Dosimetric impact of placement errors in optically stimulated luminescent dosimetry in radiotherapy.

Introduction: Studies have suggested that optically stimulated luminescent dosimeters (OSLDs) can be used for dosimetry of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). Clinical uncertainties such as placement error have not been thoroughly investigated. The purpose of this work was to measure OSLD placement error in a clinical sample and analyze its dosimetric impact.

Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4.

Cyclin D and cyclin-dependent kinase 4 (cdk4) are overexpressed in a variety of tumors, but their levels are not accurate indicators of oncogenic activity because an accessory factor such as p27(Kip1) is required to assemble this unstable dimer. Additionally, tyrosine (Y) phosphorylation of p27 (pY88) is required to activate cdk4, acting as an "on/off switch." We identified two SH3 recruitment domains within p27 that modulate pY88, thereby modulating cdk4 activity.

Structure-Based Design of Conformationally Constrained, Cell-Permeable STAT3 Inhibitors.

We report herein the structure-based design of a class of conformationally constrained, potent, cell-permeable small-molecule inhibitors to target the SH2 domain in STAT3. Compound 11 (CJ-1383) binds to STAT3 with a K(i) value of 0.95 µM, dose-dependently inhibits cellular STAT3 signaling and cancer cell growth, and induces apoptosis in the MDA-MB-468 cancer cell line with constitutively activated STAT3.

Design, synthesis, and evaluation of peptidomimetics containing Freidinger lactams as STAT3 inhibitors.

The STAT3 oncogene is a promising molecular target for the design of a new class of anticancer drugs. In this letter, we describe the design, synthesis, and evaluation of peptidomimetics containing Freidinger lactams as novel STAT3 inhibitors. Compound 3 binds to STAT3 with a K(i) value of 190nM and is a promising lead compound for further design and optimization.

Design and synthesis of a new, conformationally constrained, macrocyclic small-molecule inhibitor of STAT3 via 'click chemistry'.

STAT3 is a promising molecular target for the design of new anticancer drugs. In this paper, we report the design and synthesis of a conformationally constrained macrocyclic peptidomimetic 2 via click chemistry. Compound 2 was determined to bind to STAT3 with a K(i) value of 7.