Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.

We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10(-13)). We also showed an association between common variation at 3q28 (TP63, rs13314271, OR = 1.13, P = 7.22 × 10(-10)) and lung adenocarcinoma that had been previously reported only in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants with substantive effects on cancer risk from preexisting genome-wide association study data

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

Method for the generation and cultivation of functional three-dimensional mammary constructs without exogenous extracellular matrix

During puberty, pregnancy, lactation and postlactation, breast tissue undergoes extensive remodelling and the disruption of these events can lead to cancer. In vitro studies of mammary tissue and its malignant transformation regularly employ mammary epithelial cells cultivated on matrigel or floating collagen rafts. In these cultures, mammary epithelial cells assemble into three-dimensional structures resembling in vivo acini. We present a novel technique for generating functional mammary constructs without the use of matrix substitutes

An intergenerational approach in the promotion of balance and strength for fall prevention: a mini-review

The risk of sustaining a fall is particularly high in children and seniors. Deficits in postural control and muscle strength either due to maturation, secular declines or biologic aging are two important intrinsic risk factors for falls. During life span, performance in variables of static postural control follows a U-shaped curve with children and seniors showing larger postural sway than healthy adults. Measures of dynamic postural control (i.e. gait speed) as well as isometric (i.e. maximal strength) and dynamic muscle strength (i.e. muscular power) follow an inverted U-shaped curve during life span, again with children and seniors showing deficits compared to adults. There is evidence that particularly balance and resistance training are effective in counteracting these neuromuscular constraints in both children and seniors. Further, these training regimens are able to reduce the rate of sustaining injuries and falls in these age groups. An intergenerational intervention approach is suggested to enhance the effectiveness of these training programs by improving compliance and increasing motivation of children and seniors exercising together. Thus, the objectives of this mini-review are: (1) to describe the epidemiology and etiology of falls in children and seniors; (2) to discuss training programs that counteract intrinsic fall risk factors by reducing the rate of falling, and (3) to present an intergenerational approach that has the potential to make training programs even more effective by including children and seniors together in one exercise group

Two-stage revision surgery with preformed spacers and cementless implants for septic hip arthritis: a prospective, non-randomized cohort study

<p>Abstract</p> <p>Background</p> <p>Outcome data on two-stage revision surgery for deep infection after septic hip arthritis are limited and inconsistent. This study presents the medium-term results of a new, standardized two-stage arthroplasty with preformed hip spacers and cementless implants in a consecutive series of adult patients with septic arthritis of the hip treated according to a same protocol.</p> <p>Methods</p> <p>Nineteen patients (20 hips) were enrolled in this prospective, non-randomized cohort study between 2000 and 2008. The first stage comprised femoral head resection, debridement, and insertion of a preformed, commercially available, antibiotic-loaded cement hip spacer. After eradication of infection, a cementless total hip arthroplasty was implanted in the second stage. Patients were assessed for infection recurrence, pain (visual analog scale [VAS]) and hip joint function (Harris Hip score).</p> <p>Results</p> <p>The mean time between first diagnosis of infection and revision surgery was 5.8 ± 9.0 months; the average duration of follow up was 56.6 (range, 24 - 104) months; all 20 hips were successfully converted to prosthesis an average 22 ± 5.1 weeks after spacer implantation. Reinfection after total hip joint replacement occurred in 1 patient. The mean VAS pain score improved from 48 (range, 35 - 84) pre-operatively to 18 (range, 0 - 38) prior to spacer removal and to 8 (range, 0 - 15) at the last follow-up assessment after prosthesis implantation. The average Harris Hip score improved from 27.5 before surgery to 61.8 between the two stages to 92.3 at the final follow-up assessment.</p> <p>Conclusions</p> <p>Satisfactory outcomes can be obtained with two-stage revision hip arthroplasty using preformed spacers and cementless implants for prosthetic hip joint infections of various etiologies.</p