Genomes and Genes
Experts and Doctors on preclinical drug evaluation in Japan
Topic: preclinical drug evaluation
- Okamoto S, Yoshii H, Ishikawa T, Akagi T, Akashi M, Takahashi M, et al. Single dose of inactivated Japanese encephalitis vaccine with poly(gamma-glutamic acid) nanoparticles provides effective protection from Japanese encephalitis virus. Vaccine. 2008;26:589-94 pubmed publisher..A similar protocol, in which a single dose of JE vaccine is mixed with gamma-PGA-NPs, may be useful for the immunization of humans. ..
- Ishii I, Mizuta H, Sei A, Hirose J, Kudo S, Hiraki Y. Healing of full-thickness defects of the articular cartilage in rabbits using fibroblast growth factor-2 and a fibrin sealant. J Bone Joint Surg Br. 2007;89:693-700 pubmed..Our findings suggest that this delivery method for FGF-2 may be useful for promoting regenerative repair of full-thickness defects of articular cartilage in humans. ..
- Kimura Y, Suto S, Tatsuka M. Evaluation of carcinogenic/co-carcinogenic activity of chikusaku-eki, a bamboo charcoal by-product used as a folk remedy, in BALB/c 3T3 cells. Biol Pharm Bull. 2002;25:1026-9 pubmed..01%), but chikusaku-eki did not act as a tumor promoter. Thus, chikusaku-eki was not carcinogenic/co-carcinogenic in the in vitro cell transformation assay examined in this study after being diluted more than 10(4)-fold with water. ..
- Sasa M, Inoue I, Shinoda Y, Takahashi S, Seo M, Komoda T, et al. Activating effect of momordin, extract of bitter melon (Momordica Charantia L.), on the promoter of human PPARdelta. J Atheroscler Thromb. 2009;16:888-92 pubmed..Our present data obtained through successful cloning of the PPARdelta promoter demonstrate that PPARdelta production and activation are upregulated through PPARdelta promoter activity following momordin treatment. ..
- Jiang S, Tsumuro T, Takubo M, Fujii Y, Kamei C. Antipruritic and antierythema effects of ascomycete Bulgaria inquinans extract in ICR Mice. Biol Pharm Bull. 2005;28:2197-200 pubmed..These results suggest that Bulgaria inquinans extract is effective in cutaneous pruritus and erythema, which were probably mediated by inhibiting the release of histamine from mast cells and antagonizing the effect on serotonin. ..
- Takami T, Momma K, Imamura S. Increased constriction of the ductus arteriosus by dexamethasone, indomethacin, and rofecoxib in fetal rats. Circ J. 2005;69:354-8 pubmed..64+/-0.07 at 8 h, compared with the DA/PA ratio of 0.92+/-0.03 with rofecoxib alone. Combined therapy may be an option in the medical management of PDA in premature infants before considering surgical treatment. ..
- Motoyama S, Saito S, Minamiya Y, Saito R, Nakamura M, Okuyama M, et al. Methylprednisolone inhibits low-flow hypoxia-induced mitochondrial dysfunction in isolated perfused rat liver. Crit Care Med. 2003;31:1468-74 pubmed..Instead, the beneficial effect of methylprednisolone seems to be related to its ability to protect against mitochondrial membrane depolarization under hypoxic conditions. ..
- Satoh K, Hayakawa T, Kase Y, Ishige A, Sasaki H, Nishikawa S, et al. Mechanisms for contractile effect of Dai-kenchu-to in isolated guinea pig ileum. Dig Dis Sci. 2001;46:250-6 pubmed..These results suggest that contractile response induced by TJ-100 is partially mediated by ACh released from the cholinergic nerve endings and that 5-HT4 receptors would be involved in the effect of TJ-100. ..
- Kitagawa S, Nabekura T, Takahashi T, Nakamura Y, Sakamoto H, Tano H, et al. Structure-activity relationships of the inhibitory effects of flavonoids on P-glycoprotein-mediated transport in KB-C2 cells. Biol Pharm Bull. 2005;28:2274-8 pubmed..These results suggested that hydrophobicity as well as planar structure is important for the inhibitory effects of flavonoids on P-gp-mediated transport. ..
- Shimamura K, Nagumo A, Miyamoto Y, Kitazawa H, Kanesaka M, Yoshimoto R, et al. Discovery and characterization of a novel potent, selective and orally active inhibitor for mammalian ELOVL6. Eur J Pharmacol. 2010;630:34-41 pubmed publisher..Compound B appears to be a useful tool to further understand the physiological roles of ELOVL6 and to evaluate the therapeutic potential of ELOVL6 inhibitors. ..
