ORCID Profile
0000-0002-4477-3078
Current Organisation
University of Queensland
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Organisational Planning And Management | Recreation And Leisure Studies | Exploration geochemistry | Inorganic geochemistry | Structural geology and tectonics | Geochemistry | Human Geography
Publisher: Elsevier BV
Date: 06-2013
Publisher: Impact Journals, LLC
Date: 07-06-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2016
Publisher: American Chemical Society (ACS)
Date: 25-02-1100
DOI: 10.1021/MP500531E
Abstract: The current study sought to explore whether the subcutaneous administration of lymph targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumor activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumor-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumor growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumor-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumor activity, possibly suggesting constrained drug release at the site of action.
Publisher: Elsevier BV
Date: 07-2008
Publisher: MyJove Corporation
Date: 28-06-2013
DOI: 10.3791/50395
Publisher: Elsevier BV
Date: 20-01-2007
Publisher: Elsevier BV
Date: 2008
Publisher: Springer Science and Business Media LLC
Date: 25-11-2015
Publisher: Springer Science and Business Media LLC
Date: 03-2016
DOI: 10.1038/NCOMMS10634
Abstract: Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes.
Publisher: Elsevier BV
Date: 05-2022
Publisher: MDPI AG
Date: 24-07-2023
DOI: 10.3390/MIN13070982
Abstract: Spatial prediction of orebody characteristics can often be challenging given the commonly complex geological structure of mineral deposits. For ex le, a high nugget effect can strongly impact variogram modelling. Geological complexity can be caused by the presence of structural geological discontinuities combined with numerous lithotypes, which may lead to underperformance of grade estimation with traditional kriging. Deep learning algorithms can be a practical alternative in addressing these issues since, in the neural network, calculation of experimental variograms is not necessary and nonlinearity can be captured globally by learning the underlying interrelationships present in the dataset. Five different methods are used to estimate an uns led 2D dataset. The methods include the machine learning techniques Support Vector Regression (SVR) and Multi-Layer Perceptron (MLP) neural network the conventional geostatistical methods Simple Kriging (SK) and Nearest Neighbourhood (NN) and a deep learning technique, Convolutional Neural Network (CNN). A comparison of geologic features such as discontinuities, faults, and domain boundaries present in the results from the different methods shows that the CNN technique leads in terms of capturing the inherent geological characteristics of given data and possesses high potential to outperform other techniques for various datasets. The CNN model learns from training images and captures important features of each training image based on thousands of calculations and analyses and has good ability to define the borders of domains and to construct its discontinuities.
Publisher: Informa UK Limited
Date: 24-06-2016
Publisher: Elsevier BV
Date: 06-2009
Publisher: Springer Science and Business Media LLC
Date: 02-10-2008
Publisher: Elsevier BV
Date: 12-2013
Publisher: Springer Science and Business Media LLC
Date: 12-12-2019
Publisher: Informa UK Limited
Date: 29-03-2022
Publisher: Elsevier BV
Date: 08-2014
Publisher: Elsevier BV
Date: 10-2006
Publisher: MDPI AG
Date: 22-09-2016
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 04-2014
Publisher: MDPI AG
Date: 17-07-2015
Publisher: Elsevier BV
Date: 2015
Publisher: Universidade de Sao Paulo, Agencia USP de Gestao da Informacao Academica (AGUIA)
Publisher: American Association for Cancer Research (AACR)
Date: 14-09-2010
DOI: 10.1158/0008-5472.CAN-10-0522
Abstract: Metastasis to distant tissues is the chief driver of breast cancer–related mortality, but little is known about the systemic physiologic dynamics that regulate this process. To investigate the role of neuroendocrine activation in cancer progression, we used in vivo bioluminescence imaging to track the development of metastasis in an orthotopic mouse model of breast cancer. Stress-induced neuroendocrine activation had a negligible effect on growth of the primary tumor but induced a 30-fold increase in metastasis to distant tissues including the lymph nodes and lung. These effects were mediated by β-adrenergic signaling, which increased the infiltration of CD11b+F4/80+ macrophages into primary tumor parenchyma and thereby induced a prometastatic gene expression signature accompanied by indications of M2 macrophage differentiation. Pharmacologic activation of β-adrenergic signaling induced similar effects, and treatment of stressed animals with the β-antagonist propranolol reversed the stress-induced macrophage infiltration and inhibited tumor spread to distant tissues. The effects of stress on distant metastasis were also inhibited by in vivo macrophage suppression using the CSF-1 receptor kinase inhibitor GW2580. These findings identify activation of the sympathetic nervous system as a novel neural regulator of breast cancer metastasis and suggest new strategies for antimetastatic therapies that target the β-adrenergic induction of prometastatic gene expression in primary breast cancers. Cancer Res 70(18) 7042–52. ©2010 AACR.
