Takaki Hiwasa

Chiba University, Tiba, Chiba, Japan

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Publications (107)370.34 Total impact

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    ABSTRACT: Because circulating antibodies against a variety of antigens have been detected in patients with coronary heart disease, carotid atherosclerosis and those who have suffered a stroke, it is suspected that immune response may be one of the mechanisms of atherogenesis The objective of this study is to identify novel antibodies in ischemic stroke patients by screening the expressed recombinant proteins using a human cDNA library (SEREX). To identify the candidate antigens, cDNA library was screened by SEREX using plasma from ten patients with ischemic stroke. Subsequently, via ELISA using recombinant proteins and synthetic peptides, the serum antibody levels were measured in two independent patient/healthy donor (HD) cohorts (142 and 78 in the 2nd screening and a validation cohort, respectively). The initial screening resulted in the identification of six candidate antigens. Of these antigens, replication protein A2 (RPA2) was determined to be the antigen associated with stroke (P < 0.05) by ELISA with 2nd screening and validation cohort. Multifactorial logistic regression analysis showed that the increased levels of the RPA2 antibodies (RPA2-Abs) associated with stroke independent of other risk factors for stroke (P < 0.05). Receiver operating curve analysis demonstrated that the area under the curve from ELISA using GST fusion RPA2 and synthetic peptides (bRPA2-132) were 0.867 (95% CI: 0.798-0.936) and 0.971 (95% CI: 0.940-1.00), respectively. If the cut-off value of the bRPA2-132-Ab level was determined to be 0.334, the sensitivity and specificity of the antibody level as the diagnostic marker for stroke were 0.323 (95% CI: 0.209-0.453) and 1.00 (95% CI: 0.713-1.00), respectively. SEREX identified RPA2 as the antigen associated with ischemic stroke and serum auto-antibodies against RPA2 elevates in stroke patients. RPA2-Abs could become a biomarker for the evaluation of ischemic stroke at risk.
    Journal of Translational Medicine 12/2015; 13(1). DOI:10.1186/s12967-015-0393-4 · 3.99 Impact Factor
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    ABSTRACT: In the pathogenesis of multiple sclerosis (MS), B cell/antibody-related mechanisms have recently received attention. To investigate the role of autoantibody in MS, we performed SEREX which can identify autoantibody cyclopedically. We identified serum antibodies against cytoskeletal protein talin1, and the levels of whom were remarkably higher in 39 MS than 43 normal controls (P < 0.01) and 35 disease controls (P = 0.06), and in MS patients without oligoclonal bands than ones with them. Moreover, we found the negative-correlations between serum anti-talin1 antibody and IgG index in MS (P = 0.03). Anti-talin1 antibody exists in MS patients’ sera, which may have some protective factor.
    Journal of Neuroimmunology 05/2015; DOI:10.1016/j.jneuroim.2015.05.005 · 2.79 Impact Factor
  • Journal of Cancer Science and Therapy 03/2015;
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    ABSTRACT: Background: Systemic lupus erythematosus (SLE) is an autoimmune disease which may be caused by development of the autoantibodies. On the other hand, SLE is a high-risk group of atherosclerosis, so it is possible that some of autoantibodies in SLE are the result of atherosclerosis-related diseases such as cerebral infarction (CI), cardiovascular disease (CVD) and diabetes mellitus (DM). Methods: The initial screening of autoantibodies was performed using the protein array method. AlphaLISA was used to analyze the serum antibody levels using synthetic polypeptides as antigens. Results: After the initial screening using protein array, we identified 67 antigens that were recognized by IgG antibodies in sera of patients with SLE. In the second screening, 170 peptides derived from amino acid sequences of 67 antigens were synthesized and used as antigens for analysis of serum antibody levels by AlphaLISA. The antibody levels for ten peptides were significantly higher in the sera of patients with SLE than in those of healthy donors. Further AlphaLISA analysis of sera of patients with CI, CVD or DM revealed that the serum antibody levels for four peptides derived from SOSTDC1, CTNND1, CLDND1 and CCNG2 were elevated in patients as compared to those of healthy donors. Conclusions: Serum antibody levels against peptide antigens of SOSTDC1, CTNND1, CLDND1 and CCNG2 are useful markers for diagnosis of the progression of CI, CVD and/or DM.
