A5073155409- Aldose Reductase and Taurine
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Peroxisome Proliferator-Activated Receptors
- Cholesterol and Lipid Metabolism
- Phagocytosis and Immune Regulation
- Liver physiology and pathology
- Epigenetics and DNA Methylation
- Cancer Mechanisms and Therapy
- Hepatocellular Carcinoma Treatment and Prognosis
- Caveolin-1 and cellular processes
- Erythrocyte Function and Pathophysiology
- Lung Cancer Treatments and Mutations
- Hippo pathway signaling and YAP/TAZ
- Eicosanoids and Hypertension Pharmacology
- Ferroptosis and cancer prognosis
- Hepatitis B Virus Studies
- Endoplasmic Reticulum Stress and Disease
Tsan Yuk Hospital
2023-2025
Queen Elizabeth Hospital
2017-2024
Queen Mary University of London
2024
University of Hong Kong
2012-2020
Chinese University of Hong Kong
2010-2020
Queen Mary Hospital
2014-2020
Hong Kong Polytechnic University
2016-2018
State Key Laboratory of Synthetic Chemistry
2015
Detroit Receiving Hospital
2009
Like normal stem cells, tumor-initiating cells (T-ICs) are regulated extrinsically within the tumor microenvironment. Because HCC develops primarily in context of cirrhosis, which there is an enrichment activated fibroblasts, we hypothesized that cancer-associated fibroblasts (CAFs) would regulate liver T-ICs. We found presence α-SMA(+) CAFs correlates with poor clinical outcome. CAF-derived HGF regulates T-ICs via activation FRA1 Erk1,2-dependent manner. Further functional analysis...
Objective We investigated the effect and mechanism of hypoxic microenvironment hypoxia-inducible factors (HIFs) on hepatocellular carcinoma (HCC) cancer stemness. Design HCC stemness was analysed by self-renewal ability, chemoresistance, expression stemness-related genes stem cell (CSC) marker-positive population. Specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) mRNA level examined with quantitative PCR in human paired HCCs. Immunoprecipitation used to examine binding...
Wnt/β‐catenin signaling is activated in CD133 liver cancer stem cells (CSCs), a subset of known to be root tumor recurrence and therapy resistance hepatocellular carcinoma (HCC). However, the regulatory mechanism this pathway CSCs remains unclear. Here, we show that human microRNA (miRNA), miR‐1246, promotes stemness, including self‐renewal, drug resistance, tumorigencity, metastasis, by activation through suppressing expression AXIN2 glycogen synthase kinase 3β (GSK3β), two key members...
Identification of therapeutic targets against tumor-initiating cells (TICs) is a priority in the development new paradigms cancer. We enriched TIC population capable tumor initiation and self-renewal by serial passages hepatospheres with chemotherapeutic agents. In chemoresistant hepatospheres, CD47 was found to be up-regulated, when compared differentiated progenies. preferentially expressed liver TICs, which contributed initiation, self-renewal, metastasis significantly affected patients'...
Sorafenib is a new standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the survival benefit of this modest, partly owing to drug resistance. Recent evidence has demonstrated existence tumor‐initiating cells (T‐ICs) as culprit To examine whether sorafenib resistance was result presence liver T‐ICs, we developed sorafenib‐resistant HCC both in vitro and vivo through continuous exposure sorafenib. Using these models, found that clones enhanced T‐IC properties,...
Abstract Frequent relapse and drug resistance in patients with hepatocellular carcinoma (HCC) can be attributed to the existence of tumor-initiating cells (TIC) within tumor bulk. Therefore, targeting liver TICs may improve prognosis these patients. From transcriptome sequencing 16 pairs clinical HCC samples, we report that interleukin-1 receptor-associated kinase 1 (IRAK1) TLR/IRAK pathway is significantly upregulated HCC. IRAK1 overexpression was further confirmed at mRNA protein levels...
Abstract The survival benefit derived from sorafenib treatment for patients with hepatocellular carcinoma (HCC) is modest due to acquired resistance. Targeting cancer stem cells (CSC) a possible way reverse drug resistance, however, inhibitors that specifically target liver CSCs are limited. In this study, we established two sorafenib-resistant, patient-derived tumor xenografts (PDX) mimicked development of resistance in HCC. RNA-sequencing analysis sorafenib-resistant PDXs and their...
