oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2018 ( 9 )

2017 ( 9 )

2016 ( 13 )

2015 ( 47 )

Custom range...

Search Results: 1 - 10 of 1147 matches for " Hitoshi Nakagama "
All listed articles are free for downloading (OA Articles)
Page 1 /1147
Display every page Item
The Anti-Proliferative Effects of the CHFR Depend on the Forkhead Associated Domain, but not E3 Ligase Activity Mediated by Ring Finger Domain
Tomokazu Fukuda, Yasuyuki Kondo, Hitoshi Nakagama
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001776
Abstract: The CHFR protein comprises fork head associated- (FHA) and RING-finger (RF) domain and is frequently downregulated in human colon and gastric cancers up to 50%. The loss of CHFR mRNA expression is a consequence of promoter methylation, suggesting a tumor suppressor role for this gene in gastrointestinal carcinogenesis. In terms of the biological functions of CHFR, it has been shown to activate cell cycle checkpoint when cells are treated with microtubule depolymerizing agents. Furthermore, CHFR was reported to have E3 ligase activity and promote ubiquitination and degradation of oncogenic proteins such as Aurora A and polo-like kinase 1. However, molecular pathways involved in the tumor suppressive function of CHFR are not yet clear since the two established roles of this protein are likely to inhibit cell growth. In this study, we have identified that the FHA domain of CHFR protein is critical for growth suppressive properties, whereas the RF and cysteine rich domains (Cys) are not required for this function. In contrast, the RF and Cys domains are essential for E3 ligase activity of CHFR. By the use of a cell cycle checkpoint assay, we also confirmed that the FHA domain of CHFR plays an important role in initiating a cell cycle arrest at G2/M, indicating a functional link exists between the anti-proliferative effects and checkpoint function of this tumor suppressor protein via this domain. Collectively, our data show that the checkpoint function of the FHA domain of CHFR is a core component of anti-proliferative properties against the gastrointestinal carcinogenesis.
Lipoprotein Lipase as a Candidate Target for Cancer Prevention/Therapy
Shinji Takasu,Michihiro Mutoh,Mami Takahashi,Hitoshi Nakagama
Biochemistry Research International , 2012, DOI: 10.1155/2012/398697
Abstract: Epidemiological studies have shown that serum triglyceride (TG) levels are linked with risk of development of cancer, including colorectal and pancreatic cancers, and their precancerous lesions. Thus, it is assumed that serum TG plays an important role in carcinogenesis, and the key enzyme lipoprotein lipase (LPL), which catalyzes the hydrolysis of plasma TG, may therefore be involved. Dysregulation of LPL has been reported to contribute to many human diseases, such as atherosclerosis, chylomicronaemia, obesity, and type 2 diabetes. Recently, it has been reported that LPL gene deficiency, such as due to chromosome 8p22 loss, LPL gene polymorphism, and epigenetic changes in its promoter region gene, increases cancer risk, especially in the prostate. In animal experiments, high serum TG levels seem to promote sporadic/carcinogen-induced genesis of colorectal and pancreatic cancers. Interestingly, tumor suppressive effects of LPL inducers, such as PPAR ligands, NO-1886, and indomethacin, have been demonstrated in animal models. Moreover, recent evidence that LPL plays important roles in inflammation and obesity implies that it is an appropriate general target for chemopreventive and chemotherapeutic agents.
Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease
Mami Takahashi,Mika Hori,Michihiro Mutoh,Keiji Wakabayashi,Hitoshi Nakagama
Cancers , 2011, DOI: 10.3390/cancers3010582
Abstract: Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K- ras activation by point mutations and p16 inactivation by aberrant methylation of 5’ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.
