Euphemia Leung

Euphemia Leung
University of Auckland · Auckland Cancer Society Research Centre

About

205
Publications
23,777
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
3,859
Citations

Publications

Publications (205)
Article
Full-text available
The development of endocrine resistance is a common reason for the failure of endocrine therapies in hormone receptor-positive breast cancer. This review provides an overview of the different types of in vitro models that have been developed as tools for studying endocrine resistance. In vitro models include cell lines that have been rendered endoc...
Article
COVID-19 has had a disastrous impact on the world. Apart from at least 6 million deaths, countless COVID-19 survivors are suffering long-term physical and psychiatric morbidity. Hundreds of millions have been plunged into poverty caused by economic misery, particularly in developing nations. Early in the pandemic, it became apparent certain groups...
Article
Introduction: COVID-19 has had a calamitous impact on the global community. Apart from at least 6M deaths, hundreds of millions have been infected and a much greater number have been plunged into poverty. Vaccines have been effective but financial and logistical challenges have hampered their rapid global deployment. Vaccine disparities have allow...
Article
Introduction: The immunological response to COVID-19 is only partly understood. It is increasingly clear that the virus triggers an inappropriate host inflammatory reaction in patients experiencing severe disease. Areas covered: The role of antibodies in COVID-19, remains to be fully defined. There is evidence for both protection and harm in dif...
Article
Full-text available
Luteolin is a flavonoid found in a wide range of plant materials, including commonly eaten fruits and vegetables. It displays a wide range of biological activities but is known to have poor bioavailability. In this study, ten different mono-acyl (nine 5- O -acyl and one 7- O -acyl) derivatives of luteolin were synthesised for the purpose of improvi...
Article
Full-text available
COVID-19 has had a calamitous effect on the global community. In spite of intense study, the immunological response to the infection is only partially understood. In addition to older age and ethnicity, patients with co-morbidities including obesity, diabetes, hypertension, coronary artery disease, malignancy, renal and pulmonary disease, may exper...
Article
Full-text available
Endoplasmic reticulum (ENR) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are upr...
Article
Full-text available
Background: COVID-19 has caused calamitous health, economic and societal consequences globally. Currently, there is no effective treatment for the infection. Areas covered: We have recently described the NZACE2-Pātari project, which seeks to administer modified Angiotensin Converting Enzyme 2 (ACE2) molecules early in the infection to intercept and...
Article
Chemoresistance is a major factor driving cancer recurrence. This study investigated the potential of zebularine, a dual cytidine deaminase (CDA)/epigenetic inhibitor, to circumvent gemcitabine-resistance in pancreatic cancer using a nanomedicine approach. The mRNA expression of key metabolic enzymes, including CDA for gemcitabine deactivation in a...
Article
Full-text available
Introduction Diagnostic tests play a critical role in the management of Sars-CoV-2, the virus responsible for COVID-19. There are two groups of tests, which are in widespread use to identify patients who have contracted the virus. The commonly used reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test becomes negative once vir...
Article
Full-text available
Quercetin is a flavonoid that is found in many plant materials, including commonly eaten fruits and vegetables. The compound is well known for its wide range of biological activities. In this study, 5-O-acyl derivatives of quercetin were synthesised and assessed for their antiproliferative activity against the HCT116 colon cancer and MDA-MB-231 bre...
Article
Thieno[2,3-b]pyridine are a class of compounds known for their potent anti-proliferative activities against a range of human cancer cell lines. In this research, a number of strategies to generate analogues that have improved aqueous solubility whilst retaining the potent anti-proliferative actions, compared to previously-explored compounds in this...
Article
Extracellular vesicles (EVs) are emerging as key players in breast cancer progression and hold immense promise as cancer biomarkers. However, difficulties in obtaining sufficient quantities of EVs for the identification of potential biomarkers hampers progress in this area. To circumvent this obstacle, we cultured BT-474 breast cancer cells in a tw...
Article
Full-text available
Activation of autophagy plays a critical role in DNA repair, especially for the process of homologous recombination. Despite upregulation of autophagy promotes both the survival and the death of cells, the pathways that govern the pro-cell death effects of autophagy are still incompletely understood. YM155 is originally developed as an expression s...
Article
The Bacillus cereus phosphatidylcholine-specific phospholipase C (PC-PLCBc) is an enzyme that catalyses the hydrolysis of phosphatidylcholines into phosphocholine and 1,2-diacylglycerols. PC-PLCBc has found applications in both the food industry and in medicinal chemistry. Herein, we report our work in the development and optimisation of a matrix a...