Background and Aims The survival benefit of sorafenib for patients with hepatocellular carcinoma (HCC) is unsatisfactory due to the development adaptive resistance. Increasing evidence has demonstrated that drug resistance can be acquired by cancer cells activating a number signaling pathways through receptor tyrosine kinases (RTKs); nevertheless, detailed mechanism activation these alternative not fully understood. Approach Results Given physiological role Src homology 2 domain–containing...
Abstract Accumulating evidence has demonstrated that drug resistance can be acquired in cancer through the repopulation of tumors by stem cell (CSC) expansion. Here, we investigated mechanisms driving and CSC hepatocellular carcinoma (HCC) as a model using two drug-resistant, patient-derived tumor xenografts mimicked development to sorafenib or lenvatinib treatment observed patients with HCC. RNA sequencing analysis revealed cholesterol biosynthesis was most commonly enriched drug-resistant...
Hepatocellular carcinoma (HCC) is often associated with metastasis and recurrence leading to a poor prognosis. Therefore, development of novel treatment regimens urgently needed improve the survival HCC patients. In this study, we aimed investigate in vitro vivo effects anti-CD47 antibody alone combination chemotherapy HCC.In examined functional (B6H12) on cell proliferation, sphere formation, migration invasion, chemosensitivity, macrophage-mediated phagocytosis tumourigenicity both vivo....
CCCTC-binding factor (CTCF) is a DNA-binding protein that interacts with large number of highly divergent target sequences throughout the genome. It implicated in variety functions, including chromatin organization and transcriptional control. The functional role CTCF tumour pathogenesis remains elusive. We showed frequently upregulated subset primary hepatocellular carcinomas (HCCs) as compared non-tumoural liver. Overexpression was associated shorter disease-free survival patients. Short...
Abstract Emerging evidence indicates the role of cancer stem cells (CSCs) in tumor relapse and therapeutic resistance patients with hepatocellular carcinoma (HCC). To identify novel targets against liver CSCs, an integrative analysis publicly available datasets involving HCC clinical stemness-related data was employed to select genes that play crucial roles via regulation CSCs. We revealed enrichment interstrand cross-link repair pathway, which ubiquitin-conjugating enzyme E2 T (UBE2T) most...
Embryonic stem cells (ESCs) possess two unique characteristics: self-renewal and pluripotency. In this study, roles of voltage-gated potassium channels (K(v)) in maintaining mouse (m) ESC characteristics were investigated. Tetraethylammonium (TEA(+)), a K(v) blocker, attenuated cell proliferation concentration-dependent manner. Possible reasons for attenuation, including cytotoxicity, cycle arrest differentiation, examined. Blocking did not change the viability mESCs. Interestingly,...
Hepatitis B virus (HBV) is a major risk factor of chronic liver disease and hepatocellular carcinoma (HCC). Random integration HBV DNA into the host genome frequent in HCC leading to truncation DNA, particularly at C-terminal end X protein (HBx). C-terminally truncated HBx (HBx-ΔC) has been implicated playing pro-oncogenic role hepatocarcinogenesis. However, mechanism whereby HBx-ΔC1 contributes hepatocarcinogenesis remains unclear. In this study, we investigated functional regulating cancer...
Significance Identification of genomic biomarkers that predict response to anticancer agents is the central research problem cancer precision medicine. While vast majority human genome encodes long noncoding RNAs (lncRNAs) as compared protein-coding genes, thus far characterization lncRNAs potential has proved challenging. Here, we leverage data from large-scale cell line screens model hundreds drugs a function lncRNA expression or somatic alteration. By carefully accounting for confounding...
// Rachel Hiu Ha Ching 1, 2 , Eunice Yuen Ting Lau Patrick Ming Tat Ling 3 Joyce Man Fong Lee Mark Kin Fai Ma Bowie Yik Cheng Regina Cheuk Lam Lo Irene Oi Lin Ng Terence Wah 1 State Key Laboratory for Liver Research, The University of Hong Kong, China Department Pathology, Li Ka Shing Faculty Medicine, Australian Prostate Cancer Research Centre-Queensland & Institute Health and Biomedical Innovation, Queensland Technology, Brisbane, Australia Correspondence to: Lee, e-mail: tkwlee@hku. hk...
Prostate cancer (PCa) frequently relapses after hormone ablation therapy. Unfortunately, once progressed to the castration resistant stage, disease is regarded as incurable prostate cells are highly conventional chemotherapy. We recently reported that two natural compounds polysaccharopeptide (PSP) and Gamma-tocotrienols (γ-T3) possessed potent anti-cancer activities through targeting of CSCs. In present study, using both cell line xenograft models, we seek investigate therapeutic potential...