研究者紹介システム

白川 利朗
シラカワ トシロウ
大学院科学技術イノベーション研究科 科学技術イノベーション専攻
教授
医学
Last Updated :2021/07/26

研究者情報

所属

  • 【主配置】

    大学院科学技術イノベーション研究科 科学技術イノベーション専攻
  • 【配置】

    医学部 保健学科, 大学院保健学研究科 保健学専攻

学位

  • 博士(医学), 神戸大学

授業科目

ジャンル

  • 医療・健康 / がん治療
  • 医療・健康 / 臨床医学

コメントテーマ

  • 遺伝子治療
  • ワクチン
  • 腸チフス
  • 前立腺がん

研究活動

研究キーワード

  • 腫瘍免疫
  • 前立腺
  • ワクチン
  • 薬剤耐性菌
  • 泌尿器癌
  • 経口ワクチン
  • 遺伝子治療

研究分野

  • ライフサイエンス / 腫瘍診断、治療学

受賞

  • 2017年06月 日本ビフィズス菌センター/腸内細菌学会, 第21回腸内細菌学会 最優秀発表賞, Wilms’ tumor 1タンパク発現ビフィズス菌を用いた 経口癌ワクチンの抗腫瘍免疫誘導効果に関する検討

    辰巳 真帆, 北川 孝一, 五ノ井 玲菜, 斉藤 大樹, 橋井 佳子, 片山 高嶺, 白川 利朗

    国内学会・会議・シンポジウム等の賞

  • 2008年06月 日本遺伝子治療学会, 第13回JSGT学会賞, 学会発表演題

    白川 利朗

  • 2006年08月 (財)クリタ水・環境科学振興財団, クリタ水・環境科学振興財団 研究助成金, 命にかかわる下痢性感染症予防のための水質汚染モニタリング法の開発

    白川利朗

  • 2004年 前立腺研究財団, 前立腺研究財団優秀研究課題受賞, 腫瘍特異的増殖型アデノウイルスおよびキャリアー細胞を用いた前立腺癌に対する遺伝子治療法の開発

    白川 利朗

論文

  • Young-Min Yang, Kayo Osawa, Koichi Kitagawa, Samiko Hosoya, Reo Onishi, Aya Ishii, Toshiro Shirakawa, Itaru Hirai, Kuntaman Kuntaman, Hiroshi Tanimoto, Katsumi Shigemura, Masato Fujisawa

    OBJECTIVES: To compare antibiotic susceptibilities between chromosomal and plasmid blaCTX-M-15 locations in urinary tract infection-causing extended-spectrum β-lactamases-producing Escherichia coli blaCTX-M-15 isolated in Indonesia. METHODS: A total of 84 strains identified as extended-spectrum β-lactamases-producing E. coli were isolated from patients with urinary tract infection in Indonesia in 2015. Antimicrobial susceptibility tests were performed on these strains using 18 antibiotics, and extended-spectrum β-lactamase bla genes were detected by polymerase chain reaction. Gene localization of blaCTX-M-15 -positive strains was confirmed by Southern blot hybridization, and epidemiological typing was conducted using multilocus sequence typing. RESULTS: Of 54 strains harboring the blaCTX-M-15 gene, 27 showed localization on chromosome, 20 on plasmid, and seven on chromosome and plasmid. Most multilocus sequence typing sequence types of the 27 strains with chromosomal blaCTX-M-15 were ST405 (25.9%) and ST131 (22.2%) strains, whereas the 20 strains with plasmid-blaCTX-M-15 were mostly ST410 (55.0%). CONCLUSIONS: Extended-spectrum β-lactamases-producing E. coli blaCTX-M-15 with plasmid genes show significantly higher resistant rates against piperacillin-tazobactam but lower resistant rates against chloramphenicol compared to chromosomal strains in Indonesian patients with urinary tract infection. Mechanistic investigations will be necessary to advance our knowledge of antimicrobial resistance in urinary tract infection.

    2021年06月, International journal of urology : official journal of the Japanese Urological Association, 28 (6), 623 - 628, 英語, 国際誌

    研究論文(学術雑誌)

  • Aya Ishii, Katsumi Shigemura, Koichi Kitagawa, Mizuki Harada, Yuki Kan, Fuka Hayashi, Kayo Osawa, K Kuntaman, Toshiro Shirakawa, Masato Fujisawa

    Urinary tract infection (UTI) by antibiotic-resistant strains has become increasingly problematic, with trends that differ from country to country. This study examined cross-resistance and the mechanisms of cephalosporin resistance in UTI-causative bacteria isolated in Indonesia. Antibiotic susceptibility tests based on Clinical Laboratory Standards Institute (CLSI) standards were done for UTI-causative strains (n = 50) isolated from patients in Indonesia in 2015-2016 and showed resistance against the third-generation cephalosporin. Mechanistic studies were carried out to confirm the presence of extended-spectrum β-lactamase (ESBL) genes, carbapenemase-related genes, the fosA3 gene related to fosfomycin resistance, and mutations of quinolone-resistance-related genes. Isolated UTI-causative bacteria included Escherichia coli (64.0%), Pseudomonas aeruginosa (16.0%), Klebsiella pneumoniae (10.0%), and others (10.0%). These strains showed 96.0% susceptibility to amikacin, 76.0% to fosfomycin, 90.0% to imipenem, 28.0% to levofloxacin, 92.0% to meropenem, and 74.0% to tazobactam/piperacillin. ESBL was produced by 68.0% of these strains. Mechanistic studies found no strains with carbapenemase genes but 6.0% of strains had the fosA3 gene. Seventy-two % of the strains had mutations in the gyrA gene and 74.0% in the parC gene. Most E. coli strains (87.5%) had Ser-83 → Leu and Asp-87 → Asn in gyrA and 93.8% of E. coli had Ser-80 → Ile in parC. There were significant correlations among mutations in gyrA and parC, and fosA3 gene detection (P < 0.05), respectively. To our knowledge, this is the first mechanistic study of antibiotic-cross-resistant UTI-causative bacteria in Indonesia. Further studies with a longer period of observation are necessary, especially for changes in carbapenem resistance without carbapenemase-related genes.

    2021年05月, Current microbiology, 78 (5), 1771 - 1777, 英語, 国際誌

    研究論文(学術雑誌)

  • Saya Yamasaki, Katsumi Shigemura, Kayo Osawa, Koichi Kitagawa, Aya Ishii, K Kuntaman, Toshiro Shirakawa, Takayuki Miyara, Masato Fujisawa

    INTRODUCTION: Extended spectrum beta-lactamase (ESBL)-producing Klebsiellapneumoniae is a serious concern for nosocomial infection and the emergence rate in Indonesia is higher than that in developed countries. The purpose of this study was to investigate the genetic characteristics of ESBL-producing K. pneumoniae isolated from UTI patients in Indonesia. MATERIALS AND METHODS: We collected K. pneumoniae resistant to ceftazidime or cefotaxime isolated from UTI patients in Dr. Soetomo's Academic Hospital in Surabaya, Indonesia in 2015. Ninety-four strains were identified as ESBL-producing bacteria by confirmation tests. The isolates were investigated by antimicrobial susceptibility testing with 20 drugs and ESBL gene detection, plasmid replicon typing and virulence genes as hypermucoviscous (HMV) strains were tested by the string test. RESULTS: High rates of resistance to ciprofloxacin (86.2%), tetracycline (80.9%) and nalidixic acid (78.7%) were observed. CTX-M-15 was the most common ESBL gene (89.4%), 33 of which also carried SHV-type ESBL. IncF was the most prevalent plasmid replicon typing (47.6%). Sixteen (17.0%) strains were judged as HMV, all of which had rmpA and more than half of which had fimH, uge, and wab. IncL/M was the most common replicon plasmid in the HMV strains, and the difference in the positive rate was statistically significant (p = 0.0024). CONCLUSION: This study showed the high prevalence of multiple-drug resistant and predominately CTX-M-15-positive ESBL-producing K. pneumoniae in Indonesia. There was a correlation between IncL/M and the HMV phenotype in this study. As such hypervirulent strains continue to emerge, studying their dissemination with resistance determinants is an urgent priority.

    2021年01月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 27 (1), 55 - 61, 英語, 国際誌

    研究論文(学術雑誌)

  • Naoto Kunimura, Koichi Kitagawa, Ryota Sako, Keita Narikiyo, Shoko Tominaga, Diosdado S Bautista, Wei Xu, Masato Fujisawa, Toshiro Shirakawa

    In this study we undertook a novel combination therapy using rAd-p53 in situ gene therapy and immunotherapy with immune checkpoint inhibitor (ICI) anti-PD-1 antibody for urogenital cancers. Three mouse syngeneic tumor cell lines, TRAMP-C2 (prostate cancer derived from C57BL/6 mice), MBT-2 (bladder cancer derived from C3H mice) and Renca (kidney cancer derived from BALB/c mice) were used in this study. The highest coxsackie and adenovirus receptor (CAR) mRNA expression was observed in TRAMP-C2 cells, followed by Renca and then MBT-2 cells. Consistent with the CAR expressions, rAd-p53 at 160 multiplicity of infection (MOI) significantly inhibited the cell proliferation of TRAMP-C2 and Renca cells, but not MBT-2 cells. In in vivo experiments, the combination of intratumoral injections of rAd-p53 (1 × 109 plaque-forming units) every other day and intraperitoneal injections of anti-mouse PD-1 antibody (200 μg) twice a week suppressed tumor growth and prolonged survival compared to rAd-p53 or anti-PD-1 antibody monotherapy in both the TRAMP-C2 and Renca models. Our results encourage the clinical development of combination therapy comprised of in situ gene therapy with rAd-p53 and immunotherapy with an ICI anti-PD-1 antibody for urogenital cancers.

    2020年10月15日, Scientific reports, 10 (1), 17464 - 17464, 英語, 国際誌

    研究論文(学術雑誌)

  • Noriaki Maeshige, Koichi Kitagawa, Saya Yamasaki, Aya Ishii, Toshiro Shirakawa, Yong-Ming Yang, Shian-Ying Sung, Kuan-Chou Chen, Zhi-Min Yuan, Katsumi Shigemura, Masato Fujisawa

    BACKGROUND: Focal therapies for prostate cancer (PC) can reduce adverse events and do not lead to androgen-independent progression. Ultrasound could be used for cancer treatments if the repetition frequency is fitted to the purpose. We investigated the possible therapeutic effect of ultrasound irradiation on PC cells. MATERIALS AND METHODS: We irradiated two PC cell lines, androgen-dependent LNCaP and -independent PC-3 with ultrasound (3.0 W/cm2 , 3 MHz, irradiation time rate: 20%) for 2 minutes for 1 day or 3 consecutive days at a repetition frequency of 1, 10, or 100 Hz in vitro. Cell proliferation and apoptosis were determined after irradiation. RESULTS: Cell proliferation of PC-3 was significantly inhibited after 1 day (P < .0001) and 3 days (P < .0001) of 10 Hz ultrasound irradiation, and that of LNCaP after 1 day (P < .0001) and 3 days (P < .0001) of irradiation. LNCaP was more sensitive to ultrasound at both lower and higher cell density but PC-3 was only sensitive at a lower cell density (P < .01). Irradiation with 10 Hz ultrasound-induced significantly more PC-3 apoptotic cells than control (1 day, P = .0137; 3 days, P = .0386) rather than irradiation with 1 Hz. Apoptosis via caspase-3 was induced at 10 Hz in 1-day (P < .05) irradiation in both cell lines. CONCLUSIONS: Ultrasound irradiation with even 1 day of 10 Hz significantly inhibited cell proliferation in both LNCaP and PC-3, especially by the remarkable induction of apoptosis in vitro. Our study indicated that ultrasound irradiation can be a therapeutic option for PC and further studies in vivo will be undertaken.

    2020年09月, The Prostate, 80 (12), 986 - 992, 英語, 国際誌

    研究論文(学術雑誌)

  • Wahyu Setyarini, Dadik Raharjo, Radita Yuniar Arizandy, Zakaria Pamoengkas, Subijanto Marto Sudarmo, Alpha Fardah Athiyyah, Toshiro Shirakawa

    Enteroaggregative haemorrhagic Escherichia coli (E. Coli, EAHEC) has been identified as the agent responsible for one of the largest outbreaks of gastroenteritis and Haemolytic-uremic syndrome (HUS) that is transmitted through food in Germany in 2011. The hypervirulent pathotype has a unique combination of two pathogens namely enterohemorrhagic E.coli strain (EHEC) which produces shiga/verotoxin and enteroaggregative E.coli toxins (EAEC) which produces toxins similar to ST and hemolysin. The toxin produced by the EAHEC strain is a hybrid pathotype that combines the virulence potential of the EAEC and EHEC strains that will damage the microcirculation, cause vasculitis and other toxic effects. The purpose of this study was to determine the percentage of samples infected with enteroaggregative hemorrhagic E. coli bacteria (EAHEC) in pediatric diarrhea patients at DR. Soetomo Hospital, Surabaya, Indonesia, 2015. This study used PCR (Polymerase Chain Reaction) method to detect enteroaggregative E. coli strains (CVD432 and aaic genes) and enterohemorrhagic E.coli (eae gene).The results showed that 33 out of 40 (82,5%) stool samples examined were detected enteroaggregative E. coli (EAEC), 4 out of 40 (10%) enterohemorrhagic E. coli (EHEC) and 3 out of 40 (7,5%) enteroaggregative haemorrhagic E. coli bacteria (EAHEC), which caused diarrhea in pediatric diarrhea patients at Dr. Soetomo General Hospital. The unique combination of genomic features of the Surabaya outbreak strain, containing characteristics from pathotypes EAEC and EHEC, suggested that it represents a new pathotype enteroaggregative haemorrhagic E. coli (EAHEC). It is expected that development of specific primer design and sequencing are needed to continue in this research.

    2020年07月07日, Infectious disease reports, 12 (Suppl 1), 8745 - 8745, 英語, 国際誌

    研究論文(学術雑誌)

  • Sarassari Rosantia, Takuya Higa, Nobuyoshi Yagi, Toshiro Tokunaga, Seina Higa, Yasuaki Yakabi, Toshiro Shirakawa, Kuntaman Kuntaman, Itaru Hirai

    Enterobacteriaceae isolates producing CTX-M-type extended-spectrum β-lactamase (ESBL) has been found in hospitalized patients and healthy individuals in communities of the Southeast Asian countries. Medical students might have more risk of ESBL-producing Enterobacteriaceae contagion, because medical students who belong to communities have direct and indirect contacts with workers and patients in healthcare facilities. The aim of this study was to collect information for evaluation of the potential risk of ESBL-producing Enterobacteriaceae contagion in Indonesian undergraduate medical students by characterizing genotypic properties of Escherichia coli isolates-producing CTX-M-type ESBL. A total 141 fecal samples collected from 207 medical students of a university in Surabaya, Indonesia were subjected to PCR, XbaI and S1 nuclease-pulsed-field gel electrophoresis (PFGE), Southern blotting, and sequencing analysis. Eighty-two ESBL-producing Enterobacteriaceae, including 75 E. coli and 7 Klebsiella pneumoniae were isolated from 79 (56.0%) students. Among 75 ESBL-producing E. coli, blaCTX-M-15 was the most prevalent type (44.0%). Although XbaI-PFGE results showed genetic background of the E. coli isolates producing CTX-M-type ESBL were diverse, five clonal spread cases of certain E. coli producing CTX-M-type ESBL isolates were observed among the medical students. Our results suggested that ESBL-producing Enterobacteriaceae might be circulating among the medical students through contaminated environment such as in a university or communities they belonged.

    2020年06月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26 (6), 575 - 581, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Kayo Osawa, Katsumi Shigemura, Koichi Kitagawa, K Kuntaman, Ni Made Mertaniasih, Wahyu Setyarini, Dita Arizandy, Dadik Rahadjo, Ro Osawa, Toshiro Shirakawa, Masato Fujisawa

    Cholera due to Vibrio cholerae has been spreading worldwide, although the reports focusing on Indonesian V. cholerae are few. In this study, in order to investigate how V. cholerae transmitted to human from environment. We extended an epidemiological report that had investigated the genotype of V. cholerae isolated from human pediatric samples and environmental samples. We examined 44 strains of V. cholerae isolated from pediatric diarrhea patients and the environment such as shrimps or oysters collected in three adjacent towns in Surabaya, Indonesia. Susceptibilities were examined for 11 antibiotics. Serotype O1 or O139 genes and pathogenic genes including cholera toxin were detected. Multi-locus sequence typing (MLST) and enterobacterial repetitive intergenic consensus (ERIC)-PCR were also performed to determine genetic diversity of those isolates. Serotype O1 was seen in 17 strains (38.6%) with all pathogenic genes among 44 isolates. Other isolates were non-O1/non-O139 V. cholerae. Regarding antibiotic susceptibilities, those isolates from environmental samples showed resistance to ampicillin (11.4%), streptomycin (9.1%) and nalidixic acid (2.3%) but those isolates from pediatric stools showed no resistance to those 3 kinds of antibiotics. MLST revealed sequence type (ST) 69 in 17 strains (38.6%), ST198 in 3 strains (6.8%) and non-types in 24 strains (54.5%). All the ST69 strains were classified to O1 type with more than 95% similarity by ERIC-PCR, including all 6 (13.6%) isolates from environmental samples with resistance to streptomycin. In conclusion, V. cholerae O1 ST69 strains has been clonally spreading in Surabaya, exhibiting pathogenic factors and antibiotic resistance to streptomycin, especially in the isolates from environment.

    2020年06月, Indian journal of microbiology, 60 (2), 230 - 238, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Natsumi Uehara, Naoki Otsuki, Mie Kubo, Junko Kitamoto, Yasutaka Kojima, Masanori Teshima, Hirotaka Shinomiya, Toshiro Shirakawa, Ken-ichi Nibu

    2020年02月03日, Cancer Reports

    [査読有り]

    研究論文(学術雑誌)

  • Yoneda T, Kunimura N, Kitagawa K, Fukui Y, Saito H, Narikiyo K, Ishiko M, Otsuki N, Nibu KI, Fujisawa M, Serada S, Naka T, Shirakawa T

    Prostate cancer is one of the most common cancers in men. The overactivation of IL-6/JAK/STAT3 signaling and silencing of SOCS3 are frequently observed in prostate cancer. In the present study we undertook to develop Ad-SOCS3 gene therapy for the treatment of prostate cancer and also investigated whether Ad-SOCS3 increased sensitivity to NK cells. We demonstrated that Ad-SOCS3 could significantly inhibit growth of castration-resistant prostate cancer (CRPC) cell lines expressing pSTAT3, DU-145 (at 10, 20, and 40 MOI), and TRAMP-C2 (at 40 MOI), but not the PC-3 CRPC cell line with the STAT3 gene deleted. Ad-SOCS3 (40 MOI) could suppress IL-6 production in DU-145 cells and PD-L1 expression induced by IFN-γ in TRAMP-C2 cells, and increased the NK cell sensitivity of both TRAMP-C2 and DU-145 cells. In the DU-145 mouse xenograft tumor model, intratumoral injections (twice/week for 3 weeks) of 1 × 108 pfu of Ad-SOCS3 significantly inhibited tumor growth and combining the Ad-SOCS3 treatment with intratumoral injections (once/week for 2 weeks) of 1 × 107 human NK cells showed the highest tumor growth inhibitory effect. These results suggested that a combination of Ad-SOCS3 gene therapy and NK cell immunotherapy could be a powerful treatment option for advanced CRPC overexpressing pSTAT3.

    2019年11月, Cancer gene therapy, 26 (11-12), 388 - 399, 英語, 国際誌

    [査読有り]

  • Masazumi Teramae, Kayo Osawa, Katsumi Shigemura, Koichi Kitagawa, Toshiro Shirakawa, Masato Fujisawa, Takayuki Miyara

    Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolates are known to tolerate superior quinolone antimicrobials compared with other antibacterial agents. Among the clones belonging to sequence type (ST) 131 by multilocus sequence typing, the involvement of the H30-Rx subclone has been reported worldwide with various fimH genes encoding type 1 pili. We investigated 83 isolates of ESBL-producing E. coli and performed antimicrobial susceptibility test, CH (fumC/fimH) ST131 by typing the specific PCR. Moreover, mutation analysis of genes involved in quinolone antibiotic resistance (gyrA and parC) and ESBL genotypes were determined. As a result, 54 of 83 isolates (65.1%) of CH40-30 clones corresponding to ST131-fimH30 were detected, and all were resistant to levofloxacin. Mutations associated with this resistance were common, and included S83L and D87N of gyrA and S80I and E84V of parC. Subclone analysis revealed a high proportion of fimH30-non-Rx (40 isolates, 74.1%). Each subclone was characterized by ESBL genotype, and the CTX-M-15 type was mainly seen for fimH30-Rx, with the CTX-M-14 type or CTX-M-27 type seen for fimH30-non-Rx. This study suggests that an increase in ESBL-producing quinolone-resistant E. coli in a city hospital in Hyogo, Japan, was caused by the spread of subclones belonging to fimH30-non-Rx of ST131.

    2019年10月18日, International journal of molecular sciences, 20 (20), 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Koichi Kitagawa, Katsumi Shigemura, Shian-Ying Sung, Kuan-Chou Chen, Chao-Ching Huang, Yi-Te Chiang, Ming-Che Liu, Tzu-Wen Huang, Fukashi Yamamichi, Toshiro Shirakawa, Masato Fujisawa

    PURPOSE: To investigate the role of sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition (EMT) in bladder cancer progression and invasion. METHODS: We cultured three bladder cancer cell lines, muscle-invasive T24 and 5637, and non-muscle-invasive KK47, in the presence of a recombinant-Shh (r-Shh) protein or cyclopamine, a Shh signaling inhibitor, to investigate proliferation and expression of EMT markers. Wound-healing assays and transwell assay were performed to evaluate cell invasion and migration. Mice were then inoculated with bladder cancer cells and treated with cyclopamine. Mouse tumor samples were stained for Shh signaling and EMT markers. RESULTS: R-Shh protein enhanced cell proliferation, whereas cyclopamine significantly suppressed cell proliferation, especially in invasive cancer (5637 and T24) (p < 0.05). R-Shh protein promoted EMT, suppressed E-cadherin and enhanced N-cadherin and vimentin and Gli1, an Shh downstream molecule, while cyclopamine blocked EMT, especially in 5637 and T24. Cyclopamine also inhibited cell invasion and migration in vitro. In the animal study, intraperitoneal injection of cyclopamine significantly suppressed tumor growth in 5637 and T24 in mice (p = 0.01 and p = 0.004, respectively) and slightly suppressing KK47 tumor growth (p = 0.298). Significant cyclopamine-induced suppression of Gli1 in 5637 and T24 mouse tumors (both p = 0.03) was seen, suggesting that muscle-invasive bladder cancer may be more dependent on Shh signaling than non-muscle-invasive bladder cancer. CONCLUSIONS: Shh signaling and EMT were especially enhanced in muscle-invasive bladder cancer progression and invasion, and suppressed by the inhibition of Shh signaling.

    2019年09月, Journal of cancer research and clinical oncology, 145 (9), 2261 - 2271, 英語, 国際誌

    [査読有り]

  • Shirakawa T, Kitagawa K, Tatsumi M, Gonoi R, Katayama T, Hashii Y, Fujisawa M, Kadowaki M

    2019年03月, Molecular cancer therapeutics

    [査読有り]

  • Kitagawa K, Shigemura K, Yamamichi F, Osawa K, Uda A, Koike C, Tokimatsu I, Shirakawa T, Miyara T, Fujisawa M

    2019年03月, International journal of urology : official journal of the Japanese Urological Association, 26 (3), 358 - 362

    [査読有り]

  • Alpha Fardah Athiyyah, Katsumi Shigemura, Koichi Kitagawa, Nazara Agustina, Andy Darma, Reza Ranuh, Dadik Raharjo, Toshiro Shirakawa, Masato Fujisawa, Subijanto Marto Sudarmo

    Background: The objective of this study was to investigate the clinical manifestation of norovirus infection between norovirus genogroup and severity of acute diarrhea in pediatric patients at the Dr. Soetomo Hospital, Surabaya, Indonesia. Methods: This cross-sectional study involved 31 participants aged 1-60 months admitted to the hospital with acute diarrhea from April 2012 to March 2013. Norovirus genogroups (GI and II) were identified from patient stool using reverse transcription polymerase chain reaction (RT-PCR). Severity was measured using the Ruuska and Vesikari scoring system. Results: In total, 94 stool samples were obtained, of which 31 (19%) were norovirus positive. Norovirus GI was found in one sample with mild diarrhea. Norovirus GII was found in 30 samples (96.8%); one sample with mild diarrhea (3.3%), 20 samples with moderate diarrhea (66.7%), and nine samples with severe diarrhea (30%). Conclusion: Norovirus GII was the most prevalent cause of acute diarrhea and 30% of the cases manifested as severe diarrhea.

    2019年, F1000Research, 8, 2130 - 2130, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Mita Y, Shigemura K, Osawa K, Kitagawa K, Kotaki T, Shirakawa T, Miyara T, Fujisawa M

    2019年, Urologia internationalis, 102 (2), 205 - 211

    [査読有り]

  • 大澤 佳代, 重村 克巳, 北川 孝一, 福田 輝雄, 高坂 綾香, Sakie Wakabayashi, Kanako Sato, 山道 深, 白川 利朗, 藤澤 正人

    2019年01月, International Journal of Urology, 26 (1), 127 - 133, 英語

    [査読有り]

    研究論文(学術雑誌)

  • K Kuntaman, 重村 克巳, 大澤 佳代, 北川 孝一, 佐藤 小春, 山田 尚輝, 西本 健人, 山道 深, Dadik Rahardjo, Usman Hadi, Ni Made Mertaniasih, 木下 承皓, 藤澤 正人, 白川 利朗

    2018年11月, International Journal of Urology, 25 (11), 966 - 972, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Kojima Y, Otsuki N, Kubo M, Kitamoto J, Takata E, Saito H, Kosaka K, Morishita N, Uehara N, Shirakawa T, Nibu KI

    Human papillomavirus (HPV) infection has been identified as an etiologic factor of head and neck cancers (HNCs). We explored the potential use of antisense HPV RNA transcripts for gene therapy and its effect in combination with cisplatin (CDDP) for HPV-positive HNCs. We introduced the antisense RNA transcripts of the E6 and E7 genes of HPV type 16 into UM-SCC-47 cells harboring HPV 16 and YCU-T892 cells that were HPV-negative using a recombinant adenoviral vector, Ad-E6/E7-AS. We then analyzed the effects of the introduction of Ad-E7-AS on cell and tumor growth and the synergistic effect with CDDP in vitro and in vivo. After infection of Ad-E6/E7-AS, the cellular growth of UM-SCC-47 cells were suppressed, but not that of YCU-T892 cells. E7 protein expression was suppressed, and p53 and pRb protein expression increased after infection of Ad-E7-AS. Cell growth and tumorigenicity were greatly suppressed in combination with CDDP compared with Ad-E7-AS or CDDP treatment alone in vitro. Ad-E7-AS combined with CDDP treatment significantly reduced the volumes of established subcutaneous tumors. Transfection with HPV 16 E7 antisense RNA combined with CDDP treatment might be a potentially useful approach to the therapy of HPV 16-positive HNC.

    2018年10月, Cancer gene therapy, 25 (9-10), 274 - 283, 英語, 国際誌

    [査読有り]

  • Osawa K, Shigemura K, Kitagawa K, Fukuda T, Takasaka A, Wakabayashi S, Sato K, Yamamichi F, Shirakawa T, Fujisawa M

    2018年10月, International journal of urology : official journal of the Japanese Urological Association

    [査読有り]

  • Nakanishi N, Nomoto R, Sato K, Koike C, Kusuki M, Nakamura T, Shigemura K, Shirakawa T, Fujisawa M, Tokimatsu I, Osawa K

    2018年08月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

    [査読有り]

  • Kusuki M, Osawa K, Arikawa K, Tamura M, Shigemura K, Shirakawa T, Nakamura T, Nakamachi Y, Fujisawa M, Saegusa J, Tokimatsu I

    2018年07月, Diagnostic microbiology and infectious disease, 91 (3), 256 - 259

    [査読有り]

  • Improved bacterial identification directly from urine samples with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

    KitagawaK, ShigemuraK, OnumaKI, NishidaM, FujiwaraM, KobayashiS, YamasakiM, NakamuraT, YamamichiF, ShirakawaT, TokimatsuI, FujisawaM

    2018年03月, J Clin Lab Anal, 32 (3), 英語

    [査読有り]

    研究論文(学術雑誌)

  • Kitagawa K, Shigemura K, Yamamichi F, Alimsardjono L, Rahardjo D, Kuntaman K, Shirakawa T, Fujisawa M

    2018年01月, Jpn J Infect Dis., 71 (1), 8 - 13, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 白川利朗, 北川孝一

    2018年01月, Hum Vaccin Immunother, 14 (1), 159 - 162, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Kayo Osawa, Katsumi Shigemura, Yukie Nukata, Koichi Kitagawa, Fukashi Yamamichi, Hiroyuki Yoshida, Toshiro Shirakawa, Soichi Arakawa, Masato Fujisawa

    AMER SOC MICROBIOLOGY, 2017年08月, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 61 (8), pii: e01174 - 17., 英語

    [査読有り]

    研究論文(学術雑誌)

  • H. Saito, K. Kitagawa, T. Yoneda, Y. Fukui, M. Fujsawa, D. Bautista, T. Shirakawa

    Recently, the US FDA approved sipuleucel-T, which is composed of autologous DCs stimulated with a recombinant fusion protein of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF), as the first immunotherapeutic agent for metastatic castration resistant prostate cancer (mCRPC). However, sipuleucel-T demonstrated only modest efficacy in mCPRC patients. Researchers are now investigating the potential of p53 protein as a tumor-associated antigen (TAA) loaded in DC-based cancer vaccine. Approximately half of all tumors overexpress p53, and up to 20% of prostate cancer cells overexpresses p53. In this study, we evaluated the feasibility of combining p53-DC vaccine and rAd-p53 gene therapy, using the p53-overexpressing and non-expressing prostate cancer cells in vitro. We successfully generated the p53-DC vaccine by culturing autologous DCs infected with rAd-p53. This p53-DC vaccine can differentiate CTLs specifically cytotoxic to p53-overexpressing prostate cancer cells. In addition, rAd-p53 infection can induce overexpression of p53 and thus the cytotoxicity of CTLs differentiated by the p53-DC vaccine in p53 non-expressing prostate cancer cells. These findings suggest that this combination therapy using p53-DC vaccine and rAd-p53 gene therapy together may represent a new paradigm for the treatment of mCRPC.

