Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Takeshi Uchiumi Last modified date:2018.07.02

Associate Professor / Department of Clinical Chemistry and Laboratory Medicine / Department of Basic Medicine / Faculty of Medical Sciences

1. masaki shiota, Naohiro Fujimoto, Katuyoshi Higashijima, Kenjiro Imada, Eiji Kashiwagi, ario takeuchi, Junichi Inokuchi, Katsunori Tatsugami, Shunichi Kajioka, Takeshi Uchiumi, Masatoshi Eto, Mineralocorticoid receptor signaling affects therapeutic effect of enzalutamide, Prostate, 10.1002/pros.23661, 2018.01, Background: Corticosteroids play important roles in prostate cancer therapeutics. However, their role when combined with enzalutamide remains obscure. Then, we aimed to elucidate the functional and clinical impact of corticosteroids on steroid receptors in androgen receptor (AR)-targeting therapy utilizing enzalutamide. Methods: The therapeutic effect was studied according to concomitant use of corticosteroids in 86 men treated with enzalutamide. The sensitivity to various agents was evaluated using cytotoxicity assays in prostate cancer cells. Gene expression levels were evaluated by quantitative real-time polymerase chain reaction in prostate cancer cells and tissues. Results: The therapeutic effect of enzalutamide was particularly lessened with concomitant treatment with dexamethasone. Consistently, dexamethasone increased cellular resistance to enzalutamide while prednisolone and aldosterone decreased cellular resistance to enzalutamide in prostate cancer cells. Inversely, mineralocorticoid receptor (MR) knockdown augmented the activity of AR signaling and the cellular resistance to enzalutamide. Conclusions: MR plays a critical role in resistance to AR-targeting therapies, which may be overcome by activation of MR signaling..
2. masaki shiota, Naohiro Fujimoto, ario takeuchi, Eiji Kashiwagi, Takashi Dejima, Junichi Inokuchi, Katsunori Tatsugami, Akira Yokomizo, Shunichi Kajioka, Takeshi Uchiumi, Masatoshi Eto, The Association of Polymorphisms in the Gene Encoding Gonadotropin-Releasing Hormone with Serum Testosterone Level during Androgen Deprivation Therapy and Prognosis of Metastatic Prostate Cancer, Journal of Urology, 10.1016/j.juro.2017.09.076, 2018.01, Purpose: Serum testosterone suppression during androgen deprivation therapy has been reported to affect the efficacy of androgen deprivation therapy. However, the factors impacting hormonal variations during androgen deprivation therapy remain unclear. Therefore, in this study we investigated the significance of missense polymorphisms in the gene encoding GNRH in men treated with primary androgen deprivation therapy for metastatic prostate cancer. Materials and Methods: This study included 80 Japanese patients with metastatic prostate cancer with available serum testosterone levels during androgen deprivation therapy. We examined the association of GNRH1 (rs6185, S20W) and GNRH2 (rs6051545, A16V) gene polymorphisms with clinicopathological parameters, including serum testosterone levels during androgen deprivation therapy, as well as prognosis, including progression-free and overall survival. Results: The CT and CT/TT alleles in the GNRH2 gene (rs6051545) were associated with higher serum testosterone during androgen deprivation therapy compared with those of the CC allele. Consequently the CT alleles were associated with a higher risk of progression after adjustment for age and serum testosterone during androgen deprivation therapy (HR 1.73, 95% CI 1.00-3.00, p = 0.049). Conclusions: Taken together these findings suggest that rs6051545 (GNRH2) genetic variation may result in inadequate suppression of serum testosterone during androgen deprivation therapy. This may lead to detrimental effects of androgen deprivation therapy on prognosis in men with metastatic prostate cancer..
3. Yuichi Matsushima, Yuta Hirofuji, Masamune Aihara, Song Yue, Takeshi Uchiumi, Laurie S. Kaguni, Dongchon Kang, Drosophila protease ClpXP specifically degrades DmLRPPRC1 controlling mitochondrial mRNA and translation, Scientific Reports, 10.1038/s41598-017-08088-6, 7, 1, 2017.12, ClpXP is the major protease in the mitochondrial matrix in eukaryotes, and is well conserved among species. ClpXP is composed of a proteolytic subunit, ClpP, and a chaperone-like subunit, ClpX. Although it has been proposed that ClpXP is required for the mitochondrial unfolded protein response, additional roles for ClpXP in mitochondrial biogenesis are unclear. Here, we found that Drosophila leucine-rich pentatricopeptide repeat domain-containing protein 1 (DmLRPPRC1) is a specific substrate of ClpXP. Depletion or introduction of catalytically inactive mutation of ClpP increases DmLRPPRC1 and causes non-uniform increases of mitochondrial mRNAs, accumulation of some unprocessed mitochondrial transcripts, and modest repression of mitochondrial translation in Drosophila Schneider S2 cells. Moreover, DmLRPPRC1 over-expression induces the phenotypes similar to those observed when ClpP is depleted. Taken together, ClpXP regulates mitochondrial gene expression by changing the protein level of DmLRPPRC1 in Drosophila Schneider S2 cells..
4. Satomi Mezuki, Kenji Fukuda, Tomonaga Matsushita, Yoshihisa Fukushima, ryu matsuo, Yu ichi Goto, Takehiro Yasukawa, Takeshi Uchiumi, Dongchon Kang, Takanari Kitazono, Tetsuro Ago, Isolated and repeated stroke-like episodes in a middle-aged man with a mitochondrial ND3 T10158C mutation
A case report, BMC Neurology, 10.1186/s12883-017-1001-4, 17, 1, 2017.12, Background: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, is the most common phenotype of mitochondrial disease. It often develops in childhood or adolescence, usually before the age of 40, in a maternally-inherited manner. Mutations in mitochondrial DNA (mtDNA) are frequently responsible for MELAS. Case presentation: A 55-year-old man, who had no family or past history of mitochondrial disorders, suddenly developed bilateral visual field constriction and repeated stroke-like episodes. He ultimately presented with cortical blindness, recurrent epilepsy and severe cognitive impairment approximately 6 months after the first episode. Genetic analysis of biopsied biceps brachii muscle, but not of peripheral white blood cells, revealed a T10158C mutation in the mtDNA-encoded gene of NADH dehydrogenase subunit 3 (ND3), which has previously been thought to be associated with severe or fatal mitochondrial disorders that develop during the neonatal period or in infancy. Conclusion: A T10158C mutation in the ND3 gene can cause atypical adult-onset stroke-like episodes in a sporadic manner..
5. Mikako Yagi, Takeshi Uchiumi, Noriaki Sagata, Daiki Setoyama, Rie Amamoto, Yuichi Matsushima, Dongchon Kang, Neural-specific deletion of mitochondrial p32/C1qbp leads to leukoencephalopathy due to undifferentiated oligodendrocyte and axon degeneration, Scientific Reports, 10.1038/s41598-017-15414-5, 7, 1, 2017.12, Mitochondrial dysfunction is a critical step in the pathogenesis of many neurodegenerative diseases. The p32/ C1qbp gene functions as an essential RNA and protein chaperone in mitochondrial translation, and is indispensable for embryonic development. However, little is known about the consequences of mitochondrial dysfunction of p32 deletion in the brain development. Here, we found that mice lacking p32 in the central nervous system (p32cKO mice) showed white matter degeneration accompanied by progressive oligodendrocyte loss, axon degeneration and vacuolation in the mid brain and brain stem regions. Furthermore, p32cKO mice died within 8 weeks of birth. We also found that p32-deficient oligodendrocytes and neurons showed reduced oligodendrocyte differentiation and axon degeneration in primary culture. We show that mitochondrial disruption activates an adaptive program known as the integrated stress response (ISR). Mitochondrial respiratory chain function in oligodendrocytes and neurons is, therefore, essential for myelination and axon maintenance, respectively, suggesting that mitochondrial respiratory chain dysfunction in the central nervous system contributes to leukoencephalopathy..
6. Kensuke Yamamichi, Takao Fukuda, Terukazu Sanui, Kyousuke Toyoda, Urara Tanaka, Yuki Nakao, Karen Yotsumoto, Hiroaki Yamato, Takaharu Taketomi, Takeshi Uchiumi, Fusanori Nishimura, Amelogenin induces M2 macrophage polarisation via PGE2/cAMP signalling pathway, Archives of Oral Biology, 10.1016/j.archoralbio.2017.08.005, 83, 241-251, 2017.11, Objectives Amelogenin, the major component of the enamel matrix derivative (EMD), has been suggested as a bioactive candidate for periodontal regeneration. Apart from producing a regenerative effect on periodontal tissues, amelogenin has also been reported to have an anti-inflammatory effect. However, the precise molecular mechanisms underlying these effects remain unclear. In the present study, we examined the immunomodulatory effects of amelogenin on macrophages. Design Human phorbol 12-myristate 13-acetate (PMA)-differentiated U937 macrophages and CD14+ peripheral blood-derived monocytes (PBMC)-derived macrophages were stimulated with recombinant amelogenin (rM180). After performing a detailed microarray analysis, the effects of rM180 on macrophage phenotype and signal transduction pathways were evaluated by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, confocal microscopy and flow cytometry. Results The microarray analysis demonstrated that rM180 increased the expression of anti-inflammatory genes in lipopolysaccharide (LPS)-challenged macrophages after 24 h, while it temporarily up-regulated inflammatory responses at 4 h. rM180 significantly enhanced the expression of M2 macrophage markers (CD163 and CD206). rM180-induced M2 macrophage polarisation was associated with morphological changes as well as vascular endothelial growth factor (VEGF) production. rM180 enhanced prostaglandin E2 (PGE2) expression, and the activation of the cAMP/cAMP-responsive element binding (CREB) signaling pathway was involved in amelogenin-induced M2 macrophage polarisation. Blocking of PGE2 signaling by indomethacin specifically abrogated rM180 with or without LPS-induced M2 shift in PBMC-derived macrophages. Conclusion Amelogenin could reprogram macrophages into the anti-inflammatory M2 phenotype. It could therefore contribute to the early resolution of inflammation in periodontal lesions and provide a suitable environment for remodeling-periodontal tissues..
