Predictive features of ligand-specific signaling through the estrogen receptor.

Some estrogen receptor-α (ERα)-targeted breast cancer therapies such as tamoxifen have tissue-selective or cell-specific activities, while others have similar activities in different cell types. To identify biophysical determinants of cell-specific signaling and breast cancer cell proliferation, we synthesized 241 ERα ligands based on 19 chemical scaffolds, and compared ligand response using quantitative bioassays for canonical ERα activities and X-ray crystallography. Ligands that regulate the dynamics and stability of the coactivator-binding site in the C-terminal ligand-binding domain, called activation function-2 (AF-2), showed similar activity profiles in different cell types.

Triaryl-substituted Schiff bases are high-affinity subtype-selective ligands for the estrogen receptor.

We have explored the isoelectronic replacement of the C═C double bond found at the core of many nonsteroidal estrogen ligands with a simple Schiff base (C═N). Di- and triaryl-substituted imine derivatives were conveniently prepared by the condensation of benzophenones with various anilines without the need for phenolic hydroxy protection. Most of these imines demonstrated high affinity for the estrogen receptors, which, in some cases exceeded that of estradiol.

Novel highly branched water-soluble heteropolysaccharides as immunopotentiators to inhibit S-180 tumor cell growth in BALB/c mice.

The in vitro antitumor activities and in vivo immunomodulatory effects of water-soluble highly branched heteropolysaccharides isolated from Rhizoma panacis Japonici were evaluated by three cell lines and BALB/c mice implanted with Sarcoma 180 (S-180) tumors. The heteropolysaccharides showed potent tumor therapeutic effect by potentiating the animal's immune responses including an increase in white blood cell count and lymphocyte number. The heteropolysaccharides also induced apoptosis in the S-180 cells and alleviate the short-term side effect of cisplatin (DDP) to the animal during the treatment period.