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546 results on '"Gobe, Glenda C."'

9. PAR2 activation on human tubular epithelial cells engages converging signaling pathways to induce an inflammatory and fibrotic milieu.

Author

Vesey, David A., Iyer, Abishek, Owen, Evan, Kamato, Danielle, Johnson, David W., Gobe, Glenda C., Fairlie, David P., and Nikolic-Paterson, David J.

Subjects
EPITHELIAL cells, PRIMARY cell culture, G protein coupled receptors, CELLULAR signal transduction, HUMAN cell culture
Abstract

Key features of chronic kidney disease (CKD) include tubulointerstitial inflammation and fibrosis. Protease activated receptor-2 (PAR2), a G-protein coupled receptor (GPCR) expressed by the kidney proximal tubular cells, induces potent proinflammatory responses in these cells. The hypothesis tested here was that PAR2 signalling can contribute to both inflammation and fibrosis in the kidney by transactivating known disease associated pathways. Using a primary cell culture model of human kidney tubular epithelial cells (HTEC), PAR2 activation induced a concentration dependent, PAR2 antagonist sensitive, secretion of TNF, CSF2, MMP-9, PAI-1 and CTGF. Transcription factors activated by the PAR2 agonist 2F, including NFκB, AP1 and Smad2, were critical for production of these cytokines. A TGF-β receptor-1 (TGF-βRI) kinase inhibitor, SB431542, and an EGFR kinase inhibitor, AG1478, ameliorated 2F induced secretion of TNF, CSF2, MMP-9, and PAI-1. Whilst an EGFR blocking antibody, cetuximab, blocked PAR2 induced EGFR and ERK phosphorylation, a TGF-βRII blocking antibody failed to influence PAR2 induced secretion of PAI-1. Notably simultaneous activation of TGF-βRII (TGF-β1) and PAR2 (2F) synergistically enhanced secretion of TNF (2.2-fold), CSF2 (4.4-fold), MMP-9 (15-fold), and PAI-1 (2.5-fold). In summary PAR2 activates critical inflammatory and fibrotic signalling pathways in human kidney tubular epithelial cells. Biased antagonists of PAR2 should be explored as a potential therapy for CKD. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Incident Chronic Kidney Disease After Radical Nephrectomy for Renal Cell Carcinoma

Author

Giles, Graham, White, Victoria, Coory, Michael, Millar, Jeremy, Bolton, Damien, Davis, Ian, Winship, Ingrid, Roos, Ian, Southey, Melissa, Severi, Gianlucca, Prince, Miles, Harrison, Simon, Seymour, John, Jefford, Michael, Hill, David, Kay, Anne, Ellis, Robert J., White, Victoria M., Bolton, Damien M., Coory, Michael D., Davis, Ian D., Francis, Ross S., Giles, Graham G., Gobe, Glenda C., Marco, David J.T., Neale, Rachel E., Wood, Simon T., and Jordan, Susan J.

Published
2019
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36. Evidence Linking Cadmium Exposure and β 2 -Microglobulin to Increased Risk of Hypertension in Diabetes Type 2.

Author

Yimthiang, Supabhorn, Pouyfung, Phisit, Khamphaya, Tanaporn, Vesey, David A., Gobe, Glenda C., and Satarug, Soisungwan

Subjects
TYPE 2 diabetes, SYSTOLIC blood pressure, BLOOD pressure, CADMIUM, HYPERTENSION, CHRONIC kidney failure
Abstract

The most common causes of chronic kidney disease, diabetes, and hypertension are significant public health issues worldwide. Exposure to the heavy metal pollutant, cadmium (Cd), which is particularly damaging to the kidney, has been associated with both risk factors. Increased levels of urinary β2-microglobulin (β2M) have been used to signify Cd-induced kidney damage and circulating levels have been linked to blood pressure control. In this study we investigated the pressor effects of Cd and β2M in 88 diabetics and 88 non-diabetic controls, matched by age, gender and locality. The overall mean serum β2M was 5.98 mg/L, while mean blood Cd and Cd excretion normalized to creatinine clearance (Ccr) as ECd/Ccr were 0.59 µg/L and 0.0084 µg/L of filtrate (0.95 µg/g creatinine), respectively. The prevalence odds ratio for hypertension rose by 79% per every ten-fold increase in blood Cd concentration. In all subjects, systolic blood pressure (SBP) showed positive associations with age (β = 0.247), serum β2M (β = 0.230), and ECd/Ccr (β = 0.167). In subgroup analysis, SBP showed a strong positive association with ECd/Ccr (β = 0.303) only in the diabetic group. The covariate-adjusted mean SBP in the diabetics of the highest ECd/Ccr tertile was 13.8 mmHg higher, compared to the lowest tertile (p = 0.027). An increase in SBP associated with Cd exposure was insignificant in non-diabetics. Thus, for the first time, we have demonstrated an independent effect of Cd and β2M on blood pressure, thereby implicating both Cd exposure and β2M in the development of hypertension, especially in diabetics. [ABSTRACT FROM AUTHOR]

