Kevin Nguyen | University of Technology Sydney (original) (raw)

Papers by Kevin Nguyen

Journal of Clinical Oncology, 2018

114 Background: The utility of serial magnetic resonance imaging (MRI)/ultrasound (US) fusion tar... more 114 Background: The utility of serial magnetic resonance imaging (MRI)/ultrasound (US) fusion targeted prostate biopsy in men with prostate cancer (PCa) on active surveillance (AS) have not been clearly defined. We sought to investigate the rate of Gleason upgrading both on sequential fusion targeted and systematic biopsies among men with low-risk PCa managed with AS. Methods: We retrospectively queried an institutional database of 800 patients undergoing MRI/US fusion biopsy to identify 209 patients on AS with at least two fusion biopsies between December 2013 and November 2016. Men with National Comprehensive Cancer Network (NCCN) very low-risk and low-risk criteria were included. Gleason upgrade was defined as detection of Gleason score >=3+4. The proportion of patients experiencing upgrade on systematic, fusion, or both biopsy techniques was tabulated. Associations of clinical, pathologic, and imaging factors with biopsy upgrade were analyzed by logistic regression. Results: ...

The Journal of Urology, 2018

Otolaryngology - Head and Neck Surgery, 2003

mation of the larynx. Future studies are planned to assess long-term biocompatibility and functio... more mation of the larynx. Future studies are planned to assess long-term biocompatibility and functioning of the electrode. Significance: While these results are preliminary, they lay the foundation for future research. This technique offers the potential to aid restoration of vocal fold movement in patients with a paralyzed vocal cord and intact recurrent laryngeal nerve.

Many diseases, such as diabetes, Alzheimer’s, Parkinson’s, hemophilia, and lysosomal storage dise... more Many diseases, such as diabetes, Alzheimer’s, Parkinson’s, hemophilia, and lysosomal storage diseases and cancer involve folding defects or impaired transport of proteins from the endoplasmic reticulum (ER). Cells activate the Unfolded Protein Response (UPR) to restore homeostatic protein processing by clearing out the stress of accumulated misfolded proteins (adaptive arm). However, with prolonged stress an apoptotic arm of the UPR leads to selective cell death. We herein report the successful development of a first-in-class, potent (762 nM EC50), not generally cytotoxic, chemical probe, ML291, that selectively activates the apoptotic but not the adaptive arm of the UPR, that demonstrates efficacy in inducing cell death through activation of the apoptotic arm in relevant cells, and moreover activate genes associated with the apoptotic arm of the UPR (by qRT-PCR). The progenitor of this probe was identified through a high-throughput screen of the NIH Molecular Libraries Small Molecu...

At least six cellular pathways leading to activation of NFκB-family transcription factors have be... more At least six cellular pathways leading to activation of NFκB-family transcription factors have been identified, participating in host-defense, immunity, inflammation, and cancer. The pathway initiated by Protein Kinase C (PKC) family kinase is critical for signaling downstream of antigen receptors in T-cells and B-cells, as well as many growth factor receptors and some GPCRs that stimulate intracellular Ca2+ elevations. This pathway often involves a multi-component protein complex that includes CARMA, Bcl-10, and MALT1. Previously, a potent (~67 nM) and selective probe (ML029, Pubchem CID2858522) was identified as an inhibitor of the PKC-initiated NF-κB pathway after a battery of 12 secondary and counter-screen assays. However, this probe appeared potent only in the original HEK293 reporter cell line and some types of primary lymphocytes, with little potency in several other tumor cell lines. We used HTS assays employing NF-κB reporter genes in T-cell and B-cell lines for screening ...

