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Now showing items 1 - 15 of 15

  • Synthesis of new camptothecin analogs with improved antitumor activities

    Niizuma, Satoshi   Tsukazaki, Masao   Suda, Hitomi   Murata, Takeshi   Ohwada, Jun   Ozawa, Sawako   Fukuda, Hiroshi   Murasaki, Chikako   Kohchi, Masami   Morikami, Kenji   Yoshinari, Kiyoshi   Endo, Mika   Ura, Masako   Tanimura, Hiromi   Miyazaki, Yoko   Takasuka, Tsuyoshi   Kawashima, Akira   Nanba, Eitaro   Nakano, Kounosuke   Ogawa, Kotaro   Kobayashi, Kazuko   Okabe, Hisafumi   Umeda, Isao  

    Novel hexacyclic camptothecin analogs containing cyclic amidine, urea, or thiourea moiety were designed and synthesized based on the proposed 3D-structure of the topoisomerase I (Topo I)/DNA/camptothecin ternary complex. The analogs were prepared from 9-nitrocamptothecin via 7,9-diaminocamptothecin derivatives as a key intermediate. Among them, 7c exhibited in vivo antitumor activities superior to CPT-11 in human cancer xenograft models in mice at their maximum tolerated doses though its in vitro antiproliferative activity was comparable to SN-38 against corresponding cell lines. (C) 2009 Elsevier Ltd. All rights reserved.
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  • Anti-Glypican 3 Antibody as a Potential Antitumor Agent for Human Liver Cancer

    Ishiguro, Takahiro   Sugimoto, Masamichi   Kinoshita, Yasuko   Miyazaki, Yoko   Nakano, Kiyotaka   Tsunoda, Hiroyuki   Sugo, Izumi   Ohizumi, Iwao   Aburatani, Hiroyuki   Hamakubo, Takao   Kodama, Tatsuhiko   Tsuchiya, Masayuki   Yamada-Okabe, Hisafumi  

    Human glypican 3 (GPC3) is preferentially expressed in the tumor tissues of liver cancer patients. In this study, we obtained a monoclonal antibody (mAb) against the COOH-terminal part of GPC3, which induced antibody-dependent cellular cytotoxicity (ADCC). The mAb, designated GC33, exhibited marked tumor growth inhibition of s.c. transplanted Hep G2 and HuH-7 xenografts that expressed GPC3 but did not inhibit growth of the SK-HEP-1 that was negative for GPC3. GC33 was efficacious even in an orthotopic model; it markedly reduced the blood a-fetoprotein levels of mice intrahepatically transplanted with Hep G2 cells. Humanized GC33 (hGC33) was as efficacious as GC33 against the Hep G2 xenograft, but hGC33 lacking carbohydrate moieties caused neither ADCC nor tumor growth inhibition. Depletion of CD56(+) cells from human peripheral blood mononuclear cells markedly abrogated the ADCC caused by hGC33. The results show that the antitumor activity of hGC33 is mainly attributable to ADCC, and in human, natural killer cell-mediated ADCC is one possible mechanism of the antitumor effects by GC33. hGC33 will provide a novel treatment option for liver cancer patients with GPC3-positive tumors. [Cancer Res 2008;68(23):9832-8]
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  • Expression of genes responsible for biomineralization of Pinctada fucata during development

    Miyazaki, Yoko   Nishida, Takuma   Aoki, Hideo   Samata, Tetsuro  

    This study compares the expression levels of nacrein, N16, MS160, Prismalin-14, aspein and MSI31 genes during the ontogeny of Pinctada fucata. Several novel findings were obtained: 1) The early calcitic prismatic layer was distinguished as a thin membrane-like structure. 2) Initial formation of the nacreous layer started from the mantle pallial region at the age of 31 days. 3) 18S rRNA of A fucata was determined to be more suitable as a real-time PCR reference gene compared with GAPDH and beta-actin genes. 4) A relationship was recognized between the expression levels of the above six organic matrix genes and biomineralization of the larval shell. The lack of calcite in the shells of the veliger and pediveliger stages, when MSI31 and Prismalin-14 genes were expressed, makes a role of polymorph control by these genes less likely. The hypothetical involvement of N16 and MS160 proteins in aragonitic nacreous layer formation was corroborated by the expression levels of N16 and MS160 genes during ontogeny. Our results are important with respect to the control of CaCO(3) crystal polymorphism and shell microstructures in P. fucata. (C) 2009 Elsevier Inc. All rights reserved.
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    MIYAZAKI, Yoko   TAJIMI, Sakon  