Article
Full-text available
X-linked inhibitor of apoptosis protein (XIAP), survivin, and BRUCE are members of the inhibitor-of-apoptosis protein (IAP) family known for their inhibitory effects on caspase activity and dysregulation of these molecules has widely been shown to cause embryonic defects and to promote tumorigenesis in human. Besides the anti-apoptotic functions, r...
Article
Extracellular vesicles (EVs) are emerging as key players in breast cancer progression and hold immense promise as cancer biomarkers. However, difficulties in obtaining sufficient quantities of EVs for the identification of potential biomarkers hampers progress in this area. To circumvent this obstacle, we cultured BT-474 breast cancer cells in a tw...
Preprint
Full-text available
Extracellular vesicles (EVs) are emerging as key players in breast cancer progression and hold immense promise as cancer biomarkers. However, difficulties in obtaining sufficient quantities of EVs for the identification of potential biomarkers hampers progress in this area. To circumvent this obstacle, we cultured BT-474 breast cancer cells in a tw...
Conference Paper
Increased expression of Hypoxia-Inducible Factor 1α (HIF-1α) in breast tumours is associated with poor survival outcome. HIF-1α promotes phenotypic adaptations including metabolic reorganisation, angiogenesis and increased cell invasiveness. Notably, HIF-1α activity is increased in Triple receptor Negative Breast Cancer (TNBC) compared with other b...
Article
Upregulation of ABCB1/MDR1 (P-gp) and BIRC5/Survivin promotes multidrug resistance in a variety of human cancers. LCL161 is an anti-cancer DIABLO/SMAC mimetic currently being tested in patients with solid tumors, but the molecular mechanism of action of LCL161 in cancer cells is still incompletely understood. It is still unclear whether LCL161 is t...
Article
Full-text available
Background: Glutamine serves as an important nutrient with many cancer types displaying glutamine dependence. Following cellular uptake glutamine is converted to glutamate in a reaction catalysed by mitochondrial glutaminase. This glutamate has many uses, including acting as an anaplerotic substrate (via alpha-ketoglutarate) to replenish TCA cycle...
Article
Full-text available
COVID-19 is a new zoonotic disease caused by the SARS-CoV-2 virus. Since its emergence in Wuhan City, China, the virus has rapidly spread across the globe causing calamitous health, economic and societal consequences. It causes disproportionately severe disease in the elderly and those with co-morbidities, such as hypertension and diabetes. There i...
Article
Creating synergies: The combination of more than one bioactive moiety resulted in an organometallic compound featuring a metal center, a 2‐pyridinecarbothioamide (PCA), and a hydroxamic acid, which is found in the anticancer drug vorinostat (SAHA). The compound displayed different modes of action than its components, supporting the development of n...
Article
Full-text available
Breast cancer stem(-like) cells (BCSCs) have been found to be responsible for therapeutic resistance and disease relapse. BCSCs are difficult to eradicate due to their high resistance to conventional treatments and high plasticity. Functionalised nanoparticles have been investigated as smart vehicles to transport across various barriers and increas...
Article
The combination of more than one bioactive moiety in a mulitargeted anticancer agent may result in synergistic activity of its components. Using this concept, bioorganometallic compounds were designed to feature a metal center, a 2‐pyridinecarbothioamide (PCA), and a hydroxamic acid, which is found in the anticancer drug vorinostat (SAHA). The orga...
Article
Full-text available
Endoplasmic reticulum (ER) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are up-r...
Article
Autophagy plays a role in several human diseases, but each of the current methods to measure autophagy have significant drawbacks. ATG5 and ATG16L1 are regulators necessary for autophagy therefore, drugs which inhibit the interaction of these proteins may be therapeutically useful. To evaluate the interaction of ATG5 and ATG16L1 in cells, their cDN...
Preprint
Full-text available
Background Glutamine serves as an important nutrient with many cancer types displaying glutamine dependence. Following cellular uptake glutamine is converted to glutamate in a reaction catalysed by mitochondrial glutaminase. This glutamate has many uses, including acting as an anaplerotic substrate ( via alpha-ketoglutarate) to replenish TCA cycle...
Preprint
Full-text available
Background Glutamine serves as an important nutrient with many cancer types displaying glutamine dependence. Following cellular uptake glutamine is converted to glutamate in a reaction catalysed by mitochondrial glutaminase. This glutamate has many uses, including acting as an anaplerotic substrate ( via alpha-ketoglutarate) to replenish TCA cycle...
