5032 results for "*oma"

in 33.09 milliseconds.

• Characterizing the immune and genome landscapes for osteosarcoma

  Osteosarcoma have heavily rearranged genomes and moderate tumor mutation burden, which suggests that the patients may express neoantigens that could be targeted by immune cells. To characterize the immunogenomic landscape of this disease, we performed genome, transcriptome, immune and proteomic profiling of 48 patients comprised largely of relapsed and metastatic cases from both pediatric and adult patients.

  Study EGAS00001003247

• Single-cell analysis for metastatic gastric adenocarcinoma

  Intra-tumoral heterogeneity (ITH) is the fundamental property of cancer, however, the origins of ITH remain poorly understood. Here we performed single-cell RNA sequencing of peritoneal carcinomatosis (PC) from patients with advanced gastric adenocarcinoma (GAC), constructed a transcriptome map of 45,048 PC cells, profiled the transcriptome states of diverse tumor cell lineages and types, incisively explored ITH of PC tumor cells, and identified significant correlates with patient survival.

  Study EGAS00001004443

• Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

  ABACUS is a single arm phase 2 study that investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in 95 patients with muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint.

  Study EGAS00001004445

• Genomic characterization of co-existing biliary tract intraepithelial neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer

  Gallbladder carcinoma is the most common cancer of the biliary tract with dismal survival largely due to delayed diagnosis. Biliary tract intraepithelial neoplasia (BilIN) is the common benign tumor that is suspected to be precancerous lesions. However, the genetic and evolutionary relationships between BilIN and carcinoma remain unclear. Here we performed whole-exome sequencing of coexisting low-grade BilIN (adenoma), high-grade BilIN, and carcinoma lesions, and normal tissues from the same patients.

  Study EGAS00001005402

• Mutational_burden_in_human_hair_follicles

  We would like to dissect human hair follicles and assess the mutations found in diffferent parts of the follicle eg bulge, root etc. We can also compare this with mutations found in the surrounding epidermis of the same patients (this is done under a different study). This may provide insights into the origin of PTCH1 mutants frequently seen in basal cell carcinoma but so far not located in our whole epidermis work as well as defining the clonality of the hair follicle

  Study EGAS00001004462

• Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma

  Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose-deprived conditions. Increased fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy.

  Study EGAS00001003251

• ctDNA monitoring using patient-specific sequencing and integration of variant reads - Breast cohort

  Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to individual parts per million. This resulted in median Area Under the Curve (AUC) values of 0.98 in advanced cancers, and 0.80 in early stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that the INVAR may be applied without requiring personalized sequencing panels, so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

  Study EGAS00001004446

• CRISPR/Cas9-mediated genome editing of Schistosoma mansoni acetylcholinesterase

  Here we report successful gene knock-in (KI) in the eggs of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We targeted the acetylcholinesterase (AChE) gene of S. mansoni using two synthetic guide RNAs (gRNAs), X5 and X7, respectively. Liver eggs of S. mansoni were exposed to CRISPR-vector containing X5 or X7 by electroporation. Simultaneously, eggs were transfected with a ssODN donor encoding a stop codon in all six frames. Next generation sequencing analysis revealed that CRISPR/Cas9-mediated editing in S. mansoni eggs resulted in Homology-Directed Repair (HDR) when template DNA ssODN provided. Furthermore, soluble egg antigen (SEA) from AChE-modified eggs exhibited markedly reduced AChE activity compared with controls, indicative that programmed Cas9 cleavage mutated the AChE gene. Following injection of modified schistosome eggs into the tail veins of mice, a significant decrease in granuloma size in the lungs of these animals. Notably, an enhanced Th2 response induced by eggs in lung, and splenocytes small intestine-draining mesenteric lymph node cells was also generated in mice injected with X5-KI eggs in different methods. These findings further demonstrate the power and utility of CRISPR/Cas9-based genome editing for undertaking functional genomics studies in schistosomes.

  Study EGAS00001004455

• Single cell RNA sequencing of normal endometrial derived organoids uncovers novel cell type markers for prognostication

  Endometrial carcinoma, the most common gynecologic cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification is unreliable and there is a need for prognostic tools. We used single cell sequencing to study organoid model systems derived from normal endometrial endometrium to discover novel markers specific for endometrial ciliated or secretory cells. We performed single cell sequencing on endometrial and ovarian tumors and found both secretory-like and ciliated-like tumor cells.

  Study EGAS00001004466

• Targeted sequencing of diffuse large B-cell lymphoma tumour samples from the UK's Haematological Malignancy Research Network

  The UK’s Haematological Malignancy Research Network (www.HMRN.org) was established in 2004 to provide robust generalizable data to inform clinical practice and research. HMRN is a collaboration between researchers in the Epidemiology & Statistics Group (ECSG) at the University of York, a unified Clinical Network operating across 14 hospitals, and an integrated Haematological Malignancy Diagnostic Service (HMDS) in Leeds. Covering a population of around 4 million, HMRN collects detailed information about all patients diagnosed with a haematological malignancy within the HMRN region, accruing around 2,400 new diagnoses each year. The population has a similar socio-demographic profile to the country as a whole, and HMRN’s maturing data present an increasingly valuable resource to address real questions of concern to haematologists, commissioners and health service researchers – locally, nationally and internationally. This study forms part of a larger project employing targeted exome sequencing on tumour samples from patients diagnosed with a variety of both lymphoid and myeloid malignancies. The results for samples collected from 928 diffuse large B-cell lymphoma patients, diagnosed within HMRN from 2005 to 2012, are provided.

  Study EGAS00001005953