ORCID Profile
0000-0002-5215-7208
Current Organisation
Flinders University
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Enzymes | Cell Physiology | Biochemistry and Cell Biology not elsewhere classified | Medical Physiology |
ANZSRC Socio-Economic Objective (SEO)
Nervous System and Disorders | Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified | Immune System and Allergy
Related Links
Publications
Gadolinium-Free Cardiovascular Magnetic Resonance Stress T1 Mapping in Patients With Chronic Kidney Disease
Publisher: Elsevier BV
Date: 10-2019
Prognostic Utility of Oxygen-Sensitive Cardiac Magnetic Resonance Imaging in Diabetic and Nondiabetic Chronic Kidney Disease Patients With No Known Coronary Artery Disease
Publisher: Elsevier BV
Date: 06-2019
F1000Prime Recommendation
Publisher: No publisher found
Date: 2012
Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
Publisher: Cold Spring Harbor Laboratory
Date: 03-08-2021
DOI: 10.1101/2021.07.30.21261234
Abstract: Increasing evidence suggests immune dysregulation in in iduals recovering from SARS- CoV-2 infection. We have undertaken an integrated analysis of immune responses at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 in iduals recovering from mild, moderate, severe, or critical COVID-19. Anti-Spike and anti-RBD IgG responses were largely stable up to 24wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3 + monocytes) and adaptive immune populations (T helper, T follicular helper and regulatory T cells) in COVID-19 convalescents compared to healthy controls, which were most strongly evident at 12 and 16wpi. RNA sequencing suggested ongoing immune and metabolic dysregulation in convalescents months after infection. Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some in iduals.
The Role of the Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) in Hypoxic Induction of Gene Expression
Publisher: Elsevier BV
Date: 06-1996
Lack of appropriate investigations in making a diagnosis of syndrome of inappropriate antidiuretic hormone
Publisher: Wiley
Date: 03-2017
DOI: 10.1111/IMJ.13364
Abstract: The syndrome of inappropriate antidiuretic hormone (SIADH) is reported as the most common cause of hyponatraemia. This retrospective cross-sectional study evaluated the diagnosis of SIADH in 110 hospitalised patients in an Australian tertiary hospital with reference to recently published clinical guidelines. Investigation of SIADH was incomplete in all but 20% of cases. Adrenal insufficiency and hypothyroidism were not excluded in a significant number of cases.
Iron status in patients with chronic heart failure
Publisher: Oxford University Press (OUP)
Date: 23-11-2012
F1000Prime Recommendation
Publisher: No publisher found
Date: 2011
Improving hexaminolevulinate enabled cancer cell detection in liquid biopsy immunosensors
Publisher: Springer Science and Business Media LLC
Date: 31-03-2021
DOI: 10.1038/S41598-021-86649-6
Abstract: Hexaminolevulinate (HAL) induced Protoporphyrin IX (PpIX) fluorescence is commonly used to differentiate cancer cells from normal cells in vivo, as for instance in blue light cystoscopy for bladder cancer diagnosis. A detailed approach is here provided to use this diagnostic principle ex vivo in an immunosensor device, towards enabling non-invasive cancer diagnostic from body fluids, such as urine. Several factors susceptible to affect the applicability of HAL-assisted diagnosis in body fluids were tested. These included the cell viability and its impact on PpIX fluorescence, the storage condition and shelf life of HAL premix reagent, light exposure (360–450 nm wavelengths) and its corresponding effect on both intensity and bleaching of the PpIX fluorescence as a function of the microscopy imaging conditions. There was no significant decrease in the viability of bladder cancer cells after 6 h at 4 °C (student’s t-test: p 0.05). The cellular PpIX fluorescence decreased in a time-dependent manner when cancer cells were kept at 4 °C for extended period of time, though this didn’t significantly reduce the fluorescence intensity contrast between cancer and non-cancer cells kept in the same condition for 6 h. HAL premix reagent kept in long term storage at 4 °C induced stronger PpIX fluorescence than reagent kept in the − 20 °C freezer. The PpIX fluorescence was negatively affected by repeated light exposure but increased with illumination intensity and exposure time. Though this applied to both healthy and cancer cell lines, and therefore did not statistically improved the differentiation between cell types. This study revealed important experimental settings that need to be carefully considered to benefit from the analytical potential of HAL induced fluorescence when used in technologies for the diagnosis of cancer from body fluids.
Mending a broken heart but breaking the kidney
Publisher: Wiley
Date: 12-09-2016
DOI: 10.1111/NEP.12799
Abstract: The incidence of acute kidney injury (AKI) is a frequent and serious complication of cardiac surgery. In 2013, 95% of cardiac surgical procedures performed in Australia and New Zealand used cardiopulmonary bypass (CPB). AKI following CPB is well known, yet the perioperative factors contributing to its development are incompletely understood. AKI following CPB has significant implications on both short-term and long-term outcomes. The techniques for conducting CPB have evolved, moving towards evidence-based practice however, there is still no generally accepted definition of optimal perfusion and its conduct. This review examines the current incidence of AKI following cardiac surgery and the short-term and longer-term effects of AKI on morbidity and mortality. The purpose of this review is to discuss the perioperative risk factors related to CPB and their contribution to the development of AKI. This review will also discuss outcomes in regard to off-pump cardiac surgery, the role of remote ischaemic preconditioning on AKI and outcomes in patients with chronic renal failure undergoing cardiac surgery.
State of the Art Lecture: Regulation of the erythropoietin gene
Publisher: Oxford University Press (OUP)
Date: 1995
Abstract: In most modern bony vertebrates, a considerable portion of the chondrocranium remains cartilaginous only during a relatively small window of embryonic development, making it difficult to study this complex structure. Yet, the transient nature of some chondrocranial elements is precisely why it is so intriguing. Since the chondrocranium has never been lost in any vertebrate, its function is critical to craniofacial development, disease, and evolution. Experimental evidence for the various roles of the chondrocranium is limited, and though snapshots of chondrocranial development in various species at isolated time points are valuable and informative, these cannot provide the data needed to determine the functions of the chondrocranium, or its relationship to the dermatocranium in evolution, in development, or in disease. Observations of the spatiotemporal associations of chondrocranial cartilage, cartilage bone, and dermal bone over early developmental time are available for many vertebrate species and these observations represent the data from which we can build hypotheses. The testing of those hypotheses requires precise control of specific variables like developmental time and molecular signaling that can only be accomplished in a laboratory setting. Here, we employ recent advances in contrast-enhanced micro computed tomography to provide novel 3D reconstructions of the embryonic chondrocranium in relation to forming dermal and cartilage bones in laboratory mice across three embryonic days (E13.5, E14.5, and E15.5). Our observations provide support for the established hypothesis that the vertebrate dermal (exo-) skeleton and endoskeleton evolved as distinct structures and remain distinct. Additionally, we identify spatiotemporal patterning in the development of the lateral wall, roof, and braincase floor of the chondrocranium and the initial mineralization and growth of the bones associated with these cartilages that provides support for the hypothesis that the chondrocranium serves as a scaffold for developing dermatocranial bones. The experimental protocols described and data presented provide tools for further experimental work on chondrocranial development.
Plasma enabled devices for the selective capture and photodynamic identification of prostate cancer cells
Publisher: American Vacuum Society
Date: 05-2020
DOI: 10.1116/6.0000047
Abstract: Prostate cancer is the second most common cancer in men and the second leading cause of male cancer deaths. The current blood test for detecting prostate cancers measures prostate-specific antigen. It has many limitations including a very high rate of false positives. Herein, prostate-specific membrane antigen (PSMA) based immunocapture and hexaminolevulinate (HAL) based photodetection are integrated into a new diagnostic device designed to selectively identify whole prostate cancer cells from voided urine with the aim of providing an accurate noninvasive alternative to current diagnosis methods. Prestained, prostate cancer cells spiked in urine s les at concentrations ranging from 1500 to 2000 cells/ml were captured with 89% sensitivity and 95% specificity. HAL, a cancer specific photosensitizer, was then used to circumvent the need for prestaining. Optimum HAL incubation conditions were identified (50 μM at 37 °C for 2 h) where the mean HAL-induced fluorescence intensity of LNCaP cells was three times that of healthy PNT2 cells, thus providing an independent way to discriminate captured cancer cells from background metabolites. Combining anti-PSMA immunocapture with HAL-induced fluorescent detection, 86% sensitivity and 88% selectivity were achieved, thereby proving the validity of the dual-method for the selective photospecific detection of prostate cancer cells.
Transitional cell carcinoma in a renal allograft with BK nephropathy
Publisher: Wiley
Date: 18-09-2013
DOI: 10.1111/TID.12142
F1000Prime Recommendation
Publisher: No publisher found
Date: 2008
Mitochondrial haplogroups are not associated with diabetic retinopathy in a large Australian and British Caucasian sample
Publisher: Springer Science and Business Media LLC
Date: 24-01-2019
DOI: 10.1038/S41598-018-37388-8
Abstract: Mitochondrial haplogroups H1, H2 and UK have previously been reported to be associated with proliferative diabetic retinopathy (PDR) in Caucasian patients with diabetes. We aimed to replicate this finding with a larger s le and expand the analysis to include different severities of DR, and diabetic macular edema (DME). Caucasian participants (n = 2935) with either type 1 or type 2 diabetes from the Australian Registry of Advanced Diabetic Retinopathy were enrolled in this study. Twenty-two mitochondrial single nucleotide polymorphisms were genotyped by MassArray and haplogroups reconstructed using Haplogrep. Chi square tests and logistic regressions were used to test associations between haplogroup and DR phenotypes including any DR, non-proliferative DR (NPDR), proliferative DR (PDR) and DME. After stratifying the s les in type 1 and type 2 diabetes groups, and adjusting for sex, age, diabetes duration, concurrent HbA1c and hypertension, neither haplogroups H1, H2, UK, K or JT were associated with any DR, NPDR, PDR or DME.