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    ABSTRACT: Background: Systemic lupus erythematosus (SLE) is an autoimmune disease which may be caused by development of the autoantibodies. On the other hand, SLE is a high-risk group of atherosclerosis, so it is possible that some of autoantibodies in SLE are the result of atherosclerosis-related diseases such as cerebral infarction (CI), cardiovascular disease (CVD) and diabetes mellitus (DM). Methods: The initial screening of autoantibodies was performed using the protein array method. AlphaLISA was used to analyze the serum antibody levels using synthetic polypeptides as antigens. Results: After the initial screening using protein array, we identified 67 antigens that were recognized by IgG antibodies in sera of patients with SLE. In the second screening, 170 peptides derived from amino acid sequences of 67 antigens were synthesized and used as antigens for analysis of serum antibody levels by AlphaLISA. The antibody levels for ten peptides were significantly higher in the sera of patients with SLE than in those of healthy donors. Further AlphaLISA analysis of sera of patients with CI, CVD or DM revealed that the serum antibody levels for four peptides derived from SOSTDC1, CTNND1, CLDND1 and CCNG2 were elevated in patients as compared to those of healthy donors. Conclusions: Serum antibody levels against peptide antigens of SOSTDC1, CTNND1, CLDND1 and CCNG2 are useful markers for diagnosis of the progression of CI, CVD and/or DM.
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    Journal of Neurological Surgery 01/2015; DOI:10.1055/s-0034-1396657 · 0.49 Impact Factor
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    ABSTRACT: Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable due to its invasive nature. Establishment of serum biomarkers for glioma would be beneficial both for early diagnosis and adequate therapeutic intervention. Filamins are an actin cross-linker and filamin C (FLNC), normally restricted in muscle tissues, offers many signaling molecules an essential communication fields. Recently, filamins have been considered important for tumorigenesis in cancers. Methods We searched for novel glioma-associated antigens by serological identification of antigens utilizing recombinant cDNA expression cloning (SEREX), and found FLNC as a candidate protein. Tissue expressions of FLNC (both in normal and tumor tissues) were examined by immunohistochemistry and quantitative RT-PCR analyses. Serum anti-FLNC autoantibody level was measured by ELISA in normal volunteers and in the patients with various grade gliomas. Results FLNC was expressed in glioma tissues and its level got higher as tumor grade advanced. Anti-FLNC autoantibody was also detected in the serum of glioma patients, but its levels were inversely correlated with the tissue expression. Serum anti-FLNC autoantibody level was significantly higher in low-grade glioma patients than in high-grade glioma patients or in normal volunteers, which was confirmed in an independent validation set of patients’ sera. The autoantibody levels in the patients with meningioma or cerebral infarction were at the same level of normal volunteers, and they were significantly lower than that of low-grade gliomas. Total IgG and anti-glutatione S-transferase (GST) antibody level were not altered among the patient groups, which suggest that the autoantibody response was specific for FLNC. Conclusions The present results suggest that serum anti-FLNC autoantibody can be a potential serum biomarker for early diagnosis of low-grade gliomas while it needs a large-scale clinical study.
    BMC Cancer 06/2014; 14(1):452. DOI:10.1186/1471-2407-14-452 · 3.32 Impact Factor
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    ABSTRACT: Cooperative gene regulation by different neurotransmitters likely underlies the long-term forms of associative learning and memory, but this mechanism largely remains to be elucidated. Following cDNA microarray analysis for genes regulated by Ca(2+) or cAMP, we found that the secretogranin II gene (Scg2) was cooperatively activated by glutamate and dopamine in primary cultured mouse hippocampal neurons. The Ca(2+) chelator BAPTA-AM and the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 prevented Scg2 activation by glutamate or dopamine; thus, the Ca(2+) /MEK pathway is predicted to include a convergence point(s) of glutamatergic and dopaminergic signaling. Unexpectedly, the protein kinase A (PKA) inhibitor KT5720 enhanced Scg2 activation by dopamine. The protein-synthesis inhibitor cycloheximide also enhanced Scg2 activation, and the proteasome inhibitor ZLLLH diminished the KT5720-mediated augmentation of Scg2 activation. These results are concordant with the notion that dopaminergic input leads to accumulation of a KT5720-sensitive transcriptional repressor, which is short-lived because of rapid degradation by proteasomes. This repression pathway may effectively limit the time window permissive to Scg2 activation by in-phase glutamate and dopamine inputs via the Ca(2+) /MEK pathway. We propose that the regulatory system of Scg2 expression is equipped with machinery that is refined for the signal integration of in-phase synaptic inputs. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 10/2013; DOI:10.1111/jnc.12467 · 4.24 Impact Factor
