Design, synthesis and biological evaluation of quinoline-2-carbonitrile-based hydroxamic acids as dual tubulin polymerization and histone deacetylases inhibitors.

A series of quinoline and quinazoline analogs were designed and synthesized as new tubulin polymerization (TP) and histone deacetylases (HDAC) inhibitors. Compounds 12a and 12d showed the best cytotoxicity activities against a panel of human cancer cell lines with an averaged IC50 value of 0.6 and 0.7 nM, respectively. Furthermore, these lead compounds showed good activities against CA-4-resistant colon-carcinoma and multidrug-resistant leukemia cells. In addition, compounds 12a and 12d induced HT29 cell cycle arrest in the G2/M phase and produced caspase-induced apoptosis of HT29 cells through mitochondrial dysfunction. Also, 12a and 12d inhibited HDAC8, 6, and 11 activities. Furthermore, lead compound 12a exhibited higher metabolic stability than isoCA-4 and was highly potent in suppressing tumor growth in the fibrosarcoma MCA205 tumor model. Collectively, these studies suggest that 12a represents a new dual inhibitor of TP and HDAC activities, which makes it a suitable candidate for further investigations in clinical development.

Medical physics personnel for medical imaging: requirements, conditions of involvement and staffing levels-French recommendations.

The French regulations concerning the involvement of medical physicists in medical imaging procedures are relatively vague. In May 2013, the ASN and the SFPM issued recommendations regarding Medical Physics Personnel for Medical Imaging: Requirements, Conditions of Involvement and Staffing Levels. In these recommendations, the various areas of activity of medical physicists in radiology and nuclear medicine have been identified and described, and the time required to perform each task has been evaluated. Criteria for defining medical physics staffing levels are thus proposed. These criteria are defined according to the technical platform, the procedures and techniques practised on it, the number of patients treated and the number of persons in the medical and paramedical teams requiring periodic training. The result of this work is an aid available to each medical establishment to determine their own needs in terms of medical physics.