- Tanaka T, Oka T, Shimada Y, Umemoto N, Kuroyanagi J, Sakamoto C, et al. Pharmacogenomics of cardiovascular pharmacology: pharmacogenomic network of cardiovascular disease models. J Pharmacol Sci. 2008;107:8-14 pubmed..These results suggest that pharmacogenomic network analysis has the potential to bridge the gap between in vitro and in vivo studies and could define strategies for identifying novel drug targets in various cardiovascular diseases. ..
- Miyamoto T, Matsumori A, Hwang M, Nishio R, Ito H, Sasayama S. Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis. J Am Coll Cardiol. 2001;37:1713-8 pubmed..This report is the first to describe a beneficial effect by an immunosuppressive agent in the treatment of acute viral myocarditis. ..
- Sagara N, Kawaji T, Takano A, Inomata Y, Inatani M, Fukushima M, et al. Effect of pitavastatin on experimental choroidal neovascularization in rats. Exp Eye Res. 2007;84:1074-80 pubmed..Thus, we demonstrated that the therapeutic dose of pitavastatin for human hypocholesterolemia effectively suppressed experimental CNV in rats. The use of pitavastatin may be helpful in preventing CNV development in AMD patients. ..
- Eiki J, Saeki K, Nagano N, Iino T, Yonemoto M, Takayenoki Iino Y, et al. A selective small molecule glucagon-like peptide-1 secretagogue acting via depolarization-coupled Ca(2+) influx. J Endocrinol. 2009;201:361-7 pubmed publisher..Identifying a specific target molecule for compound A will reveal a selective regulatory pathway that leads to depolarization-mediated GLP-1 secretion. ..
- Lee Y, Noh E, Kwon K, Lee Y, Chu J, Kim E, et al. Radix clematidis extract inhibits UVB-induced MMP expression by suppressing the NF-kappaB pathway in human dermal fibroblasts. Int J Mol Med. 2009;23:679-84 pubmed..These findings suggest that RCE prevents UVB-induced MMP expression through inhibition of NF-kappaB activation. In conclusion, RCE is a potential agent for the prevention and treatment of skin photoaging...
- Sato K, Fukata H, Kogo Y, Ohgane J, Shiota K, Mori C. Neonatal exposure to diethylstilbestrol alters expression of DNA methyltransferases and methylation of genomic DNA in the mouse uterus. Endocr J. 2009;56:131-9 pubmed..Two loci were cloned, and differential DNA methylation was quantified. Our results indicated that DES altered the expression levels of Dnmts and DNA methylation. ..
- Nojima M, Maruyama R, Yasui H, Suzuki H, Maruyama Y, Tarasawa I, et al. Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma. Clin Cancer Res. 2009;15:4356-64 pubmed publisher..Moreover, they show the utility of demethylation therapy in cases of advanced multiple myeloma. ..
- Watanabe M, Masaoka N, Nakajima Y, Nagaishi M, Yamamoto T. Changes of expression of glucose transporters in the fetal lamb brain after MCI-186 administration to the maternal circulation with 10-min persistent umbilical cord occlusion. J Matern Fetal Neonatal Med. 2009;22:829-36 pubmed publisher..GLUT-5 was recognised only in Group B. On the basis of expression of GLUT, the protective effect of MCI-186 on brain injury resulting from hypoxia/ ischemia-reperfusion is documented. ..
- Harada T, Levounis P, Constantinou C. Rapid evaluation of the efficacy of pharmacologic agents and their analogs in enhancing bladder capacity and reducing the voiding frequency. J Pharmacol Toxicol Methods. 1992;27:119-26 pubmed..This model allows the rapid evaluation of drugs designed to increase bladder capacity and decrease the frequency of voiding, and it is particularly useful in evaluating the relative efficacy of drugs that are chemical analogs. ..
- Azuma T, Dojyo M, Ito S, Yamazaki Y, Miyaji H, Ito Y, et al. Bile reflux due to disturbed gastric movement is a cause of spontaneous gastric ulcer in W/Wv mice. Dig Dis Sci. 1999;44:1177-83 pubmed..These results suggest that bile reflux due to the disturbance of gastric antral movement is a cause of the spontaneous gastric ulcers in W/Wv mice...
- Nishiyama T, Mishima K, Obara K, Inoue H, Doi T, Kondo S, et al. Amelioration of lacrimal gland inflammation by oral administration of K-13182 in Sjögren's syndrome model mice. Clin Exp Immunol. 2007;149:586-95 pubmed..These data reveal that VCAM-1 is a promising target molecule for the treatment of autoimmune diseases as a therapeutic strategy and that K-13182 has the potential as a new anti-inflammatory drug for SS...