    NATURE PUBLISHING GROUP, 2017年07月, CANCER GENE THERAPY, 24 (7), 289 - 296, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Eddy Bagus Wasitou, Katsumi Shigemura, Kayo Osawa, Alpha Fardah, Akiho Kanaida, Dadik Raharjo, K. Kuntaman, Usman Hadi, Sugeng Harijono, Subijanto Marto Sudarmo, Tatsuya Nakamura, Keigo Shibayama, Masato Fujisawa, Toshiro Shirakawa

    The purpose of this study was to investigate extended-spectrum beta-lactamase (ES-BL)-producing Escherichia coli isolates from pediatric (aged 0 to 3 years) diarrhea patients in Surabaya, Indonesia, where this kind of survey is rare; our study included assessment of their antibiotic susceptibilides, as well as ESBL typing, multilocus sequence typing (MLST), and diarrheagenic E. coli (DEC)-typing. ESBL-producing E. coli were detected in 18.8% of all the samples. Many ESBL-producing E. coli had significantly lower susceptibility to gentamicin (p < 0.0001) and the quinolones nalidixic acid (p = 0.004) and ciprofloxacin (p < 0.0001) than non-producers. In ESBL-producing E. coli, 84.0% of strains expressed CTX-M-15 alone or in combination with other ESBL types. MLST revealed that 24.0% of ESBL-producers had sequence type 617, all of which expressed the CTX-M-15 gene; we also detected expression of 3 DEC-related genes: 2 enteroaggregative E. coli genes and 1 enteropathogenic E. coli gene. In conclusion, CTX-M-15-type ESBL-producing E. coli ST617 appear to have spread to Indonesia.

    NATL INST INFECTIOUS DISEASES, 2017年07月, JAPANESE JOURNAL OF INFECTIOUS DISEASES, 70 (4), 378 - 382, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Koichi Kitagawa, Tsugumi Oda, Hiroki Saito, Ayame Araki, Reina Gonoi, Katsumi Shigemura, Yoshiko Hashii, Takane Katayama, Masato Fujisawa, Toshiro Shirakawa

    Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein. B. longum 420 was orally administered into mice inoculated with WT1-expressing tumor cells for 4 weeks to examine anti-tumor effects. To analyze the WT1-specific cellular immune responses to oral B. longum 420, mice splenocytes were isolated and cytokine production and cytotoxic activities were determined. Oral administrations of B. longum 420 significantly inhibited WT1-expressing tumor growth and prolonged survival in mice. Immunohistochemical study and immunological assays revealed that B. longum 420 substantially induced tumor infiltration of CD4(+)T and CD8(+)T cells, systemic WT1-specific cytokine production, and cytotoxic activity mediated by WT1-epitope specific cytotoxic T lymphocytes, with no apparent adverse effects. Our novel oral cancer vaccine safely induced WT1-specific cellular immunity via activation of the gut mucosal immune system and achieved therapeutic efficacy with several practical advantages over existing non-oral vaccines.

    SPRINGER, 2017年06月, CANCER IMMUNOLOGY IMMUNOTHERAPY, 66 (6), 787 - 798, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Kitagawa Koichi, Omoto Chika, Oda Tsugumi, Araki Ayame, Saito Hiroki, Shigemura Katsumi, Katayama Takane, Hotta Hak, Shirakawa Toshiro

    We previously generated an oral hepatitis C virus (HCV) vaccine using Bifidobacterium displaying the HCV nonstructural protein 3 (NS3) polypeptide. NS3-specific cellular immunity is important for viral clearance and recovery from HCV infection. In this study, we enhanced the cellular immune responses induced by our oral HCV vaccine, Bifidobacterium longum 2165 (B. longum 2165), by combining interferon-alpha (IFN-alpha) as an adjuvant with the vaccine in a mouse experimental model. IFN-alpha is a widely used cytokine meeting the standard of care (SOC) for HCV infection and plays various immunoregulatory roles. We treated C57BL/6N mice with B. longum 2165 every other day and/or IFN-alpha twice a week for a month and then analyzed the immune responses using spleen cells. We determined the induction of NS3-specific cellular immunity by cytokine quantification, intracellular cytokine staining, and a cytotoxic T lymphocyte (CTL) assay targeting EL4 tumor cells expressing NS3/4A protein (EL4-NS3/4A). We also treated mice bearing EL4-NS3/4A tumor with the combination therapy in vivo. The results confirmed that the combination therapy of B. longum 2165 and IFN-a induced significantly higher IFN-gamma secretion, higher population of CD4(+)T and CD8(+)T cells secreting IFN-gamma, and higher CTL activity against EL4-NS3/4A cells compared with the control groups of phosphate-buffered saline, B. longum 2165 alone, and IFN-alpha alone (p < 0.05). We also confirmed that the combination therapy strongly enhanced tumor growth inhibitory effects in vivo with no serious adverse effects (p < 0.05). These results suggest that the combination of B. longum 2165 and IFN-alpha could induce a strong cellular immunity specific to NS3 protein as a combination therapy augmenting the current SOC immunotherapy against chronic HCV infection.

    MARY ANN LIEBERT, INC, 2017年04月, Viral Immunol, 30 (3), 196 - 203, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Yoshio Iijimal, Joseph O. Oundo, Takumi Hibino, Suleiman M. Saidi, Atsushi Hinenoya, Kayo Osawa, Toshiro Shirakawa, Ro Osawa, Shinji Yamasaki

    Diarrheagenic Escherichia coli (DEC) is an important agent of endemic and epidemic diarrhea worldwide, particularly in developing countries. DEC cannot be differentiated from commensal E. coli on selective media, although there are a few exceptions. Most studies use the colony isolation method, which cannot detect low numbers of DEC, and therefore, these studies might underestimate the incidence of DEC. In the present study, we employed a colony sweep method with real-time PCR targeting virulence genes of 5 categories of DEC; this technique can detect very low numbers of DEC among hundreds of commensal E. coli. DEC was detected in 171 (55.9%) of 306 children with diarrhea in Kenya. The prevalence of DEC in Kenya was notably higher than that (30 in 143, 21.0%) in Indonesia. Occurrences of multiple DEC infection in Kenya were frequent (69 in 306, 23.2%), suggesting that the source of DEC infection may be related to grossly contaminated food and water. In contrast, only 9 (6.0%) of 150 healthy adults in Kenya carried DEC. Considering that healthy adults naturally harbor non-DEC, it is interesting how children exclude DEC but not non-DEC as they grow up. Several mechanisms, such as mucosal immunity and intestinal microbiota, might be involved in the exclusion of DEC.

    NATL INST INFECTIOUS DISEASES, 2017年01月, JAPANESE JOURNAL OF INFECTIOUS DISEASES, 70 (1), 80 - 83, 英語

    [査読有り]

    研究論文(学術雑誌)

  • セフェム系抗菌薬低感受性淋菌の遺伝学的解析

    額田雪絵, 大澤佳代, 重村克巳, 吉田弘之, 藤澤正人, 荒川創一, 白川利朗

    2016年05月, 日本化学療法学会雑誌, 64 (Suppl.A), 164, 日本語

    研究論文(その他学術会議資料等)

  • カルバペネム耐性腸内細菌科細菌の分離状況

    朝比奈桃花, 大澤佳代, 重村克巳, 吉田弘之, 高羽桂, 時松一成, 藤澤正人, 荒川創一, 白川利朗

    2016年05月, 日本化学療法学会雑誌, 64 (Suppl.A), 178, 日本語

    研究論文(その他学術会議資料等)

  • 兵庫県内で分離されたメタロβラクタマーゼ産生緑膿菌の解析

    高坂綾香, 大澤佳代, 重村克巳, 山道深, 吉田弘之, 中村竜也, 藤澤正人, 荒川創一, 白川利朗

    2016年03月, 感染症学雑誌, 90 (2号), 183 - 184, 日本語

    研究論文(その他学術会議資料等)

  • MRSA疫学手法としてもPOT法とrep-PCR法の比較

    大澤佳代, 重村克巳, 吉田弘之, 白川利朗, 藤澤正人, 荒川創一

    2016年03月, 感染症学雑誌, 90 (臨増), 345, 日本語

    研究論文(その他学術会議資料等)

  • Beta-3 adrenergic receptors could be significant factors for overactive bladder-related symptoms.

    Yamamichi F, 重村 克巳, Behnsawy HM, Yamashita M, 白川 利朗, Fujisawa M

    2015年09月, Int J Clin Exp Pathol., 8 (9), 11863 - 70, 英語

    [査読有り]

    研究論文(学術雑誌)

  • BACTERIAL IDENTIFICATION USING SSRA ENCODING TRANSFER-MESSENGER RNA.

    Osawa K, Shigemura K, Shirai H, Kato A, Okuya Y, Jikimoto T, Arakawa S, Fujisawa M, Shirakawa T

    2015年07月, The Southeast Asian journal of tropical medicine and public health, 46 (4), 720 - 727

    [査読有り]

  • Tada Y, Hiroshima K, Shimada H, Morishita N, Shirakawa T, Matsumoto K, Shingyoji M, Sekine I, Tatsumi K, Tagawa M

    2015年07月, Springerplus, 4, 358, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Shigemura K, Osawa K, Miura M, Tanaka K, Arakawa S, Shirakawa T, Fujisawa M

    2015年05月, Antimicrob Agents Chemother, 59 (5), 2695 - 9, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Osawa K, Shigemura K, Shimizu R, Kato A, Kusuki M, Jikimoto T, Nakamura T, Yoshida H, Arakawa S, Fujisawa M, Shirakawa T

    2015年04月, Microb Drug Resist, 21 (2), 130 - 9, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Shigemura K, Osawa K, Kato A, Tokimatsu I, Arakawa S, Shirakawa T, Fujisawa M

    2015年04月, J Antibiot (Tokyo), 68 (9), 568 - 572, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Sudarmo SM, Shigemura K, Athiyyah AF, Osawa K, Wardana OP, Darma A, Ranuh R, Raharjo D, Arakawa S, Fujisawa M, Shirakawa T

    2015年02月, Gut Pathog, 7, 3, 英語

    [査読有り]

    研究論文(学術雑誌)

  • [Development of the novel oral vaccine against hepatitis C virus utilizing bifidobacteria]

    ShirakawaT

    2015年02月, Nihon Rinsho, 73 (2), 239 - 242, 英語

    研究論文(学術雑誌)

  • Fukashi Yamamichi, Katsumi Shigemura, Hosny M. Behnsawy, Fatma Y. Meligy, Wen-Chin Huang, Xiangyan Li, Kunito Yamanaka, Keisuke Hanioka, Hideaki Miyake, Kazushi Tanaka, Masato Kawabata, Toshiro Shirakawa, Masato Fujisawa

    Objective. Sonic hedgehog (Shh) signaling, androgens and epithelial-mesenchymal transition (EMT) are related to prostate cancer (PCa) progression. The aim of this study was to investigate how Shh and androgen [dihydrotestosterone (DHT)] signaling act in prostate epithelial and stromal compartments and whether this signaling pathway drives EMT and promotes PCa progression. Material and methods. LNCaP, normal prostate fibroblast (NPF) and cancer-associated prostate fibroblast (CPF) cells were studied with DHT and/or the Shh signaling inhibitor cyclopamine. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the expressions of a potential Shh target gene, osteonectin (ON) and EMT-associated markers (E-cadherin, N-cadherin and vimentin). Immunohistochemical studies using PCa prostatectomy samples were performed to assess the expression levels of ON, Gli-1, androgen receptor, Shh, E-cadherin, N-cadherin and vimentin. Results. While DHT enhanced cell proliferation in CPF more than LNCaP or NPF, cyclopamine inhibited cell proliferation enhanced by DHT in CPF. Real-time RT-PCR showed whereas both Shh and DHT induced N-cadherin and vimentin, DHT also induced the expression of osteonectin in LNCaP and cyclopamine blocked these expressions in osteonectin, N-cadherin and vimentin (p = 0.0084, 0.0002 and 0.0373, respectively). Immunohistochemistry showed that high expression of stromal, but, not epithelial, ON was significantly correlated with serum prostate-specific antigen (PSA) (p = 0.031), and high expression of Gli-1 and low expression of stromal ON with PSA recurrence (p = 0.0114 and p = 0.0005, respectively). Conclusions. Shh and androgen signaling in prostate tumor and stromal compartments drives EMT, and thus may play some role in PCa progression. Cyclopamine may be one therapeutic strategy for PCa.

    INFORMA HEALTHCARE, 2014年12月, SCANDINAVIAN JOURNAL OF UROLOGY, 48 (6), 523 - 532, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 兵庫県におけるアジスロマイシン(AZM)耐性淋菌の分子遺伝学的解析

    三浦 真希子, 重村 克巳, 大澤 佳代, 吉田 弘之, 藤原 美樹, 澤村 暢, 奈須 聖子, 荒川 創一, 藤澤 正人, 白川 利朗

    2014年10月, 日本性感染症学会誌, 25 (2号), 78, 日本語

    研究論文(その他学術会議資料等)

  • セフェム系薬剤感受性低下Neisseria gonorrhoeaeの遺伝解析

    大澤 佳代, 重村 克巳, 額田 雪絵, 吉田 弘之, 藤原 美樹, 奈須 聖子, 白川 利朗, 藤澤 正人, 荒川 創一

    2014年10月, 日本性感染症学会誌, 25 (2号), 78, 日本語

    研究論文(その他学術会議資料等)

  • Kayo Osawa, Katsumi Shigemura, Takumi Jikimoto, Toshiro Shirakawa, Masato Fujisawa, Soichi Arakawa

    The methods for typing and epidemiological study for especially antibiotic-resistant bacteria has been issued but there are the debates regarding which method is best for this purpose. The purpose of this study is to investigate and apply a comparatively new technology, phage-open-reading frame typing (POT) and repetitive-sequence-based PCR (rep-PCR) using DiversiLab system and compare for the discrimination of major methicillin-resistant Staphylococcus aureus (MRSA) lineages in epidemiological surveillance. We analyzed 47 representative MRSA stains isolated in Kobe University Hospital between January and December 2009. We performed MRSA typing using the POT kit and rep-PCR using the DiversiLab system. POT method classified all the MRSA strains into 35 clusters, whereas rep-PCR method typed all the MRSA strains in 10 kinds of clusters with a definition of 95% similarity. The discriminatory power and congruence between the methods were compared using the Simpson's index of diversity, adjusted Rand's and Wallace's coefficients. Our statistical analyses showed that the POT (POT 1-2-3 and POT 2-3) revealed a higher discriminatory power in the Simpson's index of diversity (SID; 0.969, range 0.939-4.000 and 0.967, range 0.935-0.998, respectively) for MRSA isolates than the rep-PCR (0.821 (0.767-0.876)). The adjusted Rand's and Wallace's coefficients did not show higher concordance among the methods. In conclusion, we demonstrated that the POT can perform accurate and reliable epidemiological surveillance studies for analyzing the genetic relatedness of MRSA strains.

    JAPAN ANTIBIOTICS RESEARCH ASSOC, 2014年08月, JOURNAL OF ANTIBIOTICS, 67 (8), 565 - 569, 英語

    [査読有り]

    研究論文(学術雑誌)

  • A Combined Lymphokine-activated Killer (LAK) Cell Immunotherapy and Adenovirus-p53 Gene Therapy for Head and Neck Squamous Cell Carcinoma

    Hiroki Saito, Satoshi Ando, Naoya Morishita, Kyung-Mi Lee, Dante Dator, David Dy, Katsumi Shigemura, Zainal Adhim, Ken-Ichi Nibu, Masato Fujisawa, Toshiro Shirakawa

    Background: The antitumor activity of lymphokine activated killer (LAK) cells immunotherapy is not always effective in all patients, especially when used alone. In this study, we investigated the in vitro antitumor activities of a combination of LAK immunotherapy and gene therapy employing an adenovirus carrying the p53 gene (Ad-p53) in human head and neck squamous cell carcinoma. Materials and Methods: The in vitro cytotoxicity of LAK cells was tested in H891 cells infected with or without Ad-p53, and the mRNA expression levels of natural killer group 2D ligands (UL16 binding protein (ULBP) 1 to 5) and tumor necrosis factor (TNF-alpha) in these cells were measured by real-time reverse transcription polymerase chain reaction. Results: Ad-p53 infection increased the cytotoxicity of LAK cells against H891 cells, and also increased the mRNA expression levels of the ULBPs in H891 cells and TNF-alpha in the LAK cells. Conclusion: The antitumor activities of LAK cells in H891 cells were enhanced by Ad-p53. Conclusion: The combinational therapy of LAK immunotherapy and Ad-p53 gene therapy may represent a new paradigm for the treatment of head and neck cancer.

    INT INST ANTICANCER RESEARCH, 2014年07月, ANTICANCER RESEARCH, 34 (7), 3365 - 3370, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 兵庫県下で分離されたメタロβラクタマーゼ産生腸内細菌の解析

    大澤 佳代, 重村 克巳, 吉田 弘之, 藤原 美樹, 荒川 創一, 藤澤 正人, 白川 利朗

    2014年05月, 日本化学療法学会雑誌, 62 (Suppl.A), 402, 日本語

    研究論文(その他学術会議資料等)

  • 当院で分離されたESBLs産生Escherichia coliの遺伝子解析

    大澤 佳代, 吉田 弘之, 重村 克巳, 楠木 まり, 直本 拓己, 中村 竜也, 荒川 創一, 藤澤 正人, 白川 利朗

    2014年05月, 日本化学療法学会雑誌, 62 (Suppl.A), 400, 日本語

    研究論文(その他学術会議資料等)

  • Saki Takei, Chika Omoto, Koichi Kitagawa, Naoya Morishita, Takane Katayama, Katsumi Shigemura, Masato Fujisawa, Masato Kawabata, Hak Hotta, Toshiro Shirakawa

    More than 170 million people worldwide are chronic HCV (Hepatitis C virus) carriers, and about 30% of them will develop progressive liver disease, such as cirrhosis and hepatocellular carcinoma. A combination of pegylated interferon-alpha with ribavirin, the standard treatment for HCV infection, has been effective in fewer than 50% of patients infected with HCV genotype 1. A strong T cell response against the nonstructural protein 3 (NS3) is important for recovery from acute HCV infection, and an early multi-specific CD4+ helper and CD8+ cytotoxic T cell response is critical for HCV clearance. In the present study, we successfully constructed a genetically modified Bifidobacterium longum (B. longum) displaying recombinant HCV-NS3 peptides containing some CD4 and CD8 epitopes located in the HCV-NS3 region as an oral vaccine against chronic HCV infection. The oral administration of this vaccine could induce NS3-specific immune responses in mice through intestinal mucosal immunity. Our findings suggest that this novel oral vaccine has great potential as a novel oral vaccine against chronic HCV infection. (C) 2014 Elsevier Ltd. All rights reserved.

    ELSEVIER SCI LTD, 2014年05月, VACCINE, 32 (25), 3066 - 3074, 英語

    [査読有り]

    研究論文(学術雑誌)

  • DEVELOPMENT OF MULTIPLEX PCR FOR RAPID IDENTIFICATION OF FOUR SALMONELLA SEROVARS MOST COMMONLY ISOLATED IN JAPAN

    Rika Shimizu, Kayo Osawa, Katsumi Shigemura, Hiroyuki Yoshida, Miki Fujiwara, Yoshio Iijima, Masato Fujisawa, Toshiro Shirakawa

    More than 2,500 serovars of Salmonella species have been reported to date. A multiplex-PCR method was developed and evaluated for discriminating the four Salmonella enterica subsp enterica serovars, namely, S. Enteritidis, S. Typhimurium, S. Thompson and S. Infantis, most commonly isolated in Japan. Twenty-two serovars of 84 Salmonella strains and 7 species of non-Salmonella strains were evaluated using primer pairs specific for the detection of Salmonella spp. Multiplex PCR generated, with 100% specificity, the expected amplicon of 333, 413,551 and 658 bp of S. Enteritidis, S. Inf antis, S. Typhimurium, and S. Thompson, respectively, while an additional non-specific amplicon (about 1,000 bp) was observed for S. Infantis, but it had no practical impact in the bacterial detection. This multiplex PCR assay can be applied to identify and discriminate clinically significant strains of Salmonella serovars rapidly and accurately without the need for serological examination.

    SOUTHEAST ASIAN MINISTERS EDUC ORGANIZATION, 2014年05月, SOUTHEAST ASIAN JOURNAL OF TROPICAL MEDICINE AND PUBLIC HEALTH, 45 (3), 654 - 661, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 前立腺癌増悪において上皮ならびに間質でのShhとandrogenシグナル伝達が上皮間葉移行を作動させる

    山道 深, 重村 克巳, ホスニー・ベンソイ, ファトマ・メリジ, ウェンチン・ファン, シャン・ギアン・リ, リーランド・チャン, 川端 眞人, 後藤 章暢, 三宅 秀明, 田中 一志, 白川 利朗, 藤澤 正人

    2014年04月, 日本泌尿器科学会総会 102回, 415, 日本語

    研究論文(その他学術会議資料等)

  • Katsuyuki Hamada, Toshiro Shirakawa, Shuji Terao, Akinobu Gotoh, Kenzaburo Tani, Wenlin Huang

    The use of carrier cells infected with oncolytic viruses in cancer gene therapy is an attractive method because it can overcome viral immunogenicity and induce tumor immunity and significant antitumor activity. To enable human clinical trials of this treatment, acute and chronic toxicity tests must first be performed to ensure safety. IAI.3B promoter, oncolytic adenovirus AdE3-IAI.3B introduced by IAI.3B promoter, and A549 carrier cells infected with AdE3-IAI.3B were highly active in cancer cells but not in normal cells. Freeze-thawing increased the antitumor effect of A549 carrier cells by promoting the translocation of oncolytic adenovirus particles from the nucleus to the cytoplasm following the rupture of the nuclear membranes. No deaths or abnormal blood test data resulted from acute toxicity tests conducted in nude mice after a single dose. In chronic toxicity tests in rabbits, there were no serious side effects after eight doses of 1.25 x 10(7) cells/kg or less for 4 weeks; a significant immune response is known to elicit increased numbers of antiadenovirus antibodies and enlarge the spleen. From these results, it could be concluded that cancer gene therapy of recurrent solid tumors using carrier cells can be safely trialed in humans.

    CELL PRESS, 2014年, MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT, 1, 14019, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Kayo Osawa, Katsumi Shigemura, Rika Shimizu, Ayaka Kato, Mayuha Kimura, Yuki Katayama, Yuma Okuya, Shunichiro Yutaka, Akiko Nishimoto, Akane Kishi, Miki Fujiwara, Hiroyuki Yoshida, Yoshio Iijima, Masato Fujisawa, Toshiro Shirakawa

    The purpose of this study was to examine the in vitro susceptibilities to antimicrobial agents and genetic diversity of 195 clinical strains of Salmonella spp., which were isolated and examined for the extended-spectrum beta-lactamase (ESBL) bla(CTX-M) gene and the presence of gyrA, gyrB, parC, and parE genes mutations in Hyogo, Japan, from 2009 to 2012. Forty-three of the 195 strains were antimicrobial resistant. Two Salmonella enterica subsp. enterica strains, 1 serovar Schwarzengrund, and 1 serovar Enteritidis were identified as ESBL-producing strains possessing bla(CTX-M-15) and bla(CTX-M-2), respectively. Among 8 nalidixic acid-resistant strains, 7 had mutations in gyrA alone or in gyrA and parC. In conclusion, we identified CTX-M ESBL-producing Salmonella clinical strains with multidrug resistance. Further studies are needed to monitor these serious drug-resistant Salmonella strains in Japan.

    NATL INST INFECTIOUS DISEASES, 2014年01月, JAPANESE JOURNAL OF INFECTIOUS DISEASES, 67 (1), 54 - 57, 英語

    [査読有り]

    研究論文(学術雑誌)

  • BPH/LUTSに対するデュタステリドの有用性に関する検討

    原口 貴裕, 三宅 秀明, 江夏 徳寿, 白川 利朗, 田中 一志, 藤澤 正人

    2013年09月, 日本排尿機能学会誌, 24 (1号), 282, 日本語

    [査読有り]

    研究論文(その他学術会議資料等)

  • Toshiro Shirakawa, Takahiro Haraguchi, Katsumi Shigemura, Shinichi Morishita, Kohji Minayoshi, Jiro Miyazaki, Yuji Yamada, Hideaki Miyake, Kazushi Tanaka, Masato Fujisawa

    Objectives: Silodosin is a novel drug that is highly selective to subtype alpha 1A and, since 2006, has been used in Japan for treating benign prostatic hyperplasia. This study aimed to compare the clinical effects of the alpha-adrenoceptor antagonist, silodosin, with those of naftopidil in patients presenting lower urinary tract symptoms associated with benign prostatic hyperplasia. Methods: This was a randomized, open-label, controlled multicenter study carried out in Japan. Overall, 121 participants with lower urinary tract symptoms associated with benign prostatic hyperplasia were randomized to receive silodosin (4mg twice daily) or naftopidil (50mg once daily) for 4 or 8 weeks. Patients were divided into four groups: the alpha-blocker-naive groups received silodosin (35 patients) or naftopidil (33 patients) and the drug-switching groups changed from tamsulosin to silodosin (26 patients) or naftopidil (27 patients). The outcomes parameters were the International Prostate Symptom Score, quality of life, maximum urinary flow rate and post-void residual urine volume. P<0.05 was considered statistically significant by using the Wilcoxon signed-rank and rank-sum tests, and analysis of covariance. Results: In all the groups, silodosin and naftopidil significantly improved the total International Prostate Symptom Score and quality of life. However, silodosin obtained significantly better improvement in total International Prostate Symptom Score in the alpha-blocker-naive patients at 4 and 8 weeks. The maximum urinary flow rate and residual urine did not change significantly in all the treatment groups. Conclusions: The present study confirms the clinical usefulness of silodosin in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia.

    WILEY-BLACKWELL, 2013年09月, INTERNATIONAL JOURNAL OF UROLOGY, 20 (9), 903 - 910, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Osawa K, Shigemura K, Iguchi A, Shirai H, Imayama T, Seto K, Raharjo D, Fujisawa M, Osawa R, Shirakawa T

    2013年09月, Microbiol Immunol, 57 (9), 616 - 23, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Kayo Osawa, Dadik Raharjo, Eddy Bagus Wasito, Sugeng Harijono, Katsumi Shigemura, Ro Osawa, Subijanto Marto Sudarmo, Yoshio Iijima, Toshiro Shirakawa

    Diarrheagenic Escherichia coli (DEC) is a major etiologic agent of childhood diarrhea in developing countries. We investigated the frequency of DEC in stool samples from 125 diarrheal children (age, 1-10 years) and 92 non-diarrheal children in Surabaya, Indonesia. The non-diarrheal children served as healthy controls. DEC was detected in 23 of 125 (18.4%) and 47 of 92 (51.1%) samples in the diarrheal and non-diarrheal children, respectively. Enteropathogenic E. coli was the most prevalent in the non-diarrheal children (25.0%), and its prevalence was significantly higher than that in the diarrheal children (0.8%) (P < 0.0001). Interestingly, Shiga toxin-producing E. coli (4.3%) was detected only in the non-diarrheal children (P = 0.031). This is the first study comparing between diarrheal children with non-diarrheal or healthy children to investigate the role of DEC in pediatric diarrheal diseases in Indonesia.

    NATL INST INFECTIOUS DISEASES, 2013年09月, JAPANESE JOURNAL OF INFECTIOUS DISEASES, 66 (5), 446 - 448, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Behnsawy HM, Shigemura K, Meligy FY, Yamamichi F, Yamashita M, Haung WC, Li X, Miyake H, Tanaka K, Kawabata M, Shirakawa T, Fujisawa M

    2013年08月, Korean J Urol, 54 (8), 547 - 54, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Adhim Z, Otsuki N, Kitamoto J, Morishita N, Kawabata M, Shirakawa T, Nibu K

    2013年07月, Acta Otolaryngol, 133 (7), 761 - 71, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 尿路感染症患者より分離したPseudomonas aeruginosa薬剤耐性株におけるefflux pump遺伝子の発現についての検討

    加藤 綾香, 大澤 佳代, 重村 克巳, 田中 一志, 荒川 創一, 藤澤 正人, 白川 利朗

    2013年05月, 感染症学雑誌, 87 (臨増), 297, 日本語

    研究論文(その他学術会議資料等)

  • Katsumi Shigemura, Kazushi Tanaka, Fukashi Yamamichi, Toshiro Shirakawa, Hideaki Miyake, Masato Fujisawa

    There are several mechanisms of fluoroquinolone (FQ) resistance, such as mutations in the quinolone resistance-determining regions (QRDRs) of target genes and efflux pump expression. The purpose of this study was to investigate which factor plays the main role in FQ resistance in Escherichia coli causing urinary tract infections (UTIs) from a statistical analysis of our two previous works. DNA sequencing of the QRDRs of the FQ resistance-related genes gyrA and parC as well as real-time reverse transcriptase (RT)-PCR for the expression of efflux pump genes such as marA or yhiU were performed and the correlations of mutations or efflux pump gene expression with FQ minimal inhibitory concentrations (MICs) were investigated. Significant factors for high MICs of sitafloxacin (STFX), ciprofloxacin (CPFX) and levofloxacin were the mutations S83L and D87N in gyrA and S80I and E84V in parC as well as the expression of marA. Mutations in the QRDRs of gyrA or parC had a greater effect on FQ MICs than efflux pump gene expression. Based on the regression coefficient, these mutations correlated with MICs to CPFX most, and STFX had the lowest effects from these mutations among the three tested FQs. In conclusion, in E. coli causing UTIs, mutations in the QRDRs of gyrA or parC had a greater effect on FQ resistance, especially to CPFX, than efflux pump gene expression from a statistical analysis study of our two previous works. Further research into the molecular basis for FQ resistance could lead to new therapeutic strategies against FQ-resistant E. coli. (c) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

    ELSEVIER SCIENCE BV, 2012年12月, INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 40 (6), 516 - 520, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Minori Matsumoto, Katsumi Shigemura, Toshiro Shirakawa, Yuzo Nakano, Hideaki Miyake, Kazushi Tanaka, Shohiro Kinoshita, Soichi Arakawa, Masato Kawabata, Masato Fujisawa

    Fluoroquinolone (FQ) resistance in Pseudomonas aeruginosa has spread. The purpose of this study was to investigate the correlation between representative FQ, i.e. levofloxacin (LVX), resistance and mutations in the gyrA and parC genes of P. aeruginosa clinical isolates from the urine of urinary tract infection patients and their rapid detection by denaturing high-performance liquid chromatography (DHPLC). The susceptibility to LVX of 114 clinical isolates was measured and the quinolone resistance-determining regions (QRDRs) in the gyrA and parC genes of these isolates were sequenced. DHPLC was undertaken to correlate the distinctive chromatograms with their DNA mutation patterns. Among 114 isolates tested, 22 isolates (19.3%) were resistant to LVX. Six amino acid mutations were detected (Thr83Ile, Asp87Tyr and Asp87Asn in gyrA and Ser87Leu, Ser87Trp and Glu91Arg in parC), existing alone or in combination. There were 10 kinds of mutation patterns. The presence of two or more kinds of mutation significantly correlated with LVX resistance compared with the wild-type or a single mutation (P < 0.0001). DHPLC data identified the number of amino acid mutations with reproducibility distinguishable by peak number and profile of the DHPLC chromatogram. In conclusion, two or more mutations in gyrA and parC were significantly related to LVX resistance in P. aeruginosa. DHPLC facilitated the detection of resistant alleles, providing a rapid (5 min per sample), economical (96 samples per run) and reliable technique for characterising LVX resistance in P. aeruginosa. This rapid detection system could forecast LVX resistance by the DHPLC profile. (C) 2012 Published by Elsevier B.V.

