ORCID Profile
0000-0003-2557-234X
Current Organisations
The University of Auckland
,
Griffith University
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Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2LC21170J
Abstract: We present a novel centrifugal microfluidic platform for the highly efficient manipulation and analysis of particles for applications in bead-based assays. The platform uses an array of geometrical V-cup barriers to trap particles using stopped-flow sedimentation under highly reproducible hydrodynamic conditions. The impact parameters governing the occupancy distribution and capture efficiency of the arrayed traps are investigated. The unique, nearly 100% capture efficiency paired with the capability to establish sharply peaked, single occupancy distributions enables a novel, digital readout mode for color-multiplexed, particle-based assays with low-complexity instrumentation. The presented technology marks an essential step towards a versatile platform for the integration of bead- and cell-based biological assays.
Publisher: MDPI AG
Date: 16-12-2019
DOI: 10.3390/MI10120883
Abstract: The polymerase chain reaction (PCR) is a robust technique used to make multiple copies of a segment of DNA. However, the available PCR platforms require elaborate and time-consuming operations or costly instruments, hindering their application. Herein, we introduce a sandwiched glass–polydimethylsiloxane (PDMS)–glass microchip containing an array of reactors for the real-time PCR-based detection of multiple waterborne bacteria. The PCR solution was loaded into the array of reactors in a single step utilising capillary filling, eliminating the need for pumps, valves, and liquid handling instruments. Issues of generating and trapping bubbles during the loading chip step were addressed by creating smooth internal reactor surfaces. Triton X-100 was used to enhance PCR compatibility in the chip by minimising the nonspecific adsorption of enzymes. A custom-made real-time PCR instrument was also fabricated to provide thermal cycling to the array chip. The microfluidic device was successfully demonstrated for microbial faecal source tracking (MST) in water.
Publisher: Springer Science and Business Media LLC
Date: 27-09-2021
DOI: 10.1057/S41599-021-00898-4
Abstract: In responding to the widespread impacts of the COVID-19 pandemic, countries have proposed and implemented documentation policies that confer varying levels of freedoms or restrictions (e.g., ability to travel) based on in iduals’ infection status or potential immunity. Most discussions around immunity- or infection-based documentation policies have focused on scientific plausibility, economic benefit, and challenges relating to ethics and equity. As COVID-19 vaccines are rolled out, attention has turned to confirmation of immunity and how documentation such as vaccine certificates or immunity passports can be implemented. However, the contextual inequities and local variabilities interacting with COVID-19 related documentation policies hinder a one-size-fits-all approach. In this Comment, we argue that social science perspectives can and should provide additional insight into these issues, through a erse range of current and historical ex les. This would enable policymakers and researchers to better understand and mitigate current and longer-term differential impacts of COVID-19 immunity-based documentation policies in different contexts. Furthermore, social science research methods can uniquely provide feedback to inform adjustments to policy implementation in real-time and help to document how these policy measures are felt differently across communities, populations, and countries, potentially for years to come. This Comment, updated as of 15 August 2021, combines precedents established in historical disease outbreaks and current experiences with COVID-19 immunity-based documentation policies to highlight valuable lessons and an acute need for further social science research which should inform effective and context-appropriate future public health policy and action.
