Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer.

PURPOSE: Targeted therapies that use the signaling pathways involved in prostate cancer are required to overcome chemoresistance and improve treatment outcomes for men. Molecular chaperones play a key role in the regulation of protein homeostasis and are potential targets for overcoming chemoresistance.Experimental Design: We established 4 chemoresistant prostate cancer cell lines and used image-based high-content siRNA functional screening, based on gene-expression signature, to explore mechanisms of chemoresistance and identify new potential targets with potential roles in taxane resistance. The functional role of a new target was assessed by in vitro and in vivo silencing, and mass spectrometry analysis was used to identify its downstream effectors. RESULTS: We identified FKBP7, a prolyl-peptidyl isomerase overexpressed in docetaxel-resistant and in cabazitaxel-resistant prostate cancer cells. This is the first study to characterize the function of human FKBP7 and explore its role in cancer. We discovered that FKBP7 was upregulated in human prostate cancers and its expression correlated with the recurrence observed in patients receiving docetaxel. FKBP7 silencing showed that FKBP7 is required to maintain the growth of chemoresistant cell lines and chemoresistant tumors in mice. Mass spectrometry analysis revealed that FKBP7 interacts with eIF4G, a component of the eIF4F translation initiation complex, to mediate the survival of chemoresistant cells. Using small-molecule inhibitors of eIF4A, the RNA helicase component of eIF4F, we were able to kill docetaxel- and cabazitaxel-resistant cells. CONCLUSIONS: Targeting FKBP7 or the eIF4G-containing eIF4F translation initiation complex could be novel therapeutic strategies to eradicate taxane-resistant prostate cancer cells.

Use of computed tomography to determine body composition of heavy strain turkey hens (Meleagris gallopavo) from rearing to early laying.

Genetic selection has improved the growth performance of poultry, but also influenced other metabolic parameters and physiological functions such as reproduction. To counter the negative effects of this enhanced development, modifications of the environment or diet are frequently used. As all animals are not equally sensitive and do not respond in the same way, the evolution of the body composition has got to be better characterized with non-invasive tools to reach a higher flock homogeneity and improve production yield. Thus, we have analyzed turkey breeder hens' body composition using computed tomography scan and measurements of biochemical markers from 16 to 34 wk old. During rearing, body weight was strongly correlated to muscle, fat, and bone volumes (r > 0.75), and increased with hen age until sexual maturity (31 wk). These correlations did not maintain after photostimulation was initiated (29 wk). Muscle volume linear regression with hen age resulted in a R² value of 0.626 over the whole trial study. Bone volume was better fitted by a quadratic regression (R² = 0.7) and was proportional to calcium plasma level evolution, both increasing after 28 wk of age. Conversely, fat volume quadratic regression (R² = 0.5) was symmetrical to triglyceride levels, the first decreasing notably at sexual maturity, the other increasing massively after 28 wk. Egg, yolk, and albumen weights increased with hen age, as did yolk triglyceride levels. In conclusion, computed tomography allows to investigate turkey breeders' body composition and bring new data in the genetic selection strategy. In addition, the evolution of the fat deposition and bone changes have been monitored over time and could help to optimize breeders' diet strategy.

Cardiac complications during pregnancy are better predicted with the modified WHO risk score.

BACKGROUND/OBJECTIVE: Several risk scores (RSs) have been used to stratify risk of cardiac complications (CCs) in pregnant patients with heart disease. We aimed to compare and contrast the accuracy of several RSs for predicting CC in this population. METHODS: Prospective inclusion of all consecutive pregnant patients with heart disease, and follow-up until 6 months postpartum. CCs were defined as primary if admission was required due to heart failure, arrhythmia or thromboembolic events, and secondary if the decline in NYHA class compared with baseline was >2 or urgent invasive cardiac procedures were needed. The discriminatory power of each RS was assessed by the area-under-the receiver-operating characteristic (ROC) curve (AUC). RESULTS: 179 patients, mean age: 32 years, accounted for 13.4% of CC (primary 11.7%, secondary 1.7%); the main diagnosis was congenital heart disease (CHD) in 68% followed by valvulopathies in 16%, arrhythmia in 7% and myocardiopathies in 5%. 22% (n=40) were classified as mWHO=1, 59% (n=105) mWHO=2 including subgroup 2-3, 14% (n=26) mWHO=3 and 4%(n=7) mWHO=4; 1 patient was unclassifiable. mWHO showed a better AUC (0.763) than CARPREG (0.67). For the CHD population, ZAHARA RS showed an AUC of 0.74, and Khairy an AUC of 0.632. CONCLUSIONS: mWHO was better at predicting CC than CARPREG; mWHO was also better at predicting CC than the specific CHD RS in the CHD subgroup. PRACTICE: There are an increasing number of pregnant women with HD. IMPLICATIONS: Improved prediction of CC risk during pregnancy can provide better preconception assessment in women with HD.

[An anthropometric study of a Sassari population 3 to 6 years of age]. / Studio antropometrico della popolazione sassarese da 3 a 6 anni.

The average values (+/- SD) for height and weight of 812 males and 686 females between 3 and 6 years of age from the city of Sassari (Sardinia) have been determined. Numerical values and smooth curves from the 3rd to the 97th percentile for height and weight have also been calculated. The results were compared with those of the literature and particularly with those published by De Toni et Al. 20 years ago. The data show a significant increase in height and weight among Sardinian children during the past 20 years. The availability of these new curves will permit a more correct evaluation of growth in Sardinian children.