Hiromi Kumon

Okayama University, Okayama, Okayama, Japan

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Publications (377)686.63 Total impact

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    ABSTRACT: Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) was identified as a gene whose expression is reduced in many human cancers. REIC/Dkk-3 expression is also downregulated in malignant glioma and regulates cell growth through caspase-dependent apoptosis. cRGD (EMD121974), an antagonist of integrins, has demonstrated preclinical efficacy against malignant glioma. In this study, we investigated the antiglioma effect of combination therapy using an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) and cRGD. Quantitative real-time reverse-transcription PCR revealed the reduction of REIC/Dkk-3 mRNA levels in malignant glioma cell lines. The reduction of REIC/Dkk-3 protein expression in malignant glioma cell lines was also confirmed with western blot analysis. After treatment with Ad-REIC and cRGD, the proliferative rate of malignant glioma cells was significantly reduced in a time-dependent manner. In vivo, there was a statistically significant increase in the survival of mice treated with Ad-REIC and cRGD combination therapy compared with Ad-REIC monotherapy. We identified an apoptotic effect following monotherapy with Ad-REIC. Moreover, cRGD augmented the antiglioma efficacy of Ad-REIC. These results may lead to a promising new approach for the treatment of malignant glioma.Gene Therapy advance online publication, 13 November 2014; doi:10.1038/gt.2014.100.
    Gene therapy. 11/2014;
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    ABSTRACT: Through genome wide association analysis and an independent replication study using a total of 1,131 bladder cancer cases and 12,558 non-cancer controls of Japanese populations, we identified a susceptibility locus on chromosome 15q24. SNP rs11543198 was associated with bladder cancer risk with odds ratio (OR) of 1.41 and P value of 4.03 x 10(-9). Subgroup analysis revealed rs11543198 to have a stronger effect in male smokers with OR of 1.66. Imputational analysis in this region suggested CYP1A2, which metabolizes tobacco-derived carcinogen, as a causative candidate gene. We also confirmed the association of previously-reported loci, namely SLC14A1, APOBEC3A, PSCA, and MYC, with bladder cancer. SNP rs8041357, which is in complete linkage disequilibrium (r(2)=1) with rs11543198, was also associated with bladder cancer risk in Europeans (P=0.045 for an additive and P=0.025 for a recessive model), despite much lower MAF in Europeans (3.7%) compared to the Japanese (22.2%). Our finding implies the crucial roles of genetic variations on the chemically-associated development of bladder cancer.
    Human Molecular Genetics 10/2014; · 7.69 Impact Factor
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    ABSTRACT: The Wnt signaling pathway plays a crucial role in human cancer development, and axis inhibition protein 2 (Axin2) is a master scaffold protein involved in Wnt signaling. Axin2 negatively regulates Wnt signaling and acts as a tumor suppressor protein. The present study evaluated the association between the Axin2 single nucleotide polymorphism (SNP) rs2240308 [guanine (G)/adenine (A)] and the incidence of prostate cancer. In total, 103 patients with prostate cancer and 100 cancer-free control males were included in this case-control study, and were genotyped using the genomic DNA extracted from peripheral blood samples. The results revealed a higher incidence of prostate cancer in the subjects with the homozygous GG genotype and a reduced cancer incidence in the patients with the GA genotype of the rs2240308 SNP (G/A) in the Axin2 gene. The adjusted odds ratio for carriers with the GA genotype was 0.377 (95% CI, 0.206-0.688; P=0.001) and that for the AA genotype was 0.830 (95% CI, 0.309-2.232; P=0.712) compared with the GG genotype. Therefore, the GA genotype was found to exhibit a protective effect that decreased the risk of prostate cancer. To the best of our knowledge, this is the first study to demonstrate the significant association between this SNP (rs2240308, G/A) and the risk of prostate cancer. This association indicates the possibility that the variations in the Axin2 gene in this position may play a significant role in promoting the development of cancer in the prostate. We believe that the Axin2 SNP (rs2240308) could be a useful biomarker for the predisposition and early diagnosis of the disease.
