Digital Commons Network^™

Two Maximal Isometric Contractions Attenuate The Magnitude Of Eccentric Exercise-Induced Muscle Damage, Hsin-Lian Chen, Kazunori Nosaka, Alan Pearce, Trevor C Chen

Research outputs 2012

This study investigated whether maximal voluntary isometric contractions (MVC-ISO) would attenuate the magnitude of eccentric exercise-induced muscle damage. Young untrained men were placed into one of the two experimental groups or one control group (n = 13 per group). Subjects in the experimental groups performed either two or 10 MVC-ISO of the elbow flexors at a long muscle length (20° flexion) 2 days prior to 30 maximal isokinetic eccentric contractions of the elbow flexors. Subjects in the control group performed the eccentric contractions without MVC-ISO. No significant changes in maximal voluntary concentric contraction peak torque, peak torque angle, range of …

Maternal Work Hours In Early To Middle Childhood Link To Later Adolescent Diet Quality, Jianghong Li, Therese O'Sullivan, Sarah Johnson, Fiona Stanley, Wendy H. Oddy

Research outputs 2012

Objective: Previous studies on maternal work hours and child diet quality have reported conflicting findings possibly due to differences in study design, lack of a comprehensive measure of diet quality and differing ages of the children under investigation. The present study aimed to prospectively examine the impact of parental work hours from age 1 year to age 14 years on adolescent diet quality.

Design: Multivariate linear regression models were used to examine independent associations between parents' work hours at each follow-up and across 14 years and adolescent diet quality at age 14 years. A diet quality index was based on …

Anxiety, Depression, And Comorbid Anxiety And Depression: Risk Factors And Outcome Over Two Years, O P Almeida, B Draper, J Pirkis, J Snowdon, N T Lautenschlager, G Byrne, Moira Sim, N Stocks, N Kerse, L Flicker, J J Pfaff

Research outputs 2012

Background: This study aimed to determine: (1) the prevalence of depression, anxiety, and depression associated with anxiety (DA); (2) the risk factor profile of depression, anxiety, and DA; (3) the course of depression, anxiety, and DA over 24 months. Methods: Two-year longitudinal study of 20,036 adults aged 60+ years. We used the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale anxiety subscale to establish the presence of depression and anxiety, and standard procedures to collect demographic, lifestyle, psychosocial, and clinical data. Results: The prevalence of anxiety, depression, and DA was 4.7%, 1.4%, and 1.8%. About 57% of depression …

Age And Premorbid Intelligence Suppress Complaint-Performance Congruency In Raw Score Measures Of Memory, Matthew Merema, Craig Speelman, Elizabeth Kaczmarek, Jonathan Foster

Research outputs 2012

Background: We aimed to examine the role of age and premorbid intelligence (IQ) in suppressing the relationship between subjective memory complaints (SMCs) and raw score memory performance. Methods: We used a community sample of older adults aged 66"90 years (N = 121) to test whether the inclusion of age and a premorbid IQ measure in multiple regression analyses increased semipartial correlations of raw score memory performance in predicting SMCs. Rank contrast correlations were also carried out to observe how age and premorbid IQ are related to complaint"performance congruency. Measures utilized in the study included the Memory Functioning Questionnaire (for SMCs), …

Lifestyle And Late Life Cognitive Health: Sufficient Evidence To Act Now?, Bruce Barber, D Ames, Kathryn Ellis, Ralph Martins, C Masters, C Szoeke

Research outputs 2012

No abstract provided.

Predictors Of Rapid Cognitive Decline In Alzheimer's Disease: Results From The Australian Imaging, Biomarkers And Lifestyle (Aibl) Study Of Ageing, A Sona, P Zhang, D Ames, A I Bush, N T Lautenschlager, Ralph Martins, C L Masters, C C Rowe, C Szoeke, Kevin Taddei, Kathryn A Ellis

Research outputs 2012

Background: The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients.

