Equine strongylids: Ivermectin efficacy and fecal egg shedding patterns.

Equine cyathostomins are ubiquitous in grazing horses around the world and a main target in parasite control programs. Anthelmintic resistance has been reported with increasing frequency in these parasites over the past decades, and recent findings of fulminant resistance to the macrocyclic lactone class have raised severe concerns. This study aimed to evaluate ivermectin efficacy in cohorts of yearlings and mares present on four different farms in Central Kentucky.

Targeting B-Raf inhibitor resistant melanoma with novel cell penetrating peptide disrupters of PDE8A - C-Raf.

Background: Recent advances in the treatment of melanoma that involve immunotherapy and B-Raf inhibition have revolutionised cancer care for this disease. However, an un-met clinical need remains in B-Raf inhibitor resistant patients where first-generation B-Raf inhibitors provide only short-term disease control. In these cases, B-Raf inhibition leads to paradoxical activation of the C-Raf - MEK - ERK signalling pathway, followed by metastasis.

Anti-inflammatory Activity of MTL-CEBPA, a Small Activating RNA Drug, in LPS-Stimulated Monocytes and Humanized Mice.

Excessive or inappropriate inflammatory responses can cause serious and even fatal diseases. The CCAAT/enhancer-binding protein alpha (CEBPA) gene encodes C/EBPα, a transcription factor that plays a fundamental role in controlling maturation of the myeloid lineage and is also expressed during the late phase of inflammatory responses when signs of inflammation are decreasing. MTL-CEBPA, a small activating RNA targeting for upregulation of C/EBPα, is currently being evaluated in a phase 1b trial for treatment of hepatocellular carcinoma.

Blood-based identification of non-responders to anti-TNF therapy in rheumatoid arthritis.

Background: Faced with an increasing number of choices for biologic therapies, rheumatologists have a critical need for better tools to inform rheumatoid arthritis (RA) disease management. The ability to identify patients who are unlikely to respond to first-line biologic anti-TNF therapies prior to their treatment would allow these patients to seek alternative therapies, providing faster relief and avoiding complications of disease.

Methods: We identified a gene expression classifier to predict, pre-treatment, which RA patients are unlikely to respond to the anti-TNF infliximab.

Create a translational medicine knowledge repository--research downsizing, mergers and increased outsourcing have reduced the depth of in-house translational medicine expertise and institutional memory at many pharmaceutical and biotech companies: how will they avoid relearning old lessons?

Pharmaceutical industry consolidation and overall research downsizing threatens the ability of companies to benefit from their previous investments in translational research as key leaders with the most knowledge of the successful use of biomarkers and translational pharmacology models are laid off or accept their severance packages. Two recently published books may help to preserve this type of knowledge but much of this type of information is not in the public domain. Here we propose the creation of a translational medicine knowledge repository where companies can submit their translational research data and access similar data from other companies in a precompetitive environment.

Translational strategies to implement personalized medicine: rheumatoid arthritis examples.

Advances in the molecular definition of disease, biomarker technologies and informatics have brought us to the threshold of a new way to individualize treatment for patients - personalized medicine. However, while the clinical translation of drug metabolism and cancer-related genomics data has resulted in accepted individualized treatment paradigms, this has not occurred as frequently or efficiently for patients with common chronic diseases such as rheumatoid arthritis. This gap between the rapidly increasing amount of disease-related genomic information and its clinical translation can be addressed through the creation and testing of personalized medicine treatment hypotheses using the same strategies that translational medicine scientists utilize to achieve proof-of-concept for drugs with novel targets.

What's next in translational medicine?

Translational medicine is the integrated application of innovative pharmacology tools, biomarkers, clinical methods, clinical technologies and study designs to improve disease understanding, confidence in human drug targets and increase confidence in drug candidates, understand the therapeutic index in humans, enhance cost-effective decision making in exploratory development and increase phase II success. Translational research is one of the most important activities of translational medicine as it supports predictions about probable drug activities across species and is especially important when compounds with unprecedented drug targets are brought to humans for the first time. Translational research has the potential to deliver many practical benefits for patients and justify the extensive investments placed by the private and public sector in biomedical research.

Experiences with dose finding in patients in early drug development: the use of biomarkers in early decision making.

With the increasing cost and complexity of drug development, biomarkers will play an increasing role in the early phases. Biomarkers can be classified into target, mechanistic, or outcome with varying degrees of linkage to disease or treatment effect. They can be used to determine proof of concept by characterising the efficacy or safety profiles, or determining differentiation from any competitor drugs.

Fibromyalgia syndrome.

The objectives of the first OMERACT Fibromyalgia Syndrome (FM) Workshop were to identify and prioritize symptom domains that should be consistently evaluated in FM clinical trials, and to identify aspects of domains and outcome measures that should be part of a concerted research agenda of FM researchers. Such an effort will help standardize and improve the quality of outcomes research in FM. A principal assumption in this workshop has been that there exists a clinical syndrome, generally known as FM, characterized by chronic widespread pain typically associated with fatigue, sleep disturbance, mood disturbance, and other symptoms and signs, and considered to be related to central neuromodulatory dysregulation.

The ultimate model organism: progress in experimental medicine.

Experimental medicine is the use of innovative measurements, models and designs in studying human subjects for establishing proof of mechanism and concept of new drugs, for exploring the potential for market differentiation for successful drug candidates, and for efficiently terminating the development of unsuccessful ones. Humans are the ultimate 'model' because of the uncertain validity and efficacy of novel targets and drug candidates that emerge from genomics, combinatorial chemistry and high-throughput screening and the use of poorly predictive preclinical models. The in-depth investigation of the effects of drugs and the nature of disease progression is becoming ever more feasible because of advances in clinical biomarkers.