7. Takashi Matsumoto, Takeshi Uchiumi, Keisuke Monji, Mikako Yagi, Daiki Setoyama, Rie Amamoto, Yuichi Matsushima, masaki shiota, Masatoshi Eto, Dongchon Kang, Doxycycline induces apoptosis via ER stress selectively to cells with a cancer stem cell-like properties
Importance of stem cell plasticity, Oncogenesis, 10.1038/s41389-017-0009-3, 6, 11, 2017.11, Tumor heterogeneity can be traced back to a small subset of cancer stem cells (CSCs), which can be derived from a single stem cell and show chemoresistance. Recent studies showed that CSCs are sensitive to mitochondrial targeting antibiotics such as doxycycline. However, little is known about how cancer cells undergo sphere formation and how antibiotics inhibit CSC proliferation. Here we show that under sphere-forming assay conditions, prostate cancer cells acquired CSC-like properties: promoted mitochondrial respiratory chain activity, expression of characteristic CSC markers and resistance to anticancer agents. Furthermore, those CSC-like properties could reversibly change depending on the culture conditions, suggesting some kinds of CSCs have plasticity in tumor microenvironments. The sphere-forming cells (i.e. cancer stem-like cells) showed increased contact between mitochondria and mitochondrial associated-endoplasmic reticulum (ER) membranes (MAM). Mitochondrial targeting doxycycline induced activating transcription factor 4 (ATF4) mediated expression of ER stress response and led to p53-upregulated modulator of apoptosis (PUMA)-dependent apoptosis only in the cancer stem-like cells. We also found that doxycycline effectively suppressed the sphere formation in vitro and blocked CD44v9-expressing tumor growth in vivo. In summary, these data provide new molecular findings that monolayer cancer cells acquire CSC-like properties in a reversible manner. These findings provide important insights into CSC biology and a potential new treatment of targeting mitochondria dependency..
8. René G. Feichtinger, Monika Oláhová, Yoshihito Kishita, Caterina Garone, Laura S. Kremer, Mikako Yagi, Takeshi Uchiumi, Alexis A. Jourdain, Kyle Thompson, Aaron R. D'Souza, Robert Kopajtich, Charlotte L. Alston, Johannes Koch, Wolfgang Sperl, Elisa Mastantuono, Tim M. Strom, Saskia B. Wortmann, Thomas Meitinger, Germaine Pierre, Patrick F. Chinnery, Zofia M. Chrzanowska-Lightowlers, Robert N. Lightowlers, Salvatore DiMauro, Sarah E. Calvo, Vamsi K. Mootha, Maurizio Moggio, Monica Sciacco, Giacomo P. Comi, Dario Ronchi, Kei Murayama, Akira Ohtake, Pedro Rebelo-Guiomar, Masakazu Kohda, Dongchon Kang, Johannes A. Mayr, Robert W. Taylor, Yasushi Okazaki, Michal Minczuk, Holger Prokisch, Biallelic C1QBP Mutations Cause Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies, American Journal of Human Genetics, 10.1016/j.ajhg.2017.08.015, 101, 4, 525-538, 2017.10, Complement component 1 Q subcomponent-binding protein (C1QBP; also known as p32) is a multi-compartmental protein whose precise function remains unknown. It is an evolutionary conserved multifunctional protein localized primarily in the mitochondrial matrix and has roles in inflammation and infection processes, mitochondrial ribosome biogenesis, and regulation of apoptosis and nuclear transcription. It has an N-terminal mitochondrial targeting peptide that is proteolytically processed after import into the mitochondrial matrix, where it forms a homotrimeric complex organized in a doughnut-shaped structure. Although C1QBP has been reported to exert pleiotropic effects on many cellular processes, we report here four individuals from unrelated families where biallelic mutations in C1QBP cause a defect in mitochondrial energy metabolism. Infants presented with cardiomyopathy accompanied by multisystemic involvement (liver, kidney, and brain), and children and adults presented with myopathy and progressive external ophthalmoplegia. Multiple mitochondrial respiratory-chain defects, associated with the accumulation of multiple deletions of mitochondrial DNA in the later-onset myopathic cases, were identified in all affected individuals. Steady-state C1QBP levels were decreased in all individuals’ samples, leading to combined respiratory-chain enzyme deficiency of complexes I, III, and IV. C1qbp−/− mouse embryonic fibroblasts (MEFs) resembled the human disease phenotype by showing multiple defects in oxidative phosphorylation (OXPHOS). Complementation with wild-type, but not mutagenized, C1qbp restored OXPHOS protein levels and mitochondrial enzyme activities in C1qbp−/− MEFs. C1QBP deficiency represents an important mitochondrial disorder associated with a clinical spectrum ranging from infantile lactic acidosis to childhood (cardio)myopathy and late-onset progressive external ophthalmoplegia..
9. Toshiro Saito, Takeshi Uchiumi, Mikako Yagi, Rie Amamoto, Daiki Setoyama, Yuichi Matsushima, Dongchon Kang, Cardiomyocyte-specific loss of mitochondrial p32/C1qbp causes cardiomyopathy and activates stress responses, Cardiovascular Research, 10.1093/cvr/cvx095, 113, 10, 1173-1185, 2017.08, Aims Mitochondria are important organelles, dedicated to energy production. Mitochondrial p32/C1qbp, which functions as an RNA and protein chaperone, interacts with mitochondrial mRNA and is indispensable for mitochondrial function through its regulation of mitochondrial translation in cultured cell lines. However, the precise role of p32/C1qbp in vivo is poorly understood because of embryonic lethality in the systemic p32-deficient mouse. The goal of this study was to examine the physiological function of mitochondrial p32/C1qbp in the heart. Methods and results We investigated the role of p32 in regulating cardiac function in mice using a Cre-loxP recombinase technology against p32 with tamoxifen-inducible knockdown or genetic ablation during postnatal periods. Cardiomyocyte-specific deletion of p32 resulted in contractile dysfunction, cardiac dilatation and cardiac fibrosis, compared with hearts of control mice. We also found decreased COX1 expression, decreased rates of oxygen consumption and increased oxidative stress, indicating that these mice had cardiac mitochondrial dysfunction provoked by p32-deficiency at early stage. Next, we investigated lifespan in cardiac-specific p32-deficient mice. The mice died beginning at 12 months and their median lifespan was ∼14 months. Cardiac mitochondria in the p32-deficient mice showed disordered alignment, enlargement and abnormalities in their internal structure by electron microscopy. We observed that, in p32-deficient compared with control myocytes, AMPKI' was constitutively phosphorylated and 4EBP-1 and ribosomal S6K were less phosphorylated, suggesting impairment of mammalian target of rapamycin signalling. Finally, we found that expression levels of mitokines such as FGF21 and of integrated stress response genes were significantly increased. Metabolic analysis demonstrated that the urea cycle was impaired in the p32-deficient hearts. Conclusion These findings support a key role for mitochondrial p32 protein in cardiac myocytes modulating mitochondrial translation and function, and thereby survival..
10. Hirofumi Inoue, Shin Ichi Terachi, Takeshi Uchiumi, Tetsuji Sato, Michiyo Urata, masataka ishimura, Yui Koga, Taeko Hotta, Toshiro Hara, Dongchon Kang, Shoichi Ohga, The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene, Pediatric Blood and Cancer, 10.1002/pbc.26404, 64, 7, 2017.07, Background: Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF). Procedure: We studied the onset of disease and the genotype of 22 PC-deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan. Results: Twenty-two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19–52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late-onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset. Conclusions: The genotype of double-PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset)..
11. Katsuhiko Sasaki, Kazuhito Gotou, Sho Miake, Daiki Setoyama, Mikako Yagi, Ko Igami, Takeshi Uchiumi, Dongchon Kang, p32 is Required for Appropriate Interleukin-6 Production Upon LPS Stimulation and Protects Mice from Endotoxin Shock, EBioMedicine, 10.1016/j.ebiom.2017.05.018, 20, 161-172, 2017.06, Sepsis is a major cause of morbidity and mortality in seriously ill patients and mitochondrial dysfunction is associated with poor outcomes in septic patients. Although interleukin-6 (IL-6) is a good prognostic marker for sepsis, the relationship between mitochondrial dysfunction and IL-6 remains poorly understood. We identified p32/C1QBP/HABP1 as a regulator of IL-6 production in response to lipopolysaccharide (LPS). LPS induced IL-6 overproduction in p32 deficient mouse embryonic fibroblasts (MEFs) through NF-κB independent but activating transcription factor (ATF) 4 dependent pathways. Short hairpin RNA-based knockdown of ATF4 in p32 deficient MEFs markedly inhibited LPS-induced IL-6 production. Furthermore, MEFs treated with chloramphenicol, an inhibitor of mitochondrial translation, produced excessive IL-6 via ATF4 pathways. Using a LPS-induced endotoxin shock model, mice with p32 ablation in myeloid cells showed increased lethality and overproduction of IL-6. Thus, this study provides a molecular link how mitochondrial dysfunction leads to IL-6 overproduction and poor prognosis of sepsis..
