Alice S T Wong

Alice S T Wong
The University of Hong Kong | HKU · School of Biological Sciences

MPhil, PhD

About

112
Publications
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Publications

Publications (112)
Article
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Overcoming drug resistance is an inevitable challenge to the success of cancer treatment. Recently, in ovarian cancer, a highly chemoresistant tumor, we demonstrated an important role of shear stress in stem-like phenotype and chemoresistance using a three-dimensional microfluidic device, which most closely mimics tumor behavior. Here, we examined...
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Tumor heterogeneity plays a key role in cancer relapse and metastasis, however, the distinct cellular behaviors and kinetics of interactions among different cancer cell subclones and the tumor microenvironment are poorly understood. By profiling an isogenic model that resembles spontaneous human ovarian cancer metastasis with an highly metastatic (...
Article
Among gynecological malignancies, ovarian cancer (OC) accounts for the highest mortality rate due to high therapeutic resistance, prolonged latency and a lack of effective treatments. This calls for preclinical models that could recapitulate the histological, molecular and pathophysiological features of distinct OC subtypes. Various mouse models in...
Article
p70 S6 kinase (p70S6K) is best-known for its regulatory roles in protein synthesis and cell growth by phosphorylating its primary substrate, ribosomal protein S6, upon mitogen stimulation. The enhanced expression/activation of p70S6K has been correlated with poor prognosis in some cancer types, suggesting that it may serve as a biomarker for diseas...
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Background: Colorectal cancer (CRC) and the associated metastatic lesions are reported to be hypoxic. Hypoxia is a common feature in the tumor microenvironment and a potent stimulant of CRC. We have identified a regulatory role of Nur77 on Akt activation to enhance β-catenin signaling essential for CRC progression under hypoxic conditions. Methods:...
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Ovarian cancer is the most lethal gynecological malignancy worldwide. Unlike most other tumor types that metastasize via the vasculature, ovarian cancer metastasizes predominantly via the transcoelomic route within the peritoneal cavity. As cancer metastasis accounts for the majority of deaths, there is an urge to better understand its determinants...
Article
The tumor microenvironment is actively involved in cancer progression and is becoming an attractive therapeutic target. It is increasingly clear that both biotic and abiotic factors in the microenvironment play a crucial role in disease progression. Using a three-dimensional microfluidic platform that mimics the peritoneum, we previously demonstrat...
Article
Female genital melanomas are rare. At diagnosis, most affected patients have advanced disease. Surgery remains the primary treatment, and adjuvant therapy is largely ineffective. Recently, immune checkpoints and the mitogen-activated protein kinase pathway have been explored as treatment targets. However, evaluation of these biomarkers in genital m...
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Organ-specific colonization suggests that specific cell-cell recognition is essential. Yet, very little is known about this particular interaction. Moreover, tumor cell lodgement requires binding under shear stress, but not static, conditions. Here, we successfully isolate the metastatic populations of cancer stem/tumor-initiating cells (M-CSCs). W...
Article
In this study, we develop a method to detect multiple DNAs of foodborne pathogens by encapsulating emulsion droplets for loop-mediated isothermal amplification (LAMP). In contrast to the traditional bulk-phase LAMP, which involves a labor-intensive mixing process, with our method, different primers are automatically mixed with DNA samples and LAMP...
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A key to successful metastasis is the formation of new vasculature, known as angiogenesis. Therefore, it is of great interest to unravel the underlying molecular mechanisms of tumor angiogenesis. Cadherins are a major class of cell surface receptors. The loss of cadherins, especially E-cadherin, is a well-established marker for tumor metastasis. Lo...
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The limitations of current anti-angiogenic therapies necessitate other targets with complimentary mechanisms. Here, we show for the first time that soluble E-cadherin (sE-cad) (an 80-kDa soluble form), which is highly expressed in the malignant ascites of ovarian cancer patients, is a potent inducer of angiogenesis. In addition to ectodomain sheddi...
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Metastasis is the cause of most (>90%) cancer deaths, and currently lack of effective treatments. Approaches to understanding the biological process, unraveling the most effective molecular target(s), and implementing nanotechnology to increase the therapeutic index are expected to facilitate cancer therapy against metastasis. Here, we demonstrate...
Article
Presence of Met receptor tyrosine kinase in the nucleus of cells has been reported. However, the functions of Met which expresses in the nucleus (nMet) remain elusive. In this study, we found that nMet was increased in 89% of HCC tumorous tissues when compared with the corresponding non-tumorous liver tissues. nMet expression increased progressivel...