    Oncology letters 08/2014; 8(2):789-794. · 0.24 Impact Factor
  • Yasuyuki Fujii, Tyuji Hoshino, Hiromi Kumon
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    ABSTRACT: Dickkopf (DKK) proteins interact with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to modulate WNT signaling. The interaction is mediated by a cysteine-rich domain (C2) in the DKK protein and beta-propeller domains (PD) of LRP5/6. However, the third member of the DKK family (DKK3) does not bind to LRP5/6. To determine why DKK3 does not bind to the receptor domains, we performed a molecular modeling simulation study including homology modeling, protein-protein docking and molecular dynamics (MD). The computed affinities (ΔGbinding) between the C2 and PD models were consistent with the previously reported experimental results. The C2 model of DKK3 showed the lowest affinity for PD models. Multiple sequence alignment of C2 domains revealed that the DKK3 genes have a unique 7-amino-acid insertion (L249-E255 in human DKK3) and P258 in a finger loop 1 (FL1). Interestingly, the insertion sequence is evolutionally conserved. MD simulations of high-affinity complex models of C2 and PD showed that FL1 directly interacts with the PD models and stabilizes the complex models. We also built a 7-amino-acid-deletion/P258G mutant model of DKK3C2 and estimated its affinities for the PD models. The affinity for human LRP5PD2 was increased by the substitution (ΔGbinding=-48.9kcal/mol) and the affinity was compatible with that of high-affinity ligands. The results suggested that the lack of affinity between human DKK3 and human LRP5/6 results from: i) insertion of the 7 amino acids, and ii) P258 in human DKK3. The sequence differences thus suggest an explanation for this unique property of DKK3.
    Acta medica Okayama 04/2014; 68(2):63-78. · 0.65 Impact Factor
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    ABSTRACT: We conducted a study on molecular epidemiology and clinical implications of metallo-beta-lactamase (MBL)-producing Pseudomonas aeruginosa isolated from urine. Over a 10-year period from 2001 through 2010, a total of 92 MBL-producing P. aeruginosa urine isolates were collected from patients (one isolate per patient) who were admitted to 5 hospitals in Okayama Prefecture, Japan. When cross-infection was suspected in the hospital, pulsed-field gel electrophoresis was performed. In the resulting dendrogram of 79 MBL-producing P. aeruginosa urine isolates, no identical isolates and 7 pairs of isolates with >80% similarity were found. The biofilm-forming capabilities of 92 MBL-producing P. aeruginosa urine isolates were significantly greater than those of 92 non-MBL-producing urine isolates in a medium of modified artificial urine. The imipenem resistance transferred in 16 of 18 isolates tested, and these frequencies were in the range of 10-3 to 10-9. All of 18 isolates tested belonged to internationally spread sequence type 235 and had 3 gene cassettes of antimicrobial resistance genes in the class 1 integron. The strong biofilm-forming capabilities of MBL-producing P. aeruginosa urine isolates could be seriously implicated in nosocomial infections. To prevent spread of the organism and transferable genes, effective strategies to inhibit biofilm formation in medical settings are needed.
    Acta medica Okayama 04/2014; 68(2):89-99. · 0.65 Impact Factor
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    ABSTRACT: The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) is the standard questionnaire that determines the degree of symptoms and efficacy of treatment in patients with chronic prostatitis/chronic pelvic pain syndrome. Because there was no officially approved Japanese version of the NIH-CPSI, the Japanese Urological Association (JUA) formed a committee to develop one chaired by Dr. Masayuki Takeda, who also chairs the special field of voiding function and neurourology in the JUA. Consequently, the committee produced a Japanese version, referring to previous proposals and the Japanese version of the International Prostate Symptom Score. The committee strongly expects that the Japanese version of the NIH-CPSI will be taken full advantage of in future clinical research.
    Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology. 04/2014; 105(2):62-5.
