25 research outputs found
Characterising pancreatic organoids from hereditary pancreatitis patients and their viability as a disease model
No full textAbstract #265.8James Zuiani, Griffith Perkins, Denghao Wu, Christopher Drogemuller, Toby Coate
118.9: Growing pancreatic organoids for hereditary pancreatitis
No full textAbstract - 118.9James Zuiani, Denghao Wu, Griffith Perkins, Shane Grey, Christopher Drogemuller, Patrick Toby Coate
337.2: The Epidemiology of Hereditary Pancreatitis in Australia and its effect on patient of Total Pancreatectomy with Islet Auto-Transplantation (TPIAT).
No full textAbstract - 337.2Denghao Wu, James Zuiani, Christopher Drogemuller, Sunita De Sousa, David Adelson, David J Torpy, Patrick Toby H Coate
South Australian experience with pediatric total pancreatectomy and islet autotransplantation for PRSS1-associated hereditary pancreatitis
No full textPerspectivesJessica Eldredge, Michael R Couper, David J Moore, Sanjeev Khurana, John WC Chen, Jennifer J Couper, Christopher J Drogemuller, Toni Radford, Thomas W Kay, Tom Loudovaris, Michael Wilks, Patrick T Coates, Richard TL Coupe
Concurrent vaccination of kidney transplant recipients and close household cohabitants against COVID-19
No full textResearch LetterGriffith B. Perkins ... Cheng Sheng Chai ... Arthur Eng Lip Yeow ... Zahraa Al-Delfi ... Pablo Garcia-Valtanen ... Makutiro G. Masavuli ... Branka Grubor-Bauk ... Christopher J. Drogemuller ... P. Toby Coates ... Pravin Hissaria ... Simon C. Barry ... et al
In vitro covalent binding of Nafenopin-CoA to human liver proteins
No full textEndogenous fatty acyl-CoAs play an important role in the acylation of proteins. A number of xenobiotic carboxylic acids are able to mimic fatty acids, forming CoA conjugates and acting as substrates in pathways of lipid metabolism. In this study nafenopin, a substrate for human hepatic fatty acid-CoA ligases, was chosen as a model compound to study xenobiotic acylation of human liver proteins. (3)H-nafenopin (+/- unlabeled palmitate) or (14)C-palmitate (+/- unlabeled nafenopin) were incubated for up to 120 min at 37 degrees C with ATP, CoA, and homogenate protein (1 mg/ml) from four individual human livers. Nafenopin covalently bound to proteins was detectable in all human livers and increased with time. Nafenopin adduct formation was directly proportional to nafenopin-CoA formation (r = 0.985, p 100 and 50-100 kDa, respectively. Protein acylation by palmitate was also demonstrated. Palmitate significantly inhibited nafenopin-CoA formation by 29% but had no effect on nafenopin-CoA-mediated protein acylation. In contrast, nafenopin significantly inhibited protein palmitoylation by palmitoyl-CoA. This is the first study to demonstrate a direct relationship between xenobiotic-CoA formation, acylation of human liver proteins, and inhibition of endogenous palmitoylation. The ability of xenobiotics to acylate tissue proteins may have important biological consequences including perturbation of endogenous regulation of protein localization and function.Sallustio, Benedetta C. ; Nunthasomboon, Sirimas ; Drogemuller, Christopher J. ; Knights, Kathleen M
Phenoxodiol, an experimental anticancer drug, shows potent antiangiogenic properties in addition to its antitumour effects
No full textPhenoxodiol (2H-1-benzopyran-7-0,1, 3-[4-hydroxyphenyl], PXD) is a synthetic analogue of the naturally-occurring plant isoflavone and anticancer agent, genistein. PXD directly induces mitotic arrest and apoptosis in most cancer cells and is currently undergoing clinical trials, as a chemotherapeutic in ovarian and prostate cancers. We show here that PXD also exhibits potent antiangiogenic properties. Thus, it inhibited endothelial cell proliferation, migration and capillary tube formation and inhibited expression of the matrix metalloproteinase MMP-2, a major matrix degrading enzyme. Importantly, we demonstrate that PXD is functional in vivo since it inhibited the extent of capillary tube invasion in an in vivo model of angiogenesis. We show that phenoxodiol inhibits hallmarks of endothelial cell activation, namely TNF or IL-1 induced E-selectin and VCAM-1 expression and IL-8 secretion. However, PXD had no effect on unstimulated endothelial cells. We also describe that PXD inhibits the lipid kinase sphingosine kinase, which recently has been implicated in endothelial cell activation and angiogenesis as well as oncogenesis. Thus, our results suggest that PXD may be an effective anticancer drug targeting the two drivers of tumour growth--the proliferation of the tumour cells themselves and the angiogenic and inflammatory stimulation of the vasculature.Gamble, Jennifer R. ; Xia, Pu ; Hahn, Christopher N. ; Drew, Jenny J. ; Drogemuller, Christopher J. ; Brown, David ; Vadas, Mathew A