    ELSEVIER SCIENCE BV, 2012年11月, INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 40 (5), 440 - 444, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Chung Hee Sonn, Jong Rip Choi, Tae-Jin Kim, Young-Bin Yu, Kwanghee Kim, Suk Chul Shin, Gil-Hong Park, Toshiro Shirakawa, Hee Sun Kim, Kyung-Mi Lee

    The possible beneficial effects of chronic low-dose irradiation (LDR) and its mechanism of action in a variety of pathophysiological processes such as cancer are a subject of intense investigation. While animal studies involving long-term exposure to LDR have yielded encouraging results, the influence of LDR at the cellular level has been less well defined. We reasoned that since natural killer (NK) cells constitute an early responder to exogenous stress, NK cells may reveal sentinel alterations in function upon exposure to LDR. When purified NK cells received LDR at 4.2 mGy/h for a total of 0.2 Gy in vitro, no significant difference in cell viability was observed. Likewise, no functional changes were detected in LDR-exposed NK cells, demonstrating that LDR alone was insufficient to generate changes at the cellular level. Nonetheless, significant augmentation of cytotoxic, but not proliferative, function was detected when NK cells were stimulated with low-dose IL-2 prior to irradiation. This enhancement of NK cytotoxicity was not due to alterations in NK-activating receptors, NK1.1, NKG2D, CD69 and 2B4, or changes in the rate of early or late apoptosis. Therefore, LDR, in the presence of suboptimal cytokine levels, can facilitate anti-tumor cytotoxicity of NK cells without influencing cellular proliferation or apoptosis. Whether these results translate to in vivo consequences remains to be seen; however, our data provide initial evidence that exposure to LDR can lead to subtle immune-enhancing effects on NK cells and may explain, in part, the functional basis underlying, diverse beneficial effects seen in the animals chronically exposed to LDR.

    OXFORD UNIV PRESS, 2012年11月, JOURNAL OF RADIATION RESEARCH, 53 (6), 823 - 829, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Fukashi Yamamichi, Takayuki Matsuoka, Katsumi Shigemura, Masato Kawabata, Toshiro Shirakawa, Masato Fujisawa

    OBJECTIVE: To establish a mouse xenograft model of metastatic prostate cancer (PCa) and investigate the relationship between metastasis and circulating tumor cells. METHODS: Flow cytometry (FACS) was used to detect suitable PCa cells and markers for detecting circulating tumor cells in vivo. We orthotopically injected androgen receptor-positive and androgen-independent C4-2B PCa cells into 12 severe combined immunodeficiency (SCID) mouse prostates, including 1 vehicle control. We measured the serum prostate-specific antigen levels biweekly after tumor inoculation. Circulating tumor cells (CTCs) were measured qualitatively by fluorescent microscopy immediately after the mice were sacrificed. The mouse prostates and lungs were examined for tumor formation using immunohistochemistry because we found no apparent metastasis, except in the lung. RESULTS: FACS analyses in vitro identified the marker, prostate-specific membrane antigen, and C4-2B cells to be appropriate for additional in vivo study. We confirmed that the serum prostate-specific antigen increase was dependent on time and prostate tumor weight in mice. Of the 11 mice, 6 could be used as the mouse PCa xenograft model. Fluorescent microscopy detected CTCs in the peripheral blood in 5 of the 6 mice constituting the PCa model. Human prostate-specific antigen expression was detected by immunohistochemistry in the prostates of all the mice and in the lung of 2 of the 6 mice, suggesting 2 mice with lung metastasis. CONCLUSION: We have shown the potential establishment of a mouse lung metastatic xenograft model of androgen receptor-positive and androgen-independent C4-2B PCa tumor. However, the present model requires improvement to be a more reproducible, accurate and complete experimental model. Additional study is necessary to verify the relationship between metastasis and CTCs.

    2012年10月, Urology, 80 (4), 951.e1-7 - 7, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • 排尿障害患者におけるデュタステリド内服療法の性機能および血中テストステロン値への影響についての検討

    千葉公嗣, 中野雄造, 原口貴裕, 白川利朗, 田中一志, 荒川創一, 藤澤正人

    2012年09月, 日本性機能学会雑誌, 27 (2号), 175, 日本語

    研究論文(その他学術会議資料等)

  • BPH/LUTSに対するデュタステリドの有用性に関する検討

    原口貴裕, 三宅秀明, 白川利朗, 田中一志, 藤澤正人

    2012年08月, 日本排尿機能学会誌, 23 (1号), 194, 日本語

    研究論文(その他学術会議資料等)

  • Detection of tumor markers in prostate cancer and comparison of sensitivity between real time and nested PCR.

    Takayuki Matsuoka, Katsumi Shigemura, Fukashi Yamamichi, Masato Fujisawa, Masato Kawabata, Toshiro Shirakawa

    The objective of this study is to investigate and compare the sensitivity in conventional PCR, quantitative real time PCR, nested PCR and western blots for detection of prostate cancer tumor markers using prostate cancer (PCa) cells. We performed conventional PCR, quantitative real time PCR, nested PCR, and western blots using 5 kinds of PCa cells. Prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), and androgen receptor (AR) were compared for their detection sensitivity by real time PCR and nested PCR. In real time PCR, there was a significant correlation between cell number and the RNA concentration obtained (R(2)=0.9944) for PSA, PSMA, and AR. We found it possible to detect these markers from a single LNCaP cell in both real time and nested PCR. By comparison, nested PCR reached a linear curve in fewer PCR cycles than real time PCR, suggesting that nested PCR may offer PCR results more quickly than real time PCR. In conclusion, nested PCR may offer tumor maker detection in PCa cells more quickly (with fewer PCR cycles) with the same high sensitivity as real time PCR. Further study is necessary to establish and evaluate the best tool for PCa tumor marker detection.

    2012年06月27日, The Kobe journal of medical sciences, 58 (2), E51-9 - 9, 英語, 国内誌

    [査読有り]

    研究論文(学術雑誌)

  • Fatma Y. Meligy, Katsumi Shigemura, Hosny M. Behnsawy, Masato Fujisawa, Masato Kawabata, Toshiro Shirakawa

    The objective of the study is to evaluate efficiency of in vitro isolation and myogenic differentiation of mesenchymal stem cells (MSCs) derived from adipose connective tissue (AD-MSCs), bone marrow (BM-MSCs), and skeletal muscle tissue (MC-MSCs). MSCs were isolated from adipose connective tissue, bone marrow, and skeletal muscle tissue of two adult 6-wk-old rats. Cultured MSCs were treated with 5-azacytidine (AZA) to induce myogenic differentiation. Isolated MSCs and differentiated cells were evaluated by immunocytochemistry (ICC), fluorescence-activated cell sorting (FACS), PCR, and RT-PCR. AD-MSCs showed the highest proliferation rate while BM-MSCs had the lowest one. In ICC, isolated MSCs had strong CD90- and CD44-positive expression and negative expression of CD45, CD31, and CD34, while AZA-treated MSCs had strong positive desmin expression. In FACS analysis, AD-MSCs had the highest percentage of CD90- and CD44-positive-expressing cells (99% and 96%) followed by BM-MSCs (97% and 94%) and MC-MSCs (92% and 91%).At 1 wk after incubation with AZA treatment, the peak of myogenin expression reached 93% in differentiated MC-MSCs, 83.3% in BM-MSCs, and 77% in AD-MSCs. MSCs isolated from adipose connective tissue, bone marrow, and skeletal muscle tissue have the same morphology and phenotype, but AD-MSCs were the most easily accessible and had the highest rate of growth on cultivation and the highest percentage of stem cell marker expression. Moreover, although MC-MSCs showed the highest rate of myogenic differentiation potential and expression of myoblast markers, AD-MSCs and BM-MSCs still can be valuable alternatives. The differentiated myoblastic cells could be an available new choice for myoblastic auto-transplantation in regeneration medicine.

    SPRINGER, 2012年04月, IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 48 (4), 203 - 215, 英語

    [査読有り]

    研究論文(学術雑誌)

  • K. Iguchi, F. Sakurai, K. Tomita, K. Katayama, T. Yamaguchi, K. Kawabata, M. Tagawa, M. Kawabata, T. Shirakawa, H. Mizuguchi

    Carrier cells delivering a conditionally replicating adenovirus (CRAd), which selectively replicates in tumor cells and induces tumor cell lysis, have promising potential for treatment of cancer because CRAd-loaded carrier cells evade inhibition by neutralizing anti-adenovirus (Ad) antibodies and because the carrier cells are locally retained at the injection point after local injection. A previous study by Hamada et al. demonstrated that carrier cells (CRAd-containing cell fragments derived from the carrier cells) are engulfed into the target cells, probably through a pathway independent of the primary receptor for Ad, the coxsackievirus and Ad receptor (CAR) (Mol Ther, 15: 1121-1128; 2007); however, it remains to be elucidated whether carrier cells infected with a conventional CRAd, which is composed of subgroup-C Ad serotype-5 (Ad5), mediate antitumor effects on CAR-negative cells. In order to examine whether carrier cells delivering a conventional CRAd (Carrier-F5) induce lysis of CAR-negative tumor cells, CAR-positive and CAR-negative tumor cells were incubated with Carrier-F5. Carrier-F5 mediated efficient killing of CAR-positive tumor cells; however, CAR-negative tumor cells were almost refractory to Carrier-F5. On the other hand, carrier cells loaded with a fiber-substituted CRAd containing fiber proteins of Ad serotype-35 (Ad35) (CRAd-F35), which binds to human CD46 for infection, showed efficient killing of both CAR-positive and CAR-negative tumor cells. Intra-tumoral injection of carrier cells loaded with CRAd-F35 (Carrier-F35) also resulted in efficient regression of both CAR-positive and CAR-negative tumors. These results demonstrated that the expression levels of receptors for Ad are an important factor for CRAd-loaded carrier cell-mediated cancer therapy, and that Carrier-F35 would have potential as a cancer treatment for not only CAR-positive tumors but also CAR-negative tumors. Cancer Gene Therapy (2012) 19, 118-125; doi: 10.1038/cgt.2011.74; published online 11 November 2011

    NATURE PUBLISHING GROUP, 2012年02月, CANCER GENE THERAPY, 19 (2), 118 - 125, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Z. Adhim, X. Lin, W. Huang, N. Morishita, T. Nakamura, H. Yasui, N. Otsuki, K. Shigemura, M. Fujisawa, K. Nibu, T. Shirakawa

    Most cancer chemotherapeutic agents are administered at the maximum-tolerated dose (MTD) in short cycles with treatment breaks. However, MTD-based chemotherapies are often associated with significant toxicity and treatment breaks allow the opportunity for tumor regrowth and acquisition of chemoresistance. To minimize these drawbacks, a metronomic strategy, in which chemotherapeutics are administered at doses significantly below the MTD without treatment breaks, has been suggested by many investigators. The antitumor effect of metronomic chemotherapy may be partially due to inhibition of tumor angiogenesis, and it could be enhanced by a combination therapy, including antiangiogenic agents. In this study, we evaluated the synergistic effect of E10A, an adenovirus carrying the endostatin gene, the most potent inhibitors of tumor angiogenesis, in combination with weekly low-dose cisplatin in a xenograft mouse model for head and neck squamous-cell carcinoma. The E10A induced mRNA and protein expressions of endostatin in H891 cells in vitro. E10A significantly enhanced the in vivo tumor growth inhibitory effect of cisplatin. Immunohistochemical analysis with a TUNEL (terminal deoxynucleotidyl transferase-mediated nick-end labeling) assay and anti-CD31 antibodies revealed that the combination of E10A and cisplatin induced high levels of cell apoptosis and inhibited tumor angiogenesis. Importantly, E10A increased the platinum concentrations in tumors to fivefold higher than that induced by cisplatin alone. Cancer Gene Therapy (2012) 19, 144-152; doi: 10.1038/cgt.2011.79; published online 25 November 2011

    NATURE PUBLISHING GROUP, 2012年02月, CANCER GENE THERAPY, 19 (2), 144 - 152, 英語

    研究論文(学術雑誌)

  • Tomihiko Yasufuku, Katsumi Shigemura, Toshiro Shirakawa, Minori Matsumoto, Yuzo Nakano, Kazushi Tanaka, Soichi Arakawa, Masato Kawabata, Masato Fujisawa

    We examined Enterococcus faecalis strains clinically isolated from 100 patients with urinary tract infections (UTIs) for their susceptibility to levofloxacin (LVX) by measuring the MIC and investigated amino acid mutations by direct DNA sequencing, which were then correlated with LVX resistance. Next, we studied risk factors for LVX resistance, such as age, gender, and previous fluoroquinolone use, and investigated the statistical correlation of these risk factors with each amino acid mutation and LVX resistance. Of the 100 isolates tested, 14 isolates showed LVX resistance and all of these isolates had amino acid mutations. We demonstrated that 2 out of 4 mutations (Ser83-to-Ile in gyrA and Ser80-to-Ile in parC) had a significant correlation with LVX resistance. There was a significant relationship between isolates with 2 or 3 amino acid mutations and LVX resistance. In addition, we found a significant correlation between the previous use of fluoroquinolones and LVX resistance or the presence of mutations and also demonstrated that previous use of other types of antibiotics was significantly related to the presence of mutations by multivariate analysis. In conclusion, we found significant correlation between amino acid mutations in E. faecalis, LVX resistance, and risk factors such as previous use of fluoroquinolones.

    AMER SOC MICROBIOLOGY, 2011年11月, JOURNAL OF CLINICAL MICROBIOLOGY, 49 (11), 3912 - 3916, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Z. Adhim, T. Matsuoka, T. Bito, K. Shigemura, K-M Lee, M. Kawabata, M. Fujisawa, K. Nibu, T. Shirakawa

    BACKGROUND: Although the anti-tumour effect of cyclooxygenase-2 (Cox-2) inhibitors in invasive bladder cancer has been confirmed, its mechanisms of action are unclear. Recently, the concept of an epithelial-to-mesenchymal transition (EMT) promoting carcinoma progression has been suggested, and a key feature of the EMT is the downregulation of E-cadherin. In this study, we investigated the effect of Cox-2 inhibitors on reversal EMT and tumour growth inhibition in bladder cancer cells. METHODS: We used three Cox-2 inhibitors, etodolac, celecoxib and NS-398 and three human bladder cancer cell lines, T24, 5637 and KK47, in this study. T24 xenograft tumour mouse model was used in the in vivo study. RESULTS: Within the clinical drug concentrations, only etodolac showed the in vitro growth inhibition in T24 not in the other cell lines. Etodolac reduced SNAIL mRNA and vimentin cell surface expression, and induced E-cadherin mRNA and E-cadherin cell surface expression, in T24. Etodolac also most strongly inhibited the cell migration of T24 in vitro and showed the highest tumour growth inhibition in T24 tumour in vivo. CONCLUSION: Etodolac at clinical doses exhibited induced in vitro and in vivo anti-tumour effects and reversal effect of EMT in T24. These results suggest that etodolac is a good candidate for an anti-tumour or chemopreventive reagent for high-grade bladder cancer. British Journal of Cancer (2011) 105, 393-402. doi:10.1038/bjc.2011.262 www.bjcancer.com Published online 12 July 2011 (C) 2011 Cancer Research UK

    NATURE PUBLISHING GROUP, 2011年07月, BRITISH JOURNAL OF CANCER, 105 (3), 393 - 402, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Aya Saito, Naoya Morishita, Chihomi Mitsuoka, Shunichi Kitajima, Katsuyuki Hamada, Kyung-Mi Lee, Masato Kawabata, Masato Fujisawa, Toshiro Shirakawa

    Background Although cancer therapy using replication-selective oncolytic adenoviruses has been available for many years, its anti-tumor efficacy is suboptimal as a result of low and nonspecific infectivity that depends on coxsackie adenovirus receptor expression of the target cancer and normal cells, and generation of an anti-adenovirus neutralizing antibody. In addition, concerns of triggering a severe innate immune response against the adenovirus limit the systemic administration. We developed the carrier cell-based oncolytic virus system (CBOVS) using irradiated tumor cells as carrier cells and concealing the adenovirus (Ad-IAI.3B) inside to improve the specific infectivity. We investigated the anti-tumor effect of CBOVS in a multiple lung tumor mouse model. Methods The ability of CBOVS to infect Ad-IAI.3B to the target cancer cells was examined in vitro in the presence of anti-adenovirus antibodies. To evaluate the systemic effect of CBOVS, we intravenously injected CBOVS into mice with lung tumors (KLN205 cell lines). Results CBOVS enhanced the infectivity of Ad-IAI.3B to tumor cells in the presence of anti-adenovirus antibodies in vitro. Intravenous injections of CBOVS produced an accumulation of the adenovirus in the lung-bearing tumors and produced a strong anti-tumor effect in vivo. Furthermore, lymphocytes collected from the CBOVS-treated mice induced an increase in cytokines related to the Th1 response (interferon-gamma, interleukin-12) by pulsing with KLN205. Conclusions These findings suggest that CBOVS could protect adenoviruses from neutralizing antibodies and systemically deliver them to lung tumors. Furthermore, CBOVS appears to have potential as a tumor cell vaccine that activates cytotoxic immunity against cancer cells. Copyright (C) 2011 John Wiley & Sons, Ltd.

    WILEY-BLACKWELL, 2011年06月, JOURNAL OF GENE MEDICINE, 13 (6), 353 - 361, 英語

    研究論文(学術雑誌)

  • Tomihiko Yasufuku, Katsumi Shigemura, Toshiro Shirakawa, Yuzo Nakano, Kazushi Tanaka, Soichi Arakawa, Shouhiro Kinoshita, Kunihiro Nishimura, Masato Kawabata, Masato Fujisawa

    As fluoroquinolone-resistant strains of Escherichia coli emerge, several risk factors for fluoroquinolone resistance have become evident, such as amino acid mutations in the quinolone resistance determining regions (QRDR) of gyrA and parC and previous use of fluoroquinolone. This study investigated risk factors for fluoroquinolone resistance and amino acid mutation in the QRDR in E. coli. We investigated the statistical correlation between each amino acid mutation and resistance to levofloxacin. We examined the minimum inhibitory concentration (MIC) of levofloxacin and the amino acid mutations of gyrA and parC by direct DNA sequence in E. coli clinically isolated from urinary tract infection (UTI) patients. We investigated risk factors for levofloxacin resistance, such as age, sex, and previous use of fluoroquinolone. We found a significant correlation between the number of mutations and resistance to levofloxacin (p < 0.001) and between the presence of underlying urinary tract disease and the presence of mutations (p = 0.004) by multivariate analyses. Three mutations in QRDR were demonstrated to be significantly correlated with levofloxacin resistance. In conclusion, these findings contribute to our understanding of the molecular mechanisms and risk factors for fluoroquinolone resistance.

    INFORMA HEALTHCARE, 2011年02月, SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, 43 (2), 83 - 88, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Phenotypic and Genotypic Characterization of Vibrio cholerae Clinically Isolated in Surabaya, Indonesia

    Tomoyuki Nishibori, Garry Cores de Vries, Dadik Rahardjo, Eddy Bagus Wasito, Ismoedijanto De, Shouhiro Kinoshita, Yoshitake Hayashi, Hak Hotta, Masato Kawabata, Toshiro Shirakawa, Yoshio Iijima, Ro Osawa

    The phenotypic and genotypic characteristics of 6 clinical strains of Vibrio cholerae isolated in Surabaya, Indonesia in 2009 were examined. The DNA fingerprints obtained suggested that these isolates were not from a single clone. Furthermore, all isolates produced cholera toxin and possessed the classical type of toxin B subunit gene, thus meaning that this is the first report of the occurrence of El Tor variants of V. cholerae in Indonesia. Although all isolates were sensitive to almost all antibiotics tested, including ampicillin, chloramphenicol, ciprofloxacin, gentamicin, levofloxacin, kanamycin, nalidixic acid, norfloxacin, streptomycin, trimethoprim-sulfamethoxazole, and tetracycline, and had no mutation in the gyrA and parC genes, they nevertheless possessed the class 1 integron that is a molecular vehicle for the acquisition of antibiotic resistance genes, suggesting that they have the potential to acquire the genetic element for drug resistance.

    NATL INST INFECTIOUS DISEASES, 2011年01月, JAPANESE JOURNAL OF INFECTIOUS DISEASES, 64 (1), 7 - 12, 英語

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    研究論文(学術雑誌)

  • Tomihiko Yasufuku, Katsumi Shigemura, Toshiro Shirakawa, Minori Matsumoto, Yuzo Nakano, Kazushi Tanaka, Soichi Arakawa, Shouhiro Kinoshita, Masato Kawabata, Masato Fujisawa

    Escherichia coli is one of the most common pathogens in urinary tract infections (UTIs), and antibiotic resistance in E. coli is becoming a serious problem in treating UTI. Efflux system overexpression is reported to contribute to E. coli resistance to several antibiotics. This study investigated the correlation of antibiotic susceptibilities with the overexpression of the efflux pump genes such as marA, yhiU, yhiV, and mdfA and with risk factors for antibiotic resistance in E. coli isolated from UTI patients. We examined the expression level of efflux pump genes using quantitative real-time reverse transcription-PCR (qRT-PCR). We also tested the in vitro susceptibilities to 12 kinds of antibiotics in 64 clinical strains of E. coli isolated from UTI patients. By multivariate analyses we revealed significant relationships between the overexpression of (i) marA and MICs of cefepime (FEP) and nalidixic acid (NAL), (ii) yhiV and MICs of minocycline (MIN), and (iii) mdfA and MICs of sitafloxacin (STX). In our investigation of the efflux pump genes, risk factors such as gender and the previous use of fluoroquinolones correlated with the overexpression of marA, and indwelling catheter use correlated with the overexpression of mdfA. In conclusion, we demonstrated that the increased expression of efflux pump genes such as marA and mdfA can lead to fluoroquinolone resistance in E. coli. These results contribute to our knowledge of the efflux system and raise the possibility of developing new agents, such as efflux pump inhibitors (EPIs), to antibiotic-resistant E. coli.

    AMER SOC MICROBIOLOGY, 2011年01月, JOURNAL OF CLINICAL MICROBIOLOGY, 49 (1), 189 - 194, 英語

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    研究論文(学術雑誌)

  • Sakura Yamamoto, Jun Wada, Takane Katayama, Takumi Jikimoto, Masakuni Nakamura, Shohiro Kinoshita, Kyung-Mi Lee, Masato Kawabata, Toshiro Shirakawa

    We developed a novel vaccine platform utilizing Bifidobacterium as an antigen delivery vehicle for mucosal immunization. Genetically modified Bifidobacterium longum displaying Salmonella-flagellin on the cell surface was constructed for the oral typhoid vaccine. The efficiency of this vaccine was evaluated in a murine model of typhoid fever. We then orally administered 2.5 x 10(7) CFU of the recombinant Bifidobacterium longum (vaccine) or parental Bifidobacterium longum, or PBS to BALB/C mice every other day for 2 weeks. After the administration, a total of 42 mice (14 mice in each group) were challenged with Salmonella Typhimurium (1.0 x 10(7) CFU/mouse). While 12 mice in the PBS group, and 9 in the parental Bifidobacterium longum group died (median survival: 14 and 25 days), only two in the vaccine group died. These data support that our genetically modified Bifidobacterium antigen delivery system offers a promising vaccine platform for inducing efficient mucosal immunity. (C) 2010 Elsevier Ltd. All rights reserved.

    ELSEVIER SCI LTD, 2010年09月, VACCINE, 28 (41), 6684 - 6691, 英語

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    研究論文(学術雑誌)

  • Toshinori Bito, Naoko Sumita, Taro Masaki, Toshiro Shirakawa, Masato Ueda, Ryutaro Yoshiki, Yoshiki Tokura, Chikako Nishigori

    Stat3 is activated by the outer stressors, such as ultraviolet (UV) exposure. In this study, we investigated the Stat3 response to UV irradiation in human epidermal keratinocytes and dermal fibroblasts. Results indicated that UVB and UVC differentially activate Stat3 in these cells. The UV-induced Stat3 activation was mediated by both reactive oxygen species (ROS) and DNA damage, and the dominancy of ROS and DNA damage to activate Stat3 depended on the wavelength of UV. By using fibroblasts from a patient with xeroderma pigmentosum A (XP-A) and those transfected with human XPA gene, we found that UVB activates Stat3 via both ROS and DNA damage, while UVC does so mainly via DNA damage. The present data suggest that Stat3 activation in UV-exposed human skin is one of the initial events where DNA damage and ROS are involved.

    WILEY-BLACKWELL, 2010年07月, EXPERIMENTAL DERMATOLOGY, 19 (7), 654 - 660, 英語

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    研究論文(学術雑誌)

  • NRAMP1/SLC11A1 GENE POLYMORPHISMS AND HOST SUSCEPTIBILITY TO MYCOBACTERIUM TUBERCULOSIS AND M. LEPRAE IN SOUTH SULAWESI, INDONESIA

    Mochammad Hatta, Ratnawati, Motoko Tanaka, Jun Ito, Toshiro Shirakawa, Masato Kawabata

    Genetic host factor may play an important role in controlling mycobacterial infections such as tuberculosis and leprosy Natural resistance associated macrophage protein 1 (Nramp1, alias Slc11a1) gene has been suggested to an associated gene of the host susceptibility to mycobacterium infection. To determine the association of Nramp1/Slc11a1 with tuberculosis and leprosy, we analyzed using polymerase chain reaction restriction fragment length polymorphisms threevariants (D543N, 3'UTR and INT4) of Nramp1/Slc11a1 gene in 58 tuberculosis patients (mean age, 34 0 +/- 13 1), 42 leprosy patients (mean age, 35 0 +/- 14 3) and 198 healthy controls (mean age, 32 0 +/- 12 9) from South Sulawesi, Indonesia We observed an association of INT4 polymorphism with paucibacillary type of leprosy (p=0.032, 1df, OR=2 975, CI=1.057-8.373), but not to multibacillary type (p=0 173, 1df, OR=2 248, CI=0.682-7.404). No significant association was found in the three variants with tuberculosis in this population.

    SOUTHEAST ASIAN MINISTERS EDUC ORGANIZATION, 2010年03月, SOUTHEAST ASIAN JOURNAL OF TROPICAL MEDICINE AND PUBLIC HEALTH, 41 (2), 386 - 394, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Yanagi D, de Vries GC, Rahardjo D, Alimsardjono L, Wasito EB, De I, Kinoshita S, 林 祥剛, 堀田 博, Osawa R, 川端 眞人, 白川 利朗

    2009年08月, Diagn Microbiol Infect Dis, 64(4):422-6., 英語

    [査読有り]

    研究論文(学術雑誌)

  • A pilot study of quality of life of patients with hormone-refractory prostate cancer after gene therapy

    Shirakawa T

    2009年05月, Anticancer research, Vol. 29, No. 5, pp. 1533-7, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Shirakawa T

    2009年04月, Oncology reports, Vol. 21, No. 4, pp. 903-8, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Nakagawa T, Tanaka H, Shirakawa T, Gotoh A, Hayashi Y, Hamada K, Tsukuda M, Nibu K

    2009年03月, Arch Otolaryngol Head Neck Surg., 135(3):282-6 (3), 282 - 286, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Okamura N, Masuda T, Gotoh A, Shirakawa T, Terao S, Kaneko N, Suganuma K, Watanabe M, Matsubara T, Seto R, Matsumoto J, Kawakami M, Yamamori M, Nakamura T, Yagami T, Sakaeda T, Fujisawa M, Nishimura O, Okumura K

    2008年08月, Proteomics, Vol. 8, No. 15, pp. 3194-3203 (15), 3194 - 3203, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Clinical study results of a phase I/II study of AD-OC-TK/VAL gene therapy for the patients with metastatic or local recurrent prostate cancer

    Shirakawa Toshiro, Gotoh Akinobu, Terao Shuji, Hinata Nobuyuki, Goda Kazumasa, Tanka Kazushi, Takenaka Atsushi, Hara Isao, Kamidono Sadao, Fujisawa Masato

    2008年04月, JOURNAL OF GENE MEDICINE, 10 (4), 433 - 434

    [査読有り]

  • Ito J, Dung DT, Vuong MT, Tuyen do G, Vinh le D, Huong NT, Ngoc TB, Ngoc NT, Hien MT, Hao DD, Oanh LT, Lieu do T, Fujisawa M, Kawabata M, Shirakawa T

    2008年, Nephron Clinical practice, Vol. 109, No. 1, pp. c25-32 (1), c25 - 32, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Okamoto A, Shirakawa T, Bito T, Shigemura K, Hamada K, Gotoh A, Fujisawa M, Kawabata M

    2008年01月, Urology, Vol. 71, No. 1, pp. 156-60 (1), 156 - 160, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Toshiro Shirakawa, Shuji Terao, Nobuyuki Hinata, Kazushi Tanaka, Atsushi Takenaka, Isao Hara, Kazuro Sugimura, Masafumi Matsuo, Katsuyuki Hamada, Kohzo Fuji, Takatsugu Okegawa, Eiji Higashihara, Thomas A. Gardner, Chinghai Kao, Leland W. K. Chung, Sadao Kamidono, Masato Fujisawa, Akinobu Gotoh

    We evaluated the long-term safety and efficacy of Ad-OC-TK (recombinant adenoviral vector carrying an osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) gene therapy for hormone-refractory prostate cancer. Ad-OC-TK/VAL therapy is the first in vivo adenovirus-mediated gene therapy to be used to treat metastatic prostate cancer, including bone metastasis. Six patients were enrolled in this trial, and two doses of Ad-OC-TK (2.5 x 10(9) or 2.5 x 10(10) plaque-forming units) were injected into locally recurrent tumor or bone metastasis on day 1 and day 8. Patients were also given VAL (3 g/day) for 21 days. Safety and efficacy were evaluated for at least 8 months in each patient. All patients tolerated this therapy with no serious adverse events. One prostate-specific antigen (PSA) response (from 318.3 to 4.9 ng/ml) was observed with a time to PSA progression (TTP) of 12 months. Docetaxel (30 mg/m(2) per week) and estramustine (560 mg/day) combination chemotherapy (DE) was given to three docetaxel-naive patients on PSA failure after gene therapy. All three patients had a PSA response to DE therapy with 21, 7, and 4 months of TTP. These results suggest that additional trials are warranted.