Publisher: InTech
Date: 23-08-2011
DOI: 10.5772/23013
Publisher: American Association for Cancer Research (AACR)
Date: 04-2012
DOI: 10.1158/1538-7445.AM2012-4301
Abstract: A coordinated mode of motility is required for dissemination and invasion of esophageal metastases through the vasculature. This motility is largely driven by the activation of GTPases Rac1 and Rab5 which regulate 2 and 3-dimensional motility respectively however, little is known about the localization and activation of these GTPases under hydrodynamic flow. In this study, the effect of Rac1 activation on tumor motility was investigated in a controlled microfluidic chip that simulates venous flow conditions. A metastatic esophageal cell line derived from the ascites of a male patient with squamous cell cancer of the esophagus (OC-1), was transiently transfected with cDNA encoding active (L61), dominant negative (N17) and wild type (WT) Rac1 fused to GFP to enable visual localization of Rac1 in real time under static and fluid flow conditions. Transfected OC-1 cells were allowed to adhere to fibronectin (Fn) for 30 minutes under static conditions or allowed to adhere to Fn for 5 minutes followed by exposure to a continuous venous shear rate of 200 s-1 for 25 minutes. Cell motility and Rac1 localization was monitored over a 30-minute period followed by cell fixation and co-staining with a polyclonal antibody directed against Rab5 to visualize endosomal trafficking within the cells. The results of our study show that the over-expression of constitutively active Rac1 enhances circular ruffling, pseudopodia formation and motility in OC-1 cells under static conditions when compared to N17 and WT Rac1. Moreover, this activation response in L61-transfected cells is significantly increased in the presence of venous shear rates, (p& .0013) and completely inhibited in cells expressing the N17 active mutant which display rounded quiescent morphology states. Co-localization studies confirmed that both Rac1 and Rab5 GTPases are recruited to distinct populations of endosomes containing actin at the apical membrane of OC-1 cells under shear, measuring between 0.6 and 1.5 μm. These results suggest that Rab5/Rac1 circular ruffling/endosomal recruitment at the apical surface is an important adaptive response to enhance motility under fluid flow conditions. Moreover, this study may offer insight into mechano-receptor signaling and how metastatic cells adapt and disseminate in circulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research 2012 Mar 31-Apr 4 Chicago, IL. Philadelphia (PA): AACR Cancer Res 2012 (8 Suppl):Abstract nr 4301. doi:1538-7445.AM2012-4301
Publisher: F1000 Research Ltd
Date: 18-01-2016
DOI: 10.12688/F1000RESEARCH.7668.1
Abstract: Protein arrays are frequently used to profile antibody repertoires in humans and animals. High-throughput protein array characterisation of complex antibody repertoires requires a platform-dependent, lot-to-lot validation of secondary detection antibodies. This article details the validation of an affinity-isolated anti-chicken IgY antibody produced in rabbit and a goat anti-rabbit IgG antibody conjugated with alkaline phosphatase using protein arrays consisting of 7,390 distinct human proteins. Probing protein arrays with secondary antibodies in absence of chicken serum revealed non-specific binding to 61 distinct human proteins. The cross-reactivity of the tested secondary detection antibodies points towards the necessity of platform-specific antibody characterisation studies for all secondary immunoreagents. Secondary antibody characterisation using protein arrays enables generation of reference lists of cross-reactive proteins, which can be then excluded from analysis in follow-up experiments. Furthermore, making such cross-reactivity lists accessible to the wider research community may help to interpret data generated by the same antibodies in applications not related to protein arrays such as immunoprecipitation, Western blots or other immunoassays.
Publisher: F1000 Research Ltd
Date: 23-05-2017
DOI: 10.12688/F1000RESEARCH.7668.2
Abstract: Protein arrays are frequently used to profile antibody repertoires in humans and animals. High-throughput protein array characterisation of complex antibody repertoires necessitates the use of extensively validated secondary detection antibodies. This article details the validation of an affinity-isolated anti-chicken IgY antibody produced in rabbit and a goat anti-rabbit IgG antibody conjugated with alkaline phosphatase using protein arrays consisting of 7,390 distinct human proteins. Probing protein arrays with secondary antibodies in absence of chicken serum revealed non-specific binding to 61 distinct human proteins. Despite the identified non-specific binding, the tested antibodies are well suited for use in protein array experiments as the cross-reactive binding partners can be readily excluded from further analysis. The evident cross-reactivity of the tested secondary detection antibodies points towards the necessity of platform-specific antibody characterisation studies for all secondary immunoreagents. Furthermore, secondary antibody characterisation using protein arrays enables the generation of reference lists of cross-reactive proteins, which can be then marked as potential false positives in follow-up experiments. Providing such cross-reactivity reference lists accessible to the wider research community may help to interpret data generated with the same antibodies in applications not only related to protein arrays such as immunoprecipitation, Western blots or other immunoassays.