Article
Recent studies have indicated that the nanoindentation measured stiffness of carcinoma adherent cells is in general lower than normal cells, thus suggesting that cell stiffness may serve as a bio-marker for carcinoma. However, the proper establishment of such a conclusion would require biophysical understanding of the underlying mechanism of the ce...
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Ovarian cancer is a nearly uniform lethal disease and its highly aggressive metastatic phenotype portends a poor prognosis. Lack of a well-controlled, relevant experimental model has been a major obstacle to identifying key molecules causing metastasis. Here we describe the creation of a new isogenic model of spontaneous human ovarian cancer metast...
Article
Ovarian cancer is characterized by extensive peritoneal metastasis, with tumor spheres commonly found in the malignant ascites. This is associated with poor clinical outcomes and currently lacks effective treatment. Both the three-dimensional (3D) environment and the dynamic mechanical forces are very important factors in this metastatic cascade. H...
Article
An anti-cancer active gold(III) pyrrolidinedithiocarbamato complex [(PDTC)Au(III)Cl2] (1) has been synthesized and characterized by means of X-ray crystallography. Compared to the pyrrolidinedithiocarbamate ligand itself, this gold(III) complex displays an up to 33-fold higher anti-cancer potency towards a panel of cancer cell lines including the c...
Article
One of greatest challenges to the successful treatment of cancer is drug resistance. An exciting approach is the eradication of cancer stem cells (CSCs). However, little is known about key signals regulating the formation and expansion of CSCs. Moreover, lack of a reliable predictive preclinical model has been a major obstacle to discover new cance...
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Ovarian cancer is the leading cause of death of all gynecologic tumors, associated with widespread peritoneal dissemination and malignant ascites. Key to this is the ability to form multicellular spheroids (MCS); however, the tumor-specific factors that regulate MCS formation are unclear. p70 S6 kinase (p70S6K), which is a downstream effector of ph...
Article
A dinuclear gold(I) pyrrolidinedithiocarbamato complex (1) with a bidentate carbene ligand showing potent in vitro cytotoxic activities towards cisplatin-resistant ovarian carcinoma A2780cis has been constructed. Its rigid scaffold enables a zinc(II)-based metal-organic framework (Zn-MOF) to be used as a carrier in facilitating the uptake and relea...
Article
Sprouty (SPRY) proteins are well-characterized factors that inhibit receptor tyrosine kinase signaling. Our Human Exonic Evidence-Based Oligonucleotide (HEEBO) microarray results showed that the mRNA levels of SPRY2, but not of SPRY1 or SPRY4, are down-regulated in high-grade serous ovarian carcinoma (HGSC) tissues and epithelial ovarian cancer (EO...
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The marine medaka (Oryzias melastigma) has been increasingly used as a fish model for detecting environmental stresses and chemical contaminants in the marine environment. Recent mammalian studies have shown that environmental stresses can alter the expression profiles of microRNAs (miRNAs), leading to transgenerational effects. Here, we use high-t...
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Covering: 2000 to 2014Cancer is one of the leading causes of death worldwide. Ginseng, a key ingredient in traditional Chinese medicine, shows great promise as a new treatment option. As listed by the U.S. National Institutes of Health as a complementary and alternative medicine, its anti-cancer functions are being increasingly recognized. This rev...
Article
The loss of E-cadherin, a cell-cell adhesion molecule, is a well-established marker for metastasis of cancer. Although E-cadherin is synthesized as a transmembrane molecule, it can be cleaved of the ectodomain and released in a soluble form (sE-cad), and this accounts a key mechanism for a rapid reduction of functional E-cadherin at the cell surfac...
Article
Ovarian cancer is a highly metastatic tumor characterized by malignant ascites spheroids, which represent one of the most important prognostic factors of poor clinical outcome. Multicellular aggregates known as spheroids (MCS) are important for anchorage-independent growth and metastasis. MCS are also an important phenomenon of cancer stem cells. H...
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Peritoneal dissemination as a manifestation of ovarian cancer is an adverse prognostic factor associated with poor clinical outcome, and is thus a potentially promising target for improved treatment. Sphere forming cells (multicellular spheroids) present in malignant ascites of patients with ovarian cancer represent a major impediment to effective...
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The recently discovered small-interfering RNA (siRNA) holds great promise in cancer therapy. However, efficient and safe delivery systems are required for the development of new therapeutic paradigms. Ovarian cancer has the highest mortality of all gynecologic tumors, and there is an urgent need for specific and effective therapies. The phosphatidy...
