2023 |
Burns GL, Potter M, Mathe A, Bruce J, Minahan K, Barnes JL, et al., 'TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia.', Clin Transl Gastroenterol, 14 e00638 (2023) [C1]
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Nova |
2022 |
Burns GL, Bruce JK, Minahan K, Mathe A, Fairlie T, Cameron R, et al., 'Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia.', Front Immunol, 13 1051632 (2022) [C1]
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Nova |
2021 |
Pariyar M, Johns A, Thorne RF, Scott RJ, Avery-Kiejda KA, 'Copy number variation in triple negative breast cancer samples associated with lymph node metastasis', Neoplasia (United States), 23 743-753 (2021) [C1]
Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This stud... [more]
Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs. CNV-associated genes were analyzed using GO-enrichment and Pathway analysis. The prognostic role for genes showing CNV-based changes in messenger RNA expression was determined using the Kaplan-Meier plotter database. For the IDCs, there were a number of variations that were common in both the study and independent cohorts in the amplified regions of 1q, 8q, 19 (p and q), 2p, 5p and the deleted regions in 8p followed by 5q, and 19p. The most frequently amplified regions in the LNmets of the study cohort were 4q28.3, 2p, 3q24, 1q21.2, 10p, 12p11.1, 8q, 20p11.22-20p11.21, 21q22.13, 6p22.1 and the most frequently deleted regions were in 1p36.23, 4q21.1 and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with LNmets. The LNmet-associated genes were highly enriched for ¿regulation of complement activation,¿ ¿regulation of protein activation cascade,¿ ¿regulation of humoral immune response,¿ ¿oxytocin signalling pathway,¿ and ¿TRAIL binding¿ pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse-free survival. This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.
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2021 |
Goggins BJ, Minahan K, Sherwin S, Soh WS, Pryor J, Bruce J, et al., 'Pharmacological HIF-1 stabilization promotes intestinal epithelial healing through regulation of a-integrin expression and function', AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 320 G420-G438 (2021) [C1]
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Nova |
2020 |
Liu G, Baird AW, Parsons MJ, Fan K, Skerrett-Byrne DA, Nair PM, et al., 'Platelet activating factor receptor acts to limit colitis-induced liver inflammation', FASEB JOURNAL, 34 7718-7732 (2020) [C1]
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Nova |
2020 |
Carroll GM, Burns GL, Petit JA, Walker MM, Mathe A, Smith SR, et al., 'Does postoperative inflammation or sepsis generate neutrophil extracellular traps that influence colorectal cancer progression? A systematic review', Surgery Open Science, 2 57-69 (2020) [C1]
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Nova |
2019 |
Nixon B, De Iuliis GN, Hart HM, Zhou W, Mathe A, Bernstein IR, et al., 'Proteomic profiling of mouse epididymosomes reveals their contributions to post-testicular sperm maturation', Molecular and Cellular Proteomics, 18 S91-S108 (2019) [C1]
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Nova |
2019 |
Arthurs AL, Lumbers ER, Delforce SJ, Mathe A, Morris BJ, Pringle KG, 'The role of oxygen in regulating microRNAs in control of the placental renin-angiotensin system.', Mol Hum Reprod, 25 206-217 (2019) [C1]
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Nova |
2019 |
Liu G, Mateer SW, Hsu A, Goggins BJ, Tay H, Mathe A, et al., 'Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome', Mucosal Immunology, 12 862-873 (2019) [C1]
Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patient... [more]
Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patients. In animal models of colitis, pulmonary inflammation is driven by neutrophilic infiltrations, primarily in response to the systemic bacteraemia and increased bacterial load in the lungs. Platelet activating factor receptor (PAFR) plays a critical role in regulating pulmonary responses to infection in conditions, such as chronic obstructive pulmonary disease and asthma. We investigated the role of PAFR in pulmonary EIMs of IBD, using dextran sulfate sodium (DSS) and anti-CD40 murine models of colitis. Both models induced neutrophilic inflammation, with increased TNF and IL-1ß levels, bacterial load and PAFR protein expression in mouse lungs. Antagonism of PAFR decreased lung neutrophilia, TNF, and IL-1ß in an NLRP3 inflammasome-dependent manner. Lipopolysaccharide from phosphorylcholine (ChoP)-positive bacteria induced NLRP3 and caspase-1 proteins in human alveolar epithelial cells, however antagonism of PAFR prevented NLRP3 activation by ChoP. Amoxicillin reduced bacterial populations in the lungs and reduced NLRP3 inflammasome protein levels, but did not reduce PAFR. These data suggest a role for PAFR in microbial pattern recognition and NLRP3 inflammasome signaling in the lung.
