Ten percent to 15% of all lung cancers are small-cell lung cancer (SCLC). SCLC usually grows and metastasizes before it is diagnosed and relapses rapidly upon treatment. Unfortunately, no new targeted agent has been approved in the past 30 years for patients with SCLC. The BET (bromodomain and extraterminal) proteins bind acetylated histones and recruit protein complexes to promote transcription initiation and elongation. BET proteins have been shown to regulate expression of key genes in oncogenesis, such as MYC, CCND2, and BCL2L1. Here, we demonstrate that approximately 50% of SCLC cell lines are exquisitely sensitive to growth inhibition by the BET inhibitor, ABBV-075. The majority of these SCLC cell lines underwent apoptosis in response to ABBV-075 treatment via induction of caspase-3/7 activity. ABBV-075 enhanced the expression of proapoptotic protein BIM and downregulated antiapoptotic proteins BCL2 and BCLxl to a lesser extent. Furthermore, BET inhibition increased BCL2–BIM complex, thus priming the cells for apoptosis. Indeed, strong synergy was observed both in vitro and in vivo when cotreating the cells with BET inhibitor and the BH3-mimetic, BCL2 inhibitor venetoclax (ABT-199). ABBV-075 interaction with venetoclax positively correlated with BCL2 expression. Taken together, our studies provide a rationale for treating SCLC with BET and BCL2 inhibitors in tumors with high BCL2 protein expression. Mol Cancer Ther; 16(8); 1–10. ©2017 AACR.

The existence of odors in drainage pipelines is one of the most prominent environmental problems that urban residents complain about nowadays. Odorous substances in sewage can cause corrosion and erosion in drainage pipelines, and even lead to great harm to the human body and environments. Ideas for in situ odor control can be divided into two main categories: the elimination of odorous substances and the inhibition of the production of odorous substances. However, there is a lack of comprehensive summary of in situ overall deodorization techniques, which has limited the wide application of these methods. We conducted a systematic review to summarize recent advances in in situ overall deodorization. Firstly, the main odorous substances in drainage pipelines and their basic characteristics are concluded. Special attention has been paid to volatile sulfur compounds (VSCs) and nitrogen-containing compounds, as the main odorous substances. Subsequently, typical sources of these odorous substances are summarized based on their formation mechanisms. Then, in situ deodorization techniques (including pipeline condition optimization techniques, odor source control techniques, chemical control techniques, and biological control techniques) are introduced. Finally, upcoming research efforts on deodorization mechanism improvement, research gap supplementation, and economic efficiency enhancement to meet practical conditions are proposed.