Diphenylene Iodonium Inhibits the Induction of Erythropoietin and Other Mammalian Genes by Hypoxia. Implications for the Mechanism of Oxygen Sensing
Publisher: Wiley
Date: 11-1995
DOI: 10.1111/J.1432-1033.1995.092_C.X
Abstract: Recent studies on the induction of erythropoietin gene expression by hypoxia have indicated that erythropoietin forms part of a widely operative system of gene regulation by oxygen. Similar responses to hypoxia, cobaltous ions and desferrioxamine have indicated that the action of these agents is closely connected with the mechanism of oxygen sensing. To consider further the mechanisms underlying these responses, the effect of iodonium compounds was tested on five genes which show oxygen-regulated expression erythropoietin, vascular endothelial growth factor (VEGF), lactate dehydrogenase-A (LDH-A), glucose transporter-1 (GLUT-1) and placental growth factor (PLGF). In each case, the response to hypoxia was specifically inhibited by low doses of diphenylene iodonium (Ph1I+). This occurred irrespective of whether the hypoxic response was induction of gene expression (erythropoietin, vascular endothelial growth factor, lactate dehydrogenase-A, glucose transporter-1) or inhibition of gene expression (PLGF). In contrast, the induction of gene expression by cobaltous ions or desferrioxamine was not inhibited by Ph2I+. The differential action of Ph2I+ on the response to hypoxia versus the response to cobaltous ions or desferrioxamine must reflect a difference in the mechanism of action of these stimuli, which will require accommodation in any model of the oxygen-sensing mechanism. Based on the known properties of Ph2I+, the implication of these findings is that the mechanism of oxygen sensing most probably involves the operation of a flavoprotein oxidoreductase.
Review article: How cells sense oxygen: Lessons from and for the kidney
Publisher: Wiley
Date: 02-2009
DOI: 10.1111/J.1440-1797.2008.01064.X
Abstract: The kidney has contributed two critical insights to an understanding of the mechanism by which all mammalian cells sense oxygen. The first followed from the detailed characterization of the regulation of expression of erythropoietin by oxygen and led to the discovery of the hypoxically regulated transcription factor, HIF (hypoxia-inducible factor). The second insight developed from the exploration of the molecular pathogenesis of von Hippel Lindau disease protein whose mutation is characterized by the development of renal cancers. The essential role for the von Hippel Lindau disease protein in the oxygen-dependent degradation of HIF led directly to the discovery of the oxygen sensing mechanism that regulates HIF by oxygen-dependent peptidyl hydroxylation. This understanding now generates novel therapeutic possibilities and is providing insights into the mechanisms of other renal diseases.
BK virus encoded MicroRNAs are present in blood of renal transplant recipients with BK viral nephropathy
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1111/AJT.12694
Abstract: BK viral infection is an important cause of renal transplant dysfunction and failure. Current strategies utilize surveillance for infection with DNA polymerase chain reaction assays and modulation of immunosuppression. Many viruses including polyomaviruses encode microRNAs (miRNAs). We have detected BK virus (BKV) encoded miRNAs in the blood of infected renal transplant recipients, and see a strong correlation between BKV encoded miRNA and BKV DNA in blood and a relationship between levels of bkv-miR-B1-5p and the presence of biopsy-proven BK viral nephropathy. Further research is needed to determine whether the detection of this and other virally encoded miRNAs may be useful in the diagnosis of active viral replication.
Sirolimus vs azathioprine
Publisher: Elsevier BV
Date: 11-2000
Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1α
Publisher: Portland Press Ltd.
Date: 26-11-2008
DOI: 10.1042/BJ20081238
Abstract: The transcription factor HIF (hypoxia-inducible factor) mediates a highly pleiotrophic response to hypoxia. Many recent studies have focused on defining the extent of this transcriptional response. In the present study we have analysed regulation by hypoxia among transcripts encoding human Fe(II)- and 2-oxoglutarate-dependent oxygenases. Our results show that many of these genes are regulated by hypoxia and define two groups of histone demethylases as new classes of hypoxia-regulated genes. Patterns of induction were consistent across a range of cell lines with JMJD1A (where JMJD is Jumonji-domain containing) and JMJD2B demonstrating robust, and JMJD2C more modest, up-regulation by hypoxia. Functional genetic and chromatin immunoprecipitation studies demonstrated the importance of HIF-1α in mediating these responses. Given the importance of histone methylation status in defining patterns of gene expression under different physiological and pathophysiological conditions, these findings predict a role for the HIF system in epigenetic regulation.
Ankyrin Repeat Proteins of Orf Virus Influence the Cellular Hypoxia Response Pathway
Publisher: American Society for Microbiology
Date: 2017
DOI: 10.1128/JVI.01430-16
Abstract: Hypoxia-inducible factor (HIF) is a transcriptional activator with a central role in regulating cellular responses to hypoxia. It is also emerging as a major target for viral manipulation of the cellular environment. Under normoxic conditions, HIF is tightly suppressed by the activity of oxygen-dependent prolyl and asparaginyl hydroxylases. The asparaginyl hydroxylase active against HIF, factor inhibiting HIF (FIH), has also been shown to hydroxylate some ankyrin repeat (ANK) proteins. Using bioinformatic analysis, we identified the five ANK proteins of the parapoxvirus orf virus (ORFV) as potential substrates of FIH. Consistent with this prediction, coimmunoprecipitation of FIH was detected with each of the ORFV ANK proteins, and for one representative ORFV ANK protein, the interaction was shown to be dependent on the ANK domain. Immunofluorescence studies revealed colocalization of FIH and the viral ANK proteins. In addition, mass spectrometry confirmed that three of the five ORFV ANK proteins are efficiently hydroxylated by FIH in vitro . While FIH levels were unaffected by ORFV infection, transient expression of each of the ORFV ANK proteins resulted in derepression of HIF-1α activity in reporter gene assays. Furthermore, ORFV-infected cells showed upregulated HIF target gene expression. Our data suggest that sequestration of FIH by ORFV ANK proteins leads to derepression of HIF activity. These findings reveal a previously unknown mechanism of viral activation of HIF that may extend to other members of the poxvirus family. IMPORTANCE The protein-protein binding motif formed from multiple repeats of the ankyrin motif is common among chordopoxviruses. However, information on the roles of these poxviral ankyrin repeat (ANK) proteins remains limited. Our data indicate that the parapoxvirus orf virus (ORFV) is able to upregulate hypoxia-inducible factor (HIF) target gene expression. This response is mediated by the viral ANK proteins, which sequester the HIF regulator FIH (factor inhibiting HIF). This is the first demonstration of any viral protein interacting directly with FIH. Our data reveal a new mechanism by which viruses reprogram HIF, a master regulator of cellular metabolism, and also show a new role for the ANK family of poxvirus proteins.
MicroRNA Biogenesis in Hypoxia
Publisher: Bentham Science Publishers Ltd.
Date: 16-08-2017
DOI: 10.2174/2211536606666170313114821
Abstract: MicroRNAs (miRNAs) are 17-22 nucleotide, non-coding, single stranded RNA molecules that play a key role in post-transcriptional gene regulation. Hypoxia is a reduction in the normal level of tissue oxygen (O2) tension, and is a feature of chronic vascular disease, pulmonary disease and many cancers. Tissue hypoxia can have widespread effects on cellular functions, as O2 availability is critical for many cellular processes. Cells respond to changes in O2 tension through multiple molecular and cellular mechanisms, including changes in gene expression through transcriptional and translational mechanisms. The transcription factor, hypoxia inducible factor-1, plays a dominant role in transcriptional gene regulation in hypoxia. Several hypoxically induced miRNAs have been shown to play important roles in the hypoxic adaptation of cancer cells. Global repression of enzymes critical for miRNA biogenesis seems to be a widespread phenomenon with several different mechanisms operating. This review describes the effects of hypoxia on specific miRNAs and more global effects on miRNA biogenesis, demonstrating that hypoxia is an important regulator of miRNA biogenesis and function.
Prostate cancer detection: a systematic review of urinary biosensors
Publisher: Springer Science and Business Media LLC
Date: 08-01-2022
DOI: 10.1038/S41391-021-00480-8
Abstract: Current diagnostic methods for prostate cancer are invasive and lack specificity towards aggressive forms of the disease, which can lead to overtreatment. A new class of non-invasive alternatives is under development, in which urinary biomarkers are detected using biosensing devices to offer rapid and accurate prostate cancer diagnosis. These different approaches are systematically reviewed and their potential for translation to clinical practice is evaluated. A systematic review of the literature was performed in May 2021 using PubMed Medline database, Embase, and Web of Science. The objective was to review the structural designs and performance of biosensors tested on urine s les from patients with prostate cancer. A total of 76 records were identified. After screening and eligibility, 14 articles were included and are discussed in this paper. The biosensors were discussed based on the target biomarkers and detection technologies used, as well as the results of the clinical studies. Most of the works reported good discrimination between patients with prostate cancer and controls. This review highlights the potential of urinary biosensors for non-invasive prostate cancer detection. However, clinical studies have so far only been conducted on small cohorts of patient, with large scale trials still needed to validate the proposed approaches. Overall, the consensus arising from the proof of concepts studies reviewed here, is that an adequate combination of biomarkers into multiplex biosensor platforms is required to achieve accurate diagnostic tests. Furthermore, whether such devices can discriminate between aggressive and indolent cancer has not yet been addressed, because it entails optimized biomarkers panels and long-term clinical trials.