The Laryngoscope, 2010

Background: The immune system of advanced stage head and neck cancer patients is frequently suppr... more Background: The immune system of advanced stage head and neck cancer patients is frequently suppressed. Poor immune function has been correlated with poor clinical outcome. Immunotherapeutic strategies have been previously attempted in an effort to enhance immune function and improve survival. Previous studies have shown surgical suture can be transformed into an immune stimulant capable of activating the T lymphocytes of cancer patients. The development of a process for covalently linking proteins and cytokines to suture could have enormous potential for the in vivo manipulation of the immune system. Hypothesis: We hypothesize proteins and cytokines can be covalently linked to surgical suture while preserving their functional properties. Study Design: Prospective study testing normal donor and head and neck squamous cell carcinoma (HNSCC) patient lymphocytes. Method: Polyester suture was acid hydrolyzed followed by reacting with 1‐ethyl‐3(‐3‐dimethylamino propyl carbodiimide) (EDAC...

Otolaryngology - Head and Neck Surgery, 2004

PMS assay to determine the number of viable cells at 0, 2, 4, 6, 8, and 10 days postradiation (as... more PMS assay to determine the number of viable cells at 0, 2, 4, 6, 8, and 10 days postradiation (as cells would not grow in colonies). We determined expression of eIF4E by western blots after radiation and apoptosis was evaluated after radiation via flow cytometry using the CaspACE FITC-VAD-FMK In Situ Marker kit (Promega). Results: HEp3 with a 2.5-fold higher expression of 4E compared to FaDu was significantly more radioresistant at ¡Ý 6 Gy (P ϭ 0.02). There was a 20% to 25% (significant). Conclusion: Overexpression of eIF4E appears to be associated with radiation resistance. Significance: Overexpression of eIF4E appears to be associated with radiation resistance.

SLAS Discovery, 2013

Excess caloric consumption leads to triacylglyceride (TAG) accumulation in tissues that do not ty... more Excess caloric consumption leads to triacylglyceride (TAG) accumulation in tissues that do not typically store fat, such as skeletal muscle. This ectopic accumulation alters cells, contributing to the pathogenesis of metabolic syndrome, a major health problem worldwide. We developed a 1536-well assay to measure intracellular TAG accumulation in differentiating H9c2 myoblasts. For this assay, cells were incubated with oleic acid to stimulate TAG accumulation prior to adding compounds. We used Nile red as a fluorescent dye to quantify TAG content with a microplate reader. The cell nuclei were counterstained with DAPI nuclear stain to assess cell count and filter cytotoxic compounds. In parallel, we developed an image-based assay in H9c2 cells to measure lipid accumulation levels via high-content analysis, exploiting the dual-emission spectra characteristic of Nile red staining of neutral and phospholipids. Using both approaches, we successfully screened ~227,000 compounds from the Nat...

International Journal of Hydrogen Energy, 2011

The redox performance of pure iron oxide (Fe 2 O 3) and iron oxide modified with ceria (CeO 2) an... more The redox performance of pure iron oxide (Fe 2 O 3) and iron oxide modified with ceria (CeO 2) and/or zirconia (ZrO 2) as an oxygen carrier was investigated for hydrogen (H 2) production through a methaneesteam redox process. The addition of both CeO 2 and ZrO 2 were found to be a more effective modification of Fe 2 O 3 than the addition CeO 2 or ZrO 2 alone. It was found that the reducibility of Fe 2 O 3 was enhanced by CeO 2 and the thermal stability of Fe 2 O 3 was improved by ZrO 2. These results, therefore, led to the conclusion of the synergistic effect in the Fe 2 O 3-CeO 2-ZrO 2 mixed oxide. As a result, both the redox activity and the thermal stability were significantly improved, and increases in H 2 yield and purity could be maintained by the modification. The redox temperature was found to have a significant effect on redox performance. The production of H 2 was considerably improved when the redox temperature was increased from 650 to 750 C. The ZrO 2 concentration in Fe 2 O 3-CeO 2-ZrO 2 mixed oxide samples was also found to influence performance with the highest H 2 yield observed at a ZrO 2 concentration of 75 wt.%. Although all materials tested showed a reduction in surface area in the first redox cycle, the change in surface area in subsequent cycles was found to be smaller and the yield of H 2 could be maintained at a constant level over a longer period for the mixed oxide containing 75 wt.% ZrO 2 .

