Timelapse viability assay to detect division and death of primary multiple myeloma cells in response to drug treatments with single cell resolution.

Heterogeneity among cancer cells and in the tumor microenvironment (TME) is thought to be a significant contributor to the heterogeneity of clinical therapy response observed between patients and can evolve over time. A primary example of this is multiple myeloma (MM), a generally incurable cancer where such heterogeneity contributes to the persistent evolution of drug resistance. However, there is a paucity of functional assays for studying this heterogeneity in patient samples or for assessing the influence of the patient TME on therapy response.

A Hyaluronan and Proteoglycan Link Protein 1 Matrikine: Role of Matrix Metalloproteinase 2 in Multiple Myeloma NF-κB Activation and Drug Resistance.

Unlabelled: The NF-κB signaling pathway plays key roles in inflammation and the pathogenesis of many solid and hematologic malignancies, including multiple myeloma, a malignancy of the plasma cells. While proteasome inhibitors, such as bortezomib, employed in multiple myeloma treatments may inhibit NF-κB signaling pathways, multiple myeloma cells often become drug resistant in part due to non-cell autonomous mechanism(s) from the multiple myeloma tumor microenvironment. We previously found that fragments of, but not full-length, hyaluronan and proteoglycan link protein 1 (HAPLN1), produced by multiple myeloma bone marrow stromal cells (BMSC), activate an atypical bortezomib-resistant NF-κB pathway in multiple myeloma cells.

Bone Marrow Stromal Cells Transcriptionally Repress ESR1 but Cannot Overcome Constitutive ESR1 Mutant Activity.

Estrogen receptor α (ER) is the target of endocrine therapies in ER-positive breast cancer (BC), but their therapeutic effectiveness diminishes with disease progression. Most metastatic BCs retain an ER-positive status, but ER expression levels are reduced. We asked how the bone tumor microenvironment (TME) regulates ER expression.

Intermittent hypoxia is a proinflammatory stimulus resulting in IL-6 expression and M1 macrophage polarization.

The biological factors that promote inflammation or nonalcoholic steatohepatitis (NASH) in the setting of nonalcoholic fatty liver disease remain incompletely understood. Clinical studies have demonstrated an association between obstructive sleep apnea (OSA) and both inflammation and fibrosis in NASH, but the mechanism has not been identified. In this study, we use modeling to examine the impact of intermittent hypoxia on the liver.

Immobilisation of barley aleurone layers enables parallelisation of assays and analysis of transient gene expression in single cells.

The barley aleurone layer is an established model system for studying phytohormone signalling, enzyme secretion and programmed cell death during seed germination. Most analyses performed on the aleurone layer are end-point assays based on cell extracts, meaning each sample is only analysed at a single time point. By immobilising barley aleurone layer tissue on polydimethylsiloxane pillars in the lid of a multiwell plate, continuous monitoring of living tissue is enabled using multiple non-destructive assays in parallel.

Apolipoprotein B100 is required for hepatitis C infectivity and Mipomersen inhibits hepatitis C.

Aim: To characterize the role of apolipoprotein B100 (apoB100) in hepatitis C viral (HCV) infection.

Methods: In this study, we utilize a gene editing tool, transcription activator-like effector nucleases (TALENs), to generate human hepatoma cells with a stable genetic deletion of to assess of apoB in HCV. Using infectious cell culture-competent HCV, viral pseudoparticles, replicon models, and lipidomic analysis we determined the contribution of apoB to each step of the viral lifecycle.

Monitoring intra- and extracellular redox capacity of intact barley aleurone layers responding to phytohormones.

Redox regulation is important for numerous processes in plant cells including abiotic stress, pathogen defence, tissue development, seed germination and programmed cell death. However, there are few methods allowing redox homeostasis to be addressed in whole plant cells, providing insight into the intact in vivo environment. An electrochemical redox assay that applies the menadione-ferricyanide double mediator is used to assess changes in the intracellular and extracellular redox environment in living aleurone layers of barley (Hordeum vulgare cv.

Development and automation of a novel NET-PET tracer: [11C]Me@APPI.

Introduction: The norepinephrine transporter (NET) is an important target for research in neurology and psychology and is involved in the pathophysiology of many neurodegenerative diseases such as Alzheimer's disease and attention deficient hyperactivity disorder. For visualization of NET abundance and deregulation, a novel PET tracer--[(11)C]Me@APPI--has been developed.

Methods: For precursor synthesis, a 4-step synthesis starting from N-phenyl-o-phenylenediamine was set up.