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    ABSTRACT: Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable in spite of various therapeutic approaches. Clarification of the oncogenic process in its early stage is important for the diagnosis and effective therapy. Methods In the present study, we used the serological identification of antigens by recombinant cDNA expression cloning (SEREX) to explore the subtle changes of the protein expression in low-grade glioma. The levels of serum autoantibodies to the SEREX-identified glioma-related antigens were analyzed by ELISA, and the epitope site was identified using deletion mutants and overlap peptide array. Changes in the serum autoantibody levels were examined in the rat glioma model using C6 and 9 L glioma cell lines. Results We identified 31 glioma-related antigens by SEREX. Among them, the serum level of autoantibody to src-homology 3-domain GRB2-like 1 (SH3GL1) was significantly higher in patients with low-grade glioma than healthy volunteers or high-grade gliomas. The 10 amino-acids at the C-terminal were identified as the epitope site by the overlap peptide array and the ELISA using deletion mutants. The tissue expression of SH3GL1 protein increased in proportion to glioma progression. The rat glioma models confirmed the increase of anti-SH3GL1 autoantibody level in the early stage and the suppression in the late stage. Conclusion SH3GL1 may be involved in the oncogenic process of gliomas and effectively elicit an autologous antibody response in low-grade gliomas. The immunological reaction to SH3GL1 would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas.
    Journal of Experimental & Clinical Cancer Research 10/2012; 31(1):85. DOI:10.1186/1756-9966-31-85 · 3.27 Impact Factor
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    ABSTRACT: Esophageal squamous cell carcinoma (SCC) is frequently associated with a high mortality rate as a result of late diagnosis and/or aggressive behavior. Although multimodal treatment is applied for advanced tumors, many patients suffer from progressive disease and rapid recurrence. Besides various imaging techniques, serum biomarkers should also be useful for early diagnosing and treatment monitoring. A comprehensive review is provided here mainly on advancements of our clinical research in serum biomarkers to diagnose and/or monitor esophageal SCC. First, we focused on conventional secretory type serum markers, SCC-antigen and CYFRA 21-1. Both serum markers are useful to predict high-risk patients to develop recurrent disease. Second, we reviewed the clinicopathological significance of various angiogenic factors, vascular endothelial growth factor, thymidine phosphorylase, fibroblast growth factor, midkine, and hepatocyte growth factor. These growth factors could be useful biomarkers to predict lymph node and/or distant metastases. Finally, we reviewed advancements of clinical research on autoantibodies against tumor-specific antigens, particularly focused on serum p53 antibody. Because serum antibodies frequently respond to a small volume of tumors, they are useful in early tumor detection and prediction of residual cancer cells. Serum biomarkers may be a useful tool in the management of esophageal SCC.
    Esophagus 09/2012; 9(3). DOI:10.1007/s10388-012-0332-x · 0.74 Impact Factor
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    ABSTRACT: Diagnosis of esophageal squamous cell carcinoma (SCC) may improve with early diagnosis. Currently it is difficult to diagnose SCC in the early stage because there is a limited number of tumor markers available. Fifty-two esophageal SCC SEREX antigens were identified by SEREX (serological identification of antigens by recombinant cDNA expression cloning) using a cDNA phage library and sera of patients with esophageal SCC. Sequence analysis revealed that three of these antigens were similar in amino acid sequences, and they were designated as ECSA (esophageal carcinoma SEREX antigen)-1, -2 and -3. The ECSA family was also similar to an EST clone, hepatocellular carcinoma-associated antigen 25a (HCA25a). Serum antibody levels to ECSA-1, -2 and -3 were significantly higher in patients with esophageal SCC than in healthy donors. Based on the conserved amino acid sequences, three peptides were synthesized and used for enzyme-linked immunosorbent assays (ELISA). The serum antibody levels against one of these peptides were significantly higher in patients with esophageal SCC. This peptide sequence was also conserved in FAM119A, GOSR1 and BBS5, suggesting that these are also ECSA family members. Reverse transcription followed by quantitative PCR analysis showed that the mRNA expression levels of ECSA-1, -2 and -3 and FAM119A but not of HCA25a, GOSR1 and BBS5 were frequently elevated in esophageal SCC tissues. We have identified a new gene family designated ECSA. Serum antibodies against the conserved domain of the ECSA family may be a promising tumor marker for esophageal SCC.