    MARY ANN LIEBERT INC, 2007年12月, HUMAN GENE THERAPY, 18 (12), 1225 - 1232, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Shuji Terao, Toshiro Shirakawa, Shuji Kubo, Acharya Bishunu, Sang-Jin Lee, Kazumasa Goda, Mamoru Tsukuda, Katsuyuk Hamada, Masatoshi Tagawa, Atsushi Takenaka, Masato Fujisawa, Akinobu Gotoh

    OBJECTIVES To develop a novel therapeutic strategy against human bladder cancer using Ad-MK-Ela-a midkine (MK) promoter-regulated, conditionally replicating, adenovirus. METHODS We tested several human cancer cell lines in vitro, including those of bladder cancer (KK47, 5637, and T24), lung cancer (A549), and head and neck cancer (H891). In each cell line, we examined MK mRNA expression by TaqMan real-time quantitative polymerase chain reaction, MK promoter activity, after plasmid transfection, using a luciferase assay, and the transduction efficiency by co-transfection with the cytomegalovirus-beta-gal plasmid. In these cells, we assessed the cell type-specific replication of Ad-MK-Ela virus by measuring the Ela DNA copy number by real-time polymerase chain reaction and the cell growth inhibition due to this virus using the Alamar blue assay. In animal studies, nude mice were subcutaneously inoculated with KK47 cells and later intratumorally injected with phosphate-buffered saline or Ad5-CMV-LacZ or Ad-MK-Ela. RESULTS The MK mRNA expression level and MK promoter-driven luciferase activity were relatively greater and markedly increased, respectively, in the 5637, A549, and KK47 cells than in the T24 and H891 cells. After Ad-MK-EIa infection, the Ela DNA copy number increased more significantly in the KK47, 5637, and A549 cells than in the T24 and H891 cells. At a multiplicity of infection of 0.01, Ad-MK-Ela significantly inhibited KK47 and 5637 cell growth. In vivo, Ad-MK-Ela injection markedly inhibited KK47 tumor growth. CONCLUSIONS We have demonstrated the antitumor effect of Ad-MK-Ela in a human bladder cancer model overexpressing MK mRNA.

    ELSEVIER SCIENCE INC, 2007年11月, UROLOGY, 70 (5), 1009 - 1013, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Katsuyuki Hamada, Junzo Desaki, Kou Nakagawa, Ting Zhang, Toshiro Shirakawa, Akinobu Gotoh, Masatoshi Tagawa

    Although replication-competent viruses have been developed to treat cancers, their cytotoxic effects are insufficient, as infection is inhibited by the generation of neutralizing antibodies. To address this limitation, we developed a carrier cell system to deliver a replication-competent adenovirus. Carrier cells infected with replication-competent adenovirus were incubated with target cancer cells in a high titer of anti-adenovirus antibody. Carrier cells were injected into syngeneic subcutaneous tumors after immunization with adenovirus. Carrier cell-derived cell fragments containing viral particles were engulfed by proliferative target cancer cells. This engulfment-mediated transfer of adenovirus was not inhibited by the anti-adenovirus antibody and enabled repetitive infection. After the induction of anti-adenoviral cytotoxic T-lymphocyte (CTL) responses by immunization with adenovirus, administration of carrier cells infected with a replication-competent adenovirus induced complete tumor regression. Adenovirus-GM-CSF augmented the anti-tumor effect of carrier cells by increasing anti-adenoviral and anti-tumoral CTL responses and decreased the number of injections of carrier cells required to induce complete tumor regression. This novel carrier cell mediated viral transfection system might prove useful in a variety of cancer therapies.

    NATURE PUBLISHING GROUP, 2007年06月, MOLECULAR THERAPY, 15 (6), 1121 - 1128, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Yasuhiko Hoshitani, Haruhiko Ishida, Naoki Otsuki, Toshiro Shirakawa, Akinobu Gotoh, Ken-ichi Nibu

    Objective: To evaluate the antitumor immune effects of B7-1 gene expression mediated by adenoviral vectors against squamous cell carcinoma. Transfection of the costimulatory molecule B7-1 gene into certain murine tumors increases antitumor immunity and suppresses tumor growth. Design: In vitro and in vivo study. Interventions: A murine squamous cell carcinoma cell line, KLN205, was infected with adenoviral vectors carrying either B7-1 (AdB7) or LacZ (AdCL) genes. Infected cells were injected subcutaneously into the flanks of DBA/2 mice. Main Outcome Measures: The growth of tumors infected with adenviral vectors was measured. Results: AdB7-infected cells grew significantly slower than AdCL-infected cells in vivo, while there was no significant difference in the growth rates between the 2 groups in vitro. Moreover, significant growth suppression of rechallenged noninfected parental cells was observed in the mice immunized with AdB7-infected cells but not in those immunized with AdCL-infected cells. Conclusion: These results suggest that the B7-1 gene has therapeutic potential for immunotherapy against head and neck squamous cell carcinoma.

    AMER MEDICAL ASSOC, 2007年03月, ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY, 133 (3), 270 - 275, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Katsuyuki Hamada, Toshiro Shirakawa, Akinobu Gotoh, Jack A. Roth, Michele Follen

    Objective. In most cervical cancers, human papillornaviruses (HPVs) are identified. The E6 and E7 genes of HPVs encode proteins, that interfere with the function of the tumor suppressor proteins p53 and Rb. We are exploring the potential use of antisense HPV RNA transcripts for gene therapy for HPV-positive cervical cancers. Methods. Via a recombinant adenoviral vector, Ad5CMV-HPV 16 AS, we introduced the antisense RNA transcripts of the E6 and E7 genes of HPV type 16 into human cervical cancer SiHa cells harboring HPV 16. We then analyzed the effects of expression of these genes on cell and tumor growth. Results. HPV 16 E6/E7 antisense RNA was detected for 14 days in Ad5CMV-HPV 16 AS-infected cells. After infection, E6 and E7 protein expression was suppressed, and p53 and Rb protein expression increased. The Ad5CMV-HPV 16 AS-infected cells underwent apoptosis in vitro and in vivo. Cell growth and tumorigenicity were greatly suppressed. Ad5CMV-HPV 16 AS treatment significantly reduced the volumes of established subcutaneous tumors. Conclusion. Transfection of cervical cancer cells with HPV 16 E61E7 antisense RNA in a form such as Ad5CMV-HPV 16 AS might be a potentially useful approach to the therapy of HPV 16-positive cervical cancer. Published by Elsevier Inc.

    ACADEMIC PRESS INC ELSEVIER SCIENCE, 2006年12月, GYNECOLOGIC ONCOLOGY, 103 (3), 820 - 830, 英語

    [査読有り]

    研究論文(学術雑誌)

  • SCCmec typing and detection of VISA-related genes in methicillin-resistant Staphylococcus aureus clinical strains from Kobe University Hospital, Japan

    Shirakawa T

    2006年11月, The Southeast Asian Journal Of Tropical Medicine And Public Health, Vol. 37, No. 6, pp. 1149-55, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Tetsuo Takata, Toshiro Shirakawa, Yoshiko Kawasaki, Shohiro Kinoshita, Akinobu Gotoh, Yasunobu Kano, Masato Kawabata

    Background A critical component of the host defense against enteric infections is the immunological response of the mucosal membrane, a major starting point of infectious disease, such as typhoid fever. The mucosal immune system consists of an integrated network of lymphoid tissues, mucous membrane-associated cells, and effector molecules. In the present study, we developed a recombinant Bifidobacterium animalis (B. animalis) genetically modified with the Salmonella flagellin gene for mucosal immunization as an oral typhoid vaccine. Methods We constructed an oral vaccine against Salmonella typhimurium, consisting of recombinant B. animalis containing the flagellin gene of Salmonella. The recombinant B. animalis was administered orally to mice every other day for 6 weeks. Anti-flagellin antibodies in the serum and stools were measured by enzyme-linked immunosorbent assay (ELISA). Results We detected significantly higher levels of flagellin-specific IgA in the serum and stools of the mice treated with the recombinant B. animalis containing the flagellin gene than was seen in those treated with parental B. animalis. Conclusions Our findings suggest that an oral vaccination using recombinant B. animalis genetically modified with the flagellin gene of Salmonella may be effective against Salmonella infections. Copyright (c) 2006 John Wiley & Sons, Ltd.

    JOHN WILEY & SONS LTD, 2006年11月, JOURNAL OF GENE MEDICINE, 8 (11), 1341 - 1346, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Hiroshi Okada, Toshiro Shirakawa, Akinobu Gotoh, Yutaka Kamiyama, Satoru Muto, Hisamitsu Ide, Yukio Hamaguchi, Shigeo Horie

    A new, automated How cytometry-based urine bacterium analyzer (UBA) was developed. We assessed the UBA for linearity of measurement, reproducibility of results, carryover rate, and correlation of measured results with those determined by urine culture. We also evaluated its ability to screen urine samples for significant bacteriuria. The UBA showed excellent linearity and a minor carryover rate. Results from the UBA were highly reproducible, and in between-run precision assays, the coefficients of variation for the UBA results were smaller than those for the urine culture results. Two hundred seventy-three urine specimens from patients attending the outpatient clinics of two university-based hospitals were examined. The results for the UBA were compared with those for urine culture. The UBA detected significant bacteriuria with a sensitivity of 96.6%, a specificity of 79.9%, a positive predictive value of 57.0%, a negative predictive value of 98.8%, a false-positive rate of 15.8%, a false-negative rate of 0.7%, and an accuracy of 83.5%. These results were comparable to or better than those obtained with previously reported screening procedures. The UBA can perform accurate enumeration of bacterial cells automatically in 90 seconds and can be used for the screening of significant bacteriuria.

    AMER SOC MICROBIOLOGY, 2006年10月, JOURNAL OF CLINICAL MICROBIOLOGY, 44 (10), 3596 - 3599, 英語

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    研究論文(学術雑誌)

  • Claudia Marcia Benedetto de Carvalho, Luciana Werneck Zuccherato, Masato Fujisawa, Toshiro Shirakawa, Andrea Kely Campos Ribeiro-dos-Santos, Sidney E. B. Santos, Sergio Danilo Junho Pena, Fabricio Rodrigues Santos

    A recurrent partial azoospermia factor C (AZFc) deletion, called gr/gr, has been reported to be a male infertility risk factor. A specific type of Y chromosome observed in approximately 30% of Japanese males (haplogroup D derived at YAP+) is believed to have a fixed gr/gr deletion. A recent study claimed that spermatogenic failure is more likely in males with D Y chromosomes, because of the gr/gr deletion, the presence of which is not well characterized among D haplogroup chromosomes. We therefore decided to perform a systematic study of the frequency of the gr/gr deletion in the Japanese. We studied fertile and infertile males to investigate the possibility of different gr/gr frequencies. The deletions were detected by use of single tagged-sequences (STSs) and the D haplogroup sub-lineages typing were done by use of the biallelic markers M174, M64, M116.1, 12f2.2, M15, M151, and M125. Analysis of gr/gr deleted Y chromosomes showed that all are classified as haplogroup D2, suggesting a lineage association. The subtype D2b1 was most frequent among the Japanese, in control and infertile samples. The haplogroups D2b2, D*, and D1 were not found in any population group. Remarkably, we observed no statistical difference between haplogroup D sub-lineages of the infertile and control groups, although the statistical power of this study is low. This study suggests lack of significant evidence of increased infertility risk in haplogroup D Japanese males. We were also able to establish the ancestral chromosome that suffered a gr/gr deletion, and propose a new Y chromosome phylogeny for haplogroup D and its derivatives. In summary, we were able to define the frequency of gr/gr deletion in Japanese males and show that the gr/gr deletion was probably present in the ancestral Y chromosome that entered Japan at least 12,000 years ago.

    SPRINGER TOKYO, 2006年09月, JOURNAL OF HUMAN GENETICS, 51 (9), 794 - 799, 英語

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    研究論文(学術雑誌)

  • N Hinata, T Shirakawa, S Terao, K Goda, K Tanaka, Y Yamada, Hara, I, S Kamidono, M Fujisawa, A Gotoh

    There is no effective therapy for hormone-refractory prostate cancer and a novel therapeutic modality, such as a gene therapy, should be actively pursued. Previously, Gardner and Chung conducted a phase I clinical trial of Ad-OC-TK (recombinant adenoviral vector containing osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) for the treatment of hormone-refractory prostate cancer at the University of Virginia. We report on our ongoing phase I/II clinical trial of Ad-OC-TK plus VAL for the treatment of advanced prostate cancer at the Kobe University Hospital, Japan.

    BLACKWELL PUBLISHING, 2006年06月, INTERNATIONAL JOURNAL OF UROLOGY, 13 (6), 834 - 837, 英語

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    研究論文(学術雑誌)

  • M Miyata, T Shirakawa, B Acharya, S Terao, A Gotoh

    Nafamostat mesilate (NM), a synthetic protease inhibitor, is the most commonly used anticoagulant in the setting of extracorporeal circulation (ECQ in patients with bleeding tendency. It inhibits both platelet aggregation and activation of coagulation factors. Although it has been reported that NM disaggregates aggregated platelets, little is known about such an effect in the setting of hemodialysis therapy (HD). We examined the effects of NM on adenosine 5'-diphosphate (ADP)-induced platelet aggregation and disaggregation using platelet-rich plasma obtained from 6 HD patients. The platelet aggregation was stimulated by 3 mu M ADP and change of aggregation was monitored by an aggregometer. NM adjusted to the final concentrations of 0.1 (1.9 x 10(-7)), 1.0 (1.9 x 10(-6)), 10, (1.9 x 10(-5)), and 100 (1.9 x 10(-4)) mu g/ml (M) or veronal-buffered saline (VBS) as control was added before or after to the stimulation of ADP. NM not only inhibited platelet aggregation, but also disaggregated already aggregated platelets at concentrations of 1.0 mu g/mln or higher. Moreover, NM almost completely disaggregated at 100 mu g/ml. This NM concentration of 1.0 mu g/ml was lower than the therapeutic concentration in ECC of HD (i.e., 10(-5)M). Both inhibitory and disaggregatory effects of NM expressed a dose-related dependency. Our results suggest that NM can exert both aggregation inhibitory and disaggregatory effects on platelets of HD patients within the therapeutic concentration.

    LIPPINCOTT WILLIAMS & WILKINS, 2006年05月, ASAIO JOURNAL, 52 (3), 272 - 275, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Shirakawa, B Acharya, S Kinoshita, S Kumagai, A Gotoh, M Kawabata

    Typhoid fever is the most common clinical diagnosis among febrile patients presenting to hospital in Katmandu. Salmonella enterica serovar Typhi (S. enterica serovar Typhi) and Salmonella enterica serovar Paratyphi A (S. enterica serovar Paratyphi A) with decreased susceptibility to fluoroquinolones and resistance to nalidixic acid are common in recent years. In the present study, we examined the in vitro susceptibility to fluoroquinolones and the presence of gyrA gene mutations in 30 clinical strains of S. Typhi and 39 of S. Paratyphi A, all of which were isolated in Katmandu, Nepal, in 2003. In those strains, we found that 73.3% and 94.9% of S. Typhi and S. Paratyphi A strains contained gyrA gene mutation, and showed the resistance to a quinolone, nalidixic acid, and decreased susceptibility to fluoroquinolones, ciprofloxacin, and levofloxacin. Although fluoroquinolones may still be useful as antibiotics for the treatment of typhoid fever, clinicians should be aware of the possibility of treatment failures of infections with S. Typhi and S. Paratyphi A strains with decreased susceptibility to fluoroquinolones. (c) 2006 Elsevier Inc. All rights reserved.

    ELSEVIER SCIENCE INC, 2006年04月, DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 54 (4), 299 - 303, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 視床下部下垂体精巣軸におけるNeuropeptide YおよびPancreatic polypeptideの役割

    合田上政, 後藤章暢, 白川利朗, 寺尾秀治, 土橋正樹, 大岡均至, 岡田弘, 上野尚彦, 乾明夫, 藤澤正人

    2006年03月, 日本泌尿器科学会雑誌, 97巻, 2号, pp.378-378, 日本語

    研究論文(国際会議プロシーディングス)

  • α1受容体遮断薬による前立腺肥大症の薬物療法についての排尿症状(I-PSS)を中心とした長期薬効の検討

    白川利朗, 寺尾秀治, 大場健司, 山田裕二, 日向信之, 和田義孝, 合田上政, 岡田弘, 後藤章暢, 藤澤正人

    2006年03月, 日本泌尿器科学会雑誌, 97巻, 2号, pp.506-506, 日本語

    研究論文(国際会議プロシーディングス)

  • ヒト膀胱癌細胞に対するミドカインプロモーターを組み込んだ増殖制限型アデノウイルスベクター(AD-MK-E1a)の有用性の検討

    寺尾秀治, 白川利朗, 合田上政, 濱田雄行, 田川雅敏, 後藤章暢, 藤澤正人

    2006年03月, 日本泌尿器科学会雑誌, 97巻, 2号, pp.513-513, 日本語

    研究論文(国際会議プロシーディングス)

  • K Shigemura, T Shirakawa, K Tanaka, S Arakawa, A Gotoh, M Fujisawa

    Backgrounds: In fluoroquinolone-resistant Neisseria gonorrhoeae, the amino acid mutations in the fluoroquinolone-resistant determining region (QRDR) of the parC gene are an important factor. The aim of the present study was to develop a rapid detection method of a serine 88 to proline substitution in parC which we previously showed as having significantly higher fluoroquinolone minimal inhibitory concentrations (MIC) using the TaqMan discrimination system. Methods: We extracted DNA from 90 urine or urethral swab samples obtained from male patients with urethritis caused by N. gonorrhoeae. After DNA extraction, they were subjected to real-time polymerase chain reaction (PCR) using a TaqMan discrimination system and compared with the results of conventional DNA sequencing. Results: Of the 90 samples, the TaqMan technique result showed 13 samples that were classified as having a serine 88 to proline mutation in parC, and 77 samples that did not have a serine 88 to proline mutation in parC. The classifications of all samples completely corresponded to those determined by conventional DNA sequencing. We also found that N. gonorrhoeae with a serine 88 to proline mutation in parC have a significantly higher MIC to ciprofloxacin than that without a serine 88 to proline mutant in parC. Conclusions: The present genotyping method of real-time PCR using a TaqMan discrimination system could be applied to the rapid detection of a serine 88 to proline amino acid mutation in parC of N. gonorrhoeae. This point mutation is significant for the determination of fluoruquinolone resistance. This rapid detection system may lead to the prevention of use of noneffective antimicrobial agents and a decrease of resistant strains.

    BLACKWELL PUBLISHING, 2006年03月, INTERNATIONAL JOURNAL OF UROLOGY, 13 (3), 277 - 281, 英語

    [査読有り]

    研究論文(学術雑誌)

  • M Higuchi, T Kudo, S Suzuki, TT Evans, R Sasaki, Y Wada, T Shirakawa, Sawyer, JR, A Gotoh

    Prostate cancer progresses from an androgen-dependent to androgen-independent stage after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic large-deletion mitochondrial DNA is very common in prostate cancer. To investigate the role of mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted mitochondrial DNA in accordance with the progression of prostate cancer. We demonstrated that the androgen-independent cell line C4-2, established by inoculation of the androgen-dependent LNCaP cell line into castrated mice, has a greatly reduced amount of normal mitochondrial DNA and an accumulation of large-deletion DNA. Strikingly, the depletion of mitochondrial DNA from androgen-dependent LNCaP resulted in a loss of androgen dependence. Reconstitution of normal mitochondrial DNA to the mitochondrial DNA-depleted clone restored androgen dependence. These results indicate that mitochondrial DNA determines androgen dependence of prostate cancer cell lines. Further, mitochondrial DNA-deficient cells formed tumors in castrated athymic mice, whereas LNCaP did not. The accumulation of large deletion and depletion of mitochondrial DNA may thus play a role in the development of androgen independence, leading to progression of prostate cancers.

    NATURE PUBLISHING GROUP, 2006年03月, ONCOGENE, 25 (10), 1437 - 1445, 英語

    研究論文(学術雑誌)

  • K Shigemura, T Shirakawa, Y Wada, S Kamidono, M Fujisawa, A Gotoh

    Objectives. To investigate the effects of the selective cyclooxygenase-2 (COX-2) inhibitor etodolac on prostate cancer cell lines in vitro and in vivo and on E-cadherin expression in prostate cancer cells. Methods. We evaluated the cytotoxicity of etodolac on the three prostate cancer cell lines LNCaP, C4-2, and PC-3. We also performed quantitative real-time polymerase chain reaction to measure the mRNA expression of COX-2, Bcl-2, and E-cadherin in these cell lines after etodolac treatment. In addition, we investigated the in vivo antitumor effects of etodolac on a human prostate cancer xenograft model. Results. Etodolac exhibited significant antitumor effect in vivo and in vitro. The cytotoxicity of etodolac in LNCaP and C4-2 was markedly increased at a dose of 1000 nM in a time-dependent and dose-dependent manner. In the in vivo tumor growth study, the etodolac-treated mice exhibited more significant cytotoxicity than the phosphate-buffered saline-treated mice. Expression of E-cadherin after etodolac treatment tended to increase and that of Bcl-2 to decrease, but the expression of COX-2 had no definite tendency. Conclusions. The COX-2 inhibitor etodolac exhibited an antitumor effect on prostate cancer cell lines in vitro and in vivo, and it might be useful for the treatment of hormone-resistant prostate cancer.

    ELSEVIER SCIENCE INC, 2005年12月, UROLOGY, 66 (6), 1239 - 1244, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 腎臓癌におけるVEGF発現量と遺伝子型

    田中久登, 岡村昇, 後藤章暢, 白川利朗, 寺尾秀治, 山森元博, 瀬戸亮太, 中村任, 栄田敏之, 奥村勝彦

    2005年11月, 臨床薬理, 36巻, Suppl., pp.S268-S268, 日本語

    研究論文(国際会議プロシーディングス)

  • 前立腺肥大症に対するα1受容体遮断薬長期投与症例における排尿症状動態に関する検討

    白川利朗, 寺尾秀治, 日向信之, 合田上政, 大場健史, 和田義孝, 山田裕二, 後藤章暢, 岡田弘, 藤澤正人

    2005年10月, 日本排尿機能学会誌, 16巻, 1号, pp.92-92, 日本語

    研究論文(国際会議プロシーディングス)

  • 視床下部下垂体精巣軸におけるNeuropeptide YおよびPancreatic polypeptideの役割に関する検討

    合田上政, 寺尾秀治, 山口耕平, 土橋正樹, 大場健史, 守殿貞夫, 藤澤正人, 後藤章暢, 白川利朗, 岡田弘

    2005年10月, 日本不妊学会雑誌, 50巻, 4号, pp.321-321, 日本語

    研究論文(国際会議プロシーディングス)

  • Shigemura K, Shirakawa T, Massi N, Tanaka K, Arakawa S, Gotoh A, Fujisawa M

    2005年10月, Journal Of Infection And Chemotherapy, Vol. 11, No. 5, pp. 226-230 (5), 226 - 230, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Sakaeda, N Okamura, A Gotoh, T Shirakawa, S Terao, M Morioka, K Tokui, H Tanaka, T Nakamura, M Yagi, Y Nishimura, M Yokoyama, K Okumura

    Purpose. Heterozygous somatic mutations of epidermal growth factor receptor (EGFR) in exons 18, 19, and 21 were recently reported to be associated with response to gefitinib in patients having nonsmall cell lung cancer. Such mutations are more frequently found among Japanese than Europeans. In this work, the frequency of mutations was investigated in renal cell carcinoma (RCC) samples obtained from Japanese subjects to examine the potential of gefitinib as a therapeutic agent for RCC. Methods. Nineteen patients with RCC, who gave written informed consent, were enrolled in this study. mRNA expression levels of EGFR were measured in RCC and its adjacent noncancerous renal tissue via the real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Somatic mutations were determined using genomic DNA extracted from RCC by direct sequencing method. Results. mRNA expression was confirmed to be about 19 times higher in RCC than in adjacent noncancerous renal tissues, but no such mutations were detected in both. Conclusion. Results from this study do not support the validity of further clinical trials on gefitinib for RCC with genotyping even in Japanese patients, although EGFR plays a key role in tumor progression.

    SPRINGER/PLENUM PUBLISHERS, 2005年10月, PHARMACEUTICAL RESEARCH, 22 (10), 1757 - 1761, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 視床下部下垂体精巣軸におけるNeuropeptide YおよびPancreatic polypeptideの役割

    合田上政, 後藤章暢, 白川利朗, 寺尾秀治, 山口耕平, 土橋正樹, 大場健史, 岡田弘, 上野尚彦, 乾明夫, 守殿貞夫, 藤澤正人

    2005年09月, 日本内分泌学会雑誌, 81巻, 2号, pp.493-493, 日本語

    研究論文(国際会議プロシーディングス)

  • ヒト膀胱癌細胞株に対するフラロデンドリマーを用いた光線力学療法の可能性

    合田上政, 後藤章暢, 白川利朗, 寺尾秀治, 高口豊, 藤澤正人

    2005年09月, 日本癌治療学会誌, 40巻, 2号, pp.627-627, 日本語

    研究論文(国際会議プロシーディングス)

  • ヒト膀胱癌細胞株に対するフラロデンドリマーを用いた光線力学療法の可能性

    合田上政, 後藤章暢, 白川利朗, 寺尾秀治, 高口豊, 藤澤正人

    2005年09月, 日本癌学会64回総会記事, pp.393-393, 日本語

    研究論文(国際会議プロシーディングス)

  • ヒト膀胱癌細胞に対するミドカインプロモーターを組み込んだ増殖制限型アデノウイルスベクター(AdMKE1a)の有用性の検討

    寺尾秀治, 白川利朗, 合田上政, 藤澤正人, 後藤章暢

    2005年09月, 日本癌学会64回総会記事, pp.506-506, 日本語

    研究論文(国際会議プロシーディングス)

  • バングラデシュ,ランガマティ県における熱帯熱マラリアのクロロキン プリマキン治療の有効性

    松本安代, 白川利朗, 高田哲男, 川端眞人

    2005年09月, 感染症学雑誌, 79巻, 9号, pp.717-718, 日本語

    研究論文(国際会議プロシーディングス)

  • Real-time PCR法を用いた腸チフスの血中細菌定量法の開発

    白川利朗, 松本安代, 高田哲男, 荒川創一, 木下承晧, 熊谷俊一, 後藤章暢, 川端眞人

    2005年09月, 感染症学雑誌, 79巻, 9号, pp.794-794, 日本語

    研究論文(国際会議プロシーディングス)

  • 2003年臨床分離MRSAにおけるバンコマイシン耐性関連遺伝子保有状況

    高田哲男, 白川利朗, 松本安代, 木下承晧, 熊谷俊一, 後藤章暢, 川端眞人

    2005年08月, 感染症学雑誌, 79巻, 8号, pp.581-582, 日本語

    研究論文(国際会議プロシーディングス)

  • Recombinant interleukin-2 enhanced the antitumor effect of ADV/RSV-HSV-tk/ACV therapy in a murine bladder cancer model

    S Terao, T Shirakawa, K Goda, S Kamidono, M Fujisawa, A Gotoh

    Background: Previous studies demonstrated the antitumor effects of IL-2 and ADV/RSV-HSV-tk in bladder tumor models. In our study, we employed the intramuscular injection of recombinant IL-2 combined with ADV/RSV-HSV-tk gene therapy in the MBT-2 murine bladder tumor model. Materials and Methods: In the in vitro study, after adenoviral gene transduction efficiency had been assessed, the cytotoxicity of ADV/RSV-HSV-tk/ACV was examined. In the in vivo study, ADV/RSV-HSV-tk was injected into MBT-2 subcutaneous tumors, ACV was injected intraperitoneally daily for 13 days and recombinant IL-2 was injected intramuscularly daily for 10 days. Results: The X-gal staining of MBT-2 cells infected with 125 multiplicity of injection (MOI) indicated > 20% adenoviral gene transduction efficiency. The cell growth of MBT-2 infected with 125 MOI was significantly inhibited by 40 mu M of ACV. In the in vivo study, the combination therapy significantly inhibited tumor growth in the MBT-2 tumor model. Conclusion: The systemic administration Of recombinant IL-2 in combination with HSV-tk gene therapy exhibited an enhanced antitumor effect.

    INT INST ANTICANCER RESEARCH, 2005年07月, ANTICANCER RESEARCH, 25 (4), 2757 - 2760, 英語

    研究論文(学術雑誌)

  • H Tanaka, T Shirakawa, ZJ Zhang, K Hamada, A Gotoh, K Nibu

    Objective: To test the oncolytic activity of cyclooxygenase 2 (COX-2) promoter-based conditional replication-selective adenovirus vector for squamous cell carcinoma cells of the head and neck. Design: In vitro study. Subjects: None. Interventions: A conditional replication-selective adenovirus vector in which the expression of E1a, required for viral replication, is controlled by the COX-2 promoter, Ad-COX2-E1a, was generated. Its oncolytic activity according to the levels of COX-2 and of Coxsackie and adenovirus receptor expression was tested in a series of human head and neck squamous cell carcinoma cell lines. Results: The respective COX-2 messenger RNA expression ratios of KB, H891, T891, T892, and L871 were 1.5, 60.0, 1.0, 14.6, and 1.3. The corresponding Coxsackie and adenovirus receptor messenger RNA expression ratios were 1, 1, 5, 3, and 1. In vitro assays showed significant growth suppression of cancer cell lines with strong expressions of COX-2. Conclusion: This study demonstrated the possibility of oncolytic therapy using the COX-2 promoter-based conditional replication-selective adenovirus for head and neck squamous cell carcinoma expressing COX-2.

    AMER MEDICAL ASSOC, 2005年07月, ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY, 131 (7), 630 - 634, 英語

    [査読有り]

    研究論文(学術雑誌)

  • ラット副腎皮質細胞のMicroencapsulationによるホルモン補充の可能性

    合田上政, 寺尾秀治, 山口耕平, 近藤有, 土橋正樹, 守殿貞夫, 藤澤正人, 白川利朗, 後藤章暢, 岡田弘

    2005年06月, 泌尿器科紀要, 51巻, 6号, pp.429-429, 日本語

    研究論文(国際会議プロシーディングス)

  • MN Massi, T Shirakawa, A Gotoh, A Bishnu, M Hatta, M Kawabata

    We quantified the gene copies from Salmonella enterica serovar Typhi (S. Typhi) in the blood of patients suspected of having typhoid fever by using TaqMan-based real-time PCR (TaqMan assay) to target the S. Typhi flagellin gene in genomic DNAs isolated from blood samples. Of 55 blood samples taken from suspected typhoid fever patients, eight blood samples with a positive blood culture had S. Typhi loads ranging from 1.01 x 10(3) to 4.35 x 10(4) copies/ml blood, and from 47 blood samples with negative blood culture, there were 40 (85.1%) TaqMan assay-positive samples with loads ranging from 3.9 to 9.9 x 10(2) copies/ml blood. In the present study, the TaqMan assay detected more than 10(3) copies/ml blood of S. Typhi in all of the blood culture-positive samples, whereas less than 10(3) copies/ml blood of S. Typhi were detected in the blood culture-negative samples. Our findings suggest that a TaqMan assay may be useful for assessing S. Typhi loads, especially in cases of suspected typhoid fever with negative results from the standard blood culture test. (c) 2005 Elsevier GmbH. All rights reserved.