Published
2023
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37. Two-dimensional correlated spectroscopy distinguishes clear cell renal cell carcinoma from other kidney neoplasms and non-cancer kidney

Author

Del Vecchio, Sharon J., primary, Urquhart, Aaron J., additional, Dong, Xin, additional, Ellis, Robert J., additional, Ng, Keng Lim, additional, Samaratunga, Hemamali, additional, Gustafson, Sonja, additional, Galloway, Graham J., additional, Gobe, Glenda C., additional, Wood, Simon, additional, and Mountford, Carolyn E., additional

Published
2022
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45. Tumor size and postoperative kidney function following radical nephrectomy

Author

Ellis,Robert J, White,Victoria M, Bolton,Damien M, Coory,Michael D, Davis,Ian D, Francis,Ross S, Giles,Graham G, Gobe,Glenda C, Neale,Rachel E, Wood,Simon T, and Jordan,Susan J

Subjects
renal cell carcinoma, glomerular filtration rate, tumor size, kidney cancer, Clinical Epidemiology, selection bias, Original Research, living kidney donors
Abstract

Robert J Ellis,1–4 Victoria M White,5,6 Damien M Bolton,7,8 Michael D Coory,8 Ian D Davis,9,10 Ross S Francis,2–4 Graham G Giles,5,8 Glenda C Gobe,3,4 Rachel E Neale,1 Simon T Wood,3–4,10 Susan J Jordan1,31Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 2Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD, Australia; 3Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia; 4Kidney Disease Research Collaborative, Translational Research Institute, Brisbane, QLD, Australia; 5Cancer Council Victoria, Melbourne, VIC, Australia; 6School of Psychology, Deakin University, Melbourne, VIC, Australia; 7Department of Urology, Austin Health, Melbourne, VIC, Australia; 8Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia; 9Eastern Health Clinical School, Monash University and Eastern Health, Melbourne, VIC, Australia; 10Department of Urology, Princess Alexandra Hospital, Melbourne, VIC, AustraliaBackground: Chronic kidney disease (CKD) following nephrectomy for kidney tumors is common, and both patient and tumor characteristics may affect postoperative kidney function. Several studies have reported that surgery for large tumors is associated with a lower likelihood of postoperative CKD, but others have reported CKD to be more common before surgery in patients with large tumors.Objective: The aim of this study was to clarify inconsistencies in the literature regarding the prognostic significance of tumor size for postoperative kidney function.Study design and setting: We analyzed data from 944 kidney cancer patients managed with radical nephrectomy between January 2012 and December 2013, and 242 living kidney donors who underwent surgery between January 2011 and December 2014 in the Australian states of Queensland and Victoria. Multivariable logistic regression was used to assess the primary outcome of CKD upstaging. Structural equation modeling was used to evaluate causal models, to delineate the influence of patient and tumor characteristics on postoperative kidney function.Results: We determined that a significant interaction between age and tumor size (P=0.03) led to the observed inverse association between large tumor size and CKD upstaging, and was accentuated by other forms of selection bias. Subgrouping patients by age and tumor size demonstrated that all patients aged ≥65 years were at increased risk of CKD upstaging, regardless of tumor size. Risk of CKD upstaging was comparable between age-matched living donors and kidney cancer patients.Conclusion: Larger tumors are unlikely to confer a protective effect with respect to postoperative kidney function. The reason for the previously reported inconsistency is likely a combination of the analytical approach and selection bias.Keywords: renal cell carcinoma, glomerular filtration rate, selection bias, tumor size, kidney cancer, living kidney donors

Published
2019

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