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Port Adelaide, Australia

Hope C.M.,University of Adelaide | Grace B.S.,University of Adelaide | Pilkington K.R.,Hanson Institute | Coates P.T.,University of Adelaide | And 2 more authors.
Kidney International | Year: 2014

High regulatory T-cell (Treg) numbers predict recurrent cutaneous squamous cell carcinoma in kidney transplant recipients, and the Treg immune phenotype may identify kidney transplant recipients at risk of developing squamous cell carcinoma and/or solid-organ cancer. To investigate this, a total of 116 kidney transplant recipients, of whom 65 had current or past cancer, were immune-phenotyped and followed up prospectively for a median of 15 months. Higher Treg (CD3+CD4+FOXP3+CD25 Hi CD127 Lo) proportion and numbers significantly increased the odds of developing cancer (odds ratios (95% CI) 1.61 (1.17-2.20) and 1.03 (1.00-1.06), respectively) after adjusting for age, gender, and duration of immunosuppression. Class-switched memory B cells (CD19+CD27+IgD-) had a significant association to cancer, 1.04 (1.00-1.07). Receiver operator characteristic (ROC) curves for squamous cell carcinoma development within 100 days of immune phenotyping were significant for Tregs, memory B cells, and γδ T cells (AUC of 0.78, 0.68, and 0.65, respectively). After cancer resection, Treg, NK cell, and γδ T-cell numbers fell significantly. Immune-phenotype profiles associated with both squamous cell carcinoma and solid-organ cancer in kidney transplant recipients and depended on the presence of cancer tissue. Thus, immune profiling could be used to stratify kidney transplant recipients at risk of developing cancers to identify those who could qualify for prevention therapy. © 2014 International Society of Nephrology. Source

Helps S.C.,University of Adelaide | Thornton E.,University of Adelaide | Kleinig T.J.,University of Adelaide | Manavis J.,Hanson Institute | Vink R.,University of Adelaide
Applied Immunohistochemistry and Molecular Morphology | Year: 2012

We describe a method for the automatic, nonsubjective estimation of 3,3′ diaminobenzidine (DAB) in digital images obtained from routine central nervous system immunohistochemistry using freely available, platform-independent public domain image processing software. This technique estimates the amount of antigen visualized but does not measure antigen content directly. Combined with whole brain section high-resolution scanning, a "virtual dissection" (extracting the region of interest) makes it possible to estimate relative antigen content in either subcellular structures, specific brain regions, or in whole tissue sections at magnifications up to 40×. The digital image is processed using Ruifrok and Johnston's color deconvolution method to separate the brown DAB chromogen from the hematoxylin counterstain on a microscope slide. A monochrome image representing the DAB content is then subjected to frequency analysis using NIH-ImageJ and a weighting calculation to estimate the amount of DAB (antigen) as a dimensionless index. The method described produces results that agree with enzyme-linked immunosorbent assays, and is automatic and nonsubjective. The method could easily be adapted to other types of tissue or cell cultures. © 2012 by Lippincott Williams & Wilkins. Source

Ween M.P.,Hanson Institute | Armstrong M.A.,University of Adelaide | Oehler M.K.,Royal Adelaide Hospital | Oehler M.K.,University of Adelaide | Ricciardelli C.,University of Adelaide
Critical Reviews in Oncology/Hematology | Year: 2015

Over 80% of ovarian cancer patients develop chemoresistance which results in a lethal course of the disease. A well-established cause of chemoresistance involves the family of ATP-binding cassette transporters, or ABC transporters that transport a wide range of substrates including metabolic products, nutrients, lipids, and drugs across extra- and intra-cellular membranes. Expressions of various ABC transporters, shown to reduce the intracellular accumulation of chemotherapy drugs, are increased following chemotherapy and impact on ovarian cancer survival. Although clinical trials to date using ABC transporter inhibitors have been disappointing, ABC transporter inhibition remains an attractive potential adjuvant to chemotherapy. A greater understanding of their physiological functions and role in ovarian cancer chemoresistance will be important for the development of more effective targeted therapies. This article will review the role of the ABC transporter family in ovarian cancer progression and chemoresistance as well as the clinical attempts used to date to reverse chemoresistance. © 2015 Elsevier Ireland Ltd. Source

Brierley S.M.,University of Adelaide | Brierley S.M.,Hanson Institute
Current Opinion in Pharmacology | Year: 2012

Guanylate cyclase-C (GC-C) is a transmembrane receptor activated by bacterial heat-stable enterotoxins and by the endogenous hormones guanylin and uroguanylin. GC-C plays key roles in the regulation of intestinal fluid and electrolyte homeostasis. This is highlighted by several recently identified human mutations in GUCY2C, the gene encoding GC-C, which leads to the respective gain or loss of function of GC-C, resulting in profound effects on gastrointestinal function. However, a wealth of recent studies indicates GC-C signalling extends to a multitude of diverse additional functions. Recent pre-clinical and clinical studies demonstrate a novel first-in-class GC-C activating peptide, Linaclotide, provides effective relief from constipation and abdominal pain in patients with chronic constipation and constipation- predominant Irritable Bowel Syndrome. Accumulating evidence also suggests GC-C plays protective roles in mucosal barrier function, tissue injury and inflammation, whilst GC-C signalling is a key regulator of intestinal cell proliferation and apoptosis. Finally, recently identified extra-intestinal GC-C signalling pathways make novel contributions to the regulation of food intake and symptoms associated with Attention Deficit Hyperactivity Disorder. Consequently, these findings provide GC-C expression and its associated mutations as potential diagnostic markers for disease. They also provide current and future therapeutic potential for GC-C signalling within and outside the gastrointestinal tract. © 2012 Published by Elsevier Ltd. Source

Findlay D.M.,University of Adelaide | Atkins G.J.,Hanson Institute
Osteoporosis International | Year: 2011

It is now well accepted that the molecule receptor activator of NFκB ligand (RANKL) and osteoprotegerin play key roles in regulating physiological and pathological bone turnover. There are a large number of published reports of circulating RANKL levels in both health and pathology. However, interpretation of these data has been elusive, and the relationship between circulating RANKL and RANKL levels in bone is still not clear. This review explores this subject, documenting the possible origins of circulating RANKL and suggesting additional information that is required before serum RANKL levels can provide useful diagnostic or research information. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011. Source

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