Sungkyunkwan University

About: Sungkyunkwan University is a education organization based out in Seoul, South Korea. It is known for research contribution in the topics: Thin film & Graphene. The organization has 28229 authors who have published 56428 publications receiving 1352733 citations. The organization is also known as: 성균관대학교.

Single-cell mRNA sequencing identifies subclonal heterogeneity in anti-cancer drug responses of lung adenocarcinoma cells

Abstract: Intra-tumoral genetic and functional heterogeneity correlates with cancer clinical prognoses. However, the mechanisms by which intra-tumoral heterogeneity impacts therapeutic outcome remain poorly understood. RNA sequencing (RNA-seq) of single tumor cells can provide comprehensive information about gene expression and single-nucleotide variations in individual tumor cells, which may allow for the translation of heterogeneous tumor cell functional responses into customized anti-cancer treatments. We isolated 34 patient-derived xenograft (PDX) tumor cells from a lung adenocarcinoma patient tumor xenograft. Individual tumor cells were subjected to single cell RNA-seq for gene expression profiling and expressed mutation profiling. Fifty tumor-specific single-nucleotide variations, including KRAS G12D , were observed to be heterogeneous in individual PDX cells. Semi-supervised clustering, based on KRAS G12D mutant expression and a risk score representing expression of 69 lung adenocarcinoma-prognostic genes, classified PDX cells into four groups. PDX cells that survived in vitro anti-cancer drug treatment displayed transcriptome signatures consistent with the group characterized by KRAS G12D and low risk score. Single-cell RNA-seq on viable PDX cells identified a candidate tumor cell subgroup associated with anti-cancer drug resistance. Thus, single-cell RNA-seq is a powerful approach for identifying unique tumor cell-specific gene expression profiles which could facilitate the development of optimized clinical anti-cancer strategies.

Clinical profile of autoimmune pancreatitis and its histological subtypes: An international multicenter survey

Abstract: OBJECTIVE The objective of this study was to clarify the clinical and pathophysiological characteristics of autoimmune pancreatitis (AIP) and its subtypes (lymphoplasmacytic sclerosing pancreatitis [LPSP] and idiopathic duct-centric pancreatitis [IDCP]) seen around the world. METHODS An international multicenter survey of AIP was conducted in 15 institutes from 8 countries. We compared clinical and pathologic profiles of AIP (n = 731) and the clinical profiles of LPSP (n = 204) and IDCP (n = 64) patients. RESULTS Patients with LPSP were approximately 16 years older than IDCP patients. Obstructive jaundice was a more frequent presentation in LPSP versus IDCP (75% vs 47%, P < 0.001), whereas abdominal pain (41% vs 68%, P < 0.001) and acute pancreatitis (5% vs 34%, P < 0.001) were more frequent in IDCP patients. Patients with LPSP were more likely to have diffuse swelling of the pancreas (40% vs 25%, P = 0.037) and elevated serum IgG4 levels (63% vs 23%, P < 0.001) but less likely to be associated with ulcerative colitis (1% vs 16%, P < 0.001). Clinical profiles of non-histologically confirmed AIP from Asia, the United States, and United Kingdom corresponded with that of LPSP, whereas those from Italy and Germany suggested a mixture of LPSP and IDCP. CONCLUSIONS Autoimmune pancreatitis is seen all around the world, with regional differences in the pathologic and clinical features. Lymphoplasmacytic sclerosing pancreatitis and IDCP have distinct clinical profiles.

Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking

Abstract: Parkinson disease and dementia with Lewy bodies are featured with the formation of Lewy bodies composed mostly of α-synuclein (α-Syn) in the brain Although evidence indicates that the large oligomeric or protofibril forms of α-Syn are neurotoxic agents, the detailed mechanisms of the toxic functions of the oligomers remain unclear Here, we show that large α-Syn oligomers efficiently inhibit neuronal SNARE-mediated vesicle lipid mixing Large α-Syn oligomers preferentially bind to the N-terminal domain of a vesicular SNARE protein, synaptobrevin-2, which blocks SNARE-mediated lipid mixing by preventing SNARE complex formation In sharp contrast, the α-Syn monomer has a negligible effect on lipid mixing even with a 30-fold excess compared with the case of large α-Syn oligomers Thus, the results suggest that large α-Syn oligomers function as inhibitors of dopamine release, which thus provides a clue, at the molecular level, to their neurotoxicity