Metronomic S-1 dosing and thymidylate synthase silencing have synergistic antitumor efficacy in a colorectal cancer xenograft model

Metronomic chemotherapy is currently considered an emerging therapeutic option in clinical oncology. S-1, an oral formulation of Tegafur (TF), a prodrug of 5-fluorouracil (5-FU), is designed to improve the antitumor activity of 5-FU in tandem with reducing its toxicity. Clinically, metronomic S-1 dosing has been approved for the standard first- and second-line treatment of metastatic or advanced stage of colorectal (CRC). However, expression of intratumor thymidylate synthase (TS), a significant gene in cellular proliferation, is associated with poor outcome to 5-FU-based chemotherapeutic regimens. In this study, therefore, we examined the effect of a combination of TS silencing by an RNA interfering molecule, chemically synthesized short hairpin RNA against TS (shTS), and 5-FU on the growth of human colorectal cancer cell (DLD-1) both in vitro and in vivo. The combined treatment of both shTS with 5-FU substantially inhibited cell proliferation in vitro. For in vivo treatments, the combined treatment of metronomic S-1 dosing with intravenously injected polyethylene glycol (PEG)-coated shTS-lipoplex significantly suppressed tumor growth, compared to a single treatment of either S-1 or PEG-coated shTS-lipoplex. In addition, the combined treatment increased the proportion of apoptotic cells in the DLD-1 tumor tissue. Our results suggest that metronomic S-1 dosing combined with TS silencing might represent an emerging therapeutic strategy for the treatment of patients with advanced CRC

Thermoelectric properties of Zintl arsenide EuCuAs

We demonstrate thermoelectric transport properties of Zintl arsenide EuCuAs. The crystal structure of EuCuAs (hexagonal P63/mmc space group) consists of a covalently-bonded honeycomb-type [CuAs] network sandwiched by Eu2+ ions. Undoped EuCuAs exhibit the thermoelectric power factor of 1.2 and 0.4 mW/mK2 at 673 K along directions perpendicular and parallel to the uniaxial hot-pressing direction, respectively. Despite the relatively high power factor, dimensionless figure of merit is limited to 0.1 at 673 K due to the high lattice thermal conductivity, >2.0 W/mK. In addition to relatively high power factor, first-principles calculations predicted that, owing to a peculiar shape of the Fermi surface, heavy hole doped EuCuAs with hole concentration of >1.5 x 10^21 cm^-3 will exhibit the axis-dependent conduction polarity, which enables us to construct the transverse thermoelectric devices. We investigated the synthesis and thermoelectric transport properties of Eu1-xNaxCuAs using sodium (Na) as a hole dopant, resulting in a hole concentration of 1.0 x 10^21 cm^-3. The absolute value of the Seebeck coefficient decreased by Na-doping, as predicted by first-principles calculations, but no conduction polarity switching was observed. This may have resulted from insufficient hole concentration and/or preferred orientation of the samples

Thermoelectric Properties of the As/P-Based Zintl Compounds EuIn2As2−xPx (X = 0 to 2) and SrSn2As2

Zintl compounds containing Sb have been studied extensively because of their promising thermoelectric properties. In this study, we prepared As/P-based Zintl compounds, EuIn2As2-xPx (x = 0 to 2) and SrSn2As2, and examined their potential for use as thermoelectric materials. These compounds show hole carrier concentrations of ~10^19 /cm3 for EuIn2As2-xPx and ~10^21 /cm3 for SrSn2As2 at 300 K. The high carrier concentration of SrSn2As2 is likely owing to self-doping by hole-donating Sn vacancies. The electrical power factor reaches ~1 mW/mK2 at ~600 K for EuIn2As2-xPx with x = 0.1 and 0.2. The lattice thermal conductivity is determined to be 1.6–2.0 W/mK for EuIn2As2 and SrSn2As2, and 2.8 W/mK for EuIn2P2 at 673 K. The dimensionless figure of merit reaches ZT = 0.29 at 773 K for EuIn2As2-xPx with x = 0.2. First-principles calculations show that EuIn2As2 and SrSn2As2 are topologically nontrivial materials with band inversion, while EuIn2P2 is a conventional semiconductor with a bandgap. The present study demonstrates that As/P-based Zintl compounds can also show promising thermoelectric properties, thus expanding the frontier for efficient thermoelectric materials