T Hiwasa

Chiba University, Tiba, Chiba, Japan

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Publications (103)352.99 Total impact

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    ABSTRACT: 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 FLNC, normally restricted in muscle tissues, offers many signaling molecules an essential communication fields. Recently, filamins have been considered important for tumorigenesis in cancers.
    BMC Cancer 06/2014; 14(1):452. · 3.33 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; · 3.97 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. · 3.07 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 01/2012; · 0.83 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. · 2.42 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. · 3.48 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. · 1.41 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. · 4.65 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. · 2.68 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. · 3.79 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. · 3.54 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. · 2.66 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. · 3.37 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. · 3.29 Impact Factor
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    ABSTRACT: Esophageal squamous cell carcinoma (SCC) represents one of the most malignant tumors. To improve the poor prognosis, it is necessary to diagnose esophageal SCC at early stages using new tumor markers. SEREX (serological identification of antigens by recombinant cDNA expression cloning) is suitable for large-scale screening of tumor antigens and has been applied for various types of human tumors. Tumor markers of esophageal squamous cell carcinoma (SCC) were screened by SEREX method. The presence of serum anti-makorin 1 (MKRN1) antibodies (s-MKRN1-Abs) was examined by Western blotting using bacterially expressed MKRN1 protein. The expression levels of MKRN1 mRNA in tissues were examined by RT-PCR. The biological activity of MKRN1 was examined by transfection of ras-NIH3T3 mouse fibroblasts with MKRN1 cDNA. Major ubiquitinated proteins in MKRN1-transfected cells were identified by immunoprecipitation with anti-ubiquitin antibody followed by mass spectrometry. MKRN1 was identified as a novel SEREX antigen of esophageal SCC. Although a total of 18 (25%) of 73 patients with esophageal SCC had s-MKRN1-Abs, none of the 43 healthy donors had a detectable level of s-MKRN1-Abs. There was no correlation between the presence of s-MKRN1-Abs and clinicopathological variables other than histological grading. Well-differentiated tumors were associated significantly with the presence of s-MKRN1-Abs in the patients. The mRNA levels of MKRN1 were frequently higher in esophageal SCC tissues than in the peripheral normal esophageal mucosa. Stable transfection of ras-NIH3T3 cells with MKRN1 cDNA induced prominent morphological changes such as enlargement of the cell body and spreading. Ubiquitination of 80- and 82-kDa proteins were clearly observed in MKRN1-transfected cells but not in the parental cells, which were identified as L-FILIP (filamin A interacting protein 1). MKRN1 is a novel SEREX antigen of esophageal SCC, and s-NKRN1-Abs can be a candidate of diagnostic markers of esophageal SCC with high specificity. It is plausible that MKRN1 is involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of L-FILIP.
    BMC Cancer 02/2009; 9:232. · 3.33 Impact Factor
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    ABSTRACT: There is an ongoing search for plant-derived diterpenes, especially for diterpenes with anti-inflammatory activity that also have anti-proliferative effects on human cancer cells. A cyathane-type diterpene, Sarcodonin G (SG), isolated from the mushroom Sarcodon scabrosus and already reported to have anti-inflammatory activity, inhibited proliferation of HeLa cells to the greatest extent among 4 cyathane diterpenes tested. SG showed an IC50 (50% inhibition concentration) of 20 microM, estimated by MTT assay 2 days after culture of cells with the chemical. SG treatment of HeLa cells resulted in dose-dependent generation of apoptotic events such as DNA-laddering (< or =100 microM). Moreover, SG-treated HeLa cells showed activation of caspase-3 and caspase-9 and increase of Bax/Bcl-2 ratios, as analyzed by Western blot analysis. The anti-proliferative effects of SG treatment on HeLa cells were lessened by a caspase inhibitor, Z-VAD-FMK. SG also showed anti-proliferative effects toward 5 other human cancer cell lines with IC50 values of 20-40 microM. Because of these anti-proliferative effects via possible caspase activation, SG holds promise of being a novel anti-proliferative agent deserving further investigation.
    International Journal of Oncology 01/2009; 34(1):201-7. · 2.66 Impact Factor
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    ABSTRACT: No serum marker is currently available for the diagnosis and treatment of gliomas. Plasminogen activator inhibitor-1 (PAI-1) controls the proteolytic activity in cancer cells and cellular migration during angiogenesis. To verify the potential of PAI-1 as a serum marker for gliomas, the serum PAI-1 concentrations were measured by ELISA in 57 glioma patients and 34 healthy volunteers. We found significantly higher serum levels in the patients with high-grade gliomas than in the healthy volunteers (p = 0.0009, unpaired t-test) and those with low-grade tumors (p = 0.0074). Furthermore, high-grade glioma patients with a low serum level of PAI-1 survived significantly longer than those with high levels (p = 0.0082). Immunohistochemical analysis using anti-PAI-1 antibody revealed dense and spotty staining in the high-grade tumor tissues from the patients with high serum PAI-1 levels. These results suggest that the serum PAI-1 level can be a marker for the prediction of histological grade in intracerebral glioma.