Lipoprotein Lipase as a Candidate Target for Cancer Prevention/Therapy
Shinji Takasu,Michihiro Mutoh,Mami Takahashi,Hitoshi Nakagama
Biochemistry Research International , 2012, DOI: 10.1155/2012/398697
Abstract: Epidemiological studies have shown that serum triglyceride (TG) levels are linked with risk of development of cancer, including colorectal and pancreatic cancers, and their precancerous lesions. Thus, it is assumed that serum TG plays an important role in carcinogenesis, and the key enzyme lipoprotein lipase (LPL), which catalyzes the hydrolysis of plasma TG, may therefore be involved. Dysregulation of LPL has been reported to contribute to many human diseases, such as atherosclerosis, chylomicronaemia, obesity, and type 2 diabetes. Recently, it has been reported that LPL gene deficiency, such as due to chromosome 8p22 loss, LPL gene polymorphism, and epigenetic changes in its promoter region gene, increases cancer risk, especially in the prostate. In animal experiments, high serum TG levels seem to promote sporadic/carcinogen-induced genesis of colorectal and pancreatic cancers. Interestingly, tumor suppressive effects of LPL inducers, such as PPAR ligands, NO-1886, and indomethacin, have been demonstrated in animal models. Moreover, recent evidence that LPL plays important roles in inflammation and obesity implies that it is an appropriate general target for chemopreventive and chemotherapeutic agents. 1. Introduction A high-calorie diet and low physical activity, part of the so-called “Westernization” of lifestyle, are associated with elevated incidences of the breast, colon, liver, pancreas, and prostate cancers. Moreover, they are also linked with the risk of obesity, type 2 diabetes, and dyslipidemia. The World Cancer Research Fund and American Institute for Cancer Research have evaluated causal relationships between body fat and cancer and provided strong evidence for roles in such as colorectum and pancreas cancers [1]. In Japan, overweight and obesity (body mass index ≥25) are reported to be associated with cancers of specific organs, such as the colorectum (male), postmenopausal breast (female), and the liver in individuals positive for hepatitis C virus infection [2–4]. Greater body fatness is a major risk factor for the metabolic syndrome, which presents as a combination of symptoms, such as dyslipidemia (elevated triglyceride (TG) levels or low high-density lipoprotein (HDL) cholesterol), elevated blood pressure, and elevated fasting glucose levels. Hypertriglyceridemia is associated with the risk of colon cancer in Japanese men ( ) and being overweight with the risk of breast cancer ( ) [5]. In addition, most epidemiological studies, including our own, have consistently showed that serum TG levels are associated with the risk of colorectal
Origins of Albino and Hooded Rats: Implications from Molecular Genetic Analysis across Modern Laboratory Rat Strains
Takashi Kuramoto,Satoshi Nakanishi,Masako Ochiai,Hitoshi Nakagama,Birger Voigt,Tadao Serikawa
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043059
Abstract: Albino and hooded (or piebald) rats are one of the most frequently used laboratory animals for the past 150 years. Despite this fact, the origin of the albino mutation as well as the genetic basis of the hooded phenotype remained unclear. Recently, the albino mutation has been identified as the Arg299His missense mutation in the Tyrosinase gene and the hooded (H) locus has been mapped to the ~460-kb region in which only the Kit gene exists. Here, we surveyed 172 laboratory rat strains for the albino mutation and the hooded (h) mutation that we identified by positional cloning approach to investigate possible genetic roots and relationships of albino and hooded rats. All of 117 existing laboratory albino rats shared the same albino missense mutation, indicating they had only one single ancestor. Genetic fine mapping followed by de novo sequencing of BAC inserts covering the H locus revealed that an endogenous retrovirus (ERV) element was inserted into the first intron of the Kit gene where the hooded allele maps. A solitary long terminal repeat (LTR) was found at the same position to the ERV insertion in another allele of the H locus, which causes the so called Irish (hi) phenotype. The ERV and the solitary LTR insertions were completely associated with the hooded and Irish coat patterns, respectively, across all colored rat strains examined. Interestingly, all 117 albino rat strains shared the ERV insertion without any exception, which strongly suggests that the albino mutation had originally occurred in hooded rats.
