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991.
Watanabe N Nakadate H Haruta M Sugawara W Sasaki F Tsunematsu Y Kikuta A Fukuzawa M Okita H Hata J Soejima H Kaneko Y 《Genes, chromosomes & cancer》2006,45(6):592-601
We evaluated the WT1 and IGF2 status and performed chromosome and/or comparative genomic hybridization analysis in 43 tumor samples from patients with Wilms tumor. On this basis, we classified them into 4 groups: WT1 abnormality, loss of heterozygosity (LOH) of IGF2, loss of imprinting (LOI) of IGF2, and retention of imprinting (ROI) of IGF2, which were seen in 12%, 30%, 16%, and 42% of the tumors, respectively. Patients in the LOI group were older than those in other groups (P < 0.01), and tumors in the WT1 group had fewer cytogenetic changes than did those in the other groups (P < 0.01). It was found that 11q- and +12 were more frequent in the LOI group than in the WT1+LOH+ROI group (P < 0.01 and P < 0.01). There was no difference in the incidence of 16q- between the LOI group and the other groups; however, when we excluded 16 tumors with LOH on 11p15, 16q- tended to be more frequent in the LOI group than in the WT1+ROI group (P = 0.06). The association of 11q- or +12 with LOI of IGF2 found in the present study suggests that many tumors with no WT1 abnormalities need overexpression of IGF2 together with biallelic inactivation of the tumor-suppressor gene on 11q and/or overexpression of growth-promoting genes on chromosome 12. The 11q gene may code for one of the proteins that constitute a CTCF insulator complex, and its mutation, deletion, or haploinsufficiency may cause insulator abnormalities that might lead to LOI of IGF2. 相似文献
992.
A central event in synapse development is formation of the presynaptic active zone in response to positional cues. Three active zone proteins, RIM, ELKS (also known as ERC or CAST) and Liprin-alpha, bind each other and are implicated in linking active zone formation to synaptic vesicle release. Loss of function in Caenorhabditis elegans syd-2 Liprin-alpha alters the size of presynaptic specializations and disrupts synaptic vesicle accumulation. Here we report that a missense mutation in the coiled-coil domain of SYD-2 causes a gain of function. In HSN synapses, the syd-2(gf) mutation promotes synapse formation in the absence of syd-1, which is essential for HSN synapse formation. syd-2(gf) also partially suppresses the synaptogenesis defects in syg-1 and syg-2 mutants. The activity of syd-2(gf) requires elks-1, an ELKS homolog; but not unc-10, a RIM homolog. The mutant SYD-2 shows increased association with ELKS. These results establish a functional dependency for assembly of the presynaptic active zone in which SYD-2 plays a key role. 相似文献
993.
Kudo N Kasai K Itoh K Koshida I Yumoto M Kato M Kamio S Araki T Nakagome K Fukuda M Yamasue H Yamada H Abe O Kato N Iwanami A 《Biological psychology》2006,71(1):54-62
The auditory mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch field, MMF) has been widely used to assess the ability of stimulus-driven change detection process in humans. The authors evaluated the similarity of inter-individual variation of the response strength between MMN and MMF recordings. Three types of MMN or MMF were recorded in ten healthy subjects: change in duration of pure-tone stimuli, change in duration of the Japanese vowel /a/, and difference between the Japanese vowels /a/ and /o/. There was no significant correlation between MMN amplitude and MMF strength under any condition and in either hemisphere. These results suggest that widely used indices of MMN in the two technologies, i.e., EEG-amplitude and MEG-ECD may not be proportional in an individual. To further clarify the differential significance of recording MMN/MMF may be important to establish MMN/MMF as clinical indices of individual ability of preattentive stage of auditory processing. 相似文献
994.
Natural history of human aberrant crypt foci and correlation with risk factors for colorectal cancer
Ohkubo H Takahashi H Yamada E Sakai E Higurashi T Uchiyama T Hosono K Endo H Taguri M Nakajima A 《Oncology reports》2012,27(5):1475-1480
Although aberrant crypt foci (ACF) are estimated to have potential usefulness as a biomarker for colorectal carcinoma (CRC), this remains uncertain because the natural history of ACF has not been well-clarified. To determine the usefulness of ACF as a surrogate marker for CRC, it is necessary to understand the natural history of ACF. A total of 82 subjects who underwent total colonoscopy and whose ACF number was examined at least 2 times at Yokohama City University Hospital were enrolled. We retrospectively evaluated the changes in the ACF number at four different surveillance periods (6 months, 1 year, 2 years, 3 years) and in groups with and without colorectal neoplasms. Furthermore, we classified the subjects into an increased ACF group and a no change/decreased ACF group, and investigated the relationship between the changes in the ACF number and known risk factors for CRC. No significant differences were observed in the ACF number between the first and second observations in any surveillance period groups, and in the groups classified according to the presence or absence of colorectal neoplasms. There were no significant differences between the increased and no change/decreased ACF group in terms of gender, smoking habit, current alcohol consumption, age, BMI, HbA1c or serum triglyceride level (TG), whereas a significant difference between the groups was observed in the serum total cholesterol level (TC) (p=0.012). ACF are a reliable surrogate marker that are not affected by any risk factors for adenomas or CRC, except TC, and may therefore be considered as a useful marker in chemopreventive trials. 相似文献
995.
996.