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  • Aqueous Extracts of Rhizopus oryzae Induced Nitric Oxide Production in Rat Hepatocyte Cell Line RLN-10

    Suzuki, Takehito   Uchida, Mayuko   Takeda, Yuji   Mori, Chiemi   Onuki, Atsushi   Miyazaki, Yoko   Onda, Ken   Ushikoshi, Setsuo   Shitori, Kotaro   Tanaka, Kazuaki   Morita, Hidetoshi   Takizawa, Tatsuya  

    Aqueous extracts of Rhizopus oryzae (Aq-ROU) have a broad range of physiological activity. Here we identified a new physiological effect of Aq-ROU in rat hepatocyte cell line RLN-10. Aq-ROU induced the accumulation of nitrite, a stable metabolite nitric oxide (NO), in cell culture medium and induced potent diaminofluorescein-FM diacetate staining in the cells. Real-time reverse transcriptase (RT)-PCR analysis showed marked inducible NO synthase gene expression. Additionally, markedly enhanced expression of p(22Phox) and temporally increased expression of NADPH oxidase1 indicated that superoxide was produced. Nuclear translocation of nuclear factor-kappa (NF-kappa) B p65 increased remarkably following Aq-ROU and following lipopolysaccharide treatment, a potent activator of NF-kappa B. Ammonium pyrrolidine-l-carbodithioate, an inhibitor of NF-kappa B, inhibited NO production following Aq-ROU treatment. Our data indicate that Aq-ROU induces NO production and potentially the production of superoxide, which may contribute to the broad range of physiological effects observed for Aq-ROU ingested by animals.
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  • Nitric Oxide Induces Vascular Endothelial Growth Factor Expression in the Rat Placenta in Vivo and in Vitro

    Abe, Hideaki   Ishikawa, Wataru   Kushima, Takahiro   Nishimura, Tomoka   Mori, Chiemi   Onuki, Atsushi   Suzuki, Takehito   Ishii, Yasuo   Kansaku, Norio   Miyazaki, Yoko   Tanaka, Kazuaki   Morita, Hidetoshi   Takizawa, Tatsuya  

    We investigated the role of nitric oxide (NO) in vascular endothelial growth factor (VEGF) expression in the rat placenta. A nitric oxide synthase (NOS) inhibitor, N-G-nitro-L-arginine-methyl ester (L-NAME), was constantly infused into pregnant rats 6-24 h before sacrifice on gestational day (GD) 15.5. NO production declined to about 15% of the control level as monitored by NO trapping and electron paramagnetic resonance spectroscopy. VEGF mRNA expression was temporally decreased by L-NAME, but recovered to normal levels after 24h of treatment, whereas hypoxia inducible factor (HIF)-1 alpha and induced NOS (iNOS) expression increased. VEGF expression decreased significantly in placental explants after 6h of co-treatment with L-NAME and lipopolysaccharide, an iNOS inducer. Our data indicate that NO induce VEGF expression in vivo and in vitro in the rat placenta, suggesting that peaked NO production was maintained by a reciprocal relationship between NO and VEGF via HIF-1 alpha.
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  • Valproic acid promotes mature neuronal differentiation of adipose tissue-derived stem cells through iNOS-NO-sGC signaling pathway.

    Okubo, Takumi   Fujimoto, Shinri   Hayashi, Daiki   Suzuki, Takehito   Sakaue, Motoharu   Miyazaki, Yoko   Tanaka, Kazuaki   Usami, Makoto   Takizawa, Tatsuya  

    Valproic acid (VPA) remarkably promotes the differentiation of adipose tissue-derived stem cells (ASCs) to mature neuronal cells, enabling neuronal induction within only three days. Here, we investigated the involvement of NO-signaling in the VPA-promoted neuronal differentiation of ASCs as a possible mechanism. Cultured rat ASCs were differentiated to matured neuronal cells rich in dendrites and expressing betaIII-tubulin protein, a neuronal marker, by treatments with VPA at 2=E2=80=AFmM for 3 days and subsequently with the neuronal induction medium (NIM) containing cAMP-elevating agents for 2=E2=80=AFh. Increased intracellular NO was detected in neuronal cells differentiated from ASCs treated with VPA by a fluorescence NO-specific probe, diaminofluorescein-FM diacetate. However, a NO donor (NOC18) increased the incidence of neuronal cells only to a lesser extent than VPA, indicating the insufficiency of exogenous NO. RT-PCR analysis of ASCs treated with VPA showed increased mRNA expression of inducible nitric oxide synthase (iNOS) with the acetylation of its associated histone H3K9. iNOS inhibitors (1400=E2=80=AFW and dexamethasone) or a soluble guanylate cyclase (sGC) inhibitor (ODQ) decreased the incidence of neuronal cells differentiated from ASCs treated with VPA. These inhibitors also decreased the mRNA expression of mature neuronal markers, neurofilament medium polypeptide (NeFM) and microtubule-associated protein 2 (MAP2), as well as betaIII-tubulin (TUBB3), to various extents. It was considered from these results that VPA promoted mature neuronal differentiation of ASCs through the iNOS-NO-sGC signaling pathway. This provided insights into the regulated neuronal differentiation of ASCs in clinical applications. Copyright =C2=A9 2019 Elsevier Inc. All rights reserved.
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  • Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid,a histone deacetylase inhibitor

