features.

  Study EGAS00001001916

• A spatiotemporal organ-wide gene expression and cell atlas of the developing human heart

  The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages, and which maps cell type-specific gene expression to specific anatomical domains. Spatial Transcriptomics identified unique gene profiles corresponding to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA-sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.

  Study EGAS00001003996

• A living biobank of breast cancer organoids captures disease heterogeneity

  Breast Cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Xeno-transplantation and direct culturing of tumor tissue are increasingly used in drug development and personalized medicine strategies. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, 101 BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor-, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene expression-based classification groups and allowed drug screens in vitro and upon xenotransplantation. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion.

  Study EGAS00001002158

• Resolving the immune landscape of human prostate at a single cell level in health and cancer

  The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with limited treatment efficacy in castration-resistant metastatic disease, including with immune checkpoint inhibitors. We used single-cell RNA-sequencing to perform an unbiased assessment of the cellular landscape of human prostate and identified a previously unappreciated subset of tumour-enriched androgen receptor-negative luminal epithelial cells, with increased expression of cancer-associated genes. We also found a variety of innate and adaptive immune cells in normal prostate that were transcriptionally perturbed in prostate cancer. An exception was a unique, prostate-specific, zinc transporter-expressing macrophage population (MAC-MT), that contributed to tissue zinc accumulation in homeostasis, but showed enhanced inflammatory gene expression in tumours, including T cell-recruiting chemokines. Remarkably, enrichment of the MAC-MT signature in cancer biopsies was associated with improved disease-free survival, suggesting beneficial anti-tumour functions.

  Study EGAS00001005787

• A longitudinal single-cell atlas of treatment response in pediatric AML

  Pediatric acute myeloid leukemia (pAML) is a disease characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains relatively understudied in pediatric patients. We therefore used single-cell RNA sequencing and single-cell ATAC sequencing to profile 684,031 diagnosis, remission and relapse cells from 28 patients representing different pAML subtypes. Analysis revealed that at diagnosis, cellular compositions differed between distinct subgroups. Upon relapse, cellular hierarchies transitioned towards a more primitive state regardless of subtype. These primitive cells were distinct compared to cells at diagnosis, having underrepresentation of transcriptional programs involved in myeloid differentiation while programs commonly found in other lineages were overrepresented. In a subset of patients, this appeared to accompany the appearance of a B-lymphoid-like hierarchy. Together, our data reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potential novel therapeutic angles to target these cell populations.

  Study EGAS00001007323