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    ABSTRACT: Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3 is a tumor suppressor and therapeutic gene and has been studied with respect to the application of cancer gene therapy. Our previous studies demonstrated that the intratumoral injection of an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC) suppresses tumor growth in mouse models of prostate, breast and testicular cancer and malignant mesothelioma. The mechanisms underlying these antitumor therapeutic effects have only been clarified recently. It has been demonstrated that Ad-REIC treatment inhibits cancer progression via the upregulation of systemic anticancer immunity. Under experimental conditions, autologous cancer vaccination via cancer-specific apoptosis and anticancer immune activation is a possible therapeutic mechanism. The robust anticancer effects observed in previous preclinical studies support the clinical utility of Ad-REIC. At present, a phase I-IIa study of Ad-REIC gene therapy in prostate cancer patients is ongoing. The current study reviews the observations of previous fundamental studies and summarizes the anticancer mechanisms of intratumoral Ad-REIC treatment in terms of cancer vaccination.
    Oncology letters 03/2014; 7(3):595-601. · 0.24 Impact Factor
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    ABSTRACT: For expression of genes in mammalian cells, various vectors have been developed using promoters including CMV, EF-1α, and CAG promoters and have been widely used. However, such expression vectors sometimes fail to attain sufficient expression levels depending on the nature of cargo genes and/or on host cell types. In the present study, we aimed to develop a potent promoter system that enables high expression levels of cargo genes ubiquitously in many different cell types. We found that insertion of an additional promoter downstream of a cargo gene greatly enhanced the expression levels. Among the constructs we tested, C-TSC cassette (C: CMV-RU5' located upstream; TSC: another promoter unit composed of triple tandem promoters, hTERT, SV40, and CMV, located downstream of the cDNA plus a polyadenylation signal) had the most potent capability, showing far higher efficiency than that of potent conventional vector systems. The results indicate that the new expression system is useful for production of recombinant proteins in mammalian cells and for application as a gene therapeutic measure.
    Molecular Biotechnology 02/2014; · 2.26 Impact Factor
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    ABSTRACT: The purpose of this study was to compare the positive surgical margin (PSM) rates of 2 techniques of robot-assisted radical prostatectomy (RARP) for pT2 (localized) prostate cancer. A retrospective analysis was conducted of 361 RARP cases, performed from May 2005 to September 2008 by a single surgeon (KHR) at our institution (Yonsei University College of Medicine). In the conventional technique, the bladder neck was transected first. In the modified ultradissection, the lateral border of the bladder neck was dissected and then the bladder neck was transected while the detrusor muscle of the bladder was well visualized. Perioperative characteristics and outcomes and PSM rates were analyzed retrospectively for pT2 patients (n=217), focusing on a comparison of those undergoing conventional (n=113) and modified ultradissection (n=104) techniques. There was no difference between the conventional and modified ultradissection group in mean age, BMI, PSA, prostate volume, biopsy Gleason score, and D'Amico prognostic criteria distributions. The mean operative time was shorter (p<0.001) and the estimated blood loss was less (p<0.01) in the modified ultradissection group. The PSM rate for the bladder neck was significantly reduced by modified ultradissection, from 6.2% to 0% (p<0.05). In conclusion, modified ultradissection reduces the PSM rate for the bladder neck.
    Acta medica Okayama 02/2014; 68(1):35-41. · 0.65 Impact Factor
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    ABSTRACT: We report 3 patients with the rare complication of an indwelling urethral catheter misdirected into the ureter. This is the largest series to date. Patients were referred to us for a variety of reasons following exchange of their chronic indwelling urinary catheters. CT in all cases demonstrated the urinary catheters residing in the left ureter. The ages of the patients were 37, 67 and 81 years old. All patients suffered from neurogenic bladder. Two patients were female, one was male, and 2 of the 3 had a sensory disorder inhibiting their pain response. The catheters were replaced with open-end Foley catheters. Extensive follow-up CT scans were obtained in one case, demonstrating improvement of hydronephrosis and no evidence of ureteral stenosis. Cystoscopy in this patient demonstrated normally positioned and functioning ureteral orifices. Although the placement of an indwelling urethral catheter is a comparatively safe procedure, one must keep in mind that this complication can occur, particularly in female patients with neurogenic bladder. CT without contrast is a noninvasive, definitive diagnostic tool.