    Okubo, Takumi   Hayashi, Daiki   Yaguchi, Takayuki   Fujita, Yudai   Sakaue, Motoharu   Suzuki, Takehito   Tsukamoto, Atsushi   Murayama, Ohoshi   Lynch, Jonathan   Miyazaki, Yoko   Tanaka, Kazuaki   Takizawa, Tatsuya  

    Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to modulate the neuronal differentiation of adipose tissue-derived stem cells (ASCs) in humans and dogs. However, controversy exists as to whether VPA really acts as an inducer of neuronal differentiation of ASCs. The present study aimed to elucidate the effect of VPA in neuronal differentiation of rat ASCs. One or three days of pretreatment with VPA (2 mM) followed by neuronal induction enhanced the ratio of immature neuron marker beta III-tubulin-positive cells in a time-dependent manner, where the majority of cells also had a positive signal for neurofilament medium polypeptide (NEFM), a mature neuron marker. RT-PCR analysis revealed increases in the mRNA expression of microtubule-associated protein 2 (MAP2) and NEFM mature neuron markers, even without neuronal induction. Three-days pretreatment of VPA increased acetylation of histone H3 of ASCs as revealed by immunofluorescence staining. Chromatin immunoprecipitation assay also showed that the status of histone acetylation at H3K9 correlated with the gene expression of TUBB3 in ASCs by VPA. These results indicate that VPA significantly promotes the differentiation of rat ASCs into neuron-like cells through acetylation of histone H3, which suggests that VPA may serve as a useful tool for producing transplantable cells for future applications in clinical treatments.
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  • Synthesis and biological activities of a pH-dependently activated water-soluble prodrug of a novel hexacyclic camptothecin analog

    Ohwada, Jun   Ozawa, Sawako   Kohchi, Masami   Fukuda, Hiroshi   Murasaki, Chikako   Suda, Hitomi   Murata, Takeshi   Niizuma, Satoshi   Tsukazaki, Masao   Ori, Kazutomo   Yoshinari, Kiyoshi   Itezono, Yoshiko   Endo, Mika   Ura, Masako   Tanimura, Hiromi   Miyazaki, Yoko   Kawashima, Akira   Nagao, Shunsuke   Namba, Eitarou   Ogawa, Koutarou   Kobayashi, Kazuko   Okabe, Hisafumi   Umeda, Isao  

    CH0793076 (1) is a novel hexacyclic camptothecin analog showing potent antitumor activity in various human caner xenograft models. To improve the water solubility of 1, water-soluble prodrugs were designed to generate an active drug 1 nonenzymatically, thus expected to show less interpatient PK variability than CPT-11. Among the prodrugs synthesized, 4c (TP300, hydrochloride) having a glycylsarcosyl ester at the C-20 position of 1 is highly water-soluble (> 10 mg/ml), stable below pH 4 and rapidly generates 1 at physiological pH in vitro. The rapid (ca. < 1 min) generation of 1 after incubation of TP300 with plasma (mouse, rat, dog and monkey) was also demonstrated. TP300 showed a broader antitumor spectrum and more potent antitumor activity than CPT-11 in various human cancer xenograft models. (C) 2009 Elsevier Ltd. All rights reserved.
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  • A water soluble prodrug of a novel camptothecin analog is efficacious against breast cancer resistance protein-expressing tumor xenografts

    Endo, Mika   Miwa, Masanori   Ura, Masako   Tanimura, Hiromi   Taniguchi, Kenji   Miyazaki, Yoko   Ohwada, Jun   Tsukazaki, Masao   Niizuma, Satoshi   Murata, Takeshi   Ozawa, Sawako   Suda, Hitomi   Ogawa, Kotaro   Nanba, Eitaro   Nagao, Shunsuke   Shimma, Nobuo   Yamada-Okabe, Hisafumi  