- Yonetoku Y, Kubota H, Okamoto Y, Ishikawa J, Takeuchi M, Ohta M, et al. Novel potent and selective calcium-release-activated calcium (CRAC) channel inhibitors. Part 2: Synthesis and inhibitory activity of aryl-3-trifluoromethylpyrazoles. Bioorg Med Chem. 2006;14:5370-83 pubmed..These compounds were potent inhibitors of IL-2 production in vitro and also acted as inhibitors in pharmacological models of diseases resulting from T-lymphocyte activation, after oral administration. ..
- Uchio E. [New medical treatment for viral conjunctivitis]. Nippon Ganka Gakkai Zasshi. 2005;109:962-84; discussion 985 pubmed..It is expected that eye drops for specific treatment of adenoviral conjunctivitis are going to be available in the near future following investigation of therapeutic effect in adenoviral infected animals and clinical trials in humans...
- Kamata R, Shiraishi F, Takahashi S, Shimizu A, Shiraishi H. Reevaluation of the developmental toxicity of dieldrin by the use of fertilized Japanese quail eggs. Comp Biochem Physiol C Toxicol Pharmacol. 2010;152:84-90 pubmed publisher..The results indicated that not only does the neurotoxicity of dieldrin bring early death, but its effects on reproductive and hepatic functions (detected as gene transcriptional changes in hatchlings) persist harmfully after maturity. ..
- Tomikawa T, Shin ya K, Seto H, Okusa N, Kajiura T, Hayakawa Y. Structure of aspochalasin H, a new member of the aspochalasin family. J Antibiot (Tokyo). 2002;55:666-8 pubmed
- Fujimoto H, Nozawa M, Okuyama E, Ishibashi M. Six new constituents from an Ascomycete, Chaetomium quadrangulatum, found in a screening study focused on monoamine oxidase inhibitory activity. Chem Pharm Bull (Tokyo). 2003;51:247-51 pubmed..The structures of 6-11 have been deduced on the basis of spectral and chemical data, and 7 and 8 have shown appreciable monoamine oxidase inhibitory activity...
- Suwa A, Kurama T, Yamamoto T, Sawada A, Shimokawa T, Aramori I. Glucose metabolism activation by SHIP2 inhibitors via up-regulation of GLUT1 gene in L6 myotubes. Eur J Pharmacol. 2010;642:177-82 pubmed publisher..These results suggest that pharmacological inhibition of SHIP2 activates glucose metabolism due, at least in part, to up-regulation of GLUT1 gene expression. ..
- Okamoto N, Ito Y, Nagai N, Murao T, Takiguchi Y, Kurimoto T, et al. Preparation of ophthalmic formulations containing cilostazol as an anti-glaucoma agent and improvement in its permeability through the rabbit cornea. J Oleo Sci. 2010;59:423-30 pubmed..5% CLZ fine particle suspensions into rabbit eyes reduced the enhanced IOP. These results demonstrate that the instillation of CLZ ophthalmic solutions and fine particle suspensions may represent an effective anti-glaucoma formulation. ..
- Sekigawa M, Kunoh T, Wada S, Mukai Y, Ohshima K, Ohta S, et al. Comprehensive screening of human genes with inhibitory effects on yeast growth and validation of a yeast cell-based system for screening chemicals. J Biomol Screen. 2010;15:368-78 pubmed publisher..The actions of one group are exerted through direct interactions with the human proteins, whereas those of the other group are mediated through interactions with chaperones. ..
- Yamagishi Y, Ueno C, Kato A, Kai H, Sasamura H, Ueno M, et al. Discovery of anti-varicella zoster virus activity of polyether antibiotic CP-44161. J Antibiot (Tokyo). 2009;62:89-93 pubmed publisher..Moreover, CP-44161 showed lower cytotoxicity than other antiviral polyethers, such as monensin and nigericin. Its better safety margin and strong anti-VZV properties make it a good candidate for a new anti-VZV agent. ..
- Hayashi K, Yamazoe A, Ishibashi Y, Kusaka N, Oono Y, Nozaki H. Active core structure of terfestatin A, a new specific inhibitor of auxin signaling. Bioorg Med Chem. 2008;16:5331-44 pubmed publisher..The structure-activity relationships revealed the essential active core structure of TrfA, 3-butoxy-4-methylbiphenyl-2,6-diol, which will lead to the design of biotin-tagged active TrfA. ..
