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High-resolution magic-angle spinning (MAS) 1H nuclear magnetic resonance spectroscopy has been employed to characterize the metabolite composition (i.e., metabonome) of the human hepatocellular carcinoma (HCC) tumor in combination with principal component analysis (PCA). The results showed that (a) the metabonomes of both low-grade HCC and high-grade HCC(More)
Constitutive activation of signal transducer and activator of transcription 3 (STAT3) signaling is frequently detected in cancer, promoting its emergence as a promising target for cancer treatment. Inhibiting constitutive STAT3 signaling represents a potential therapeutic approach. We used structure-based design to develop a nonpeptide, cell-permeable,(More)
Purine nucleoside phosphorylase catalyzes reversible phosphorolysis of purine nucleosides and 2'-deoxypurine nucleosides to the free base and ribose (or 2'-deoxyribose) 1-phosphate. Whereas the human enzyme is specific for 6-oxopurine ribonucleosides, the Escherichia coli enzyme accepts additional substrates including 6-oxopurine ribonucleosides,(More)
The biologic and clinical significance of KIT overexpression that associates with KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that KIT mutations lead to MYC-dependent miR-29b repression and increased levels of the miR-29b target Sp1 in KIT-driven leukemia. Sp1(More)
Molecular docking of the interaction of curcumin and DNMT1 suggested that curcumin covalently blocks the catalytic thiolate of C1226 of DNMT1 to exert its inhibitory effect. This was validated by showing that curcumin inhibits the activity of M. SssI with an IC(50) of 30 nM, but no inhibitory activity of hexahydrocurcumin up to 100 microM. In addition,(More)
Although the antitumor effect of alpha-tocopheryl succinate (vitamin E succinate) has been well demonstrated, its underlying mechanism remains elusive. This study provides evidence that inhibition of Bcl-xL/Bcl-2 function represents a major pathway whereby alpha-tocopheryl succinate mediates apoptosis induction in prostate cancer cells. In vitro data(More)
Interleukin (IL)-6 overexpression and constitutive STAT3 activation occur in many cancers, including prostate cancer. However, their contribution to prostate stem and progenitor cells has not been explored. In this study, we show that stem-like cells from patients with prostate cancer secrete higher levels of IL-6 than their counterparts in non-neoplastic(More)
Driven by recent vision and graphics applications such as image segmentation and object recognition, computing pixel-accurate saliency values to uniformly highlight foreground objects becomes increasingly important. In this paper, we propose a unified framework called pixelwise image saliency aggregating (PISA) various bottom-up cues and priors. It(More)
We characterized the biologic effects of a novel small molecule STAT3 pathway inhibitor that is derived from the natural product curcumin. We hypothesized this lead compound would specifically inhibit the STAT3 signaling pathway to induce apoptosis in melanoma cells. FLLL32 specifically reduced STAT3 phosphorylation at Tyr705 (pSTAT3) and induced apoptosis(More)
The immunovariant N-ethyl-N-nitrosourea-induced mutations Pococurante (Poc) and Lackadaisical were found to alter MyD88, creating striking receptor-selective effects. Poc, in particular, prevented sensing of all MyD88-dependent Toll-like receptor (TLR) ligands except diacyl lipopeptides. Furthermore, Poc-site and classical BB loop mutations caused(More)