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991.
Asahi Ito Takashi Ishida Hiroki Yano Atsushi Inagaki Susumu Suzuki Fumihiko Sato Hisashi Takino Fumiko Mori Masaki Ri Shigeru Kusumoto Hirokazu Komatsu Shinsuke Iida Hiroshi Inagaki Ryuzo Ueda 《Cancer immunology, immunotherapy : CII》2009,58(8):1195-1206
Purpose There are no suitable small animal models to evaluate human antibody-dependent cellular cytotoxicity (ADCC) in vivo, due to
species incompatibilities. Thus, the first aim of this study was to establish a human tumor-bearing mouse model in which human
immune cells can engraft and mediate ADCC, but where the endogenous mouse immune cells cannot mediate ADCC. The second aim
was to evaluate ADCC mediated in these humanized mice by the defucosylated anti-CC chemokine receptor 4 (CCR4) monoclonal
antibody (mAb) which we have developed and which is now in phase I clinical trials.
Experimental design NOD/Shi-scid, IL-2Rγnull (NOG) mice were the recipients of human immune cells, and CCR4-expressing Hodgkin lymphoma (HL) and cutaneous T-cell lymphoma
(CTCL) cell lines were used as target tumors.
Results Humanized mice have been established using NOG mice. The chimeric defucosylated anti-CCR4 mAb KM2760 showed potent antitumor
activity mediated by robust ADCC in these humanized mice bearing the HL or CTCL cell lines. KM2760 significantly increased
the number of tumor-infiltrating CD56-positive NK cells which mediate ADCC, and reduced the number of tumor-infiltrating FOXP3-positive
regulatory T (Treg) cells in HL-bearing humanized mice.
Conclusions Anti-CCR4 mAb could be an ideal treatment modality for many different cancers, not only to directly kill CCR4-expressing tumor
cells, but also to overcome the suppressive effect of Treg cells on the host immune response to tumor cells. In addition,
using our humanized mice, we can perform the appropriate preclinical evaluation of many types of antibody based immunotherapy. 相似文献
992.
Guangming Chen Hongyu Ren Anthony Turpoff Alexander Arefolov Richard Wilde James Takasugi Atiyya Khan Neil Almstead Zhengxian Gu Takashi Komatsu Connie Freund Jamie Breslin Joseph Colacino Jean Hedrick Marla Weetall Gary M. Karp 《Bioorganic & medicinal chemistry letters》2013,23(13):3942-3946
A series of novel 2-phenylindole analogs were synthesized and evaluated for activity in subgenomic HCV replicon inhibition assays. Several compounds containing small alkyl sulfonamides on the phenyl ring exhibiting submicromolar EC50 values against the genotype 1b replicon were identified. Among these, compound 25d potently inhibited the 1b replicon (EC50 = 0.17 μM) with 147-fold selectivity with respect to cytotoxicity. Compound 25d was stable in the presence of human liver microsomes and had a good pharmacokinetic profile in rats with an IV half-life of 4.3 h and oral bioavailability (F) of 58%. 相似文献
993.
994.
Ryuhei Nishikawa Kiichiro Teruya Yoshinori Katakura Kazuhiro Osada Takeki Hamasaki Taichi Kashiwagi Takaaki Komatsu Yuping Li Jun Ye Akira Ichikawa Kazumichi Otsubo Shinkatsu Morisawa Qianghua Xu Sanetaka Shirahata 《Cytotechnology》2005,47(1-3):97-105
In the two-stage cell transformation theory, cancer cells first receive initiation, which is mainly caused by DNA damage,
and then promotion, which enhances transformation. Murine Balb/c 3T3 cells are widely used for transformation experiments
because they lose contact inhibition ability when transformed. Electrolyzed reduced water (ERW), which is produced near a
cathode during electrolysis of water, is an alkaline drinking water that is beneficial to health. ERW contains a high concentration
of dissolved hydrogen and scavenge reactive oxygen species (ROS), along with a small amount of platinum (Pt) nanoparticles
(Pt nps) derived from Pt-coated titanium electrodes. Pt nps stably disperse in aqueous solution for a long time, and convert
hydrogen molecules to active hydrogen (atomic hydrogen) that can scavenge ROS. Therefore, ERW supplemented with synthesized
Pt nps is a model strong reduced water. This is the first report that ERW supplemented with synthesized Pt nps strongly prevents
transformation of Balb/c 3T3 cells. ERW was prepared by electrolysis of 0.002 M NaOH solution using a batch-type electrolysis
device. Balb/c 3T3 cells were treated with 3-methyl cholanthrene (MCA) as an initiation substance, followed by treatment with
phorbol-12-myristate-13-acetate (PMA) as a promotion substance. MCA/PMA-induced formation of a transformation focus was strongly
suppressed by ERW supplemented with Pt nps but not by ERW or Pt nps individually. ERW supplemented with Pt nps suppressed
transformation at the promoter stage, not at initiation, suggesting that ERW supplemented with Pt nps suppressed the PMA-induced
augmentation of intracellular ROS. ERW supplemented with Pt nps is a potential new antioxidant against carcinogenesis. 相似文献
995.