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Nova |
2018 |
Wang Y, Lumbers ER, Arthurs AL, de Meaultsart CC, Mathe A, Avery-Kiejda KA, et al., 'Regulation of the human placental (pro)renin receptor-prorenin-angiotensin system by microRNAs.', Molecular human reproduction, 24 453-464 (2018) [C1]
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Nova |
2018 |
Mateer SW, Mathe A, Bruce J, Liu G, Maltby S, Fricker M, et al., 'IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis', American Journal of Pathology, 188 1625-1639 (2018) [C1]
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathol... [more]
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathology, most commonly neutrophil-mediated diseases, such as bronchiectasis and chronic bronchitis. Using murine models of colitis, we aimed to identify the immune mechanisms driving pulmonary manifestations of IBD. We found increased neutrophil numbers in lung tissue associated with the pulmonary vasculature in both trinitrobenzenesulfonic acid¿ and dextran sulfate sodium¿induced models of colitis. Analysis of systemic inflammation identified that neutrophilia was associated with bacteremia and pyrexia in animal models of colitis. We further identified IL-6 as a systemic mediator of neutrophil recruitment from the bone marrow of dextran sulfate sodium animals. Functional inhibition of IL-6 led to reduced systemic and pulmonary neutrophilia, but it did not attenuate established colitis pathology. These data suggest that systemic bacteremia and pyrexia drive IL-6 secretion, which is a critical driver for pulmonary manifestation of IBD. Targeting IL-6 may reduce neutrophil-associated extraintestinal manifestations in IBD patients.
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Nova |
2017 |
Avery-Kiejda KA, Mathe A, Scott RJ, 'Genome-wide miRNA, gene and methylation analysis of triple negative breast cancer to identify changes associated with lymph node metastases', Genomics Data, 14 1-4 (2017) [C1]
Triple negative breast cancer (TNBC) is a particularly important breast cancer subtype with an aggressive clinical phenotype that is associated with a higher likelihood of metasta... [more]
Triple negative breast cancer (TNBC) is a particularly important breast cancer subtype with an aggressive clinical phenotype that is associated with a higher likelihood of metastasis. This subtype is characterized by an absence of the estrogen (ER) and progesterone (PR) receptors, as well as the human epidermal growth factor receptor 2 (HER2/HER neu). The absence of the three receptors significantly reduces targeted treatment options for patients with TNBC and as such, there is an urgent need to identify novel treatment targets. Here, we provide detailed information regarding the design of a multi-platform dataset that describes genome-wide assessment of miRNA (assessed by microarray, GSE38167) and gene expression (assessed by microarray, GSE61723), as well as methylation (assessed by Illumina HM450K BeadChip, GSE78751) in TNBCs, matched normal adjacent tissues and matched lymph node metastases. The use of this multi-platform dataset is likely to uncover novel markers and key pathways involved in progression to lymph node metastasis in TNBC.
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Nova |
2016 |
Mathe A, Wong-Brown M, Locke WJ, Stirzaker C, Braye SG, Forbes JF, et al., 'DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients', SCIENTIFIC REPORTS, 6 (2016) [C1]
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Nova |
2015 |
Mathe A, Scott RJ, Avery-Kiejda KA, 'MiRNAs and other epigenetic changes as biomarkers in triple negative breast cancer', International Journal of Molecular Sciences, 16 28347-28376 (2015) [C1]
Triple negative breast cancer (TNBC) is characterised by the lack of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2). Since it cannot be... [more]
Triple negative breast cancer (TNBC) is characterised by the lack of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2). Since it cannot be treated by current endocrine therapies which target these receptors and due to its aggressive nature, it has one of the worst prognoses of all breast cancer subtypes. The only treatments remain chemo- and/or radio-therapy and surgery and because of this, novel biomarkers or treatment targets are urgently required to improve disease outcomes. MicroRNAs represent an attractive candidate for targeted therapies against TNBC, due to their natural ability to act as antisense interactors and regulators of entire gene sets involved in malignancy and their superiority over mRNA profiling to accurately classify disease. Here we review the current knowledge regarding miRNAs as biomarkers in TNBC and their potential use as therapeutic targets in this disease. Further, we review other epigenetic changes and interactions of these changes with microRNAs in this breast cancer subtype, which may lead to the discovery of new treatment targets for TNBC.
