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Design, synthesis, and biological activity of folate receptor-targeted prodrugs of thiolate histone deacetylase inhibitors 总被引:1,自引:0,他引:1
Suzuki T Hisakawa S Itoh Y Suzuki N Takahashi K Kawahata M Yamaguchi K Nakagawa H Miyata N 《Bioorganic & medicinal chemistry letters》2007,17(15):4208-4212
Aiming to develop selective anticancer drugs, we designed and synthesized three disulfides bearing a folic acid moiety as candidate folate receptor (FR)-targeted prodrugs of thiolate histone deacetylase inhibitors. Among them, compound 1 displayed growth-inhibitory activity toward folate receptor-positive MCF-7 breast cancer cells. The activity of 1 was significantly reduced by free folic acid, suggesting that cellular uptake of 1 is mediated by FR. 相似文献
83.
Atf1 is a target of the mitogen-activated protein kinase Pmk1 and regulates cell integrity in fission yeast 总被引:1,自引:1,他引:0 下载免费PDF全文
Takada H Nishimura M Asayama Y Mannse Y Ishiwata S Kita A Doi A Nishida A Kai N Moriuchi S Tohda H Giga-Hama Y Kuno T Sugiura R 《Molecular biology of the cell》2007,18(12):4794-4802
In fission yeast, knockout of the calcineurin gene resulted in hypersensitivity to Cl(-), and the overexpression of pmp1(+) encoding a dual-specificity phosphatase for Pmk1 mitogen-activated protein kinase (MAPK) or the knockout of the components of the Pmk1 pathway complemented the Cl(-) hypersensitivity of calcineurin deletion. Here, we showed that the overexpression of ptc1(+) and ptc3(+), both encoding type 2C protein phosphatase (PP2C), previously known to inactivate the Wis1-Spc1-Atf1 stress-activated MAPK signaling pathway, suppressed the Cl(-) hypersensitivity of calcineurin deletion. We also demonstrated that the mRNA levels of these two PP2Cs and pyp2(+), another negative regulator of Spc1, are dependent on Pmk1. Notably, the deletion of Atf1, but not that of Spc1, displayed hypersensitivity to the cell wall-damaging agents and also suppressed the Cl(-) hypersensitivity of calcineurin deletion, both of which are characteristic phenotypes shared by the mutation of the components of the Pmk1 MAPK pathway. Moreover, micafungin treatment induced Pmk1 hyperactivation that resulted in Atf1 hyperphosphorylation. Together, our results suggest that PP2C is involved in a negative feedback loop of the Pmk1 signaling, and results also demonstrate that Atf1 is a key component of the cell integrity signaling downstream of Pmk1 MAPK. 相似文献
84.
The usefulness of semi‐solid medium in the isolation of highly virulent Leptospira strains from wild rats in an urban area of Fukuoka,Japan 下载免费PDF全文
Mitsumasa Saito Sharon Y. A. M. Villanueva Toshiyuki Masuzawa Yusuke Haraguchi Shuhei Ita Satoshi Miyahara Ryo Ozuru Takayoshi Yamaguchi Michinobu Yoshimura Mami Ikejiri Natsumi Aramaki Muhammad Yunus Amran Lisa Tenriesa Muslich Ken‐ichiro Iida Yasutake Yanagihara Nina G. Gloriani Shin‐ichi Yoshida 《Microbiology and immunology》2015,59(6):322-330
Leptospirosis is a worldwide zoonosis. The importance of urban leptospirosis is recognized in Japan: urban rats carry pathogenic leptospires and people acquire these pathogens through contact with surface water or soil contaminated by the urine of the infected animals. To determine the current Leptospira carriage rate in urban rats, 29 wild rats were trapped in the central area of Fukuoka and strains isolated from their kidneys and urine analyzed. When semi‐solid Korthof's medium containing 0.1% agar was used for isolation, 72.2% and 30.8% of the kidney and urine cultures, respectively, were found to be Leptospira‐positive. The isolates belonged to Leptospira interrogans, and were classified into two groups (serogroups Pomona and Icterohaemorrhagiae) based on the results of gyrB sequence analysis and microscopic agglutination testing (MAT). Strains belonging to serogroup Icterohemorrhagiae grew well in liquid medium. On the other hand, serogroup Pomona isolates multiplied very little in liquid medium, but did grow in a semi‐solid medium. Although strains belonging to serogroup Pomona have not been recognized as native to Japan, this strain may be widely distributed in urban rats. Representative strains from each group were found to be highly pathogenic to hamsters. Our findings should serve as a warning that it is still possible to become infected with leptospires from wild rats living in inner cities of Japan. Furthermore, the use of semi‐solid medium for culture will improve the isolation rate of leptospires from the kidneys of wild rats. 相似文献
85.
Koichi Ohkuma Kouki Matsuda Ryusho Kariya Hiroki Goto Shintaro Kamei Takayoshi Hamamoto Seiji Okada 《Microbiology and immunology》2015,59(7):381-388
Activated protein C (APC) has an anticoagulant action and plays an important role in blood coagulation homeostasis. In addition to its anticoagulant action, APC is known to have cytoprotective effects, such as anti‐apoptotic action and endothelial barrier protection, on vascular endothelial cells and monocytes. However, the effects of APC on DCs have not been clarified. To investigate the effects of APC on human DCs, monocytes were isolated from peripheral blood and DC differentiation induced with LPS. APC significantly inhibited the production of inflammatory cytokines TNF‐α and IL‐6 during differentiation of immature DCs to mature DCs, but did not inhibit the production of IL‐12 and anti‐inflammatory cytokine IL‐10. Interestingly, treatment with 5 μg/mL, but not 25 μg/mL, of APC significantly enhanced production of IL‐10. In addition, protein C, which is the zymogen of APC, did not affect production of these cytokines. On the other hand, flow cytometric analysis of DC's surface molecules indicated that APC does not significantly affect expression of CD83, a marker of mDC differentiation, and the co‐stimulatory molecules CD40, CD80 and CD86. These results suggest that APC has anti‐inflammatory effects on human DCs and may be effective against some inflammatory diseases in which the pathogenesis involves TNF‐α and/or IL‐6 production. 相似文献
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Enthalpies of mixing of R- and S-limonene in non-polar solvents in the entire range of mole fractions were measured at 298.15 K. The enthalpies of mixing were negative for all concentrations in dilute concentration, but increased by increasing the concentration of limonenes in solutions. Ultimately positive excess enthalpies were shown in high concentration. Enthalpies of mixing were compared with theoretical estimation by COSMO-RS. 相似文献
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