Methods: We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as …

Viability Of Healthcare Service Delivery Alternatives For The Australian Mining Sector, Patricia Williams, Margaret Giles

Research outputs 2012

The changing and demanding nature of the mining workforce in rural and remote Australia brings unique challenges to the delivery of healthcare services. In an attempt to control costs whilst delivering cost effective and quality healthcare, new models of delivery must be considered. For a workforce that is fly-in/fly-out, the provision of healthcare is problematic given the lack of consistency in location. A cost-benefit framework is analysed comparing three models of service provision using travel to a major location, locum services and remote health monitoring. Ultimately, new models of care must be considered to address the issues of increasing workforce …

Comparative Genomics Of Brachyspira Pilosicoli Strains: Genome Rearrangements, Reductions And Correlation Of Genetic Compliment With Phenotypic Diversity, Luke Mappley, Michael Black, Manal Abuoun, Alistair C. Darby, Martin J. Woodward, Julian Parkhill, A. Keith Turner, Matthew I. Bellgard, Tom La, Nyree D. Phillips, Roberto M. La Ragione, David J. Hampson

Research outputs 2012

Background: The anaerobic spirochaete Brachyspira pilosicoli causes enteric disease in avian, porcine and human hosts, amongst others. To date, the only available genome sequence of B. pilosicoli is that of strain 95/1000, a porcine isolate. In the first intra-species genome comparison within the Brachyspira genus, we report the whole genome sequence of B. pilosicoli B2904, an avian isolate, the incomplete genome sequence of B. pilosicoli WesB, a human isolate, and the comparisons with B. pilosicoli 95/1000. We also draw on incomplete genome sequences from three other Brachyspira species. Finally we report the first application of the high-throughput Biolog phenotype screening …

Drug Education In Victorian Schools (Devs): The Study Protocol For A Harm Reduction Focused School Drug Education Trial, Richard Midford, Helen Cahill, David Foxcroft, Leanne Lester, Lynne Venning, Robyn Ramsden, Michelle Pose

Research outputs 2012

Background: This study seeks to extend earlier Australian school drug education research by developing and measuring the effectiveness of a comprehensive, evidence-based, harm reduction focused school drug education program for junior secondary students aged 13 to 15 years. The intervention draws on the recent literature as to the common elements in effective school curriculum. It seeks to incorporate the social influence of parents through home activities. It also emphasises the use of appropriate pedagogy in the delivery of classroom lessons. Methods/Design. A cluster randomised school drug education trial will be conducted with 1746 junior high school students in 21 Victorian …

Chronic Low Back Pain Is Associated With Reduced Vertebral Bone Mineral Measures In Community-Dwelling Adults, Andrew Briggs, Leon Straker, Angus Burnett, John Wark

Research outputs 2012

Background: Chronic low back pain (CLBP) experienced in middle-age may have important implications for vertebral bone health, although this issue has not been investigated as a primary aim previously. This study investigated the associations between CLBP and dual energy X-ray absorptiometry (DXA)-derived vertebral bone mineral measures acquired from postero-anterior and lateral-projections, among community-dwelling, middle-aged adults. Methods. Twenty-nine adults with CLBP (11 male, 18 female) and 42 adults with no history of LBP in the preceding year (17 male, 25 female) were evaluated. Self-reported demographic and clinical data were collected via questionnaires. Areal bone mineral density (aBMD) was measured in the …

Evaluation Of A Multi-Marker Immunomagnetic Enrichment Assay For The Quantification Of Circulating Melanoma Cells, James Freeman, Elin Gray, Michael Milward, Robert Pearce, Melanie Ziman

Research outputs 2012

Background: Circulating melanoma cells (CMCs) are thought to be valuable in improving measures of prognosis in melanoma patients and may be a useful marker of residual disease to identify non-metastatic patients requiring adjuvant therapy. We investigated whether immunomagnetic enrichment targeting multiple markers allows more efficient enrichment of CMCs from patient peripheral blood than targeting a single marker. Furthermore, we aimed to determine whether the number of CMCs in patient blood was associated with disease stage.Methods: We captured CMCs by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271, both individually …

