A5080031908- Pancreatic and Hepatic Oncology Research
- Protease and Inhibitor Mechanisms
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Renal cell carcinoma treatment
- Proteoglycans and glycosaminoglycans research
- Cell Adhesion Molecules Research
- Neuroendocrine Tumor Research Advances
- Osteoarthritis Treatment and Mechanisms
- Phagocytosis and Immune Regulation
- Colorectal Cancer Treatments and Studies
- Blood Coagulation and Thrombosis Mechanisms
- Cancer, Lipids, and Metabolism
- Pancreatic function and diabetes
- PI3K/AKT/mTOR signaling in cancer
- Cancer Research and Treatments
- Erythrocyte Function and Pathophysiology
- NF-κB Signaling Pathways
- Gastric Cancer Management and Outcomes
- Peptidase Inhibition and Analysis
- Angiogenesis and VEGF in Cancer
- Caveolin-1 and cellular processes
- Wound Healing and Treatments
- Cardiovascular Function and Risk Factors
Westmead Institute for Medical Research
2020-2025
The University of Sydney
2013-2025
Westmead Institute
2023
Royal North Shore Hospital
2010-2020
Kyoto University
2003-2010
Abstract Objective To investigate the mechanism of inhibitory action hyaluronan (HA) on interleukin‐1β (IL‐1β)‐stimulated production matrix metalloproteinases (MMPs) in human articular cartilage. Methods IL‐1β was added to normal and osteoarthritic (OA) cartilage explant culture stimulate MMP production. Articular incubated or preincubated with a clinically used form 800‐kd HA assess its effect IL‐1β‐induced MMPs. Levels secreted MMPs 1, 3, 13 conditioned media were detected by...
We investigated the effects of hyaluronan (HA) on interleukin-1β (IL-1β)-stimulated matrix metalloproteinase (MMP)-13 production in human chondrocytes from patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Secreted levels MMP-13 conditioned media were detected by immunoblotting, while intracellular synthesis articular cartilage was evaluated immunofluorescence microscopic analysis. Mitogen-activated protein kinases (MAPKs), p38, extracellular signal-regulated (ERK), and c-jun...
Patients with chronic kidney disease (CKD) face a high risk of cardiovascular disease. Previous studies reported that endogenous thrombospondin 1 (TSP1) involves right ventricular remodeling and dysfunction. Here we show murine model CKD increased myocardial TSP1 expression produced left hypertrophy, fibrosis, knockout mice were protected from these features. In vitro, indoxyl sulfate is driving deleterious changes in cardiomyocyte through the TSP1. patients CKD, aryl hydrocarbon receptor...
The aged population is currently at its highest level in human history and expected to increase further the coming years. In humans, aging accompanied by impaired angiogenesis, diminished blood flow altered metabolism, among others. A cellular mechanism that impinges upon these manifestations of can be a suitable target for therapeutic intervention. Here we identify cell surface receptor CD47 as novel age-sensitive driver vascular metabolic dysfunction. With natural process, ligand...
In rheumatoid arthritis (RA), it is well known that synovial fibroblasts (RSF) produce matrix metalloproteinases (MMPs) when stimulated with proinflammatory cytokines such as interleukin-1beta (IL-1beta), which causes joint destruction. We have previously shown hyaluronan (HA) inhibits IL-1beta actions in RSF via CD44, the principal HA receptor. However, CD44 mediates effects only partially, and intracellular events after binding to its receptors remain unclear. investigated role of...
Diabetes is a global public health burden and characterized clinically by relative or absolute insulin deficiency. Therapeutic agents that stimulate secretion improve sensitivity are in high demand as treatment options. CD47 cell surface glycoprotein implicated multiple cellular functions including recognition of self, angiogenesis, nitric oxide signaling; however, its role the regulation remains unknown. Here, we demonstrate receptor signaling inhibits release from human well mouse...
Abstract Pyroptosis, the most inflammatory form of cell death, is dependent on membrane pore formation governed by assembly cleaved Gasdermin D (GSDMD). We hypothesized that regulated necrosis pathways are crucial in pathophysiology acute kidney injury (AKI). Mice with an isoleucine‐to‐asparagine loss‐of‐function mutation gene (GSDMD I105N/I105N ) generated ethylnitrosourea‐mutagenesis were subjected to bilateral renal ischemia–reperfusion (IRI) bio‐molecular readouts performed at 24 h. IRI...
Keratinocytes play a critical role in maintaining epidermal barrier function. Activated protein C (APC), natural anticoagulant with anti-inflammatory and endothelial protective properties, significantly increased the impedance of keratinocyte monolayers, measured by electric cell substrate sensing FITC-dextran flux. In response to APC, Tie2, tyrosine kinase receptor, was rapidly activated within 30 min, relocated cell-cell contacts. APC also junction proteins zona occludens, claudin-1...