    URBAN & FISCHER VERLAG, 2005年06月, INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, 295 (2), 117 - 120, 英語

    研究論文(学術雑誌)

  • 前立腺癌骨転移巣に対する遺伝子治療臨床研究 神戸大学医学部附属病院での実施例の報告

    白川利朗, 後藤章暢, 寺尾秀治, 日向信之, 原勲, 守殿貞夫

    2005年05月, 泌尿器外科, 18巻, 臨増, pp.498-498, 日本語

    研究論文(国際会議プロシーディングス)

  • S Terao, Y Yamada, T Shirakawa, Hara, I, N Kanomata, S Kamidono

    We report a case of granulocyte-colony stimulating factor (G-CSF) producing urothelial carcinoma of the renal pelvis in a 39-year old man. The patient was admitted to Kobe University Hospital, Kobe, Japan, complaining of macrohematuria and a 6-month history of left abdominal swelling. Abdominal computed tomography showed a large mass in the left kidney and para-aortic lymph node enlargement. A remarkable degree of leukocytosis was detected without any acute infectious disease. Enzyme immunoassay of the serum demonstrated a remarkable high concentration of G-CSF. The patient underwent left nephroureterectomy and para-aortic lymphadenectomy. Histochemical examination revealed urothelial carcinoma. Immunohistochemical staining with an anti-G-CSF antibody demonstrated G-CSF secreting cells. The patient died 8 weeks after the surgical operation. To our knowledge, this is the second case of G-CSF producing urothelial carcinoma of renal pelvis reported in the English literature.

    BLACKWELL PUBLISHING ASIA, 2005年05月, INTERNATIONAL JOURNAL OF UROLOGY, 12 (5), 500 - 502, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Matsumoto Y, Morimoto I, Shibutani T, Mukubou M, Shirakawa T, Gotoh A, Kawabata M

    2005年04月, Journal Of Infection And Chemotherapy, Vol. 11, No. 2, pp. 97-100 (2), 97 - 100, 英語

    [査読有り]

    研究論文(学術雑誌)

  • K Shigemura, T Shirakawa, H Okada, K Tanaka, S Kamidono, S Arakawa, A Gotoh

    Urinary tract infection has been shown to be quite complicated and often difficult to diagnose and treat. For appropriate diagnosis, it is very important to find the correct Gram stain classification as soon as possible, especially in severe cases where there is a possibility of severe sepsis developing. In order to solve this problem, we developed a new method to detect a Gram stain of bacteria obtained from 1 ml of urine from urinary tract infection patients using a consensus real-time PCR protocol with a TaqMan probe that allows detection of spiked bacterial 16S DNA from urine. We extracted DNA of 55 urine samples obtained from patients with complicated urinary tract infection and at the same time performed urine culture testing. After DNA extraction, they were subjected to real-time PCR using a TaqMan discrimination system. Sixteen kinds of bacteria were cultured from the urine culture testing. Of these bacteria, eight were classified as Gram-positive bacteria and the other eight were classified as Gram-negative bacteria. Of the 55 samples, the TaqMan technique result showed 27 samples that were classified as Gram-negative bacteria; 11 samples that were Gram-positive, 10 that included both Gram-negative and -positive bacteria, and 7 that showed no amplification. The classifications of all samples corresponded exactly to those determined by urine culture testing. The present genotyping method of real-time PCR using a TaqMan discrimination system could be applied to the rapid detection of Gram-positive or -negative bacteria in urine of urinary tract infection patients. This assay can differentiate those species tested, but whether the presence of other (untested) bacteria could lead to misinterpretation is unknown. For further investigation, it is important to test other (untested) bacteria in the near future.

    SPRINGER, 2005年03月, CLINICAL AND EXPERIMENTAL MEDICINE, 4 (4), 196 - 201, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 腎癌における各種遺伝子のmRNA発現変動及び遺伝子型

    岡村昇, 後藤章暢, 白川利朗, 寺尾秀治, 中村任, 盛岡正志, 徳井健次, 田中久登, 八木麻理子, 栄田敏之, 奥村勝彦

    2005年03月, 薬剤学, 65巻, Suppl., pp. 189-189, 日本語

    研究論文(国際会議プロシーディングス)

  • マウス膀胱癌におけるADV/RSV-HSV-TK遺伝子治療とRecombinant IL-2免疫療法との併用療法

    寺尾秀治, 白川利朗, 合田上政, 日向信之, 守殿貞夫, 後藤章暢

    2005年03月, 日本泌尿器科学会雑誌, 96巻, 2号, pp. 284-284, 日本語

    研究論文(国際会議プロシーディングス)

  • マウス造精機能障害モデルにおけるTRAIL発現抑制の効果

    合田上政, 藤澤正人, 白川利朗, 寺尾秀治, 山口耕平, 近藤有, 土橋正樹, 大場健史, 後藤章暢, 岡田弘, 守殿貞夫

    2005年03月, 日本泌尿器科学会雑誌, 96巻, 2号, pp. 220-220, 日本語

    研究論文(国際会議プロシーディングス)

  • バングラデシュ,ランガマティ県における熱帯熱マラリアのクロロキン プリマキン治療の有効性

    松本安代, 白川利朗, 高田哲男, 川端眞人

    2005年03月, 感染症学雑誌, 79巻, 臨増, pp. 214-214, 日本語

    研究論文(国際会議プロシーディングス)

  • Real-time PCR法を用いた腸チフスの血中細菌定量法の開発

    白川利朗, 松本安代, 高田哲男, 荒川創一, 木下承晧, 熊谷俊一, 後藤章暢, 川端眞人

    2005年03月, 感染症学雑誌, 79巻, 臨増, pp. 303-303, 日本語

    研究論文(国際会議プロシーディングス)

  • 2003年臨床分離MRSAにおけるバンコマイシン耐性関連遺伝子保有状況

    高田哲男, 白川利朗, 松本安代, 木下承晧, 熊谷俊一, 後藤章暢, 川端眞人

    2005年03月, 感染症学雑誌, 79巻, 臨増, pp. 141-141, 日本語

    研究論文(国際会議プロシーディングス)

  • [Gene therapy].

    Gotoh A, Shirakawa T, Wada Y, Hinata N, Terao S, Hara I, Arakawa S, Kamidono S, Okada H, Takenaka A, Fujisawa M

    2005年02月, Hinyokika kiyo. Acta urologica Japonica, 51 (2), 75 - 79

    [査読有り]

  • ホルモン抵抗性前立腺癌転移巣に対する治療法について

    後藤章暢, 白川利朗, 和田義孝, 日向信之, 寺尾秀治, 原勲, 荒川創一, 守殿貞夫, 岡田弘, 武中篤, 藤澤正人

    2005年, 泌尿器科紀要, 51巻, pp.75-79, 日本語

    研究論文(学術雑誌)

  • Identification and sequencing of Salmonella enterica serotype typhi isolates obtained from patients with perforation and non-perforation typhoid fever

    Muhammad Nasrum Massi, Toshiro Shirakawa, Akinobu Gotoh, Mochammad Hatta, Masato Kawabata

    2005年01月, The Southeast Asian Journal Of Tropical Medicine And Public Health, Vol. 36, No. 1, pp. 118-122, 英語

    研究論文(学術雑誌)

  • 遺伝子治療が奏功した進行性前立腺癌の1例

    白川利朗, 後藤章暢, 寺尾秀治, 日向信之, 重村克己, 合田上政, 和田義孝, 村蒔基次, 田中一志, 山田裕二, 原勲, 守殿貞夫

    2004年12月, 泌尿器科紀要, 50巻, 12号, pp. 911-911, 日本語

    研究論文(国際会議プロシーディングス)

  • K Shigemura, T Shirakawa, H Okada, K Tanaka, T Udaka, S Kamidono, S Arakawa, A Gotoh

    The detection of DNA sequence variation is fundamental to the identification of the genomic basis of phenotypic variability. Denaturing high-performance liquid chromatography (DHPLC) is a novel technique that is used to detect mutations in human DNA. This is the first report that this technique is used as a tool to detect mutations in genes encoding fluoroquinolone resistance in Neisseria gonorrhoeae. Eighty-one strains of N. gonorrhoeae were used in this study. Genomic DNA from each strain was subjected to PCR amplification of 225 bp in gyrA and 166 bp in parC spanning the fluoroquinolone-resistance determining regions (QRDRs). After we per-formed DNA sequencing of these amplicons and identification of mutations in the QRDRs, DHPLC was undertaken to investigate whether its results correlate the distinctive chromatogram with their DNA mutations pattern. The profilings detected by DHPLC completely corresponded to the results of the DNA sequencing in mutation patters in gyrA and parC genes. They resulted in the following amino acid substitutions: Ser-91Phe, Asp-95Gly, and Asp-95Asn in gyrA; and Gly-85Asp, Asp-86Asn, Ser-87Arg, and Ser-88Pro in parC, respectively. These mutations existed alone or as combinations. and we identified five mutations patterns in gyrA and six in parC including wild-type. These mutations and their patterns could be rapidly and reproducibly identified from the PCR products using DHPLC, producing specific peak patterns that correlate with genotypes. This novel detection system facilitates the detection of resistance.

    ELSEVIER SCIENCE BV, 2004年12月, JOURNAL OF MICROBIOLOGICAL METHODS, 59 (3), 415 - 421, 英語

    [査読有り]

    研究論文(学術雑誌)

  • M Yamamori, T Sakaeda, T Nakamura, N Okamura, T Tamura, N Aoyama, T Kamigaki, M Ohno, T Shirakawa, A Gotoh, Y Kuroda, M Matsuo, M Kasuga, K Okumura

    The mRNA expression of vascular endothelial growth factor (VEGF) was evaluated in colorectal adenocarcinomas and adjacent noncancerous colorectal tissues in IS Japanese patients. The expression was confirmed to be up-regulated in the colorectal adenocarcinomas, when compared with the noncancerous tissues. Twelve genotypes of VEGF: six positions in the promoter region, two in the 5'UTR, and four in the 3'UTR, and their association with the expression of VEGF mRNA were evaluated. While G-1877A, T-1455C, G-1154A, C702T, and G1612A were not detected, C-2578A, T-1498C, G-1190A,C-634G, C-7T, C936T, and C1451T were found at allele frequencies of 4/36, 15/36, 15/36, 20/36, 8/36, 6/36, and 6/36, respectively, suggesting that C-2578A, G-1154A, and G1612A were associated with a decreased-risk for colorectal adenocarcinoma. T-1498C (G-1190A) and C-7T were found to be associated with higher levels of VEGF mRNA, and may be a risk factor for the development of liver metastasis and/or prognosis of colorectal adenocarcinoma. (C) 2004 Elsevier Inc. All rights reserved.

    ACADEMIC PRESS INC ELSEVIER SCIENCE, 2004年12月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 325 (1), 144 - 150, 英語

    [査読有り]

    研究論文(学術雑誌)

  • A Gotoh, K Goto, A Sengoku, T Shirakawa, Y Akao, M Fujisawa, H Okada, S Arakawa, S Kamidono

    We investigated the actions of Gosha-jinki-gan, a traditional Japanese medicine containing processed Aconiti tubers, on urinary bladder function in anesthetized rats. In cystometrical investigations, Gosho-jinki-gan (1.0 g/kg, i.d.) increased bladder capacity as well as micturition threshold pressure. In addition, it decreased the frequency of distension-induced rhythmic bladder contractions. However, it did not influence the amplitude of bladder contractions induced by electrical stimulation of the pontine micturition center. The inhibitory effect of Gosha-jinki-gan on bladder motility was abolished by pretreatment with nor-binaltorphimine (10 mg/kg, s.c.), and was diminished by the concomitant use of anti-dynorphin A antiserum (10 mug, i.t.), yohimbine (10 mug, i.t.), or methysergide (20 mug, i.t.). Processed Aconiti tuber extract (27 mg/kg, i.d.) also suppressed bladder motility, and the effect was abolished by nor-binaltorphimine. These results suggest that Gosha-jinki-gan attenuates bladder sensation via the kappa-opioid receptor-stimulating action of processed Aconiti tuber. Gosha-jinki-gan may be a useful anti-pollakiuria agent that does not influence bladder contractility at micturition.

    JAPANESE PHARMACOLOGICAL SOC, 2004年10月, JOURNAL OF PHARMACOLOGICAL SCIENCES, 96 (2), 115 - 123, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 膀胱癌におけるAd-RSV-tk遺伝子治療とIL-2免疫療法との併用療法(Interleukin-2 enhanced the anti-tumor effect of adenoviral-mediated HSV-tk gene therapy in a murine bladder cancer model)(英語)

    白川利朗, 日向信之

    2004年09月, 日本癌学会総会記事, (63回), 518, 日本語

    研究論文(その他学術会議資料等)

  • 膀胱癌におけるAd-RSV-tk遺伝子治療とIL-2免疫療法との併用療法(Interleukin-2 enhanced the anti-tumor effect of adenoviral-mediated HSV-tk gene therapy in a murine bladder cancer model)(英語)

    寺尾秀治, 守殿貞夫, 後藤章暢, 白川利朗, 日向信之, 合田上政

    2004年09月, Cancer Science, 95巻, Suppl., pp. 518-518, 日本語

    研究論文(国際会議プロシーディングス)

  • 前立腺癌治療戦略 ホルモン抵抗性前立腺癌転移巣に対する遺伝子治療臨床研究

    後藤章暢, 白川利朗, 原勲, 守殿貞夫

    2004年09月, 日本癌治療学会誌, 39巻, 2号, pp. 315-315, 日本語

    研究論文(国際会議プロシーディングス)

  • マウス造精機能障害モデルにおけるTRAIL発現抑制の効果

    合田上政, 藤澤正人, 白川利朗, 近藤有, 土橋正樹, 後藤章暢, 岡田弘, 守殿貞夫

    2004年09月, 日本内分泌学会雑誌, 80巻, 2号, pp. 454-454, 日本語

    研究論文(国際会議プロシーディングス)

  • ヒト前立腺小細胞癌株(SO-MI)に対するp53遺伝子導入の効果

    合田上政, 白川利朗, 後藤章暢, 岡田弘, 原勲, 守殿貞夫, 藤澤正人

    2004年09月, Cancer Science, 95巻, Suppl., pp. 515-515, 日本語

    研究論文(国際会議プロシーディングス)

  • K Goda, M Fujisawa, T Shirakawa, M Dobashi, G Shiota, ZJ Zhang, A Gotoh, S Kamidono

    Background Prior studies have shown that the hepatocyte growth factor (HGF), as known for its multiple biological effects, possibly regulates spermatogenesis or tubulogenesis in the testis. To clarify the effect of HGF on restoration of spermatogenesis, or testicular weight, we transferred the HGF gene into the testis of the rat experimental cryptorchid model. Methods Replication-deficient recombinant adenoviral vectors containing the CAG promoter driving rat HGF (pAxCAHGF) and LacZ (pAxCALacZ) were constructed. Sprague-Dawley rats surgically induced with unilateral cryptorchidism and subsequent orchidopexy were divided into three groups: control (PBS), pAxCALacZ and pAxCAHGF by intratesticular injection. At 2 and 4 weeks after subsequent orchidopexy, testes were removed and weighed. These specimens were analyzed histopathologically, and examined for cell apoptosis. HGF expression in these specimens associated with c-Met receptor-mediated signal molecules was examined by reverse transcription-polymerase chain reaction (RT-PCR), Western blot or immunohistochemical study. Results Adenovirus-mediated HGF gene transfer induced overexpression of HGF in some seminiferous epithelial cells and interstitial cells, increased the phosphorylation of ERK and Akt, and decreased numbers of apoptotic cells of germ cells. HGF transduction also significantly increased the numbers of germ cells and testicular weight by 4 weeks compared with the other control groups. Conclusions Adenoviral-mediated HGF gene transfer into the testis in the cryptorchidism rats inhibited germ cell apoptosis and restored spermatogenesis. Copyright (C) 2004 John Wiley Sons, Ltd.

    JOHN WILEY & SONS LTD, 2004年08月, JOURNAL OF GENE MEDICINE, 6 (8), 869 - 876, 英語

    [査読有り]

    研究論文(学術雑誌)

  • H Okada, T Shirakawa, T Ishikawa, K Goda, M Fujisawa, S Kamidono

    We measured testosterone levels in 24 patients with nonmosaic Klinefelter syndrome before and at 6 and 12 months after conventional or microdissection testicular sperm extraction. Testosterone levels decreased after surgery by either technique, and they did not recover to baseline concentrations, even when using less invasive microdissection techniques.

    ELSEVIER SCIENCE INC, 2004年07月, FERTILITY AND STERILITY, 82 (1), 237 - 238, 英語

    [査読有り]

    研究論文(学術雑誌)

  • A Gotoh, T Sakaeda, T Kimura, T Shirakawa, Y Wada, A Wada, T Kimachi, Y Takemoto, A Iida, S Iwakawa, M Hirai, H Tomita, N Okamura, T Nakamura, K Okumura

    Rhinacanthus nasutus (L.) KURZ (Acanthaceae) is a shrub widely distributed in South China and India. In this study, the antiproliferative activity of the ethanol extract of root and aqueous extract of leaves of R. nasutus, and the supposed active moiety rhinacanthin C was assessed in vitro using the human cervical carcinoma cell line HeLa, its MDR1-overexpressing subline Hvr100-6, human prostate carcinoma PC-3 cells and human bladder carcinoma T24 cells. Rhinacanthin C was chemically synthesized and its content in the R. nasutus extracts was determined by HPLC with a photodiode array detector. The antiproliferative activity of the R. nasutus extracts was also assessed in vivo using sarcoma 180-bearing mice. It was suggested that 1) the in vitro antiproliferative activity of rhinacanthin C was comparable with or slightly weaker than that of 5-FU, 2) rhinacanthin C showed antiproliferative activity for MDR1-overexpressing Hvr100-6 cells, similarly to parent HeLa cells, 3) the in vitro antiproliferative activity of the ethanol extract of root R. nasutus was due to rhinacanthin C, whereas that of the aqueous extract of leaves of R. nasutus was due to constituents other than rhinacanthin C, and 4) both of the R. nasutus extracts showed in vivo antiproliferative activity after oral administration once daily for 14 d.

    PHARMACEUTICAL SOC JAPAN, 2004年07月, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 27 (7), 1070 - 1074, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Shirakawa, K Hamada, ZJ Zhang, H Okada, M Tagawa, S Kamidono, M Kawabata, A Gotoh

    Purpose: Cyclooxygenase-2 (Cox-2), an enzyme that catalyzes the synthesis of prostaglandins, is overexpressed in a variety of premalignant and malignant conditions, including urinary bladder cancer. In the present study, we examined the feasibility of using Cox-2 promoter-based replication-selective adenovirus for targeting bladder cancer cells that express Cox-2 transcriptional activity. Experimental Design: A series of human cancer cell lines, including three bladder cancer cell lines (KK47, T24, and 5637), were evaluated for their Cox-2 and CAR (the Coxsackievirus and adenovirus receptor) mRNA expression levels by quantitative real-time PCR. AdE3-cox2-327, a replication-selective adenovirus in which the expression of E1a is controlled by the Cox-2 promoter, was generated, and its tissue-specific activity was tested in vitro and in vivo. Results: Three bladder cancer cell lines express higher levels of Cox-2 mRNA than does the human prostate cancer cell line PC3, the primary cultured human benign prostatic fibroblast, PF cells, and the human colon cancer cell line Colo320. Relatively higher expression of CAR mRNA was detected in the KK47, 5637, respectively, and Colo320 than in the T24, PC-3, and PF cells. In vitro assays revealed significant growth suppression of both Cox-2- and CAR-expressing bladder cancer cells KK47 and 5637 in comparison with the other cells that lack Cox-2 expression and/or CAR expression. Conclusions: The present study demonstrated both specificity and efficacy of AdE3-cox2-327, a selectively replicated adenovirus, toward the Cox-2-expressing bladder cancer cells in vitro and in vivo. We also found that CAR expression in the target cancer cells is an important factor for the efficacy of selectively replicated adenovirus-based gene therapy.

    AMER ASSOC CANCER RESEARCH, 2004年07月, CLINICAL CANCER RESEARCH, 10 (13), 4342 - 4348, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 薬剤耐性淋菌性尿道炎の分子生物学的検討およびDHPLCを用いた迅速遺伝子診断法の開発

    重村克巳, 岡田弘, 田中一志, 荒川創一, 守殿貞夫, 白川利朗, 後藤章暢, 木下承皓

    2004年05月, 泌尿器科紀要, 50巻, 5号, pp. 381-381, 日本語

    研究論文(国際会議プロシーディングス)

  • nafamostat mesilateの血小板凝集解離作用

    白川利朗, 日向信之

    2004年05月, 日本透析医学会雑誌, 37 (Suppl.1), 856, 日本語

    研究論文(その他学術会議資料等)

  • A Gotoh, T Shirakawa, N Hinata, Y Wada, Hara, I, M Fujisawa, G Kawabata, H Okada, S Akakawa, S Kamidono

    Aim: To investigate the long-term efficacy of postoperative interferon-alpha (IFN-alpha) adjuvant therapy in preventing recurrence in non-metastatic renal cell carcinoma treated with radical nephrectomy and to identify related prognostic markers. Methods: Long-term follow-up was conducted to study rates of survival and non-recurrence in 88 subjects following radical nephrectomy for non-metastatic disease. Results: The overall survival rate was 90% at 5 years and 88% at 10, with corresponding non-recurrence rates of 81% and 74%. Survival rates reviewed by preadministration pT stage showed a falling tendency from T1 through to T3 in line with pathological progression; when cases at stage pT1b or below were compared with those at stage pT2 or above, the latter showed a tendency to lower survival rates (P = 0.0966, Breslow-Gehan-Wilcoxon). Similarly, non-recurrence rates tended to fall in line with pathological progression, with a significant difference found in the comparison of cases at stage pT1b or below with those at stage pT2 or above (P = 0.0265, log-rank, Mantel-Cox). Duration of IFN-alpha administration showed a tendency to positive correlation with long-term survival (P = 0.3765, Breslow-Gehan-Wilcoxon). Non-recurrence rate was not found to differ according to duration of administration. Comparison of groups with normal and abnormal preadministration inummosuppressive acidic protein values showed that the normal group tended to have higher rates of survival and non-recurrence (P = 0.3371, Breslow-Gehan-Wilcoxon). Conclusions: Immunosuppressive acidic protein values appear to be a useful predictive marker for recurrence. A randomized trial, examining long-term outcome according to tumor stage and variables such as duration of administration, dose, administration time, and dosing schedule is required.

    BLACKWELL PUBLISHING ASIA, 2004年05月, INTERNATIONAL JOURNAL OF UROLOGY, 11 (5), 257 - 263, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 後藤章暢, 白川利朗, 日向信之, 和田義孝, 守殿貞夫

    2004年04月, 臨床泌尿器科, 58巻, 5号, pp. 301-306, 日本語

    [査読有り]

    研究論文(学術雑誌)

  • K Shigemura, H Okada, T Shirakawa, K Tanaka, S Arakawa, S Kinoshita, A Gotoh, S Kamidono

    Objectives: Decreasing susceptibility of Neisseria gonorrhoeae to fluoroquinolones has been reported in several countries. Knowledge of local N gonorrhoeae susceptibilities to various antimicrobials is important for establishing a rational treatment strategy in each region. Methods: Isolates of N gonorrhoeae from male urethritis patients attending four urological clinics in Hyogo and Osaka prefectures in Japan were collected during 2002. The MICs for nine antimicrobials: penicillin G, tetracycline, cefixime, ceftriaxone, levofloxacin, gatifloxacin, ciprofloxacin, moxifloxacin, and spectinomycin were determined for each isolate. All isolates were also tested for beta lactamase producing profiles. Results: Among the 87 isolates obtained, only one isolate was revealed to produce beta lactamase. MIC90 values for ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin were over 8 mug/ml, over 8 mug/ml, 4 mug/ml, and 2 mug/ml, respectively. The proportion of isolates resistant to fluoroquinolones was over 60% (ciprofloxacin, 70.1%; levofloxacin, 65.5%; gatifloxacin, 70.1%). Chromosomally mediated penicillin and tetracycline resistance was identified in 12.6% and 33.3% of the isolates. MIC90 values for cefixime and ceftriaxone and were 0.5 mug/ml and 0.0063 mug/ml. All isolates were sensitive to ceftriaxone and 90.8% of them were sensitive to cefixime. MIC90 for spectinomycin was 32 mug/ml and all isolates were sensitive to it. Fluoroquinolone resistance correlated significantly with MICs for penicillin G but not tetracycline. Conclusion: Ceftriaxone and spectinomycin demonstrated lower MICs and so are recommended for N gonorrhoeae. Susceptibilities of N gonorrhoeae should be monitored periodically by region.

    B M J PUBLISHING GROUP, 2004年04月, SEXUALLY TRANSMITTED INFECTIONS, 80 (2), 105 - 107, 英語

    [査読有り]

    研究論文(学術雑誌)

  • K Shigemura, T Shirakawa, H Okada, N Hinata, B Acharya, S Kinoshita, T Kofuku, M Kawabata, S Kamidono, S Arakawa, A Gotoh

    Background and Objectives: Fluoroquinolone resistance in Neisseria gonorrhoeae has been associated with alternations in the quinolone-resistance determining regions in the gyrA and parC genes. Goal: The goal of this study was to investigate the correlation between fluoroquinolone minimum inhibitory concentrations (MICs) and mutations in the gyrA and parC genes of 91 N. gonorrhoeae clinical isolates from Japan. Study Design: The MICs of fluoroquinolones ciprofloxacin, levofloxacin, and gatifloxacin for 91 clinical isolates from male gonococcal urethritis in Hyogo or Osaka, Japan, were measured, and the gyrA and parC genes of these isolates were sequenced. Results: Among 91 isolates tested, over 70% isolates were resistant to ciprofloxacin. We found that 4 mutations (Ser-91-Phe, Ser-91-Ile, Asp-95-Gly in gyrA, and Ser-88-Pro in parC) had significant correlation to MICs of fluoroquinolone (ciprofloxacin, levofloxacin, and gatifloxacin). Conclusion: Some mutations in QRDR had a significant relationship to the fluoroquinolone resistance of 91 N. gonorrhoeae clinical isolates from Japan.

    LIPPINCOTT WILLIAMS & WILKINS, 2004年03月, SEXUALLY TRANSMITTED DISEASES, 31 (3), 180 - 184, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Shirakawa, A Gotoh, ZJ Zhang, CH Kao, LWK Chung, TA Gardner

    Objectives. To develop a new toxic gene therapy using the tissue-specific human chorionic gonadotropin-beta (hCG-beta) promoter for testicular cancer. Although most patients presenting with disseminated testicular tumor are cured through the use of chemotherapy with or without surgery, those patients with relapse after initial therapy present a difficult clinical problem. The serum tumor marker hCG-beta is frequently elevated in patients with testicular cancer, and the pretreatment and post-treatment levels of serum hCG-beta are highly predictive of treatment outcome. Methods. Human testicular embryonal carcinoma cell line, NEC 8, a human prostate cancer cell line, PC-3, and a human bladder cancer cell line, WH, were used in this study. A transient expression experiment was used to analyze the activity of a 729-bp hCG-beta promoter in all three cell lines. A recombinant adenovirus carrying thymidine kinase (Ad-hCG-beta-TK) under control of the hCG-beta promoter was generated. The tissue-specific activity of Ad-hCG-beta-TK was tested in vitro and in vivo. Results. The hCG-beta promoter had significantly greater activity in the hCG-beta-producing cell line (NEC 8) than in the non-hCG-beta-producing cell lines (PC-3 and WH). In vitro, Ad-hCG-beta-TK with acyclovir significantly inhibited NEC 8 growth but not PC-3 or WH cell growth. In vivo, Ad-hCG-beta-TK with acyclovir significantly inhibited NEC 8 subcutaneous tumor growth in nude mice. Conclusions. In this study, we explored the possibility of developing a new therapeutic agent to target and induce the killing of testicular germ cell tumor selectively by using tissue-specific hCG-beta promoters. UROLOGY 63: 613-618, 2004. (C) 2004 Elsevier Inc.

    ELSEVIER SCIENCE INC, 2004年03月, UROLOGY, 63 (3), 613 - 618, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Nakahara, T Sakaeda, T Nakamura, T Tamura, C Nishioka, N Aoyama, N Okamura, T Shirakawa, A Gotoh, T Kamigaki, M Ohno, Y Kuroda, M Matsuo, M Kasuga, K Okumura

    Purpose. To evaluate chemosensitivity and its correlation with expression levels of the multidrug resistant transporter (MDR1) and the multidrug resistance-associated proteins 1 and 2 (MRP1, MRP2) mRNA in human colorectal adenocarcinomas. Methods. Colorectal adenocarcinomas were obtained as surgical samples from 25 patients. The chemosensitivity of 12 anticancer drugs was assessed by the collagen gel droplet embedded culture drug sensitivity test (CD-DST). The expression levels of MDR1, MRP1, and MRP2 mRNA in colorectal adenocarcinomas were also evaluated by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results. The chemosensitivity was successfully evaluated for 16 of 25 patients, and the anticancer drugs were effective against the samples showing a relatively high growth rate. Gemcitabine hydrochloride was found to be more promising than those often prescribed for the treatment of colorectal adenocarcinoma. There was no correlation of the mRNA expression levels of MDR1 and MRP1 with the chemosensitivity of any anticancer drugs tested, but mitomycin C was found to be more effective for the colorectal adenocarcinoma with relatively high expression of MRP2 mRNA.

    KLUWER ACADEMIC/PLENUM PUBL, 2004年03月, PHARMACEUTICAL RESEARCH, 21 (3), 406 - 412, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 外傷性膀胱・直腸破裂術後,回腸Blind loop部に小腸膀胱瘻を生じた1例

    熊野晶文, 白川利朗, 田中一志, 原勲, 川端岳, 岡田弘, 守殿貞夫, 生田繁, 藤澤正人

    2004年02月, 泌尿器科紀要, 50巻, 2号, pp. 140-140, 日本語

    研究論文(国際会議プロシーディングス)

  • Gotoh A, Shirakawa T, Hinata N, Wada Y, Kamidono S

    2004年, Japanese Journal of Clinical Urology, 58 (5), 301 - 306

    [査読有り]

  • Hinata Nobuyuki, Shirakawa Toshiro, Okada Hiroshi, Shigemura Katsumi, Kamidono Sadao, Gotoh Akinobu

    2004年, Molecular Diagnosis, Vol. 8, No. 3, pp. 179-184, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Hinata Nobuyuki, Shirakawa Toshiro, Okada Hiroshi, Achaya Bishnu, Kamidono Sadao, Gotoh Akinobu

    2004年, Molecular Diagnosis, Vol. 8, No. 1, pp. 17-22, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Shirakawa, H Okada, B Acharya, ZJ Zhang, N Hinata, Y Wada, T Uji, S Kamidono, A Gotoh

    BACKGROUND. Benign prostatic hyperplasia (BPH) development requires testicular androgens and aging. The principle prostatic androgen is dihydrotestosterone (DHT). Testosterone is converted to DHT by the enzyme 5 alpha-reductase. Two distinct 5 alpha-reductase enzymes, types 1 and 2, have been identified. While some studies have suggested that type 2 isoenzyme predominates in the prostate, studies on the prostatic localization of the two isoenzymes are controversial. The purpose of this study was to determine the quantitative expressions of 5 alpha-reductase types 1 and 2 in BPH tissues. METHODS. We examined the localizations of types 1 and 2 isoenzymes in BPH tissues using immunohistochemical staining and a real-time quantitative RT-PCR assay using the TaqMan system. We measured the enzyme activities of types 1 and 2 at pH values of 7.5 and 5.0, respectively. RESULTS. Our immunohistochemical study showed that type 1 isoenzyme was expressed predominantly in epithelial cells, whereas type 2 isoenzyme was expressed in both stromal and epithelial cells. The real-time RT-PCR assay demonstrated that the copy numbers of type 1 isoenzyme mRNA were significantly higher than those of type 2 isoenzyme mRNA. There were significant associations between enzyme activity at pH 7.5 and type 1 isoenzyme mRNA expression, and between the activity at pH 5.0 and type 2 mRNA expressions. CONCLUSIONS. We demonstrated that 5 alpha-reductase type 1 had a specific enzyme activity in the prostate, which supports the hypothesis that the type I isoenzyme may play a significant role in maintaining prostate enlargement along with the type 2 isoenzyme. (C) 2004 Wiley-Liss, Inc.

