An efficient production of pyruvate by the oxidative dehydrogenation of lactate is achieved using a micro flow system based on gas−liquid slug flow. In this micro flow system, oxidizing agents and acetonitrile solutions of lactates and vanadium species are used, and lactate is converted into the corresponding pyruvate. For reasons of atom economy and enhanced mass transfer of oxygen into the liquid phase, due to internal circulation flow within slugs, molecular oxygen is the preferred agent. In a catalyst screening, vanadium oxytrichloride (VOCl3) gave the highest pyruvate yield. A continuous system is developed, consisting of the following two processes using T-shaped mixers: the mixing of an acetonitrile solution of lactate with that of VOCl3 and the injection of oxygen gas into the solution mixture. Compared with the conventional batch system, the oxidative dehydrogenation of lactate to the corresponding pyruvate proceeds more effectively using this micro flow system.
The acquisition of stemness is a hallmark of aggressive human hepatocellular carcinoma (hHCC). The stem cell marker OCT4 is frequently expressed in HCCs, and its expression correlates with those of putative cancer stem cell (CSC) markers and CSC properties. Here, we describe a novel mechanism of CSC maintenance by SRY through OCT4. We previously reported that Sry is involved in tumor malignancy in rodent HCCs. However, the oncogenic function of SRY in hHCCs is poorly understood. Ectopic expression of SRY increased multiple stem cell factors, including OCT4 and CD13. The OCT4 promoter contained SRY-binding sites that were directly activated by SRY. In HCC-derived cells, SRY knockdown decreased OCT4 expression and cancer stem-like phenotypes such as self-renewal, chemoresistance, and tumorigenicity. Conversely, OCT4 and SRY overexpression promoted cancer stem-like phenotypes. OCT4 knockdown in SRY clones downregulated the self-renewal capacity and chemoresistance. These data suggest that SRY is involved in the maintenance of cancer stem-like characteristics through OCT4. Moreover, CSCs of HCCderived cells differentiated into Tuj1-positive neuron-like cells by retinoic acid. Noteworthily, SRY was highly expressed in some hHCC patients. Taken together, our findings imply a novel therapeutic strategy against CSCs of hHCCs. STEM CELLS 2015;33:2652-2663
SIGNIFICANCE STATEMENTWe demonstrated that SRY, sex-determining factor, is involved in maintenance of cancer stemlike properties such as self-renewal, chemoresistance, and tumorigenicity through upregulation of OCT4. SRY induced the expression of ES markers and cancer stem cell (CSC) markers in HCCderived cell lines. CSC of HCC-derived cell lines differentiated to neuronal cells and hepatocytes, indicating that CSCs of HCC have multipotency. Our data ssuggest that SRY and OCT4 enhance cancer stem-like features, and it can be a potential target of differentiation therapy.
The oxidative dehydrogenation of sodium lactate to sodium pyruvate in an aqueous phase proceeded favorably using Pd/C and that doped with Te at 358 K with no adjustment in solution pH under pressurized oxygen, although previous reports had stated that this reaction would not proceed using Pd/C while Pd/C doped with either Pb, Bi or Te showed the activity at atmospheric pressure, 363 K, and a pH of 8.
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