Site-Specific Quantitation of Drug Conjugations on Antibody-Drug Conjugates (ADCs) Using a Protease-Assisted Drug Deconjugation and Linker-like Labeling (PADDLL) Method.

Antibody-drug conjugates (ADCs) are biopharmaceuticals for the targeted delivery of antitumor agents. ADCs can be highly heterogeneous with various drug-to-antibody ratio (DAR) species, conjugation sites, and occupancy levels. The conjugation site can modulate the ADC stability and efficacy and therefore can be considered to be a critical quality attribute (CQA) during development.

Interleukin 1 Receptor-Like 1 Protein (ST2) is a Potential Biomarker for Cardiomyopathy in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a rare, fatal X-linked disorder characterized by the lack of dystrophin, a key sarcolemma muscle protein. Cardiac failure is a significant cause of death in DMD subjects. The purpose of our research was to identify potential cardiac serum biomarkers associated with DMD cardiomyopathy.

Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children.

Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.

Correction: Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study.

[This corrects the article DOI: 10.1371/journal.pone.

Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study.

Serum metabolite profiling in Duchenne muscular dystrophy (DMD) may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS) for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate) in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age.

Clinical utility of serum biomarkers in Duchenne muscular dystrophy.

Assessments of disease progression and response to therapies in Duchenne muscular dystrophy (DMD) patients remain challenging. Current DMD patient assessments include complex physical tests and invasive procedures such as muscle biopsies, which are not suitable for young children. Defining alternative, less invasive and objective outcome measures to assess disease progression and response to therapy will aid drug development and clinical trials in DMD.

Discovery of serum protein biomarkers in the mdx mouse model and cross-species comparison to Duchenne muscular dystrophy patients.

It is expected that serum protein biomarkers in Duchenne muscular dystrophy (DMD) will reflect disease pathogenesis, progression and aid future therapy developments. Here, we describe use of quantitative in vivo stable isotope labeling in mammals to accurately compare serum proteomes of wild-type and dystrophin-deficient mdx mice. Biomarkers identified in serum from two independent dystrophin-deficient mouse models (mdx-Δ52 and mdx-23) were concordant with those identified in sera samples of DMD patients.

The human secretome atlas initiative: implications in health and disease conditions.

Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts toward secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings.

Secretome survey of human plexiform neurofibroma derived Schwann Cells reveals a secreted form of the RARRES1 protein.

To bring insights into neurofibroma biochemistry, a comprehensive secretome analysis was performed on cultured human primary Schwann cells isolated from surgically resected plexiform neurofibroma and from normal nerve tissue. Using a combination of SDS-PAGE and high precision LC-MS/MS, 907 proteins were confidently identified in the conditioned media of Schwann cell cultures combined. Label free proteome profiling revealed consistent release of high levels of 22 proteins by the four biological replicates of NF1 Schwann cell cultures relative to the two normal Schwann cell cultures.

Advances in the proteomic investigation of the cell secretome.

Studies of the cell secretome have greatly increased in recent years owing to improvements in proteomic platforms, mass spectrometry instrumentation and to the increased interaction between analytical chemists, biologists and clinicians. Several secretome studies have been implemented in different areas of research, leading to the generation of a valuable secretome catalogs. Secreted proteins continue to be an important source of biomarkers and therapeutic target discovery and are equally valuable in the field of microbiology.