    WILEY-LISS, 2004年01月, PROSTATE, 58 (1), 33 - 40, 英語

    [査読有り]

    研究論文(学術雑誌)

  • N Hinata, T Shirakawa, ZJ Zhang, A Matsumoto, M Fujisawa, H Okada, S Kamidono, A Gotoh

    Purpose. It has been reported in several studies that the absence in cancer cells of the p53 tumor suppressor gene, mutations of which are frequently found in bladder cancer, increases their resistance to ionizing radiation. Other studies, however, suggest that mutations of the p53 gene could increase the radiosensitivity of cancer cells, although the evidence is still inconclusive. In the present study, we investigated the relationship between p53 status and radiation response in five different bladder cancer cell lines. Materials and Methods. Five different human bladder cancer cell lines (KK47: with wt-p53, RT4: with wt-p53, T24: with mutated p53, 5637: with mutated p53, UM-UC-3: with mutated p53) were used in the study. Cells were irradiated with 0, 2, 4, 6 or 8 Gy, then trypsinized and re-plated for clonogenic survival assay, quantitative RT-PCR assay, flow-cytometry analysis and TUNEL assay. Results. The clonogenic assay demonstrated that KK47 and RT4 had significantly higher radiosensitivity than other cell lines. Quantitative RT-PCR analysis showed that radiation induced increased expression of p53, Bax, and p21 mRNA in KK47 and RT4. After irradiation, G1 cell-cycle arrest was observed in KK47 and RT4 under flow cytometry analysis, while T24, 5637, and UM-UC-3 showed an increase in the proportion of G2 cells. Increased cell apoptosis was also observed under TUNEL assay in KK47 and RT4, but not in other cell lines. Conclusions: It was demonstrated that ionizing radiation induces p53-dependent cell apoptosis in bladder cancer cells with wt-p53 but not in those with mutated p53.

    SPRINGER-VERLAG, 2003年12月, UROLOGICAL RESEARCH, 31 (6), 387 - 396, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 前立腺癌骨転移巣におけるオステオカルシン発現の意義

    白川利朗, 日向信之

    2003年11月, 泌尿器科紀要, 49 (11号), 696, 日本語

    研究論文(その他学術会議資料等)

  • ZJ Zhang, T Shirakawa, N Hinata, A Matsumoto, M Fujisawa, H Okada, S Kamidono, M Matsuo, A Gotoh

    Background Resistance to radiation and chemotherapy is a significant obstacle to the treatment of advanced bladder cancer. Gene therapy combined with radiation represents a new approach to cancer treatment. In the present study, we investigated whether adenovirally directed, cytosine deaminase (CD)/5-fluorocytosine (5-FC) gene therapy could induce cell toxicity and radiosensitization through the intracellular production of 5-fluorouracil (5-FU) in bladder-cancer cells. Methods Three human bladder-cancer cell lines, KK47 (wild-type p53+), T24 (p53 mutated) and 5637 (p53 mutated), were investigated. A recombinant adenovirus vector containing the CD gene (Ad-RSV-CD) was used. Cells were infected with Ad-RSV-CD and treated with 5-FC. Forty-eight hours after infection, the cells were irradiated and cytotoxicity assays performed to determine the extent of increase in in vitro cytotoxicity. A KK47 subcutaneous tumor-xenografts model was used in an animal study to examine the tumor growth inhibitory effect of this combination therapy. Ad-RSV-CD was directly injected into the tumor and daily 5-FC was intraperitoneally injected. Forty-eight hours after injection of Ad-RSV-CD, the tumor was irradiated. The tumor volume was measured every day. Results in all three cell lines, the combination treatment enhanced the cell killing of human bladder-cancer cells in vitro. It also enhanced the tumor-growth inhibition in the KK47 tumor model. Conclusions In the present study, we demonstrated that CD/5-FC gene therapy combined with radiation therapy enhances cell killing of human bladder-cancer cells in in vitro and in vivo animal models. Copyright (C) 2003 John Wiley Sons, Ltd.

    JOHN WILEY & SONS LTD, 2003年10月, JOURNAL OF GENE MEDICINE, 5 (10), 860 - 867, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 前立腺癌細胞内の亜鉛分布状態の変化 ホルモンと亜鉛の関係

    白川利朗, 後藤章暢, 北村ゆり, 杉村和朗, 川上拓男, 井手亜里

    2003年09月, Biomedical Research on Trace Elements, 14巻, 3号, pp. 215-218, 日本語

    [査読有り]

    研究論文(学術雑誌)

  • 前立腺癌骨転移巣に対する遺伝子治療臨床研究の現況

    白川利朗, 日向信之, 原勲

    2003年09月, 日本癌治療学会誌, 38 (2号), 239, 日本語

    研究論文(その他学術会議資料等)

  • ホルモン抵抗性前立腺癌に対するEstramustine,COX-2阻害剤併用療法の治療効果の検討

    白川利朗, 日向信之

    2003年09月, 日本癌治療学会誌, 38 (2号), 659, 日本語

    研究論文(その他学術会議資料等)

  • Massi MN, Shirakawa T, Gotoh A, Bishnu A, Hatta M, Kawabata M

    2003年09月, Journal Of Infection And Chemotherapy, Vol. 9, No. 3, pp. 233-237 (3), 233 - 237, 英語

    [査読有り]

    研究論文(学術雑誌)

  • irritative symptomを主症状とするBPH患者に対する塩酸プロピベリンの効果

    日向信之, 白川利朗

    2003年09月, 日本排尿機能学会誌, 14 (1号), 86, 日本語

    研究論文(その他学術会議資料等)

  • A Gotoh, T Shirakawa, Y Wada, M Fujisawa, H Okada, S Kamidono, K Hamada

    To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) human prostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying human p21 cDNA. The LNCaP, DU145 and PC-3 human prostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice. Growth was inhibited in Ad5CMV-p21 viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice. These results suggest that Ad5CMV-p21 may be a new therapeutic agent for human prostate cancer gene therapy.

    BLACKWELL PUBLISHING LTD, 2003年08月, BJU INTERNATIONAL, 92 (3), 314 - 318, 英語

    [査読有り]

    研究論文(学術雑誌)

  • A Gotoh, T Shirakawa, Y Wada, M Fujisawa, H Okada, S Kamidono, K Hamada

    To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) human prostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying human p21 cDNA. The LNCaP, DU145 and PC-3 human prostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice. Growth was inhibited in Ad5CMV-p21 viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice. These results suggest that Ad5CMV-p21 may be a new therapeutic agent for human prostate cancer gene therapy.

    BLACKWELL PUBLISHING LTD, 2003年08月, BJU INTERNATIONAL, 92 (3), 314 - 318, 英語

    [査読有り]

    研究論文(学術雑誌)

  • H Okada, T Shirakawa, H Miyake, A Gotoh, M Fujisawa, S Arakawa, S Kamidono

    BACKGROUND. Prostatic small-cell carcinoma is an extremely rare, highly aggressive disease. We established a cell line from this tumor. MATERIALS AND METHODS. Tumor tissue obtained from a 24-year-old Japanese man was used to establish the cell line. Cultured cells and tumors transplanted into nude mice were characterized by histologic, immunohistologic, immunocytologic, and molecular biologic methods. RESULTS. An immortal culture cell line (SO-MI) was successfully established. SO-MI cells adhered weakly to plastic surfaces in vitro, showing a 52- to 72-hr doubling time. SO-MI cells were heterotopically and orthotopically transplantable in nude mice. The cells were immunoreactive for NSE, chromogranin A, and NCAM, but not for ACTH, calcitonin, serotonin, gastrin, insulin, glucagons, LCA, EMA, PAP, PSA, androgen receptor, and p53. SO-MI cells secreted NSE in vitro and in vivo. SO-MI cells at passage 30 contained 50-59 chromosomes with a modal number of 55. PCR suggested that the p53 gene was deleted in SO-MI cells. RT-PCR detected no mRNA encoding androgen receptor in these cells. CONCLUSIONS. SC-MI cells retain the neuroendocrine nature of the original tumor, and should be useful in studying possible etiologies and new treatments. (C) 2003 Wiley-Liss, Inc.

    WILEY-LISS, 2003年08月, PROSTATE, 56 (3), 231 - 238, 英語

    [査読有り]

    研究論文(学術雑誌)

  • AH Zhou, H Ueno, M Shimomura, R Tanaka, T Shirakawa, H Nakamura, M Matsuo, K Iijima

    Background. We tested whether the entire soluble extracellular domain of the human transforming growth factor-P (TGF-beta) type II receptor, fused to the Fc portion of human immunoglobulin G (IgG1) (Tbeta-ExR) and expressed in skeletal muscles by adenovirus-mediated gene transfer (AdTbeta-ExR), can ameliorate renal dysfunction and histologic progression in a rat experimental anti-glomerular basement membrane (GBM) nephritis. Methods. Anti-GBM nephritis was induced in Wistar Kyoto rats by an intravenous injection of anti-rat glomerular basement membrane (GBM) sera. At day 1 (24 hours after induction), AdTbeta-ExR (1 X 10(9) pfu/mL) was injected into the femoral muscle in the treatment group, and an adenovirus vector-expressing bacterial P-galactosidase (AdLacZ) was injected into the control group. Then, clinical and histologic changes were examined for 3 weeks after the induction of anti-GBM nephritis. Results. Tbeta-ExR was detected in the serum at day 7, but the serum concentration of Tbeta-ExR had decreased below the detectable level by day 14. Although blood pressure and the degree of proteinuria were similar in both groups, the deterioration of renal function was significantly blunted in the treatment group. Crescent formation and interstitial fibrosis were also ameliorated in the treatment group. These histologic improvements were accompanied by the decreased interstitial infiltration of macrophages and the decreased a-smooth muscle actin (alpha-SMA)-positive cells in the glomeruli and the interstitium. Conclusion. This study demonstrated for the first time that the blockade of TGF-beta action by AdTbeta-ExR in the early stage of anti-GBM nephritis ameliorates the clinical and histologic progression. In addition, this study shed light on the development of a specific gene therapy for human crescentic glomerulonephritis.

    BLACKWELL PUBLISHING INC, 2003年07月, KIDNEY INTERNATIONAL, 64 (1), 92 - 101, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 尿中分離菌に対するフローサイトメトリーを用いた迅速薬剤感受性試験について

    重村克巳, 田中一志, 日向信之, 白川利朗, 荒川創一

    2003年05月, 感染症学雑誌, 77 (5号), 363 - 364, 日本語

    研究論文(その他学術会議資料等)

  • 尿中分離菌に対するフローサイトメトリーを用いた迅速薬剤感受性試験について

    重村克巳, 田中一志, 日向信之, 白川利朗, 荒川創一

    2003年04月, 尿路感染症研究会記録集, (11号), 18, 日本語

    研究論文(その他学術会議資料等)

  • Complete resection of synovial sarcoma of prostatic fascia

    Shirakawa Toshiro, Fujisawa Masato, Gotoh Akinobu

    2003年03月, Urology, Vol. 61, No. 3, pp. 644-644, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 定量的PCR法を用いた細菌尿中の大腸菌の定量

    日向信之, 白川利朗, 重村克巳

    2003年02月, 日本泌尿器科学会雑誌, 94 (2号), 384, 日本語

    研究論文(その他学術会議資料等)

  • T Nakamura, T Sakaeda, N Ohmoto, Y Moriya, C Komoto, T Shirakawa, A Gotoh, M Matsuo, K Okumura

    Purpose. The mRNA levels of MDR1 (P-glycoprotein), multidrug resistance-associated proteins (MRP1, MRP2), cytochrome P450 3A (CYP3A) and villin in human colorectal cell lines (HCT-15, LoVo, DLD-1, HCT-116 and SW620) were quantitatively compared with those in Caco-2 cells. Methods. The mRNA levels were determined by real time quantitative polymerase chain reaction and expressed as the relative concentrations of MDR1 mRNA to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA. Results. MDR1 mRNA was expressed in HCT-15 LoVo and DLD-1 cells at similar or lower level to Caco-2. The expression of MRP1 mRNA in the cell lines tested was comparable with Caco-2. MRP2 mRNA was detected only in HCT-116 and SW620 at significantly lower level than Caco-2. CYP3A mRNA was detected in HCT-15, LoVo, DLD-1 and SW620 at similar level to Caco-2. Conclusions. HCT-15 LoVo and DLD-1 cells express proteins important for regulating the intestinal absorption of drugs, i.e., MDR1, MRP1 and CYP3A, whereas HCT-116 and SW620 cells were not acceptable for evaluation of absorption properties of drug candidates.

    KLUWER ACADEMIC/PLENUM PUBL, 2003年02月, PHARMACEUTICAL RESEARCH, 20 (2), 324 - 327, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Effects of mefloquine usage on genetic polymorphism of Plasmodium falciparum in Thai-Myanmarese border

    Matsuo Toshiaki, Shirakawa Toshiro, Singhasivanon Pratap, Looareesuwan Sornchai, Kawabata Masato

    2003年, The Kobe Journal Of Medical Sciences, Vol. 49, No. 5-6, pp. 143-151, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Carvalho CM, Fujisawa M, Shirakawa T, Gotoh A, Kamidono S, Freitas Paulo T, Santos SE, Rocha J, Pena SD, Santos FR

    2003年01月, American Journal Of Medical Genetics Part B, Vol. 116, No. , pp. 152-158 (2), 152 - 158, 英語

    [査読有り]

    研究論文(学術雑誌)

  • A Gotoh, K Goto, A Sengoku, T Shirakawa, Y Akao, M Fujisawa, H Okada, S Arakawa, H Sasaki, S Kamidono

    We examined the effect of a kappa agonist, U-50488H, upon the bladder motility of anaesthetized rats. The frequency of distension-induced rhythmic bladder contractions was reduced by the intravenous (10 mg kg(-1)) or intrathecal (10-100 mug) administration of U-50488H. The effect of intravenous U-50488H was inhibited by pre-treatment with nor-binaltorphimine (10 mg kg(-1), s.c.). The inhibition of bladder contractions by intrathecal U-50488H (30 mug) was eliminated with the concomitant use of nor-binaltorphimine (10 mg kg(-1), s.c.), and diminished by reserpine (4 mg kg(-1), i.p.), yohimbine (10 mug, i.t.) or methysergicle (20 mug, i.t.). The amplitude of bladder contractions induced by an electrical stimulation of the pontine micturition centre was not inhibited by intrathecal U-50488H (30 and 100 mug). These results suggested that a kappa agonist could inhibit micturition reflex as well as other opioids, and at least part of the inhibition was due to the diminishment of bladder sensation based on the activation of the descending monoaminergic systems through the spinal kappa-opioid receptors.

    ROYAL PHARMACEUTICAL SOC GREAT BRITAIN, 2002年12月, JOURNAL OF PHARMACY AND PHARMACOLOGY, 54 (12), 1645 - 1650, 英語

    [査読有り]

    研究論文(学術雑誌)

  • [Gene therapy for prostate cancer].

    Gotoh A, Shirakawa T, Wada Y, Hinata N, Matsubara S, Hara I, Fujisawa M, Okada H, Arakawa S, Kamidono S

    2002年11月, Hinyokika kiyo. Acta urologica Japonica, 48 (11), 729 - 732

    [査読有り]

  • Y Moriya, T Nakamura, M Horinouchi, T Sakaeda, T Tamura, N Aoyama, T Shirakawa, A Gotoh, S Fujimoto, M Matsuo, M Kasuga, K Okumura

    In the present study, we examined whether polymorphisms in the ATP-binding cassette (ABC) transporter genes, MDR1, MRP1 and MRP2, were associated with their respective mRNA expression levels in duodenal enterocytes of 13 healthy Japanese volunteers. MDR1 genotypes of T-129C, G2677(A,T) and C3435T, MRP1 genotypes of G128C, C218T, G2168A and G3173A, and MRP2 genotypes of C-24T, G1249A, C2302T, C2366T and G4348A were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or direct sequencing. Mutations T-129C, G2677(A,T) and C3435T of MDR1 gene were found at allele frequencies of 2/26, 16/26 and 12/26, respectively. Mutations G2168A of the MRP1 gene and C-24T of the MRP2 gene were also found at allele frequencies of 1/26 and 6/26, respectively, whereas other mutations were not detected in MRP1 and MRP2 genes. The relative concentrations (mean+/-S.E.) of MDR1 mPNA to villin mRNA were 0.38+/-0.15, 0.56+/-0.14 and 1.13+/-0.42 in the subjects with C/C-3435, C/T-3435 and T/T-3435, respectively, which supported the lower serum concentrations of digoxin after single oral administration in the subjects with the mutant T-allele at position 3435. Genetic collaboration between positions 3435 and 2677 was suggested, and those in G/G(2677), G/(A,T)(2677) and T/(A,T)(2677) were 0.16+/-0.05, 1.10+/-0.40, and 0.63+/-0.16, respectively (p = 0.107). However, there was no remarkable effect of the G2168A of the MRP1 gene or of C-24T of the MRP2 gene on the relative MRP1 or MRP2 mRNA concentrations, respectively.

    PHARMACEUTICAL SOC JAPAN, 2002年10月, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 25 (10), 1356 - 1359, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Sakaeda, T Nakamura, M Hirai, T Kimura, A Wada, T Yagami, H Kobayashi, S Nagata, N Okamura, T Yoshikawa, T Shirakawa, A Gotoh, M Matsuo, K Okumura

    Purpose. Recently, MDR1 (P-glycoprotein) and related transporters have been suggested to play a fundamental role in regulating apoptosis, but little information is available concerning the role of MDR1. Here, the effect of apoptotic stimuli on the MDR1 mRNA and apoptotic signaling was examined in MDR1-overexpressing cells. Methods. The expression levels of mRNA for MDR1, MRP1, MRP2, p53, p21, Bax, and Bcl-2 were measured by real time quantitative polymerase chain reaction in HeLa and its MDR1-overexpressing sublines. The effects of apoptotic stimuli by cisplatin (CDDP) on their levels were also assessed as well as on caspase 3, 8, and 9 activities. Results. MDR1 was rapidly upregulated when the cells were exposed to apoptotic stimuli by CDDP. The increase in Bax mRNA to Bcl-2 mRNA ratio after treatment with CDDP was suppressed in MDR1-overexpressing cells. The increases in caspase 3 and 9 activities after treatment with CDDP were suppressed in MDR1-overexpression cells. Conclusion. MDR1 is upregulated by apoptotic stimuli suppressed apoptotic signaling presumably via the mitochondrial pathway.

    KLUWER ACADEMIC/PLENUM PUBL, 2002年09月, PHARMACEUTICAL RESEARCH, 19 (9), 1323 - 1329, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Bito, S Roy, CK Sen, T Shirakawa, A Gotoh, M Ueda, M Ichihashi, L Packer

    The effect of plant flavonoids on intercellular adhesion molecule-1 (ICAM-1) expression in human keratinocyte was investigated. ICAM-1 is known to mediate skin inflammation. Among the flavonoids tested, taxifolin was the most potent in inhibiting interferon gamma (IFNgamma)-induced ICAM-1 protein as well as mRNA expression in human keratinocytes. Much smaller dosages of taxifolin were required in primary keratinocytes compared to HaCaT (immortalized cell) to achieve similar levels of inhibition in the inducible ICAM-1 expression. Regulation of inducible ICAM-1 expression by taxifolin was at transcriptional level by inhibiting the activation of signa transducers and activators of transcription (STAT)1 and protein tyrosine phosphorylation of Janus kinase (JAK)1 suggesting that the JAK-STAT pathway may be the molecular site of action of taxifolin. Finally, taxifolin pre-treatment also potently inhibited IFNgamma-induced ICAM-1 expression in a reconstructed human skin equivalent suggesting therapeutic potential of taxifolin in skin pathological conditions related to increased cell adhesion and inflammation. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

    ELSEVIER SCIENCE BV, 2002年06月, FEBS LETTERS, 520 (1-3), 145 - 152, 英語

    [査読有り]

    研究論文(学術雑誌)

  • S Matsubara, H Okada, T Shirakawa, A Gotoh, T Kuno, S Kamidono

    Objectives. To observe the expression of beta-3-adrenoceptor in the detrusor muscle in female rats and investigate the relaxant effect of beta-adrenoceptor agonists on detrusor muscle in ovariectomized rats with or without estrogen replacement therapy. Methods. We first performed reverse transcriptase-polymerase chain reaction to demonstrate mRNA encoding the beta-3-adrenoceptor in the detrusor muscle from female rats. We then performed pharmacologic and physiologic studies to determine the effect of estrogen replacement therapy on the beta-adrenoceptor-mediated relaxation of the detrusor muscle of the ovariectomized rats. Results. Beta-3-adrenoceptor was expressed in the detrusor muscle in female rats with or without ovariectomy. A nonselective beta-adrenoceptor agonist relaxed precontracted detrusor muscle irrespective of ovariectomy or estrogen replacement in a dose-dependent manner; and a selective beta-3-adrenoceptor agonist relaxed the detrusor muscle more in ovariectomized rats than in ovariectomized rats with estrogen replacement or in control rats. Conclusions. Selective beta-3-adrenoceptor agonists relaxed the detrusor muscle of female rats with low estrogen levels. This result may give a clue to the treatment of frequent urination or incontinence in postmenopausal women who are not receiving hormonal replacement therapy.

    ELSEVIER SCIENCE INC, 2002年04月, UROLOGY, 59 (4), 621 - 625, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Nakamura, T Sakaeda, M Horinouchi, T Tamura, N Aoyama, T Shirakawa, M Matsuo, M Kasuga, K Okumura

    The effect of the C3435T mutation at exon 26 of the MDR1 gene on the expression levels of MDR1 messenger ribonucleic acid (mRNA) was evaluated by means of real-time polymerase chain reaction in 51 biopsy specimens of duodenum obtained from 13 healthy Japanese subjects. The mRNA levels of MDR1 were 0.38 +/- 0.15, 0.56 +/- 0.14, and 1.13 +/- 0.42 (mean value +/- SE) in the subjects with the homozygote of wild-type allele (C/C), compound heterozygote with mutant T allele (C/T), and the homozygote of the mutant allele (T/T), respectively, reasonably explaining the lower digoxin serum concentration after administration of a single oral dose to subjects harboring a mutant T allele. Good correlation (r =.797; P <.01) was observed between the mRNA concentrations of MDR1 and CYP3A4 in the individual biopsy specimens. This finding suggested a lower plasma concentration of the substrates for CYP3A4 in subjects harboring the C3435T mutation of the MDR1 gene.

    MOSBY, INC, 2002年04月, CLINICAL PHARMACOLOGY & THERAPEUTICS, 71 (4), 297 - 303, 英語

    [査読有り]

    研究論文(学術雑誌)

  • T Nakamura, T Sakaeda, N Ohmoto, T Tamura, N Aoyama, T Shirakawa, T Kamigaki, T Nakamura, KI Kim, Kim, SR, Y Kuroda, M Matsuo, M Kasuga, K Okumura

    The expression levels of mRNAs for MDR1 (P-glycoprotein), multidrug resistance-associated proteins (MRP1, MRP2), and cytochrome P450 3A (CYP3A) in Caco-2 cells were quantitatively compared with those in human duodenal enterocytes, normal colorectal tissues, and colorectal adenocarcinomas. Caco-2 cells (passages 36-38) were kindly supplied by several laboratories in Japan. Human duodenal enterocytes were obtained from five healthy male volunteers. Normal colorectal tissues and colorectal adenocarcinomas were simultaneously obtained from seven patients with primary colorectal adenocarcinoma. MDR1, MRP1, MRP2, and CYP3A mRNA levels were determined by real-time quantitative polymerase chain reactions (PCR). Relative concentrations of mRNAs for target proteins (MDR1, MRP1, MRP2, and CYP3A) and glyceraldehyde-3-phosphate dehydrogenase in Caco-2 cells were 1.00 +/- 0.15, 1.02 +/- 0.06, 0.94 +/- 0.10, and 0.68 +/- 0.60, respectively, and those in human enterocytes were about 12-, 3-, 7-, and 8000-fold higher than in the Caco-2 cells, respectively. In contrast, MDR1, MRP1, and CYP3A mRNA levels in Caco-2 cells were comparable to those in normal colorectal tissue and colorectal adenocarcinoma.

    AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS, 2002年01月, DRUG METABOLISM AND DISPOSITION, 30 (1), 4 - 6, 英語

    [査読有り]

    研究論文(学術雑誌)

  • [Prospects for molecular research in urological oncology: gene therapy]

    Gotoh A, Shirakawa T, Wada Y, Hinata N, Hara I, Fujisawa M, Okada H, Arakawa S, Kamidono S, Hinyokika kiyo, Acta urologica Japonica

    Gotoh A, Shirakawa T, Wada Y, Hinata N, Hara I, Fujisawa M, Okada H, Arakawa S, Kamidono S, Hinyokika kiyo. Acta urologica Japonica, 2001, vol. 47, no. 11, pp. 829-832

    2001年11月, 47 (11), 829 - 832

    [査読有り]

  • Shirakawa T, Sasaki R, Gardner TA, Kao C, Zhang ZJ, Sugimura K, Matsuo M, Kamidono S, Gotoh A

    2001年10月, International journal of cancer, 94 (2), 282 - 289

    [査読有り]

  • T Shirakawa, A Gotoh, TA Gardner, CH Kao, ZJ Zhang, S Matsubara, Y Wada, N Hinata, M Fujisawa, K Hanioka, M Matsuo, S Kamidono

    Background Benign prostatic hyperplasia (BPH) is the most common proliferative disease affecting men. Numerous minimally invasive technologies are being developed or are currently in use to obviate the need for transurethral surgery. The goal of the present study was to develop a novel molecular based approach for the treatment of BPH using recombinant p53 adenoviral vector. The over-expression of wt-p53 can cause cell apoptosis or cell growth arrest, thus preventing the uncontrolled cell proliferation underlying BPH pathophysiology. Methods Ad-CMV-p53, a replication-deficient recombinant adenovirus containing cytomegalovirus promoter driving p53 gene, was used. Human prostate stromal CPS) cells were evaluated for apoptosis (TUNEL assay), mRNA levels of key cell cycle regulators influencing apoptosis (p-53, Bax and Bcl-2) using quantitative RT-PCR and cytotoxicity after Ad-CMV-p53. Ad-CMV-p53 was unilaterally injected into rat ventral prostates and growth inhibition was measured by prostate weight 3 weeks after injection. Results In vitro exposure to Ad-CMV-p53 significantly inhibited the proliferation of PS cells, induced mRNA over-expression of both wt-p53 and Bax, and increased the proportion of apoptotic cells. A 30% decrease in average prostate weight was demonstrated in rodents after Ad-CMV-p53 injection. Conclusions The results suggest that further investigation of molecular gene therapy with recombinant wt-p53 adenovirus for the treatment of BPH is warranted. Copyright (C) 2000 John Wiley & Sons, Ltd.

    JOHN WILEY & SONS LTD, 2000年11月, JOURNAL OF GENE MEDICINE, 2 (6), 426 - 432, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Shirakawa T, Gotoh A, Wada Y, Kamidono S, Ko SC, Kao C, Gardner TA, Chung LW

    2000年, Molecular urology, 4 (2), 73 - 82

    [査読有り]

  • T Shirakawa, TA Gardner, SC Ko, N Bander, S Woo, A Gotoh, S Kamidono, LWK Chung, C Kao

    Purpose: An estimated 11,600 Americans will die of renal cell carcinoma in 1998. The lack of effective chemotherapy or radiotherapy requires the investigation of novel treatment modalities. We compared two forms of toxic gene therapy, cytosine deaminase (CD) plus 5-fluorocytosine (5-FC) and thymidine kinase (TK) plus acyclovir (ACV), in pre-clinical models of human renal cell carcinoma. Materials and Methods: Replication-deficient recombinant adenoviral vectors containing the Rous sarcoma virus promoter driving CD (Ad-RSV-CD) or TK (Ad-RSV-TK) gene expression were constructed and tested for in vitro cell-killing assays at various viral multiplicity of infection (MOI) and in vivo for growth inhibition of a human renal cell carcinoma, SK-RC-29 models. Subcutaneous tumors of SK-RC-29 were examined by electron microscopy for presence of intercellular gap junctions. Levels of expression of the gap junctional associated connexin 43 protein in SK-RC-29, 31, 38, 42, 52 human RCC cell lines were examined by western immunoblotting. Results: In vitro cell-killing assay comparing Ad-RSV-CD/5F-C and Ad-RSV-TK/ACV at a wide range of MOI (2.5 to 20) revealed superior cell-kill by Ad-RSV-CD/5-FC over Ad-RSV-TK/ACV. Consistent with these results, we observed that Ad-RSV-CD/5-FC but not Ad-RSV-TKIACV demonstrated a significant in vivo tumor growth inhibition. These results are corroborated by the lack of gap junctions in SK-RC-29 subcutaneous tumors by the electron microscopy and the absence of connexin-43 in all five human RCC cell lines by western immunoblotting. Conclusion: We have demonstrated in this study that Ad-RSV-CD/5-FC is superior to Ad-RSV-TK/ACV for the treatment of human RCC in cell culture and animal models. The results are supported by the lack of gap junctional communication between RCC cells assessed by connexin-43 expression.

