Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting in vitro and in vivo anti-tumor activity on breast cancer model

Neuropilin-1/-2 (+33 NRPs), VEGF-A₁₆₅ co-receptors_, are over-expressed during cancer progression. Thus, NRPs targeted drug development is challenged using a multistep in silico/in vitro screening procedure. The first fully non-peptidic VEGF-A₁₆₅/NRPs protein–protein interaction antagonist (IC₅₀ = 34 μM) without effect on pro-angiogenic kinases has been identified (compound-1). This hit showed breast cancer cells anti-proliferative activity (IC₅₀ = 0.60 μM). Compound-1 treated NOG-xenografted mice significantly exerted tumor growth inhibition, which is correlated with Ki-67^low expression and apoptosis. Furthermore, CD31⁺/CD34⁺ vessels are reduced in accordance with HUVEC-tube formation inhibition (IC₅₀ = 0.20 μM). Taking together, compound-1 is the first fully organic inhibitor targeting NRPs.     

Involvement of foot in patients with spondyloarthritis: Prevalence and clinical features

Background

The purpose of this study was to evaluate the foot involvement in a group of patients with spondyloarthritis in regard to symptoms, type and frequency of deformities, location and radiological changes.

Association between age and disease specific mortality in medullary thyroid cancer

BackgroundThe aim of this study was to evaluate the association between age and disease specific mortality (DSM) among adults diagnosed with medullary thyroid cancer (MTC).MethodSurveillance, Epidemiology, and End Results (SEER-18) was used to analyze adult MTC patients stratified by age (18–64, 65–79, ≥80 years). Associations between patient demographics, tumor size, nodal status, metastatic disease, and extent of surgery on DSM was assessed with multivariable Cox regression.ResultsAmong 1457 patients with MTC, 1008 (69.2%) were younger adults, 371 (25.5%) older adults, and 78 (5.4%) were super-elderly. A significantly higher proportion of older adults and super-elderly had less than the recommended operation for MTC. On multivariable analysis, older adults and super-elderly were 2.9 and 6.7 times more likely to have an increased DSM (HR:2.91, 95% CI: 1.83–4.63; p < 0.001 and HR: 6.70, 95%CI: 3.69–12.20; p < 0.001). Extent of surgery or lymphadenectomy did not affect DSM.ConclusionsIncreased age is an independent predictor of DSM in patients with MTC.     

Are preoperative sestamibi scans useful for identifying ectopic parathyroid glands in patients with expected multigland parathyroid disease?

Background

The role of preoperative localization studies in patients with hyperparathyroidism and expected multigland disease remains poorly defined. Our study investigates the usefulness of obtaining preoperative sestamibi scans and ultrasonography of the neck in identifying ectopic glands in this group of patients.