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.HUMPATH.2022.06.017
Abstract: The presence of IgA- and IgM-specific autoantibody (AAb) isotypes and their relationship to p53 tissue expression patterns are not well understood. This study aims to investigate the clinical utility of the anti-p53 AAb isotypes and tissue positivity in colorectal cancer (CRC). We analyzed anti-p53 IgG, IgM, and IgA AAbs in sera of 99 CRC patients and 99 non-cancer control subjects. Corresponding tissue expression of the p53 protein was evaluated by immunohistochemistry (IHC). Anti-p53 AAbs of the IgG isotype were present in the sera of 21 out of 99 patients (21%), whereas IgM AAbs were observed in 9 (9%) and IgA in 2 (2%) CRC patients. Anti-p53 AAbs of all 3 isotypes were generally associated with IHC staining indicative of mutated TP53. Seropositive anti-p53 IgM cases in the absence of anti-p53 IgG were linked to wild-type p53. Anti-p53 IgA in the absence of IgG AAbs was detected in 2 non-cancer controls indicating a potential p53 epitope mimicry. Although seropositivity was not associated with patient survival (P = .650), mutant-pattern p53 tissue expression was associated with reduced 5-year overall survival (P = .032) however, it was not an independent prognostic marker (multivariate Cox regression, P = .193). In conclusion, immunoglobulin isotyping revealed that anti-p53 IgM and IgA AAbs were predominantly concurrent with anti-p53 serum IgG and the mutant-pattern p53 tissue phenotype. IgM and IgA seropositive cases in absence of anti-p53 IgG were linked to wild-type p53 tissue phenotype indicating early anti-p53 immune responses preceding isotype class-switch (IgM) or p53 antigen mimicry (IgA).
Publisher: Springer Science and Business Media LLC
Date: 08-07-2012
Publisher: Springer Science and Business Media LLC
Date: 10-04-2018
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: Wiley
Date: 12-11-2014
DOI: 10.1002/CYTO.A.22588
Abstract: We present a substantially improved design and functionality of a centrifugo-magnetophoretic platform which integrates direct immunoseparation and cost-efficient, bright-field detection of cancer cells in whole blood. All liquid handling takes place in a disposable cartridge with geometry akin to a conventional compact disc (CD). The instrumentation required to process such a "lab-on-a-disc" cartridge can be as simple and cost-efficient as the rotor on a common optical disc drive. In a first step, target cells in a blood s le are specifically bound to paramagnetic microbeads. The s le is then placed into the disc cartridge and spun. In the second step, magnetically tagged target cells are separated by a co-rotating, essentially lateral magnetic field from the background population of abundant blood cells, and also from unbound magnetic beads. A stream of target cells centrifugally sediments through a stagnant liquid phase into a designated detection chamber. The continuous, multiforce immunoseparation proceeds very gently, i.e. the mechanical and hydrodynamic stress to the target cells is minimized to mitigate the risk of cell loss by collective entrapment in the background cells or vigorous snapping against a wall. We successfully demonstrate the extraction of MCF7 cancer cells at concentrations as low as 1 target cell per μl from a background of whole blood, with capture efficiencies of up to 88%. Its short time-to-answer is a notable characteristic of this system, with 10% of target cells collected in the first minute after their loading to the system and the remainder captured within the following 10 min. All the above-mentioned factors synergetically combine to leverage the development of a prospective point-of-care device for CTC detection.
Publisher: American Association for Cancer Research (AACR)
Date: 2015
DOI: 10.1158/1538-7445.CHTME14-B55
