A5056480807- Gastric Cancer Management and Outcomes
- Gastrointestinal Tumor Research and Treatment
- Helicobacter pylori-related gastroenterology studies
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- CAR-T cell therapy research
- Radiomics and Machine Learning in Medical Imaging
- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Angiogenesis and VEGF in Cancer
- Diet and metabolism studies
- HER2/EGFR in Cancer Research
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- Extracellular vesicles in disease
- Colorectal Cancer Treatments and Studies
- Parvovirus B19 Infection Studies
- Prenatal Screening and Diagnostics
- Genetic factors in colorectal cancer
- Ferroptosis and cancer prognosis
- Chemokine receptors and signaling
- Inflammatory Bowel Disease
Samsung Medical Center
2020-2025
Sungkyunkwan University
2020-2025
Samsung (South Korea)
2020-2021
Genome and Company (South Korea)
2016
Abstract Sequence alterations in microsatellites and an elevated mutational burden are observed 20% of gastric cancers associated with clinical response to anti–PD-1 antibodies. However, 50% microsatellite instability–high (MSI-H) intrinsically resistant PD-1 therapies. We conducted a phase II trial pembrolizumab patients advanced MSI-H cancer included serial multi-region tissue samples addition peripheral blood analyses. The number whole-exome sequencing (WES)–derived nonsynonymous...
Chemotherapy is ubiquitous in first-line treatment of advanced gastric cancer, yet responses are heterogeneous, and little known about mediators chemotherapy response. To move forward, an understanding the effects standard on tumor-immune microenvironment (TME) needed. Coupling whole-exome sequencing, bulk RNA single-cell transcriptomics from paired pretreatment on-treatment samples treatment-naïve patients with HER2-positive HER2-negative we define features associated response to...
Adding anti-programmed cell death protein 1 (anti-PD-1) to 5-fluorouracil (5-FU)/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy, we conducted a phase II first-line trial (n = 47) sequentially adding pembrolizumab 5-FU/platinum GEA. Using serial biopsy primary tumor at baseline, after one cycle 5-FU/platinum, addition pembrolizumab, transcriptionally profiled 358,067 single cells identify evolving...
Single-cell ribonucleic acid (RNA) sequencing (scRNA-seq) is an effective technique for estimating the cellular composition and transcriptional profiles of individual cells from fresh tissue. Single-nucleus RNA (snRNA-seq) necessary to perform this type analysis in frozen or difficult-to-dissociate tissues, which cannot be subjected scRNA-seq. This difference state tissues leads variation cell-type distributions among each platform. To identify characteristics these methods their...
Abstract Purpose: Adding pembrolizumab to first-line fluoropyrimidine (5-FU)/platinum chemotherapy plus trastuzumab improves outcomes in advanced HER2+ gastroesophageal adenocarcinomas, but the benefit is largely confined dual and PD-L1+ patients. To assess contributions of components, we conducted a phase II trial evaluating 5-FU/platinum/trastuzumab added cycle 2 patients with metastatic disease. Patients Methods: Treatment-naïve cancer underwent baseline biopsy received single dose...
<title>Abstract</title> A ‘gut-brain axis’ is an intricate bidirectional connection between the gut and central nervous system, serving as a key pathway for signal exchange. However, current <italic>in vitro</italic> models do not fully capture dynamics of interactions these organs, which limits mechanistic understanding therapeutic exploration. Here, we present 3D human gut-brain vascular (GBV) model that simulates communication entities, allowing us to investigate disorders originating...
Background & AimsTumor necrosis factor alpha (TNFα) is considered a major tissue damage-promoting effector in Crohn's disease (CD) pathogenesis. Patient-derived intestinal organoid (enteroid) recapitulates the disease-specific characteristics of epithelium. This study aimed to evaluate epithelial responses TNFα enteroids derived from healthy controls and compare them with those CD patient-derived enteroids.MethodsHuman patients were treated (30 ng/mL), cell viability gene expression patterns...
<div>Abstract<p>Adding anti–programmed cell death protein 1 (anti–PD-1) to 5-fluorouracil (5-FU)/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy, we conducted a phase II first-line trial (<i>n</i> = 47) sequentially adding pembrolizumab 5-FU/platinum GEA. Using serial biopsy primary tumor at baseline, after one cycle 5-FU/platinum, addition pembrolizumab, transcriptionally...