Can Exercise Ameliorate Treatment Toxicity During The Initial Phase Of Testosterone Deprivation In Prostate Cancer Patients? Is This More Effective Than Delayed Rehabilitation?, Robert Newton, Dennis Taaffe, Nigel Spry, Prue Cormie, Suzanne Chambers, Robert Gardiner, David Shum, David Joseph, Daniel Galvao

Research outputs 2012

Background: There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a …

Adjusting For Under-Identification Of Aboriginal And/Or Torres Strait Islander Births In Time Series Produced From Birth Records: Using Record Linkage Of Survey Data And Administrative Data Sources, D Lawrence, D Christensen, F Mitrou, Glenn Draper, G Davis, S Mckeown, Daniel Mcaullay, G Pearson, S R Zubrick

Research outputs 2012

Background: Statistical time series derived from administrative data sets form key indicators in measuring progress in addressing disadvantage in Aboriginal and Torres Strait Islander populations in Australia. However, inconsistencies in the reporting of Indigenous status can cause difficulties in producing reliable indicators. External data sources, such as survey data, provide a means of assessing the consistency of administrative data and may be used to adjust statistics based on administrative data sources. Methods. We used record linkage between a large-scale survey (the Western Australian Aboriginal Child Health Survey), and two administrative data sources (the Western Australia (WA) Register of Births and …

A Randomised Trial Of Robotic And Open Prostatectomy In Men With Localised Prostate Cancer, Robert Gardiner, J Yaxley, G Coughlin, N Dunglison, S Occhipinti, S Younie, R Carter, S Williams, R J Medcraft, Bennett Nigel, M F Lavin, Suzanne Chambers

Research outputs 2012

Background: Prostate cancer is the most common male cancer in the Western world however there is ongoing debate about the optimal treatment strategy for localised disease. While surgery remains the most commonly received treatment for localised disease in Australia more recently a robotic approach has emerged as an alternative to open and laparoscopic surgery. However, high level data is not yet available to support this as a superior approach or to guide treatment decision making between the alternatives. This paper presents the design of a randomised trial of Robotic and Open Prostatectomy for men newly diagnosed with localised prostate cancer …

Prolonged Sedentary Time And Physical Activity In Workplace And Non-Work Contexts: A Cross-Sectional Study Of Office, Customer Service And Call Centre Employees, A A Thorp, G N Healy, E Winkler, B K Clark, P A Gardiner, N Owen, David Dunstan

Research outputs 2012

Background: To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts.Methods: A convenience sample of 193 employees working in offices (131), call centres (36) and customer service (26) was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary (<100 counts per>minute; cpm), in prolonged sedentary bouts (≥20 minutes or ≥30 minutes), light-intensity activity (100-1951 cpm) and moderate-to-vigorous physical activity (MVPA; ≥1952 cpm). Using mixed models adjusted for confounders, these were compared for: work days versus non-work days; work hours versus non-work hours (work days only); …

Changes In Dairy Food And Nutrient Intakes In Australian Adolescents, Carole Parker, Wendy Vivian, Wendy H. Oddy, Lawrie J Beilin, Trevor A. Mori, Therese O'Sullivan

Research outputs 2012

Dairy nutrients, such as calcium, are particularly important in adolescence, a critical time for growth and development. There are limited Australian data following individuals through adolescence, evaluating changes in dairy nutrient and dairy product consumption. We used a validated food frequency questionnaire to investigate consumption in adolescents participating in both the 14 and 17 year follow-ups of the Western Australian Pregnancy Cohort (Raine) Study. Most adolescents did not reach age and gender specific recommended daily intakes for calcium or magnesium at 14 years, and this decreased as they aged to 17 years (from 33.0% to 29.2% meeting for calcium, P < 0.05, and from 33.6% to 20.5% meeting for magnesium, P < 0.01). Mean intakes of calcium, potassium, riboflavin and vitamin A also decreased with age (P < 0.01). Mean dairy intake decreased from 536 ± 343 g/day to 464 ± 339 g/day (P < 0.01), due mostly to a decrease in regular milk, although flavoured milk consumption increased in boys. Cheese and butter were the only products to show a significantly increased consumption over the period. Girls decreased from 2.2 to 1.9 serves/day of dairy, while boys remained relatively steady at 2.9 to 2.8 serves/day. Our findings suggest that dairy product consumption decreases over adolescence. This may have implications for bone mass, development and later health.