Publisher: Society of Economic Geologists
Date: 07-2001
DOI: 10.2113/96.4.817
Publisher: Springer Science and Business Media LLC
Date: 05-07-2003
Publisher: Wiley
Date: 17-11-2015
DOI: 10.1096/FJ.15-277798
Publisher: The Company of Biologists
Date: 2016
DOI: 10.1242/JCS.194803
Abstract: Invasion by cancer cells is a critical step in metastasis. An oversimplified view in the literature is that cancer cells become more deformable as they become more invasive. β-adrenergic receptor (βAR) signaling drives invasion and metastasis, but the effects on cell deformability are not known. Here we show that activation of β-adrenergic signaling by βAR agonists reduces the deformability of highly metastatic human breast cancer cells, and that these stiffer cells are more invasive in vitro. We find that βAR activation also reduces the deformability of ovarian, prostate, melanoma, and leukemia cells. Mechanistically, we show that βAR-mediated cell stiffening depends on the actin cytoskeleton and myosin II activity. These changes in cell deformability can be prevented by pharmacologic β-blockade or genetic knockout of the β2-adrenergic receptor. Our results identify a β2-adrenergic-Ca2+-actin axis as a novel regulator of cell deformability, and suggest that the relationship between cell mechanical properties and invasion may be dependent on context.
Publisher: Proceedings of the National Academy of Sciences
Date: 22-02-2010
Abstract: To identify genetic factors that interact with social environments to impact human health, we used a bioinformatic strategy that couples expression array–based detection of environmentally responsive transcription factors with in silico discovery of regulatory polymorphisms to predict genetic loci that modulate transcriptional responses to stressful environments. Tests of one predicted interaction locus in the human IL6 promoter (SNP rs1800795) verified that it modulates transcriptional response to β-adrenergic activation of the GATA1 transcription factor in vitro. In vivo validation studies confirmed links between adverse social conditions and increased transcription of GATA1 target genes in primary neural, immune, and cancer cells. Epidemiologic analyses verified the health significance of those molecular interactions by documenting increased 10-year mortality risk associated with late-life depressive symptoms that occurred solely for homozygous carriers of the GATA1-sensitive G allele of rs1800795. Gating of depression-related mortality risk by IL6 genotype pertained only to inflammation-related causes of death and was associated with increased chronic inflammation as indexed by plasma C-reactive protein. Computational modeling of molecular interactions, in vitro biochemical analyses, in vivo animal modeling, and human molecular epidemiologic analyses thus converge in identifying β-adrenergic activation of GATA1 as a molecular pathway by which social adversity can alter human health risk selectively depending on in idual genetic status at the IL6 locus.
Publisher: MDPI AG
Date: 29-12-2020
DOI: 10.3390/MIN11010029
Abstract: The weathering of Paleoproterozoic itabirites (metamorphic-banded iron formations) and dolomites from the Cauê and Gandarela Formations in the Quadrilátero Ferrífero (QF), Brazil, produces supergene iron ore with different mineralogical, chemical, and physical properties. In this work, we present a methodology to assess the changes in chemical and physical features of those rocks during weathering, via quantitative analyses of mineral assemblages. These mineral assemblages were calculated from chemical analyses of fresh and weathered s les collected from drill holes drilled in different iron ore deposits in the QF. In general, the number of mineral species found in fresh or/and weathered itabirite is restricted, which helps the quantification of the mass and volumes of minerals by normative calculation in a large dataset of drilling and channel s les. The calculation of the bulk density takes into consideration, besides the mineral phases, the voids and free water in the altered rock matrix. This study shows that the estimated porosity in supergene ore varies from 0% to 20%, for compact materials, and from 15% to 55% for friable rocks, indicating an important process of rock matrix dissolution during the weathering of itabirites. In this process, MgO, CaO, and FeO are leached out from carbonates, talc, and hiboles. Magnetite is oxidized to hematite, releasing Fe2+, which is oxidized and precipitates as Fe-hydroxide. There is a concentration of Fe2O3, MnO, Al2O3, and SiO2 in the supergene ore (saprolite) by residual enrichment or recrystallization of hematite, goethite, quartz, manganese oxides, and kaolinite. A calculation of weathering effects on the original protoliths allowed for the establishment of a correlation between different types of fresh itabirites and their corresponding weathered materials. The calculation was carried out in several steps, to account for changes in porosity and masses and has taken into consideration differences in the mineralogical composition of the protolith. Within the weathered zones, a strong link is observed between the existence of collapse on the topographic surface and the presence of supergene ore underneath. The partial to total dissolution of quartz and carbonates from the protolith itabirite results in very porous materials and leads to gravitational collapses.