Abstract: Background: TRIM28 is a universal transcriptional co-repressor with pleotropic effects in both normal and tumor cells. We have previously shown that varying TRIM28 levels in epithelial cells and stromal fibroblasts have a prognostic value in colorectal cancer patients. The pathophysiological role of TRIM28 in carcinogenesis may therefore be associated with TRIM28 expression levels and cell type of expression within the tumor microenvironment. In this study we aim to dissect the molecular pathways associated with TRIM28 expression ratios within the tumor microenvironment by isolating in idual populations of neoplastic epithelial and stromal cells and investigating their protein signaling networks. Methods: TRIM28 expression was analyzed by immunohistochemistry on FFPE tissue from 19 colorectal cancer patients. TRIM28 staining was evaluated in both epithelial and stromal compartments. IHC scoring of at least 2 units of difference in staining intensity between stromal fibroblasts and epithelial cells was defined as a high TRIM28 expression ratio and a low TRIM28 expression ratio was defined as 1 or 0 units of difference in staining intensity. Reverse-phase protein microarrays (RPMA) were constructed from laser capture micro-dissection (LCM) enriched tumor epithelium and stroma isolated from fresh-frozen tissue of the same patient cohort. The protein signaling networks were measured for 32 downstream signaling endpoints. Spearman rank analysis was used to assess the correlations between in idual protein pairs. Correlation coefficient ρ ≥ 0.75 with P ≤ 0.01 was considered significant. Results: Immunohistochemical analysis of the FFPE tissue sections identified 10 TRIM28 high ratio cases and 9 TRIM28 low ratio cases. Proteomic networks were assessed in TRIM28 high and low ratio cases in fresh-frozen tissue using RPMA. Spearman ρ rank correlation analyses for the 32 signaling proteins revealed that 184 highly correlated protein pairs exclusive to the TRIM28 high ratio group, whereas 157 protein pairs were found exclusively in the TRIM28 low ratio group. In addition 191 protein pairs were shared across both TRIM28 high and low ratio groups. The caspases 3 and 7, as well as the cell surface receptor RAGE, were prominent in the high TRIM28 ratio group proteomic network, whereas the Metalloprotease MMP9 and the GTPase Ras-GRF1 were exclusive to the low TRIM28 ratio group. Furthermore we found Survivin and JNK to be prominent in the stromal compartment of the high TRIM28 cases. Conclusions: We characterized molecular pathways associated with TRIM28 expression ratios within the tumor microenvironment. Proteomic analysis revealed distinct protein signaling networks associated with varying TRIM28 expression levels in epithelial and stromal compartments. The study presents a novel way of deciphering molecular crosstalk between the epithelial and stromal compartments within the microenvironment. Citation Format: Seán Fitzgerald, Virginia Espina, Katherine M. Sheehan, Robert Cummins, Anthony O'Grady, Dermot Kenny, Richard O'Kennedy, Lance Liotta, Elaine W. Kay, Gregor Kijanka. Molecular characterization of epithelial and stromal crosstalk associated with TRIM28 expression levels in colorectal cancer. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment 2014 Feb 26-Mar 1 San Diego, CA. Philadelphia (PA): AACR Cancer Res 2015 (1 Suppl):Abstract nr B55. doi:10.1158/1538-7445.CHTME14-B55
Publisher: Wiley
Date: 2021
DOI: 10.1002/CTI2.1330
Abstract: Tumor‐associated autoantibodies (AAbs) in in iduals with cancer can precede clinical diagnosis by several months to years. The objective of this study was to determine whether the primary immune response in form of IgM and gut mucosa‐associated IgA can aid IgG AAbs in the detection of early‐stage colorectal cancer (CRC). We developed a novel protein array comprising 492 antigens seropositive in CRC. The array was used to profile IgG, IgM and IgA antibody signatures in 99 CRC patients and 99 sex‐ and age‐matched non‐cancer controls. A receiver operating curve (ROC), Kaplan–Meier survival analysis and univariate and multivariate Cox regression analyses were conducted. We identified a panel of 16 multi‐isotype AAbs with a cumulative sensitivity of 91% and specificity of 74% (AUC 0.90, 95% CI: 0.850–0.940) across all CRC stages. IgM and IgG isotypes were conversely associated with disease stage with IgM contributing significantly to improved stage I and II sensitivity of 96% at 78% specificity (AUC 0.928, 95% CI: 0.884–0.973). A single identified IgA AAb reached an overall sensitivity of 5% at 99% specificity (AUC 0.520, 95% CI: 0.440–0.601) balanced across all CRC stages. Kaplan–Meier analysis revealed that se33‐1 (ZNF638) IgG AAbs were associated with reduced 5‐year overall survival (log‐rank test, P = 0.012), whereas cumulative IgM isotype signatures were associated with improved 5‐year overall survival (log‐rank test, P = 0.024). IgM AAbs are associated with early‐stage colorectal cancer. Combining IgG, IgM and IgA AAbs is a novel strategy to improve early diagnosis of cancers.