Olfactory Discrimination Predicts Cognitive Decline Among Community-Dwelling Older Adults, Hamid Sohrabi, Kristyn Bates, Mg Weinborn, A N Johnston, A Bahramian, Kevin Taddei, Simon Laws, Mark Rodrigues, Michael Morici, Matthew Howard, Georgia Martins, A Mackay-Sim, Se Gandy, Ralph Martins

Research outputs 2012

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions …

Intense Physical Activity Is Associated With Cognitive Performance In The Elderly, Belinda Brown, Jeremiah Peiffer, Hamid Sohrabi, Alinda Mondal, Veer Bala Gupta, Stephanie Rainey-Smith, Kevin Taddei, S Burnham, K Ellis, C Szoeke, C L Masters, D Ames, C Rowe, Ralph Martins

Research outputs 2012

Numerous studies have reported positive impacts of physical activity on cognitive function. However, the majority of these studies have utilised physical activity questionnaires or surveys, thus results may have been influenced by reporting biases. Through the objective measurement of routine levels of physical activity via actigraphy, we report a significant association between intensity, but not volume, of physical activity and cognitive functioning. A cohort of 217 participants (aged 60-89 years) wore an actigraphy unit for 7 consecutive days and underwent comprehensive neuropsychological assessment. The cohort was stratified into tertiles based on physical activity intensity. Compared with individuals in the lowest …

Eae/Ase Recommendations For Image Acquisition And Display Using Three-Dimensional Echocardiography., Roberto M. Lang, Luigi P. Badano, Wendy Tsang, David H. Adams, Eustachio Agricola, Thomas Buck, Francesco F. Faletra, Andreas Franke, Judy Hung, Leopoldo Pérez De Isla, Otto Kamp, Jaroslaw D. Kasprzak, Patrizio Lancellotti, Thomas H. Marwick, Marti L. Mcculloch, Mark J. Monaghan, Petros Nihoyannopoulos, Natesa G. Pandian, Patricia A. Pellikka, Mauro Pepi, David A. Roberson, Stanton K. Shernan, Girish S. Shirali, Lissa Sugeng, Folkert J. Ten Cate, Mani A. Vannan, Jose Luis Zamorano, William A. Zoghbi, American Society Of Echocardiography, European Association Of Echocardiography

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Structural Insight Into Mr1-Mediated Recognition Of The Mucosal Associated Invariant T Cell Receptor, Rangsima Reantragoon, Lars Kjer-Nielsen, Onisha Patel, Zhenjun Chen, Patricia T. Illing, Mugdha Bhati, Lyudmila Kostenko, Mandvi Bharadwaj, Bronwyn Meehan, Ted H. Hansen, Dale I. Godfrey, Jamie Rossjohn, James Mccluskey

Open Access Publications

Mucosal-associated invariant T (MAIT) cells express a semiinvariant αβ T cell receptor (TCR) that binds MHC class I-like molecule (MR1). However, the molecular basis for MAIT TCR recognition by MR1 is unknown. In this study, we present the crystal structure of a human Vα7.2Jα33-Vβ2 MAIT TCR. Mutagenesis revealed highly conserved requirements for the MAIT TCR-MR1 interaction across different human MAIT TCRs stimulated by distinct microbial sources. Individual residues within the MAIT TCR β chain were dispensable for the interaction with MR1, whereas the invariant MAIT TCR α chain controlled specificity through a small number of residues, which are conserved across …

