Medicine and Health Sciences Commons^™

Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray

Research outputs 2014 to 2021

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.

METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1.

RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1

CONCLUSION: Our results reveal the potential of …

Eftilagimod Alpha, A Soluble Lymphocyte Activation Gene-3 (Lag-3) Protein Plus Pembrolizumab In Patients With Metastatic Melanoma, Victoria Atkinson, Adnan Khattak, Andrew Haydon, Melissa Eastgate, Amitesh Roy, Prashanth Prithviraj, Christian Mueller, Chrystelle Brignone, Frederic Triebel

Research outputs 2014 to 2021

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab. METHODS: The study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine …

The Prognostic Impact Of Circulating Tumour Dna In Melanoma Patients Treated With Systemic Therapies—Beyond Braf Mutant Detection, Gabriela Marsavela, Peter A. Johansson, Michelle R. Pereira, Ashleigh C. Mcevoy, Anna L. Reid, Cleo Robinson, Lydia Warburton, Muhammad A. Khattak, Tarek M. Meniawy, Benhur Amanuel, Michael Millward, Nicholas K. Hayward, Melanie R. Ziman, Elin S. Gray, Leslie Calapre

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection. Plasma ctDNA was detected in 56% of patients prior to first-line anti-PD1 and/or anti-CTLA-4 treatment. The detection rate in the immunotherapy cohort was comparably lower than those with BRAF inhibitors …

The Effects Of Yam Gruel On Lowering Fasted Blood Glucose In T2dm Rats, Xinjun Lin, Zongting Luo, Shuqin Pang, Carol Chunfeng Wang, Li Ge, Yanling Dai, Jian Zhou, Fang Chen, Xuepei Hong, Jiahui Zhang

Research outputs 2014 to 2021

© 2020 Xinjun Lin et al., published by De Gruyter 2020. There is increasing evidence of the linkage between type 2 diabetes mellitus (T2DM) and gut microbiota. Based on our previous studies, we investigated the hypoglycemic mechanisms of yam gruel to provide a scientific basis for its popularization and application. Wistar rats were randomly divided into control and T2DM model groups. Rats in the model group were stimulated by a high-sugar/high-fat diet combined with an intraperitoneal injection of streptozotocin to induce T2DM. The T2DM rats were further subdivided randomly into three groups: (1) DM, (2) DM + yam gruel, and …

Concordant Peripheral Lipidome Signatures In Two Large Clinical Studies Of Alzheimer’S Disease, Kevin Huynh, Wei Ling Florence Lim, Corey Giles, Kaushala S. Jayawardana, Agus Salim, Natalie A. Mellett, Adam Alexander T. Smith, Gavriel Olshansky, Brian G. Drew, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Matthias Arnold, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Rima Kaddurah-Daouk, Ralph N. Martins, Peter J. Meikle

Research outputs 2014 to 2021

© 2020, The Author(s). Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM3 gangliosides) and lipid …

Influence Of Strength Level On The Acute Post-Activation Performance Enhancement Following Flywheel And Free Weight Resistance Training, Borja Sañudo, Moisés De Hoyo, Guy Gregory Haff, Alejandro Muñoz-López

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This study aimed to compare the post-activation potentiation performance enhancement (PAPE) response to the acute inertial flywheel (FW) and free weight resistance training (TRA) on subsequent countermovement jump (CMJ) and sprint performance (10 m sprint). This study used a randomized crossover design including twenty-eight healthy males that were divided into strong (relative one-repetition maximum (1RM) back squat > 2.0 × body mass) and weak (relative 1RM back squat < 2.0 × body mass) groups. All participants performed the following: (a) three reps at 90% of their 1RM back squat (TRA) and (b) three reps on an inertial FW (plus one repetition to initiate flywheel movement) with an intensity that generated a mean propulsive velocity equal to that achieved with 90% of the 1RM back squat. Before and after the conditioning activity, participants performed two CMJs and two 10 m sprints. Within-group analyses showed significantly greater CMJ (d > 0.9, p < 0.001) and sprint performance (d > 0.5, p < 0.05) in the FW and the TRA group. Between-group analysis showed that sprint changes were significantly greater in the FW-strong group when compared with the TRA (F1,18 = 5.11, p = 0.036, η2p = 0.221—large) group. These results suggest that using a squat activation protocol on a FW may lead to an acute positive effect on jump and sprint performance, especially in stronger individuals.

Impact Of A Multimodal Exercise Program On Tibial Bone Health In Adolescents With Development Coordination Disorder: An Examination Of Feasibility And Potential Efficacy, Jocelyn L. Tan, Aris Siafarikas, Timo Rantalainen, Nicolas H. Hart, Fleur Mcintyre, Beth Hands, Paola Chivers

Research outputs 2014 to 2021

© 2020, International Society of Musculoskeletal and Neuronal Interactions. All rights reserved. Objectives: Developmental coordination disorder (DCD) compromises bone health purportedly due to lower levels of physical activity. The potential of an exercise intervention to improve bone health parameters in adolescents with DCD has not previously been studied. This study thus aimed to determine the impact of a multimodal exercise intervention on bone health in this population at-risk of secondary osteoporosis. Methods: Twenty-eight adolescents (17 male, 11 female) aged between 12-17 years (Mage =14.1) with DCD participated in a twice weekly, 13-week generalised multimodal exercise intervention. Peripheral quantitative computed tomography …

Population-Based Case-Control Study Revealed Metabolomic Biomarkers Of Suboptimal Health Status In Chinese Population—Potential Utility For Innovative Approach By Predictive, Preventive, And Personalized Medicine, Hao Wang, Qiuyue Tian, Jie Zhang, Hongqi Liu, Xiaoyu Zhang, Weijie Cao, Jinxia Zhang, Enoch Odame Anto, Xingang Li, Xueqing Wang, Di Liu, Yulu Zheng, Zheng Guo, Lijuan Wu, Manshu Song, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Background: Suboptimal health status (SHS) is a subclinical stage of chronic diseases, and the identification of SHS provides an opportunity for the predictive, preventive, and personalized medicine (PPPM) of chronic diseases. Previous studies have reported the associations between metabolic signatures and early signs of chronic diseases. Methods: This study aimed to detect the metabolic biomarkers for the identification of SHS in a case-control study. SHS questionnaire-25 (SHSQ-25) was used in a population-based health survey to measure the SHS levels of participants. The liquid chromatography-mass spectrometry-based untargeted metabolomics analysis was conducted on plasma samples collected from 50 SHS participants and 50 …