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Epithelial-mesenchymal transition (EMT) represents a key event in cancer progression and has emerged as a promising anticancer target. Estrogen-related receptor alpha (ERRα) is frequently elevated in advanced-stage ovarian cancer, but its potential role in tumor progression is not known. Here we show that ERRα functions in EMT and subsequent stem c...
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Background: β-Catenin is a potent oncogenic protein in colorectal cancer (CRC), but the targets and regulation of this important signalling molecule are not completely understood. Hypoxia is a prominent feature of solid tumours that contributes to cancer progression. Methods: Here, we analysed the regulation between Nur77 and β-catenin under hypox...
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Ginseng is often referred to as the King of all herbs, and is found to be a promising agent to improve general well-being. Ginseng has also been reputed as an aphrodisiac, and is used to treat sexual dysfunction as well as to enhance sexual behavior in traditional Chinese medical practices. Data from animal studies have shown a positive correlation...
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The female reproductive system is a complex system. Epithelia of the female reproductive system including the ovaries, the oviduct, and the uterus are important sites for follicular development, ovulation, fertilization, implantation, and embryo development. They are also able to synthesize and secrete various hormones, growth factors, and cytokine...
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A cytotoxic gold(iii) complex of meso-tetraphenylporphyrin ([Au(TPP)]Cl, denoted gold-) blocks the self-renewal ability of cancer stem-like cells and shows appealing safety pharmacological profiles in rodents.
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Ovarian cancer has a clear predilection to metastasize to the peritoneum, which represents one of the most important prognostic factors of poor clinical outcome. Gonadotropin-releasing hormone (GnRH) receptor is significantly overexpressed during the malignant progression of human ovarian cancer. Here, using lentiviral-based small interfering RNA (...
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Cisplatin and paclitaxel are standard chemotherapy for metastatic ovarian cancer, but with limited efficacy. Cancer stem/progenitor cells (or tumor-initiating cells, TICs) are hypothesized to be chemoresistant, and the existence of TICs in ovarian cancer has been previously demonstrated. However, the key signals and molecular events regulating the...
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Introduction: The p70 S6 kinase (p70(S6K)) is frequently active in ovarian and a wide range of cancer types, and it has a crucial role in several processes considered hallmarks of cancer. Therefore, blocking p70(S6K) expression or activity may present a promising strategy for anticancer treatment. Areas covered: The current understanding of the...
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Introduction: The orphan nuclear receptor Nur77 (also known as NR4A1, NGFIB, TR3, TIS1, NAK-1, or N10) is a unique transcription factor encoded by an immediate early gene. Nur77 signaling is deregulated in many cancers and constitutes an important molecule for drug targeting. Areas covered: Nur77 as a versatile transcription factor that displays...
Article
Caveolin-1 (Cav1) has been implicated in diverse human cancers, yet its role in hepatocellular carcinoma (HCC) tumourigenesis and metastasis remains elusive. In the current study, we aim to provide a comprehensive understanding regarding the functional role of Cav1 in HCC tumourigenesis and metastasis. Cav1 expression was examined in a panel of hum...
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p70 S6 kinase (p70(S6K)), a member of the AGC serine/threonine kinase family, was initially identified as a key player, together with its downstream effector S6, in the regulation of cellular growth and survival. The p70(S6K) protein has emerged in recent years as a multifunctional protein which also regulates the actin cytoskeleton and thus plays...
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Hypoxia-inducible factor (HIF-1) is the key transcription regulator for multiple angiogenic factors and is an appealing target. Ginsenoside-Rg1, a nontoxic saponin isolated from the rhizome of Panax ginseng, exhibits potent proangiogenic activity and has the potential to be developed as a new angiotherapeutic agent. However, the mechanisms by which...
Article
Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL One emerging concept of the development of drug-resistant tumors involves a pool of self-renewing malignant progenitors. However, the factors and molecular mechanisms that govern this process remain largely elusive. It has been reported that the high malignancy of these cells...
Article
Ovarian cancer has the highest mortality of all gynecological cancers. These deaths are mainly due to the highly metastatic characteristic with already widespread peritoneal dissemination and malignant ascites at the time of diagnosis. However the molecular mechanisms that regulate ovarian cancer progression are poorly understood. A key step in thi...
Article
The PFTK1 gene encodes a cdc2-related serine/threonine protein kinase that has been shown to confer cell migratory properties in hepatocellular carcinoma (HCC). However, the prognostic value and biological mechanism by which PFTK1 promotes HCC motility remain largely unknown. Here, we showed from tissue microarray that common upregulations of PFTK1...