Poly(ADP-ribose) Preparation Using Anion-Exchange Column Chromatography
Takashi Shimokawa, Hideki Ogino, Daisuke Maeda, Hitoshi Nakagama, Takashi Sugimura and Mitsuko Masutani
Organic Chemistry Insights , 2012,
Abstract: Poly(ADP-ribose) polymerase (PARP) polyADP-ribosylates proteins involved in various physiological processes. Accumulated evidence suggests not only protein-conjugated poly(ADP-ribose) but also protein-free poly(ADP-ribose) function in various physiological processes. There are increasing occasions that require protein-free poly(ADP-ribose) to study the function and dynamics of poly(ADP-ribose) in cells. However, the availability of poly(ADP-ribose) is still limited because a chemical synthesis method has not been established. Here, we describe an improved method for the preparation of protein-free poly(ADP-ribose), synthesized enzymatically by using a recombinant PARP-1 expression system and purified with an anion-exchange column chromatography. This method will be useful for biochemical and biological investigation of poly(ADP-ribose) functions and dynamics.
Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles
Kousuke Ishino,Tatsuya Kato,Mamoru Kato,Tatsuhiro Shibata,Masatoshi Watanabe,Keiji Wakabayashi,Hitoshi Nakagama,Yukari Totsuka
International Journal of Molecular Sciences , 2015, DOI: 10.3390/ijms16023474
Abstract: Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome) analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA) against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC), revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice.
Loss of Parp-1 affects gene expression profile in a genome-wide manner in ES cells and liver cells
Hideki Ogino, Tadashige Nozaki, Akemi Gunji, Miho Maeda, Hiroshi Suzuki, Tsutomu Ohta, Yasufumi Murakami, Hitoshi Nakagama, Takashi Sugimura, Mitsuko Masutani
BMC Genomics , 2007, DOI: 10.1186/1471-2164-8-227
Abstract: In the article, we used six replicates of microarray data of wild-type ES cells for comparison with the microarray data of Parp-1 knockout ES cells. We found that three replicate data were carelessly included in the data for wild-type ES cells. The comparison should have been carried out between three replicates for the Parp-1+/+ ES cell line, J1, and three replicates for two Parp-1-/- ES cell lines, 210–58 and 226–47, respectively.Therefore, we re-analyzed the data in ES cells according to the same criteria. The consequences of this error are reflected in changes to our results although the conclusions we obtained in the study are not affected.Here, we demonstrate that of the 9,640 genes analyzed, in Parp-1-/- ES cells. 3.6% showed altered gene expression. Of these, 2.5% and 1.1% of the genes were down- or up-regulated by 2-fold or greater, respectively, compared with Parp-1+/+ ES cells (p < 0.05).A comparison of the basal gene expression profiles in Parp-1-/-EScells to their wild-type (Parp-1+/+) counterparts, is presented in Fig. 1A &1B (corrected) and Table 1 (corrected). We found the expression of (344/9,640) genes, namely 3.6%, was different by at least 2-fold between Parp-1-/-and Parp-1+/+ES cells (p < 0.05) (Fig. 1B (corrected) and Table 1 (corrected)). Notably, a larger fraction of the genes, being 2.5%(238/9,640), was down-regulated, whereas only 1.1% (106/9,640) of the genes were up-regulated (see Table 1 (corrected)).We also made the heatmaps using the gene lists containing the 893 genes that showed a difference at p < 0.05 in ES cells (Fig. 2A (corrected)). Although we used independently isolated Parp-1-/- ES cell clones, a clear and common alteration in the gene expression profile was observed (see Fig. 2A (corrected), and Tables 2 (corrected) and 3 (corrected)).We further selected the genes that showed relatively high expression levels (the "Flag value" in GeneSpring ver. 6.1 of the genes should be either "Present" (high level of expression) or "Margi
Loss of Parp-1 affects gene expression profile in a genome-wide manner in ES cells and liver cells
