ORCID Profile
0000-0002-3063-531X
Current Organisation
University of South Australia
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Organometallic Chemistry | Other Chemical Sciences | Analytical Spectrometry
Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Biological Sciences |
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5OB00621J
Abstract: A family of structurally hiphilic norbornanes has been constructed several of which possess broad spectrum antibacterial activity.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Elsevier BV
Date: 12-2018
Publisher: MDPI AG
Date: 24-10-2023
DOI: 10.3390/BIOS13110949
Publisher: Elsevier BV
Date: 04-2012
Publisher: Georg Thieme Verlag KG
Date: 21-05-2015
Publisher: Oxford University Press (OUP)
Date: 2022
Abstract: Cholesterol is vital to control membrane integrity and fluidity, but is also a precursor to produce steroid hormones, bile acids, and vitamin D. Consequently, altered cholesterol biology has been linked to many diseases, including metabolic syndromes and cancer. Defining the intracellular pools of cholesterol and its trafficking within cells is essential to understand both normal cell physiology and mechanisms of pathogenesis. We have synthesized a new cholesterol mimic (ReTEGCholestanol), comprising a luminescent rhenium metal complex and a cholestanol targeting unit, linked using a tetraethylene glycol (TEG) spacer. ReTEGCholestanol demonstrated favourable imaging properties and improved water solubility when compared to a cholesterol derivative, and structurally related probes lacking the TEG linker. A non-malignant and three malignant prostate cell lines were used to characterize the uptake and intracellular distribution of ReTEGCholestanol. The ReTEGCholestanol complex was effectively internalized and mainly localized to late endosomes/lysosomes in non-malignant PNT1a cells, while in prostate cancer cells it also accumulated in early endosomes and multivesicular bodies, suggesting disturbed cholesterol biology in the malignant cells. The ReTEGCholestanol is a novel imaging agent for visualizing endosomal uptake and trafficking, which may be used to define cholesterol related biology including membrane integration and altered lipid trafficking rocessing.
Publisher: Elsevier BV
Date: 02-2023
DOI: 10.1016/J.PATHOL.2022.08.001
Abstract: Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient s les, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy s le cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient s les. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology.
Publisher: American Chemical Society (ACS)
Date: 19-05-2020
Publisher: Wiley
Date: 07-02-2019
Publisher: MDPI AG
Date: 05-03-2020
DOI: 10.3390/MOLECULES25051182
Abstract: Breast cancer (BC) is one of the leading causes of death from cancer in women second only to lung cancer. Tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA for hormone therapy of BC. Despite having striking efficacy in BC therapy, concerns regarding the dose-dependent carcinogenicity of TAM still persist, restricting its therapeutic applications. Nanotechnology has emerged as one of the most important strategies to solve the issue of TAM toxicity, owing to the ability of nano-enabled-formulations to deliver smaller concentrations of TAM to cancer cells, over a longer period of time. Various TAM-containing-nanosystems have been successfully fabricated to selectively deliver TAM to specific molecular targets found on tumour membranes, reducing unwanted toxic effects. This review begins with an outline of breast cancer, the current treatment options and a history of how TAM has been used as a combatant of BC. A detailed discussion of various nanoformulation strategies used to deliver lower doses of TAM selectively to breast tumours will then follow. Finally, a commentary on future perspectives of TAM being employed as a targeting vector, to guide the delivery of other therapeutic and diagnostic agents selectively to breast tumours will be presented.
Publisher: Proceedings of the National Academy of Sciences
Date: 19-11-2018
Abstract: Artemisinin-based combination therapies (ACTs) are first-line antimalarial therapies used worldwide. The artemisinin drug (ART) component clears the bulk of infection rapidly, but small numbers of persistent parasites must be removed by the partner drug. Longer parasite clearance t 1/2 values have been associated with a Kelch-propeller mutation (K13 C580Y), raising concerns of increased ART resistance. We investigated effects of C580Y by using a Plasmodium falciparum cross and a monkey malaria model. Following three standard doses of ART, infections with or without the C580Y mutation cleared to microscopically undetectable levels, as in humans however, frequent recrudescences occurred with both types of infection. These results emphasize the importance of effective partner drugs to kill the parasites that persist through the ART component of ACT.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Public Library of Science (PLoS)
Date: 23-08-2016
Publisher: Wiley
Date: 17-06-2021
Abstract: Re(I) complexes have potential in biomedical sciences as imaging agents, diagnostics and therapeutics. Thus, it is crucial to understand how Re(I) complexes interact with carrier proteins, like serum albumins. Here, two neutral Re(I) complexes were used ( fac ‐[Re(CO) 3 (1,10‐phenanthroline)L], in which L is either 4‐cyanophenyltetrazolate (1) or 4‐methoxycarbonylphenyltetrazole ester (2) , to study the interactions with bovine serum albumin (BSA). Spectroscopic measurements, calculations of thermodynamic and Förster resonance energy transfer parameters, as well as molecular modelling, were performed to study differential binding between BSA and complex 1 and 2 . Induced‐fit docking combined with quantum‐polarised ligand docking were employed in what is believed to be a first for a Re(I) complex as a ligand for BSA. Our findings provide a basis for other molecular interaction studies and suggest that subtle functional group alterations at the terminal region of the Re(I) complex have a significant impact on the ability of this class of compounds to interact with BSA.
