A5001311997- CRISPR and Genetic Engineering
- Intraperitoneal and Appendiceal Malignancies
- CAR-T cell therapy research
- Ovarian cancer diagnosis and treatment
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Virus-based gene therapy research
- Genetic factors in colorectal cancer
- Inflammatory Biomarkers in Disease Prognosis
- Sarcoma Diagnosis and Treatment
- Oil Palm Production and Sustainability
- Hepatocellular Carcinoma Treatment and Prognosis
- Pancreatic function and diabetes
- Liver physiology and pathology
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Diverticular Disease and Complications
- Protease and Inhibitor Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Galectins and Cancer Biology
National Cancer Centre Singapore
2014-2024
Singapore General Hospital
2021-2022
National University of Singapore
2016
In this study, unique methyl-functionalized derivatives (T*PP+) of the drug carrier triphenylphosphonium (TPP+) that exhibit significant enhancement accumulation both cation and its conjugated cargo in cell mitochondria are designed. We show presence methyl group(s) at key positions within phenyl ring results an increase hydrophobicity solvent accessible surface area T*PP+. particular, when para position T*PP+ is functionalized with a group, most exposed to surrounding environment, leading...
Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. Despite the widespread adoption sorafenib as standard HCC treatment, its efficacy constrained, frequently encountering resistance. To augment effectiveness sorafenib, this study investigated synergy and vinorelbine using 22 patient-derived xenograft (PDX) models. In study, mice bearing tumors were treated with vehicle, (15 mg/kg), (3 sorafenib–vinorelbine combination (Sora/Vino). Rigorous monitoring tumor...
Biosafety and efficacy considerations that impede clinical application of gene therapy could be addressed by nonviral ex vivo cell therapy, utilizing transgenic cells have been comprehensively pre-evaluated for genotoxic potential transgene expression. We evaluated the phiC31 bacteriophage integrase-mediated integration in cord-lining epithelial (CLECs) readily cultured from outer membrane human umbilical cords, sequencing mapping sites, spectral karyotyping, high-resolution genome copy...
Abstract Ovarian cancer is associated with poor prognosis. Platinum resistance contributes significantly to the high rate of tumour recurrence. We aimed identify a set molecular markers for predicting platinum sensitivity. A signature cisplatin sensitivity was generated using Genomics Drug Sensitivity in Cancer and The Genome Atlas databases. Four potential biomarkers (CYTH3, GALNT3, S100A14, ERI1) were identified optimized immunohistochemistry (IHC). Validation performed on cohort patients...
Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of fluids, obtained from the anatomic site pathology, could reveal diagnostic proteomic fingerprints. Protein profiles were generated fluid samples 19 and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on...
Peritoneal carcinomatosis (PC) present a ubiquitous clinical conundrum in all intra-abdominal malignancies. Via functional and transcriptomic experiments of ascites-treated PC cells, we identify STAT3 as key signaling pathway. Integrative analysis publicly available databases correlation with cohorts (n = 7,359) reveal putative clinically significant activating ligands signaling. We further validate 3-biomarker prognostic panel ascites independent covariates prospective study 149)....
BackgroundCurrent gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we sought to overcome these by ex vivo electrotransfer of nonviral insulin expression vector into primary hepatocytes followed immediate autologous reimplantation in preclinical model diabetes.Methods ResultsIn single 3-hour procedure, were isolated from surgically resected liver wedge, electroporated with an plasmid reimplanted...
Abstract Generation of large amounts genomic data is now feasible and cost-effective with improvements in next generation sequencing (NGS) technology. Ribonucleic acid (RNA-Seq) becoming the preferred method for comprehensively characterising global transcriptome activity. Unique to cytoreductive surgery (CRS), multiple spatially discrete tumour specimens could be systematically harvested analysis. To facilitate such downstream analyses, laser capture microdissection (LCM) utilized obtain...
Hepatocellular carcinoma (HCC) is a challenging cancer to treat, as traditional chemotherapies have shown limited effectiveness. The mammalian target of rapamycin/sirolimus (mTOR) and microtubules are prominent druggable targets for HCC. In this study, we demonstrated that co-targeting mTOR using inhibitors (everolimus sirolimus) along with the microtubule inhibitor vinorelbine yielded results superior those monotherapies in HCC PDX models. Our research showed arrests cells at mitotic phase,...
Gastric cancer remains highly fatal due to a dearth of diagnostic biomarkers for early stage disease and molecular targets therapy. Plasma membrane proteins, including cluster differentiation (CD) proteins receptor tyrosine kinases (RTKs), are rich reservoir biomarkers. Recognizing that interrogating plasma individually overlooks extensive interactions among them, we have systematically investigated the proteomes transcriptomes six gastric cell lines. Our data revealed aberrantly high...
