Genome-wide association study identifies multiple risk loci for renal cell carcinoma

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility

Cellular pharmacology studies of anticancer agents: recommendations from the EORTC-PAMM group

An increasing number of manuscripts focus on the in vitro evaluation of established and novel anti-tumour agents in experimental models. Whilst the design of such in vitro assays is inherently flexible, some of these studies lack the minimum information necessary to critically evaluate their relevance or have been carried out under unsuitable conditions. The use of appropriate and robust methods and experimental design has important implications for generating results that are reliable, relevant, and reproducible. The Pharmacology and Molecular Mechanisms (PAMM) group of the European Organization for Research and Treatment of Cancer (EORTC) is the largest group of academic scientists working on drug development and bundle decades of expertise in this field. This position paper addresses all researchers with an interest in the preclinical and cellular pharmacology of anti-tumour agents and aims at generating basic recommendations for the correct use of compounds to be tested for anti-tumour activity using a range of preclinical cellular models of cancer

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates

The Influence of Fatigued Core Muscles on Head Acceleration during Headers in Soccer

The core muscles play a central role in stabilizing the head during headers in soccer. The objective of this study was to examine the influence of a fatigued core musculature on the acceleration of the head during jump headers and run headers. Acceleration of the head was measured in a pre-post-design in 68 soccer players (age: 21.5 ± 3.8 years, height: 180.0 ± 13.9 cm, weight: 76.9 ± 8.1 kg). Data were recorded by means of a telemetric 3D acceleration sensor and with a pendulum header. The treatment encompassed two exercises each for the ventral, lateral, and dorsal muscle chains. The acceleration of the head between pre- and post-test was reduced by 0.3 G (p = 0.011) in jump headers and by 0.2 G (p = 0.067) in run headers. An additional analysis of all pretests showed an increased acceleration in run headers when compared to stand headers (p < 0.001) and jump headers (p < 0.001). No differences were found in the sub-group comparisons: semi-professional vs. recreational players, offensive vs. defensive players. Based on the results, we conclude that the acceleration of the head after fatiguing the core muscles does not increase, which stands in contrast to postulated expectations. More tests with accelerated soccer balls are required for a conclusive statement

Measurement of Contractility and Calcium Release in Cardiac Spheroids.

There is a need for organotypic in vitro models that resemble the native tissue in functionality and tissue architecture for disease models and drug development. To this end, many 3D culture formats have been developed over time. Among the most often used type is the scaffold-free multicellular aggregate, also called spheroid, that forms by self-assembly. However, working with 3D cultures can be challenging because single cells are not as accessible as in 2D cultures and standard lab procedures must be adapted or replaced altogether. This chapter describes methods to create cardiac spheroids consisting of human iPSC-derived cardiomyocytes and cardiac fibroblasts and how to measure contractility or calcium signals using quantitative video analysis and confocal microscopy. Emphasis is on the particular challenges that 3D cultures pose and on affordable methods that do not require specialized equipment

The Influence of Fatigued Core Muscles on Head Acceleration during Headers in Soccer

The core muscles play a central role in stabilizing the head during headers in soccer. The objective of this study was to examine the influence of a fatigued core musculature on the acceleration of the head during jump headers and run headers. Acceleration of the head was measured in a pre-post-design in 68 soccer players (age: 21.5 ± 3.8 years, height: 180.0 ± 13.9 cm, weight: 76.9 ± 8.1 kg). Data were recorded by means of a telemetric 3D acceleration sensor and with a pendulum header. The treatment encompassed two exercises each for the ventral, lateral, and dorsal muscle chains. The acceleration of the head between pre- and post-test was reduced by 0.3 G (p = 0.011) in jump headers and by 0.2 G (p = 0.067) in run headers. An additional analysis of all pretests showed an increased acceleration in run headers when compared to stand headers (p < 0.001) and jump headers (p < 0.001). No differences were found in the sub-group comparisons: semi-professional vs. recreational players, offensive vs. defensive players. Based on the results, we conclude that the acceleration of the head after fatiguing the core muscles does not increase, which stands in contrast to postulated expectations. More tests with accelerated soccer balls are required for a conclusive statement