12. masaki shiota, Akira Yokomizo, ario takeuchi, Eiji Kashiwagi, Takashi Dejima, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Masatoshi Eto, Protein kinase C regulates Twist1 expression via NF-κB in prostate cancer, Endocrine-Related Cancer, 10.1530/ERC-16-0384, 24, 4, 171-180, 2017.04, The progression of prostate cancer to metastatic and castration-resistant disease represents a critical step. We previously showed that protein kinase C (PKC) activation followed by Twist1 and androgen receptor (AR) induction played a critical role in castration resistance, but the precise molecular mechanism remains unknown. This study aimed to elucidate the relevant molecular mechanism, focusing on NF-κB transcription factor. We examined the activity of NF-κB after PKC inhibition, and the expression of Twist1 and AR after inhibition of NF-κB in human prostate cancer cells. We also investigated the status of PKC/NF-κB after inhibition of AR signaling in cells resistant to hormonal therapy. As a result, inhibition of PKC signaling using knockdown and smallmolecule inhibition of PKC suppressed RelA activity, while blocking NF-κB suppressed Twist1 and AR expression. Conversely, inhibition of AR signaling by androgen depletion and the novel antiandrogen enzalutamide induced PKC and RelA activation, resulting in Twist1/AR induction at the transcript level. Moreover, inhibition of NF-κB signaling prevented enzalutamide-induced Twist1 and AR induction. Finally, NF-κB was activated in both castration-resistant and enzalutamide-resistant cells. In conclusion, NF-κB signaling was responsible for Twist1 upregulation by PKC in response to AR inhibition, resulting in aberrant activation of AR. NF-κB signaling thus appears to play a critical role in promoting both castration resistance and enzalutamide resistance in PKC/Twist1 signaling in prostate cancer..
13. Jun Yokoyama, hiroo yamaguchi, Hiroshi Shigeto, Takeshi Uchiumi, Hiroyuki Murai, Jun-Ichi Kira, A case of rhabdomyolysis after status epilepticus without stroke-like episodes in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Clinical Neurology, 10.5692/, 57, 7, 400-401, 2017.01.
14. Eiichi Ogawa, Norihiro Furusyo, Murata Masayuki, Motohiro Shimizu, Kazuhiro Toyoda, Taeko Hotta, Takeshi Uchiumi, Jun Hayashi, Comparison of the Abbott RealTime HCV and Roche COBAS Ampliprep/COBAS TaqMan HCV assays for the monitoring of sofosbuvir-based therapy, Antiviral Therapy, 10.3851/IMP3085, 22, 1, 61-70, 2017.01, Background: On-treatment HCV kinetics play an invaluable role in evaluating the efficacy of interferon-based therapies. However, the importance of HCV RNA monitoring has not been well discussed concerning treatment with sofosbuvir (SOF)-based regimens, especially for the utility of the Abbott RealTime HCV (ART) assay. Methods: This study consisted of 151 patients infected with HCV genotype-1 or -2, including patients with prior treatment-experience or cirrhosis. HCV genotype-1 patients were treated with SOF/ledipasvir and genotype-2 patients with SOF/ribavirin, both for 12 weeks. Serial measurements of HCV RNA were performed with both the ART and COBAS AmpliPrep/COBAS TaqMan v2.0 (CAP/CTM) assays simultaneously at weeks 0, 1, 2, 4, 6, 8, 10 and 12 of treatment. Results: The rates of HCV RNA target not detected (TND) by ART were significantly lower than those by CAP/CTM between weeks 2 and 12 (end of treatment [EOT]), irrespective of prior treatment-experience or cirrhosis. 11 (11.6%) genotype-1 and 8 (14.3%) genotype-2 patients did not achieve HCV RNA TND by ART at EOT, in contrast to all having HCV RNA TND by CAP/CTM; however, all achieved sustained virological response. The time at which HCV RNA became TND or unquantifiable was not associated with treatment outcome by either the ART or CAP/CTM assay. Conclusions: Over 10% of the patients continued to have detectable HCV RNA by ART at EOT, irrespective of HCV genotype, prior treatment-experience and/or cirrhosis. However, prolonged residual HCV RNA was not associated with treatment failure..
15. masaki shiota, N. Fujimoto, M. Itsumi, ario takeuchi, Junichi Inokuchi, Katsunori Tatsugami, A. Yokomizo, Shunichi Kajioka, Takeshi Uchiumi, Masatoshi Eto, Gene polymorphisms in antioxidant enzymes correlate with the efficacy of androgen-deprivation therapy for prostate cancer with implications of oxidative stress, Annals of Oncology, 10.1093/annonc/mdw646, 28, 3, 569-575, 2017.01, Background: Oxidative stress mitigated by antioxidant enzymes is thought to be involved in the progression to castrationresistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). This study investigated the association between genetic variations in antioxidant enzymes and the efficacy of ADT as well as its biological background. Patients and methods: The non-synonymous or promoter-locating polymorphisms of antioxidant enzymes were examined as well as the time to CRPC progression and overall survival in 104 and 92 patients treated with ADT for metastatic and nonmetastatic prostate cancer, respectively. In addition, intracellular reactive oxygen species and expression levels of antioxidant enzymes were examined in castration-resistant and enzalutamide-resistant cells. Results: In metastatic prostate cancer, the AG/GG allele in GSTM3 rs7483 and CT/TT allele in CAT rs564250 were associated with a significantly lower risk of progression to CRPC and all-cause death compared with homozygotes of the major AA allele (hazard ratio [HR]; [95% confidence interval (CI)], 0.55 [0.34-0.86], P=0.0086) and CC allele (HR; [95% CI], 0.48 [0.24-0.88], P=0.016), respectively. On multivariate analyses, only GSTM3 rs7483 was associated with significant progression risk (AG/GG versus AA; HR; [95% CI], 0.45 [0.25-0.79], P=0.0047) even after Bonferroni adjustment. In non-metastatic prostate cancer, the AG/GG allele in GSTM3 rs7483 was associated with a significantly lower risk of progression to CRPC (HR; [95% CI], 0.35 [0.10-0.93], P=0.034) and all-cause death (HR; [95% CI], 0.26 [0.041-0.96], P=0.043) compared with the AA allele. Intracellular reactive oxygen species levels were increased, accompanied with augmented GSTM3 expression in both castration-resistant and enzalutamide-resistant cells. Conclusions: Differential activity of antioxidant enzymes caused by the polymorphism in GSTM3 may contribute to resistance to hormonal therapy through oxidative stress. The GSTM3 rs7483 polymorphism may be a promising biomarker for prostate cancer patients treated with ADT..
16. Takeshi Uchiumi, Dongchon Kang, Mitochondrial nucleic acid binding proteins associated with diseases, Frontiers in Bioscience - Landmark, 10.2741/4479, 22, 168-179, 2017.01, Mammalian mitochondrial DNA (mtDNA) exists in structures called nucleoids, which correspond to the configuration of nuclear DNA. Mitochondrial transcription factor A (TFAM), first cloned as an mtDNA transcription factor, is critical for packaging and maintaining mtDNA. To investigate functional aspects of TFAM, we identified many RNA-binding proteins as candidate TFAM interactors, including ERAL1 and p32. In this review, we first describe the functions of TFAM, replication proteins such as polymerase gamma and Twinkle, and mitochondrial RNA binding proteins. We describe the role of mitochondrial nucleic acid binding proteins within the mitochondrial matrix and two oxidative phosphorylation-related proteins within the mitochondrial intermembrane space. We then discuss how mitochondrial dysfunction is related to several diseases, including mitochondrial respiratory disease, Miller syndrome and cancer. We also describe p32 knockout mice, which are embryonic lethal and exhibit respiratory chain defects. Miller syndrome is a recessive disorder characterized by postaxial acrofacial dysostosis and caused by a mutation in DHODH. Finally, we explain that p32 and mitochondrial creatine kinase may be novel markers for the progression of prostate cancer..
17. Hideya Ando, Yoshiaki Ohagi, Moemi Yoshida, Satoshi Yoshimoto, Yusuke Higashi, Masayuki Yagi, Keisuke Monji, Mikako Yagi, Takeshi Uchiumi, Dongchon Kang, Masamitsu Ichihashi, Melanin pigment interrupts the fluorescence staining of mitochondria in melanocytes, Journal of Dermatological Science, 10.1016/j.jdermsci.2016.08.533, 84, 3, 349-351, 2016.12.
18. Amamoto R, Uchiumi T, Yagi M, Monji K, Song Y, Oda Y, , The Expression of Ubiquitous Mitochondrial Creatine Kinase Is Downregulated as Prostate Cancer Progression. , J Cancer , 10.7150/jca.13207, 7, 50-59, 2016.07, BACKGROUND: Mitochondria play crucial roles in cell signaling events, interorganellar communication, aging, cell proliferation and apoptosis, and mitochondrial impairment has been shown to accelerate or modulate cancer progression. Ubiquitous mitochondrial creatine kinase (uMtCK) is predominantly localized in the intermembrane space of mitochondria and catalyzes the reversible exchange of high-energy phosphate between adenosine tri-phosphate (ATP) and phosphocreatine. However, little is known about its expression and function in human prostate cancer progression. METHOD: We investigated the expression of uMtCK in 148 prostate carcinoma tissues and matched normal tissue by immunohistochemistry. The expression and localization of uMtCK and hexokinase II, a marker of glycolysis, were examined in prostate carcinoma cell lines using western blot and immunofluorescence. RESULTS: MtCK expression was significantly lower in high Gleason grade carcinoma compared with normal prostate or low grade carcinoma. Western blot further revealed that uMtCK was highly expressed in LNCaP and 22Rv1 cell lines, as well as in the normal prostate cell line RWPE-1. However, uMtCK expression was almost absent in PC3 and DU145 cell lines, in correlation with absent or mutant p53 expression, respectively. In contrast, hexokinase II was overexpressed in PC3 cells. Moreover, in the low uMtCK expressing cell lines, glycolytic ATP production was increased, whereas mitochondrial ATP production was decreased. CONCLUSIONS: These data suggest that uMtCK is downregulated as prostate cancer progresses in correlation with a metabolic switch in ATP usage..