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Ginsenoside-Rg1, the most prevalent active constituent of Panax ginseng, has been shown to possess potent pro-angiogenic properties and therefore poses special interest for the development as a novel modality for angiotherapy. Rg1 can activate the glucocorticoid receptor (GR). However, the mechanism that transmits these pro-angiogenic effects is st...
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Gonadotropin-releasing hormone (GnRH) is a potent prometastatic factor in ovarian cancer, but the intracellular signaling events are not well understood. The classical Gα(q)-phospholipase C signal transduction pathway known to operate in the pituitary is not involved in GnRH actions at non-pituitary targets. Here we showed that GnRH treatment of ov...
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Ovarian cancer is highly metastatic with a poor prognosis. The serine/threonine kinase, p70 S6 kinase (p70(S6K)), which is a downstream effector of phosphatidylinositol 3-kinase/Akt pathway, is frequently activated in ovarian cancer. Here, we show that p70(S6K) is a critical regulator of the actin cytoskeleton in the acquisition of the metastatic p...
Article
The orphan nuclear receptor Nur77 is an immediate-early response gene whose expression is rapidly induced by various extracellular stimuli. The aims of this study were to study the role of Nur77 expression in the growth and survival of colon cancer cells and the mechanism by which Nur77 expression was regulated. We showed that levels of Nur77 were...
Article
Gonadotropins (FSH and LH) are detectable in ovarian tumor fluid, suggesting a possible role for gonadotropins in ovarian carcinogenesis and progression. However, the molecular mechanisms behind the role of gonadotropins in ovarian cancer development are unknown. Cyclooxygenase (COX) enzymes, COX-1 and COX-2, play crucial roles in the pathogenesis...
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The therapeutic potential of ginseng has been studied extensively, and ginsenosides, the active components of ginseng, are shown to be involved in modulating multiple physiological activities. This article will review the structure, systemic transformation and bioavailability of ginsenosides before illustration on how these molecules exert their fu...
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Many clustering techniques and classification methods for analysing microarray data require a complete dataset. However, very often gene expression datasets contain missing values due to various reasons. In this paper, we first propose to use vector angle as a measurement for the similarity between genes. We then propose the Weighted Local Least Sq...
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Gonadotropin-releasing hormone (GnRH) receptor expression is often elevated in ovarian cancer, but its potential role in ovarian cancer metastasis has just begun to be revealed. Cadherin switching is a crucial step during tumorigenesis, particularly in metastasis. Here, we showed that GnRH is an inducer of E- to P-cadherin switching, which is remin...
Article
Cancer metastasis remains a major cause of cancer morbidity and mortality in individuals diagnosed with hepatocellular carcinoma (HCC). We previously reported on regional chromosome 7q21-q22 gains in close association with HCC progression, and discerned a candidate proto-oncogene PFTK1 within this region by array-based CGH mapping. The PFTK1 protei...
Article
Ovarian cancer has the highest mortality of all gynecological cancers. It is often diagnosed at a late stage characterized by widespread peritoneal dissemination and malignant ascites. A key initial step in metastasis is the adhesion of ovarian cancer cells to the peritoneal mesothelium and extracellular matrix (ECM). Gonadotropin-releasing hormone...
Chapter
Ovarian cancer is a highly metastatic disease and has the highest mortality rate of all gynecological tumors. In contrast to many other types of cancer that metastasize through lymphatics and/or hematogenous routes, ovarian cancer metastasizes by peritoneal dissemination, which relies on the ability of cancer cells to detach from the primary tumor,...
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Ovarian cancer is the most lethal gynecologic cancer mainly because of widespread peritoneal dissemination and malignant ascites. Key to this is the capacity of tumor cells to escape suspension-induced apoptosis (anoikis), which also underlies their resistance to chemotherapy. Here, we used a nonadherent cell culture model to investigate the molecu...
Article
Full-text available
Ovarian cancer is the most lethal gynecologic cancer mainly because of widespread peritoneal dissemination and malignant ascites. Key to this is the capacity of tumor cells to escape suspension-induced apoptosis (anoikis), which also underlies their resistance to chemotherapy. Here, we used a nonadherent cell culture model to investigate the molecu...
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Comment on: Induction of high grade serous carcinoma in human ovarian surface epithelial cells using combined genetic elements and peritoneal microenvironment. Zheng J, et al. Cell Cycle 2010; 9:In press.