Watanabe K Emoto N Hamano E Sunohara M Kawakami M Kage H Kitano K Nakajima J Goto A Fukayama M Nagase T Yatomi Y Ohishi N Takai D 《International journal of cancer. Journal international du cancer》2012,130(11):2580-2590
MicroRNA (miRNA) expression is frequently altered in human cancers. To search for epigenetically silenced miRNAs in non-small-cell lung cancer (NSCLC), we mapped human miRNAs on autosomal chromosomes and selected 55 miRNAs in silico. We treated six NSCLC cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) and determined the expressions of the 55 miRNAs. Fourteen miRNAs were decreased in the cancer cell lines and were induced after 5-aza-CdR treatment. After a detailed DNA methylation analysis, we found that mir-34b and mir-126 were silenced by DNA methylation. Mir-34b was silenced by the DNA methylation of its own promoter, whereas mir-126 was silenced by the DNA methylation of its host gene, EGFL7. A chromatin immunoprecipitation assay revealed H3K9me2 and H3K9me3 in mir-34b and EGFL7, and H3K27me3 in EGFL7. The overexpression of mir-34b and mir-126 decreased the expression of c-Met and Crk, respectively. The 5-aza-CdR treatment of lung cancer cell line resulted in increased mir-34b expression and decreased c-Met protein. We next analyzed the DNA methylation status of these miRNAs using 99 primary NSCLCs. Mir-34b and mir-126 were methylated in 41 and 7% of all the cases, respectively. The DNA methylation of mir-34b was not associated with c-Met expression determined by immunohistochemistry, but both mir-34b methylation (p = 0.007) and c-Met expression (p = 0.005) were significantly associated with lymphatic invasion in a multivariate analysis. The DNA methylation of mir-34b can be used as a biomarker for an invasive phenotype of lung cancer. 相似文献
997.
998.
Salam KA Furuta A Noda N Tsuneda S Sekiguchi Y Yamashita A Moriishi K Nakakoshi M Tsubuki M Tani H Tanaka J Akimitsu N 《Journal of natural products》2012,75(4):650-654
The hepatitis C virus (HCV) causes one of the most prevalent chronic infectious diseases in the world, hepatitis C, which ultimately develops into liver cancer through cirrhosis. The NS3 protein of HCV possesses nucleoside triphosphatase (NTPase) and RNA helicase activities. As both activities are essential for viral replication, NS3 is proposed as an ideal target for antiviral drug development. In this study, we identified manoalide (1) from marine sponge extracts as an RNA helicase inhibitor using a high-throughput screening photoinduced electron transfer (PET) system that we previously developed. Compound 1 inhibits the RNA helicase and ATPase activities of NS3 in a dose-dependent manner, with IC(50) values of 15 and 70 μM, respectively. Biochemical kinetic analysis demonstrated that 1 does not affect the apparent K(m) value (0.31 mM) of NS3 ATPase activity, suggesting that 1 acts as a noncompetitive inhibitor. The binding of NS3 to single-stranded RNA was inhibited by 1. Manoalide (1) also has the ability to inhibit the ATPase activity of human DHX36/RHAU, a putative RNA helicase. Taken together, we conclude that 1 inhibits the ATPase, RNA binding, and helicase activities of NS3 by targeting the helicase core domain conserved in both HCV NS3 and DHX36/RHAU. 相似文献
999.
1000.
Yoshihiro Tsujimoto Eiji Ishimura Hideki Tahara Ryuusuke Kakiya Hidenori Koyama Masanori Emoto Tetsuo Shoji Masaaki Inaba Hiroshi Kishimoto Tsutomu Tabata Yoshiki Nishizawa 《Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy》2009,13(4):358-365
We investigated the impact of glycemic control on the emergence of cardiovascular disease (CVD) in diabetic patients who were on maintenance hemodialysis in a prospective observational study. One hundred and thirty‐four diabetic hemodialysis patients (63 ± 10 years‐old, hemodialysis duration of 4.5 ± 3.9 years) at a single dialysis center were enrolled. The cohort was observed prospectively for 5 years, and the emergence of fatal and non‐fatal CVD was recorded. Patients were categorized into two groups; good (mean hemoglobin (Hb) A1C <7.0%, N = 65) and poor HbA1C (mean HbA1C ≥7.0%, N = 69). The relationship between glycemic control and CVD emergence was evaluated by Kaplan‐Meier estimation and Cox proportional hazard models. During the follow‐up period, 50 CVD events were observed. The cumulative CVD incidence in the poor HbA1C group was significantly higher than that of the good HbA1C group, as determined by Kaplan‐Meier estimation (P = 0.0250, log‐rank test). After adjustment for gender, age, duration of dialysis, and past history of CVD, a multivariate Cox proportional hazard model showed that poor HbA1C was a significant predictor of CVD events (hazards ratio [HR] 1.828 [95% CI, 1.008–3.314], P = 0.0470). When ischemic heart disease, cerebral infarction, and arteriosclerosis obliterans were determined as an endpoint, both HbA1C levels and the poor HbA1C group were significant predictors for the emergence of CVD (HR 1.269 per 1% HbA1C [95%CI, 1.022–1.574], P = 0.0307,and HR 2.816 [95% CI, 1.377–5.759], P = 0.0046, respectively). In diabetic hemodialysis patients, poor glycemic control is a significant, independent predictor of the emergence of CVD, indicating the importance of careful management of glycemic control in hemodialysis patients. 相似文献