19. Momoe Itsumi, masaki shiota, ario takeuchi, Eiji Kashiwagi, Junichi Inokuchi, Katsunori Tatsugami, Shunichi Kajioka, Takeshi Uchiumi, Seiji Naito, Masatoshi Eto, Akira Yokomizo, Equol inhibits prostate cancer growth through degradation of androgen receptor by S-phase kinase-associated protein 2, Cancer Science, 10.1111/cas.12948, 107, 7, 1022-1028, 2016.07, Chemopreventive and potential therapeutic effects of soy isoflavones have been shown to be effective in numerous preclinical studies as well as clinical studies in prostate cancer. Although the inhibition of androgen receptor signaling has been supposed as one mechanism underlying their effects, the precise mechanism of androgen receptor inhibition remains unclear. Thus, this study aimed to clarify their mechanism. Among soy isoflavones, equol suppressed androgen receptor as well as prostate-specific antigen expression most potently in androgen-dependent LNCaP cells. However, the inhibitory effect on androgen receptor expression and activity was less prominent in castration-resistant CxR and 22Rv1 cells. Consistently, cell proliferation was suppressed and cellular apoptosis was induced by equol in LNCaP cells, but less so in CxR and 22Rv1 cells. We revealed that the proteasome pathway through S-phase kinase-associated protein 2 (Skp2) was responsible for androgen receptor suppression. Taken together, soy isoflavones, especially equol, appear to be promising as chemopreventive and therapeutic agents for prostate cancer based on the fact that equol augments Skp2-mediated androgen receptor degradation. Moreover, because Skp2 expression was indicated to be crucial for the effect of soy isoflavones, soy isoflavones may be applicable for precancerous and cancerous prostates..
20. Jingxian Fang, Haruyoshi Yamaza, Takeshi Uchiumi, Yoshihiro Hoshino, Keiji Masuda, Yuta Hirofuji, Frank A.D.T.G. Wagener, Dongchon Kang, Kazuaki Nonaka, Dihydroorotate dehydrogenase depletion hampers mitochondrial function and osteogenic differentiation in osteoblasts, European Journal of Oral Sciences, 10.1111/eos.12270, 124, 3, 241-245, 2016.06, Mutation of the dihydroorotate dehydrogenase (DHODH) gene is responsible for Miller syndrome, which is characterized by craniofacial malformations with limb abnormalities. We previously demonstrated that DHODH was involved in forming a mitochondrial supercomplex and that mutated DHODH led to protein instability, loss of enzyme activity, and increased levels of reactive oxygen species in HeLa cells. To explore the etiology of Miller syndrome in more detail, we investigated the effects of DHODH inhibition in the cells involved in skeletal structure. Dihydroorotate dehydrogenase in MC3T3-E1 cells derived from mouse calvaria osteoblast precursor cells was knocked down by specific small interfering RNAs (siRNAs), and cell proliferation, ATP production, and expression of bone-related genes were investigated in these cells. After depletion of DHODH using specific siRNAs, inhibition of cell proliferation and cell cycle arrest occurred in MC3T3-E1 cells. In addition, ATP production was reduced in whole cells, especially in mitochondria. Furthermore, the levels of runt-related transcription factor 2 (Runx2) and osteocalcin (Ocn) mRNAs were lower in DHODH siRNA-treated cells compared with controls. These data suggest that depletion of DHODH affects the differentiation and maturation of osteoblasts. This study shows that mitochondrial dysfunction by DHODH depletion in osteoblasts can be directly linked to the abnormal bone formation in Miller syndrome..
21. Hideyuki Ikematsu, Yong Jeong, Kenjiro Shirane, Hidehiro Toh, Hiroyuki Sasaki, Shinya Matsumoto, Nozomi Noda, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Neuraminidase Amino Acid Sequences of Influenza A/H3N2 and B Viruses Isolated from Influenza Patients in the 2014/15 Japanese Influenza Season, Fukuoka Acta Medica, 107, 5, 98-104, 2016.05, Background: Neuraminidase (NA) is a surface protein essential for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan. Several mutations that reduce the effect of NA inhibitors have been reported. We sequenced the whole NA segment of isolated virus from influenza patients and investigated the relation between the NA amino acid sequence and the 50% inhibitory concentration (IC_50) of four NA inhibitors.
Materials and Methods: Forty A/H3N2 and 19 B influenza virus isolated from patients in the 2014/15 influenza season were analyzed. The IC_50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. Viral RNA was amplified by RT-PCR and the genome was sequenced using a next generation sequencer. The deduced amino acid sequences were analyzed.
Results: There was no AA change in the NA catalytic site of the A/H3N2 and B viruses isolated in the 2014-15 influenza season. There was no significant relation between the NA amino acids and the IC_50 of the four NA inhibitors for A/H3N2 or B viruses.
Conclusion: The catalytic site of NA was highly conserved for these A/H3N2 and B viruses. No emergence of NA amino acid mutations related to the sensitivity of the four currently used NA inhibitors was observed..
22. Eiichi Ogawa, Norihiro Furusyo, Murata Masayuki, Takeo Hayashi, Motohiro Shimizu, Haru Mukae, Kazuhiro Toyoda, Taeko Hotta, Takeshi Uchiumi, Jun Hayashi, Impact of HCV kinetics on treatment outcome differs by the type of real-time HCV assay in NS3/4A protease inhibitor-based triple therapy, Antiviral Research, 10.1016/j.antiviral.2015.12.001, 126, 35-42, 2016.02, Repeated measurement of the HCV RNA level is essential for properly monitoring treatment efficacy. The aim of this study was to determine the utility of two HCV real-time assays in the evaluation of the impact of hepatitis C virus (HCV) kinetics on the outcome of triple therapy with NS3/4A protease inhibitors (PIs), telaprevir or simeprevir. This study consisted of 171 Japanese patients infected with HCV genotype 1. All 3266 serum samples taken during and post treatment were tested with both the COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HCV Test v2.0 and the Abbott RealTime (ART) HCV Test. Of the 2597 samples undetectable (lower limit of detection [
23. Jun Yokoyama, hiroo yamaguchi, Hiroshi Shigeto, Takeshi Uchiumi, Hiroyuki Murai, Jun-Ichi Kira, A case of rhabdomyolysis after status epilepticus without stroke-like episodes in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Clinical Neurology, 10.5692/, 56, 3, 204-207, 2016.01, A 24-year-old man was referred to our hospital emergency department due to a sudden onset of convulsions after drinking. On arrival he presented status epilepticus and was managed by artificial ventilation. He had no brainstem signs or meningeal irritation. Head MRI showed an old infarction-like lesion in the left occipital lobe, but no abnormal signals on diffusion-weighted images. The patient showed acute rhabdomyolysis (CK 18,000 IU/l) and renal failure, and hemodialysis was started. On 18 day after admission, he was transferred to our department with mild proximal limb muscle weakness and bilateral sensorineural hearing impairment. Electroencephalography demonstrated diffuse intermittent slow wave activities. We suspected a mitochondrial disease because of a significant increase in the lactate/pyruvate ratio (24.1) in the spinal fluid, and identified A3243G mutations in mitochondrial DNA (heteroplasmy 20%) in peripheral white blood cells. We diagnosed his illness as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). This is a rare case presenting an acute onset of rhabdomyolysis following alcohol intake related to A3243G mitochondrial mutation without preceding stroke-like episodes..
24. Kyousuke Toyoda, Takao Fukuda, Terukazu Sanui, Urara Tanaka, Kensuke Yamamichi, Ryo Atomura, Hidefumi Maeda, Atsushi Tomokiyo, Takaharu Taketomi, Takeshi Uchiumi, Fusanori Nishimura, Grp78 Is Critical for Amelogenin-Induced Cell Migration in a Multipotent Clonal Human Periodontal Ligament Cell Line, Journal of Cellular Physiology, 10.1002/jcp.25087, 231, 2, 414-427, 2016.01, Periodontal ligament stem cells (PDLSCs) are known to play a pivotal role in regenerating the periodontium. Amelogenin, which belongs to a family of extracellular matrix (ECM) proteins, is a potential bioactive molecule for periodontal regenerative therapy. However, its downstream target molecules and/or signaling patterns are still unknown. Our recent proteomic study identified glucose-regulated protein 78 (Grp78) as a new amelogenin-binding protein. In this study, we demonstrate, for the first time, the cellular responses induced by the biological interaction between amelogenin and Grp78 in the human undifferentiated PDL cell line 1-17, which possesses the most typical characteristics of PDLSCs. Confocal co-localization experiments revealed the internalization of recombinant amelogenin (rM180) via binding to cell surface Grp78, and the endocytosis was inhibited by the silencing of Grp78 in 1-17 cells. Microarray analysis indicated that rM180 and Grp78 regulate the expression profiles of cell migration-associated genes in 1-17 cells. Moreover, Grp78 overexpression enhanced rM180-induced cell migration and adhesion without affecting cell proliferation, while silencing of Grp78 diminished these activities. Finally, binding of rM180 to Grp78 promoted the formation of lamellipodia, and the simultaneous activation of Rac1 was also demonstrated by NSC23766, a widely accepted Rac1 inhibitor. These results suggest that Grp78 is essential for enhancing amelogenin-induced migration in 1-17 cells. The biological interaction of amelogenin with Grp78 offers significant therapeutic potential for understanding the biological components and specific functions involved in the signal transduction of amelogenin-induced periodontal tissue regeneration. J. Cell. Physiol. 231: 414-427, 2016..