    Proteome Science 06/2011; 9(1):31. DOI:10.1186/1477-5956-9-31 · 1.88 Impact Factor
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    ABSTRACT: Thymidylate synthase (TS) plays a major role in the response to 5-fluorouracil (5-FU) by binding directly to the 5-FU metabolite, 5-fluoro-dUMP (FdUMP). The change in the TS expression levels after 5-FU administration was examined in parallel to 5-FU responsiveness in six human gastric adenocarcinoma cell lines to elucidate the source of variability of 5-FU sensitivity. MKN-1, SH-10-TC and MKN-74 cells were more resistant to 5-FU than MKN-28, KATO III and MKN-45 cells. Western blotting analysis revealed that the 5-FU sensitivity of these cells did not correlate with the basal TS expression levels but did correlate with rapid detection of the TS-FdUMP complex after exposure to 5-FU. In 5-FU-resistant cells, very low levels of the TS-FdUMP complex early after 5-FU exposure were elevated by pretreatment with calpain inhibitors such as benzyloxycarbonyl-leucyl-leucinal (ZLLH), benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLH) and ALLN, but not by other protease inhibitors. In contrast, ONO-3403, which causes calpain activation, stimulated downregulation of the TS-FdUMP complex in 5-FU-sensitive cells. The expression levels of calpastatin, an endogenous calpain inhibitor, were higher in 5-FU-sensitive cells than in 5-FU-resistant cells. ZLLH increased the 5-FU sensitivity of 5-FU-resistant cells, whereas ONO-3403 decreased the sensitivity of 5-FU-sensitive cells. In addition, knockdown of m-calpain by siRNA increased the 5-FU sensitivity in 5-FU-resistant cells, while knockdown of calpastatin reduced the sensitivity in 5-FU-sensitive cells. These results suggest that calpain might reduce the chemosensitivity of human gastric cancer cells to 5-FU possibly by rapid degradation of the TS-FdUMP complex, a finding that is considered to have novel therapeutic implications.
    Cancer Science 05/2011; 102(8):1509-15. DOI:10.1111/j.1349-7006.2011.01978.x · 3.53 Impact Factor
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    ABSTRACT: Neuromyelitis optica (NMO) is an acute inflammatory disease that preferentially involves the optic nerves and spinal cord. Although many infectious agents, including mumps virus, are postulated to have a role in the pathogenesis of multiple sclerosis (MS), the relationship between NMO and infectious agents remains uncertain. To investigate the relationship between NMO and viruses that have special affinity for the central nervous system, we performed a nested polymerase chain reaction (PCR) to detect mumps virus or enterovirus RNA in cerebrospinal fluid samples from 13 patients with MS, 8 with NMO and 20 with other neurological diseases (ONDs). Nested PCR was positive for mumps virus in 2 (25%) of NMO patients, but in none of those with MS and ONDs. Moreover, nested PCR results became negative in the remission phase in the two PCR-positive NMO patients. Mumps virus may have some role in the pathogenesis of NMO.
    Neurological Sciences 04/2011; 32(5):795-9. DOI:10.1007/s10072-011-0564-x · 1.50 Impact Factor
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    ABSTRACT: Sterol regulatory element-binding protein-1 (SREBP-1) plays a central role in transcriptional regulation of genes for hepatic lipid synthesis that utilizes diet-derived nutrients such as carbohydrates and amino acids, and expression of SREBP-1 exhibits daily rhythms with a peak in the nocturnal feeding period under standard housing conditions of mice. Here, we report that the Srebp-1 expression rhythm shows time cue-independent and Clock mutation-sensitive circadian nature, and is synchronized with varied photoperiods apparently through entrainment of locomotor activity and food intake. Fasting caused diminution of Srebp-1 expression, while diabetic db/db and ob/ob mice showed constantly high expression with loss of rhythmicity. Time-restricted feedings during mid-light and mid-dark periods exhibited differential effects, the latter causing more severe damping of the oscillation. Therefore, "when to eat in a day (the light/dark cycle)," rather than "whenever to eat in a day," is a critical determinant to shape the daily rhythm of Srebp-1 expression. We further found that a high-carbohydrate diet and a high-protein diet, as well as a high-fat diet, cause phase shifts of the oscillation peak into the light period, underlining the importance of "what to eat." Daily rhythms of SREBP-1 protein levels and Akt phosphorylation levels also exhibited nutrient-responsive changes. Taken together, these findings provide a model for mechanisms by which time of day and nutrients in feeding shape daily rhythms of the Srebp-1 expression and possibly a number of other physiological functions with interindividual and interdaily differences in human beings and wild animals subjected to day-by-day changes in dietary timing and nutrients.
