Diseases Commons^™

Future Perspectives Of Uveal Melanoma Blood Based Biomarkers, Aaron B. Beasley, Fred K. Chen, Timothy W. Isaacs, Elin S. Gray

Research outputs 2022 to 2026

Uveal melanoma (UM) is the most common primary intraocular malignancy affecting adults. Despite successful local treatment of the primary tumour, metastatic disease develops in up to 50% of patients. Metastatic UM carries a particularly poor prognosis, with no effective therapeutic option available to date. Genetic studies of UM have demonstrated that cytogenetic features, including gene expression, somatic copy number alterations and specific gene mutations can allow more accurate assessment of metastatic risk. Pre-emptive therapies to avert metastasis are being tested in clinical trials in patients with high-risk UM. However, current prognostic methods require an intraocular tumour biopsy, which is a …

Exercise In Advanced Prostate Cancer Elevates Myokine Levels And Suppresses In-Vitro Cell Growth, Jin Soo Kim, Dennis R. Taaffe, Daniel A. Galvão, Nicolas H. Hart, Elin Gray, Charles J. Ryan, Stacey A. Kenfield, Fred Saad, Robert U. Newton

Research outputs 2022 to 2026

Background:

Altering the systemic milieu through exercise has been proposed as a potential mechanism underlying exercise-driven tumour suppression. It is not yet known whether men with advanced prostate cancer can elicit such adaptations following a program of exercise. The purpose is to examine myokine levels of serum acquired from metastatic castrate-resistant prostate cancer (mCRPC) patients recruited to the INTERVAL-GAP4 trial before and after 6 months of exercise and its tumour-suppressive effect.

Methods:

Twenty-five men with mCRPC (age = 74.7 ± 7.1 yrs) were randomised to supervised multimodal (aerobic and resistance) exercise (EX) or self-directed exercise control group (CON). Body composition …

Ancestral Sars-Cov-2, But Not Omicron, Replicates Less Efficiently In Primary Pediatric Nasal Epithelial Cells, Yanshan Zhu, Keng Yih Chew, Melanie Wu, Anjana C. Karawita, Georgina Mccallum, Lauren E. Steele, Ayaho Yamamoto, Larisa I. Labzin, Tejasri Yarlagadda, Alexander A. Khromykh, Xiaohui Wang, Julian D. J. Sng, Claudia J. Stocks, Yao Xia, Tobias R. Kollmann, David Martino, Merja Joensuu, Frédéric A. Meunier, Giuseppe Balistreri, Helle Bielefeldt-Ohmann, Asha C. Bowen, Anthony Kicic, Peter D. Sly, Kirsten M. Spann, Kirsty R. Short

Research outputs 2022 to 2026

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to …

Identification Of Leukocyte Surface P2x7 As A Biomarker Associated With Alzheimer's Disease, Yihan Li, Xin Huang, Christopher Fowler, Yen Y. Lim, Simon M. Laws, Noel Faux, James D. Doecke, Brett Trounson, Kelly Pertile, Rebecca Rumble, Vincent Doré, Victor L. Villemagne, Christopher C. Rowe, James S. Wiley, Paul Maruff, Colin L. Masters, Ben J. Gu

Research outputs 2022 to 2026

Alzheimer's disease (AD) has shown altered immune responses in the periphery. We studied P2X7 (a proinflammatory receptor and a scavenger receptor) and two integrins, CD11b and CD11c, on the surface of circulating leukocytes and analysed their associations with Aβ-PET, brain atrophy, neuropsychological assessments, and cerebrospinal fluid (CSF) biomarkers. Total 287 age-matched, sex-balanced participants were recruited in a discovery cohort and two validation cohorts through the AIBL study and studied using tri-colour flow cytometry. Our results demonstrated reduced expressions of P2X7, CD11b, and CD11c on leukocytes, particularly monocytes, in Aβ +ve cases compared with Aβ -ve controls. P2X7 and integrin downregulation …

Polygenic Resilience Scores Capture Protective Genetic Effects For Alzheimer’S Disease, Jiahui Hou, Jonathan L. Hess, Nicola Armstrong, Joshua C. Bis, Benjamin Grenier-Boley, Ida K. Karlsson, Ganna Leonenko, Katya Numbers, Eleanor K. O’Brien, Alexey Shadrin, Anbupalam Thalamuthu, Qiong Yang, Ole A. Andreassen, Henry Brodaty, Margaret Gatz, Nicole A. Kochan, Jean Charles Lambert, Simon M. Laws, Colin L. Masters, Karen A. Mather, Nancy L. Pedersen, Danielle Posthuma, Perminder S. Sachdev, Julie Williams, Alzheimer’S Disease Neuroimaging Initiative, Chun Chieh Fan, Stephen V. Faraone, Christine Fennema-Notestine, Shu-Ju Lin, Valentina Escott-Price, Peter Holmans, Sudha Seshadri, Ming T. Tsuang, William S. Kremen, Stephen J. Glatt

Research outputs 2022 to 2026

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience …

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

Current State Of The Art In Hypoplastic Left Heart Syndrome, Aditya K Birla, Sunita Brimmer, Walker D Short, Oluyinka O Olutoye, Jason A Shar, Suriya Lalwani, Philippe Sucosky, Anitha Parthiban, Sundeep G Keswani, Christopher A Caldarone, Ravi K Birla

Faculty, Staff and Students Publications

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart condition in which a neonate is born with an underdeveloped left ventricle and associated structures. Without palliative interventions, HLHS is fatal. Treatment typically includes medical management at the time of birth to maintain patency of the ductus arteriosus, followed by three palliative procedures: most commonly the Norwood procedure, bidirectional cavopulmonary shunt, and Fontan procedures. With recent advances in surgical management of HLHS patients, high survival rates are now obtained at tertiary treatment centers, though adverse neurodevelopmental outcomes remain a clinical challenge. While surgical management remains the standard of care for …

An Automated Risk Index For Diabetic Ketoacidosis In Pediatric Patients With Type 1 Diabetes: The Ri-Dka, David D Schwartz, Rosa Banuelos, Serife Uysal, Mili Vakharia, Kristen R Hendrix, Kelly Fegan-Bohm, Sarah K Lyons, Rona Sonabend, Sheila K Gunn, Selorm Dei-Tutu

Faculty, Staff and Students Publications

Identifying patients at high risk for diabetic ketoacidosis (DKA) is crucial for informing efforts at preventive intervention. This study sought to develop and validate an electronic medical record (EMR)-based tool for predicting DKA risk in pediatric patients with type 1 diabetes. Based on analysis of data from 1,864 patients with type 1 diabetes, three factors emerged as significant predictors of DKA: most recent A1C, type of health insurance (public vs. private), and prior DKA. A prediction model was developed based on these factors and tested to identify and categorize patients at low, moderate, and high risk for experiencing DKA within …