    LIPPINCOTT WILLIAMS & WILKINS, 1999年09月, JOURNAL OF UROLOGY, 162 (3), 949 - 954, 英語

    [査読有り]

    研究論文(学術雑誌)

  • In vivo suppression of osteosarcoma pulmonary metastasis with intravenous osteocalcin promoter-based toxic gene therapy

    T Shirakawa, SC Ko, TA Gardner, J Cheon, T Miyamoto, A Gotoh, LWK Chung, CH Kao

    Pulmonary metastases are the main cause of death of patients with several types of cancer, including osteosarcoma, renal cell carcinoma, malignant melanoma, and breast cancer. Previously, we demonstrated that intralesional injection of the recombinant adenovirus (Ad) vector containing the herpes simplex virus thymidine kinase (TK) gene driven by an osteocalcin (OC) promoter (Ad-OC-TK) effectively suppressed the growth of osteosarcoma cells in vitro and tumors in vivo in a tumor-specific manner when supplemented with the prodrug acyclovir (ACV). In this communication, we studied the potential efficacy of the treatment of osteosarcoma pulmonary metastases with a systemic delivery route of Ad-OC-TK supplemented with ACV. We established osteosarcoma lung metastases in nude mice by the intravenous injection of rat osteosarcoma cells, ROS 17/2.8. These cells colonized and formed tumor nodules within 1 week in the lungs of nude mice. Whereas systemic delivery of a recombinant Ad vector containing the Escherichia coli beta-galactosidase (beta-gal) gene driven by a Rous sarcoma virus universal promoter (Ad-RSV-beta-gal) resulted in the nonspecific expression of beta-gal activity in the lung parenchyma, Ad-OC-beta-gal administration resulted in specific beta-gal expression in tumor cells deposited in the lung. When nude mice bearing ROS 17/2.8 lung tumors were treated with systemic Ad-OC-TK through tail vein administration, subsequent intraperitoneal ACV treatment significantly decreased the number of tumor nodules (P < .0001) and the net lung wet weight (P = .0005) while significantly increasing (.005 < P < .01) the survival of animals, when compared with untreated and Ad-OC-TK- or ACV-treated control groups. These results suggest that Ad-OC-TK/ACV may be used as a systemic therapy for the treatment of osteosarcoma lung metastasis.

    APPLETON & LANGE, 1998年09月, CANCER GENE THERAPY, 5 (5), 274 - 280, 英語

    [査読有り]

    研究論文(学術雑誌)

  • A Gotoh, SC Ko, T Shirakawa, J Cheon, CH Kao, T Miyamoto, TA Gardner, LJ Ho, CBJ Cleutjens, J Trapman, FL Graham, LWK Chung

    Purpose: The goal of this study is to develop a tissue-specific toxic gene therapy utilizing the prostate specific antigen (PSA) promoter for both androgen-dependent (AD) and androgen-independent (AI) PSA-secreting prostate cancer cells. Ideally this gene therapy would be effective without the necessity of exposing the target cells to circulating androgens. Materials and Methods: An AI subline of LNCaP, an AD PSA-secreting human prostate cancer cell line, C4-2, was used in this study. Castrated mice bearing C4-2 tumors secrete PSA. A transient expression experiment was used to analyze the activity of two PSA promoters, a 5837 bp long PSA promoter and a 642 bp short PSA promoter, in C4-2 cells. A recombinant adenovirus (Ad-PSA-TK) carrying thymidine kinase under control of the long PSA promoter was generated. The tissue-specific activity of Ad-PSA-TK was tested in vitro and in vivo. Results: The long PSA promoter had superior activity over short PSA promoter, and higher activity in C4-2 cells than in LNCaP cells. High activity of Ad-PSA-TK was observed in C4-2 cells in an androgen deprived condition. In vitro, Ad-PSA-TK was further demonstrated to induce marked C4-2 cell-kill by acyclovir in medium containing 5% FBS. No cell-kill was observed in control WH cells (a human bladder cancer cell line). In vivo, Ad-PSA-P-TK with acyclovir significantly inhibited subcutaneous C4-2 tumor growth and PSA production in castrated animals. Conclusion: The 5837 bp long PSA promoter was active in the androgen free environment and could be used to target both androgen-dependent and independent PSA-producing prostate cancer cells in vitro, and prostate tumors in castrated hosts.

    LIPPINCOTT WILLIAMS & WILKINS, 1998年07月, JOURNAL OF UROLOGY, 160 (1), 220 - 229, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Chemogene therapy: Osteocalcin promoter-based suicide gene therapy in combination with methotrexate in a murine osteosarcoma model

    J Cheon, SC Ko, TA Gardner, T Shirakawa, A Gotoh, C Kao, LWK Chung

    We previously reported that the recombinant adenovirus (Ad) vector containing the thymidine kinase (TK) gene driven by the osteocalcin (OC) promoter (Ad-OC-TK), when delivered concurrently with acyclovir (ACV), is highly selective in blocking the growth of osteosarcoma in experimental models (Cancer Res. 1996;56:4614-4619). To investigate the possible additive effects of the combined treatment of gene therapy and conventional chemotherapy (chemogene therapy), we compared the effect of low dose (IC10) methotrexate (MTX) and OC promoter-based toxic gene therapy with either of these single modalities alone. We choose low dose MTX with the intent of determining whether chemosensitization of the osteosarcoma may be possible in combination with gene therapy with an overall reduced toxicity profile and enhanced therapeutic efficacy when compared to a single agent alone. In vitro, the combined treatments of MTX (3 ng/mL) and Ad-OC-TK (20 multiplicity of infection (MOI)/target cell) plus ACV (10 mg/mL) had an additive therapeutic effect over that of either MTX (P < 0.05) or Ad-OC-TK plus ACV treatment alone (P < 0.05). In vivo, nude mice with subcutaneous tumors of either human osteosarcoma (MG-63) or rat osteosarcoma (ROS) received three intratumoral injections of Ad-OC-TK (5 X 10(8) PFU) plus daily intraperitoneal ACV (40 mg/kg body weight) for 2 weeks in combination with five weekly bolus intraperitoneal MTX (87.5 mg/kg). Osteosarcoma tumor growth was inhibited more efficiently than by either Ad-OC-TK plus ACV (P < 0.05) or MTX treatment (P < 0.005) alone. At day 45 in the ROS group, 100% of the animals survived when treated with chemogene therapy, whereas 80% survived with gene therapy and no animals survived in the MTX-treated or untreated controls. In summary, we developed a novel therapeutic strategy for the treatment of osteosarcoma employing both chemotherapy and gene therapy. Chemogene therapy could potentially achieve better antitumor effects with reduced toxicity than the conventional chemotherapy or gene therapy protocols alone.

    APPLETON & LANGE, 1997年11月, CANCER GENE THERAPY, 4 (6), 359 - 365, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma in experimental models

    SC Ko, J Cheon, CH Kao, A Gotoh, T Shirakawa, RA Sikes, G Karsenty, LWK Chung

    Osteocalcin (OC), a noncollagenous bone matrix protein, is expressed in high levels by osteoblasts. To determine whether the OC promoter mediates cell-specific gene expression in cells of osteoblast lineage, we constructed a recombinant adenovirus, Ad-OC-TK, which contains the OC promoter that drives the expression of herpes simplex virus thymidine kinase (TK). We tested the expression of TK by this virus in osteoblast cell lines as well as in non-osteoblastic cell lines by assessing the enzyme activity of TK in vitro. Whereas the OC promoter failed to drive the expression of the TK gene in several non osteoblastic cell lines such as WH, a human bladder transitional carcinoma, and NIH 3T3, an embryonic mouse fibroblast cell line, the OC promoter mediated high levels of expression in osteoblast cell lines including murine ROS and human MG-63 cells. The addition of acyclovir (ACV), a pro-drug for the inhibition of cell proliferation, resulted in the induction of osteoblast-specific cell death in vitro. Intratumoral injection of Ad-OC-TK into murine ROS osteosarcoma abolished tumor growth in a host treated with subsequent i.p. ACV injection in vivo. The Ad-OC-TK virus plus ACV treatment appears to be highly selective in blocking the growth of both murine and human osteosarcoma cell lines in vitro and murine osteosarcoma in vivo.

    AMER ASSOC CANCER RESEARCH, 1996年10月, CANCER RESEARCH, 56 (20), 4614 - 4619, 英語

    [査読有り]

    研究論文(学術雑誌)

MISC

  • 尿路感染症の遺伝子診断

    白川 利朗, 藤澤 正人

    2020年02月, 泌尿器外科, 33 (2), 117 - 120, 日本語

    [招待有り]

    記事・総説・解説・論説等(学術雑誌)

  • 神戸大学インドネシア拠点のあゆみと実績

    内海 孝子, 清水 一史, 小瀧 将裕, 亀岡 正典, 白川 利朗, 堀田 博, 林 祥剛

    2015年04月, 最新医学, 74 (4), 745 - 743, 日本語

    [査読有り][招待有り]

    その他

  • 【C型肝炎治療update】 基礎研究の進歩 ビフィズス菌を利用したC型肝炎経口ワクチンの開発(解説/特集)

    白川利朗

    2014年02月, 日本臨床, 73 (2), 239 - 242, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • Katsumi Shigemura, Kazushi Tanaka, Minori Matsumoto, Yuzo Nakano, Toshiro Shirakawa, Masahiro Miyata, Masuo Yamashita, Soichi Arakawa, Masato Fujisawa

    The purpose of this study was to investigate the association between prophylactic antibiotic administration (PAA) and post-operative infection in radical cystectomy with orthotopic neobladder urinary diversion carried out for patients with bladder cancer. Fifty-seven consecutive cases were analyzed retrospectively. Post-operative infections were categorized as urinary tract, wound, and remote infections. We used the antibiotics tazobactam/piperacillin (TAZ/PIPC), sulbactam/ampicillin (SBT/ABPC), flomoxef (FMOX), cefazolin (CEZ), cefotiam (CTM), and cefmetazole (CMZ). Twenty-five (43.9%) patients had post-operative infections. Five of these (8.77%) patients had wound infections, 22 (38.6%) patients had urinary tract infections, and 2 (3.51%) had remote infections. Our statistical analysis demonstrated that the patients with TAZ/PIPC used for PAA (5/18: 27.8%) had a significantly lower post-operative infection rate than patients with other antibiotics (24/39: 61.5%) (p = 0.0442). In addition, the patients with a shorter-duration PAA (within 72 h after the operation (48-72 h)) had a significantly lower rate of post-operative infections (12/33: 36.4%) than those with longer-duration PAA (longer than 72-96 h after the operation) (16/24: 66.7%) (p = 0.0239). Taken together, these results suggest that TAZ/PIPC with shorter PAA duration (within 72 h) might lead to a lower rate of post-operative infections. In conclusion, our data showed that PAA with TAZ/PIPC with a shorter duration PAA (within 72 h) might be recommended for radical cystectomy with orthotopic neobladder reconstruction. A prospective study based on our data is desirable to establish or revise guidelines for prophylactic medication for preventing post-operative infection after radical cystectomy with orthotopic neobladder urinary diversion.

    SPRINGER JAPAN KK, 2012年08月, JOURNAL OF INFECTION AND CHEMOTHERAPY, 18 (4), 479 - 484, 英語

    [査読有り]

    記事・総説・解説・論説等(学術雑誌)

  • エンドスタチン遺伝子導入による腫瘍内プラチナ濃度の増大

    中村 任, Adhim Zainal, Lin Xubin, Huang Wenlin, 安井 裕之, 大月 直樹, 丹生 健一, 藤澤 正人, 白川 利朗

    (公社)日本薬剤学会, 2011年05月, 日本薬剤学会年会講演要旨集, 26年会, 229 - 229, 日本語

  • 前立腺癌患者末梢血中Circulating tumor cells(CTCs)の検出法の開発

    山道 深, 森下 真一, 白川 利朗, 藤澤 正人, 松岡 孝幸, 川端 眞人

    泌尿器科紀要刊行会, 2011年05月, 泌尿器科紀要, 57 (5), 275 - 275, 日本語

  • 白川 利朗, ザイナル・アドヒム, 松岡 孝幸, 重村 克己, 丹生 健一, 川端 眞人, 藤澤 正人

    (一社)日本泌尿器科学会, 2010年02月, 日本泌尿器科学会雑誌, 101 (2), 250 - 250, 日本語

  • Shirakawa T

    2009年04月, Drug news & perspectives, Vol. 22, No. 3, pp. 140-5, 英語

    [査読有り]

    記事・総説・解説・論説等(学術雑誌)

  • 【がん化学療法個別化の現状と展望】 泌尿器科腫瘍の遺伝子診断と個別化治療を目指した分子標的療法

    白川利朗

    2008年12月, 医薬ジャーナル, 44巻, 12号, pp. 83-86, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 腎臓がん患者におけるsorcinの発現低下(Suppression of sorcin mRNA in patients with renal cell carcinoma)

    川上 恵, 中村 任, 岡村 昇, 寺尾 秀治, 後藤 章暢, 白川 利朗, 藤澤 正人, 山森 元博, 栄田 敏之

    日本癌学会, 2008年09月, 日本癌学会総会記事, 67回, 390 - 391, 英語

  • The current status of adenovirus-based cancer gene therapy

    Shirakawa T

    2008年06月, Molecules and cells, Vol. 25, No. 4, pp. 462-6, 英語

    [査読有り]

    記事・総説・解説・論説等(学術雑誌)

  • 腎癌におけるSorcin発現の検討とVEGF発現に及ぼす影響

    寺尾 秀治, 岡村 昇, 白川 利朗, 中村 任, 栄田 敏之, 奥村 勝彦, 武中 篤, 藤澤 正人, 後藤 章暢

    (一社)日本泌尿器科学会, 2008年02月, 日本泌尿器科学会雑誌, 99 (2), 485 - 485, 日本語

  • Shirakawa T, Fujisawa M

    2008年01月, Frontiers In Bioscience, Vol. 13, No. 1, pp. 2115-9, 英語

    [査読有り]

    記事・総説・解説・論説等(学術雑誌)

  • ホルモン不応性再燃前立腺癌の治療 骨転移を有するホルモン不応性前立腺癌に対する遺伝子治療臨床研究の長期成績

    白川 利朗, 後藤 章暢, 寺尾 秀治, 日向 信之, 田中 一志, 武中 篤, 原 勲, 守殿 貞夫, 藤澤 正人

    (一社)日本癌治療学会, 2007年09月, 日本癌治療学会誌, 42 (2), 337 - 337, 日本語

  • 腎癌におけるSorcinおよびVEGFの発現に関する検討(Effect of sorcin on VEGF expression in renal cell carcinoma)

    寺尾 秀治, 岡村 昇, 白川 利朗, 中村 任, 栄田 敏之, 武中 篤, 藤澤 正人, 後藤 章暢

    日本癌学会, 2007年08月, 日本癌学会総会記事, 66回, 182 - 182, 英語

  • 新しい抗癌剤の臨床研究 ホルモン療法抵抗性の転移性前立腺癌の患者に対するAd-OC-TK遺伝子療法の臨床試験成績(Clinical Studies of New Anticancer Drugs Results of clinical study of Ad-OC-TK gene therapy for the patients with hormone refractory metastatic prostate cancer)

    白川 利朗, 後藤 章暢, 寺尾 秀治, 日向 信之, 田中 一志, 武中 篤, 原 勲, 守殿 貞夫, 藤澤 正人

    日本癌学会, 2007年08月, 日本癌学会総会記事, 66回, 71 - 71, 英語

  • プロテオーム解析による腎臓癌に対する新規診断マーカー・創薬ターゲットの探索

    松本 隼, 岡村 昇, 増田 太郎, 金子 直樹, 渡辺 真, 後藤 章暢, 白川 利朗, 寺尾 秀治, 瀬戸 亮太, 中村 任, 矢上 達郎, 藤澤 正人, 栄田 敏之, 西村 紀, 奥村 勝彦

    (公社)日本薬学会, 2007年03月, 日本薬学会年会要旨集, 127年会 (3), 232 - 232, 日本語

  • 腎臓癌のタンパク発現プロファイル解析

    瀬戸 亮太, 岡村 昇, 増田 太郎, 西村 紀, 後藤 章暢, 白川 利朗, 寺尾 秀治, 中村 任, 田中 久登, 栄田 敏之, 奥村 勝彦

    (一社)日本TDM学会, 2006年07月, TDM研究, 23 (3), s138 - s138, 日本語

  • 【再燃前立腺癌に対する治療戦略】 遺伝子治療の現状と展望

    白川利朗, 後藤章暢

    2006年02月, Urology View, 4巻, 1号, pp.71-75, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 連載講座、なくならない感染症⑫、クラミジア

    白川利朗

    2005年12月, Circles, 7巻, 3, pp.21-23, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • マウス造精機能障害モデルにおけるTRAIL発現抑制の効果

    合田上政, 後藤章暢, 白川利朗, 寺尾秀治, 土橋正樹, 岡田弘, 守殿貞夫, 藤澤正人

    2005年09月, 日本生殖内分泌学会雑誌, 10巻, pp.37-42, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • COX-2臓器特異性プロモーターを組み込んだ増殖型アデノウイルスベクターによる頭頸部扁平上皮癌に対する治療法の検討

    田中博紀, 丹生健一, ZhangZhujun, 白川利朗, 後藤彰暢

    2005年05月, 日本耳鼻咽喉科学会会報, 108巻, 5増刊, pp.595-595, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • Acharya Bishnu, Shirakawa Toshiro, Pungky Ardanykusuma, Damanik Parlin, Massi Muh Nasrum, Miyata Masahiro, Matsuo Masafumi, Gotoh Akinobu

    2005年, American Journal Of Nephrology, Vol. 25, No. 1, pp. 30-35, 英語

    [査読有り]

    記事・総説・解説・論説等(学術雑誌)

  • 【泌尿器科ガイドラインの背景と現況】 学会とガイドライン

    守殿貞夫, 白川利朗, 後藤章暢, 原勲

    2003年11月, Urology View, 1巻, 6号, pp. 45-49, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 前立腺癌に対するカテキン及びアントシアニンの抗腫瘍効果の比較検討

    後藤 章暢, 和田 義孝, 松本 浩彦, 白川 利朗, 日向 信之, 荒川 創一, 守殿 貞夫, 藤澤 正人

    日本腎泌尿器疾患予防医学研究会, 2003年03月, 日本腎泌尿器疾患予防医学研究会誌, 11 (1), 90 - 91, 日本語

  • 前立腺肥大症組織における5-Alpha-Reductaseのサブタイプ、Type-1およびType-2の発現と酵素活性に関する検討

    白川 利朗, 岡田 弘, 後藤 章暢, 日向 信之, 和田 義孝, 守殿 貞夫, 宇治 達哉, 山本 明良

    社団法人日本泌尿器科学会, 2003年02月15日, 日本泌尿器科學會雜誌, 94 (2), 日本語

  • 定量的PCR法を用いた細菌尿中の大腸菌の定量

    日向 信之, 白川 利朗, 和田 義孝, 守殿 貞夫, 後藤 章暢

    西日本泌尿器科学会, 2002年11月, 西日本泌尿器科, 64 (増刊), 174 - 174, 日本語

  • 難治性前立腺癌に対する治療の現状と問題点 遺伝子治療

    後藤 章暢, 白川 利朗, 和田 義孝, 日向 信之, 松原 重治, 原 勲, 藤澤 正人, 岡田 弘, 荒川 創一, 守殿 貞夫

    泌尿器科紀要刊行会, 2002年11月, 泌尿器科紀要, 48 (11), 729 - 732, 日本語

  • 堀之内 正則, 中村 任, 栄田 敏之, 阪井 俊介, 森田 圭紀, 田村 孝雄, 青山 伸郎, 白川 利朗, 松尾 雅文, 春日 雅人

    (一社)日本臨床薬理学会, 2002年03月, 臨床薬理, 33 (2), 255S - 256S, 日本語

  • 守屋 友加, 中村 任, 栄田 敏之, 堀之内 正則, 田村 孝雄, 青山 伸郎, 白川 利朗, 松尾 雅文, 藤本 貞毅, 春日 雅人

    (一社)日本臨床薬理学会, 2002年03月, 臨床薬理, 33 (2), 377S - 378S, 日本語

  • CD/5-FC遺伝子治療による、膀胱癌の放射線感受性増強効果についての基礎的検討

    白川 利朗, 後藤 章暢, 張 竹君, 日向 信之, 和田 義孝, 原 勲, 藤澤 正人, 川端 岳, 岡田 弘, 荒川 創一, 松尾 雅文, 守殿 貞夫

    社団法人日本泌尿器科学会, 2002年02月20日, 日本泌尿器科學會雜誌, 93 (2), 168 - 168, 日本語

  • 膀胱癌細胞株におけるp53変異と放射線感受性に関する検討

    日向 信之, 白川 利朗, 後藤 章暢, 原 勲, 藤澤 正人, 川端 岳, 岡田 弘, 荒川 創一, 守殿 貞夫

    社団法人日本泌尿器科学会, 2002年02月20日, 日本泌尿器科學會雜誌, 93 (2), 321 - 321, 日本語

  • 泌尿器科腫瘍学における分子研究の展望 遺伝子治療

    後藤 章暢, 白川 利朗, 和田 義孝, 日向 信之, 原 勲, 藤澤 正人, 岡田 弘, 荒川 創一, 守殿 貞夫

    泌尿器科紀要刊行会, 2001年11月, 泌尿器科紀要, 47 (11), 829 - 832, 日本語

  • 自殺遺伝子を用いた癌遺伝子治療における臓器特異性プロモーターの有用性についての基礎研究

    後藤 章暢, 和田 義孝, 白川 利朗, 日向 信之, 藤澤 正人, 岡田 弘, 守殿 貞夫

    日本癌学会, 2001年09月, 日本癌学会総会記事, 60回, 619 - 619, 日本語

  • 膀胱癌に対するCD/5-FC遺伝子治療及び放射線療法の併用療法の有用性についての基礎的検討

    白川 利朗, 後藤 章暢, 日向 信之, 藤澤 正人, 岡田 弘, 守殿 貞夫

    日本癌学会, 2001年09月, 日本癌学会総会記事, 60回, 618 - 618, 日本語

  • ヒト大腸がん及び大腸ポリープにおける薬物輸送担保のリアルタイムPCR解析

    角本 幹夫, 中村 任, 大本 暢子, 栄田 敏之, 森田 圭紀, 田村 孝雄, 青山 伸郎, 春日 雅人, 白川 利朗, 松尾 雅文

    (公社)日本薬学会, 2001年03月, 日本薬学会年会要旨集, 121年会 (3), 28 - 28, 日本語

  • Caco-2細胞及びヒト十二指腸上皮細胞における薬物輸送担体・代謝酵素発現量のリアルタイムPCR解析

    大本 暢子, 角本 幹夫, 中村 任, 栄田 敏之, 森田 圭紀, 田村 孝雄, 青山 伸郎, 白川 利朗, 松尾 雅文, 春日 雅人

    (公社)日本薬学会, 2001年03月, 日本薬学会年会要旨集, 121年会 (3), 113 - 113, 日本語

  • 前立腺癌細胞に対する放射線・アデノウイルスp53遺伝子併用療法の検討

    佐々木 良平, 白川 利朗, 後藤 章暢, 松尾 雅文, 杉村 和朗

    (公社)日本医学放射線学会, 2001年02月, 日本医学放射線学会雑誌, 61 (2), S201 - S201, 日本語

  • カテキン及びアントシアニンの前立腺癌に対する抗腫瘍効果の比較検討

    松本 浩彦, 後藤 章暢, 白川 利朗, 和田 義孝, 日向 信之, 藤澤 正人, 荒川 創一, 守殿 貞夫

    日本癌学会, 2000年09月, 日本癌学会総会記事, 59回, 607 - 607, 日本語

  • 【がん遺伝子治療の進展と現状での問題点】 前立腺癌に対する新しい遺伝子治療法の確立

    和田 義孝, 後藤 章暢, 白川 利朗, 日向 信之, 岡田 弘, 荒川 創一, 守殿 貞夫, Kao Chinghai, Gardner Thomas A, Chung Leland

    (一社)日本癌治療学会, 2000年09月, 日本癌治療学会誌, 35 (2), 249 - 249, 日本語

  • 癌遺伝子治療におけるアデノウイルスベクターの毒性比較

    和田 義孝, 後藤 章暢, 白川 利朗, 日向 信之, 原 勲, 藤澤 正人, 岡田 弘, 荒川 創一, 守殿 貞夫, Gardner Thomas

    日本癌学会, 2000年09月, 日本癌学会総会記事, 59回, 404 - 405, 日本語

  • 膀胱癌に対する放射線療法及びp53遺伝子治療による併用療法の検討

    日向 信之, 白川 利朗, 佐々木 良平, 後藤 章暢, 和田 義孝, 藤澤 正人, 荒川 創一, 松尾 雅文, 守殿 貞夫

    日本癌学会, 2000年09月, 日本癌学会総会記事, 59回, 63 - 64, 日本語

  • 抗癌剤抵抗性ヒト膀胱腫瘍に対するp53アデノウイルスベクターを用いた遺伝子治療の検討

    白川 利朗, 後藤 章暢, 佐々木 良平, 日向 信之, 和田 義孝, 藤澤 正人, 岡田 弘, 荒川 創一, 松尾 雅文, 守殿 貞夫

    日本癌学会, 2000年09月, 日本癌学会総会記事, 59回, 407 - 407, 日本語

  • 前立腺肥大症に対する遺伝子治療の検討

    日向 信之, 白川 利朗, 後藤 章暢, 松原 重治, 和田 義孝, 藤澤 正人, 荒川 創一, 守殿 貞夫

    泌尿器科紀要刊行会, 2000年09月, 泌尿器科紀要, 46 (9), 681 - 681, 日本語

  • 抗癌剤抵抗性ヒト膀胱腫瘍に対するp53アデノウイルスベクターを用いた遺伝子治療の検討

    白川 利朗, 後藤 章暢, 佐々木 良平, 日向 信之, 和田 義孝, 藤澤 正人, 岡田 弘, 荒川 創一, 内藤 誠二, 松尾 雅文, 守殿 貞夫

    社団法人日本泌尿器科学会, 2000年03月20日, 日本泌尿器科學會雜誌, 91 (3), 250 - 250, 日本語

  • 前立腺癌骨転移モデルを想定した癌遺伝子治療

    和田 義孝, 後藤 章樹, 白川 利朗, 日向 信之, Chung Leland, Gardner Thomas, 守殿 貞夫

    社団法人日本泌尿器科学会, 2000年03月20日, 日本泌尿器科學會雜誌, 91 (3), 354 - 354, 日本語

書籍等出版物

  • 細胞表層工学の進展

    白川 利朗, 北川 孝一

    分担執筆, 第2章 医療応用 2 ビフィズス菌を用いた新規経口ワクチンの開発, 株式会社CMC出版, 2020年04月

  • 先端治療技術の実用化と開発戦略

    白川 利朗, 北川 孝一

    その他, (株)技術情報協会, 2017年04月, 日本語

    学術書

  • 第7章 経口ワクチン

    白川 利朗

    その他, 株式会社 情報機構, 2013年10月, 日本語

    学術書

  • Cancer Gene Therapy / 14.Current therapeutic strategies in gene therapy for prostate cancer

    白川利朗

    共著, Research Signpost, 2010年01月, 英語

    学術書

  • Welcome to ゲノムワールド / 5-3 遺伝子治療 5-4 再生医療

    白川利朗

    共著, 廣川書店, 2009年10月, 日本語

    教科書・概説・概論

  • Gene Therapy 2007 / Gene Therapy in prostate cancer: past, present and future

    Shirakawa T, Fujisawa M

    共著, 21st Century's Center of Excellence Program of Japanese Ministry of Education and Science, 2007年01月, 英語

    学術書

講演・口頭発表等

  • WT1 oral cancer vaccine combined with anti-PD-1 antibody completely suppressed tumor growth in a murine bladder cancer model

    白川 利朗, 北川 孝一, 辰巳 真帆, 門脇 雅英, 片山 高嶺, 橋井 佳子, 藤澤 正人

    CIMT 2019 Annual Meeting, 2019年05月, 英語, ドイツ, 国際会議

    口頭発表(一般)

  • Cross-resistance and the mechanisms of cephalosporine-resistant urinary tract infection (UTI)-causative bacteria isolated in Indonesia

    katsumi Shigemura, Koichi Kitagawa, Toshiro Shirakawa, Masato Fujisawa

    34th Annual EAU Congress, 2019年03月, 英語, Barcelona, 国際会議

    ポスター発表

  • Comparison of molecular characteristics of carbapenem-resistant urinary tract infection- causing pathogens between Japan, Taiwan and Indonesia

    katsumi Shigemura, Kento Nishimoto, Kayo Osawa, Kuntaman K, Sung S, Chen K, Kitagawa K, Huang T, Toshiro Shirakawa, Masato Fujisawa

    34th Annual EAU Congress, 2019年03月, 英語, Barcelona, 国際会議

    ポスター発表

  • 尿路感染症におけるカルバペネム耐性腸内細菌科細菌の分子生物学的検討ならびに迅速診断法の確立

    重村 克巳, 大澤 佳代, 江夏 徳寿, 北川 孝一, 白川 利朗, 中野 雄造, 藤澤 正人

    第28回 泌尿器科分子・細胞研究会, 2019年02月, 日本語, 下関, 国内会議

    ポスター発表

  • 日本(神戸)とインドネシア(Yogyakarta)における尿路感染症の国際間比較

    北川 孝一, 重村 克巳, 西本 健人, 山田 尚輝, Prahara Yuri, Andy Zulfiqqar, 大澤 佳代, 宇田 篤史, 白川 利朗, 荒川 創一, 宮良 高維, 藤澤 正人

    第34回日本環境感染学会総会・学術集会, 2019年02月, 日本語, 神戸, 国内会議

    ポスター発表

  • 改変型ヒトWilms’ tumor 1タンパク表層発現ビフィズス菌を用いた経口癌ワクチンの各種固形癌に対する抗腫瘍免疫誘導効果に関する検討

    辰巳 真帆, 北川 孝一, 加藤 真子, 駒井 翔太, 橋井 佳子, 片山 高嶺, 白川 利朗

    第22回日本ワクチン学会学術集会, 2018年12月, 日本語, 神戸, 国内会議

    口頭発表(一般)

  • 遺伝子組換えビフィズス菌を用いた次世代型経口結核ワクチンの開発

    古田 拓也, 門脇 雅英, 北川 孝一, 土井 教生, 片山 高嶺, 白川 利朗

    第22回日本ワクチン学会学術集会, 2018年12月, 日本語, 神戸, 国内会議

    口頭発表(一般)

  • Cancer immunotherapy combining oral vaccination of recombinant Bifidobacterium longum displaying human Wilms’ tumor 1 protein and anti-PD-1 checkpoint blockade for solid tumors in mice experimental model.

    北川 孝一, 辰巳 真帆, 加藤 真子, 駒井 翔太, 橋井 佳子, 片山 高嶺, 白川 利朗

    CRI-CIMT-EATI-AACR Fourth International Cancer Immunotherapy Conference, 2018年09月, 英語, New York, USA, 国際会議

    ポスター発表

  • インドネシアの尿路感染症患者より分離されたカルバペネマーゼ産生グラム陰性桿菌の 分子疫学的調査

    大澤 佳代, 重村 克巳, 北川 孝一, 藤澤 正人, 白川 利朗

    第13回日本臨床検査学教育学会学術大会, 2018年08月, 日本語, 札幌, 国内会議

    口頭発表(一般)

  • インドネシアで分離されたCTX-M-15型ESBL産生Escherichia coliにおける染色体性およびプラスミド性についての分子疫学調査

    大澤 佳代, 重村 克巳, 藤澤 正人, 白川 利朗

    第13回日本臨床検査学教育学会学術大会, 2018年08月, 日本語, 札幌, 国内会議

    口頭発表(一般)

  • Overexpression of SOCS3 mediated by adenovirus vector in prostate cancer cells increased the sensitivity to lymphokine-activated killer cells in vitro and in vivo.