Publisher: Elsevier BV
Date: 05-2012
Publisher: Elsevier BV
Date: 02-2008
Publisher: Wiley
Date: 16-06-2021
DOI: 10.1002/GJ.4195
Abstract: The geochemical differences of magmatic rocks can be influenced by melt source and magmatic processes, including partial melting, fractional crystallization and magma mixing. New whole‐rock geochemical analyses, zircon U–Pb ages and Hf‐isotope data on granitoids from the Qingshanbao complex in the Longshoushan belt highlight a significant Late Ordovician–Early Silurian magmatic episode during the collision between the Alxa and Qilian‐Qaidam blocks, in which magma mixing was a fundamental process. The Qingshanbao complex comprises K‐feldspar granite, granodiorite and diorite emplaced coevally from 442 to 433 Ma. They exhibit peraluminous to metaluminous I‐type features, are enriched in large‐ion lithophile elements (LILEs) and light rare earth elements (LREEs) and depleted in high‐field‐strength elements (HFSEs). Chondrite‐normalized REE patterns are fractionated (La N /Yb N = 10.2–34.9) with weakly negative Eu anomalies (Eu/Eu* = 0.66–0.94). The 176 Lu/ 177 Hf zircon two‐stage model ages ( T DM2 ) and the ε Hf ( t ) on zircons extracted from the K‐feldspar granite (1613–2,316 Ma, ε Hf ( t ) = −14.4 to −3.0) and granodiorite (1640–2015 Ma, ε Hf ( t ) = −9.6 to −3.6) suggest they were formed by the mixing of melts produced by the melting of Mesoproterozoic crustal materials, most likely meta‐basic rocks from the Longshoushan Group, and to a lesser extent mantle materials. In contrast, zircons in the diorite yield T DM2 ages ranging from 964 to 1767 Ma and ε Hf ( t ) values of −5.5 to 7.1, implying melting of depleted mantle rocks with subordinate participation of lower crust materials. We suggest that the Qingshanbao complex was emplaced when the North Qilian area was in a transitional stage from a compressional to an extensional environment as early as approximately 442 Ma.
Publisher: Proceedings of the National Academy of Sciences
Date: 23-09-2013
Abstract: Chronic exposure to adverse social environments is associated with increased risk of disease, and stress-related increases in the expression of proinflammatory genes appear to contribute to these effects. The present study identifies a biological mechanism of such effects in the ability of the sympathetic nervous system to up-regulate bone marrow production of immature, proinflammatory monocytes. These effects are mediated by β-adrenergic receptors and the myelopoietic growth factor GM-CSF, and suggest new targets for interventions to protect health in the context of chronic social stress.
Publisher: Elsevier BV
Date: 03-2020
Publisher: American Association for Cancer Research (AACR)
Date: 14-08-2012
DOI: 10.1158/0008-5472.CAN-11-3873
Abstract: Hypoxia within a tumor acts as a strong selective pressure that promotes angiogenesis, invasion, and metastatic spread. In this study, we used immune competent bone marrow chimeric mice and syngeneic orthotopic mammary cancer models to show that hypoxia in the primary tumor promotes premetastatic niche formation in secondary organs. Injection of mice with cell-free conditioned medium derived from hypoxic mammary tumor cells resulted in increased bone marrow–derived cell infiltration into the lung in the absence of a primary tumor and led to increased metastatic burden in mammary and melanoma experimental metastasis models. By characterizing the composition of infiltrating bone marrow–derived cells, we identified CD11b+/Ly6Cmed/Ly6G+ myeloid and CD3−/NK1.1+ immune cell lineages as key constituents of the premetastatic niche. Furthermore, the cytotoxicity of natural killer (NK) cells was significantly decreased, resulting in a reduced antitumor response that allowed metastasis formation in secondary organs to a similar extent as ablation of NK cells. In contrast, metastatic burden was decreased when active NK cells were present in premetastatic lungs. Together, our findings suggest that primary tumor hypoxia provides cytokines and growth factors capable of creating a premetastatic niche through recruitment of CD11b+/Ly6Cmed/Ly6G+ myeloid cells and a reduction in the cytotoxic effector functions of NK cell populations. Cancer Res 72(16) 3906–11. ©2012 AACR.
Start Date: 07-2005
End Date: 06-2009
Amount: $72,444.00
Funder: Australian Research Council
View Funded ActivityStart Date: 10-2023
End Date: 10-2026
Amount: $454,101.00
Funder: Australian Research Council
View Funded Activity