    Acta medica Okayama 02/2014; 68(1):47-51. · 0.65 Impact Factor
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    ABSTRACT: REIC/Dkk-3 is down-regulated in a broad range of human cancer cells and is considered to function as a tumor suppressor. We previously reported that REIC/Dkk-3-expressing adenovirus vector (Ad-REIC) induced endoplasmic reticulum (ER) stress and cancer-specific apoptosis in human prostate cancer. In this study, we examined the therapeutic impact of Ad-REIC on non-small cell lung cancer (NSCLC). We examined the anti-tumor effect of Ad-REIC on 25 NSCLC cell lines in vitro and A549 cells in vivo. Two of these cell lines were artificially established as EGFR-tyrosine kinase inhibitor (TKI) resistant sublines. Ad-REIC-treatment inhibited the cell viability by 40% or more in 13 (52%) of the 25 cell lines at multiplicity of infection (MOI) of 20 (20 MOI). These cell lines were regarded as being highly sensitive cells. The cell viability of a non-malignant immortalized cell line, OUMS-24, was not inhibited at 200 MOI of Ad-REIC. The effects of Ad-REIC on EGFR-TKI resistant sublines were equivalent to those in the parental cell lines. Here, we demonstrated that Ad-REIC treatment activated c-Jun N-terminal kinase (JNK) in NSCLC cell lines, indicating the induction of ER stress with GRP78/BiP (GRP78) up-regulation and resulting in apoptosis. A single intratumoral injection of Ad-REIC significantly inhibited the tumorigenic growth of A549 cells in vivo. As predictive factors of sensitivity for Ad-REIC treatment in NSCLC, we examined the expression status of GRP78 and coxsackievirus and adenovirus receptor (CAR). We found that the combination of the GRP78 and CAR expressional statuses may be used as a predictive factor for Ad-REIC sensitivity in NSCLC cells. Ad-REIC induced JNK activation and subsequent apoptosis in NSCLC cells. Our study indicated that Ad-REIC has therapeutic potential against NSCLC and that the expression statuses of GRP78 and CAR may predict a potential therapeutic benefit of Ad-REIC.
    PLoS ONE 01/2014; 9(2):e87900. · 3.53 Impact Factor
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    ABSTRACT: Gene expression systems with various promoters, including the cytomegalovirus (CMV) promoter, have been developed to increase the gene expression in a variety of normal and cancer cells. In particular, in the clinical trials of cancer gene therapy, a more efficient and robust gene expression system is required to achieve sufficient therapeutic outcomes. By inserting the triple translational enhancer sequences of human telomerase reverse transcriptase (hTERT), Simian virus 40 (SV40) and CMV downstream of the sequence of the BGH polyA, we were able to develop a novel gene expression system that significantly enhances the expression of the genes of interest. We termed this novel gene expression cassette the super gene expression (SGE) system, and herein verify the utility of the SGE cassette for a replication-deficient adenoviral vector. We newly developed an adenoviral vector expressing the tumor suppressor, reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), based on the CMV promoter-driven SGE system (Ad-SGE-REIC) and compared the therapeutic utility of Ad-SGE-REIC with that of the conventional adenoviral vectors (Ad-CMV-REIC or Ad-CAG-REIC). The results demonstrated that the CMV promoter-SGE system allows for more potent gene expression, and that the Ad-SGE-REIC is superior to conventional adenoviral systems in terms of the REIC protein expression and therapeutic effects. Since the SGE cassette can be applied for the expression of various therapeutic genes using various vector systems, we believe that this novel system will become an innovative tool in the field of gene expression and gene therapy.
    Oncology Reports 12/2013; · 2.30 Impact Factor
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    ABSTRACT: The reduced expression in immortalized cells REIC/Dkk-3 gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/Dkk-3 gene (Ad-REIC) induces apoptosis. In the current study, we examined the effects of REIC/Dkk-3 gene therapy in pancreatic cancer. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines (ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT-2, KLM1 and T3M4) and pancreatic cancer tissues. The Ad-REIC agent was used to investigate the apoptotic effect in vitro and anti-tumor effects in vivo. We also assessed the therapeutic effects of Ad-REIC therapy with gemcitabine. The REIC/Dkk-3 expression was lost in the pancreatic cancer cell lines, and decreased in pancreatic cancer tissues. Ad-REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad-REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The anti-tumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mTOR signaling. Ad-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.