Hideki Ogino, Tadashige Nozaki, Akemi Gunji, Miho Maeda, Hiroshi Suzuki, Tsutomu Ohta, Yasufumi Murakami, Hitoshi Nakagama, Takashi Sugimura, Mitsuko Masutani
BMC Genomics , 2007, DOI: 10.1186/1471-2164-8-41
Abstract: We employed a microarray analysis covering 12,488 genes and ESTs using mouse Parp-1-deficient (Parp-1-/-) embryonic stem (ES) cell lines and the livers of Parp-1-/- mice and their wild-type (Parp-1+/+) counterparts. Here, we demonstrate that of the 9,907 genes analyzed, in Parp-1-/- ES cells, 9.6% showed altered gene expression. Of these, 6.3% and 3.3% of the genes were down- or up-regulated by 2-fold or greater, respectively, compared with Parp-1+/+ ES cells (p < 0.05). In the livers of Parp-1-/- mice, of the 12,353 genes that were analyzed, 2.0% or 1.3% were down- and up-regulated, respectively (p < 0.05). Notably, the number of down-regulated genes was higher in both ES cells and livers, than that of the up-regulated genes. The genes that showed altered expression in ES cells or in the livers are ascribed to various cellular processes, including metabolism, signal transduction, cell cycle control and transcription. We also observed expression of the genes involved in the pathway of extraembryonic tissue development is augmented in Parp-1-/- ES cells, including H19. After withdrawal of leukemia inhibitory factor, expression of H19 as well as other trophoblast marker genes were further up-regulated in Parp-1-/- ES cells compared to Parp-1+/+ ES cells.These results suggest that Parp-1 is required to maintain transcriptional regulation of a wide variety of genes on a genome-wide scale. The gene expression profiles in Parp-1-deficient cells may be useful to delineate the functional role of Parp-1 in epigenetic regulation of the genomes involved in various biological phenomena.Poly(ADP-ribose) polymerase-1 (Parp-1) is a nuclear protein that catalyzes the transfer of ADP-ribose units to various nuclear proteins as a post-translational modification [1]. Poly (ADP-ribose) is a highly negatively charged molecule and poly (ADP-ribosylation) of chromatin-bound proteins including histone may change the interaction of the modified proteins with DNA or other proteins. A 'histon
PPAR Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study
Hirokazu Takahashi,Kunihiro Hosono,Takashi Uchiyama,Michiko Sugiyama,Eiji Sakai,Hiroki Endo,Shin Maeda,Katherine L. Schaefer,Hitoshi Nakagama,Atsushi Nakajima
PPAR Research , 2010, DOI: 10.1155/2010/257835
Abstract: Activating synthetic ligands for peroxisome proliferator-activated receptor gamma (PPAR), such as pioglitazone, are commonly used to treat persons with diabetes mellitus with improvement of insulin resistance. Several reports have clearly demonstrated that PPAR ligands could inhibit colorectal cancer cell growth and induce apoptosis. Meanwhile, aberrant crypt foci (ACF) have come to be established as a biomarker of the risk of CRC in azoxymethane-treated mice and rats. In humans, ACF can be detected using magnifying colonoscopy. Previously, CRC and adenoma were used as a target for chemopreventive agents, but it needs a long time to evaluate, however, ACF can be a surrogate marker of CRC even for a brief period. In this clinical study, we investigated the chemopreventive effect of pioglitazone on the development of human ACF as a surrogate marker of CRC. Twenty-nine patients were divided into two groups, 20 were in the endoscopically normal control group and 9 were in the pioglitazone (15 mg/day) group, and ACF and adenoma were examined before and after 1-month treatment. The number of ACF was significantly decreased (5.8±1.1 to 3.3±2.3) after 1 month of pioglitazone treatment, however, there was no significant change in the number of crypts/ACF or in the number and size of adenomas. Pioglitazone may have a clinical application as a cancer-preventive drug. This investigation is just a pilot study, therefore, further clinical studies are needed to show that the PPAR ligand may be a promising candidate as a chemopreventive agent for colorectal carcinogenesis.
Page 1 /1147
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.