The HDAC and PI3K dual inhibitor CUDC-907 synergistically enhances the antileukemic activity of venetoclax in preclinical models of acute myeloid leukemia

Venetoclax is a promising agent in the treatment of acute myeloid leukemia (AML), though its antileukemic activity is limited to combination therapies. Mcl-1 downregulation, Bim upregulation, and DNA damage have been identified as potential ways to enhance venetoclax activity. In this study, we combine venetoclax with the dual PI3K and histone deacetylase inhibitor CUDC-907, which can downregulate Mcl-1, upregulate Bim, and induce DNA damage, as well as downregulate c-Myc. We establish that CUDC-907 and venetoclax synergistically induce apoptosis in AML cell lines and primary AML patient samples ex vivo. CUDC-907 downregulates CHK1, Wee1, RRM1, and c-Myc, which were found to play a role in venetoclax-induced apoptosis. Interestingly, we find that venetoclax treatment enhances CUDC-907-induced DNA damage potentially through inhibition of DNA repair. In vivo results show that CUDC-907 enhances venetoclax efficacy in an AML cell line derived xenograft mouse model, supporting the development of CUDC-907 in combination with venetoclax for the treatment of AML.     

Comparative effectiveness of mycophenolate mofetil versus cyclophosphamide in systemic sclerosis-related interstitial lung disease

Clinical Rheumatology -     

Acceptability of a Dapivirine/Placebo Gel Administered Rectally to HIV-1 Seronegative Adults (MTN-026)

AIDS and Behavior - This study describes the acceptability of a rectal microbicide gel formulation using dapivirine (DPV) among men and women from two countries (United States and Thailand)...     

Motivations and Barriers to Routine HIV Testing Among Men Who Have Sex with Men in New York City

AIDS and Behavior - In-depth qualitative interviews explored the experiences and understandings of men 18–39 years old who have sex with men that could facilitate or prevent HIV...     

Does Intraprocedural CT Improve the Success Rate of Adrenal Venous Sampling? A Systematic Review and Meta-Analysis of Data from 809 Patients

CardioVascular and Interventional Radiology - To perform a systematic review and meta-analysis to quantify the technical success rate of adrenal venous sampling (AVS) with and without...