    Journal of Biological Chemistry 10/2010; 285(43):33028-36. DOI:10.1074/jbc.M109.089391 · 4.60 Impact Factor
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    ABSTRACT: ONO 3403, a new synthetic serine protease inhibitor, is a derivative of camostat mesilate and has a higher protease-inhibitory activity. The effect of ONO 3403 on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and nitric oxide (NO) production in RAW 264.7 macrophage-like cells was examined. ONO 3403 significantly inhibited LPS-induced TNF-α production at a lower concentration than camostat mesilate. It also inhibited LPS-induced NO production. Their inhibition was responsible for the reduced mRNA expression of TNF-α and inducible NO synthase. In LPS-stimulated cells, ONO 3403 prevented the augmentation of MyD88 expression and inhibited the phosphorylation of IκB-α, stress-activated protein kinase (SAPK) and IRF-3, and the production of interferon-β. ONO 3403 abolished the elevation of the extracellular serine protease activity in response to LPS. Further, it reduced the circulating TNF-α level, hepatic injury and mortality in mice receiving an injection of D-galactosamine and LPS. ONO 3403 was suggested to inhibit LPS-induced inflammatory responses via inactivation of MyD88-dependent and independent pathways.
    Innate Immunity 12/2009; 17(1):97-105. DOI:10.1177/1753425909353641 · 2.46 Impact Factor
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    ABSTRACT: The tumor suppressor p53 is activated by phosphorylation and/or acetylation. We constructed 14 non-phosphorylated, 11 phospho-mimetic, and 1 non-acetylated point p53 mutations and compared their transactivation ability in U-87 human glioblastoma cells by the luciferase reporter assay. Despite mutations at the phosphorylation sites, only the p53-K120R and p53-S9E mutants had marginally reduced activities. On the other hand, the Nuclear factor of activated T-cells (NFAT)-luciferase reporter was more potently activated by p53-K120R than by wild-type p53 and other mutants in glioblastoma, hepatoma and esophageal carcinoma cells. This suggests that acetylation at Lys-120 of p53 negatively regulates a signaling pathway leading to NFAT activation.
    FEBS letters 06/2009; 583(12):1916-22. DOI:10.1016/j.febslet.2009.04.041 · 3.34 Impact Factor
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    ABSTRACT: Serological identification of antigens by recombinant cDNA expression cloning (SEREX) is an established method for detecting new tumor-specific antigens. Antibodies to SEREX antigens may be useful for the detection of esophageal squamous cell carcinoma (SCC). A phage cDNA library of a human esophageal SCC cell line was screened using sera of patients with esophageal SCC. The presence and levels of serum antibodies to SEREX antigens were established by Western blotting and enzyme-linked immunosorbent assay (ELISA) using purified recombinant antigen proteins, respectively. The newly identified esophageal SCC antigen is encoded by a novel gene located on chromosome 1, here designated CUEC-23. Serum CUEC-23-antibodies (s-CUEC-23-Abs) were detected in 14 of 54 patients with esophageal SCC (26%) by Western blot analysis. Esophageal SCCs were positive for s-CUEC-23-Abs together with CEA, SCC-Ag or CYFRA21-1 in 44, 41 and 52% of cases, respectively. There was no detectable association between the presence of s-CUEC-23-Abs and clinicopathological variables. ELISA showed that the levels of s-CUEC-23-Abs were significantly higher in patients with esophageal SCC than in healthy volunteers (17% in the former using the mean+3 SD of s-CUEC-23-Abs in healthy controls as the cutoff). A new tumor antigen, CUEC-23, was identified by SEREX screening. s-CUEC-23-Abs might be a useful serum marker to detect esophageal SCC.