Schistosome-Derived Omega-1 Drives Th2 Polarization By Suppressing Protein Synthesis Following Internalization By The Mannose Receptor, Bart Everts, Leonie Hussaarts, Nicole N. Driessen, Moniek H.J. Meevissen, Gabriele Schramm, Alwin J. Van Der Ham, Barbara Van Der Hoeven, Thomas Scholzen, Sven Burgdorf, Markus Mohrs, Edward J. Pearce, Cornelis H. Hokke, Helmut Haas, Hermelijn H. Smits, Maria Yazdanbakhsh

Open Access Publications

Omega-1, a glycosylated T2 ribonuclease (RNase) secreted by Schistosoma mansoni eggs and abundantly present in soluble egg antigen, has recently been shown to condition dendritic cells (DCs) to prime Th2 responses. However, the molecular mechanisms underlying this effect remain unknown. We show in this study by site-directed mutagenesis of omega-1 that both the glycosylation and the RNase activity are essential to condition DCs for Th2 polarization. Mechanistically, we demonstrate that omega-1 is bound and internalized via its glycans by the mannose receptor (MR) and subsequently impairs protein synthesis by degrading both ribosomal and messenger RNA. These experiments reveal an unrecognized …

Peripartum Cardiomyopathy: A Review, Anirban Bhattacharyya, Sukhdeep Singh Basra, Priyanka Sen, Biswajit Kar

The Texas Heart Institute Journal

Peripartum cardiomyopathy is idiopathic heart failure occurring in the absence of any determinable heart disease during the last month of pregnancy or the first 5 months postpartum. The incidence varies worldwide but is high in developing nations; the cause of the disease might be a combination of environmental and genetic factors. Diagnostic echocardiographic criteria include left ventricular ejection fraction2.7 cm/m(2). Electrocardiography, magnetic resonance imaging, endomyocardial biopsy, and cardiac catheterization aid in the diagnosis and management of peripartum cardiomyopathy. Cardiac protein assays can also be useful, as suggested by reports of high levels of NT-proBNP, cardiac troponin, tumor necrosis factor-α, interleukin-6, …

Neurofibromatosis 2011: A Report Of The Children's Tumor Foundation Annual Meeting., Michel Kalamarides, Maria T. Acosta, Dusica Babovic-Vuksanovic, Olli Carpen, Karen Cichowski, Dg Evans, Filippo Giancotti, Co Hanemann, David Ingram, Alison C. Lloyd, Debra A. Mayes, Ludwine Messiaen, Helen Morrison, Kathryn North, Roger Packer, Duojia Pan, Anat Stemmer-Rachamimov, Meena Upadhyaya, David Viskochil, Margret R. Wallace, Kim Hunter-Schaedle, Nancy Ratner

Peninsula Medical School

The 2011 annual meeting of the Children's Tumor Foundation, the annual gathering of the neurofibromatosis (NF) research and clinical communities, was attended by 330 participants who discussed integration of new signaling pathways into NF research, the appreciation for NF mutations in sporadic cancers, and an expanding pre-clinical and clinical agenda. NF1, NF2, and schwannomatosis collectively affect approximately 100,000 persons in US, and result from mutations in different genes. Benign tumors of NF1 (neurofibroma and optic pathway glioma) and NF2 (schwannoma, ependymoma, and meningioma) and schwannomatosis (schwannoma) can cause significant morbidity, and there are no proven drug treatments for any form …

Age Before Stage: Insulin Resistance Rises Before The Onset Of Puberty: A 9-Year Longitudinal Study (Earlybird 26)., An Jeffery, Bs Metcalf, J Hosking, Aj Streeter, Ld Voss, Tj Wilkin

Peninsula Medical School

OBJECTIVE: Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1. RESEARCH DESIGN AND METHODS: The EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5-14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity …

