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991.
Suda A Koyano H Hayase T Hada K Kawasaki K Komiyama S Hasegawa K Fukami TA Sato S Miura T Ono N Yamazaki T Saitoh R Shimma N Shiratori Y Tsukuda T 《Bioorganic & medicinal chemistry letters》2012,22(2):1136-1141
Macrocyclic compounds bearing a 2-amino-6-arylpyrimidine moiety were identified as potent heat shock protein 90 (Hsp90) inhibitors by modification of 2-amino-6-aryltriazine derivative (CH5015765). We employed a macrocyclic structure as a skeleton of new inhibitors to mimic the geldanamycin-Hsp90 interactions. Among the identified inhibitors, CH5164840 showed high binding affinity for N-terminal Hsp90α (K(d)=0.52nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC(50)=0.15μM, NCI-N87 IC(50)=0.066μM). CH5164840 displayed high oral bioavailability in mice (F=70.8%) and potent antitumor efficacy in a HCT116 human colorectal cancer xenograft model (tumor growth inhibition=83%). 相似文献
992.
Yoshito Terao Hideo Suzuki Masato Yoshikawa Hiroaki Yashiro Shiro Takekawa Yasushi Fujitani Kengo Okada Yoshihisa Inoue Yoshio Yamamoto Hideyuki Nakagawa Shuhei Yao Tomohiro Kawamoto Osamu Uchikawa 《Bioorganic & medicinal chemistry letters》2012,22(24):7326-7329
Imidazo[1,2-a]pyridine derivatives were designed, synthesized, and evaluated as inhibitors of the apoptosis signal-regulating kinase 1 (ASK1). These were based on a benzothiazole derivative that was discovered from high-throughput screening of our compound library. As a result, we identified potent, selective, and orally bioavailable ASK1 inhibitors for wide range of therapeutic targets. 相似文献
993.
Shimizu N Kawamoto JK Utani K 《Biochemical and biophysical research communications》2007,359(3):806-810
We used fluorescence in situ hybridization (FISH) to detect c-myc RNA subspecies in human COLO 320DM tumor cells. Although the FISH procedure removed the majority of RNAs from the nucleolus, c-myc RNA continued to be detected in both the nucleoplasm and nucleolus. This finding suggests stable association between c-myc RNA and the nucleolus. Nucleolar accumulation of c-myc RNA appeared to be temporally regulated by cell-cycle progression. Hybridization with exon- and strand-specific RNA probes indicated that the non-protein coding exon 1 plays a novel role in determining the subnuclear localization of c-myc RNA. Antisense RNA targeting exon 2 localized only with nucleoplasmic foci, where it might interact with the sense strand. Thus, c-myc gene expression may be regulated by intranuclear localization of its RNA. 相似文献
994.
Takuo Hayashi Igor Odintsov Roger S. Smith Kota Ishizawa Allan J. W. Liu Lukas Delasos Christopher Kurzatkowski Huichun Tai Eric Gladstone Morana Vojnic Shinji Kohsaka Ken Suzawa Zebing Liu Siddharth Kunte Marissa S. Mattar Inna Khodos Monika A. Davare Alexander Drilon Emily Cheng Elisa de Stanchina Marc Ladanyi Romel Somwar 《Disease models & mechanisms》2021,14(2)
995.
Syun‐Ichi Urayama Toshiyuki Fukuhara Hiromitsu Moriyama Akio Toh‐E Susumu Kawamoto 《Microbiology and immunology》2014,58(5):294-302
Magnaporthe oryzae chrysovirus 1 strain A (MoCV1‐A) is the causal agent of growth repression and attenuated virulence (hypovirulence) of the rice blast fungus, M. oryzae. We have previously reported that heterologous expression of MoCV1‐A ORF4 in Saccharomyces cerevisiae results in growth defects, a large central vacuole and other cytological changes. In this study, the effects of open reading frame (ORF) 4 expression in Cryptococcus neoformans, a human pathogenic fungus responsible for severe opportunistic infection, were investigated. Cells expressing the ORF4 gene in C. neoformans showed remarkably enlarged vacuoles, nuclear diffusion and a reduced growth rate. In addition, expression of ORF4 apparently suppressed formation of the capsule that surrounds the entire cell wall, which is one of the most important components of expression of virulence. After 5‐fluoroorotic acid treatment of ORF4‐expressing cells to remove the plasmid carrying the ORF4 gene, the resultant plasmid‐free cells recovered normal morphology and growth, indicating that heterologous expression of the MoCV1‐A ORF4 gene induces negative effects in C. neoformans. These data suggest that the ORF4 product is a candidate for a pharmaceutical protein to control disease caused by C. neoformans. 相似文献
996.
Sayaka Yamaguchi Ayako Sano Midori Hiruma Michiko Murata Takashi Kaneshima Yoshiteru Murata Hideo Takahashi Sana Takahashi Yoko Takahashi Hiroji Chibana Hidemi Touyama Nguyen Thi Thanh Ha Yasutomo Nakazato You Uehara Morihiko Hirakawa Yoshimi Imura Yoshie Terashima Yasuhiro Kawamoto Keji Takahashi Kazutoshi Sugiyama Masataro Hiruma Masaru Murakami Atsushi Hosokawa Hiroshi Uezato 《Mycopathologia》2014,178(1-2):135-143
We investigated 793 bird combs [645 chickens and 148 fighting cocks (Shamo)] to determine the prevalence of dermatophytes and their related fungal species. The targeted fungal species were recovered from 195 of the 793 examined birds (24.6 %). Prevalence ratios were compared in temperate (the mainland) and subtropical (Nansei Islands) areas, genders, strains, breeding scale (individual and farm), and housing system (in cage and free ranging). The frequency of the fungal species in the mainland, males, fighting cocks, breeding scale by individual nursing, and free-range housing system exhibited significantly higher positive ratios than that in the other groups. A total of 224 dermatophytes and related species were isolated, including 101 Arthroderma (Ar.) multifidum, 83 Aphanoascus (Ap.) terreus, five Uncinocarpus queenslandicus, two U. reesii, two Ap. pinarensis, one Amauroascus kuehnii, one Ar. simii, one Gymnoascus petalosporus, one Microsporum gallinae, and 28 Chrysosporium-like (Chrysosporium spp.) isolates, which were identified using internal transcribed spacer regions of ribosomal RNA gene sequences. The predominant fungal species in the mainland was Ap. terreus and that in the Nansei Islands was Ar. multifidum. Pathogenic fungal species to humans and animals were limited to M. gallinae and Ar. simii, which corresponded to 0.025 % of the isolates in this study. 相似文献
997.