    Journal of Gastroenterology and Hepatology 12/2013; · 3.33 Impact Factor
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    ABSTRACT: We retrospectively investigated the incidence of genitourinary tract infection in 5895 patients who underwent transrectal and/or transperineal prostate biopsy procedure between January and December 2011 at 46 institutions belonging to Japanese Research Group for Urinary Tract Infection (JRGU). The total rate of genitourinary tract infection after prostate biopsy was 0.76%, while that following transrectal procedure was 0.83% and following transperineal procedure was 0.57%, which were not significantly different. In contrast, febrile infection associated with a fever (≥38 °C) occurred significantly more frequently after transrectal (0.71%) than transperineal (0.16%) approach (P = 0.04). Notably, in infectious cases, Escherichia coli was most frequently isolated. Of the 9 E. coli strains isolated by urine culture, 6 (66.7%) produced extended spectrum β-lactamase (ESBL) and 7 (77.8%) showed levofloxacin resistance. Similarly, of 6 E. coli strains isolated by blood culture, 4 (66.7%) produced ESBL and 6 (100%) showed levofloxacin resistance. When the efficacy of antimicrobial prophylaxis (AMP) with levofloxacin for the patients undergoing transrectal or transperineal biopsy was compared between a single dose (500 mg) and that given for 2 or more days, no significant difference was observed for the rate of infection (transrectal: 0.82% vs. 1.04%, p = 0.94; transperineal: 0.30% vs. 0.46%, p = 0.68). Although a single dose of levofloxacin for AMP is sufficient to prevent genitourinary infection after transrectal or transperineal prostate biopsy, and recommended in this era of increased multi-drug resistant pathogens, the increase in fluoroquinolone-resistant E. coli and ESBL-producing E. coli has emerged as a profound problem for surveillance.
    Journal of Infection and Chemotherapy 12/2013; · 1.55 Impact Factor
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    ABSTRACT: Gender identity disorder (GID) results from a disagreement between a person's biological sex and the gender to which he or she identifies. With respect to the treatment of female to male GID, testosterone replacement therapy (TRT) is available. The uric acid (UA) level can be influenced by testosterone; however, the early effects and dose-dependency of TRT on the serum UA concentration have not been evaluated in this population. We herein conducted a dose-response analysis of TRT in 160 patients with female to male GID. The TRT consisted of three treatment groups who received intramuscular injections of testosterone enanthate: 125 mg every two weeks, 250 mg every three weeks and 250 mg every two weeks. Consequently, serum UA elevation was observed after three months of TRT and there was a tendency toward testosterone dose-dependency. The onset of hyperuricemia was more prevalent in the group who received the higher dose. We also demonstrated a positive correlation between increased levels of serum UA and serum creatinine. Since the level of serum creatinine represents an individual's muscle volume and the muscle is a major source of purine, which induces UA upregulation, the serum UA elevation observed during TRT is at least partially attributed to an increase in muscle mass. This is the first study showing an association between serum UA elevation and a TRT-induced increase in muscle mass. The current study provides important information regarding TRT for the follow-up and management of the serum UA levels in GID patients.
    Endocrine Journal 09/2013; · 2.23 Impact Factor
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    ABSTRACT: The term nanobacteria, sometimes referred to as nanobacteria-like particles (NLPs), is presently recognized as a misnomer for inert calcified nanoparticles. However, misinterpretation of its propagation as a living organism still continues. Ultrastructural and elemental analyses, combining immuno-electron microscopy with an original NLP isolate (P-17) derived from urinary stones, and an IgM monoclonal antibody (CL-15) raised against P-17 have now revealed that, oxidized lipids with acidified functional groups were key elements in NLP propagation. Lamellar structures composed of acidic/oxidized lipids provided structural scaffolds for carbonate apatite crystals. During in vitro culture, lipid peroxidation induced by ■-irradiation of FBS was a major cause of accelerated NLP propagation. In pathological tissue samples from hyperlipidemic atherosclerosis-prone mice, CL-15 co-localized with fatty plaques, macrophage infiltrates and osteocalcin staining of aortic valve lesions. These observations indicate that naturally occurring NLP composed of mineralo-oxidized lipids complexes are generated as byproducts rather than etiological agents of chronic inflammation. (150 words).