    Identification of a novel topoisomerase I inhibitor which shows superior efficacy and less individual variation than irinotecan hydrochloride (CPT-11). A novel camptothecin analog that is effective against breast cancer resistance protein (BCRP)-positive cells was screened, and a water soluble prodrug was generated. Antitumor activity of the prodrug was examined in BCRP-positive and -negative xenografts both as a single agent and in combination with other anti-cancer drugs. A novel camptothecin analog, CH0793076, was discovered. Because CH0793076 was found to be highly lipophilic, a water soluble prodrug (TP300) was generated. TP300 is stable in an acidic solution but is rapidly converted to CH0793076 under physiological pH conditions such as in sera. This efficient prodrug activation would minimize interpatient differences in pharmacokinetic and toxicity profiles. Unlike CPT-11, TP300 does not exhibit cholinergic interaction or cause acute diarrhea at effective doses. In mouse xenograft models, TP300 showed antitumor activity against both BCRP-positive and -negative xenografts, whereas CPT-11 was less active against BCRP-positive xenografts. In addition, the effective dose range (MTD/ED(50)) for TP300 was wider than for CPT-11 and TP300 showed additive or synergistic antitumor effects in combination with other anti-cancer drugs such as capecitabine, oxaliplatin, cisplatin, bevacizumab and cetuximab. It is therefore expected that TP300 will provide an additional treatment option for patients who will undergo chemotherapy with camptothecins.
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  • Negative air pressure treatment accelerates the penetration of permeable cryoprotectants into bovine ovarian tissue in vitrification protocol and improves cell density after vitrification

    Toyama-Mori, Chiemi   Suzuki, Kurumi   Miyazaki, Yoko   Suzuki, Takehito   Katsumata, Masaya   Tanaka, Kazuaki   Usami, Makoto   Takizawa, Tatsuya  

    Effects of additional physical treatments during vitrification of the bovine ovarian tissue were examined for increasing of permeability of ethylene glycol (EG) and dimethyl sulfoxide (Me2SO). The concentrations of EG and Me2SO and histological changes in the ovarian tissue were evaluated. In the first equilibration step (7.5% EG and 7.5% Me2SO), all the 10-min physical treatments, i.e., negative (679 hPa) or positive (1347 hPa) air pressure applied with a disposable syringe, and shaking (60 rpm) applied with a laboratory shaker, were comparable to 25-min non-physical treatment (plain) vitrification. When effects of the negative air pressure were examined in the second equilibration step (20% EG and 20% Me2SO), its 10-min treatment was equivalent to 15-min plain vitrification (140-170 mg/g tissue). It was thus indicated that the negative air pressure treatment accelerates the penetration of permeable cryoprotectants into the ovarian tissue slices. Histological examination showed that the cell density and the amount of pan-cadherin in the tunica albuginea of the ovary was reduced by the vitrification, but was improved by the negative air pressure treatment. The amount of pan-cadherin in the tunica albuginea was recommended as a biomarker for evaluation of effectiveness of protocol for cryopreservation of bovine ovarian tissue and considered to be a candidate biomarker for human ovarian tissue cryopreservation.
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  • Negative air pressure treatment accelerates the penetration of permeable cryoprotectants into bovine ovarian tissue in vitrification protocol and improves cell density after vitrification

    Toyama-Mori, Chiemi   Suzuki, Kurumi   Miyazaki, Yoko   Suzuki, Takehito   Katsumata, Masaya   Tanaka, Kazuaki   Usami, Makoto   Takizawa, Tatsuya  

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  • SPIE Proceedings [SPIE Microlithography \"97 - Santa Clara, CA (Monday 10 March 1997)] Metrology, Inspection, and Process Control for Microlithography XI - Characterization of real particle size for the process particle monitor using laser surface scanners

    Miyazaki, Yoko   Mugibayashi, Toshiaki   Ikeno, Masahiko   Jones, Susan K.  

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  • SPIE Proceedings [SPIE Micro - DL Tentative - San Jose, CA (Sunday 1 March 1992)] Integrated Circuit Metrology, Inspection, and Process Control VI - Surface defect inspection system with an optical spatial frequency filter for semiconductor patterned wafers

    Miyazaki, Yoko   Tanaka, Hitoshi   Kosaka, Nobuyuki   Tomoda, Toshimasa   Postek, Jr., Michael T.  

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  • [American Institute of Aeronautics and Astronautics 46th AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Materials Conference - Austin, Texas ()] 46th AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Materials Conference - Effects of Initial Configuration on Large Deformation Analysis for One-Dimensional Deployable Membrane

    Miyazaki, Yoko   Furuya, Hiroshi   Murata, Satoshi   Takadama, Keiki  

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