Utilizing Tissue Microarrays for Medium-Throughput Validation of Antibodies Against Immune Markers

https://openworks.mdanderson.org/sumexp21/1201/thumbnail.jp

Organoid Imaging Strategies for Accelerating Translational Research

View full abstracthttps://openworks.mdanderson.org/leading-edge/1063/thumbnail.jp

Multi-disciplinary efforts to evaluate the therapeutic potential of CDK11, a novel transcription associated cyclin dependent kinase.

View full abstracthttps://openworks.mdanderson.org/leading-edge/1043/thumbnail.jp

Humidity-Responsive Polymeric Films Based on AOT - Water Reverse Microemulsions

Hydrophobic polymer films, having an aqueous phase distributed throughout the matrix, were formed by polymerizing a solution of dodecyl acrylate and 1,6 hexanediol diacrylate containing nanometer-sized drops of water stabilized by sodium bis(2-ethylhexyl) sulfosuccinate (ACT). Photopolymerization-incluced aggregation of the water drops and/or phase separation occurred, as the initially clear solutions became opaque films. The polymerized films became clear, as the relative humidity was reduced. Clear films still contained 20-50% of the initial water. The transition from opaque to clear films was reversible provided that the film did not become completely dry and form cracks. (c) 2007 Wiley Periodicals, Inc

Combinatory therapy targeting mitochondrial oxidative phosphorylation improves efficacy of IDH mutant inhibitors in acute myeloid leukemia

Isocitrate dehydrogenases (IDH) are involved in redox control and central metabolism. Mutations in IDH induce epigenetic and transcriptional reprogramming, differentiation bias, BCL-2 dependence and susceptibility to mitochondrial inhibitors in cancer cells. Here we show that high sensitivity to mitochondrial oxidative phosphorylation (OxPHOS) inhibitors is due to an enhanced mitochondrial oxidative metabolism in cell lines, PDX and patients with acute myeloid leukemia (AML) harboring IDH mutation. Along with an increase in TCA cycle intermediates, this AML-specific metabolic behavior mechanistically occurs through the increase in methylation-driven CEBPα- and CPT1a-induced fatty acid oxidation, electron transport chain complex I activity and mitochondrial respiration in IDH1 mutant AML. Furthermore, an IDH mutant inhibitor that significantly and systematically reduces 2-HG oncometabolite transiently reverses mitochondrial FAO and OxPHOS gene signature and activities in patients who responded to the treatment and achieved the remission. However, at relapse or in patients who did not respond, IDH mutant inhibitor failed to block these mitochondrial properties. Accordingly, OxPHOS inhibitors such as IACS-010759 improve anti-AML efficacy of IDH mutant inhibitors alone and in combination with chemotherapy in vivo . This work provides a scientific rationale for combinatory mitochondrial-targeted therapies to treat IDH mutant-positive AML patients, especially those unresponsive to or relapsing from IDH mutant-specific inhibitors