    Nanomedicine: nanotechnology, biology, and medicine 09/2013; · 6.93 Impact Factor
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    ABSTRACT: Cluster of differentiation (CD)24 was originally described as a B lymphocyte marker and has recently received considerable attention in cancer research as its overexpression has been observed in several types of carcinoma. The CD24 molecule is a glycosyl-phosphatidylinositol-linked cell surface protein that appears to be associated with aggressive cancers involving invasion and metastasis. However, the expression of CD24 in human bladder cancer and its clinical significance remains largely unknown and no association has been reported between CD24 overexpression and human bladder tumor recurrence. In the present study, the CD24 expression in cancer tissues obtained during transurethral surgery and the subsequent intra-bladder tumor recurrence following surgery were assessed. Immunohistochemical staining was performed and the intensity of CD24 staining was semi-quantitatively evaluated. CD24 expression was observed more frequently in high-grade bladder tumors (G2-G3) than low-grade tumors (G1). Positive CD24 expression was significantly associated with intra-bladder tumor recurrence following surgery and increased staining intensity was also correlated with recurrence. The positive association between CD24 expression and tumor recurrence was observed in each tumor category (stages Ta and T1, low and high grade). The results demonstrated that CD24 expression is significantly associated with bladder tumor recurrence. To the best of our knowledge, this is the first study to reveal the significance of CD24 as a predictor of bladder cancer recurrence. These insights may lead to future therapeutic strategies targeting CD24 to prevent the dissemination of bladder cancer cells and tumor recurrence.
    Oncology letters 07/2013; 6(1):96-100. · 0.24 Impact Factor
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    ABSTRACT: To survey the present condition of administration method of the antimicrobial prophylactic (AMP) agents for the perioperative infection in Japan on revising "The Japanese guidelines for prevention of perioperative infections in urologic field (2006)". With the approval of the Japanese Urological Association (JUA) in 2011, all of the principal urological training institutions certified by JUA (n = 836) were encouraged to participate to survey their adherence to the JUA guidelines (published in 2006) for AMP to prevent perioperative infection in urological field, and 446 (53.3%) institutions responded to the questionnaire. The rates of following the JUA guidelines of, "completely", "mainly", "not too much", and "not at all" were 6.5%, 69.7%, 22.0% and 1.6%, respectively. The guidelines were followed for open clean operations in 48.5%, open clean-contaminated operations in 66.4%, open contaminated operations in 61.8%, laparoscopic clean operations in 54.1%, laparoscopic clean-contaminated operations in 61.2%, transurethral resection of bladder tumor in 71.5%, transurethral resection of prostate in 68.9%, ureteroscopy and transurethral ureterolithotomy in 68.2%, prostate biopsy in 43.2%, and cystoscopy were in 42.2%, respectively. However, in terms of duration of AMP administration, the longer duration than those recommended by the guidelines were observed for clean surgery, transurethral resection of bladder tumor, ureteroscopy and transurethral ureterolithotomy, prostate biopsy, and cystoscopy. In terms of kinds of AMP, the guidelines were almostly followed in all operative procedures. However, the duration of AMP administration were longer than those recommended by the guidelines. On revision of "Japanese guidelines for prevention of perioperative infections in urologic field (2006)", these data would be taken into consideration to avoid dissociation between the guidelines and the practical side in the urologists.
    Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 07/2013; 104(4):579-88.