Daisuke Takeda Takumi Hasegawa Takeshi Ueha Yusuke Imai Akiko Sakakibara Masaya Minoda Teruya Kawamoto Tsutomu Minamikawa Yasuyuki Shibuya Toshihiro Akisue Yoshitada Sakai Masahiro Kurosaka Takahide Komori 《PloS one》2014,9(7)
Squamous cell carcinoma (SCC) is the main histological type of oral cancer. Its growth rate and incidence of metastasis to regional lymph nodes is influenced by various factors, including hypoxic conditions. We have previously reported that transcutaneous CO2 induces mitochondrial apoptosis and decreases lung metastasis by reoxygenating sarcoma cells. However, previous studies have not determined the sequential mechanism by which transcutaneous CO2 suppresses growth of epithelial tumors, including SCCs. Moreover, there is no report that transcutaneous CO2 suppresses lymphogenous metastasis using human cell lines xenografts. In this study, we examined the effects of transcutaneous CO2 on cancer apoptosis and lymphogenous metastasis using human SCC xenografts. Our results showed that transcutaneous CO2 affects expressions of PGC-1α and TFAM and protein levels of cleavage products of caspase-3, caspase-9 and PARP, which relatives mitochondrial apoptosis. They also showed that transcutaneous CO2 significantly inhibits SCC tumor growth and affects expressions of HIF-1α, VEGF, MMP-2 and MMP-9, which play essential roles in tumor angiogenesis, invasion and metastasis. In conclusion, transcutaneous CO2 suppressed tumor growth, increased mitochondrial apoptosis and decreased the number of lymph node metastasis in human SCC by decreasing intra-tumoral hypoxia and suppressing metastatic potential with no observable effect in vivo. Our findings indicate that transcutaneous CO2 could be a novel therapeutic tool for treating human SCC. 相似文献
998.
Growth experiments with macrophytes revealed anomalies in the growth and development of Najas intermedia. Further analyses showed that these anomalies were caused by differences between the male and female plants. To examine the gender-related differences, the results of two field experiments and a phenological monitoring programme were analysed. The field experiments were conducted in four different lakes in Southern Germany. Over the course of 2 years, eight different sediments were used to research the interaction between the gender and the growth of N. intermedia plants. The phenological monitoring programme, on the other hand, was focused on the development of three different populations of N. intermedia in three Southern German lakes. The results of the experiments revealed significant differences in the gender-related development: Depending on the environmental conditions, male plants grew between 20 and 40% faster than female plants. Additionally, the male plants developed flowers earlier in the vegetation period and died before the female plants. As a result, male and female plants coexisted in the same lake only for a short period of time. This might be a strategy to reduce the competitive pressure between the genders and to gain an advantage over rival species. 相似文献
999.
Species richness and composition of the Chrysomelidae (Coleoptera) were studied in larch (Larix kaempheri [Lamb.] Carrière) plantations, secondary forests, and primary forests. In addition, the effects of forest management practices,
such as thinning and long rotation, were examined in the larch plantation. The species richness of Chrysomelidae was higher
in the larch plantation than in the secondary forest or in the primary forest. Among the larch plantations, the species richness
in old-aged plantations was higher than that in middle-aged plantations. The composition of the beetle assemblages in the
larch plantation differed from that in the secondary forest or in the primary forest. Exosoma akkoae (Chujo), Batophila acutangula Heikertinger, and Calomicrus nobyi Chujo were caught with a bias toward the larch plantation. Longitarsus succineus (Foudras) and Sphaeroderma tarsatum Baly were caught more in the secondary forest and the primary forest, respectively. More B. acutangula and S. tarsatum were caught in stands where their host plants occurred at higher rates. Species richness of understory plants was an important
factor for chrysomlid species richness, and frequency of host occurrence affected the number of individuals of leaf beetles
examined. It seems that forest types and forest management practices affect host plants as well as Chrysomelidae, and that
these effects on the host plants also influence chrysomelid assemblages. 相似文献
1000.
The effect of morphine on the susceptibility of BALB/c mice to diarrheagenic Escherichia coli, Shigella flexneri, Listeria monocytogenes, Salmonella Enteritidis, Yersinia enterocolitica, was examined via the intraperitoneal inoculation. Morphine treatment increased the susceptibility to S. Enteritidis and L. monocytogenes, resulting in bacteremia and central nervous system (CNS) invasion (for L. monocytogenes), while the infection with other bacteria did not show the systemic dissemination in the morphinetreated mice. Notably, L. monocytogenes infection caused 100% mortality with a mean survival time (MST) of 1.3 days in morphine-treated mice, but untreated mice did not die. The present data suggested that individuals using heroin or treated with morphine derivatives might be at high risk for listeriosis, especially those who are immunocompromised. Recent increasing consumption of morphine may propose the necessity for further epidemiological surveillance on infectious diseases. 相似文献