    Anticancer research 01/2008; 28(1B):415-8. · 1.71 Impact Factor
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    ABSTRACT: Pyrroloquinoline quinone (PQQ) has been implicated in certain physiological activities in mammals such as functioning as a potent growth factor in mice, and promoting DNA synthesis in human fibroblasts. These are clearly important physiological functions, however, the molecular mechanisms involved in PQQ activity are not yet fully understood. In order to address this, in this study we analyzed the effects of PQQ on the proliferation of NIH3T3 mouse fibroblasts and on their intracellular signal transduction mechanism. When activated c-Ha-ras-transformed NIH3T3 cells were treated with PQQ in the presence of 0.5% calf serum in DMEM, the cells showed significantly increased viability. After PQQ addition, flow cytometric analysis revealed a decrease in the population of cells in the G0/G1 phase and a concomitant increase in cells in the S and G2/M phases. Although treatment with SNAP, an NO donor, reduced cell viability, this effect was abolished by the addition of PQQ. Activation of ERK and PKC-epsilon was detected immediately after the addition of PQQ, and subsequent increases in the phosphorylation of Rb and c-Jun were observed. On the other hand, protein expression levels of growth-inhibitory molecules such as IkappaB and p27 decreased after PQQ treatment. These results suggest that PQQ stimulates cell proliferation through NO-sensitive Ras-mediated signaling pathways.
    International Journal of Molecular Medicine 05/2007; 19(5):765-70. · 1.96 Impact Factor
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    ABSTRACT: In order to identify new serum markers of esophageal squamous cell carcinoma (SCC), we performed serological identification of antigens by recombinant cDNA expression cloning (SEREX). E. coli was transformed with a lambdaZAPII phage cDNA library prepared from mRNA of an esophageal cancer cell line (T.Tn), and IPTG-induced cDNA products were screened for interaction with antibodies in allogeneic sera of patients with esophageal SCC. We identified myomegalin (MMGL, phosphodiesterase 4D interacting protein/PDE4DIP) as a new SEREX antigen for esophageal SCC. Western blot analysis revealed that serum anti-myomegalin antibodies (s-MMGL-Abs) were present in 43 (47%) of 91 patients, but in only one (2.2%) of 45 healthy controls. Of the 21 patients with stage I disease, 8 (38%) were sero-positive. The positive rate of s-MMGL-Abs was greater than those of other conventional tumor markers. Reverse transcription-PCR analysis suggested that alternative splicing from myomegalin variant 1 to variant 5 may explain, in part, the development of s-MMGL-Abs. Although the presence of s-MMGL-Abs was not related to any clinicopathological features of the patients, multivariate analysis indicated that the presence of s-MMGL-Abs was significantly associated with a favorable prognosis. Consequently, s-MMGL-Abs may be a useful tumor marker to diagnose and establish a prognosis in patients with esophageal SCC.
    International Journal of Oncology 02/2007; 30(1):97-103. · 2.66 Impact Factor
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    ABSTRACT: We previously performed SEREX (serological identification of antigens by recombinant expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and isolated a variant clone (AK093616) of ubiquitin-conjugating enzyme E21 (UBE2I). This clone was tentatively designated as UBE2I-v5 and analyzed for biological function by transient transfection of the cDNA into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts. Chemosensitivity to 92 cytotoxic drugs was compared between UBE2I-v5-transfected cells and the parental ras-NIH cells. The UBE2I-v5-transfected cells were more sensitive than the parental cells to anticancer drugs such as vincristine (VCR), mitoxantrone (MIT) and etoposide (VP16). The regression analysis of the total chemosensitivity pattern of UBE2I-vS-transfected cells revealed that the function of UBE2I-v5 was positively related to RPA2 (replication protein A2), Rho-GDI (Rho guanine nucleotide dissociation inhibitor a), FUS (putative tumor suppressor) and TKT (transketolase) but negatively related to Per-1 (period-I), Ran (nuclear Ras-related protein), PTEN (phosphatase and tensin homolog), C/EBPalpha (CCAAT/enhancer binding protein a) and the tumor suppressor p53. Thus, it is possible that UBE21-v5 plays a role in carcinogenesis by suppressing the function of CIEBPa and/or p53 via RPA2-like activity.
    Anticancer research 01/2007; 27(5A):3227-33. · 1.71 Impact Factor

Publication Stats

950 Citations
352.99 Total Impact Points

Institutions

  • 1998–2013
    • Chiba University
      • • Graduate School of Medicine
      • • Department of Neurological Surgery
      • • Faculty of Education
      Tiba, Chiba, Japan
  • 1986–2011
    • Chiba Cancer Center
      Tiba, Chiba, Japan
  • 2009
    • Hebei Medical University
      Chentow, Hebei, China
  • 1999–2001
    • Chiba University Hospital
      Tiba, Chiba, Japan
  • 1997
    • Gunma Children's Medical Center
      Shibukawa, Gunma Prefecture, Japan