Radiation protection of the gastrointestinal tract and growth inhibition of prostate cancer xenografts by a single compound.

Normal tissue toxicity markedly reduces the therapeutic index of genotoxic anticancer agents, including ionizing radiation. Countermeasures against tissue damage caused by radiation are limited by their potential to also protect malignant cells and tissues. Here, we tested a panel of signal transduction modifiers for selective radioprotection of normal but not tumor tissues. These included three inhibitors of GSK3 (LiCl, SB216763, and SB415286) and two inhibitors of NF-κB (ethyl pyruvate and RTA 408). Among these, the thiol-reactive triterpenoid RTA 408 emerged as a robust and effective protector of multiple organ systems (gastrointestinal, skin, and hemopoietic) against lethal doses of radiation. RTA 408 preserved survival and proliferation of intestinal crypt cells in lethally irradiated mice while reducing apoptosis incidence in crypts and villi. In contrast, RTA 408 uniformly inhibited growth of established CWR22Rv1, LNCaP/C4-2B, PC3, and DU145 xenografts either alone or combined with radiation. Antitumor effects in vivo were associated with reduced proliferation and intratumoral apoptosis and with inhibition of NF-κB-dependent transcription in PC3 cells. Selective protection of normal tissue compartments by RTA 408 critically depended on tissue context and could not be replicated in vitro. Collectively, these data highlight the potential of RTA 408 as a cytoprotective agent that may be safely used in chemoradiation approaches

Allergic contact dermatitis to 2-octyl cyanoacrylate after surgical repair: Humidity as a potential factor

Allergic contact dermatitis to 2-octyl cyanoacrylate (Dermabond; Ethicon, Somerville, NJ) after surgical repair is an extremely rare condition with few reported cases. In recent years, contact dermatitis to Dermabond has been reported with increasing frequency.Cyanoacrylates are the most commonly used surgical adhesives and rely on their rapid polymerization to prevent sensitization from antigen presenting cells (APCs), because APCs are only capable of monomeric recognition of cyanoacrylates. It is thought that arid climates may contribute to increased sensitization of cyanoacrylates because water drives the polymerization reaction, decreasing the number of monomers capable of recognition by APCs. With less water present in the air to drive the polymerization forward, it is thought that monomers will persist longer, providing APCs more time to become sensitized.Indeed, most cases of allergic contact dermatitis to Dermabond published in the literature are from arid environments, such as a case from Las Vegas, Nevada and 4 cases from San Antonio, Texas.These observations should in theory extend to home heaters and air conditioners. We present a case of allergic contact dermatitis to 2-octyl cyanoacrylate after the use of a home heater shortly after application