25. masaki shiota, Naohiro Fujimoto, Kenjiro Imada, Akira Yokomizo, Momoe Itsumi, ario takeuchi, Hidetoshi Kuruma, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Seiji Naito, Potential role for YB-1 in castration-resistant prostate cancer and resistance to enzalutamide through the androgen receptor V7, Journal of the National Cancer Institute, 10.1093/jnci/djw005, 108, 7, 2016.01, Background: Although androgen deprivation therapy for advanced prostate cancer initially exerts excellent anticancer effects, most prostate cancer treated with androgen deprivation therapy eventually recurs as castration-resistant prostate cancer (CRPC). Although aberrant kinase activation has been proposed as a mechanism of castration resistance, comprehensive kinase profiles in CRPC remain unknown. Therefore, we aimed to elucidate the kinome in CRPC as well as the role of key molecules. Methods: We utilized a kinome array in androgen-dependent LNCaP and castration-resistant CxR cells. The effect of Y-box binding protein-1 (YB-1) on androgen receptor (AR) expression was examined by quantitative polymerase chain reaction and western blot analysis. The association between polymorphisms in the YB-1 gene determined by genotyping and YB-1 expression evaluated by immunohistochemistry in prostate cancer tissues, as well as outcome in metastatic prostate cancer, were investigated by the Cochran-Armitage test and the Cox proportional hazards model, respectively. All statistical tests were two-sided. Results: One hundred fifty-six of 180 kinase phosphorylation sites, including ERK and RSK, were activated in CRPC cells, leading to increased phosphorylation of YB-1, which is a key molecule in the progression to CRPC. YB-1 signaling regulated AR V7 expression, and YB-1 inhibition augmented the anticancer effect of enzalutamide. Moreover, polymorphism (rs12030724) in the YB-1 gene affected YB-1 expression in 93 prostate cancer tissues (YB-1 positive rate; 14.3% in TT, 40.0% in AT, and 52.9% in AA, P = .04) and associated with probability of progression in 104 metastatic prostate cancer case patients (AT/TT vs AA, hazard ratio = 0.49, 95% confidence interval = 0.32 to 0.77, P = .001). Conclusions: YB-1 appears to be a promising target to inhibit the development of castration resistance, even at the AR variant-expressing stage. Polymorphism in the YB-1 gene may be a promising predictive biomarker in hormonal therapy..
26. Keisuke Monji, Takeshi Uchiumi, Saki Hoshizawa, Mikako Yagi, Takashi Matsumoto, Daiki Setoyama, Yuichi Matsushima, Kazuhito Gotou, Rie Amamoto, Dongchon Kang, Serum depletion induced cancer stem cell-like phenotype due to nitric oxide synthesis in oncogenic HRas transformed cells, Oncotarget, 10.18632/oncotarget.12117, 7, 46, 75221-75234, 2016.01, Cancer cells rewire their metabolism and mitochondrial oxidative phosphorylation (OXPHOS) to promote proliferation and maintenance. Cancer cells use multiple adaptive mechanisms in response to a hypo-nutrient environment. However, little is known about how cancer mitochondria are involved in the ability of these cells to adapt to a hypo-nutrient environment. Oncogenic HRas leads to suppression of the mitochondrial oxygen consumption rate (OCR), but oxygen consumption is essential for tumorigenesis. We found that in oncogenic HRas transformed cells, serum depletion reversibly increased the OCR and membrane potential. Serum depletion promoted a cancer stem cell (CSC)-like phenotype, indicated by an increase in CSC markers expression and resistance to anticancer agents. We also found that nitric oxide (NO) synthesis was significantly induced after serum depletion and that NO donors modified the OCR. An NOS inhibitor, SEITU, inhibited the OCR and CSC gene expression. It also reduced anchorage-independent growth by promoting apoptosis. In summary, our data provide new molecular findings that serum depletion induces NO synthesis and promotes mitochondrial OXPHOS, leading to tumor progression and a CSC phenotype. These results suggest that mitochondrial OCR inhibitors can be used as therapy against CSC..
27. Shiota M, Akira Yokomizo, Takeshi Uchiumi, Seiji Naito, Crosstalk between epithelial-mesenchymal transition and castration resistance mediated by Twist1/AR signaling in prostate cancer, ENDOCRINE-RELATED CANCER, 10.1530/ERC-15-0225, 22, 6, 889-900, 2015.12.
28. Shiota M, Akira Yokomizo, Takeshi Uchiumi, Seiji Naito, SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy, EUROPEAN JOURNAL OF CANCER, 10.1016/j.ejca.2015.06.122, 51, 14, 1962-1969, 2015.09.
29. Hideyuki Ikematsu, Yong Jeong, Kenjiro Shirane, Hidehiro Toh, Hiroyuki Sasaki, Yui Koga, Shinya Matsumoto, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Analysis of the Neuraminidase Amino Acid Sequences of Influenza A/H1N1pdm09, A/H3N2, and B Viruses Isolated from Influenza Patients in the 2013/14 Japanese Influenza Season, Fukuoka Acta Medica, 106, 8, 231-239, 2015.08, BACKGROUND: Neuraminidase (NA) is an essential surface protein for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan. Several mutations that reduce the effect of NA inhibitors have been reported. We sequenced the whole NA segment of isolated virus from influenza patients and investigated the relation between the NA amino acid sequence and the 50% inhibitory concentration (IC50) of four NA inhibitors.
MATERIALS AND METHODS: A total of 20 viruses that showed high or low IC50 of NA inhibitors were selected from A/H1N1pdm09, A/H3N2, and B isolates from the viruses isolated from patients in the 2013-14 influenza season. Viral RNA was extracted and RT-PCR was done. The amplified genome was sequenced using a next generation sequencer", and the deduced amino acid sequences were analyzed.
RESULTS: Two A/H1N1pdm09 viruses that showed very high IC50 for oseltamivir (150 nM and 130 nM) contained the H275Y mutation. Otherwise, no significant relation was found between the NA amino acids and the IC50 of the four NA inhibitors. There was no significant relation between the NA amino acids and the IC50 of the four NA inhibitors for A/H3N2 viruses. The B viruses that showed a high IC50 for oseltamivir and laninamivir shared some amino acids. The B viruses that showed a high IC50 of zanamivir and peramivir also shared some amino acids. They were different from the shared amino acids found for oseltamivir and laninamivir.
CONCLUSION: The previously reported H275Y mutation that causes oseltamivir resistance was found in the two A/H1N1pdm09 viruses that showed a very high IC50 for oseltamivir. No additional NA amino acid sequences related to the IC50 of the four NA inhibitors was found. The meaning of the shared amino acids among B viruses that showed a high IC50 would be an interesting target for further investigation..
30. Kuniyuki Nakamura, Ago T, Takeshi Uchiumi, Kitazono T, A CADASIL-Like Case with a Novel Noncysteine Mutation of the NOTCH3 Gene and Granular Deposits in the Renal Arterioles, Case Rep Neurol Med, 2015.03.
31. Hideyuki Ikematsu, Yong Jeong, Kenjiro Shirane, Hidehiro Toh, Hiroyuki Sasaki, Yui Koga, Michiyo Urata, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Analysis of influenza A/H3N2 neuraminidase genes obtained from influenza patients in the 2011/12 and 2012/13 seasons in Japan, Fukuoka Acta Medica, 106, 1, 16-22, 2015.01, BACKGROUND: Influenza virus has neuraminidase (NA), a surface protein with enzymatic activity that is essential for virus replication. Mutation may affect the effectiveness of NA inhibitors that are used for the treatment of influenza patients. In this study, we determined the NA gene sequences from the clinical isolates of influenza patients to examine the chronological genetic changes and the relation to drug susceptibility.
METHODS: For 96 A/H3N2 virus isolates the 50% inhibitory concentration (IC50) (48 each from the 2011-12 and 12-13 influenza seasons) was measured. RT-PCR was done with extracted viral RNA, followed by nucleotide sequencing.
RESULTS: One putative amino acid mutation, D151N, was found in an NA activity-related cite in five of ninety-six tested isolate. The mutation did not affect the IC50 value. The mutations identified at amino acid positions 387 and 400 were statistically correlated with an increased IC50 value, although the change was less than ten times, suggesting no significant difference in the clinical effectiveness. A small number .of isolates showed mutation in the T and/or B cell epitope region of NA.
CONCLUSION: No mutation that affected the IC50 value or effectiveness of NAIs was detected. Antigenic mutations of NA, which influence the selection of epidemic strains, were not determined. Continuous observation will be necessary to further clarify the genetic features of NA..
32. Aihara, M, Jin, X, Kurihara, Y, Yoshida, Y., Yuichi Matsushima, Takeshi Uchiumi, Dongchon Kang, Kanki, T., Tor and the Sin3-Rpd3 complex regulate expression of the mitophagy receptor protein Atg32 in yeast, 10.1242/jcs.153254 jcs.153254 [pii], 127, 3184-3196, 2014.05.
33. Itsumi, M., Shiota, M., Yokomizo, A, Takeshi Uchiumi, PMA induces androgen receptor downregulation and cellular apoptosis in prostate cancer cells, 10.1530/JME-13-0303 JME-13-0303 [pii], 53, 1, 31-41, 2014.05.