Induction of hypoxia-inducible factor-1, erythropoietin, vascular endothelial growth factor, and glucose transporter-1 by hypoxia: Evidence against a regulatory role for Src kinase
Publisher: American Society of Hematology
Date: 15-01-1997
Abstract: The induction by hypoxia of genes such as erythropoietin, vascular endothelial growth factor (VEGF ), and glucose transporter-1 (Glut-1) is mediated in part by a transcriptional complex termed hypoxia-inducible factor-1 (HIF-1). Several lines of evidence have implicated protein phosphorylation in the mechanism of activation of HIF-1 by hypoxia. Recent reports have described the activation of the tyrosine kinase src by severe hypoxia, and a role in the induction of VEGF by severe hypoxia has been proposed. This led us to examine whether src and related kinases operated more widely in the hypoxic induction of HIF-1 and HIF-1–dependent genes regulated by hypoxia. Measurements of src kinase activity in cells exposed to varying severities of hypoxia showed activation by severe hypoxia (0.1% oxygen or catalyst induced anoxia), but not 1% oxygen. This contrasted with the marked induction of HIF-1 by exposure to 1% oxygen. Manipulations of src activity were produced by transient and stable transfection of Hep3B cells. Despite substantial changes in src activity, no alteration was seen in the normoxic or hypoxic expression of erythropoietin, VEGF, or Glut-1, or in the regulation of HIF-1–dependent reporter genes inducible by hypoxia. Similarly, we found that the expression of these genes in src- or c-src kinase-deficient cells did not differ from wild-type cells at either 1% oxygen or more severe hypoxia. These results indicate that src is not critical for the hypoxic induction of HIF-1, erythropoietin, VEGF, or Glut-1.
MicroRNAs in Renal Development and Regeneration
Publisher: Elsevier
Date: 2023
Genome-wide Association of Hypoxia-inducible Factor (HIF)-1α and HIF-2α DNA Binding with Expression Profiling of Hypoxia-inducible Transcripts
Publisher: Elsevier BV
Date: 06-2009
Pulmonary, cardiac and renal syndrome
Publisher: Oxford University Press (OUP)
Date: 05-2000
DOI: 10.1093/NDT/15.5.731
Role of the hypoxia sensing system, acidity and reproductive hormones in the variability of vascular endothelial growth factor induction in human breast carcinoma cell lines
Publisher: Wiley
Date: 02-03-1998
DOI: 10.1002/(SICI)1097-0215(19980302)75:5<706::AID-IJC8>3.0.CO;2-2
Abstract: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor implicated in many pathological processes. We investigated the regulation of 4 alternatively spliced isoforms (121, 165, 189 and 206 amino acids) by hypoxia, hypoglycemia, acidity, female reproductive hormones and vitamin D in breast carcinoma cell lines representing different tumor phenotypes. There was a 17-fold difference in total VEGF mRNA expression across the cell lines. The isoform expression, 121 > 165 > 189, was unchanged by different culture conditions. Hypoxia was the most potent stimulus, and the cell lines demonstrated a 1.4- to 6.9-fold range of VEGF induction, maintained when other hypoxically regulated genes (phosphoglycerate kinase 1 and glucose transporter 1) and a HIF-1-dependent reporter gene were examined. The relative inducibility of the genes was maintained in each cell line, but basal expression was independent of -fold induction. VEGF expression decreased under acidic conditions in 2 cell lines, but the hypoxia stimulus remained effective under acidic conditions. Hypoglycemia, female reproductive hormones and vitamin D exerted no effect on expression, nor did inhibitors of mutant ras. Our results show that VEGF expression varies widely between cell lines and that capacity to respond to hypoxia is also cell specific, relating mostly to the hypoxic sensing of the cell and the signal transduction mechanism. Such characteristics, if maintained in vivo, have implications for the angiogenic potential of different tumor cells under normal and hypoxic conditions.
Protocol for the Flinders Kidney Health Registry: patient outcomes of kidney cancers and nephrectomies
Publisher: Springer Science and Business Media LLC
Date: 21-07-2022
DOI: 10.1186/S12894-022-01065-W
Abstract: Kidney cancer accounts for 2% of new cancers diagnosed in Australia annually. Partial and radical nephrectomy are the treatment of choice for kidney cancer. Nephrectomy is also performed for living donor kidney transplantation. Nephrectomy is a risk factor for new-onset chronic kidney disease (CKD) or deterioration of pre-existing CKD. Understanding the risk factors for new-onset or deterioration of existing CKD after nephrectomy is important in developing preventive measures to provide better care for these patients. There is also a need to understand the incidence, natural history, management trends, and sequelae of radiofrequency ablation as well as surveillance of small renal cancers or small renal masses (SRMs). Clinical registries are critical in providing excellent patient-centre care and clinical research as well as basic science research. Registries evaluate current practice and guide future practice. The Flinders Kidney Health Registry will provide the key information needed to assess various treatment outcomes of patients with kidney cancer and patients who underwent nephrectomy for other reasons. The registry aims to provide clinical decision makers with longitudinal data on patient outcomes, health systems performance, and the effect of evolving clinical practice. The registry will also provide a platform for large-scale prospective clinical studies and research. Patients above the age of 18 undergoing nephrectomy or radiofrequency ablation for any indication and patients with SRMs will be included in the registry. Demographic, clinical and quality of life data will be collected from hospital information systems and directly from the patient and/or caregiver. The Registry will report a summary of patient characteristics including indication for treatment, clinical risk profiles, surgical and oncological outcomes, the proportion of patients who progress to CKD and end stage kidney disease, quality of life post treatment as well as other relevant outcomes for all patients who have undergone nephrectomy for any indication, ablation or surveillance for SRMs. The registry will record the follow-up practice after nephrectomy and patient on active surveillance, which will help to develop and enhance a best practice protocol. The collected prospective data will provide a platform for ongoing patient-orientated research and improve patient-centred healthcare delivery.
hsa-miR-210 Is Induced by Hypoxia and Is an Independent Prognostic Factor in Breast Cancer
Publisher: American Association for Cancer Research (AACR)
Date: 03-2008
DOI: 10.1158/1078-0432.CCR-07-1755
Abstract: Purpose: MicroRNA (miRNA) expression alterations have been described in cancer. Many cancers are characterized by areas of hypoxia, enhanced hypoxia-inducible factor (HIF) levels, and increased expression of hypoxically regulated genes, all of which correlate with patient outcome. We examined hypoxia-induced miRNA expression changes to identify markers of survival in breast cancer. Experimental Design: We used microarrays to analyze miRNA expression changes induced by hypoxia in MCF7 breast cancer cell lines and validated results by quantitative-PCR (Q-PCR). Small interfering RNA against HIF-1α and HIF-2α, and RCC4 cells transfected with the von Hippel-Lindau (VHL) protein were used to investigate HIF dependency of miRNA expression. miRNA Q-PCR assays were done on 219 early breast cancer s les with long-term follow-up. Correlation of expression with clinical variables was done using Pearson and Spearman's rank tests, univariate, and Cox multivariate analysis. Results: hsa-miR-210 induction was the most significant change under hypoxia by microarray analysis (3.4-fold, P & 0.001). hsa-miR-210 expression changes were validated by Q-PCR and detected in other cancer cell lines. Using small interfering RNAs and RCC4 cells transfected with VHL, we showed that the regulation by hypoxia of hsa-miR-210 was mediated by the HIF-1α/VHL transcriptional system but not HIF-2α. hsa-miR-210 expression levels in breast cancer s les correlated directly with a hypoxia score based on the expression of 99 genes. hsa-miR-210 expression levels showed an inverse correlation with disease-free and overall survival, significant in both univariate and multivariate analyses. Conclusions: We show that hsa-miR-210 overexpression is induced by hypoxia in a HIF-1α– and VHL-dependent fashion and its expression levels in breast cancer s les are an independent prognostic factor.
A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients
Publisher: Springer Science and Business Media LLC
Date: 21-03-2016
DOI: 10.1007/S00592-016-0850-4
Abstract: This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93 CI 1.23-3.03 P = 0.004), but no association found in the T2DM group (OR 1.05 CI 0.83-1.32 P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25 CI 1.03-1.53 P = 0.025). No association with DME was found in the T1DM group (OR 0.87 CI 0.54-1.42) P = 0.583), or with PDR for either type of DM. Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.
Nasty shock after an anti-emetic
Publisher: Oxford University Press (OUP)
Date: 05-2001
Concordant Regulation of Gene Expression by Hypoxia and 2-Oxoglutarate-dependent Dioxygenase Inhibition
Publisher: Elsevier BV
Date: 06-2006
Hypoxia-inducible factors: where, when and why?
Publisher: Elsevier BV
Date: 2006
Abstract: Hypoxia-inducible factor (HIF) is a family of transcription factors that regulate the homeostatic response to oxygen deprivation during development, physiological adaptation, and pathological processes such as ischemia and neoplasia. Our understanding of the function of different HIF isoforms is being advanced by understanding the processes that regulate their activity, learning where and when they are expressed and what genes they regulate.