Noninvasive prenatal testing (NIPT) using massively parallel sequencing of cell-free DNA (cfDNA) is increasingly being used to predict fetal chromosomal abnormalities. However, concerns over erroneous predictions which occur while performing NIPT still exist in pregnant women at high risk for aneuploidy. We performed the largest-scale clinical study Korea date assess false negatives and positives next-generation sequencing. A total 447 aneuploidy were enrolled 12 hospitals Korea. They...
Abstract Adding anti-PD1 antibodies to 5-FU/platinum chemotherapy improves survival in a subset of advanced gastroesophageal adenocarcinoma (GEA) patients. Beyond PD-L1 expression and mismatch repair status we have limited insight into molecular predictors response or the relative contribution PD-1 blockade. We conducted an investigator sponsored phase II trial (n = 47) sequentially adding pembrolizumab standard previously untreated GEA (ClinicalTrials.gov: NCT04249739 ). With overall rate...
e15542 Background: Colorectal cancer (CRC) is the third most common and second leading cause of cancer-related death worldwide. What makes CRC treatment a challenge synchronous or metachronous recurrence at distant organs; metastasis. Approximately half patients develop metastases in course disease prevalent metastatic site liver, followed by lung peritoneum. A 5-year survival rate much poorer than that with regional localized CRC. Methods: From 2019 to 2020, 9 who had oligo-metastases were...
Abstract Adding aPD1 to 5-FU/platinum in advanced gastroesophageal adenocarcinomas (GEA) has yielded modest and heterogeneous results. Understanding cooperativity between these two treatment modalities will inform novel combination treatments for GEA. Towards this end, we conducted a trial (n = 47) sequentially adding pembrolizumab previously untreated Using serial biopsy of the primary tumor at baseline, after one cycle 5-FU/platinum, addition transcriptionally profiled 358,067 single cells...
<p>Figure S9. (A) Cell type proportions from scSeq shown by individual patient split high-level cell types across timepoints, color coded fast vs slow progression status. (B) data timepoint and progressor status including only GS CIN patients.</p>
<p>Figure S22. Phagocytosis, angiogenesis and PDGF pathway gene module scores in different M2 macrophage subsets from scRNAseq data.</p>
<p>Figure S26. (A) Proportion of CD8 T cells in non-responder and responder patients split by timepoint. Statistical comparisons performed using a Wilcoxon signed-rank test. (B) Multiplexed immunofluorescence (mIF) images BL, FU1 FU2 samples from two patients, E40 (slow progressor) E41 (fast progressor), staining for panCK, PD-L1, CD4, Granzyme B. (C) macrophages, obtained mIF images, at patients. comparison (D) naive, memory, effector exhausted cell subsets (E) regulatory Th1 CD4 fast...
<p>Figure S4. Multiplexed immunofluorescence (mIF) images of BL and FU1 samples from two patients, E17 (slow progressor) E35 (fast progressor), staining for (A) panCK, PD-L1, CD163, CD68, CD14 CD8, (B) CD4, CD8 Granzyme B.</p>
<p>Figure S10. Mean usage of epithelial cNMF programs per sample at (A) baseline, (B) post-chemotherapy (FU1) and (C) post-immunotherapy (FU2).</p>
<p>Detailed cell type proportions</p>
<p>Annotated cNMF programs</p>
<p>Figure S5. Proportion of cells expression each the 16 markers used for multiplex immunohistochemistry (mIHC) split by timepoint and fast vs slow progressor status.</p>
<p>Figure S11. Mean usage of myeloid cNMF programs per cell subset at (A) baseline, (B) post-chemotherapy (FU1) and (C) post-immunotherapy (FU2). T (D) (E) postchemotherapy (F) (FU2).</p>
<p>Figure S3. (A) Enrichment of gene expression signatures for TME subtypes using bulk RNA-sequencing data all patient samples at baseline and after chemotherapy (follow-up 1; FU1). (B) Pathway enrichment analysis on differentially expressed genes comparing RNA-seq profiles obtained pretreatment (baseline) 1 cycle (FU1). (C) Plots demonstrating change in immune related (Treg, Treg trafficking, Th2, checkpoints, M2 macrophages, pro-tumorgenic cytokines) treatment. Lines connect from the...
<p>Figure S6. (A) UMAP embedding of single cell transcriptomes obtained from all samples in this trial. Labeled are canonical types separated by tumor v.s. normal tissue, and timepoint. (B) Heatmap (C) embeddings showing marker gene expression for broad (A). (D) Broad type composition per sample across tissue. (E) Cell proportions scSeq data timepoint tissue excluding HER2+ patients. (F) TCGA classification patients.</p>