Inorganic Chemistry, 2007

Four compounds containing tri-and diperoxodioxouranium(VI) complexes have been synthesized under ... more Four compounds containing tri-and diperoxodioxouranium(VI) complexes have been synthesized under ambient conditions and structurally characterized. The crystal structures of Na 4 (UO 2)(O 2) 3 (H 2 O) 12 (monoclinic, P2 1 /c, a) 6.7883(6) Å, b) 16.001(2) Å, c) 16.562(2) Å,) 91.917(2)°, V) 1797.9(3) Å 3 , Z) 4) and Ca 2 (UO 2)(O 2) 3-(H 2 O) 9 (orthorhombic, Pbcn, a) 9.576(3) Å, b) 12.172(3) Å, c) 12.314(2) Å, V) 1435.4(6) Å 3 , Z) 4) contain clusters of triperoxodioxouranium(VI). These clusters are bonded through a network of H bonding to H 2 O groups and in the Ca compound by bonds to Ca 2+ cations. In the crystal structure of Na 2 Rb 4 (UO 2) 2 (O 2) 5 (H 2 O) 14 (orthorhombic, Pbcm, a) 6.808(2) Å, b) 16.888(6) Å, c) 23.286(8) Å, V) 2677.5(16) Å 3 , Z) 4), triperoxodioxouranium(VI) polyhedra share a peroxide edge, forming dimers of polyhedra of composition (UO 2) 2 (O 2) 5 6-. Adjacent dimers are linked through bonding to Rb + cations and by H bonds to H 2 O groups. The crystal structure of K 6 [(UO 2)(O 2) 2-(OH)] 2 (H 2 O) 7 (orthorhombic, Pcca, a) 15.078(8) Å, b) 6.669(4) Å, c) 23.526(13) Å, V) 2366(2) Å 3 , Z) 4) contains diperoxodioxouranium(VI) polyhedra that include two OH groups. These polyhedra share an OH−OH edge, forming dimers of composition (UO 2) 2 (O 2) 4 (OH) 2 6-. The dimers are linked by bonds to K + cations and by H bonding to H 2 O groups. Di-and Triperoxodioxouranium(VI) Complexes

Inorganic Chemistry, 2013

Two chiral cage clusters built from uranyl polyhedra and (HPO 3) 2− groups have been synthesized ... more Two chiral cage clusters built from uranyl polyhedra and (HPO 3) 2− groups have been synthesized in pure yield and characterized structurally and spectroscopically in the solid state and aqueous solution. Synthesis reactions under ambient conditions in mildly acidic aqueous solutions gave clusters U 22 PO 3 and U 28 PO 3 that contain belts of four uranyl peroxide pentagonal and hexagonal bipyramids, in contrast to earlier reported uranyl peroxide cage clusters that are built from four-, five-, and six-membered rings of uranyl hexagonal bipyramids. U 22 PO 3 and U 28 PO 3 are also the first chiral uranyl-based cage clusters, the first that contain uranyl pentagonal bipyramids that contain no peroxide ligands, and the first that incorporate (HPO 3) 2− bridges between uranyl ions. They are built from 22 uranyl polyhedra and 20 (HPO 3) 2− groups, or 28 uranyl polyhedra and 24 (HPO 3) 2− groups, with the outer and inner surfaces of the cages passivated by the O atoms of uranyl ions. Small-angle X-ray scattering (SAXS) profiles demonstrated that U 22 PO 3 clusters formed in solution within 1 h after mixing of reactants, and remained in solution for 2 weeks prior to crystallization. Time-resolved electrospray ionization mass spectrometry and SAXS demonstrated that U 28 PO 3 clusters formed in solution within 1 h of mixing the reactants, and remained in solution 1 month before crystallization. Crystallization of U 22 PO 3 and U 28 PO 3 is accelerated by addition of KNO 3. Clusters of U 22 PO 3 with and without encapsulated cations exhibit markedly different aqueous solubility, reflecting the importance of cluster surface charge in fostering linkages through counterions to form a stable solid.

