Publications by authors named "Hon Leong"

Globally, prostate cancer is the second most common malignancy in males, with over 400 thousand men dying from the disease each year. A common treatment modality for localized prostate cancer is radiotherapy. However, up to half of high-risk patients can relapse with radiorecurrent prostate cancer, the aggressive clinical progression of which remains severely understudied.

View Article and Find Full Text PDF

Background: Metastatic relapse of prostate cancer after radiotherapy is a significant cause of prostate cancer-related morbidity and mortality. PLOD2 is a mediator of invasion and metastasis that we identified as being upregulated in our highly aggressive radiorecurrent prostate cancer cell line.

Methods: Patient dataset analysis was conducted using a variety of prostate cancer cohorts.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates how MT1-MMP, a protease involved in cancer cell movement, is recruited to invadopodia in metastatic breast cancer cells, focusing on its interaction with a protein called plectin.
  • Through techniques like mass spectrometry and siRNA, researchers found that plectin is crucial for forming invadopodia and facilitating the enzyme's delivery, significantly influencing cancer cell invasiveness.
  • Targeting the MT1-MMP and plectin interaction might pave the way for new therapies aimed at reducing cancer metastasis.
View Article and Find Full Text PDF

Introduction: Accurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure.

Methods: We developed a nanoscale flow cytometry (nFC)-based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls.

View Article and Find Full Text PDF

Background: Breast cancer (BC) is frequently diagnosed among Canadian women. While targeted therapies are available for most BC patients; treatment resistance is common and novel therapeutic targets are of interest. Thyroid hormones (TH) bound to thyroid hormone receptors (THR) influence cell proliferation and differentiation; they are also involved in the growth and development of normal breast tissue.

View Article and Find Full Text PDF

The retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam) are co-expressed and function additively to pattern starburst amacrine cell mosaics.

View Article and Find Full Text PDF

The loss of intercellular adhesion molecule E-cadherin is a hallmark of the epithelial-mesenchymal transition (EMT), during which tumor cells transition into an invasive phenotype. Accordingly, E-cadherin has long been considered a tumor suppressor gene; however, E-cadherin expression is paradoxically correlated with breast cancer survival rates. Using novel multi-compartment organoids and multiple in vivo models, we show that E-cadherin promotes a hyper-proliferative phenotype in breast cancer cells via interaction with the transmembrane receptor EGFR.

View Article and Find Full Text PDF

The acoustic stimulation of microbubbles within microvessels can elicit a spectrum of therapeutically relevant bioeffects from permeabilization to perfusion shutdown. These bioeffects ultimately arise from complex interactions between microbubbles and microvascular walls, though such interactions are poorly understood particularly at high pressure, due to a paucity of direct observations. The continued development of focused ultrasound methods hinges in large part on establishing links between microbubble-microvessel interactions, cavitation signals, and bioeffects.

View Article and Find Full Text PDF

Metastasis remains the leading cause of mortality in prostate cancer patients. The presence of tumor cells in lymph nodes is an established prognostic indicator for several cancer types, such as melanoma, breast, oral, pancreatic, and cervical cancers. Emerging evidence highlights the role of microRNAs enclosed within extracellular vesicles as facilitators of molecular communication between tumors and metastatic sites in the lymph nodes.

View Article and Find Full Text PDF

Application of the prostate-specific antigen (PSA) test, which measures PSA levels in blood, is standard in prostate cancer (PCa) screening. However, because PSA levels may be elevated for reasons other than PCa, it leads to high rates of misdiagnosis and overtreatment. Recently, alteration in the -glycan sialylation of PSA, specifically increased levels of α2-3-linked -acetylneuraminic acid (α2-3-Neu5Ac or α2-3-sialic acid), was identified as a potential biomarker for clinically significant PCa.

View Article and Find Full Text PDF

Background: Limited graft availability is a constant clinical concern. Hence, the umbilical cord (UC) is an attractive alternative to autologous grafts. The UC is an inexhaustible tissue source, and its removal is harmless and part of standard of care after the birth of the baby.

View Article and Find Full Text PDF

We postulate that nanoparticles (NPs) for use in therapeutic applications have largely not realized their clinical potential due to an overall inability to use results to predict NP performance . The avian embryo and associated chorioallantoic membrane (CAM) has emerged as an preclinical model that bridges the gap between and , enabling rapid screening of NP behavior under physiologically relevant conditions and providing a rapid, accessible, economical, and more ethical means of qualifying nanoparticles for use. The CAM is highly vascularized and mimics the diverging/converging vasculature of the liver, spleen, and lungs that serve as nanoparticle traps.