34. Masaki Shiota, Akira Yokomizo, Takeshi Uchiumi, Seiji Naito, Inhibition of RSK/YB-1 signaling enhances the anti-cancer effect of enzalutamide in prostate cancer, 10.1002/pros.22813, 74, 9, 959-969, 2014.04.
35. 神吉智久, 内海 健, Casein kinase 2 is essential for mitophagy, EMBO Reports, 14, 788-794, 2013.10.
36. Fang J, 内海 健, 康東天, Dihydroorotate dehydrogenase is physically associated with the respiratory complex and its loss leads to mitochondrial dysfunction., Bioscience report, 33, 217-227, 2013.03.
37. 内海 健, Mutation and functional analysis of ABCC2/multidrug resistance protein 2 in a Japanese patient with Dubin-Johnson syndrome., Hepatol. Research, 43, 569-575, 2013.02.
38. Mikako Yagi, 内海 健, 康 東天, P32/gC1qR is indispensable for fetal development and mitochondrial translation: Importance of its RNA-binding ability, Nucleic Acid Reserch, 40, 9717--9737., 2012.10.
39. Matsumoto S, Uchiumi T, Tanamachi H, Saito T, Yagi M, Takazaki S, Kanki T, Kang D., Ribonucleoprotein Y-box binding protein-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) protein expression after serum stimulation through binding to OXPHOS mRNA, Biochem J, 2012.05.
40. Matsumoto S, Uchiumi T, Saito T, Yagi M, Takazaki S, Kanki T, Kang D, Localization of mRNAs encoding human mitochondrial oxidative phosphorylation proteins., Mitochondrion, 12, 391-398, 2012.03.
41. Fotovati A, Abu-Ali S, Wang PS, Deleyrolle LP, Lee C, Triscott J, Chen JY, Franciosi S, Nakamura Y, Sugita Y, Uchiumi T, Kuwano M, Leavitt BR, Singh SK, Jury A, Jones C, Wakimoto H, Reynolds BA, Pallen CJ, Dunn SE., YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth., Cancer Res, 71, 5569-78, 2011.08.
42. Aoki Y, Kanki T, Hirota Y, Kurihara Y, Saigusa T, Uchiumi T, Kang D, Phosphorylation of Serine 114 on Atg32 mediates mitophagy., Mol Biol Cell, 22, 3206-17, 2011.08.
43. Uchiumi T, Kang D., The role of TFAM-associated proteins in mitochondrial RNA metabolism., Biochim Biophys Acta., 2011.08.
44. Shiota M, Yokomizo A, Kashiwagi E, Takeuchi A, Fujimoto N, Uchiumi T, Naito S. , Peroxiredoxin 2 in the nucleus and cytoplasm distinctly regulates androgen receptor activity in prostate cancer cells., Free Radic Biol Med, 51, 78-87, 2011.05.
45. Shiota M, Takeuchi A, Song Y, Yokomizo A, Kashiwagi E, Uchiumi T, Kuroiwa K, Tatsugami K, Fujimoto N, Oda Y, Naito S., Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression. , Endocr Relat Cancer., 18, 505-17, 2011.05.
46. Amamoto R, Yagi M, Song Y, Oda Y, Tsuneyoshi M, Naito S, Yokomizo A, Kuroiwa K, Tokunaga S, Kato S, Hiura H, Samori T, Kang D, Uchiumi T. , Mitochondrial p32/C1QBP is highly expressed in prostate cancer and is associated with shorter PSA relapse time after radical prostatectomy., Cancer Science, 2011.03.
47. Izumi H, Wakasugi T, Shimajiri S, Tanimoto A, Sasaguri Y, Kashiwagi E, Yasuniwa Y, Akiyama M, Han B, Wu Y, Uchiumi T, Arao T, Nishio K, Yamazaki R, Kohno K, Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell-cycle-associated genes, Cancer Science, 101, 2538-2545, 2010.09.
48. Twist1 and Y-box-binding protein-1 promote malignant potential in bladder cancer cells., Twist1 and Y-box-binding protein-1 promote malignant potential in bladder cancer cells., BJU Int, 2010.09.
49. Shiota M, Yokomizo A, Tada Y, Uchiumi T, Inokuchi J, Tatsugami K, Kuroiwa K, Yamamoto K, Seki N, Naito S., P300/CBP-associated factor regulates Y-box binding protein-1 expression and promotes cancer cell growth, cancer invasion and drug resistance., Cancer Science, 101, 1797-1806, 2010.07.
50. Shiota M, Song Y, Yokomizo A, Kiyoshima K, Tada Y, Uchino H, Uchiumi T, Inokuchi J, Oda Y, Kuroiwa K, Tatsugami K, Naito S, Foxo3a suppression of urothelial cancer invasiveness through Twist1, Y-box-binding protein 1, and E-cadherin regulation, Clin. Cancer Res, 16, 5654-5663, 2010.07.
51. Shiota M, Eto M, Yokomizo A, Tada Y, Takeuchi A, Itsumi M, Tatsugami K, Uchiumi T, Naito S, Sensitivity of doxorubicin-resistant cells to sorafenib: possible role for inhibition of eukaryotic initiation factor-2alpha phosphorylation, Int J Oncol, 37, 509-517, 2010.07.
52. Shiota, M. Eto, M. Yokomizo, A. Tada, Y. Takeuchi, A. Masubuchi, D. Inokuchi, J. Tatsugami, K. Kuroiwa, K. Uchiumi, T. Seki, N. Naito, S., Sorafenib with doxorubicin augments cytotoxicity to renal cell cancer through PERK inhibition, Int J Oncol, 36, 6, 1521-31, 2010.06.
53. Uchiumi, T. Ohgaki, K. Yagi, M. Aoki, Y. Sakai, A. Matsumoto, S. Kang, D., ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation, Nucleic Acids Res, 2010.05.
54. Shiota, M. Yokomizo, A. Tada, Y. Inokuchi, J. Tatsugami, K. Kuroiwa, K. Uchiumi, T. Fujimoto, N. Seki, N. Naito, S., Peroxisome proliferator-activated receptor gamma coactivator-1alpha interacts with the androgen receptor (AR) and promotes prostate cancer cell growth by activating the AR, Mol Endocrinol, 2010.05.
55. Shiota, M. Yokomizo, A. Kashiwagi, E. Tada, Y. Inokuchi, J. Tatsugami, K. Kuroiwa, K. Uchiumi, T. Seki, N. Naito, S., Foxo3a expression and acetylation regulate cancer cell growth and sensitivity to cisplatin, Cancer Sci, 2010.05.
56. Shiota, M. Song, Y. Yokomizo, A. Tada, Y. Kuroiwa, K. Eto, M. Oda, Y. Inokuchi, J. Uchiumi, T. Fujimoto, N. Seki, N. Naito, S., Human heterochromatin protein 1 isoform HP1{beta} enhances androgen receptor activity and is implicated in prostate cancer growth, Endocr Relat Cancer, 2010.05.
57. Shiota, M. Yokomizo, A. Masubuchi, D. Tada, Y. Inokuchi, J. Eto, M. Uchiumi, T. Fujimoto, N. Naito, S., Tip60 promotes prostate cancer cell proliferation by translocation of androgen receptor into the nucleus, Prostate, 70, 5, 540-54, 2010.04.
58. Shiota, M. Yokomizo, A. Tada, Y. Inokuchi, J. Kashiwagi, E. Masubuchi, D. Eto, M. Uchiumi, T. Naito, S., Castration resistance of prostate cancer cells caused by castration-induced oxidative stress through Twist1 and androgen receptor overexpression, Oncogene, 29, 2, 237-50, 2010.01.
59. Fukuoh, A. Ohgaki, K. Hatae, H. Kuraoka, I. Aoki, Y. Uchiumi, T. Jacobs, H. T.Kang, D., DNA conformation-dependent activities of human mitochondrial RNA polymerase, Genes Cells, 14, 8, 1029-42, 2009.08.
60. Niina I, Uchiumi T, Izumi H,Torigoe T, Wakasugi T, Igarashi T, Miyamoto N, Onitsuka T, Shiota M, Okayasu R, Chijiiwa K, and Kohno K, DNA topoisomerase inhibitor, etoposide, enhances GC-box-dependent promoter activity via Sp1 phosphorylation, Cancer Science, 2007.10.
61. Momii Y, Izumi H, Shiota M, Onistuka T, Abe T, Kobayasi H, Miyamoto N, Uchiumi T, and Kohno K, p73gamma transactivates the p21 promoter through preferential interaction with the p300/CBP-associated factor in human prostate cancer cells., Oncology Report, 18, 411-416, 2007.10.
62. Uramoto H, Uchiumi T, Izumi H, Kohno K, Oyama T, Sugio K, and Yasumoto K, A new mechanism for primary resistance to gefitinib in lung adenocarcinoma: the role of a novel G796A mutation in exon 20 of EGFR, Anticancer Res,, 27, 2297-2303, 2007.10.
63. Wakasugi,T., Izumi,H., Uchiumi,T., Suzuki,H., Arao,T., Nishio,K. and Kohno,K, ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes., Oncogene, 26: 5194-5203, 2007.09.
64. Igarashi,T., Izumi,H., Uchiumi,T., Nishio,K., Arao,T., Uramoto,H., Sugio,K., Yasumoto,K., Sasaguri,Y., Wang,KY., Otsuji,Y. and Kohno,K., Clock/ATF4 transcription system regulates multidrug resistance in human cancer cell line., Oncogene, 26, 4749-4760, 2007.06.