Emergency Medicine Journal, 2007

Clinical Cancer Research, 2004

Purpose: We have proposed to characterize the mechanism through which bioactive surgical sutures ... more Purpose: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a TH1 immune response and to define the immune-stimulating half-life of the sutures.Experimental Design: Bioactive sutures of interferon γ (IFNγ), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNγ sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor κB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132.Results: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNγ gen...

Bioorganic & Medicinal Chemistry Letters, 2012

The recently discovered apelin/APJ system has emerged as a critical mediator of cardiovascular ho... more The recently discovered apelin/APJ system has emerged as a critical mediator of cardiovascular homeostasis and is associated with the pathogenesis of cardiovascular disease. A role for apelin/ APJ in energy metabolism and gastrointestinal function has also recently emerged. We disclose the discovery and characterization of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4nitrobenzoate (ML221), a potent APJ functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor. ML221 was derived from an HTS of the ∼330,600 compound MLSMR collection. This antagonist showed no significant binding activity against 29 other GPCRs, except to the κ-opioid and benzodiazepinone receptors (<50/<70%I at 10 μM). The synthetic methodology, development of structure-activity relationship (SAR), and initial in vitro pharmacologic characterization are also presented.

ANZ Journal of Surgery, 2009

Society (AUSS) has steadily grown since its inception in 2003 and had a membership base of more t... more Society (AUSS) has steadily grown since its inception in 2003 and had a membership base of more than 400 medical students in 2008. The AUSS provides opportunities to medical students interested in a career in surgery. This is achieved through research and mentorship programmes, a surgical anatomy series, numerous basic surgical skills workshops, case presentation competitions, special education and training (SET) programme forums, surgical career expos, women in surgery presentation evenings and informative sessions on humanitarian and military surgery. Medical schools have a responsibility to ensure that graduates receive a thorough, undifferentiated education to prepare them for many career possibilities. As surgical training evolves to allow

Background: In previous studies from our lab we have transformed surgical suture from its classic... more Background: In previous studies from our lab we have transformed surgical suture from its classical purpose of wound closure into a vehicle, which carries immune-stimulants. Bioactive sutures of IFN , IL-2, anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFN sutures have ...

Academic Emergency Medicine, 2007

Background: An estimate of a child's weight is required for critical interventions, particularly ... more Background: An estimate of a child's weight is required for critical interventions, particularly pharmacotherapy. Weight measurement is not always practical, so weight estimation methods are used. Recently, a new weight estimation formula was suggested. The Argall formula estimates weight in kilograms as follows: (age in years + 2) Â 3. Objectives: To validate the Argall weight formula. Methods: This was a prospective, observational, cohort study conducted in the pediatric emergency department (ED) of Sunshine Hospital. Children aged up to 11 years who presented to the ED during August 18, 2005, to February 25, 2006, were included. Actual weight, height, age, and ethnicity were obtained. Data were analyzed by descriptive statistics (proportion, mean, median, and SD). Agreement between estimated weight using the Argall formula and measured weight is reported by using mean bias, SD, and root mean square error (RMSE) analysis. Results: Four hundred ten cases were included, 46% were female, and the median age was 4 years. The Argall formula had a mean bias of-1.66 kg and RMSE of 5.65. Only 37% of Argall estimates were within 10% of the child's actual weight. The formula performed less well in children weighing more than 35 kg but performed better in Asian children than white children. Conclusions: The Argall weight estimation formula has poor accuracy for weight estimation in Australian children, in particular those weighing more than 35 kg.