Large‐scale genome‐wide screening of circulating microRNAs in clear cell renal cell carcinoma reveals specific signatures in late‐stage disease

Circulating miRNAs have shown great promises as noninvasive diagnostic and predictive biomarkers in several solid tumors. While the miRNA profiles of renal tumors have been extensively explored, knowledge of their circulating counterparts is limited. Our study aimed to provide a large‐scale genome‐wide profiling of plasma circulating miRNA in clear‐cell renal cell carcinoma (ccRCC). Plasma samples from 94 ccRCC cases and 100 controls were screened for 754 circulating micro‐RNAs (miRNA) by TaqMan arrays. Analyses including known risk factors for renal cancer—namely, age, sex, hypertension, obesity, diabetes, tobacco smoking and alcohol consumption—highlighted that circulating miRNA profiles were tightly correlated with the stage of the disease. Advanced tumors, characterized as stage III and IV, were associated with specific miRNA signatures that significantly differ from both controls and earlier stage ccRCC cases. Molecular pathway enrichment analyses of their gene targets showed high similarities with alterations observed in renal tumors. Plasma circulating levels of miR‐150 were significantly associated with RCC‐specific survival and could marginally improve the predictive accuracy of clinical parameters in our series, including age at diagnosis, sex and conventional staging. In summary, our results suggest that circulating miRNAs may provide insights into renal cell carcinoma progression.     

TP53 Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data

TP53 gene mutations are one of the most frequent somatic events in cancer. The IARC TP53 Database ( http://p53.iarc.fr ) is a popular resource that compiles occurrence and phenotype data on TP53 germline and somatic variations linked to human cancer. The deluge of data coming from cancer genomic studies generates new data on TP53 variations and attracts a growing number of database users for the interpretation of TP53 variants. Here, we present the current contents and functionalities of the IARC TP53 Database and perform a systematic analysis of TP53 somatic mutation data extracted from this database and from genomic data repositories. This analysis showed that IARC has more TP53 somatic mutation data than genomic repositories (29,000 vs. 4,000). However, the more complete screening achieved by genomic studies highlighted some overlooked facts about TP53 mutations, such as the presence of a significant number of mutations occurring outside the DNA‐binding domain in specific cancer types. We also provide an update on TP53 inherited variants including the ones that should be considered as neutral frequent variations. We thus provide an update of current knowledge on TP53 variations in human cancer as well as inform users on the efficient use of the IARC TP53 Database.     

Propriétés antimicrobiennes et toxicité par détermination de la DL50 de l’huile essentielle de Prangos asperula Boissier

This research concerns the antimicrobial properties of an essential oil of a wild plant, Prangos asperula Boissier, and the determination of its toxicity threshold. Antimicrobial properties were tested against five germs

Streptococcus fecalis, Staphylococcus aureus (gram positive bacteria)

Salmonella typhi, Escherichia coli (gram negative bacteria)

Candida albicans (yeast).

The toxic effect of this essential oil was tested on mice in a laboratory. Different concentrations of the essential oil were used, ranging from 20 to 160 μl/ml. Each was tested on a series of five mice. After essential oil solution injection, the behavior of the mice was documented. The lethal dose (LD₅₀) was deduced from the straight line describing the death rate in relation to the concentration of injected essential oil solution. The LD₅₀ found was about 1,05 μmL/g.     

Étude de l’activité antimicrobienne de l’huile essentielle d’une plante sauvage Prangos asperula Boiss

Prangos asperula (Pa) grows wild in vast areas of Lebanon and Syria at altitudes between 1200 and 1500 m. Samples of Pa were collected from three regions of Lebanon. The extraction of oil was performed using hydrodistillation. Our results demonstrated that Pa oil has much stronger antibacterial properties than the common antibiotics used in comparative tests. The essential oil extracted from the plant was tested against bacteria (Staphylococcus aureus, Streptococcus faecalis, Escherichia coli and Salmonella typhi), and yeast Candida albicans). Our results showed a strong inhibitory effect against S. aureus (98 to 100%), S. faecalis (94 to 100%), E. coli (92 to 100%), S. typhi (91 to 100%) and C. albicans (100%). Its remarkable activity against some gram-positive and gram-negative bacteria demonstrates enormous potential for medicinal use.     