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Nova |
2015 |
Mathe A, Wong-Brown M, Morten B, Forbes JF, Braye SG, Avery-Kiejda KA, Scott RJ, 'Novel genes associated with lymph node metastasis in triple negative breast cancer', Scientific Reports, 5 (2015) [C1]
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and no targeted treatments. TNBC patients are more likely to develop met... [more]
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and no targeted treatments. TNBC patients are more likely to develop metastases and relapse than patients with other breast cancer subtypes. We aimed to identify TNBC-specific genes and genes associated with lymph node metastasis, one of the first signs of metastatic spread. A total of 33 TNBCs were used; 17 of which had matched normal adjacent tissues available, and 15 with matched lymph node metastases. Gene expression microarray analysis was used to reveal genes that were differentially expressed between these groups. We identified and validated 66 genes that are significantly altered when comparing tumours to normal adjacent samples. Further, we identified 83 genes that are associated with lymph node metastasis and correlated these with miRNA-expression. Pathway analysis revealed their involvement in DNA repair, recombination and cell death, chromosomal instability and other known cancer-related pathways. Finally, four genes were identified that were specific for TNBC, of which one was associated with overall survival. This study has identified novel genes involved in LN metastases in TNBC and genes that are TNBC specific that may be used as treatment targets or prognostic indicators in the future.
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Nova |
2014 |
Avery-Kiejda KA, Braye SG, Mathe A, Forbes JF, Scott RJ, 'Decreased expression of key tumour suppressor microRNAs is associated with lymph node metastases in triple negative breast cancer', BMC Cancer, 14 (2014) [C1]
Background: Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-associated death rates. Triple negative breast cancers represent... [more]
Background: Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-associated death rates. Triple negative breast cancers represent an important subtype that have an aggressive clinical phenotype, are associated with a higher likelihood of metastasis and are not responsive to current targeted therapies. miRNAs have emerged as an attractive candidate for molecular biomarkers and treatment targets in breast cancer, but their role in the progression of triple negative breast cancer remains largely unexplored.Methods: This study has investigated miRNA expression profiles in 31 primary triple negative breast cancer cases and in 13 matched lymph node metastases compared with 23 matched normal breast tissues to determine miRNAs associated with the initiation of this disease subtype and those associated with its metastasis.Results: 71 miRNAs were differentially expressed in triple negative breast cancer, the majority of which have previously been associated with breast cancer, including members of the miR-200 family and the miR-17-92 oncogenic cluster, suggesting that the majority of miRNAs involved in the initiation of triple negative breast cancer are not subtype specific. However, the repertoire of miRNAs expressed in lymph node negative and lymph node positive triple negative breast cancers were largely distinct from one another. In particular, miRNA profiles associated with lymph node negative disease tended to be up-regulated, while those associated with lymph node positive disease were down-regulated and largely overlapped with the profiles of their matched lymph node metastases. From this, 27 miRNAs were identified that are associated with metastatic capability in the triple negative breast cancer subtype.Conclusions: These results provide novel insight into the repertoire of miRNAs that contribute to the initiation of and progression to lymph node metastasis in triple negative breast cancer and have important implications for the treatment of this breast cancer subtype. © 2014 Avery-Kiejda et al.; licensee BioMed Central Ltd.
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Nova |
2014 |
Avery-Kiejda KA, Morten B, Wong-Brown MW, Mathe A, Scott RJ, 'The relative mRNA expression of p53 isoforms in breast cancer is associated with clinical features and outcome.', Carcinogenesis, 35 586-596 (2014) [C1]
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Nova |