The CYP2J2 G-50T polymorphism and myocardial infarction in patients with cardiovascular risk profile

<p>Abstract</p> <p>Background</p> <p>Cytochrome P450 (CYP) enzyme 2J2, an epoxygenase predominantly expressed in the heart, metabolises arachidonic acid to biologically active eicosanoids. One of the CYP2J2 products, 11, 12-epoxyeicosatrienoic acid, has several vasoprotective effects. The CYP2J2-G-50T-promotor polymorphism decreases gene expression and is associated with coronary artery disease. This association supports the vascular protective role of CYP-derived eicosanoids in cardiovascular disease. In the present study, we investigated the influence of this polymorphism on survived myocardial infarction in two study groups of patients with on average high cardiovascular risk profile.</p> <p>Methods</p> <p>The CYP2J2 polymorphism was genotyped in two groups of patients that were collected with the same method of clinical data collection. Data from 512 patients with sleep apnoea (group: OSA) and on average high cardiovascular risk profile and from another 488 patients who were admitted for coronary angiography (CAR-group) were evaluated for a potential correlation of the CYP2J2 polymorphism G-50T and a history of myocardial infarction. The G-50T polymorphism of the CYP2J2 gene was genotyped by allele specific restriction and light cycler analysis.</p> <p>Results</p> <p>The T-allele of the polymorphism was found in 111 (11.1%; CAR-group: N = 65, 13.3%; OSA: N = 46, 9.0%). 146 patients had a history of myocardial infarction (CAR: N = 120, 24.6%; OSA: N = 26, 5.1%). Cardiovascular risk factors were equally distributed between the different genotypes of the CYP2J2 G-50T polymorphism. In the total group of 1000 individuals, carriers of the T-allele had significantly more myocardial infarctions compared to carriers of the wild type (T/T or G/T: 21.6%; G/G: 13.7%; p = 0.026, odds ratio 1.73, 95%-CI [1.06–2.83]). In the multivariate logistic regression analysis the odds ratio for a history of myocardial infarction in carriers of the T-allele was 1.611, 95%-CI [0.957–2.731] but this trend was not significant (p = 0.073).</p> <p>Conclusion</p> <p>In presence of other risk factors, the CYP2J2 G-50T failed to show a significant role in the development of myocardial infarction. However, since our result is close to the border of significance, this question should be clarified in larger, prospective studies in the future.</p

Biosensor for deconvolution of individual cell fate in response to ion beam irradiation

Clonogenic survival assay constitutes the gold standardmethod for quantifying radiobiological effects. However, it neglects cellular radiation response variability and heterogeneous energy deposition by ion beams on the microscopic scale. We introduce "Cell-Fit-HD4D'' a biosensor that enables a deconvolution of individual cell fate in response to the microscopic energy deposition as visualized by optical microscopy. Cell-Fit-HD4D enables single-cell dosimetry in clinically relevant complex radiation fields by correlating microscopic beam parameters with biological endpoints. Decrypting the ion beam's energy deposition and molecular effects at the single-cell level has the potential to improve our understanding of radiobiological dose concepts as well as radiobiological study approaches in general

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs

The Peripheral Arterial disease study (PERART/ARTPER): prevalence and risk factors in the general population

<p>Abstract</p> <p>Background</p> <p>The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the study is to know the prevalence and associated risk factors of peripheral arterial disease in the general population.</p> <p>Methods</p> <p>We performed a cross-sectional, multicentre, population-based study in 3786 individuals >49 years, randomly selected in 28 primary care centres in Barcelona (Spain). Peripheral arterial disease was evaluated using the ankle-arm index. Values < 0.9 were considered as peripheral arterial disease.</p> <p>Results</p> <p>The prevalence (95% confidence interval) of peripheral arterial disease was 7.6% (6.7-8.4), (males 10.2% (9.2-11.2), females 5.3% (4.6-6.0); <it>p </it>< 0.001).</p> <p>Multivariate analysis showed the following risk factors: male sex [odds ratio (OR) 1.62; 95% confidence interval 1.01-2.59]; age OR 2.00 per 10 years (1.64-2.44); inability to perform physical activity [OR 1.77 (1.17-2.68) for mild limitation to OR 7.08 (2.61-19.16) for breathless performing any activity]; smoking [OR 2.19 (1.34-3.58) for former smokers and OR 3.83 (2.23-6.58) for current smokers]; hypertension OR 1.85 (1.29-2.65); diabetes OR 2.01 (1.42-2.83); previous cardiovascular disease OR 2.19 (1.52-3.15); hypercholesterolemia OR 1.55 (1.11-2.18); hypertriglyceridemia OR 1.55 (1.10-2.19). Body mass index ≥25 Kg/m²OR 0.57 (0.38-0.87) and walking >7 hours/week OR 0.67 (0.49-0.94) were found as protector factors.</p> <p>Conclusions</p> <p>The prevalence of peripheral arterial disease is low, higher in males and increases with age in both sexes. In addition to previously described risk factors we found a protector effect in physical exercise and overweight.</p

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.Peer reviewe