Myocardial Ischemia Assessment in Chronic Kidney Disease: Challenges and Pitfalls
Publisher: Frontiers Media SA
Date: 19-12-2014
Myocardial perfusion is impaired in renal transplant and liver transplant patients
Publisher: Springer Science and Business Media LLC
Date: 03-02-2015
The VHL-dependent regulation of microRNAs in renal cancer
Publisher: Springer Science and Business Media LLC
Date: 21-10-2010
Abstract: The commonest histological type of renal cancer, clear cell renal cell carcinoma (cc RCC), is associated with genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumour suppressor. VHL inactivation leads to induction of hypoxia-inducible factors (HIFs) and a hypoxic pattern of gene expression. Differential levels of specific microRNAs (miRNAs) are observed in several tumours when compared to normal tissue. Given the central role of VHL in renal cancer formation, we examined the VHL-dependent regulation of miRNAs in renal cancer. VHL-dependent miRNA expression in cc RCC was determined by microarray analysis of renal cell line RCC4 with mutated VHL (RCC4-VHL) and reintroduced wild-type VHL (RCC4 + VHL). Five miRNAs highly upregulated in RCC4 + VHL and five miRNAs highly downregulated in RCC4 + VHL were studied further, in addition to miR-210, which is regulated by the HIF-VHL system. miRNA expression was also measured in 31 cc RCC tumours compared to adjacent normal tissue. A significant increase in miR-210, miR-155 and miR-21 expression was observed in the tumour tissue. miR-210 levels also showed a correlation with a HIF-regulated mRNA, carbonic anhydrase IX (CAIX), and with VHL mutation or promoter methylation. An inverse correlation was observed between miR-210 expression and patient survival, and a putative target of miR-210, iron-sulfur cluster assembly protein (ISCU1/2), shows reciprocal levels of mRNA expression in the tumours. We have identified VHL-regulated miRNAs and found that for some the regulation is HIF-dependent and for others it is HIF-independent. This pattern of regulation was also seen in renal cancer tissue for several of these miRNAs (miR-210, miR-155, let-7i and members of the miR-17-92 cluster) when compared with normal tissue. miR-210 showed marked increases in expression in renal cancer and levels correlated with patient survival. The inverse correlation between miR-210 levels and ISCU1/2 provides support for the hypothesis that ISCU1/2 is a target of miR-210 and that it may contribute to the anaerobic respiration seen in renal (and other) tumours. See Commentary: 741-7015/8/65
Nanoparticle Tracking Analysis of Urine to Detect Exosomes Can Be Confounded by Albuminuria
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-04-2018
F1000Prime Recommendation
Publisher: No publisher found
Date: 2011
F1000Prime Recommendation
Publisher: No publisher found
Date: 2010
Familial nephropathy and multiple exostases with exostosin-1 (EXT1) gene mutation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2008
REGULATION OF ANGIOGENIC GROWTH-FACTOR EXPRESSION BY HYPOXIA, TRANSITION-METALS, AND CHELATING-AGENTS
Publisher: American Physiological Society
Date: 06-1995
DOI: 10.1152/AJPCELL.1995.268.6.C1362
Abstract: Recent work has indicated that oxygen-sensing mechanism(s) resembling those controlling erythropoietin production operate in many non-erythropoietin-producing cells. To pursue the implication that such a system might control other genes, we studied oxygen-regulated expression of mRNAs for vascular endothelial growth factor, platelet-derived growth factor (PDGF) A and B chains, placental growth factor (PLGF), and transforming growth factor in four different cell lines and compared the characteristics with those of erythropoietin regulation. Oxygen-regulated expression was demonstrated for each gene in at least one cell type. However, the response to hypoxia (1% oxygen) varied markedly, ranging from a 13-fold increase (PDGF-B in Hep G2 cells) to a 2-fold decrease (PLGF in the trophoblastic line BeWo). For each gene/cell combination, both the magnitude and direction of the response to hypoxia were mimicked by exposure to cobaltous ions or two different iron-chelating agents, desferrioxamine and hydroxypyridinones. These similarities with established characteristics of erythropoietin regulation indicate that a similar mechanism of oxygen sensing is operating on a variety of vascular growth factors, and they suggest that chelatable iron is closely involved in the mechanism.
Oxygen-dependent hydroxylation by Factor Inhibiting HIF (FIH) regulates the TRPV3 ion channel
Publisher: The Company of Biologists
Date: 2014
DOI: 10.1242/JCS.158451
Abstract: Factor Inhibiting HIF (FIH) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ankyrin repeat domain. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.
MicroRNA-10b and breast cancer metastasis
Publisher: Springer Science and Business Media LLC
Date: 10-2008
DOI: 10.1038/NATURE07362
Myocardial oxygenation is impaired in advanced chronic kidney disease and renal transplant patients
Publisher: Springer Science and Business Media LLC
Date: 03-02-2015
Arginine Metabolites as Biomarkers of Myocardial Ischaemia, Assessed with Cardiac Magnetic Resonance Imaging in Chronic Kidney Disease
Publisher: MDPI AG
Date: 11-03-2021
DOI: 10.3390/BIOM11030416
Abstract: (1) Background: Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Myocardial oxygenation and perfusion response to stress, using oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) and stress T1 mapping respectively, are impaired in CKD patients with and without known coronary artery disease (CAD). Endothelial dysfunction, assessed by circulating levels of asymmetric dimethylarginine (ADMA) and homoarginine (HMA), promotes atherosclerosis. We hypothesized that in CKD patients, worsening endothelial dysfunction is associated with worsening myocardial oxygenation and perfusion as assessed by change in OS-CMR signal intensity (Δ OS-CMR SI) and stress T1 (ΔT1) values. (2) Methods: 38 patients with advanced CKD underwent cardiovascular magnetic resonance (CMR) scanning at 3 Tesla. OS-CMR and T1 mapping images were acquired both at rest and after adenosine stress and analyzed semi-quantitatively. Serum ADMA and HMA concentrations were assessed using mass spectrometry. (3) Results: There was no significant correlation between Δ OS-CMR SI and ADMA or HMA. Interestingly, there was a significant negative correlation seen between Δ T1 and ADMA (r = −0.419, p = 0.037, n = 30) but not between Δ T1 and HMA. (4) Conclusions: Stress T1 response is impaired in CKD patients and is independently associated with higher circulating ADMA concentrations.
F1000Prime Recommendation
Publisher: No publisher found
Date: 2009
Isoenzyme-specific regulation of genes involved in energy metabolism by hypoxia: similarities with the regulation of erythropoietin
Publisher: Portland Press Ltd.
Date: 02-1996
DOI: 10.1042/BJ3130809
Abstract: Recent studies have indicated that regulatory mechanisms underlying the oxygen-dependent expression of the haematopoietic growth factor erythropoietin are widely operative in non-erythropoietin-producing cells and are involved in the regulation of other genes. An important characteristic of this system is that the inducible response to hypoxia is mimicked by exposure to particular transition metals such as cobaltous ions, and by iron chelation. We have investigated the extent of operation of this system in the regulation of a range of genes concerned with energy metabolism. The effects of hypoxia (1% oxygen), cobaltous ions and desferrioxamine on gene expression in tissue-culture cells was studied using RNase protection assays. Hypoxia induced the expression of glucose transporters in an isoform-specific manner GLUT-1 and GLUT-3 were induced by hypoxia, whereas expression of GLUT-2 was decreased. Isoenzyme-specific regulation by hypoxia was also observed for genes encoding phosphofructokinase, aldolase and lactate dehydrogenase. For all of these genes, responses to cobaltous ions and desferrioxamine correlated in both direction and magnitude with the response to hypoxia. In contrast, a reduction in mitochondrial transcripts was observed in hypoxia, but these changes were not mimicked by either cobaltous ions or desferrioxamine. These findings indicate that similarities with erythropoietin regulation extend to the oxygen-dependent regulation of genes encoding glucose transporters and glycolytic enzymes but not to the regulation of mitochondrial transcripts, and they show that in glucose metabolism regulation by this system is isoenzyme- or isoform-specific.
THE USE OF ACYCLOVIR IN SUSPECTED ENCEPHALITIS
Publisher: SAGE Publications
Date: 1994
DOI: 10.1177/014107689408700105
Abstract: The early use of intravenous acyclovir in herpes simplex encephalitis (HSE) is essential. However, rapid diagnostic tests are not freely available. Hence, all patients with suspected encephalitis may need to be commenced on acyclovir. In our study, of 34 patients with suspected encephalitis, only two eventually had HSE confirmed, 19 had encephalitis not due to herpes simplex and in 13 a non-encephalitic illness was finally diagnosed. Guidelines for the use of acyclovir in suspected encephalitis are given aimed at minimizing the drug cost whilst still protecting all cases of presumed HSE.
Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection.
Publisher: Springer Science and Business Media LLC
Date: 14-01-2022
DOI: 10.1186/S12916-021-02228-6
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered in iduals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as “long COVID”, post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects. We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and 50% reported ongoing symptoms more than 6 months post-infection. Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent in iduals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not. Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some in iduals.
Hypoxia and oxidative stress in breast cancer Hypoxia signalling pathways
Publisher: Springer Science and Business Media LLC
Date: 16-07-2001
DOI: 10.1186/BCR313
Abstract: Hypoxia-inducible factor-1 (HIF), which is centrally involved in physiological oxygen homeostasis, is also activated in the majority of tumours. Activation of HIF can occur through genetic mechanisms or as a result of hypoxia within the tumour microenvironment. In some cases HIF activation appears to be intimately linked to the proliferative stimulus itself. HIF affects patterns of gene expression and tumour growth, although precise effects vary between tumour types. Modulation of HIF activity, if correctly applied, may be therapeutically beneficial in tumour therapy.