- Satoh T, Izumi M, Inukai Y, Tsutsumi Y, Nakayama N, Kosaka K, et al. Carnosic acid protects neuronal HT22 Cells through activation of the antioxidant-responsive element in free carboxylic acid- and catechol hydroxyl moieties-dependent manners. Neurosci Lett. 2008;434:260-5 pubmed publisher..These results suggest that the neuroprotective effects of CA critically require both free carboxylic acid and catechol hydroxyl moieties. Thus, the hydrophilicity of CA might be a critical feature for its neuroprotective effects. ..
- Nakahara T, Kita A, Yamanaka K, Mori M, Amino N, Takeuchi M, et al. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res. 2007;67:8014-21 pubmed..Further extensive investigation of YM155 in many types of cancer, including HRPC, seems to be worthwhile to develop this novel therapeutic approach. ..
- Abe M, Ozawa Y, Uda Y, Morimitsu Y, Nakamura Y, Osawa T. A novel labdane-type trialdehyde from myoga (Zingiber mioga Roscoe) that potently inhibits human platelet aggregation and human 5-lipoxygenase. Biosci Biotechnol Biochem. 2006;70:2494-500 pubmed..It thus appears that a 3-formyl-3-butenal structure was essential for the potent inhibition of human platelet aggregation and human 5-LOX...
- Mita S, Suzuki H, Akita H, Hayashi H, Onuki R, Hofmann A, et al. Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Drug Metab Dispos. 2006;34:1575-81 pubmed..Our study suggests that such coexpressing cells can provide a useful system for the identification of inhibitors of these two transport systems, including potential drug candidates. ..
- Sugie C, Shibamoto Y, Ito M, Ogino H, Suzuki H, Uto Y, et al. Reevaluation of the radiosensitizing effects of sanazole and nimorazole in vitro and in vivo. J Radiat Res. 2005;46:453-9 pubmed..It was suggested that sanazole may be more suitable for clinical trials than nimorazole. ..
- Abe F, Nagafuji S, Okawa M, Kinjo J, Akahane H, Ogura T, et al. Trypanocidal constituents in plants 5. Evaluation of some Mexican plants for their trypanocidal activity and active constituents in the seeds of Persea americana. Biol Pharm Bull. 2005;28:1314-7 pubmed..From the active fractions, six 1,2,4-trihydroxyheptadecane derivatives and two 1,2,4-trihydroxynonadecane derivatives including a new one were isolated. These compounds showed moderate activity against epimastigotes and trypomastigotes...
- Hishikawa K, Nakaki T, Fujita T. Oral flavonoid supplementation attenuates atherosclerosis development in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005;25:442-6 pubmed..We examined the effects of oral CAPE supplementation on atherogenesis in apolipoprotein E-deficient (apoE-/-) mice...
- Abe F, Nagafuji S, Yamauchi T, Okabe H, Maki J, Higo H, et al. Trypanocidal constituents in plants 1. Evaluation of some Mexican plants for their trypanocidal activity and active constituents in Guaco, roots of Aristolochia taliscana. Biol Pharm Bull. 2002;25:1188-91 pubmed..Corresponding concentration of gossypol, berberine chloride and harmine was 280 microg/ml, 300 microg/ml and >500 microg/ml, respectively. ..
- Ogawa D, Shikata K, Matsuda M, Okada S, Wada J, Yamaguchi S, et al. Preventive effect of sulphated colominic acid on P-selectin-dependent infiltration of macrophages in experimentally induced crescentic glomerulonephritis. Clin Exp Immunol. 2002;129:43-53 pubmed..Moreover, SCA may inhibit intraglomerular infiltration of macrophages by interfering with P-selectin-dependent adhesion pathway, and progression of experimental crescentic glomerulonephritis. ..
- Matsumoto K, Mizowaki M, Takayama H, Sakai S, Aimi N, Watanabe H. Suppressive effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced head-twitch response in mice. Pharmacol Biochem Behav. 1997;57:319-23 pubmed..These results indicate that stimulation of postsynaptic alpha 2-adrenoceptor, blockade of 5-HT2A receptors, or both, are involved in suppression of 5-HT2A receptor-mediated head-twitch response by mitragynine...
- Sugiyama A, Motomura S, Hashimoto K. Utilization of an isolated, blood-perfused canine papillary muscle preparation as a model to assess efficacy and adversity of class I antiarrhythmic drugs. Jpn J Pharmacol. 1994;66:303-16 pubmed..Thus, the use of this model facilitates the comparison of multiple cardiac effects of class I drugs and may be an effective way to better assess new antiarrhythmic drugs. ..