The prognostic significance of inflammatory markers in solid cancers is well-established, albeit with considerable heterogeneity. This study sought to investigate the postoperative marker trend peritoneal carcinomatosis (PC), a focus on colorectal PC (CPC), and propose optimal surveillance periods cutoffs.Data were collected from prospectively maintained database patients treated at authors' institution April 2001 March 2019. platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte (NLR),...
Costly coagulation factor VIII (FVIII) replacement therapy is a barrier to optimal clinical management of hemophilia A. Therapy using FVIII-secreting autologous primary cells potentially efficacious and more affordable. Zinc finger nucleases (ZFN) mediate transgene integration into the AAVS1 locus but comprehensive evaluation off-target genome effects currently lacking. In light serious adverse in trials which employed genome-integrating viral vectors, this study evaluated potential...
Abstract Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significant perioperative morbidity mortality. We aim to generate validate a biomarker set predicting sensitivity Mitomycin-C refine selection of patients colorectal peritoneal metastasis (CPM) for this treatment. A signature was generated using data from Genomics Drug Sensitivity in Cancer The Genome Atlas. Validation performed on CPM who underwent CRS-HIPEC (n = 62)...
We have previously identified and validated a panel of molecular prognostic markers (ATP13A3, SSR3, ANO1) for Head Neck Squamous Cell Carcinoma (HNSCC). The aim this study was to investigate the consequence ATP13A3 dysregulation on signaling pathways, aid in formulating therapeutic strategy targeting ATP13A3-overexpressing HNSCC. Gene Set Enrichment Analysis (GSEA) performed HNSCC microarray expression data (Internal local dataset [n = 92], TCGA 232], EMBL 81]) identify pathways associated...
Lung cancer cells harboring activating EGFR mutations acquire resistance to tyrosine kinase inhibitors (TKIs) by several bypass mechanisms, including MET amplification and overexpression. We show that a significant proportion of activated protein in TKI-resistant HCC827 lung resides within the mitochondria. Targeting total complement plasma membrane mitochondria should render these more susceptible cell death hence provide means circumventing drug resistance. Herein, mitochondrial targeting...
Abstract Chromosomal rearrangements are common in cancer. More than 50% occur fragile sites and disrupt tumor suppressors. However, such not known gastric Here we report recurrent 18q2 breakpoints 6 of 17 cancer cell lines. The rearranged chromosome 18, t(9;18), MKN7 cells was flow sorted identified by reverse painting. High-resolution tiling array hybridization mapped to DOK6 (docking protein 6) intron 4 FRA18C (18q22.2) an intergenic region 9q22.2. same rearrangement detected FISH 22% 99...
Abstract Genetically modified FVIII‐expressing autologous bone marrow‐derived mesenchymal stromal cells (BMSCs) could cure haemophilia A. However, culture‐expanded BMSCs engraft poorly in extramedullary sites. Here, we compared the intramedullary cavity, skeletal muscle, subcutaneous tissue and systemic circulation as microenvironments that support durable engraftment of FVIII‐secreting BMSC vivo. A zinc finger nuclease integrated human FVIII transgene into PPP1R12C (intron 1) primary canine...
Cell therapy could potentially meet the need for pancreas and islet transplantations in diabetes mellitus that far exceeds number of available donors. Bone marrow stromal cells are widely used clinical trials mainly their immunomodulatory effects with a record safety. However, less focus has been paid to developing these insulin secretion by transfection. Although murine models have extensively gene cell research, few studies shown efficacy large preclinical animal models. Here we report...
Up to 10% of well-differentiated liposarcoma (WDLS) progress dedifferentiated (DDLS). We aimed identify gene expression changes associated with dedifferentiation and whether these were informative tumour biology DDLS. analysed datasets from the Gene Expression Omnibus (GEO, ID = GSE30929) database differentially expressed genes between WDLS (n 52) DDLS 39). validated signature on whole laser-capture microdissected samples patients tumours consisting mixed components. A subset this was...
Abstract Cancer proteomes have not been comprehensively studied on a genome-wide scale. In this work, we catalogued the proteome of human gastric cancer cell line, SNU5, by integrative analysis multiple proteomic data sets generated from mitochondria, nucleus and membranes, in addition to phosphoproteome whole proteome. We report total 10440 proteins, which 8578 were identified with at least two unique spectra 7042 more than one peptide. localized proteins specific organelles higher...