Impaired Myocardial Oxygenation Response to Stress in Patients With Chronic Kidney Disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-08-2015
Abstract: Coronary artery disease and left ventricular hypertrophy are prevalent in the chronic kidney disease ( CKD ) and renal transplant ( RT ) population. Advances in cardiovascular magnetic resonance ( CMR ) with blood oxygen level–dependent ( BOLD ) technique provides capability to assess myocardial oxygenation as a measure of ischemia. We hypothesized that the myocardial oxygenation response to stress would be impaired in CKD and RT patients. Fifty‐three subjects (23 subjects with CKD , 10 RT recipients, 10 hypertensive ( HT ) controls, and 10 normal controls without known coronary artery disease) underwent CMR scanning. All groups had cine and BOLD CMR at 3 T. The RT and HT groups also had late gadolinium CMR to assess infarction/replacement fibrosis. The CKD group underwent 2‐dimensional echocardiography strain to assess fibrosis. Myocardial oxygenation was measured at rest and under stress with adenosine (140 μg/kg per minute) using BOLD signal intensity. A total of 2898 myocardial segments (1200 segments in CKD patients, 552 segments in RT , 480 segments in HT , and 666 segments in normal controls) were compared using linear mixed modeling. Diabetes mellitus ( P =0.47) and hypertension ( P =0.57) were similar between CKD , RT , and HT groups. The mean BOLD signal intensity change was significantly lower in the CKD and RT groups compared to HT controls and normal controls (−0.89±10.63% in CKD versus 5.66±7.87% in RT versus 15.54±9.58% in HT controls versus 16.19±11.11% in normal controls, P .0001). BOLD signal intensity change was associated with estimated glomerular filtration rate (β=0.16, 95% CI =0.10 to 0.22, P .0001). Left ventricular mass index and left ventricular septal wall diameter were similar between the CKD predialysis, RT , and HT groups. None of the CKD patients had impaired global longitudinal strain and none of the RT group had late gadolinium hyperenhancement. Myocardial oxygenation response to stress is impaired in CKD patients and RT recipients without known coronary artery disease, and unlikely to be solely accounted for by the presence of diabetes mellitus, left ventricular hypertrophy, or myocardial scarring. The impaired myocardial oxygenation in CKD patients may be associated with declining renal function. Noncontrast BOLD CMR is a promising tool for detecting myocardial ischemia in the CKD population.
Hypoxia represses microRNA biogenesis proteins in breast cancer cells
Publisher: Springer Science and Business Media LLC
Date: 22-07-2014
The Case | Bilateral kidney tumors and lung cysts
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1038/KI.2012.366
A platform for selective immuno-capture of cancer cells from urine
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.BIOS.2017.02.011
Abstract: Urothelial cancers are amongst the 10 most common types of cancer and represent a major health problem worldwide. Current urinary diagnostic tests for urothelial cancer are expensive and have limited sensitivity and specificity. In this work, proofs of concept for a selective cancer cell capture platform are presented with the aim to achieve the first generation of specific urinary tests for the detection of cancer cells in urine specimen. The unique reactivity of plasma deposited polyoxazoline was used to covalently bind cancer specific antibodies in microchannels. Cancer cells dispersed in patient urine were successfully captured with up to 99% selectivity and 100% sensitivity over a wide range of cell concentrations. The streamlined two steps preparation process of the capture platform represents an important advance in medical diagnostics, with broader potential applications.
Compensatory renal hypertrophy following nephrectomy: When and how?
Publisher: Wiley
Date: 05-05-2019
DOI: 10.1111/NEP.13578
Abstract: Following surgical removal of one kidney, the other enlarges and increases its function. The mechanism for the sensing of this change and the growth is incompletely understood but begins within days and compensatory renal hypertrophy (CRH) is the dominant contributor to the growth. In many in iduals undergoing nephrectomy for cancer or kidney donation this produces a substantial and helpful increase in renal function. Two main mechanisms have been proposed, one in which increased activity by the remaining kidney leads to hypertrophy, the second in which there is release of a kidney specific factor in response to a unilateral nephrectomy that initiates CRH. Whilst multiple growth factors and pathways such as the mTORC pathway have been implicated in experimental studies, their roles and the precise mechanism of CRH are not defined. Unrestrained hypoxia inducible factor activation in renal cancer promotes growth and may play an important role in driving CRH.
Exosomes and the kidney: Blaming the messenger
Publisher: Wiley
Date: 17-12-2012
DOI: 10.1111/NEP.12005
Abstract: Exosomes are membrane-bound vesicles of endosomal origin, present in a wide range of biological fluids, including blood and urine. They range between 30 and 100 nm in diameter, and consist of a limiting lipid bilayer, transmembrane proteins and a hydrophilic core containing proteins, mRNAs and microRNAs (miRNA). Exosomes can act as extracellular vehicles by which cells communicate, through the delivery of their functional cargo to recipient cells, with many important biological, physiological and pathological implications. The exosome release pathway contributes towards protein secretion, antigen presentation, pathogen transfer and cancer progression. Exosomes and exosome-mediated signalling have been implicated in disease processes such as atherosclerosis, calcification and kidney diseases. Circulating levels of exosomes and extracellular vesicles can be influenced by the progression of renal disease. Advances in methods for purification and analysis of exosomes are leading to potential diagnostic and therapeutic avenues for kidney diseases. This review will focus on biophysical properties and biogenesis of exosomes, their pathophysiological roles and their potential as biomarkers and therapeutics in kidney diseases.
Myocardial perfusion is impaired in asymptomatic renal and liver transplant recipients: a cardiovascular magnetic resonance study
Publisher: Springer Science and Business Media LLC
Date: 10-07-2015
Genetic Analysis of the Role of the Asparaginyl Hydroxylase Factor Inhibiting Hypoxia-inducible Factor (HIF) in Regulating HIF Transcriptional Target Genes
Publisher: Elsevier BV
Date: 10-2004
I kind of gave up on it after a while, became too hard, closed my eyes, didn't want to know about it-adults with type 1 diabetes mellitus describe defeat in the context of low social support
Publisher: Wiley
Date: 22-11-2019
DOI: 10.1111/HEX.12850
Effects of cotransfection of antisense‐EGFR and wild‐type PTEN cDNA on human glioblastoma cells
Publisher: Wiley
Date: 22-05-2006
DOI: 10.1111/J.1440-1789.2006.00679.X
Abstract: The main molecular genetic changes identified in glioblastomas are overexpression/ lification of the epidermal growth factor receptor (EGFR) gene and mutation/ deletion of the tumor suppressor PTEN gene. These two genetic changes both play important roles in glial tumorigenesis and progression. In this study, we demonstrated that wild-type PTEN transfection inhibited the growth and transforming ability of U87MG cells by 69.3% and 73.5%, respectively. On the other hand, antisense-EGFR transfection inhibited the growth and transforming phenotype of these cells by 50.3% and 46.8%, respectively. However, cotransfection of U87MG cells with wild-type PTEN and antisense EGFR constructs could inhibit the cellular growth by 91.7%. The transforming phenotype of these cells was completely inhibited. In addition, these cotransfected cells showed a differentiated form and expressed much lower telomerase activity than cells transfected with wild-type PTEN or antisense-EGFR alone. In summary, these results suggest that cotransfection is a better approach to suppress glioma cell growth than wild-type PTEN transfer or antisense-EGFR transfection alone. This approach may prove useful as an adjunct therapy in the treatment of glioblastomas.
Early intervention in acute renal failure - Assessing fluid status is important
Publisher: BMJ
Date: 07-09-2006
Hypoxia and the regulation of gene expression
Publisher: Elsevier BV
Date: 03-1998
DOI: 10.1016/S1357-4310(97)01198-2
Abstract: The optimal delivery of oxygen to tissues is essential both to ensure adequate energy provision and to avoid the toxic effects of higher oxygen concentrations. For this to occur, organisms must be able to sense oxygen and respond to changes in oxygen tension by altering gene expression. The analysis of the regulation of erythropoiesis has provided important insights into the mechanisms of oxygen-regulated gene expression. These mechanisms have a role in the regulation of many genes, in many cell types and appear to be of relevance to many common pathologies in which disturbances of oxygen supply are central.
Common Sequence Variation in the VEGFC Gene Is Associated with Diabetic Retinopathy and Diabetic Macular Edema
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.OPHTHA.2015.05.004
Abstract: To investigate associations between single nucleotide polymorphisms (SNPs) in the VEGFC gene and the development of diabetic retinopathy (DR) in white patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Cross-sectional, case control study. White patients with T1DM or T2DM (n = 2899) were recruited from ophthalmology and endocrine clinics in Australia and the United Kingdom. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be receiving oral hypoglycemic treatment or insulin. Participants were categorized according to their worst-ever DR grading, as having "no DR" (no history of nonproliferative DR [NPDR], proliferative DR [PDR], or diabetic macular edema [DME]) or "any DR" (further subclassified as NPDR or PDR, without or with DME). Clinical characteristics, glycemic control (hemoglobin A1c [HbA1c]), and presence of diabetic complications were determined at recruitment. Genotyping was performed for 13 VEGFC tag SNPs. Odds ratios (ORs) were determined for associations with DR of VEGFC tag SNPs, in idually and within haplotypes. Logistic regression was used to adjust for clinical covariates, including DM type, age, sex, DM duration, hypertension, nephropathy, HbA1c, and smoking. Participants with DM but "no DR" (n = 980) were compared with 1919 participants with DM and "any DR." Three VEGFC SNPs were associated with DR after logistic regression: rs17697419 (P = 0.001 OR, 0.67 confidence interval [CI], 0.52-0.85), rs17697515 (P = 0.001 OR, 0.62 CI, 0.47-0.81), and rs2333526 (P = 0.005 OR, 0.69 CI, 0.54-0.90). rs17697515 Was also specifically associated with DME in those with T2DM (P = 0.004 OR, 0.53 CI, 0.35-0.82). Haplotype analysis revealed 2 significantly associated haplotypes, both protective against DR development. Significant associations were found between VEGFC tag SNPs (in idually and within haplotypes) and the presence of any DR or DME in white participants with T1DM and T2DM.