Activated protein C (APC) is a natural anticoagulant that exerts anti-inflammatory and cytoprotective properties mediated through the protease activated receptor (PAR)-1. APC can also proteolytically cleave PAR-2, although subsequent function unknown. On basis of recent evidence promotes wound healing, aim this study was to determine whether acts PARs heal murine excisional wounds or regulate human cultured keratinocyte signaling mechanisms. Topical administration accelerated healing in...
PI3K-Akt is overexpressed in 50% to 70% of pancreatic ductal adenocarcinoma (PDAC). The hypothesis this study that PI3K and EGFR coinhibition may be effective PDAC with upregulated signaling.Multiple inhibitors were tested on five cell lines. inhibitor (EGFRi)-resistant lines found have significantly AKT2 gene, total Akt, pAkt. In vitro erlotinib-resistant (ER) models (BxPC-ER PANC-ER) highly constitutively active developed. These their respective parent for sensitivity erlotinib, IGFIR...
New molecular targets are needed for women with triple-negative breast cancer (TNBC). This pre-clinical study investigated the combination of EGFR inhibitor gefitinib sphingosine kinase (SphK) FTY720 (Fingolimod), aiming to block tumorigenic signaling downstream IGFBP-3, which is abundantly expressed in basal-like TNBC.In studies cell growth culture, proliferation was monitored by IncuCyte live-cell imaging, and protein abundance determined western blotting. In vivo mammary tumor used two...
Abstract Normothermic machine perfusion (NMP) is an emerging modality for kidney preservation prior to transplantation. NMP may allow directed pharmacomodulation of renal ischemia-reperfusion injury (IRI) without the need systemic donor/recipient therapies. Three proven anti-IRI agents not in widespread clinical use, CD47-blocking antibody (αCD47Ab), soluble complement receptor 1 (sCR1), and recombinant thrombomodulin (rTM), were compared a murine model IRI. The most effective agent was then...
Objective The prevalence of comorbid chronic kidney disease (CKD) and osteoarthritis (OA) is increasing globally. While sharing common risk factors, the mechanism consequences concurrent CKD-OA are unclear. aims study were to develop a preclinical model, investigate disease-modifying interactions. Methods Seventy (70) male 8–10 week-old C57BL/6 mice subjected 5/6 nephrectomy (5/6Nx)±destabilisation medial meniscus (DMM) or sham surgery. OA pathology CKD assessed 12 weeks postinduction by...
Triple-negative breast cancer (TNBC) typically has a worse outcome than other subtypes, in part owing to lack of approved therapeutic targets or prognostic markers. We have previously described an oncogenic pathway basal-like TNBC cells, initiated by insulin-like growth factor binding protein-3 (IGFBP-3), which the epidermal receptor (EGFR) is transactivated sphingosine-1-phosphate (S1P) resulting from sphingosine kinase (SphK)-1 activation. Oncogenic IGFBP-3 signaling can be targeted...
Abstract Objective To investigate the mechanism of induction matrix metalloproteinases (MMPs) by a 40‐kd COOH‐terminal heparin‐binding fibronectin fragment (HBFN‐f) containing III12–14 and IIICS domains in human articular cartilage culture. Methods Human was removed from macroscopically normal femoral heads cultured with HBFN‐f. MMP secretion into conditioned media analyzed immunoblotting (MMPs 1 13) gelatin zymography 2 9). Type II collagen cleavage collagenase monitored culture...
Background Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization high density lipoprotein (HDL) lipid by cancer tissue. This study examined influence exogenous ApoA-II on uptake and cell growth (PC) both vitro vivo. Methods Cryo transmission electron microscopy (TEM) ApoA-II's morphology SMOFLipid emulsion. The proliferation lines was determined incubating them with lipid+/-ApoA-II anti-SR-B1...
We previously reported that human keratinocytes express protease-activated receptor (PAR)-2 and play an important role in activated protein C (APC)-induced cutaneous wound healing. This study investigated the involvement of PAR-2 production gelatinolytic matrix metalloproteinases (MMP)-2 -9 by APC during Full-thickness excisional wounds were made on dorsum male C57BL/6 mice. Wounds treated with days 1, 2, 3 post-wounding. Cultured neonatal foreskin or without intact signalling to examine...
Objectives. To examine the mechanism of nitric oxide (NO) production by a COOH-terminal heparin-binding fibronectin fragment (HBFN-f) in rheumatoid arthritis (RA) cartilage.
Abstract Gemcitabine (Gem) is a key drug for pancreatic cancer, yet limited by high systemic toxicity, low bioavailability and poor pharmacokinetic profiles. To overcome these limitations, Gem prodrug amphiphiles were synthesised with oleyl, linoleyl phytanyl chains. Self‐assembly lyotropic mesophase behaviour of examined using polarised optical microscopy Synchrotron SAXS (SSAXS). Gem‐phytanyl was found to form liquid crystalline inverse cubic mesophase. This combined phospholipids...