View Article and Find Full Text PDF

Nanomaterials are threatening the environment and human health, but there has been little discussion about the stability and mobility of nanoparticles (NPs) in saturated porous media at environmentally relevant concentrations of surfactants, which is a knowledge gap in exploring the fate of engineered NPs in groundwater. Therefore, the influences of the anionic surfactant (sodium dodecylbenzene sulfonate, SDBS), the cationic surfactant (cetyltrimethylammonium bromide, CTAB), and the nonionic surfactant (Tween-80) with environmentally relevant concentrations of 0, 5, 10, and 20 mg/L on nano-TiO (nTiO, negatively charged) and nano-CeO (nCeO, positively charged) transport through saturated porous media were examined by column experiments. On the whole, with increasing SDBS concentration from 0 to 20 mg/L, the concentration peak of nTiO and nCeO in effluents increased by approximately 0.

View Article and Find Full Text PDF

Metastasis is present in approximately 30% of patients diagnosed with renal cell carcinoma (RCC) and is associated with a 5-year survival rate of < 15%. Kidney injury molecule 1 (KIM-1), encoded by the HAVCR1 gene, is a proximal tubule cell-surface glycoprotein and a biomarker for early detection of RCC, but its pathophysiological significance in RCC remains unclear. We generated human and murine RCC cell lines either expressing or lacking KIM-1, respectively, and compared their growth and metastatic properties using validated methods.

View Article and Find Full Text PDF

Background: Liquid biopsy is promising for early detection, monitoring of response, and recurrence of cancer. The blood-brain barrier (BBB) limits the shedding of biomarker, such as cell-free DNA (cfDNA), into the blood from brain tumors, and their detection by conventional assays. Transcranial MR-guided focused ultrasound (MRgFUS) can safely and transiently open the BBB, providing an opportunity for less-invasive access to brain pathology.

View Article and Find Full Text PDF

Background: Extracellular vesicles (EVs) are cell-derived lipid bilayer enclosed structures shed from the plasma membrane by all cell types. Evidence of EV presence in biological fluids has led to considerable efforts focused on identifying their cargo and determining their utility as a non-invasive diagnostic platform for cancer. In this study, we identify circulating STEAP1 (six-transmembrane epithelial antigen of the prostate 1)-positive EVs in the plasma of healthy males and prostate cancer patients and evaluate its diagnostic and prognostic significance.

View Article and Find Full Text PDF

Gliomas are a diverse group of brain tumors comprised of malignant cells ('tumor' cells) and non-malignant 'normal' cells, including neural (neurons, glia), inflammatory (microglia, macrophage) and vascular cells. Tumor heterogeneity arises in part because, within the glioma mass, both 'tumor' and 'normal' cells secrete factors that form a unique microenvironment to influence tumor progression. Extracellular vesicles (EVs) are critical mediators of intercellular communication between immediate cellular neighbors and distantly located cells in healthy tissues/organs and in tumors, including gliomas.

View Article and Find Full Text PDF

While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug-loaded nanomaterials or monoclonal antibodies), which can experience challenges to effective delivery due to particle size-dependent diffusion barriers at the target site. As a result, disparity between therapeutic plasma kinetics and kinetics at the site of action may exist, highlighting the importance of target site concentration kinetics in determining the pharmacodynamic effects of macromolecular therapeutic agents.

View Article and Find Full Text PDF

Transport of environmental pollutants in groundwater systems can be greatly influenced by colloids. In this study, the cotransport of Pb and silica (SiO) colloids at different Pb concentrations was systematically investigated by batch adsorption and saturated sand column experiments. Results showed that SiO colloids had low adsorption capacity for Pb (less than 1% of the input) compared with sands.

View Article and Find Full Text PDF

Caveolin-1 is a transmembrane protein with both tumor promoter and suppressor functions that remain poorly understood. Cav1 phosphorylation by Src kinase on tyrosine 14 is closely associated with focal adhesion dynamics and tumor cell migration, however the role of pCav1 in tumor progression remains poorly characterized. Herein, we expressed phosphomimetic Y14D, wild type, and non-phosphorylatable Y14F forms of Cav1 in MDA-MB-435 cancer cells.

View Article and Find Full Text PDF

Background: The development of phenotypic biomarkers to aid the selection of treatment for patients with castrate-resistant prostate cancer (CRPC) is an important priority. Plasma exosomes have excellent potential as real-time biomarkers to characterize the tumor because they are easily accessible in the blood and contain DNA, RNA, and protein from the parent cell. This study aims to investigate the characteristics of putative prostate-specific plasma extracellular vesicle (EV) markers and their relationship with clinical outcomes.

View Article and Find Full Text PDF

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

View Article and Find Full Text PDF

Purpose: Colorectal cancer is a commonly encountered disease that poses several diagnostic and therapeutic challenges. The inherent heterogeneity of tumor biology and propensity to relapse despite "curative" resection pose significant challenges with regard to response assessment. Although MR imaging already plays a key role in primary staging of patients with rectal carcinoma, its reliability in restaging after neoadjuvant therapy is debatable (Van der broek et al.

View Article and Find Full Text PDF