Preprint
Full-text available
Background Glutamine serves as an important nutrient with many cancer types displaying glutamine dependence. Following cellular uptake glutamine is converted to glutamate in a reaction catalysed by mitochondrial glutaminase. This glutamate has many uses, including acting as an anaplerotic substrate (via alpha-ketoglutarate) to replenish TCA cycle i...
Article
Phospholipases are enzymes that are involved in the hydrolysis of acyl and phosphate esters of phospholipids, generating secondary messengers that have implications in various cellular processes including proliferation, differentiation and motility. As such inhibitors of phospholipases have been widely studied for their use as anti-cancer therapeut...
Article
Full-text available
Cancers express tryptophan catabolising enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) to produce immunosuppressive tryptophan metabolites that undermine patients’ immune systems, leading to poor disease outcomes. Both enzymes are validated targets for cancer immunotherapy but there is a paucity of potent TDO2 an...
Article
Phosphatidylcholine-specific phospholipase C (PC-PLC) is a promising target for new anticancer treatment. Herein, we report our work in the discovery of novel drug-like PC-PLC inhibitors. Virtual screening led to the identification of promising hits from four different structural series that contain the molecular scaffold of benzenesulphonamides (1...
Article
Full-text available
BIRC5/Survivin is known as a dual cellular functions protein that directly regulates both apoptosis and mitosis in embryonic cells during embryogenesis and in cancer cells during tumorigenesis and tumor metastasis. However, BIRC5 has seldom been demonstrated as a direct macroautophagy/autophagy regulator in cells. ATG7 expression and ATG12-ATG5-ATG...
Article
Redox-modulating anticancer drugs allow the exploitation of altered redox biology observed in many cancer cells. We discovered dinuclear Rh III (Cp*) and Ir III (Cp*) complexes that have in vitro anticancer activity superior to...
Article
TOTA (Trioxatriangulenium ion) is a close-shelled cabocation known to intercalate strongly with the DNA double helix (J. Am. Chem. Soc. 2003, 125, 2072). The cytotoxicity of TOTA and its four close structural analogues, ADOTA, Pr-ADOTA, Pr-DAOTA and n-Butyl-TATA were tested against the breast cancer cell line MDA-MB-231 and colon cancer cell line H...
Article
Full-text available
The phosphatidyl–choline-specific phospholipase C (PC-PLC) enzyme has been shown to be an important enzyme involved in various cell-signaling processes. Furthermore, PC-PLC has been shown to be upregulated in various cancer cell lines, thereby presenting itself as a potential anti-cancer therapeutic target. Current PC-PLC inhibitors, including the...
Article
Full-text available
Virtual high throughput screening of a large compound library against the regulatory enzyme phospholipase C (PLC) led to the discovery of the thieno[2,3-b]pyridine-2-carboxamides as potential inhibitors. Subsequent biological testing verified the antiproliferative activity of this compound class. Morphology and motility assays, using a number of tr...
Article
Chemoresistance poses a major challenge in cancer treatment. This study aims to investigate whether intracellular drug delivery using hyaluronic acid (HA) functionalised pH-sensitive liposomes (HA-pSL) can circumvent gemcitabine resistance in pancreatic cancer (PC). HA-pSL were obtained by covalently conjugating HA with preformed pSL. A resistant P...
Data
Sensitivity of breast cancer cell lines exposed to doxorubicin at 5 or 21% oxygen conditions. IC50 values for doxorubicin shown as the mean ± standard error of triplicate experiments.
Data
Short Tandem Repeat profiling for the NZBR cell lines.
Data
Mutation frequency in breast carcinoma and breast cancer cell lines.
Data
List of primers used in the experiments.
Article
Full-text available
Background: Most human breast cancer cell lines currently in use were developed and are cultured under ambient (21%) oxygen conditions. While this is convenient in practical terms, higher ambient oxygen could increase oxygen radical production, potentially modulating signaling pathways. We have derived and grown a series of four human breast cancer...
Article
Full-text available
The druggability of the tyrosyl-DNA phosphodiesterase 1 (Tdp1) enzyme was investigated in conjunction with topoisomerase 1 inhibition. A novel class of thiazole, aminothiazole and hydrazonothiazole usnic acid derivatives was synthesized and evaluated as Tdp1 inhibitors and their ability to sensitize tumors to topotecan, a topoisomerase inhibitor in...
Article
Full-text available
Messenger RNA (mRNA) transfection is a developing field that has applications in research and gene therapy. Potentially, mRNA transfection can be mediated efficiently by cell-penetrating peptides (CPPs) as they may be modified to target specific tissues. However, whilst CPPs are well-documented to transfect oligonucleotides and plasmids, mRNA trans...
