Browsing by Author "Wang, Feng"

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    Decoupling Lineage-Associated Genes in Acute Myeloid Leukemia Reveals Inflammatory and Metabolic Signatures Associated With Outcomes
    (Frontiers, 2021) Abbas, Hussein A.; Mohanty, Vakul; Wang, Ruiping; Huang, Yuefan; Liang, Shaoheng; Wang, Feng; Zhang, Jianhua; Qiu, Yihua; Hu, Chenyue W.; Qutub, Amina A.; Dail, Monique; Bolen, Christopher R.; Daver, Naval; Konopleva, Marina; Futreal, Andrew; Chen, Ken; Wang, Linghua; Kornblau, Steven M.; Bioengineering
    Acute myeloid leukemia (AML) is a heterogeneous disease with variable responses to therapy. Cytogenetic and genomic features are used to classify AML patients into prognostic and treatment groups. However, these molecular characteristics harbor significant patient-to-patient variability and do not fully account for AML heterogeneity. RNA-based classifications have also been applied in AML as an alternative approach, but transcriptomic grouping is strongly associated with AML morphologic lineages. We used a training cohort of newly diagnosed AML patients and conducted unsupervised RNA-based classification after excluding lineage-associated genes. We identified three AML patient groups that have distinct biological pathways associated with outcomes. Enrichment of inflammatory pathways and downregulation of HOX pathways were associated with improved outcomes, and this was validated in 2 independent cohorts. We also identified a group of AML patients who harbored high metabolic and mTOR pathway activity, and this was associated with worse clinical outcomes. Using a comprehensive reverse phase protein array, we identified higher mTOR protein expression in the highly metabolic group. We also identified a positive correlation between degree of resistance to venetoclax and mTOR activation in myeloid and lymphoid cell lines. Our approach of integrating RNA, protein, and genomic data uncovered lineage-independent AML patient groups that share biologic mechanisms and can inform outcomes independent of commonly used clinical and demographic variables; these groups could be used to guide therapeutic strategies.
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    Effectiveness of metal oxide catalysts for the degradation of 1,4-dioxane
    (Royal Society of Chemistry, 2019) Heck, Kimberly N.; Wang, Yehong; Wu, Gang; Wang, Feng; Tsai, Ah-Lim; Adamson, David T.; Wong, Michael S.
    1,4-dioxane, commonly used as a solvent stabilizer and industrial solvent, is an environmental contaminant and probable carcinogen. In this study, we explored the concept of using metal oxides to activate H2O2 catalytically at neutral pH in the dark for 1,4-dioxane degradation. Based on batch kinetics measurements, materials that displayed the most suitable characteristics (high 1,4-dioxane degradation activity and high H2O2 consumption efficiency) were ZrO2, WOx/ZrO2, and CuO. In contrast, materials like TiO2, WO3, and aluminosilicate zeolite Y exhibited both low 1,4-dioxane degradation and H2O2 consumption activities. Other materials (e.g., Fe2O3 and CeO2) consumed H2O2 rapidly, however 1,4-dioxane degradation was negligible. The supported metal oxide WOx/ZrO2 was the most active for 1,4-dioxane degradation and had higher H2O2 consumption efficiency compared to ZrO2. In situ acetonitrile poisoning and FTIR spectroscopy results indicate different surface acid sites for 1,4-dioxane and H2O2 adsorption and reaction. Electron paramagnetic resonance measurements indicate that H2O2 forms hydroxyl radicals (˙OH) in the presence of CuO, and unusually, forms superoxide/peroxyl radicals (˙O2−) in the presence of WOx/ZrO2. The identified material properties suggest metal oxides/H2O2 as a potential advanced oxidation process in the treatment of 1,4-dioxane and other recalcitrant organic compounds.