Review: The role of microRNAs in kidney disease
Publisher: Wiley
Date: 27-08-2010
DOI: 10.1111/J.1440-1797.2010.01363.X
Abstract: MicroRNAs (miRNAs) are short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocyte-specific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR-192) can also act as an effector of transforming growth factor-β activity in the high-glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future.
In order for the light to shine so brightly, the darkness must be present-why do cancers fluoresce with 5-aminolaevulinic acid?
Publisher: Springer Science and Business Media LLC
Date: 13-08-2019
Activation of Hypoxia-inducible Factor-1; Definition of Regulatory Domains within the α Subunit
Publisher: Elsevier BV
Date: 04-1997
Human cytomegalovirus encoded microRNAs: hitting targets
Publisher: Informa UK Limited
Date: 28-10-2015
DOI: 10.1586/14787210.2015.1106939
Abstract: Human cytomegalovirus (HCMV) infection is of particular concern in immunodeficient in iduals notably transplant recipients, leading to increased morbidity and mortality. HCMV is predicted to encode multiple microRNAs (miRNAs) and several have been characterized in vitro. Furthermore, these miRNAs have been shown to target human and viral mRNAs. Pathways involved in human cellular targets have key roles in vesicle trafficking, immune evasion and cell cycle control. This demonstration of viral miRNA targets provides novel insights into viral pathogenesis. This review details the evidence for the existence of HCMV-encoded miRNA and their targets. HCMV miRNA in blood and other tissues is a potential diagnostic tool and blocking the effects of specific HCMV-encoded miRNA with sequence specific antagomirs is a potential new therapy.
Plasma polymerised polyoxazoline thin films for biomedical applications
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5CC00260E
Abstract: We report novel solvent-free and substrate independent, plasma polymerised nanoscale biocompatible polyoxazoline coatings capable of controlling protein and cell adhesion, and significantly reducing biofilm build up.
Genetic Analysis of Pathways Regulated by the von Hippel-Lindau Tumor Suppressor in Caenorhabditis elegans
Publisher: Public Library of Science (PLoS)
Date: 07-09-2004
Shedding Light on Bladder Cancer Diagnosis in Urine
Publisher: MDPI AG
Date: 08-06-2020
DOI: 10.3390/DIAGNOSTICS10060383
Abstract: Blue light cystoscopy (BLC) is the most recent clinical approach in the detection and diagnosis of bladder cancer, a common type of cancer with a high rate of recurrence. Representing a significant advance over previous approaches, this photodynamic diagnostic technique uses a photosensitiser prodrug as an adjunct to white light cystoscopy to enhance the in vivo detection of malignant tissues in the bladder based on their distinctive fluorescence. Whilst it does improve detection rates, BLC remains an invasive and costly procedure. Meanwhile, a variety of noninvasive urine detection methods and related microdevices have been developed, none of which have yet entered routine clinical use due to unsatisfactory sensitivity. Following a brief description of the current approaches and their limitations, we provide here a systematic review of a newer niche research aiming to develop a noninvasive adaptation of photodynamic diagnosis. The research to date surrounding the ex situ use of photosensitiser prodrugs for urinary diagnosis of bladder cancer is also discussed.
Circulating microRNA expression is reduced in chronic kidney disease
Publisher: Oxford University Press (OUP)
Date: 02-09-2011
DOI: 10.1093/NDT/GFR485
Abstract: MicroRNAs (miRNAs) are important regulators of gene expression, which have roles in renal development and disease. They exist in biological fluids including blood and urine and may have signalling roles and potential as disease biomarkers. We measured the levels of miRNAs in patients with different stages of chronic kidney failure including those receiving maintenance haemodialysis treatment. In patients with severe chronic renal failure, circulating levels of total and specific miRNAs are reduced in comparison to patients with mild renal impairment or normal renal function. A strong correlation exists between detected circulating miRNAs and estimated glomerular filtration rate, and less strong correlations with other features of chronic kidney disease, such as anaemia and hyperparathyroidism. These findings have important implications for the use of circulating miRNAs as biomarkers in in iduals with renal impairment and for the pathogenesis of uraemia.
Control of the Hypoxic Response in Drosophila melanogaster by the Basic Helix-Loop-Helix PAS Protein Similar
Publisher: Informa UK Limited
Date: 10-2002
MicroRNA-Related Genetic Variants Are Associated With Diabetic Retinopathy in Type 1 Diabetes Mellitus.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 20-09-2019
Abstract: Few studies have explored the association of genetic variants in microRNA genes and binding sites with diabetic retinopathy (DR) in type 1 diabetes. We conducted a genome-wide scan for single nucleotide polymorphisms (SNPs) in these genes by using data from a genome-wide association study (GWAS). All known SNPs were imputed from our GWAS data (n = 325) of DR cases and diabetic controls (no DR). Relevant SNPS were extracted using miRNASNP and PolymiRTS (version 2) databases. χ2 tests and logistic regression (adjusting for age, sex, duration of diabetes, HbA1c, and hypertension) were used to test the association between the imputed SNPs and DR phenotypes (any DR, nonproliferative DR [NPDR], proliferative DR [PDR], diabetic macular edema [DME], and sight-threatening DR defined as PDR, severe NPDR, or clinically significant macula edema [CSME]) compared with diabetic controls. Top-ranking SNPs were genotyped in a larger cohort (N = 560) to confirm their association with DR. Three SNPs (rs10061133, rs1049835, rs9501255) were selected and genotyped in the final cohort. Rs10061133 in MIR449b was protective of sight-threatening DR (odds ratio [OR] = 0.32, P = 3.68 × 10-4) and PDR (OR = 0.30, P = 8.12 × 10-4), and the associations became more significant as the cohort increased in size. Rs10061133 in MIR449b is significantly associated with a decreased risk of PDR and sight-threatening DR in Caucasian patients with type 1 diabetes. This can guide future studies on genetic risk profiling and on developing microRNA-related therapies for sight-threatening DR.
F1000Prime Recommendation
Publisher: No publisher found
Date: 2011
Hypoxic enhancement of exosome release by breast cancer cells
Publisher: Springer Science and Business Media LLC
Date: 24-09-2012
Abstract: Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Breast cancer cell lines were cultured under either moderate (1% O 2 ) or severe (0.1% O 2 ) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of 0.05 considered significant. Exposure of three different breast cancer cell lines to moderate (1% O 2 ) and severe (0.1% O 2 ) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release more exosomes into their microenvironment to promote their own survival and invasion.
MicroRNAs: Are they the missing link between hypoxia and pre-eclampsia?
Publisher: Informa UK Limited
Date: 19-12-2014
DOI: 10.3109/10641955.2013.832772
Abstract: Pre-ecl sia is a multisystem disorder that occurs in the second half of pregnancy affecting 5% of pregnancies. It remains the leading cause of maternal and perinatal mortality and morbidity worldwide. Impaired placental implantation, hypoxia, endothelial dysfunction and systemic inflammation are thought to have a role in the pathogenesis of pre-ecl sia. MicroRNAs (miRNAs) are short non-coding RNAs. They are important regulators of gene expression and have been found to affect cell development, proliferation, differentiation and function. Specific patterns of miRNAs have been detected in the placenta and there is altered miRNA expression in the placenta of patients with pre-ecl sia to but their role in the pathogenesis remains unclear. Furthermore, deregulated miRNAs have also been reported in human villous trophoblasts during hypoxic stress. One of the more consistently elevated miRNAs by hypoxia and in the placenta of patients with pre-ecl sia is miR-210. Whether such miRNAs are bystander markers of hypoxia, or are directly involved in the pathogenesis of pre-ecl sia, needs to be clarified. There is potential for miRNAs to be used as predictors, markers or therapy in pre-ecl sia. This review provides current knowledge about miRNAs, particularly hypoxia-related miRNAs and the interaction of hypoxia, miRNAs and placenta in pre-ecl sia.
C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation
Publisher: Elsevier BV
Date: 10-2001
DOI: 10.1016/S0092-8674(01)00507-4
Abstract: HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. Recent studies have defined posttranslational modification by prolyl hydroxylation as a key regulatory event that targets HIF-alpha subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Here, we define a conserved HIF-VHL-prolyl hydroxylase pathway in C. elegans, and use a genetic approach to identify EGL-9 as a dioxygenase that regulates HIF by prolyl hydroxylation. In mammalian cells, we show that the HIF-prolyl hydroxylases are represented by a series of isoforms bearing a conserved 2-histidine-1-carboxylate iron coordination motif at the catalytic site. Direct modulation of recombinant enzyme activity by graded hypoxia, iron chelation, and cobaltous ions mirrors the characteristics of HIF induction in vivo, fulfilling requirements for these enzymes being oxygen sensors that regulate HIF.