Intersubject variability in cardiac output-O2 uptake relation of men during exercise 总被引:1,自引:0,他引:1
Intersubject variability in the relation between cardiac output (Q) and O2 uptake (VO2) was examined during supine cycling up to the maximum level in 40 normal untrained men age 27 +/- 4 (SD) yr. In individual subjects, Q increased linearly against VO2 in the submaximum exercise range. The SD of Q on VO2 was so small (0.47 +/- 0.25 l/min) that Q could be given by a linear function of VO2 as Q = K(VO2 - VO2 r) + Qr, where K, VO2 r, and Qr are the slope of the regression line, the resting VO2, and resting Q, respectively. K varied widely among the subjects studied, ranging from 5.5 to 10.3 and was independent of both physical characteristics and Qr, which ranged from 3.7 to 8.3 l/min. However, K correlated significantly with changes in heart rate, stroke volume, mean arterial pressure, and systemic vascular conductance. From these results, we concluded that the intersubject variability in the Q-VO2 relation was caused independently by individual variations in resting hemodynamics and in cardiovascular response to exercise. 相似文献
996.
6 BETA-Iodomethyl-19-norsitost-5(10)-en-3 beta-ol (V) was synthesized by homoallylic rearrangement of 19-iodositost-5-en-3 beta-ol (IV), which was obtained by the hydrolysis of 19-iodositost-5-en-3 beta-ol acetate (III) derived from the displacement of sitost-5-ene-3 beta, 19-diol 3-acetate 19-p-toluenesulfonate (I) with sodium iodide in isopropanol. The radioiodinated IV and V were prepared by isotope exchange with sodium iodide-I-131. 相似文献
997.
998.
Katsuji Haneda Ken-ichi Komatsu Ryoji Kodaira Hiroshi Ohsawa 《Bioscience, biotechnology, and biochemistry》2013,77(9):1453-1460
In the case of fermentative production of adenosine by the mutants derived from a Bacillus strain, abnormal fermentations due to the instability of mutants were frequently observed, and therefore studies were performed on the stabilization of mutants.Among the genetic characteristics of adenosine-producing mutants, the xanthine-requirement was the most important factor and the adenosine productivity was found to decrease significantly as the number of revertants on this genetic marker increased. By using the media supplemented with excess amount of guanine sources, the increase of xanthine-non-requiring revertants both during the transfers on slants and in the preservation periods was perfectly suppressed. Secondly, an attempt was made to derive mutants in which no revertants would appear. Such mutants (‘NB-strains’) were selected by using a medium on which revertants appeared in a high frequency. One strain of the above mutants was found defective in XMP aminase. 相似文献
999.
1000.
The globulin of the seed endosperms of rice has an isoelectric point of 6.4 and a M(r) of 26,000. There is one intra-disulphide bond, but no N-linked oligosaccharide chain. The amino acid sequence of the N-terminal and internal regions of the globulin was determined and found to be homologous with that of glutenin, the storage protein in the seed endosperms of wheat. Rice globulin and wheat glutenin were rich in glycine, and glutamic acid or glutamine, and in addition, wheat glutenin cross-reacted with antibody raised against rice globulin. These results suggest that rice seed globulin represents a protein similar to wheat seed glutenin. 相似文献