The Role Of Insulin-Like Growth Factors Signaling In Merlin-Deficient Human Schwannomas., Sylwia Ammoun, M. Caroline Schmid, Natalia Ristic, Lu Zhou, David Hilton, Emanuela Ercolano, Camille Carroll, C. Oliver Hanemann

Peninsula Medical School

Loss of the tumor suppressor merlin causes development of the tumors of the nervous system, such as schwannomas, meningiomas, and ependymomas occurring spontaneously or as part of a hereditary disease Neurofibromatosis Type 2 (NF2). Current therapies, (radio) surgery, are not always effective. Therefore, there is a need for drug treatments for these tumors. Schwannomas are the most frequent of merlin-deficient tumors and are hallmark for NF2. Using our in vitro human schwannoma model, we demonstrated that merlin-deficiency leads to increased proliferation, cell-matrix adhesion, and survival. Increased proliferation due to strong activation of extracellular-signal-regulated kinase 1/2 (ERK1/2) is caused by overexpression/activation …

Control Of Interneuron Dendritic Growth Through Nrg1/Erbb4-Mediated Kalirin-7 Disinhibition., M. E. Cahill, K. A. Jones, I. Rafalovich, Z. Xie, C. S. Barros, U. Müller, P. Penzes

Peninsula Medical School

Neuregulin 1 (NRG1) is a secreted trophic factor that activates the postsynaptic erbB4 receptor tyrosine kinase. Both NRG1 and erbB4 have been repeatedly associated with schizophrenia, but their downstream targets are not well characterized. ErbB4 is highly abundant in interneurons, and NRG1-mediated erbB4 activation has been shown to modulate interneuron function, but the role for NRG1-erbB4 signaling in regulating interneuron dendritic growth is not well understood. Here we show that NRG1/erbB4 promote the growth of dendrites in mature interneurons through kalirin, a major dendritic Rac1-GEF. Recent studies have shown associations of the KALRN gene with schizophrenia. Our data point to …

An Attentional Control Task Reduces Intrusive Thoughts About Smoking., Jon May, Jackie Andrade, Kimberley Willoughby, Chris Brown

School of Psychology

INTRODUCTION: Attentional control tasks such as body scanning and following isometric exercise instructions have been shown to reduce smoking cravings, apparently by reducing stress (Ussher, M., Cropley, M., Playle, S., Mohidin, R., & West, R. [2009]. Effect of isometric exercise and body scanning on cigarette cravings and withdrawal symptoms. Addiction, 104, 1251-1257. doi:10.1111/j.1360-0443.2009.02605.x). Related work based upon elaborated intrusion theory (Kavanagh, D. J., Andrade, J., & May, J. [2005]. Imaginary relish and exquisite torture: The elaborated intrusion theory of desire. Psychological Review, 112, 446-467. doi:10.1037/0033-295X.112.2.446) has shown that similar tasks can reduce hungry participants' involuntary food-related thoughts (May, J., Andrade, …

The Dermatan Sulfate Proteoglycan Decorin Modulates Α2Β1 Integrin And The Vimentin Intermediate Filament System During Collagen Synthesis., Oliver Jungmann, Katerina Nikolovska, Christian Stock, Jan-Niklas Schulz, Beate Eckes, Christoph Riethmüller, Rick T Owens, Renato V Iozzo, Daniela G Seidler

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/-)) mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/-) mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/-) fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, …

Decorin Protein Core Affects The Global Gene Expression Profile Of The Tumor Microenvironment In A Triple-Negative Orthotopic Breast Carcinoma Xenograft Model., Simone Buraschi, Thomas Neill, Rick T Owens, Leonardo A Iniguez, George Purkins, Rajanikanth Vadigepalli, Barry Evans, Liliana Schaefer, Stephen C Peiper, Zi-Xuan Wang, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found that …

Kaempferol Nanoparticles Achieve Strong And Selective Inhibition Of Ovarian Cancer Cell Viability., Haitao Luo, Bingbing Jiang, Bingyun Li, Zhaoliang Li, Bing-Hua Jiang, Yi Charlie Chen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles …