Armes J.E.,Materials Health Services |
Davies C.M.,Materials Health Services |
Wallace S.,Materials Health Services |
Taheri T.,Materials Health Services |
And 3 more authors.
Pathology | Year: 2013
Aims: To examine AGR2 expression in ovarian epithelial tumours and its potential role as a prognostic biomarker. Methods: Tissue microarray technology and immunohistochemistry were used to investigate AGR2 expression in ovarian epithelial tumours and in non-neoplastic ovarian epithelium. For the carcinomas, the expression data were correlated with clinicopathological features and disease outcome. Results: AGR2 was expressed in all benign, borderline and malignant mucinous tumours and in a high proportion of endometrioid carcinomas (89%). AGR2 was frequently expressed in benign and borderline serous tumours (76% and 95%, respectively), but less commonly expressed in serous carcinomas (19%, p<0.001). AGR2 expression in ovarian carcinomas was inversely correlated with p53 and p16 expression (p=0.002 and p<0.001, respectively), and independent of CA125 expression. AGR2 expression was more common in carcinomas which presented with earlystage compared with late-stage disease (p=0.009) and AGR2 was expressed in carcinomas with better outcome (22% relapse rate of AGR2 positive cancers compared with 74% relapse rate for AGR2 negative cancers, p=0.001). Conclusion: Our findings indicate that AGR2 expression is associated with mucinous carcinomas and their precursor lesions and endometrioid cancers. Additionally, AGR2 may be an important prognostic biomarker of ovarian cancer. © 2012 Royal College of Pathologists of Australasia.
Edgell T.A.,HealthLinx Ltd. |
Barraclough D.L.,University of Liverpool |
Rajic A.,HealthLinx Ltd. |
Dhulia J.,HealthLinx Ltd. |
And 7 more authors.
Clinical Science | Year: 2010
Ovarian cancer is often asymptomatic and is diagnosed at an advanced stage with poor survival rates, thus there is an urgent need to develop biomarkers for earlier detection of ovarian cancer. In the present study, we demonstrate for the first time that the previously reported metastasis-inducing protein AGR2 (anterior gradient protein 2) can be detected in the blood of ovarian cancer patients. Using a newly developed ELISA, we show significantly increased concentrations of AGR2 protein in plasma from cancer patients relative to normal controls. Plasma AGR2 concentrations were highest in stages II and III ovarian cancer patients and were similarly elevated in patients with both serous and non-serous tumours. The identification of elevated plasma concentrations of AGR2 may provide a useful biomarker to aid in the discrimination of normal and ovarian cancer patients particularly when used in combination with CA125. © The Authors.
Inex Innovations Exchange Pte Ltd and Healthlinx Ltd | Date: 2012-01-03
Medical and diagnostic testing apparatus, instruments and articles, namely, a multimarker assay test for the detection of ovarian cancer.
Rice G.E.,HealthLinx Ltd. |
Edgell T.A.,HealthLinx Ltd. |
Autelitano D.J.,HealthLinx Ltd.
Journal of Experimental and Clinical Cancer Research | Year: 2010
The aims of this study were: to characterise and compare plasma concentrations of midkine (MDK) in normal healthy women with concentrations observed in women with ovarian cancer; and to establish and compare the performance of MDK with that of anterior gradient 2 protein (AGR2) and CA125 in the development of multi-analyte classification algorithms for ovarian cancer. Median plasma concentrations of immunoreactive MDK, AGR2 and CA125 were significantly greater in the case cohort (909 pg/ml, 765 pg/ml and 502 U/ml, respectively n = 46) than in the control cohort (383 pg/ml, 188 pg/ml and 13 U/ml, respectively n = 61) (p < 0.001). The area under the receiver operator characteristic curve (AUC) for MDK and AGR2 was not significantly different (0.734 0.046 and 0.784 0.049, respectively, mean SE) but were both significantly less than the AUC for CA125 (0.934 0.030, p < 0.003). When subjected to stochastic gradient boosted logistic regression modelling, the AUC of the multi-analyte panel (MDK, AGR2 and CA125, 0.988 0.010) was significantly greater than that of CA125 alone (0.934 0.030, p = 0.035). The sensitivity and specificity of the multi-analyte algorithm were 95.2 and 97.7%, respectively. Within the study cohort, CA125 displayed a sensitivity and specificity of 87.0 and 94.6%, respectively. The data obtained in this study confirm that both MDK and AGR2 individually display utility as biomarkers for ovarian cancer and that in a multi-analyte panel significantly improve the diagnostic utility of CA125 in symptomatic women. © 2010 Rice et al; licensee BioMed Central Ltd.