Publisher: Springer Science and Business Media LLC
Date: 16-09-2015
DOI: 10.1038/SREP14081
Abstract: The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration and importantly assess reproducibility. Our standardized protocol involves testing each serum s le in singlicate with three independent neutrophil donors and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of s les from in iduals enrolled in immuno-epidemiological studies or clinical vaccine trials and requires only 6 μL of serum per s le. Using a cohort of 86 s les, we show that malaria-exposed in iduals induce higher ADRB activity than malaria-naïve in iduals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity and provides an important standardized cell-based assay in the field.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2TB00408A
Abstract: The state-of-the-art for metal ion sensing by GQD probes is reviewed. The field is discussed, along with the challenges to determine specific mechanisms of interaction. This understanding is highly desired to develop selective GQD-metal ion sensors.
Publisher: MDPI AG
Date: 16-06-2023
Abstract: Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H& E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy s les to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H& E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H& E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of in idual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2NJ01510B
Abstract: A series of acylguanidines with pre-installed ethylamino linkers are described that can be incorporated into larger structures through amide coupling.
Publisher: Elsevier BV
Date: 06-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5RA03321G
Abstract: Structurally hiphilic norbornane bisether diguanidines show activity against a range of Gram-positive and Gram-negative bacterial species.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Georg Thieme Verlag KG
Date: 07-2012
Publisher: MDPI AG
Date: 04-01-2021
DOI: 10.3390/MOLECULES26010219
Abstract: Conventional chemotherapies used for breast cancer (BC) treatment are non-selective, attacking both healthy and cancerous cells. Therefore, new technologies that enhance drug efficacy and ameliorate the off-target toxic effects exhibited by currently used anticancer drugs are urgently needed. Here we report the design and synthesis of novel mesoporous silica nanoparticles (MSNs) equipped with the hormonal drug tamoxifen (TAM) to facilitate guidance towards estrogen receptors (ERs) which are upregulated in breast tumours. TAM is linked to the MSNs using a poly-ʟ-histidine (PLH) polymer as a pH-sensitive gatekeeper, to ensure efficient delivery of encapsulated materials within the pores. XRD, HR-TEM, DLS, SEM, FT-IR and BET techniques were used to confirm the successful fabrication of MSNs. The MSNs have a high surface area ( m2/g) and a mean particle size of 150 nm, which is an appropriate size to allow the penetration of premature blood vessels surrounding breast tumours. Successful surface functionalization was supported by FT-IR, XPS and TGA techniques, with a grafting ratio of approximately 29%. The outcomes of this preliminary work could be used as practical building blocks towards future formulations.
Publisher: MDPI AG
Date: 23-12-2021
Abstract: Fluorescence microscopy has become a critical tool for researchers to understand biological processes at the cellular level. Micrographs from fixed and live-cell imaging procedures feature in a plethora of scientific articles for the field of cell biology, but the complexities of fluorescence microscopy as an imaging tool can sometimes be overlooked or misunderstood. This review seeks to cover the three fundamental considerations when designing fluorescence microscopy experiments: (1) hardware availability (2) amenability of biological models to fluorescence microscopy and (3) suitability of imaging agents for intended applications. This review will help equip the reader to make judicious decisions when designing fluorescence microscopy experiments that deliver high-resolution and informative images for cell biology.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Informa UK Limited
Date: 13-12-2015
Publisher: Wiley
Date: 19-01-2015
Publisher: MDPI AG
Date: 08-07-2022
DOI: 10.3390/BIOM12070960
Abstract: The regulation of vitamin D3 actions in humans occurs mainly through the Cytochrome P450 24-hydroxylase (CYP24A1) enzyme activity. CYP24A1 hydroxylates both 25-hydroxycholecalciferol (25(OH)D3) and 1,25-dihydroxycholecalciferol (1,25(OH)2D3), which is the first step of vitamin D catabolism. An abnormal status of the upregulation of CYP24A1 occurs in many diseases, including chronic kidney disease (CKD). CYP24A1 upregulation in CKD and diminished activation of vitamin D3 contribute to secondary hyperparathyroidism (SHPT), progressive bone deterioration, and soft tissue and cardiovascular calcification. Previous studies have indicated that CYP24A1 inhibition may be an effective strategy to increase endogenous vitamin D activity and decrease SHPT. This study has designed and synthesized a novel C-24 O-methyloxime analogue of vitamin D3 (VD1-6) to have specific CYP24A1 inhibitory properties. VD1-6 did not bind to the vitamin D receptor (VDR) in concentrations up to 10−7 M, assessed by a VDR binding assay. The absence of VDR binding by VD1-6 was confirmed in human embryonic kidney HEK293T cultures through the lack of CYP24A1 induction. However, in silico docking experiments demonstrated that VD1-6 was predicted to have superior binding to CYP24A1, when compared to that of 1,25(OH)2D3. The inhibition of CYP24A1 by VD1-6 was also evident by the synergistic potentiation of 1,25(OH)2D3-mediated transcription and reduced 1,25(OH)2D3 catabolism over 24 h. A further indication of CYP24A1 inhibition by VD1-6 was the reduced accumulation of the 24,25(OH)D3, the first metabolite of 25(OH)D catabolism by CYP24A1. Our findings suggest the potent CYP24A1 inhibitory properties of VD1-6 and its potential for testing as an alternative therapeutic candidate for treating SHPT.
Publisher: MDPI AG
Date: 19-09-2023
Publisher: American Chemical Society (ACS)
Date: 07-2021
Location: Australia
Start Date: 10-2022
End Date: 09-2025
Amount: $420,000.00
Funder: Australian Research Council
View Funded Activity