Data
E6446 is >5-fold more potent than CQ at improving EGFP mRNA transfection by XP. A plot showing the percentages of A549, AGS, and HepG2 cells expressing EGFP 24 h after transfection of EGFP mRNA using XP and E6446 (5–20 μM) or chloroquine (25–100 μM). Data are representative of 4+ independent experiments and the standard errors of the means (SEM) ar...
Data
Truncated human protamine and XP transfect mRNA at low levels into human cancer cells. Epifluorescence microscopy images of RFP expression (red) in live AGS cells 24 h after treatment with RFP mRNA mixed with either truncated human protamine or XP. As a control, another set of cells were treated with RFP mRNA mixed with Lipofectamine™ 2000 (L2000)...
Data
XP transfects mRNA at low levels into human cancer cells. Epifluorescence microscopy images of EGFP expression (green) in live AGS cells 24 h after treatment with XP which had been mixed with EGFP mRNA at XP:mRNA (w/w) ratios ranging from 2:1 to 16:1. As controls, other sets of cells were treated with EGFP mRNA only or mRNA mixed with Lipofectamine...
Data
Chloroquine (CQ) and hydroxychloroquine (HCQ) enhance mRNA transfection by XP. Epifluorescence microscopy images of EGFP expression (green) in AGS cells 24 h after treatment with EGFP mRNA mixed with XP and either CQ or HCQ (0–100 μM). As controls, other sets of cells were treated with EGFP mRNA (in the absence of XP) to which 100 μM CQ or HCQ had...
Article
RuII(η6-arene) compounds carrying bioactive flavonol ligands have shown promising anticancer activity against tumor cells via a multitargeting mode of action, i.e., through interaction with DNA and inhibition of topoisomerase IIα. By introducing a novel arene ligand based on the amino acid l-phenylalanine (Phe), we aimed to alter the pharmacologica...
Article
Full-text available
The existence of epistasis in humans was first predicted by Bateson in 1909. Epistasis describes the non-linear, synergistic interaction of two or more genetic loci, which can substantially modify disease severity or result in entirely new phenotypes. The concept has remained controversial in human genetics because of the lack of well-characterized...
Article
It is now established that the thieno[2,3-b]pyridines are a potent class of antiproliferatives. One of the main issues encountered for their clinical application is their low water solubility. In order to improve this, two strategies were pursued. First, a morpholine moiety was tethered to the molecular scaffold by substituting the sulphur atom wit...
Article
Full-text available
It is now established that the thieno[2,3-b]pyridines are a potent class of antiproliferatives. One of the main issues encountered for their clinical application is their low water solubility. In order to improve this, two strategies were pursued. First, a morpholine moiety was tethered to the molecular scaffold by substituting the sulphur atom wit...
Article
Full-text available
A panel of docking scaffolds was developed for the known molecular targets of the anticancer agents, thieno[2,3-b]pyridines, in order to glean insight into their mechanism of action. The reported targets are the copper-trafficking antioxidant 1 protein, tyrosyl DNA phosphodiesterase 1, the colchicine binding site in tubulin, adenosine A2A receptor,...
Article
Full-text available
Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+) breast cancer patients. Even though dysregulations of histone deacetylases (HDACs) are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear....
Data
HDAC5 positively modulates Sp1 expression in ER+ breast cancer cells. (A) The Sp1/miR-125a-5p interaction was predicted using miRNA target prediction software TargetScan (http://www.targetscan.org/vert_71/) and PicTar (http://pictar.mdc-berlin.de/). (B) MCF7-TamC3 and ZR-75-1 cells were transfected with either scramble or HDAC5 siRNA for 24 h and e...
Data
Molecular characteristics of human breast MCF7, MCF7-TamC3, and ZR-75-1 cancer cells. (A,B) Expression of ER-α and caspase-3 in different breast cancer cells was determined by the Western blot analysis.
Data
mTOR regulates the expression of survivin in breast cancer cells. MCF7, MCF7-TamC3, and ZR-75-1 cells were treated with the mTOR inhibitor, rapamycin, for 48 h and expression of various proteins was determined by the Western blot analysis.
Data
HDAC2 regulates p53 and Sp1 expression in ER+ breast cancer cells. (A) Results of the protein–protein interaction (PPI) networks analysis generated by the web-based software STRING version 10.0 (http://string-db.org/) showing possible regulations of survivin (BIRC5) expression via p53 (TP53) and Sp1 (SP1)-dependent mechanisms. Minimum required inte...