A THRILLING CASE OF HIATUS-HERNIA
Publisher: Oxford University Press (OUP)
Date: 11-1989
Abstract: A 65 year old woman was found to have a left parasternal heave and a systolic murmur associated with a thrill. A chest radiograph, echocardiogram and gastrograffin swallow demonstrated a massive obstructed hiatus hernia which displaced the heart anteriorly. Aspiration of the contents of the hernia led to complete resolution of the physical signs. Possible mechanisms for their production are discussed.
International Study of Comparative Health Effectiveness with Medical and Invasive Approaches–Chronic Kidney Disease (ISCHEMIA-CKD): Rationale and design
Publisher: Elsevier BV
Date: 11-2018
Cancer cell detection device for the diagnosis of bladder cancer from urine
Publisher: Elsevier BV
Date: 2021
Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor
Publisher: Elsevier BV
Date: 09-2004
Nutrition screening by nurses in dialysis
Publisher: Wiley
Date: 08-10-2012
DOI: 10.1111/J.1365-2702.2012.04286.X
Abstract: To determine whether a nurse-completed dialysis nutritional screening tool improves referral rates for nutritional support and compare nutrition sensitive biochemical indices, mortality rates and patient-centred quality of life outcomes between referred and non-referred dialysis patients. People with chronic kidney disease requiring dialysis are nutritionally at risk. Nutrition screening has been shown to identify dialysis patients who are nutritionally at risk to refer to dietitian expertise. Prospective cluster-randomised control trial. Monthly nurse-completed nutrition screening was completed for six consecutive months using a validated four-item instrument measuring weight change, serum phosphate, serum potassium and appetite. Participants (n = 81) were haemodialysis patients from four satellite haemodialysis centres in one Australian metropolitan health service. Primary outcome measure was rate of referral to dietetic services for nutrition support for intervention vs. control groups at six months. Secondary outcome measures were blood pressure, biochemical indices and mortality for referred vs. non-referred patients at six and nine months, and generic and dialysis-specific quality of life for referred vs. non-referred at nine months was examined. There were three times as many dietetic referrals in the intervention group than in the control group (26·3 vs. 9·3%). Serum phosphate increased significantly more in the referred patients than the non-referred patients. There were no clinically significant changes between groups in quality of life, blood pressure, mortality rates or other biochemical indices at either six or nine months. Nurse-completed nutritional screening can lead to appropriate dietetic referrals for nutritional support by nutritional expert clinicians. This study is the first to demonstrate that monthly systematic nurse-completed nutritional screening can facilitate appropriate dietetic referrals that may lead to increased nutritional care for people in satellite dialysis centres.
Predicting Cardiac Prognosis in Asymptomatic Chronic Kidney Disease Patients
Publisher: Elsevier BV
Date: 02-2018
Remote ischaemic preconditioning
Publisher: F1000 Research Ltd
Date: 13-12-2016
DOI: 10.12688/F1000RESEARCH.9633.1
Abstract: Brief periods of ischaemia followed by reperfusion of one tissue such as skeletal muscle can confer subsequent protection against ischaemia-induced injury in other organs such as the heart. Substantial evidence of this effect has been accrued in experimental animal models. However, the translation of this phenomenon to its use as a therapy in ischaemic disease has been largely disappointing without clear evidence of benefit in humans. Recently, innovative experimental observations have suggested that remote ischaemic preconditioning (RIPC) may be largely mediated through hypoxic inhibition of the oxygen-sensing enzyme PHD2, leading to enhanced levels of alpha-ketoglutarate and subsequent increases in circulating kynurenic acid (KYNA). These observations provide vital insights into the likely mechanisms of RIPC and a route to manipulating this mechanism towards therapeutic benefit by direct alteration of KYNA, alpha-ketoglutarate levels, PHD inhibition, or pharmacological targeting of the incompletely understood cardioprotective mechanism activated by KYNA.
Hypoxia response elements
Publisher: Elsevier BV
Date: 09-2004
Variations within oxygen-regulated gene expression in humans
Publisher: American Physiological Society
Date: 2009
DOI: 10.1152/JAPPLPHYSIOL.90578.2008
Abstract: The effects of hypoxia on gene transcription are mainly mediated by a transcription factor complex termed hypoxia-inducible factor (HIF). Genetic manipulation of animals and studies of humans with rare hereditary disease have shown that modifying the HIF pathway affects systems-level physiological responses to hypoxia. It is, however, an open question whether variations in systems-level responses to hypoxia between in iduals could arise from variations within the HIF system. This study sought to determine whether variations in the responsiveness of the HIF system at the cellular level could be detected between normal in iduals. Peripheral blood lymphocytes (PBL) were isolated on three separate occasions from each of 10 healthy volunteers. After exposure of PBL to eight different oxygen tensions ranging from 20% to 0.1%, the expression levels of four HIF-regulated transcripts involved in different biological pathways were measured. The profile of expression of all four transcripts in PBL was related to oxygen tension in a curvilinear manner. Double logarithmic transformation of these data resulted in a linear relationship that allowed the response to be parameterized through a gradient and intercept. Analysis of variance (ANOVA) on these parameters showed that the level of between-subject variation in the gradients of the responses that was common across all four HIF-regulated transcripts was significant ( P = 0.008). We conclude that statistically significant variation within the cellular response to hypoxia can be detected between normal humans. The common nature of the variability across all four HIF-regulated genes suggests that the source of this variation resides within the HIF system itself.
Characterization of different isoforms of the HIF prolyl hydroxylase PHD1 generated by alternative initiation
Publisher: Portland Press Ltd.
Date: 14-06-2006
DOI: 10.1042/BJ20051996
Abstract: The heterodimeric transcription factor HIF (hypoxia-inducible factor) is central to the regulation of gene expression by oxygen. Three oxygen-dependent prolyl hydroxylase enzymes [PHD1 (prolyl hydroxylase domain 1), PHD2 and PHD3] control the abundance of HIF. In the presence of oxygen, they hydroxylate specific proline residues in HIF-α, allowing recognition by pVHL (von Hippel-Lindau protein) and subsequent ubiquitylation and proteasomal destruction. The precise roles and regulation of these enzymes are therefore of particular importance in understanding the physiological and pathological responses to hypoxia. In the present study, we define the existence of two species of PHD1 and provide evidence that they are generated by alternative translational initiation. We demonstrate that these alternative forms are both biologically active with similar HIF prolyl hydroxylase activity but that they differ in their responses to oestrogen, cell confluence and proteasomal inhibition. We show that the two PHD1 species are subject to proteolytic regulation but differ markedly in their protein stability. Though each isoform has the potential to interact with members of the Siah (seven in absentia homologue) ubiquitin ligase family, genetic studies indicated that other proteolytic mechanisms are responsible for control of stability under the conditions examined. The data define the existence of a further level of control in the pathway that regulates cellular responses to hypoxia.
Oxygen regulated gene expression: Erythropoietin as a model system
Publisher: Elsevier BV
Date: 02-1997
DOI: 10.1038/KI.1997.72
Abstract: As the relationship between the built environment and the sense of human experience becomes increasingly important, emotional geography has begun to focus on sentiments in space and time and improving the quality of urban construction from the perspective of public emotion and mental health. While youth is a powerful force in urban construction, there are no studies on the relationship between urban youth sentiments and the built environment. With the development of the Internet, social media has provided a large source of data for the metrics of youth sentiment. Based on data from more than 10,000 geolocated Sina Weibo comments posted over one week (from 19 to 25 July 2021) in Shanghai and using a machine learning algorithm for attention mechanism, this study calculates the sentiment label and sentiment intensity of each comment. Ten elements in five aspects were selected to assess the built environment at different scales and also to explore the correlations between built environment elements and sentiment intensity at different scales. The study finds that the overall sentiment of Shanghai youth tends to be negative. Sentiment intensity is significantly associated with most built environment elements at smaller scales. Urban youth have a higher proportion of both happy and sad sentiments, within which sad sentiments are more closely related to the built environment and are significantly related to all built environment elements. This study uses a deep learning algorithm to improve the accuracy of sentiment classification and confirms that the built environment has a great impact on sentiment. This research can help cities develop built environment optimization measures and policies to create positive emotional environments and enhance the well-being of urban youth.
Selective Microfluidic Capture and Detection of Prostate Cancer Cells from Urine without Digital Rectal Examination
Publisher: MDPI AG
Date: 04-11-2021
Abstract: Urine-based biomarkers have shown suitable diagnostic potential for prostate cancer (PCa) detection. Yet, until now, prostatic massage remains required prior to urine s ling. Here, we test a potential diagnostic approach using voided urine collected without prior digital rectal examination (DRE). In this study, we evaluated the diagnostic performance of a microfluidic-based platform that combines the principle of photodynamic diagnostic with immunocapture for the detection of PCa cells. The functionality and sensitivity of this platform were validated using both cultured cells and PCa patient urine s les. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) demonstrated this platform had a detection limit of fewer than 10 cells per 60 µL and successfully validated the presence of a PCa biomarker in the urine of cancer patients without prior DRE. This biosensing platform exhibits a sensitivity of 72.4% and a specificity of 71.4%, in suitable agreement with qRT-PCR data. The results of this study constitute a stepping stone in the future development of noninvasive prostate cancer diagnostic technologies that do not require DRE.