Autelitano D.J.,Healthlinx Ltd |
Raineri L.,Healthlinx Ltd |
Knight K.,Healthlinx Ltd |
Bannister K.,Healthlinx Ltd |
Rice G.E.,University of Queensland
Journal of Translational Medicine | Year: 2012
Background: Concomitant with the development of in vitro diagnostic multivariate index assays (IVDMIAs) to improve the diagnostic efficiency of ovarian cancer detection is the need to identify appropriate biostatistical approaches to assess improvements in risk predication. In this study, we assessed the utility of three different approaches for comparing diagnostic efficiency of an ovarian cancer multivariate assay in a retrospective case - control phase 2 biomarker trial. The control cohort included both disease-free women and women with benign gynecological conditions to more accurately reflect the target population of symptomatic women.Methods: The study cohort comprised plasma samples from 244 healthy controls, 223 women with benign gynecological conditions, 53 borderline ovarian cancer cases and 222 women with malignant epithelial ovarian cancer. A multivariate classification model was developed that incorporated plasma concentrations of CA125, C-reactive protein (CRP), serum amyloid-A (SAA), interleukin-6 (IL6) and interleukin-8 (IL8) that were measured using in vitro diagnostics assays on medical device approved clinical analysers. The posterior probability values derived from the implemented algorithm were used for comparisons of the diagnostic performance between the multianalyte panel and CA125 using multiple methods; area under the curve (AUC) of the receiver operating characteristics curve, integrated discrimination improvement (IDI) and net reclassification improvement (NRI).Results: Each of the biomarkers displayed significantly elevated plasma concentrations in malignant ovarian cancer patients compared with either benign or control subjects. For the discrimination of borderline and malignant ovarian cancer from control and benign subjects, the multivariate classification model showed a significantly greater AUC than that for CA125 alone (88.4% versus 84.3%, respectively, p < 0.001). At a posterior probability threshold of 0.5, the IVDMIA delivered a specificity of 92.3% and a sensitivity of 76.4%. When set at a specificity of 95%, the multimarker diagnostic delivered a sensitivity of 69.5% compared with 62.5% for CA125. Enhanced diagnostic performance of the IVDMIA over the use of CA125 alone was confirmed statistically by alternative comparisons using IDI and NRI.Conclusions: This study confirms in an independent sample set that a blood-based multianalyte assay has significant advantages over CA125 for distinguishing symptomatic women with borderline and malignant ovarian cancer from controls or those with benign disease. © 2012 Autelitano et al; licensee BioMed Central Ltd.
Edgell T.,HealthLinx Ltd |
Martin-Roussety G.,HealthLinx Ltd |
Barker G.,Baker Medical Research Institute |
Autelitano D.J.,HealthLinx Ltd |
And 5 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2010
Purpose: The primary hypothesis to be tested in this study was that the diagnostic performance (as assessed by the area under the receiver operator characteristic curve, AUC) of a multianalyte panel to correctly identify women with ovarian cancer was significantly greater than that for CA-125 alone. Methods: A retrospective, case-control study (phase II biomarker trial) was conducted that involved 362 plasma samples obtained from women with ovarian cancer (n = 150) and healthy controls (n = 212). A multivariate classification model was developed that incorporated five biomarkers of ovarian cancer, CA-125; C-reactive protein (CRP); serum amyloid A (SAA); interleukin 6 (IL-6); and interleukin 8 (IL-8) from a modelling cohort (n = 179). The performance of the model was evaluated using an independent validation cohort (n = 183) and compared with of CA-125 alone. Results: The AUC for the biomarker panel was significantly greater than the AUC for CA-125 alone for a validation cohort (p < 0.01) and an early stage disease cohort (i.e. Stages I and II; p < 0.01). At a threshold of 0.3, the sensitivity and specificity of the multianalyte panel were 94.1 and 91.3%, respectively, for the validation cohort and 92.3 and 91.3%, respectively for an early stage disease cohort. Conclusions: The use of a panel of plasma biomarkers for the identification of women with ovarian cancer delivers a significant increase in diagnostic performance when compared to the performance of CA-125 alone. © 2010 Springer-Verlag.
Rajic A.,HealthLinx Ltd |
Dhulia J.,HealthLinx Ltd |
Hosking C.G.,HealthLinx Ltd |
Autelitano D.J.,HealthLinx Ltd
International Dairy Journal | Year: 2010
A novel, highly enriched bioactive bovine whey protein fraction (LAP001) was shown to directly inhibit adipocyte differentiation and lipid accumulation over a wide concentration range. Further in vitro characterisation showed that LAP001 suppressed induction of PPARγ expression in a dose-dependent manner. Administration of LAP001 to rats maintained on a high-fat diet over a 28-day period led to a significant reduction in weight gain and prevented a rise in plasma glucose concentration without significantly affecting plasma insulin concentrations. In additional, there was a beneficial modulation of major serum adipokines (decreased leptin and increased adiponectin concentration) that impact on metabolic parameters related to obesity. As such, LAP001 represents a novel and potentially attractive dairy-derived fraction for further development and testing as an agent that can inhibit weight gain, and aid in the control of obesity-related metabolic disorders. © 2010 Elsevier Ltd. All rights reserved.
HEALTHLINX Ltd | Date: 2010-06-11
This invention relates to methods of analysis, and in particular to methods for the preliminary fractionation of samples in which low abundance molecules of interest, for example proteins, polysaccharides or fatty acids, are present together with more abundant molecules of little or no interest. In particular, the invention relates to methods of depletion of high abundance proteins from biological samples. Products and kits for use in the method are also disclosed, and form part of the invention. In one aspect, the invention provides a method of depleting a high-abundance molecule from a biological sample, comprising the steps of a) subjecting the sample to affinity depletion using an affinity support with high affinity for a high abundance molecule, and/or b) immunodepletion using an affinity support coupled to an antibody directed against whole or previously fractionated plasma or serum.
Healthlinx Ltd | Date: 2014-02-14
The present invention relates generally to the field of diagnostic and prognostic assays for a gynecological condition. More particularly, the present invention provides an assay for diagnosing the presence of or a risk of having a gynecological cancer or a sub-type thereof or a stage of the cancer or complications arising therefrom or other gynecological condition including an inflammatory disorder.
HEALTHLINX Ltd | Date: 2014-08-06
The present invention relates generally to the field of obesity and complications arising therefrom and in particular to the control of obesity by inhibiting adipogenesis and related processes.