• Proceedings of the PSK Conference
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• 2003.10b
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• pp.137.2-137.2
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• 2003

Dendritic cells (DCs) are known to professional antigen presenting cell (APC). Due to the role as an effective activator of cytotoxic T Lymphocytes by expressing MHC, adhesion and co-stimulatory molecules, DCs are now widely recognized to play an important role in the immune responses to tumors.We investigated the effect of cultured DCs in murine melanoma pulmonary metastasis model. To follow the metastasis protocol, syngenic melanoma cells were inoculated intra-venously into the mouse (B16F10 into the C57BL/6)8 days prior to the first DC injection (1$\times$106 DCs/ mouse, i.p.) and the autologous tumor cell lysate pulsed-DCs were injected as a therapeutic module twice in two weeks. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.159.1-159.1
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• 2003

Human Topoisomerase I (topo I) helps the control of DNA supercoiling in cells by assisting breaking and religation of DNA strand. It is essential for cellular metabolism and survival, hence, a good target for a novel class of anticancer drugs. As topo I inhibitor binds to the DNA-topo I complex, the religation of DNA strand is suppressed which results in the death of the target cell. Seven compounds of H-Imidazo［4, 5-g］phthalazing-4, 9-dione derivatives with $IC_50$ in the range of 0.001 and 6.27 $\mu$M in 5 different cancer cells and four compounds of 7-chloro-6-quinazoline-5, 8-dione derivatives with positive and negative topo I inhibition activities were studied. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.160.1-160.1
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• 2003

In order to confirm the biological function of ORF10 in cephabacin biosynthesis gene cluster of Lysobacter lactamgenus as an ATP-binding-cassette (ABC) transporter, the gene for ORF10 was amplified and subcloned into pET-28a(+) expression vector. After gene induction with 0.5 mM IPTG at 30~! and further cultivation at $30^~$ !. for 8 hr, a lot of the recombinant ORF10 protein was produced as soluble form in cytoplasmic fraction as well as a membrane protein in the membrane fraction as likely as other ABC transporters. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.155.3-156
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• 2003

Flavonoids from plant origin show anti-inflammatory activity in vitro and in vivo. In addition to inhibition of inflammation-associated enzymes such as cyclooxygenases and lipoxygenases, they have been found to regulate the expression of inflammation-associated proteins from in vitro experiments. In order to prove in vivo behavior and the potential for beneficial use against inflammatory skin disorders, the effect of wogonin (5,7-dihydroxy-8-methoxyflavone) on in vivo expression of several inflammation-associated genes was examined in the intact as well as in the inflamed mouse skin by reverse transcriptase-polymerase chain reaction analysis. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.155.1-155.1
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• 2003

Polyphenol QGR (quercetin 3-O-beta-(2"-galloyl)-rhamnopyranoside) was isolated from Persicaria lapathifolia (Polygonaceae). In this study, we investigated inhibitory effects of QGR and its building blocks (quercitrin, quercetin and gallic acid) on superoxide anion and NO productions in unopsonized zymosan-stimulated murine macrophages Raw264.7. QGR and quercetin showed potent inhibitory effects on unopsonized zymosan-induced superoxide anion production with IC50 values of 3.2 uM and 4.8 uM, respectively. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.172.1-172.1
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• 2003

Luotonin A was isolated from Peganum nigellastrum Bunge (Zygophyllaceae) which was named Luo-Tuo-Hao in China and used as a Chinese traditional medicine for the treatment of rheumatism, abscess, and inflammation. The basic fractions of P. nigellastrum showed antitumor activtity, and the origin of such an activity was recently revealed by identifying its constituent luotonin A which inhibited the growth of leukemia P-388 cells ($IC_50$ = 1.8 $\mu$g/mL). Such an intriguing properties of luotonin A led developments of efficient methods for total synthesis. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.167.1-167.1
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• 2003

Here we show that panaxadiol, a ginseng saponin with a dammarane skeleton, induces acute apoptotic cell death in human hepatoma SK-HEP-1 cells as evidenced by analysis of DNA fragmentation, caspase activation, and changes in cell morphology. The kinetic study showed that panaxadiol-induced apoptosis is associated with depolarization of mitochondrial membrane potential and cytochrome c release. Sequential activations of caspases-depolarization of mitochondrial membrane potential and cytochrome c release. Sequential activations of caspases-9, and -3, or -7, but not of caspase 8 coincide well in a time dependent manner with mitochondrial membrane depolarization and cytochrome c release from mitochondria during apoptosis of SK-HEP-1 cells induced by treatment with panaxadiol. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.168.1-168.1
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• 2003

We show that panaxadiol (PD), a ginseng saponin with a dammarane skeleton, selectively interferes with the cell cycle in human cancer cell lines. PD inhibited DNA synthesis in a dose-dependent manner with $IC_{50}$ values ranging from 0.8 $\mu$M-1.2 $\mu$M in SK-HEP-1 cells and HeLa cells. PD-treated cells were arrested at G1/S phase, shich coincided well with decreases in Cyclin A-Cdk2 activity, but not in Cyclin E-Cdk2 and Cdc2 activities. The intracellular levels of $p21^{WAF1/CIP1}$ were significantly and selectively elevated in a dose and time-dependent manners in PD-treated HeLa cells. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.174.1-174.1
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• 2003

We have previously reported the synthesis and cytotoxic activities of a series of azaanthraquinone derivatives using doxorubicin as a lead compound. Doxorubicin is known to intercalate into DNA and to inhibit topoisomerase II activity. But in the case of quinone compounds like Dox, its use is limited because of systemic toxicities, primarily cardiotoxicity and myelosuppression. In this study, we discuss the synthesis of isoindolobenzoquinoxaline derivatives. The quinone group of the azaanthraquinone derivatives were removed in the target compounds. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.180.2-180.2
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• 2003

Cathepsin K, a cysteine protease of the papain superfamily, is predominantly expressed in osteoclasts and has been postulated as a target for the treatment of osteoporosis. Crystallographic and structure-activity studies on a series of azepanone-based diamino and acyclic ketone derivative inhibitors of cathepsin K have led to the design and identification. X-ray structure of the cysteine protease cathepsin K (1NL6) co-crystalized with an inhibitor with 2.8${\AA}$ resolution was used to predict the protein-ligand interactions and to estimate the binding affinity from the docking score by FlexX module. (omitted)