The use of dioxygen by HIF prolyl hydroxylase (PHD1)
Publisher: Elsevier BV
Date: 06-2002
DOI: 10.1016/S0960-894X(02)00219-6
Abstract: The hypoxic response in animals is mediated by hydroxylation of proline residues in the alpha-subunit of hypoxia inducible factor (HIF). Hydroxylation is catalysed by prolyl-4-hydroxylases (PHD isozymes in humans) which are iron(II) and 2-oxoglutarate dependent oxygenases. Mutation of the arginine proposed to bind 2-oxoglutarate and of the 2His-1-carboxylate iron(II) binding motif in PHD1 dramatically reduces its activity. The source of the oxygen of the product alcohol is (>95%) dioxygen.
F-18 fluorodeoxyglucose PET in the diagnosis of vascular invasion in renal cell carcinoma
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1999
Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth
Publisher: Proceedings of the National Academy of Sciences
Date: 22-07-1997
Abstract: Recent studies of tissue culture cells have defined a widespread system of oxygen-regulated gene expression based on the activation of a heterodimeric transcription factor termed hypoxia-inducible factor-1 (HIF-1). To determine whether the HIF-1 transcriptional response is activated within solid tumors and to define the consequences, we have studied tumor xenografts of a set of hepatoma (Hepa-1) cells that are wild type (wt), deficient (c4), and revertant (Rc4) for an obligatory component of the HIF-1 heterodimer, HIF-1β. Because HIF-1β is also essential for the xenobiotic response (in which it is termed the aryl hydrocarbon receptor nuclear translocator), we also studied c31 cells, which have a different defect in the xenobiotic response and form the HIF-1 complex normally. Two genes that show different degrees of HIF-1-dependent hypoxia-inducible expression in cell culture were selected for analysis—the glucose transporter, GLUT3, and vascular endothelial growth factor (VEGF). In situ hybridization showed intense focal induction of gene expression in tumors derived from wt, Rc4, and c31 cells, which was reduced (VEGF) or not seen (GLUT3) in those derived from c4 cells. In association with these changes, tumors of c4 cells had reduced vascularity and grew more slowly. These findings show that HIF-1 activation occurs in hypoxic regions of tumors and demonstrate a major influence on gene expression, tumor angiogenesis, and growth.
Reduced myocardial perfusion in post renal transplant population is not associated with aortic stiffness
Publisher: Springer Science and Business Media LLC
Date: 2014
Probing Hexaminolevulinate Mediated PpIX Fluorescence in Cancer Cell Suspensions in the Presence of Chemical Adjuvants
Publisher: MDPI AG
Date: 22-04-2020
DOI: 10.3390/IJMS21082963
Abstract: Exogenous administration of hexaminolevulinate (HAL) induces fluorescent protoporphyrin IX (PpIX) accumulation preferentially in cancer cells. However, the PpIX fluorescence intensities between noncancer and cancer cells are highly variable. The contrast between cancer and noncancer cells may be insufficient to reliably discriminate, especially at the single cell level in cancer diagnostics. This study examines the use of the chemical adjuvants dimethylsulphoxide (DMSO) or deferoxamine (DFO) to enhance the HAL induced PpIX accumulation in cancer cells. Our results showed that in some of the incubation conditions tested, the addition of DFO with HAL significantly increased PpIX 21 fluorescence of adherent monolayer cancer cells, but this was never the case for cells in suspension. Permeabilisation with DMSO did not increase PpIX fluorescence. Cell-to-cell interaction may well play an important role in the PpIX accumulation when suspended cells are treated in HAL and adjuvant chemicals.
Dipping your feet in the water: podocytes in urine
Publisher: Informa UK Limited
Date: 11-04-2014
DOI: 10.1586/14737159.2014.908122
Abstract: Podocyte injury and loss plays an important role in the pathogenesis and progression of many kidney diseases. Studies have shown that podocyte-related markers and products can be detected in the urine of patients with glomerular diseases such as focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis, diabetic nephropathy and pre-ecl sia. Therefore, detecting the loss of podocytes in the urine provides a useful noninvasive technique of gathering information about the disease type and/or activity of glomerular diseases. Currently, urine podocyte-related protein markers, mRNA, microRNA and exosomes have been used with varying degrees of success to study glomerular diseases. The determination of urinary podocyte loss may become an important noninvasive tool in the evaluation of glomerular diseases.
Myocardial oxygenation is reduced in end-stage renal failure: a novel blood oxygen level dependant (BOLD)-cardiac MRI study
Publisher: Springer Science and Business Media LLC
Date: 2014
Albuminuria is not associated with elevated urinary vesicle concentration but can confound nanoparticle tracking analysis
Publisher: Wiley
Date: 17-10-2017
DOI: 10.1111/NEP.12867
Abstract: Extracellular vesicles, such as exosomes, are present in urine with reports of roles in intercellular signalling and diagnostic utility. However, the extent to which the concentration and characteristics of urinary vesicles are altered in albuminuric renal disease has not been well characterized. In this study, we examined the number and characteristics of extracellular vesicles in albuminuric urine. Vesicles were isolated from the urine of 32 patients with varying levels of albuminuria using ultracentrifugation and density gradient purification and were examined using nanoparticle tracking analysis, immunoblotting and transmission electron microscopy. The size profile of particles in these urine preparations was compared with albumin-containing solutions. Overall, there were no substantial differences in the number, or characteristics, of vesicles released into proteinuric urine. Analysis of albumin-containing solutions showed particles of exosome-like size, suggesting that such particles can mimic exosomes in standard nanoparticle tracking analysis. Albumin and IgG depletion of proteinuric urine resulted in a substantial reduction in the concentration of particles detected by nanoparticle tracking analysis. There was no increase in urinary vesicle concentration in patients with albuminuria. Furthermore, these results demonstrate the need for cautious interpretation of nanoparticle tracking analysis of vesicle concentration in biological fluids containing protein and for sophisticated preparative methods in vesicle purification from urine.
Myocardial perfusion is impaired in asymptomatic patients post renal transplantation
Publisher: Springer Science and Business Media LLC
Date: 2013
Hypoxia-inducible Factor (HIF) Asparagine Hydroxylase Is Identical to Factor Inhibiting HIF (FIH) and Is Related to the Cupin Structural Family
Publisher: Elsevier BV
Date: 07-2002
Biosensor device for the photo-specific detection of immuno-captured bladder cancer cells using hexaminolevulinate: An ex-vivo study
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.PDPDT.2019.08.001
Abstract: Exogenous administration of the photodynamic agent hexaminolevulinate induces Protoporphyrin IX (PpIX) accumulation in malignant tissue. This may enable differentiation from healthy tissues by emission of a distinctive red fluorescence. It provides the photo-specific detection when excited with blue light at 405 nm. This study determines the ex-vivo processing conditions (time, concentration, temperature and addition of a fluorescent dye) required for HAL-induced PpIX fluorescence to successfully discriminate between bladder cancer and benign fibroblast cells shed in urine at the single cell level. HAL-induced fluorescence was 4.5 times brighter in cancer cells than non-cancer cells when incubated in the optimum conditions, and could be used to correctly identified bladder cancer cells captured within a newly developed immunofunctionalized biosensor with 88% efficiency. This biosensor is designed to facilitate the immuno-capture of cancer cells by interaction with carcinoma specific anti Epithelial Cell Adhesion molecule (anti-EpCAM) antibodies. Anti-EpCAM antibodies were immobilized on polyoxazoline (POx) plasma polymers by covalent bonds in microfluidic channels. Combining photodynamic and immunoselective approach therefore constitute a promising approach for the non-invasive diagnosis of bladder cancer with two independent level of confidence. This study investigate the relationship between different regulatory factors (time, concentration, temperature and addition of a fluorescent dye) and Hexaminolevulinate (HAL)-mediated photodynamic diagnosis of bladder cancer (PDD) in vitro. We examine the natural photosensitizer Protoporphyrin IX (PpIX) fluorescence induced by HAL in several human bladder cancer cell lines and one non-cancer foreskin fibroblast cell line and identify the processing conditions that maximise the difference in fluorescence intensity between malign and benign cell types. The detection of HAL induced fluorescence at a single cell level by a selective cancer cell capture platform is also tested. Experiments were performed on cultured monolayer cells and cells in suspension. The cell lines examined included the transitional epithelium carcinoma cell lines HT1197, HT1376, EJ138 and RT4, and the non-cancer foreskin fibroblasts HFF. Cells were incubated with HAL in various doses, time and temperature settings. We also used the nuclear red as a tool to study the PpIX subcellular localization. PpIX fluorescence intensities were measured and analysed using fluorescence microscope software. Finally, we evaluated the possibility of using HAL to discriminate between cancer and non-cancer cells from a mixed cell population using a newly developed immunofunctionalized microfluidic platform. The accumulation of PpIX in bladder cancer cells was significantly higher than in non-cancer cells, both cultured monolayer cells and cells in suspension. Effectively, the fluorescence intensity was 4.5 times brighter in bladder cancer cells than non-cancer foreskin fibroblast cells when incubated in the optimum condition, in which the nuclear stain adjuvant acted as a fluorescence enhancer. Cancer cells displayed PpIX accumulated mainly in mitochondria but none or very little PpIX was observed in non-cancer cells. HAL-induced fluorescence could be used to correctly identify bladder cancer cells within the EpCAM conjugated POx based microfluidic sensor with an 88% capture selectivity rate. These findings prove that the application of HAL-induced PpIX fluorescence can successfully distinguish between cancer and non-cancer cells in vitro. This test can provide advanced second level of confidence on the cancerous nature of cells captured by the immunofunctionalized bladder cancer diagnostic platform.
Related Organisations
Related Funding Activities
Discovery Projects - Grant ID: DP150102860
Start Date: 2015
End Date: 08-2019
Amount: $364,000.00
Funder: Australian Research Council
View Funded Activity