Publisher: Elsevier BV
Date: 06-2014
Abstract: In medical diagnostics, detection of cells exhibiting specific phenotypes constitutes a paramount challenge. Detection technology must ensure efficient isolation of (often rare) targets while eliminating nontarget background cells. Technologies exist for such investigations, but many require high levels of expertise, expense, and multistep protocols. Increasing automation, miniaturization, and availability of such technologies is an aim of microfluidic lab-on-a-chip strategies. To this end, we present an integrated, dual-force cellular separation strategy using centrifugo-magnetophoresis. Whole blood spiked with target cells is incubated with (super-)paramagnetic microparticles that specifically bind phenotypic markers on target cells. Under rotation, all cells sediment into a chamber located opposite a co-rotating magnet. Unbound cells follow the radial vector, but under the additional attraction of the lateral magnetic field, bead-bound target cells are deflected to a designated reservoir. This multiforce separation is continuous and low loss. We demonstrate separation efficiently up to 92% for cells expressing the HIV/AIDS relevant epitope (CD4) from whole blood. Such highly selective separation systems may be deployed for accurate diagnostic cell isolations from biological s les such as blood. Furthermore, this high efficiency is delivered in a cheap and simple device, thus making it an attractive option for future deployment in resource-limited settings.
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.CBPA.2012.06.002
Abstract: Over the past two decades, centrifugal microfluidic systems have successfully demonstrated their capability for robust, high-performance liquid handling to enable modular, multi-purpose lab-on-a-chip platforms for a wide range of life-science applications. Beyond the handling of homogeneous liquids, the unique, rotationally controlled centrifugal actuation has proven to be specifically advantageous for performing cell and particle handling and assays. In this review we discuss technologies to implement two important steps for cell handling, namely separation and capturing/counting.
Publisher: AIP Publishing
Date: 09-2023
DOI: 10.1063/5.0169421
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1LC20105K
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.ACA.2014.12.035
Abstract: We report an opto-microfluidic method for continuous and non-interfering monitoring of cell movement and dynamic molecular processes in living cells enabled by the microfluidic "Lab-in-a-Trench" (LiaT) platform. To demonstrate real-time monitoring of heterogeneous cell-cell interactions, cell tracking and agent-induced cell activation dynamics, we observe phagocytosis of Escherichia coli by murine macrophages, migration of active macrophages and LPS-induced CD86 expression in macrophages. The visualization of phagocytosis is facilitated through the loading of green fluorescent protein (GFP) expressing E. coli to the array of cell capture modules before the introduction of macrophages. Simple migration tracking of active macrophages is enabled by a spatio-temporal control of the environment conditions within the LiaT platform. Furthermore, we report an interference-free monitoring of non-modified, endogenous changes in protein expression on the surface of living cells using traditional, antibody immuno-reagents. Throughout the experiment, murine macrophages were captured in the LiaT device and exposed to sub-background levels of fluorescently labeled anti-CD86 antibody. Upon lipopolysaccharide (LPS) stimulation, CD86 changes were visualized in real-time by time-lapse microscopy. This novel opto-microfluidic effect is controlled by the equilibrium of convective-diffusive replenishment of fluorescently labeled antibodies and antibody affinity. Overall, our non-interfering analysis method allows the studying of active cellular processes and endogenous protein dynamics in live cells in a simple and cost-efficient manner.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2LC00793B
Abstract: This paper comprehensively studies the latest progress in microfluidic technology for submicron and nanoparticle manipulation by elaborating on the physics, device design, working mechanism and applications of microfluidic technologies.
Publisher: IEEE
Date: 2011
Publisher: American Chemical Society (ACS)
Date: 25-11-2022
DOI: 10.26434/CHEMRXIV-2022-PGLV8
Abstract: Protein arrays are systematically arranged, large collections of annotated proteins on planar surfaces commonly used for the characterisation of protein binding events against a wide range of possible probes. These may include analyses of protein-protein, peptide-protein, enzyme-substrate or antibody-antigen interactions from simple reagents to complex mixtures. Absence of appropriate image analysis and data processing software may bestow a substantial hurdle limiting the uptake of protein arrays in research. We developed a first, automated semiquantitative open source software package for the analysis of widely used protein macroarrays. The software allows accurate single array and inter-array comparative studies through the tackling of intra-array inconsistencies arising from experimental disparities. The innovative and automated image analysis process includes adaptive positioning, background identification and subtraction, removal of null signals, robust statistical analysis, and protein pair validation. The normalized values allow a convenient semiquantitative data analysis of different s les or timepoints, enabling accurate characterisation of s le series to identify relative changes for instance in clinical s les in response to diseases and treatment.
