A5007204095- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Cancer Mechanisms and Therapy
- Aldose Reductase and Taurine
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer-related molecular mechanisms research
- Liver physiology and pathology
- Genomics, phytochemicals, and oxidative stress
- Prostate Cancer Treatment and Research
- PI3K/AKT/mTOR signaling in cancer
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- TGF-β signaling in diseases
- Natural product bioactivities and synthesis
- Kruppel-like factors research
- Wnt/β-catenin signaling in development and cancer
- Computational Drug Discovery Methods
- Organ Transplantation Techniques and Outcomes
- Ferroptosis and cancer prognosis
- Peptidase Inhibition and Analysis
Hong Kong Polytechnic University
2016-2025
Pathwest Laboratory Medicine
2024
University of Hong Kong
2010-2023
Virginia Commonwealth University
2023
Hunter Holmes McGuire VA Medical Center
2023
Health Affairs
2022
Queen Mary Hospital
2002-2017
State Key Laboratory of Synthetic Chemistry
2015-2017
Chinese University of Hong Kong
2001-2016
Sungkyunkwan University
2016
Abstract Recent efforts in our study of cancer stem cells (CSC) hepatocellular carcinoma (HCC) have led to the identification CD133 as a prominent HCC CSC marker. Findings were based on experiments done cell lines and xenograft tumors where expression was detected at levels high 65%. Based theory, CSCs are believed represent only minority number tumor mass. This is indicative that previously characterized CD133+ population still heterogeneous, consisting perhaps subsets with differing...
Abstract Purpose: Hepatocellular carcinoma (HCC) is a rapidly growing tumor associated with high propensity for vascular invasion and metastasis. Epithelial-mesenchymal transition (EMT) key event in the process. Recently, Twist has been identified to play an important role EMT-mediated metastasis through regulation of E-cadherin expression. However, actual invasiveness remains unclear. The purpose this study investigate expression possible HCC. Experimental Design: We evaluated HCC tissue...
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...
A novel theory in the field of tumor biology postulates that cancer growth is driven by a population stem-like cells, called tumor-initiating cells (TICs). We previously identified TIC derived from hepatocellular carcinoma (HCC) characterized membrane expression CD133. Here, we describe mechanism which these mediate and angiogenesis systematic comparison gene profiles between sorted CD133 liver subpopulations through genome-wide microarray analysis. significantly dysregulated interleukin-8...
Patients with pancreatic ductal adenocarcinoma (PDAC) face a clinically intractable disease poor survival rates, attributed to exceptionally high levels of metastasis. Epithelial-to-mesenchymal transition (EMT) is pronounced at inflammatory foci within the tumor; however, immunological mechanisms promoting tumor dissemination remain unclear. It well established that tumors exhibit Warburg effect, preferential use glycolysis for energy production, even in presence oxygen, support rapid...
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'...
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...
Objective To investigate the degree and mechanism of hepatic sinusoidal injury in different graft sizes right lobe live donor liver transplantation (LDLT). Summary Background Data Liver grafts from living donors are likely to be small-for-size for adult recipients. Graft after reperfusion is common, but remain unclear. The its relationship with portal hemodynamics intragraft gene response at early phase have not been studied LDLT. Methods From May 2000 November 2001, 40 adults receiving LDLT...
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,...
Src-homology 2 domain-containing phosphatase (Shp2) has been reported to play an important role in the maintenance and self-renewal of embryonic adult stem cells, but its cancer cells (CSCs) remains obscure. Herein, we observed high expression Shp2 both chemoresistant hepatocellular carcinomas (HCCs) recurrent HCCs from patients. A remarkable increase was detected sorted epithelial cell adhesion molecule-positive or cluster differentiation 133-positive liver CSCs CSC-enriched hepatoma...
The substantial heterogeneity and hierarchical organization in liver cancer support the theory of stem cells (LCSCs). However, relationship between chronic hepatic inflammation LCSC generation remains obscure. Here, we observed a close correlation aggravated progenitor cell (LPC) propagation cirrhotic rats exposed to diethylnitrosamine. LPCs isolated from rat initiated subcutaneous cancers nonobese diabetic/severe combined immunodeficient mice, suggesting malignant transformation toward...
Most tumor cells use aerobic glycolysis (the Warburg effect) to support anabolic growth and promote tumorigenicity drug resistance. Intriguingly, the molecular mechanisms underlying this phenomenon are not well understood. In work, using gain-of-function loss-of-function in vitro studies patient-derived organoid cell cultures as vivo positron emission tomography-magnetic resonance imaging animal models, we showed that protein arginine N-methyltransferase 6 (PRMT6) regulates human...
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...