Does exposure to aircraft noise increase the mortality from cardiovascular disease in the population living in the vicinity of airports? Results of an ecological study in France

The impact of aircraft noise on health is of growing concern. We investigated the relationship between this exposure and mortality from cardiovascular disease, coronary heart disease, myocardial infarction, and stroke. We performed an ecological study on 161 communes (commune being the smallest administrative unit in France) close to the following three major French airports: Paris-Charles de Gaulle, Lyon Saint-Exupéry, and Toulouse-Blagnac. The mortality data were provided by the French Center on Medical Causes of Death for the period 2007-2010. Based on the data provided by the French Civil Aviation Authority, a weighted average exposure to aircraft noise (L_den AEI) was computed at the commune level. A Poisson regression model with commune-specific random intercepts, adjusted for potential confounding factors including air pollution, was used to investigate the association between mortality rates and L_den AEI. Positive associations were observed between L_den AEI and mortality from cardiovascular disease [adjusted mortality rate ratio (MRR) per 10 dB(A) increase in L_den AEI = 1.18; 95% confidence interval (CI): 1.11-1.25], coronary heart disease [MRR = 1.24 (1.12-1.36)], and myocardial infarction [MRR = 1.28 (1.11-1.46]. Stroke mortality was more weakly associated with L_den AEI [MRR = 1.08 (0.97-1.21]. These significant associations were not attenuated after the adjustment for air pollution. The present ecological study supports the hypothesis of an association between aircraft noise exposure and mortality from cardiovascular disease, coronary heart disease, and myocardial infarction. However, the potential for ecological bias and the possibility that this association could be due to residual confounding cannot be excluded.     

Bladder cancer risk in relation to occupations held in a nationwide case-control study in Iran

Globally, bladder cancer has been identified as one of the most frequent occupational cancers, but our understanding of occupational bladder cancer risk in Iran is less advanced. This study aimed to assess the risk of bladder cancer in relation to occupation in Iran. We used the IROPICAN case-control study data including 717 incident cases and 3477 controls. We assessed the risk of bladder cancer in relation to ever working in major groups of the International Standard Classification of Occupations (ISCO-68) while controlling for cigarette smoking, opium consumption. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). In men, decreased ORs for bladder cancer were observed in administrative and managerial workers (OR 0.4; CI: 0.2, 0.9), and clerks (OR 0.6; CI: 0.4, 0.9). Elevated ORs were observed in metal processors (OR 5.4; CI: 1.3, 23.4), and workers in occupations with likely exposure to aromatic amines (OR 2.2; CI: 1.2, 4.0). There was no evidence of interactions between working in aromatic amines-exposed occupations and tobacco smoking or opium use. Elevated risk of bladder cancer in men in metal processors and workers likely exposed to aromatic amines aligns with associations observed outside Iran. Other previously confirmed associations between high-risk occupations and bladder cancer were not observed, possibly due to small numbers or lack of details on exposure. Future epidemiological studies in Iran would benefit from the development of exposure assessment tools such as job exposure matrices, generally applicable for retrospective exposure assessment in epidemiological studies.     

Étude quantitative des coumarines d’une plante sauvage Prangos asperula Boissier

The authors report a quantitative study of the coumarins contained in the wild plant Prangos asperula. Mountain villagers living at altitudes between 1200 m and 2000 m use crushed parts of this plant to treat wounds and accelerate scar formation. This led us to study the composition of coumarins in Prangos asperula, which is known to play a role in wound healing. Samples were collected in the mountains of Lebanon and Syria. We assayed for various derivatives and revealed average scopoletin concentrations of 6.34 μg/g in the flowers and 2509 μg/g in the fruit. This wild plant stores high levels of psoralen, reaching an average of 121.30 μg/g in the flowers and 1977.76 μg/g in the fruit.