A5039995917- Melanoma and MAPK Pathways
- Cancer Mechanisms and Therapy
- Ferroptosis and cancer prognosis
- Synthesis and biological activity
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- PI3K/AKT/mTOR signaling in cancer
- Genomics, phytochemicals, and oxidative stress
- Hepatocellular Carcinoma Treatment and Prognosis
- Sarcoma Diagnosis and Treatment
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Cytomegalovirus and herpesvirus research
- Oral and Maxillofacial Pathology
- Immune Cell Function and Interaction
- Lung Cancer Treatments and Mutations
- Amino Acid Enzymes and Metabolism
- Immunotherapy and Immune Responses
- Protein Tyrosine Phosphatases
- Liver physiology and pathology
- T-cell and B-cell Immunology
- RNA modifications and cancer
- Bone Tumor Diagnosis and Treatments
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
National University Hospital
2012-2024
National University Health System
2013-2024
National University of Singapore
2013-2020
Addenbrooke's Hospital
2009
University of Cambridge
2009
Abstract The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, may contribute towards TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 miR-1290, crucial drivers initiation cancer progression human non-small lung cancer. loss of either miRNA impacted...
Hypoxia is one of the central players in shaping immune context tumor microenvironment (TME). However, complex interplay between cell infiltrates within hypoxic TME HCC remains to be elucidated.We analyzed landscapes hypoxia-low and hypoxia-high regions using cytometry by time light, immunohistochemistry, transcriptomic analyses. The mechanisms immunosuppression subsets interest were further explored vitro hypoxia assays. Regulatory T cells (Tregs) a number immunosuppressive myeloid subsets,...
The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial phenotypic immune-ITH from multiple sectors decipher relationship with disease progression hepatocellular carcinomas (HCC). Immune-ITH is associated transcriptomic-ITH, mutational burden distinct microenvironments. Tumours low experience higher immunoselective pressure escape via loss heterozygosity human...
Abstract Immune evasion is key to cancer initiation and later at metastasis, but its dynamics intermediate stages, where potential therapeutic interventions could be applied, undefined. Here we show, using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues peripheral blood, that extensive immune remodelling takes place in patients with stage I III hepatocellular carcinoma (HCC). We demonstrate the depletion anti-tumoural subsets accumulation immunosuppressive...
Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes paired transcriptomes from 67 HCC patients (331 samples). We found that while ITH was rather constant across stages, had very different...
Human cytomegalovirus (HCMV) regulates NF-kappaB during infection by a variety of mechanisms. For example, the HCMV gene product, UL144, is known to activate in tumor necrosis factor receptor (TNFR)-associated 6 (TRAF6)-dependent manner, causing upregulation chemokine CCL22 (MDC). Viral UL144 expressed from UL/b' region genome at early times postinfection and TNFR1-like homologue. Despite this homology TNFR1 superfamily, does not bind members TNF ligand superfamily. We show here that...
Human CMV (HCMV) encodes multiple genes that control NK cell activation and cytotoxicity. Some of these HCMV-encoded gene products modulate activity as ligands expressed at the surface engage inhibitory receptors, whereas others prevent infected from upregulating bind to activating receptors. A major NKR is homodimeric NKG2D receptor, which has eight distinct natural in humans. It was shown HCMV able expression five (MIC A/B ULBP1, 2, 6). In this article, we show product UL142 can ULBP3...
IL-17-producing CD8 (Tc17) T cells have been shown to play an important role in infection and chronic inflammation, however their implications hepatocellular carcinoma (HCC) remain elusive. In this study, we performed cytometry by time-of-flight (CyTOF) revealed the distinctive immunological phenotypes of two IFNγ+ IFNγ− Tc17 subsets that were preferentially enriched human HCC. Single-cell RNA-sequencing analysis further regulatory circuits governing different these subsets. particular,...
Genomic analyses of squamous cell carcinoma (SCC) have yet to yield significant strategies against pathway activation improve treatment. Platinum-based chemotherapy remains the mainstay treatment for SCC different histotypes either as a single-agent or alongside other chemotherapeutic drugs radiotherapy; however, resistance inevitably emerges, which limits duration response. To elucidate mechanisms that mediate cisplatin, we compared drug-induced perturbations gene and protein expression...
Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to clinical trajectory, may provide novel prognostic and treatment strategies.
Tocilizumab, a monoclonal antibody against interleukin-6, has been used to treat cytokine release syndrome (CRS) in subset of patients with severe COVID-19 disease. Acute ulcerative bowel disease only rarely documented treated for rheumatological conditions. The gastrointestinal side effects seen when the context are unknown. We present case CRS which acute terminal ileum and perforated caecal ulceration evolved after tocilizumab exposure. raise awareness possible causal relationship between...
Background & AimsHepatocellular carcinoma (HCC) arises in a cirrhotic, pro-angiogenic microenvironment. Inhibiting angiogenesis is key mode of action multikinase inhibitors and current non-cirrhotic models are unable to predict treatment response. We present novel mouse cirrhotic model xenotransplant that predicts the natural biology HCC allows personalized therapy.MethodsCirrhosis was induced NOD Scid gamma mice with 4 months thioacetamide administration. Patient derived xenografts (PDXs)...
Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours the matched adjacent normal tissues to understand aberrant events associated with HCC.We identified tumour differential enhancers genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) Hi-C/HiChIP data from samples of patients...
Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are rare tumors with distinct sets of morphological features, both characterized by MUC4 immunoreactivity. Tumors exhibiting features entities considered hybrid LGFMS-SEF lesions. While the majority LGFMS cases FUS-CREB3L2 gene fusions, most pure SEF show EWSR1 rearrangements. In largest study to date, all exhibited FUS rearrangements, a similar genetic profile LGFMS. We herein describe clinicopathological...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21556-y.
Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to normal samples, and may miss out dysregulated genes in small subgroup patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).Using multi-region sampled RNA-seq data 90 patients, we performed patient-specific testing, together with patients' matched adjacent samples.Comparing results from conventional DE analysis analyses, show that omits some due...
Abstract The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncovered significant spatial phenotypic immune–ITH from multiple sectors deciphered relationship with disease progression hepatocellular carcinomas (HCC). Immune–ITH was associated RNA-ITH distinct microenvironments. Tumours low experienced higher immunoselective pressure underwent escape mechanisms via loss heterozygosity human...
Although granulomatosis with polyangiitis (GPA) can affect any organ, gastrointestinal (GI) involvement is uncommon. Moreover, death from massive GI hemorrhage a rare entity, few cases described in the literature. In our report, we present case of patient GPA who developed ulcerative bleeding, which ultimately proved fatal. Given paucity reports available, significant potential for morbidity, and fact that concurrent immunosuppressive therapy may themselves exacerbate risk reviewed 49...
Hepatocellular carcinoma (HCC) is a deadly cancer with high global mortality rate, and the downregulation of GATA binding protein 4 (GATA4) has been implicated in HCC progression. In this study, we investigated role GATA4 shaping immune landscape HCC.