Publisher: Springer Science and Business Media LLC
Date: 19-08-2019
DOI: 10.1038/S41388-019-0951-Y
Abstract: Many adenocarcinomas, including colorectal cancer (CRC), overexpress the MUC13 cell surface mucin, but the functional significance and mechanisms are unknown. Here, we report the roles of MUC13 in colonic tumorigenesis and tumor progression. High-MUC13 expression is associated with poor survival in two independent patient cohorts. In a comprehensive series of in vivo experiments, we identified a critical role for MUC13 in the development of this malignancy, by promoting survival and proliferation of tumor-initiating cells and driving an immunosuppressive environment that protects tumors from checkpoint inhibitor immunotherapy. In Muc13-deficient mice, fewer tumors are generated after exposure to carcinogens and inflammation, they have markedly reduced β-catenin signaling, have more tumor-infiltrating CD103
Publisher: IEEE
Date: 2010
Publisher: Informa UK Limited
Date: 08-2008
DOI: 10.1080/01459740802222690
Abstract: Questions regarding access to and the use of medical and surgical treatment for people with disabilities revisit themes central to medical anthropology. The "Ashley Treatment" is named after a nine-year-old girl, Ashley, who has extreme physical and cognitive disabilities. The Treatment refers to extensive medical and surgical procedures that are claimed to improve quality of life and prevent future medical problems. The Treatment has stimulated lively public debate on disability, medicalization, and caregiving. We illustrate how the Ashley Treatment emphasizes the importance of medical anthropological research on the construction of personhood and childhood disability, agency and autonomy, and the rights of representation and control, as well as the ethics of invasive procedures, hormone therapy, and body modification surgery.
Publisher: Elsevier BV
Date: 2020
Publisher: Wiley
Date: 17-11-2014
DOI: 10.1002/CJP2.5
Publisher: Canadian Center of Science and Education
Date: 10-03-2016
DOI: 10.5539/IJC.V8N2P22
Abstract: Mycotoxins are secondary fungal metabolites, which occur in food and feed. They have detrimental effects on the health of humans and animals, and they are known to cause immunosuppression. In this study the effect of patulin, deoxynivalenol (DON), zearalenone (ZEN) and T-2 toxin exposure on the viability and the secretion of key pro- and anti-inflammatory cytokines from the murine macrophage cell line, J774A.1, was investigated. Exposure of macrophages to high doses of ZEN (100,000 pg/mL) and T-2 toxin (10,000 and 100,000 pg/mL) resulted in a significant decrease (P & 0.05 and P & 0.01) in cell viability. Exposure of macrophages to these mycotoxins resulted in a dose-dependent modulation of cytokine secretion. Specifically, exposure to low doses of patulin (0.001, 0.1 and 1 pg/mL) resulted in a statistically significant decrease in the secretion of the pro-inflammatory cytokines interleukin (IL) 6 (IL-6) and tumor necrosis factor alpha (TNF-α), following stimulation with lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls. Treatment with low doses of DON (0.001 pg/mL) and ZEN (0.001 and 0.01 pg/mL) significantly decreased (P & 0.01) the secretion of the pro-inflammatory cytokine IL-12p40, while several doses of T-2 toxin (0.001, 0.01, 0.1, 1 and 100 pg/mL) caused a significant decrease the expression of IL-6. Each of the mycotoxins also significantly increased the production of the anti-inflammatory cytokine IL-10, both before and after LPS stimulation. This data provides further insight into the mechanisms by which mycotoxins modulate the host immune response to exert their immunosuppressive activity.