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    ABSTRACT: Neisseria gonorrhoeae is one of the most important pathogens causing sexually transmitted infection, and strains that are resistant to several antimicrobials are increasing. To investigate the trends of antimicrobial susceptibility among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance committee conducted the first nationwide surveillance. The urethral discharge was collected from male patients with urethritis at 51 medical facilities from April 2009 to October 2010. Of the 156 specimens, 83 N. gonorrhoeae strains were tested for susceptibility to 18 antimicrobial agents. The prevalence of β-lactamase-producing strains and chromosomally mediated resistant strains were 7.2 % and 16.5 %, respectively. None of the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) of ceftriaxone for 7 strains (8.4 %) was 0.125 μg/ml. One strain was resistant to cefixime (MIC 0.5 μg/ml). The MICs of fluoroquinolones, such as ciprofloxacin, levofloxacin, and tosufloxacin, showed a bimodal distribution. The MIC of sitafloxacin was lower than those of the three fluoroquinolones listed here, and it was found that the antimicrobial activity of sitafloxacin was stronger than that of the fluoroquinolones. The MIC of azithromycin in 2 strains was 2 μg/ml, but no high-level resistance to macrolides was detected.
    Journal of Infection and Chemotherapy 06/2013; · 1.55 Impact Factor
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    ABSTRACT: REIC/Dkk-3, a member of the human Dickkopf (Dkk) family, plays a role as a suppressor of growth in several human cancers. In this study, the tumour suppression function of canine REIC/Dkk-3 was investigated. The full-length open reading frame of the canine REIC/Dkk-3 homologue was cloned and the tissue distribution of REIC/Dkk-3 mRNA was determined, along with the subcellular localisation of the REIC/Dkk-3 protein in canine cancer cell lines. Expression of REIC/Dkk-3 was lower in mammary gland tumours and in canine mammary carcinoma cell lines than in normal mammary gland tissue. Overexpression of REIC/Dkk-3 induced apoptosis in canine mammary carcinoma cell lines. These results show that expression of REIC/Dkk-3 is downregulated in canine mammary tumours and that one of the functions of this gene is induction of apoptosis.
    The Veterinary Journal 05/2013; · 2.42 Impact Factor

Publication Stats

3k Citations
686.63 Total Impact Points


  • 1987–2014
    • Okayama University
      • • Department of Urology
      • • Department of Obstetrics and Gynecology
      • • Department of Immunology
      Okayama, Okayama, Japan
  • 2013
    • Southern Medical University
      • Department of Urology
      Guangzhou, Guangdong Sheng, China
    • Hyogo College of Medicine
      • Department of Urology
      Nishinomiya, Hyogo-ken, Japan
  • 2007–2012
    • Kawasaki Medical University
      • Department of Urology
      Kurasiki, Okayama, Japan
    • Osaka University
      • Department of Surgery
      Ōsaka-shi, Osaka-fu, Japan
  • 2011
    • Minami Okayama Medical Center
      Okayama, Okayama, Japan
  • 2009
    • Hiroshima University
      • Department of Clinical Pharmacotherapy
      Hiroshima-shi, Hiroshima-ken, Japan
  • 2008
    • RIKEN
      Вако, Saitama, Japan
  • 1998–2007
    • University of Pittsburgh
      • • Department of Urology
      • • School of Medicine
      Pittsburgh, PA, United States
  • 2006
    • Kyoto University
      • Department of Urology
      Kyoto, Kyoto-fu, Japan
    • National Institute of Infectious Diseases, Tokyo
      Edo, Tōkyō, Japan
  • 2005
    • Okayama Rosai Hospital
      Okayama, Okayama, Japan
    • Singapore General Hospital
      • Department of Urology
      Singapore, Singapore
  • 2003
    • Sapporo Medical University
      • Division of Urology
      Sapporo, Hokkaidō, Japan
    • Hiroshima City Hospital
      Hirosima, Hiroshima, Japan
  • 2002
    • New York Medical College
      New York City, New York, United States
    • The University of Tokyo
      • Department of Applied Biological Chemistry
      Tokyo, Tokyo-to, Japan
  • 2001
    • Tan Tock Seng Hospital
      Tumasik, Singapore
  • 2000
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Wayne State University
      • Division of Infectious Diseases
      Detroit, MI, United States