    Journal of Gastroenterology 06/2009; 44(7):691-6. DOI:10.1007/s00535-009-0060-8 · 4.02 Impact Factor
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    ABSTRACT: We performed SEREX (serological identification of antigens by recombinant cDNA expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and examined whether some of the SEREX antigens can affect chemosensitivity against anticancer drugs. We isolated a novel gene which was designated as AISEC (antigen identified by SEREX for esophageal carcinoma). RT-PCR analysis showed that the mRNA expression levels of AISEC were higher in esophageal SCC tissues than in their normal counterparts. By transfection into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts, we isolated a clone, FAISEC-3, which stably expressed AISEC. FAISEC-3 cells were more resistant to anticancer drugs, such as mitomycin C, ifosfamide, vincristine, camptothecin and etoposide, than parental ras-NIH cells. Luciferase reporter assay after a transient transfection with AISEC cDNA or the control vector revealed that the transactivity of p53 was suppressed by AISEC in a dose-dependent manner. These results suggested that esophageal SCC tissues produce AISEC in increased amounts, which can reduce the chemosensitivity against anticancer drugs possibly by suppressing the p53 transactivation ability.
    International Journal of Oncology 04/2009; 34(3):641-8. DOI:10.3892/ijo_0000189 · 2.77 Impact Factor
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    ABSTRACT: Human cells derived from nevoid basal carcinoma syndrome (NBCCS) patients show increased levels of DNA synthesis activity after X-ray irradiation which is suggested to be casually related to reduction in cellular amounts of small ubiquitin-like protein modifier (SUMO-2/SMT-3A). In the present study, an increased level of DNA synthesis activity was found 8h after X-ray irradiation in HeLa cells with reduction in SUMO-2 amounts by siRNA treatment for SUMO-2. When comparative proteomic analysis was performed between the siRNA and mimic control siRNA treated cells using two-dimensional (2D) electrophoresis and mass spectrometry, three proteins were identified as candidates. Our research focused on Nm23-H1, a nucleoside diphosphate kinase, whose amounts decreased after X-ray irradiation in HeLa cells treated with siRNA for SUMO-2. In the Nm23-H1 siRNA treated cells, induction of DNA synthesis was also detected. Furthermore, in synchronized HeLa cells, DNA synthesis was confirmed in the S phase. Moreover, increased expression of proliferating cell nuclear antigen (PCNA) was observed in Nm23-H1 siRNA treated HeLa cells after X-ray irradiation. In addition, Nm23-H1 was modified with SUMO-2 after X-ray irradiation. The present findings suggest that the reduction of Nm23-H1 is related to the decrease in sumoylation, which in turn, is involved in the induction of DNA synthesis via the regulation of PCNA expression after X-ray irradiation.
    Archives of Biochemistry and Biophysics 04/2009; 486(1):81-7. DOI:10.1016/j.abb.2009.03.011 · 3.04 Impact Factor
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    ABSTRACT: Based on the genetic background of cancer, we have been trying to develop novel diagnostic and therapeutic strategies against human cancers. c-myc gene activation has been detected in many human cancers, indicating a key role of c-myc in tumor development. Thus targeting c-myc gene suppression is a promising strategy for cancer treatment. Recently, an interaction between FIR (FUSE-Binding Protein-Interacting Repressor) and TFIIH/p89/XPB helicase was found to repress c-myc transcription and so might be important for suppressing tumor formation. Previously, we have shown that the expression of splicing variant of FIR is elevated in colorectal cancer tissues and promotes tumor development by disabling FIR-repression to sustain high levels of c-Myc, opposing apoptosis in cancer cells. In this study, FIR recombinant adenovirus vector induces tumor growth suppression against tumor xenografts in animal model experiment. Together, one clue to the development of cancer diagnosis and therapies directed against c-Myc may go through FIR and its splicing variant.
    Frontiers in Bioscience 02/2009; 14:3401-8. · 4.25 Impact Factor

Publication Stats

1k Citations
370.34 Total Impact Points

Institutions

  • 1998–2015
    • Chiba University
      • Graduate School of Medicine
      Tiba, Chiba, Japan
  • 2011
    • Aichi Medical University
      • Department of Microbiology and Immunology
      Koromo, Aichi, Japan
  • 2009
    • Hebei Medical University
      Chentow, Hebei, China
  • 2001
    • Chiba University Hospital
      Tiba, Chiba, Japan
  • 1986–1997
    • Chiba Cancer Center
      Tiba, Chiba, Japan
  • 1989–1995
    • Juntendo University
      Edo, Tōkyō, Japan