Incorporation of endothelial progenitor cells into mosaic pseudoislets
No full textData source: Supplemental material, http://www.tandfonline.com/doi/suppl/10.4161/isl.3.3.15392?scroll=top
Link to a related website: https://www.tandfonline.com/doi/pdf/10.4161/isl.3.3.15392?needAccess=true, Open Access via UnpaywallPancreatic islet transplantation is limited by extensive apoptosis and suboptimal function of the implanted islets in the longer term. Endothelial progenitor cells (EPC) may be ideal for enhancing both the survival and function of transplanted islets. Here, we describe for the first time the in vitro formation of rat mosaic pseudoislets comprised of pancreatic β-cells with interspersed vasculogenic EPC. Bone marrow-derived EPC displayed a similar phenotype to non-adherent EPC, recently described in the human and mouse. Mosaic pseudoislet formation was enhanced by the use of an embryoid body forming medium (BPEL) and a spin protocol. Mosaic pseudoislets maintained function in vitro and may represent an enhanced cell therapy delivery approach to enhance the survival and revascularisation of transplanted islets.Daniella Penko, Daisy Mohanasundaram, Shaundeep Sen, Christopher Drogemuller, Claire Mee, Claudine S. Bonder, P. Toby H. Coates and Claire F. Jessu
A combinatorial protein microarray for probing materials interaction with pancreatic islet cell populations
No full textPancreatic islet transplantation has become a recognized therapy for insulin-dependent diabetes mellitus. During isolation from pancreatic tissue, the islet microenvironment is disrupted. The extracellular matrix (ECM) within this space not only provides structural support, but also actively signals to regulate islet survival and function. In addition, the ECM is responsible for growth factor presentation and sequestration. By designing biomaterials that recapture elements of the native islet environment, losses in islet function and number can potentially be reduced. Cell microarrays are a high throughput screening tool able to recreate a multitude of cellular niches on a single chip. Here, we present a screening methodology for identifying components that might promote islet survival. Automated fluorescence microscopy is used to rapidly identify islet derived cell interaction with ECM proteins and immobilized growth factors printed on arrays. MIN6 mouse insulinoma cells, mouse islets and, finally, human islets are progressively screened. We demonstrate the capability of the platform to identify ECM and growth factor protein candidates that support islet viability and function and reveal synergies in cell response.Bahman Delalat, Darling M. Rojas-Canales, Soraya Rasi Ghaemi, MichaelaWaibel, Frances J. Harding, Daniella Penko, Christopher J. Drogemuller, Thomas Loudovaris, Patrick T. H. Coates and Nicolas H. Voelcke
Endothelial progenitor cells enhance islet engraftment, influence beta-cell function and modulate islet connexin 36 expression
No full textThe success of pancreatic islet transplantation is limited by delayed engraftment and suboptimal function in the longer term. Endothelial progenitor cells (EPCs) represent a potential cellular therapy that may improve the engraftment of transplanted pancreatic islets. In addition, EPCs may directly affect the function of pancreatic β-cells. The objective of this study was to examine the ability of EPCs to enhance pancreatic islet transplantation in a murine syngeneic marginal mass transplant model and to examine the mechanisms through which this occurs. We found that cotransplanted EPCs improved the cure rate and initial glycemic control of transplanted islets. Gene expression data indicate that EPCs, or their soluble products, modulate the expression of the β-cell surface molecule connexin 36 and affect glucose-stimulated insulin release in vitro. In conclusion, EPCs are a promising candidate for improving outcomes in islet transplantation, and their mechanisms of action warrant further study.Daniella Penko, Darling Rojas-Canales, Daisy Mohanasundaram, Heshan S. Peiris, Wai Y. Sun, Christopher J. Drogemuller, Damien J. Keating, P. Toby H. Coates, Claudine S. Bonder, and Claire F. Jessu