65. Uchiumi,T., Fotovati,A., Sasaguri,T., Shibahara,K., Shimada,T., Fukuda,T., Nakamura,T., Izumi,H., Tsuzuki,T., Kuwano,M. and Kohno,K, YB-1 is important for an early stage embryonic development: neural tube formation and cell proliferation. , J. Biol.Chem, 281: 40440-40449, 2006.11.
66. Yamashita,F., Ohtani,H., Koyabu,N., Ushigome,F., Satoh,H., Murakami,H., Uchiumi,T., Nakamura,T., Kuwano,M., Tsujimoto,M. and Sawada,Y., Inhibitory effects of angiotensin II receptor antagonists and leukotriene receptor antagonists on the transport of human organic anion transporter 4. , J. Pharm. Pharmacol., 2006.06.
67. Kohno,K., Matsuki,Y., Tanimoto,A., Izumi,H., Uchiumi,T., Kohno,K., Shimajiri,S. and Sasaguri,Y., Expression of Y-box-binding protein dbpC/contrin, a potentially new cancer/testis antigen., Br. J. Cancer, 94: 710-716, 2006.05.
68. Yoshida,T., Izumi,H., Uchiumi,T., Sasaguri,Y., Tanimoto,A., Matsumoto,T., Naito,S. and Kohno,K., Expression and cellular localization of dbpC/Contrin in germ cell tumor cell lines., Biochim. Biophys. Acta, 1759: 80-88, 2006.03.
69. Oda,Y., Saito,T., Tateishi,N., Ohishi,Y., Tamiya,S.,Yamamoto,H.,Yokoyama,R., Uchiumi,T., Iwamoto,Y., Kuwano,M. and Tsuneyoshi,M, ATP-binding cassette superfamily transporter gene expression in human soft tissue sarcoma., Int. J. Cancer, 10.1002/ijc.20589, 114, 6, 854-862, 2005.11.
70. Sata,R., Ohtani,H., Tsujimoto,M., Murakami,H., Koyabu,N., Nakamura,T., Uchiumi,T., Kuwano,M., Nagata,H., Tsukimori,K., Nakano,H. and Sawada,Y, Functional analysis of organic cation transporter 3 expressed in human placenta. , J. Pharmacol. Exp. Ther., 10.1124/jpet.105.086827, 315, 2, 888-895, 2005.10.
71. Pulaski,L., Kania,K., Ratajewski,M., Uchiumi,T., Kuwano,M. and Bartosz,G. , Differential regulation of the human MRP2 and MRP3 gene expression by glucocorticoids. , J. Steroid Biochem. Mol. Biol., 10.1016/j.jsbmb.2005.03.004, 96, 3-4, 229-234, 96: 229-234, 2005.08.
72. Yasen,M., Kajino,K., Kano,S., Tobita,H., Yamamoto,J., Uchiumi,T., Kon,S., Maeda,M., Obulhasim,G., Arii,S. and Hino,O., The up-regulation of Y-box binding proteins (DNA binding protein A and Y-box binding protein-1) as prognostic markers of hepatocellular carcinoma., Clin. Cancer Res, 11: 7354-7361, 2005.07.
73. Pulaski,L., Szemraj,J., Uchiumi,T., Kuwano,M. and Bartosz,G., Transcriptional upregulation of the human MRP2 gene expression by serine/threonine protein kinase inhibitors., J. Biol. Regul. Homeost. Agents, 19, 3-4, 113-119, 19: 113-119, 2005.05.
74. Honda,Y., Ushigome,F., Koyabu,N., Morimoto,S., Shoyama,Y., Uchiumi,T., Kuwano,M., Ohtani H. and Sawada Y., Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux., Br. J. Pharmacol., 10.1038/sj.bjp.0706008, 143, 7, 856-864, 143: 856-864, 2004.11.
75. Shibahara,K., Uchiumi,T., Fukuda,T., Kura,S., Tominaga,Y., Maehara,Y., Kohno,K., Nakabeppu,Y., Tsuzuki,T. and Kuwano,M., Targeted disruption of one allele of the Y-box binding protein-1 (YB-1) gene in mouse embryonic stem cells and increased sensitivity to cisplatin and mitomycin C, Cancer Sci., 10.1111/j.1349-7006.2004.tb03214.x, 95, 4, 348-353, 95: 348-353, 2004.07.
76. Hisaeda,K., Inokuchi,A., Nakamura,T., Iwamoto,Y., Kohno,K., Kuwano,M. and Uchiumi,T. , Interleukin-1ß represses MRP2 gene expression through inactivation of interferon regulatory factor 3 in HepG2 cells., Hepatology, 10.1002/hep.20216, 39, 6, 1574-1582, 39: 1574-1582, 2004.04.
77. Fukuda, T., Ashizuka, M., Nakamura, T., Shibahara,K., Maeda, K., Izumi, I., Kohno, K., Kuwano, M.,and Uchiumi,T.,, Characterization of 5'untranslated region of YB-1 mRNA and plausible regulation of translation., Nucleic Acid Res, 2004.01.
78. Ushigome, F., Koyabu, N., Satoh, S., Tsukimori, K., Nakano, H., Nakamura, T., Uchiumi, T., Kuwano, M., Ohtani, H., and Sawada, Y, Kinetic analysis of P-glycoprotein-mediated transport by using normal human placental brush-border membrane vesicles., Pharm Res, 10.1023/A:1022290523347, 20, 1, 38-44, 20: 38-44, 2003.01.
79. Kuwano, M., Uchiumi, T., Hayakawa, H., Ono, M., Wada, M., Izumi, H., and Kohno, K, The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies., Cancer Sci, 10.1111/j.1349-7006.2003.tb01344.x, 94, 1, 9-14, 94: 9-14, 2003.01.
80. Konno, T., Ebihara, T., Hisaeda, K., Uchiumi, T., Nakamura, T., Shirakusa, T., Kuwano, M., and Wada, M., Identification of domains participating in the substrate specificity and subcellular localization of the multidrug resistance proteins MRP1 and MRP2., J Biol Chem, 10.1074/jbc.M302868200, 278, 25, 22908-22917, 278: 22908-22917, 2003.01.
81. Nagashige M, Ushigome F, Koyabu N, Hirata K, Kawabuchi M, Hirakawa T, Satoh, Basal membrane localization of MRP1 in human placental trophoblast., Placenta, 10.1016/S0143-4004(03)00170-X, 24, 10, 951-958, 24: 951-958, 2003.01.
82. Kohno K, Izumi H, Uchiumi T, Ashizuka M, and Kuwano M, The pleiotropic functions of the Y-box-binding protein, YB-1, Bioessays, 10.1002/bies.10300, 25, 7, 691-698, 25: 691-698, 2003.01.
83. Zhu, H. Chang,B.-D. Uchiumi, T. and Roninson, I. B, Identification of promoter elements responsible for transcriptional inhibition of PLK1 and Topoisomerase IIa genes by p21WAF1/CIP1/SDI1., Cell cycle,, 1: 59-66, 2002.01.
84. Yamamoto, C., Murakami, H., Koyabu, N., Takanaga, H., Matsuo, H., Uchiumi, T., Kuwano, M., Naito, M., Tsuruo, T., Ohtani, H., and Sawada, Y, Contribution of P-glycoprotein to efflux of ramosetron, a 5-HT3 receptor antagonist, across the blood-brain barrier., J Pharm Pharmacol, 10.1211/002235702320266208, 54, 8, 1055-1063, 54: 1055-1063., 2002.01.
85. Uramoto, H., Izumi, H., Ise, T., Tada, M., Uchiumi, T., Kuwano, M., Yasumoto, K., Funa, K., and Kohno, K., p73 Interacts with c-Myc to regulate Y-box-binding protein-1 expression, J Biol Chem,, 10.1074/jbc.M200266200, 277, 35, 31694-31702, 277: 31694-31702, 2002.01.
86. Kakehi, M., Koyabu, N., Nakamura, T., Uchiumi, T., Kuwano, M., Ohtani, H., and Sawada, Y, Functional characterization of mouse cation transporter mOCT2 compared with mOCT1., Biochem Biophys Res Commun, 10.1016/S0006-291X(02)00926-9, 296, 3, 644-650, 296: 644-650, 2002.01.
87. Hayakawa, H., Uchiumi, T., Fukuda, T., Ashizuka, M., Kohno, K., Kuwano, M., and Sekiguchi, M, Binding Capacity of Human YB-1 Protein for RNA Containing 8-Oxoguanine., Biochemistry, 10.1021/bi0201872, 41, 42, 12739-12744, 41: 12739-12744, 2002.01.
88. Ashizuka, M., Fukuda, T., Nakamura, T., Shirasuna, K., Iwai, K., Izumi, H., Kohno, K., Kuwano, M., and Uchiumi, T., Novel translational control through an iron-responsive element by interaction of multifunctional protein YB-1 and IRP2., Mol Cell Biol, 10.1128/MCB.22.18.6375-6383.2002, 22, 18, 6375-6383, 22: 6375-6383, 2002.01.
89. Hashimoto K.,Uchiumi T., Konno T., Ebihara T., Nakamura T., Wada M., Sakisaka S., Maniwa F., Amachi T., Ueda K., and Kuwano M., Trafficking and functional defects by mutations of the ATP-binding domains in MRP2 in patients with Dubin-Johnson syndrome., Hepatology, 10.1053/jhep.2002.36368, 36, 5, 1236-1245, 36:1236-1245, 2002.01.