Publisher: Wiley
Date: 22-05-2013
DOI: 10.1111/JGH.12157
Abstract: TRIM28 is a multi-domain nuclear protein with pleotropic effects in both normal and tumor cells. In this study, TRIM28 expression in epithelial and stromal tumor microenvironment and its prognostic role in colorectal cancer were investigated. Immunohistological staining of TRIM28 was evaluated in tissue microarrays constructed from 137 colorectal cancer patients. The correlations of TRIM28 expression with clinicopathological features and p53 expression were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival (OS) and recurrence-free survival (RFS). Strong epithelial TRIM28 expression was found in 42% of colorectal cancer tissues. TRIM28 expression correlated significantly with p53 expression in matched cases (P=0.0168, Spearman rank test). A high epithelial to stromal TRIM28 expression ratio was associated with shorter OS (P=0.033 log-rank test) and RFS (P=0.043 log-rank test). Multivariate analysis showed that the epithelial to stromal TRIM28 expression ratio was an independent predictor of OS (hazard ratio=2.136 95% confidence interval 1.015-4.498, P=0.046) and RFS (hazard ratio=2.100 confidence interval 1.052-4.191, P=0.035). A high TRIM28 expression ratio between stromal and epithelial compartments in colorectal cancer tissue is an independent predictor of poor prognosis. The pathophysiological role of TRIM28 in carcinogenesis may be dependent on expression levels and cell type within the tumor microenvironment.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 11-2012
Publisher: Informa UK Limited
Date: 24-01-2012
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4LC01002G
Abstract: In this work we present a centrifugal microfluidic system enabling highly efficient collective trapping and alignment of particles such as microbeads and cells, their multi-colour fluorescent detection and subsequent manipulation by optical tweezers.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2013
DOI: 10.1158/1538-7445.AM2013-1159
Abstract: Background: Ceramide synthase 5 (CerS5) is multi-pass transmembrane protein of the endoplasmic reticulum. Functioning as a bona fide (dihydro)ceramide synthase, CerS5 regulates the levels of short ceramide species. Ceramides are bioactive lipids implicated in proliferation, senescence, angiogenesis and death of normal and cancerous cells. We aimed to investigate CerS5 expression in colorectal cancer tissue and to evaluate the prognostic significance of CerS5 in colorectal cancer patients. Methods: CerS5 expression was analyzed by immunohistochemistry on tissue microarrays constructed from 125 colorectal cancer patients. The associations between CerS5 staining and the clinicopathological factors were examined using the Spearman rank correlation test. Patient survival was examined using the Kaplan-Meier survival analysis and Cox proportional hazard modeling, categorized according to high or low CerS5 staining intensity. Results: Immunohistological staining revealed an overexpression of membranous CerS5 in 63 out of 125 (50.4%) colorectal carcinomas. CerS5 overexpression significantly correlated with lymphovascular invasion and metastatic disease in matched tumor cases (P = 0.036 & P = 0.037, respectively). Patients with CerS5 overexpressing tumors had a significantly lower overall 5-year survival (OS, P = 0.029) and 5-year recurrence-free survival (RFS, P = 0.047). Cox multivariate analysis showed that the increased CerS5 expression was an independent predictor of OS (hazard ratio (HR) = 1.604 95% confidence interval (CI) 1.010-2.548, P = 0.045) and RFS (HR = 1.592 CI 1.036-2.447, P = 0.034). Conclusions: We found an increased expression of ceramide synthase 5 (CerS5) in 50% of investigated colorectal carcinomas, which was associated with lymphovascular invasion, metastasis and poor survival in colorectal cancer patients. Our study identifies CerS5 as a novel independent prognostic biomarker for patients with colorectal cancer. Citation Format: Seán Fitzgerald, Katherine M. Sheehan, Anthony O'Grady, Dermot Kenny, Richard O'Kennedy, Elaine W. Kay, Gregor Kijanka. Increased ceramide synthase 5 expression is associated with lymphovascular invasion, metastasis and poor survival in colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research 2013 Apr 6-10 Washington, DC. Philadelphia (PA): AACR Cancer Res 2013 (8 Suppl):Abstract nr 1159. doi:10.1158/1538-7445.AM2013-1159
Publisher: American Chemical Society (ACS)
Date: 13-04-2004
DOI: 10.1021/AC035357A
Abstract: Automation is the key approach for genomewide and proteomewide screening of function and interaction. Especially for proteomics, antibody microarrays are a useful tool for massive parallel profiling of complex s les. To meet the requirements of antibody microarrays and to obtain a great variety of antibodies, new technologies such as phage display have partly replaced the classical hybridoma method. While the selection process for phage-displayed antibody fragments itself has been automated, the bottleneck was shifted further downstream to the identification of monoclonal binders obtained from the selections. Here, we present a new approach to reduce time, material, and waste to extend automation beyond the selection process by application of conventional microarray machinery. We were able to express recombinant antibody fragments in a single inoculation and expression step and subjected them without purification directly to an automated high-throughput screening procedure based on the multiple spotting technique (MIST). While obtaining comparable sensitivities to enzyme-linked immunosorbent assays, we minimized manual interaction steps and streamlined the technique to be accessible within the automated selection procedure.
Publisher: Public Library of Science (PLoS)
Date: 13-04-2015
Location: Australia
No related grants have been discovered for Gregor Kijanka.