Human Cytokine Testing on Cell Culture Supernatant for SPHEROIDS project

3D Growth of Endothelial Cells During ISS Space Mission – The SPHEROIDS Project

The April 2017 issue of Biomaterials reports on an automated cell culture unit that was developed for the SpaceX CRS-ISS space mission that resulted in three dimensional growth of human endothelial cells in microgravity.

A spaceflight to the International Space Station, carried out in April – May 2016, included a study to examine endothelial cell (EC) behavior in respect to cellular proliferation and apoptosis under spaceflight conditions to examine the gravity dependency of EC tube formation.

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Phase I Clinical Results from FR104, a mAb Specific to CD28

Researchers led by Bernard Vanove of OSE Immunotherapeutics report in the December 7, 2016 issue of the Journal of Immunology on the first-in-human study of FR1041. OSE and collaborators at the University of Nantes and Janssen conducted a detailed phase I evaluation of safety, pharmacokinetics, pharmacodynamics and potency of FR104 in healthy volunteers.

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GDF-15 as a Possible Biomarker for Use and Dosing of Metformin in Type II Diabetes

Novel nonglycemic biomarker for metformin

The Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial delivers more insight on biomarkers that have potential to help treat patients with dysglycemia.1 Hertzel C. Gerstein and colleagues report Growth Differentiation Factor 15 as a novel biomarker for the use and dosing of metformin, in a study published in Diabetes Care last month.

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IL-10 (AM0010) phase I trial offers novel mechanism for immune-oncology drugs in solid tumors

More commonly known as an inhibitory cytokine, high doses of IL-10 have been shown to lead to the activation and survival of antigen stimulated CD8 T cells. According to a study published in the Journal of Clinical Oncology, the investigators in this first-in-human, phase 1 clinical trial of IL-10 (AM0010), demonstrate antitumor activity and therapy tolerability in a pretreated population.  The primary endpoint of the study was to establish safety, tolerability and the maximum tolerated dose.  This goal appears to have been met, with a low incidence of adverse events, most of which were temporary or reversible.  The dose-escalation study was followed by a renal cell cancer dose-expansion cohort.

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TruCulture and Gene Expression Profiling Characterizes Immune Responses in Landmark Study Led by Institut Pasteur

Published in the September 6, 2016 issue of Cell Reports, Standardized Whole-Blood Transcriptional Profiling Enables the Deconvolution of Complex Induced Immune Responses describes the use of the Myriad RBM TruCulture® platform for standardized ex vivo immune stimulation and a high-throughput method for gene expression profiling to explore immune variance within a population.
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DNA variants correlated with blood based biomarkers may predict disease features within COPD

By Sam LaBrie

Developing precision medicines for COPD is an important goal, as the disease is the third most common cause of death in the developed world and there are relatively few effective therapies. A recent study published in PLOS, Common Genetic Polymorphisms Influence Blood Biomarkers Measurements in COPD, explores the massive datasets from two cohorts, SPIROMICS and COPDGene, in a search for biomarkers linked to various aspects of COPD. Scientists combined single nucleotide polymorphisms (SNPs) and a custom MAP (Multi-Analyte Profile) of Myriad RBM’s serum biomarker assays to identify protein quantitative trait loci (pQTLs), i.e. genetic features that are correlated with variations in protein expression).

Data analysis revealed 527 SNPs that are associated with 38 protein biomarkers (pQTLs). For 13 of these proteins, the pQTL could explain >10% of the variation in expression levels seen in the 2 cohorts, with the strongest influence being ~75% of the change in expression of vitamin D binding protein. Several of the pQTLs show significant associations with disease phenotypes, including the pQTL linked to sRAGE, which has been previously associated with emphysema. A striking finding was that SNPs in the ABO blood group region of the genome are strongly associated with many protein biomarker levels. Interestingly, the ABO blood group and COPD have been linked in earlier studies, confirming that ABO status should be taken into consideration for future COPD studies.

The authors conclude that multi-omics studies like this one are important for understanding complex diseases like COPD.

Monitoring differences in the innate and adaptive immune response in Amish and Hutterite children

By Ralph McDade

Let your kids get dirty; it’s good for them!

In the current issue of the New England Journal of Medicine researchers explore the mechanism behind the effect of endotoxin exposure on asthma and allergies in children. The researchers used Myriad RBM’s TruCulture® tubes to collect and stimulate whole blood in order to study differences in the innate and adaptive immune response in Amish and Hutterite children. The authors also investigated cellular changes and allergy biomarkers in serum. Amish and Hutterite people are similar in genetic make-up and lifestyle, but differ in exposure to microbial antigen which has been shown to be protective for asthma and allergies in other studies.

The results show that Amish children, who –through their families’ dairy farms– are more exposed to endotoxins then their Hutterite counterparts, have a reduced incidence of asthma and allergies coinciding with lower serum IgE levels. Stimulating the innate immune system with LPS resulted in lower cytokine release in Amish then Hutterite children, but there were no differences when using a T cell specific stimulant. This data and changes in immune cell populations suggests that lower asthma incidence in children exposed to microbial antigen and their endotoxin is mediated by changes in innate immunity.

Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children by M.M. Stein et al. in the NEJM Read the full article AND watch the 2 minute QuickTake video

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