90. Ohishi Y., Oda Y., Uchiumi T., Kobayashi H., Hirakawa T., Miyamoto S.,Kinukawa N.,Nakano H., Kuwano M., and Tsuneyoshi M., ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma., Clin Cancer Res, 8, 12, 3767-3775, 8:3767-3775, 2002.01.
91. Haga, S., Hinoshita, E., Ikezaki, K., Fukui, M., Scheffer, G. L., Uchiumi, T. and Kuwano, M., Involvement of the multidrug resistance protein 3 in drug sensitivity and its expression in human glioma., Jpn. J. Cancer Res, 92, 2, 211-219, 92: 211-219, 2001.01.
92. Izumi, H., Imamura, T., Nagatani, G., Ise, T., Murakami, T., Uramoto, H., Torigoe, T., Ishiguchi, H., Nomoto, M., Okamoto, T., Uchiumi, T., Kuwano, M., Funa, K. and Kohno, K., YB-1 binds preferentially to single-stranded nucleic acid and exhibit 3'-5' exonuclease activity., Nucl. Acids Res., 29: 1200-1207, 2001.01.
93. Hinoshita, E., Taguchi, K., Inokuchi, A., Uchiumi, T., Kinukawa, N., Shimada, M., Tsuneyoshi, M., Sugimachi, K. and Kuwano, M., Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection., J. Hepatology, 10.1016/S0168-8278(01)00216-1, 35, 6, 765-773, 35,765-773, 2001.01.
94. Kawakami, A., Tomofumi, M., Higuchi, R., Uchiumi, T., Kuwano, M. and Van Soest, R. W. N., Structure of a novel multidrug resistance modulator, irciniasulfonic acid, isolated from a marin sponge, Ircinia sp., Tetrahedron Lett., 10.1016/S0040-4039(01)00426-9, 42, 19, 3335-3337, 42: 3335-3337, 2001.01.
95. Shibahara, K., Sugio, K., Osaki, T., Uchiumi, T., Maehara, Y., Kohno, K., Yasumoto, K., Sugimati, K. and Kuwano, M., Nuclear expression of the Y-box binding protein, YB-1, as a novel marker of disease progression in non-small-cell lung cancer., Clinical Cancer Res., 7, 10, 3151-3155, 7: 3151-3155, 2001.01.
96. Inokuchi, A., Hinoshita, E., Wada, M., Iwamoto, Y., Kohno, K., Kuwano, M. and Uchiumi, T., Enhanced expression of Human Multidrug resistance protein 3 by bile salt in human enterocytes: a transcriptional control of plausible bile acid transporter., J. Biol. Chem., 10.1074/jbc.M104612200, 276, 50, 46822-46829, 276: 46822-46829, 2001.01.
97. Okamoto, M., Ono, M., Uchiumi, T., Ueno, H., Kohno, K., Sugimachi, K. and Kuwano, M., Up-regulation of thrombospondin-1 gene by epidermal growth factor and transforming growth facter b in human cancer cells-transcriptional activation and messenger RNA stabilization., Biochim. Biophys. Acta, 93595, 2001.01.
98. Hinoshita, E., Uchiumi, T., Taguchi, K., Kinukawa, N., Tsuneyoshi, M., Maehara, Y., Sugimachi, K. and Kuwano, M., Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas., Clin Cancer Res, 6, 6, 2401-2407, 6:2401-2407, 2000.01.
99. Okamoto, T., Izumi, H., Imamura, T., Takano, H., Ise, T, Uchiumi, T., Kuwano, M. and Kohno, K., Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression., Oncogene, 10.1038/sj.onc.1204029, 19, 54, 6194-6202, 19: 6194-6202, 2000.01.
100. Ushigome, F., Takanaga, H., Matsuo, H., Yanai, S., Tsukimori, K., Nakano, H., Uchiumi, T., Nakamura, T., Kuwano, M., Ohtani, H., and Sawada, Y., Human placental transport of vinblastine, vincristine, digoxin and progesterone: contribution of P-glycoprotein., Eur. J. Pharmacol, 10.1016/S0014-2999(00)00743-3, 408, 1, 1-10, 408: 1-10, 2000.01.
101. Ohga,T., Uchiumi,T., Makino, Y., Koike,K., Wada,M., Kuwano, M. and Kohno,K., Direct involvement of the Y-box binding protein YB-1 in genotoxic stress-induced activation of the human multidrug resistance 1 gene., J. Biol. Chem., 10.1074/jbc.273.11.5997, 273, 11, 5997-6000, 273: 5997-6000, 1999.01.
102. Toh, S., Wada, M., Uchiumi, T., Inokuchi, A., Makino, Y., Horie, H., Adachi, Y., Sakisaka, S. and Kuwano, M., Genomic structure of the canalicular multispecitic organic anion transporter (cMOAT) gene and mutations in the ATP binding cassette region in Dubin-Johnson syndrome., Am. J. Human Genet., 10.1086/302292, 64, 3, 739-746, 64: 739-746, 1999.01.
103. Ise, T., Nagatani, G., Imamura, T., Kato, K., Takano, H., Nomoto, M., Izumi, H., Ohmori, H., Okamoto, T., Ohga, T., Uchiumi, T., Kuwano, M. and Kohno, K., Transcription factor Y box-binding protein-1 binds preferentially to cisplatin-modified DNA and interacts with proliferating cell nuclear antigen., Cancer Res, 59, 2, 342-346, 59: 342-346, 1999.01.
104. Chen, Z., Kawabe, T., Ono, M., Aoki, S., Sumizawa, T., Furukawa, T., Uchiumi, T., Wada, M., Kuwano, M. and Akiyama, S., Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter., Molec. Pharmacology, 56, 6, 1219-1228, 56: 1219-1228, 1999.01.
105. Kawabe, T., Chen, Z., Wada, M., Uchiumi, T., Ono, M., Akiyama, S. and Kuwano, M., Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter (cMOAT/MRP2)., FEBS Lett., 10.1016/S0014-5793(99)00979-5, 456, 2, 327-331, 456: 327-331, 1999.01.
106. Tanaka,T., Uchiumi,T., Hinoshita,E., Inokuchi,A., Toh,S., Wada,M., Takano,H., Kohno,K., and Kuwano,M., The human multispecific resistance protein2 gene : functional characterization of 5'-flanking region and expression in hepatic cells., Hepatology, 30: 1507-1512, 1999.01.
107. Sibao, K., Takano, H., Nakamura, Y., Okazaku, K., Nagata, N., Izumi, H., Uchiumi, T., Kuwano, M., Kohno, K. and Itoh, H., Enhanced coexpression of YB-1 and DNA topoisomerase IIαgenes in human colorectal carcinomas., Int. J.Cancer, 10.1002/(SICI)1097-0215(19991210)83:6<732::AID-IJC6>3.3.CO;2-R, 83, 6, 732-737, 83: 732-73, 1999.01.
108. Toh,S., Nakamura,T., Ohga, T., Koike,K., Uchiumi,T., Wada,M., Kuwano,M. and Kohno,K., Genomic organization of the human Y-box protein (YB-1) gene., Gene, 10.1016/S0378-1119(97)00570-2, 206, 1, 93-97, 206: 93-97, 1998.01.
109. Wada,M., Toh, S., Taniguchi, K., Uchiumi,T. , Kohno,K., Yoshida, I., Kimura,A., Sakisaka, S., Adachi, Y. and Kuwano,M., Mutation in the canalicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome., Human Molec. Genet., 10.1093/hmg/7.2.203, 7, 2, 203-207, 7: 203-207, 1998.01.
110. Torigoe, K., Harada, T., Kusaba, H., Uchiumi, T., Kohno, K., E.D.Green, S. W.Scherer, L-C.Tsui, D.Schlessinger, Kuwano,M. and Wada, M., Localization of 67 exons on YAC contigs spanning 1.5 megabases around the multidrug resistance gene region of human chromosome 7q21.1., Genomics, 10.1006/geno.1997.5200, 49, 1, 14-22, 48:14-22, 1998.01.
111. Furukawa,M., Uchiumi,T., Nomoto,M., Takano,H., Morimoto,R-I., Naitoh,S., Kuwano,M. and Kohno,K., The role of an inverted CCAAT element in transcriptional activation of the human DNA topoisomeraseIIα gene in response to heat shock., J. Biol. Chem., 10.1074/jbc.273.17.10550, 273, 17, 10550-10555, 273: 10550-10555, 1998.01.
112. Oda,Y., Sakamoto,A., Shinohara,N., Ohga,T., Uchiumi,T., Kohno,K., Tsuneyoshi,M., Kuwano,M. and Iwamoto,Y., Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma., Clin Cancer Res, 4, 9, 2273-2277, 4:2273-2277, 1998.01.
113. Uchiumi, T., Hinoshita, E., Haga, S., Nakamura, T., Tanaka, T., Toh, S., Furukawa, M., Kawabe, T., Wada, M., Kagotani, K., Okumura, K., Kohno, K., Akiyama, S. and Kuwano, M., Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport., Biochem. Biophys. Res. Commun, 10.1006/bbrc.1998.9546, 252, 1, 103-110, 252: 103-110, 1998.01.
114. Uchiumi, T., Longo, D. and Ferris, D, Cell cycle regulation of PLK promoter., J. Bio. Chem, 272,9166-9174, 1997.01.
115. Rie Amamoto, Takeshi Uchiumi, Mikako Yagi, Keisuke Monji, Song, Yoshinao Oda, Shiota M, Akira Yokomizo, Seiji Naito, Dongchon Kang, The Expression of Ubiquitous Mitochondrial Creatine Kinase Is Downregulated as Prostate Cancer Progression, JOURNAL OF CANCER, 10.7150/jca.13207, 7, 1, 50-59.