    北川 孝一, 米田 智美, 石河 求己, 門脇 雅英, 大月 直樹, 丹生 健一, 藤澤 正人, 世良田 聡, 仲 哲治, 白川 利朗

    第24回日本遺伝子細胞治療学会, 2018年07月, 日本語, 東京, 国内会議

    口頭発表(一般)

  • Analysis of antimicrobial resistance mechanism in successive infections of Pseudomonas aeruginosa

    Noriko Nakanishi, Ryohei Nomoto, Kanako Sato, Chihiro Koike, Mari Kusuki, Tatsuya Nakamura, Katsumi Shigemura, Toshiro Shirakawa, Issei Tokimatsu, Kayo Osawa

    第91回日本細菌学会総会, 2018年03月, 日本語, 日本細菌学会, 福岡, 国内会議

    ポスター発表

  • Wilms' tumor 1抗原発現ビフィズス菌を用いた経口癌ワクチンのマウス前立腺癌に対する抗腫瘍効果の検討

    五ノ井 玲菜, 北川 孝一, 古田 拓也, 辰巳 真帆, 斉藤 大樹, 橋井 佳子, 片山 高嶺, 白川 利朗

    第40回日本分子生物学会年会, 2017年12月, 日本語, 日本分子生物学会, 神戸, 国内会議

    ポスター発表

  • SOCS3遺伝子組込み型アデノウイルスによる前立腺癌遺伝子治療の開発および免疫細胞療法との併用による抗腫瘍効果の検討

    米田 智美, 斉藤 大樹, 福井 悠夏, 北川 孝一, 世良田 聡, 仲 哲治, 白川 利朗

    第40回日本分子生物学会年会, 2017年12月, 日本語, 日本分子生物学会, 神戸, 国内会議

    ポスター発表

  • Enhanced anti-tumor effect by combining oral cancer vaccine using Bifidobacterium displaying WT1 protein with anti-PD-1 antibody therapy in mouse prostate cancer model.

    北川 孝一, 斉藤 大樹, 五ノ井 玲菜, 辰巳 真帆, 古田 拓也, 橋井 佳子, 片山 高嶺, 白川 利朗

    Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference 2017, 2017年09月, 英語, Mainz, Germany, 国際会議

    ポスター発表

  • Enhanced anti-tumor effect by combining oral cancer vaccine using Bifidobacterium displaying WT1 protein with anti-PD-1 antibody therapy in mouse prostate cancer model.

    北川 孝一, 斉藤 大樹, 五ノ井 玲菜, 辰巳 真帆, 古田 拓也, 橋井 佳子, 片山 高嶺, 白川 利朗

    Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, 2017年09月, 英語, Association for Cancer Immunotherapy, Mainz, ドイツ, 国際会議

    ポスター発表

  • Development of novel oral cancer vaccine using Bifidobacterium

    白川利朗

    Hwasun Adenoviral Cancer Therapeutics Symposium, 2017年09月, 英語, Chonnam National University, 光州, 韓国, 国際会議

    [招待有り]

    シンポジウム・ワークショップパネル(指名)

  • 兵庫県内で分離されたPseudomonas aeruginosaの薬剤耐性機構の解析

    佐藤加奈子, 大澤佳代, 重村克巳, 中村竜也, 藤澤正人, 時松一成, 白川利朗

    第12回日本臨床検査学教育学会学術大会, 2017年08月, 日本語, 日本臨床検査学教育学会, 埼玉, 国内会議

    口頭発表(一般)

  • Clostridium difficileの薬剤感受性と遺伝子解析

    衣川真矢, 大澤佳代, 重村克巳, 中村竜也, 時松一成, 藤澤正人, 白川利朗

    第12回日本臨床検査学教育学会学術大会, 2017年08月, 日本語, 日本臨床検査学教育学会, 埼玉, 国内会議

    口頭発表(一般)

  • 腸管免疫を利用した新規経口がんワクチンと免疫チェックポイント阻害剤の併用療法の開発

    白川 利朗, 北川孝一, 藤澤正人

    第23 回日本遺伝子細胞治療学会学術集会, 2017年07月, 英語, 日本遺伝子細胞治療学会, 岡山, 国内会議

    シンポジウム・ワークショップパネル(公募)

  • Wilms’ tumor 1タンパク発現ビフィズス菌を用いた経口癌ワクチンの抗腫瘍免疫誘導効果に関する検討

    北川 孝一, 辰巳 真帆, 五ノ井 玲菜, 斉藤 大樹, 橋井 佳子, 片山 高嶺, 白川 利朗

    第21回腸内細菌学会, 2017年06月, 日本語, 公益財団法人日本ビフィズス菌センター, 神戸, 国内会議

    ポスター発表

  • The level of urinary titin of DMD patients is >100-times higher than that of healthy control

    Awano H, Matsumoto M, Nagai M, Shirakawa T, Takasaki T, Maruyama N, Nabeshima Y, Matsuo M, Iijima K

    第59回日本小児神経学会学術集会, 2017年06月, 日本語, 日本小児神経学会, 大阪, 国内会議

    口頭発表(一般)

  • Urinaty titin reveals persistent proteolysis in Duchenn Muscular Dystrophy

    Awano H, Matsumoto M, Nagai M, Shirakawa T, Maruyama K, Iijima K, Nabeshima Y, Matsuo M

    22nd International Congress of the World Muscle society,, 2017年05月, 英語, The World Muscle Society, Saint-Malo, France, 国際会議

    ポスター発表

  • Urinary exceation of 8-OHdG, a biomarker of oxdative DNA damage, increases with age in DMD patients

    Matsumoto M, Awano H, Nagai T, Shirakawa T, Iijima K, Matsuo M

    22nd International Congress of the World Muscle society,, 2017年05月, 英語, The World Muscle Society, Saint-Malo, France, 国際会議

    ポスター発表

  • International comparison of causative bacteria and antimicrobial susceptibilities of UTIs between developed and developing countries

    重村 克巳, 北川 孝一, K Kuntaman, 中野 雄造, 白川 利朗, 時松 一成, 藤澤 正人

    American Urological Association (AUA) 2017 Annual Meeting 112th, 2017年05月, 英語, Boston, USA, 国際会議

    ポスター発表

  • International comparison of causative bacteria and antimicrobial susceptibilities of UTIs between developed and developing countries

    Katsumi Shigemura, Koichi Kitagawa, Kuntman Kuntaman, Yuzo Nakano, Toshiro Shirakawa, issei Tokimatsu, Masato Fujisawa

    第112回米国泌尿器科学学会年次学術集会, 2017年05月, 英語, 米国泌尿器科学学会, ボストン, アメリカ, 国際会議

    ポスター発表

  • Combination of Oral WT1 Cancer Vaccine and Anti-PD-1 Antibody Induced the Synergistic Anti-tumor Effect in Mouse Prostate Cancer Model

    北川 孝一, 五ノ井 玲菜, 辰巳 真帆, 斉藤 大樹, 橋井 佳子, 片山 高嶺, 白川 利朗

    American Society of Gene & Cell Therapy 20th Annual Meeting, 2017年05月, 英語, American Society of Gene & Cell Therapy, Washington DC, USA, 国際会議

    ポスター発表

  • 尿路感染症における原因菌と薬剤感受性の国際比較

    重村 克巳, 大澤 佳代, 中野 雄造, 小瀧 将広, L. Alimsardjono, D. Rahadjo, U. Hadi, F. Setiawan, E.B.Wasito, Ni Made Merta Niasih, K. Kuntaman, M.Rusli, 時松 一成, 荒川 創一, 白川 利朗, 藤澤 正人

    第64回 日本化学療法学会西日本支部総会第86回日本感染症学会西日本地方会学術集会, 2016年11月, 日本語, 日本化学療法学会, 沖縄, 国内会議

    口頭発表(一般)

  • Development of the novel oral cancer vaccine using Bifidobacterium longum displaying Wilms’ tumor 1 protein

    北川 孝一, 小田 麗未, 荒木 綾芽, 五ノ井 玲菜, 斉藤 大樹, 橋井 佳子, 片山 高嶺, 白川 利朗

    第22回日本遺伝子細胞治療学会学術集会, 2016年07月, 日本語, 東京, 国内会議

    口頭発表(一般)

  • Molecular characteristics of extended-spectrum ?-lactamase-producing Escherichia coli isolated urinary tract infection in a university teaching hospital

    Katsumi Shigemura, Kayo Osawa, Kazushi Tanaka, Yuzo Nakano, Toshiro Shirakawa, Soichi Arakawa, Masato Fujisawa

    American Urological Association 2016 Annual Meeting L74:AA74, 2016年05月, 英語, American Urological Association, San Diego, USA, 国際会議

    ポスター発表

  • Development of the novel oral tumor vaccine using Bifidobacterium longum displaying Wilms’ tumor 1 protein.

    北川 孝一, 小田 麗未, 荒木 綾芽, 五ノ井 玲菜, 斉藤 大樹, 橋井 佳子, 片山 高嶺, 白川 利朗

    American Society of Gene & Cell Therapy 19th Annual Meeting, 2016年05月, 英語, Washington DC, USA, 国際会議

    ポスター発表

  • Azithromycinに対する Neisseria gonorrhoeae薬剤感受性の 最近7年間の変遷について

    大澤 佳代, 重村 克巳, 吉田 弘之, 白川 利朗, 藤澤 正人, 荒川 創一

    第28回 日本性感染症学会学術大会, 2015年12月, 日本語, 日本性感染症学会, 東京, 国内会議

    口頭発表(一般)

  • Development of Combination Therapy of Bifidobacterium-based Oral Vaccine Displaying HCV-NS3 with Interferon-α

    北川 孝一, 石川 博規, 小田 麗未, 斉藤 大樹, 森下 直矢, 島本 康介, 西田 典永, 松浦 洋一, 堀田 博, 白川 利朗

    American Society of Gene & Cell Therapy 18th Annual Meeting, 2015年05月, 英語, New Orleans, Louisiana, USA, 国際会議

    ポスター発表

  • 兵庫県における淋菌の薬剤感受性の最近13年間の変遷についての検討

    大澤 佳代, 白川 利朗

    第89回日本感染症学会学術講演会, 2015年04月, 日本語, 京都, 国内会議

    ポスター発表

  • 経尿道的前立腺レーザー核出術(HoLEP)における術後尿失禁に関連する因子についてのurodynamic studyを用いた検討

    重村 克巳, 田中 一志, 桃園 宏之, 長富 俊孝, 江夏 徳寿, 村蒔 基次, 白川 利朗, 三宅 秀明, 藤澤 正人

    第103回日本泌尿器科学会総会, 2015年04月, 日本語, 日本泌尿器科学会, 金沢, 国内会議

    ポスター発表

  • ビフィズス菌を応用した 新規経口ワクチン・プラットフォーム の開発

    白川利朗

    第88回日本細菌学会総会, 2015年03月, 日本語, 日本細菌学会, 岐阜, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • 兵庫県下におけるアジスロマイシン耐性淋菌の 分子遺伝学的解析

    三浦 真希子, 重村 克巳, 大澤 佳代, 吉田 弘之, 藤原 美樹, 澤村 暢, 奈須 聖子, 荒川 創一, 藤澤 正人, 白川 利朗

    第28回日本性感染症学会学術大会, 2014年12月, 日本語, 日本性感染症学会, 神戸, 国内会議

    口頭発表(一般)

  • 兵庫県におけるアジスロマイシン(AZM)耐性淋菌の分子遺伝学的解析

    大澤 佳代, 白川 利朗

    第27回日本性感染症学会学術大会, 2014年12月, 日本語, 国内会議

    口頭発表(一般)

  • セフェム系薬剤感受性低下の遺伝解析

    大澤 佳代, 重村 克巳, 額田 雪絵, 吉田 弘之, 藤原 美樹, 奈須 聖子, 白川 利朗, 藤澤 正人, 荒川 創一

    第27回日本性感染症学会学術大会, 2014年12月, 日本語, 日本性感染症学会, 神戸, 国内会議

    口頭発表(一般)

  • セフェム系薬剤感受性低下Neisseria gonorrhoeaeの遺伝解析

    大澤 佳代, 白川 利朗

    第27回日本性感染症学会学術大会, 2014年12月, 日本語, 国内会議

    口頭発表(一般)

  • Prenatal diagnosis of holoprosencephaly with proboscis and synophthalmia caused by monosomy 18p

    Yamasaki Y, Shirakawa T, Miyahara Y, Morita H, Yamada H

    20th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI), 2014年11月, 英語, Ho Chi Minh, Vietnam, 国際会議

    ポスター発表

  • Expression of epithelial-mesenchymal transition-related factors in adherent placenta

    Shirakawa T, Miyahara Y, Yamasaki Y, Morita H, Yamada H

    20th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI), 2014年11月, 英語, Ho Chi Minh, Vietnam, 国際会議

    ポスター発表

  • Diagnosis and post-operative management of the giant ovarian tumors

    Miyahara Y, Yamasaki Y, Shirakawa T, Morita H, Yamada H

    20th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI), 2014年11月, 英語, Ho Chi Minh, Vietnam, 国際会議

    ポスター発表

  • 前立腺肥大症患者の下部尿路症状(LUTS)に対するシロドシンおよびナフトピジルの臨床効果に関する比較検討

    白川 利朗, 重村 克巳, 原口 貴裕, 江夏 徳寿, 森下 真一, 源吉 顕治, 宮崎 治郎, 三宅 秀明, 田中 一志, 藤澤 正人

    第21回日本排尿機能学会総会, 2014年09月, 日本語, 日本排尿機能学会, 岡山, 国内会議

    ポスター発表

  • Development of the novel cancer therapeutic strategy incorporating the gene therapy and immune cellular therapy

    白川利朗

    CNUH International Symposium for Urogenital Translational Research, 2014年09月, 英語, Chonnam National University Hospital, Gwangju, Korea, 国際会議

    [招待有り]

    口頭発表(招待・特別)

  • Development of Combination Therapy of Bifidobacterium Displaying HCV-NS3 Oral Vaccine with Interferon-Alpha

    Koichi Kitagawa, Chika Omoto, Hiroki Ishikawa, Tsugumi Oda, Naoya Morishita, Hak Hotta, Toshiro Shirakawa

    第20回日本遺伝子治療学会, 2014年08月, 日本語, 日本遺伝子治療学会, 東京, 国内会議

    口頭発表(一般)

  • COMBINATION THERAPY OF BIFIDOBACTERIUM DISPLAYING HCV-NS3 ORAL VACCINE WITH INTERFERON-ALPHA IN MICE

    北川 孝一, 大本 知佳, 石川 博規, 小田 麗未, 森下 直矢, 堀田 博, 白川 利朗

    第20回日本遺伝子治療学会学術集会, 2014年08月, 日本語, 国内会議

    口頭発表(一般)

  • 兵庫県下で分離されたメタロβラクタマーゼ産生腸内細菌の解析

    大澤 佳代, 白川 利朗

    第88回日本感染症学会学術講演会, 2014年06月, 日本語, 福岡, 国内会議

    ポスター発表

  • 当院で分離されたESBLs産生Escherichia coli の遺伝子解析

    大澤 佳代, 白川 利朗

    第88回日本感染症学会学術講演会, 2014年06月, 日本語, 福岡, 国内会議

    ポスター発表

  • SIGNIFICANT RECEPTORS OR BIOMARKERS FOR THE SYMPTOMS OF OVERACTIVE BLADDER

    Yamamichi F, Shigemura K, Shirakawa T, Behnsawy H, Yamashita M, Miyake H, Tanaka K, Fujisawa M

    109thAUA(American Urological Association)annual meeting, 2014年05月, 英語, American Urological Association, オーランド, アメリカ, 国際会議

    ポスター発表

  • 前立腺癌増悪において上皮ならびに間質でのSonic hedgehogとandrogenシグナル伝達が上皮間葉移行を作動させる

    山道 深, 重村 克巳, Hosny M. Behnsawy, Fatma Y. Meligy, Wen-chin Huang, Xiangyan Li, Lel, W.K.Chung, 川端 眞人, 後藤 章暢, 三宅 秀明, 田中 一志, 白川 利朗, 藤澤 正人

    第102回日本泌尿器科学会総会, 2014年04月, 日本語, 日本泌尿器科学会, 神戸, 国内会議

    ポスター発表

  • Does mutation in gyrA or parC or efflux pump expression play the main role in fluoroquinolone-resistant Escherichia coli causing urinary tract infections?

    Shigemura K, Tanaka K, Shirakawa T, Arakawa S, Miyake H, Fujisawa M

    29thEAU(European Association of Urology) Annual Congress, 2014年04月, 英語, European Association of Urology, ストックホルム, スウェーデン, 国際会議

    ポスター発表

  • Expression of epithelial-mesenchymal transition-related factors in placenta accreta

    Shirakawa T, Mihayara Y, Niiya K, Morita H, Ebina Y, Yamada H

    19th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI), 2014年02月, 英語, Macau, China, 国際会議

    ポスター発表

  • Bacterial identification using the ssrA gene encoding tmRNA

    大澤 佳代, 白川 利朗

    Asian-African Research Forum on Emerging and Reemerging Infections 2014, 2014年01月, 英語, 仙台, 国際会議

    ポスター発表

  • Bacterial identification using the ssrA gene encoding tmRNA

    Ayaka Kayo, Kayo Osawa, Katsumi Shigemura, Hiroyuki Yoshida, Miki Fujiwara, Yoshio Iijima, Masato Fujisawa, Dadik Raharjo, Subijanto Marto Sudarmo, Masato Kawabata, Toshiro Shirakawa

    Asian-African Research Forum on Emerging and Reemerging Infections 2014, 2014年01月, 英語, 仙台, 国際会議

    シンポジウム・ワークショップパネル(公募)

  • Active surveillance of children's acute diarrheal disease using a novel molecular diagnostic multiplexing system in Surabaya, Indonesia

    大澤 佳代, 白川 利朗

    Asian-African Research Forum on Emerging and Reemerging Infections 2014, 2014年01月, 英語, 仙台, 国際会議

    ポスター発表

  • 遺伝子治療・細胞治療を組み入れたがん個別化医療の現況と展望

    白川 利朗

    第17回 国際個別化医療学会, 2013年11月, 英語, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • 遺伝子治療・細胞治療を組み入れたがん個別化医療の現況と展望

    白川 利朗

    第17回国際個別化医療学会学術集会, 2013年11月, 日本語, 国際個別化医療学会, 神戸, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • The p53-specific CTL induced by Ad-p53 infected dendritic cells showed the high cytotoxicity in p53-overexpressed and Ad-53 infected tumor cell lines

    斉藤 大樹, 山崎 里沙, 森下 直矢, Dody Bautista, Dante Dator, 川端 眞人, 重村 克巳, 藤澤 正人, 白川 利朗

    第17回国際個別化医療学会学術集会, 2013年11月, 日本語, 一般財団法人国際個別化医療学会, 神戸, 国内会議

    ポスター発表

  • Synergistic antitumor effect of the combination of adenoviral gene therapy and immunotherapy for head and neck cancer

    安藤 聡志, 斉藤 大樹, 森下 直矢, 川端 眞人, 大月 直樹, 丹生 健一, 藤澤 正人, 白川 利朗

    第17回国際個別化医療学会学術集会, 2013年11月, 日本語, 一般財団法人国際個別化医療学会, 神戸, 国内会議

    ポスター発表

  • BPH/LUTSに対するデュタステリドの有用性に関する検討

    原口 貴裕, 三宅 秀明, 江夏 徳寿, 白川 利朗, 田中 一志, 藤澤 正人

    第20回日本排尿機能学会, 2013年09月, 日本語, 日本排尿機能学会, 静岡, 国内会議

    ポスター発表

  • The p53-specific CTL induced by Ad-p53 infected dendritic cells showed the high cytotoxicity in p53-overexpressED and Ad-p53 infected tumor cell lines.

    斉藤 大樹, 山崎 里沙, 森下 直矢, 川端 眞人, Dody Bautista, Dante Dator, 白川 利朗

    第19回日本遺伝子治療学会学術集会, 2013年07月, 日本語, 日本遺伝子治療学会, 岡山, 国内会議

    口頭発表(一般)

  • SYNERGISTIC ANITITUMOR EFFECT OF THE COMBINATIION OF ADENOVIRAL GENE THERAPY AND IMMUNOTHERAPY FOR HEAD AND NECK CANCER

    安藤 聡志, 斉藤 大樹, 森下 直矢, 川端 眞人, 大月 直樹, 丹生 健一, 藤澤 正人, 白川 利朗

    第19回日本遺伝子治療学会学術集会, 2013年07月, 日本語, 日本遺伝子治療学会, 岡山, 国内会議

    ポスター発表

  • ORAL ADMINISTRATION OF GENETICALLY MODIFIED BIFIDOBACTERIUM DISPLAYING HCV-NS3 MULTI-EPITOPE FUSION PROTEIN CAN INDUCE THE HCV-NS3 SPECIFIC SYSTEMIC IMMUNE RESPONSE IN MICE

    大本 知佳, 北川 孝一, 竹井 咲希, 森下 直矢, 片山 高嶺, 堀田 博, 川端 眞人, 白川 利朗

    第19回日本遺伝子治療学会学術集会, 2013年07月, 日本語, 日本遺伝子治療学会, 岡山, 国内会議

    口頭発表(一般)

  • DEVELOPMENT OF THE ORAL UNIVERSAL TYPE A INFLUENZA VACCINE USING BIFIDOBACTERIUM DISPLAYING INFLUENZA-M2e PROTEIN

    尾崎 鈴佳, 北川 孝一, 代崎 千尋, 森下 直矢, 片山 高嶺, 川端 眞人, 白川 利朗

    第19回日本遺伝子治療学会学術集会, 2013年07月, 日本語, 日本遺伝子治療学会, 岡山, 国内会議

    口頭発表(一般)

  • 尿路感染症患者より分離したPseudomonas aeruginosa 薬剤耐性株におけるefflux pump遺伝子の発現についての検討

    大澤 佳代, 白川 利朗

    第87回日本感染症学会学術講演会, 2013年06月, 日本語, 横浜, 国内会議

    ポスター発表

  • 尿路感染症患者より分離したPseudomonas aeruginosa 薬剤耐性株におけるefflux pump遺伝子の発現についての検討

    加藤 綾香, 大澤 佳代, 重村 克巳, 田中 一志, 荒川 創一, 藤澤 正人, 白川 利朗

    第87回日本感染症学会学術講演会, 2013年06月, 日本語, 日本感染症学会, 横浜, 国内会議

    ポスター発表

  • Candida urinary tract isolation and Candida species susceptibilities to anti-fungus medication in Kobe University Hospital

    大澤 佳代, 白川 利朗

    28th International Congress of Chemotherapy and Infection, 2013年06月, 英語, 横浜, 国際会議

    ポスター発表

  • Candida urinary tract isolation and Candida species susceptibilities to anti-fungus medication in Kobe University Hospital

    Katsumi Shigemura, Kayo Osawa, Kazushi Tanaka, Hiroyuki Yoshida, Toshiro Shirakawa, Masato Fujisawa, Soichi Arakawa

    28th International Congress of Chemotherapy and Infection, 2013年06月, 英語, 日本感染症学会他, 横浜, 国際会議

    ポスター発表

  • Does mutation in gyrA or parC or efflux pump expression play the main role in fluoroquinolone-resistant Escherichia coli causing urinary tract infections?

    Shigemura K, Tanaka K, Shirakawa T, Arakawa S, Miyake H, Fujisawa M

    108thAUA(American Urological Association)annual meeting, 2013年05月, 英語, AUA(American Urological Association)annual meeting, サンディエゴ, アメリカ, 国際会議

    ポスター発表

  • Development of the Oral Universal Type A Influenza Vaccine Using Bifidobacterium Displaying Influenza-M2e Protein

    尾崎 鈴佳, 森下 直矢, 北川 孝一, 代崎 千尋, 斉藤 大樹, 重村 克巳, 藤澤 正人, 川端 眞人, 白川 利朗

    American Society of Gene & Cell Therapy 16th Annual Meeting, 2013年05月, 英語, American Society of Gene & Cell Therapy, Salt Lake City, America, 国際会議

    ポスター発表

  • Combination of CD3+CD56+ (NKT) Cells Immunotherapy and Adenovirus-p53 Therapy for Head and Neck Squamous Cell Carcinoma

    斉藤 大樹, 森下 直矢, Kyung-Mi Lee, Dante Dator, 川端 眞人, 藤澤 正人, 白川 利朗

    American Society of Gene & Cell Therapy 16th Annual Meeting, 2013年05月, 英語, American Society of Gene & Cell Therapy, Salt Lake City, America, 国際会議

    ポスター発表

  • Sonic hedgehog signaling and Androgens are linked in tumor-stromal interaction through Epithelial-Mesenchymal transition (EMT) in prostate cancer progression

    Shigemura K, Shirakawa T, Yamamichi F, Matsumoto M, Behnsawy HM, Meligy FY, Miyake H, Tanaka K, Fujisawa M

    28thEAU(European Association of Urology), 2013年03月, 英語, EAU(European Association of Urology), ミラノ, イタリア, 国際会議

    ポスター発表

  • Frequency of Diarrheagenic Escherichia coli among Children in Surabaya, Indoneshia

    大澤 佳代, 白川 利朗

    Asian-African Research Forum on Emerginf and Reemerging Infections, 2013年01月, 英語, 国際会議

    口頭発表(一般)

  • Development of a Multiplex PCR for the Rapid Identification of Salmonella Serotypes.

    大澤 佳代, 白川 利朗

    Asian-African Research Forum on Emerginf and Reemerging Infections, 2013年01月, 英語, 国際会議

    ポスター発表

  • tmRNAマーカーを用いたPCRによる細菌同定法の検討

    大澤 佳代, 白川 利朗

    第65回日本細菌学会関西支部総会, 2012年11月, 日本語, 国内会議

    口頭発表(一般)

  • Multiplex PCRによるSalmonella 血清型の迅速スクリーニング法の開発

    大澤 佳代, 白川 利朗

    第65回日本細菌学会関西支部総会, 2012年11月, 日本語, 国内会議

    口頭発表(一般)

  • 阪神地区における91 淋菌臨床株のgyrA, parC のアミノ酸変異とキノロン系

    重村克巳, 田中一志, 白川利朗, 三宅秀明, 荒川創一, 藤澤正人

    第41回 薬剤耐性菌研究会, 2012年10月, 日本語, 薬剤耐性菌研究会, 岐阜県, 国内会議

    ポスター発表

  • Sonic hedgehog signaling and Androgens are linked in tumor-stromal interaction through Epithelial-Mesenchymal transition (EMT) in prostate cancer progression

    Katsumi Shigemura, Fatma Y. Meligy, Hosny M. Behnsawy, Fukashi Yamamichi, Wen-Chin Haung, Xiangyan Li, Kunito Yamanaka, Keisuke Hanioka, Hideaki Miyake, Masato Kawabata, Toshiro Shirakawa, Masato Fujisawa

    107th AUA(American Urological Association)annual meeting, 2012年05月, 英語, AUA(American Urological Association)annual meeting, アトランタ, 国際会議

    ポスター発表

  • Significant biomarker for lower urinary tract symptoms in chronic prostatitis

    Shigemura K, Matsumoto M, Shirakawa T, Yamamichi F, Arakawa S, Tanaka K, Miyake H, Fujisawa M

    107th AUA(American Urological Association)annual meeting, 2012年05月, 英語, AUA(American Urological Association)annual meeting, アトランタ, 国際会議

    ポスター発表

  • Possible role of sonic hedgehog signaling and the link with Epithelial-Mesenchymal transition (EMT) in renal cancer progression

    Katsumi Shigemura, Fatma Y. Meligy, Hosny M. Behnsawy, Fukashi Yamamichi, Wen-Chin Haung, Xiangyan Li, Lela, d Chung, Masuo Yamashita, Masato Kawabata, Toshiro Shirakawa, Masato Fujisawa

    107th AUA(American Urological Association)annual meeting, 2012年05月, 英語, AUA(American Urological Association)annual meeting, アトランタ, 国際会議

    ポスター発表

  • Mechanisms of and risk factors for fluoroquinolone resistance in clinical Enterococcus faecalis isolates from patients with urinary tract infections.

    Shigemura K, Yasufuku T, Shirakawa T, Matsumoto M, Nakano Y, Tanaka K, Arakawa S, Kawabata M, Fujisawa M

    107th AUA(American Urological Association)annual meeting, 2012年05月, 英語, AUA(American Urological Association)annual meeting, アトランタ, 国際会議

    ポスター発表

  • Antimicrobial resistance in Salmonella strains clinically isolated in Hyogo, Japan (2009-2011)

    大澤 佳代, 白川 利朗

    第86回日本感染症学会総会, 2012年04月, 日本語, 長崎, 国内会議

    ポスター発表

  • Antimicrobial resistance in Salmonella strains clinically isolated in Hyogo, Japan (2009-2011)

    大澤 佳代, 白川 利朗

    Asian-African Research Forum n Emerging and Reemerging, 2012年01月, 英語, 神戸, 国際会議

    ポスター発表

  • Characterization of wzz genes in Escherichia coli O157

    大澤 佳代, 白川 利朗

    International Union of Microbiological Societies 2011 Congress, 2011年09月, 英語, 札幌, 国際会議

    ポスター発表

  • 尿路感染症由来緑膿菌臨床株における高速液体クロマトグラフィー法によるフルオロキノロン系抗菌薬耐性の迅速診断法確立への検討

    松本穣, 重村克巳, 白川利朗, 安福富彦, 中野雄造, 田中一志, 木下承皓, 川端眞人, 荒川創一, 藤澤正人

    第99回日本泌尿器科学会総会, 2011年04月, 日本語, 日本泌尿器科学会総会, 名古屋, 国内会議

    ポスター発表

  • 尿路感染症由来緑膿菌株における高速液体クロマトグラフィー法によるフルオロキノロン系抗菌薬耐性の迅速診断法に関する検討

    松本穣, 重村克巳, 白川利朗, 安福富彦, 中野雄造, 田中一志, 木下承晧, 川端眞人, 荒川創一, 藤澤正人

    第85回日本感染症学会総会・学術講演会, 2011年04月, 日本語, 日本感染症学会総会・学術講演会, 東京, 国内会議

    ポスター発表

  • 帳球菌の尿路感染症臨床株におけるgyrA,parC遺伝子変異とフルオロキノロン系抗菌薬耐性の相関についての検討

    安福富彦, 重村克巳, 白川利朗, 松本穣, 中野雄造, 田中一志, 木下承皓, 川端眞人, 荒川創一, 藤澤正人

    第99回日本泌尿器科学会総会, 2011年04月, 日本語, 日本泌尿器科学会総会, 名古屋, 国内会議

    口頭発表(一般)

  • 泌尿器科領域悪性腫瘍に対する抗癌化学療法中に生じた発熱性好中球減少症(FN)の検討

    安福富彦, 重村克巳, 松本穣, 中野雄造, 白川利朗, 田中一志, 荒川創一, 藤澤正人

    第58回日本化学療法学会西日本支部総会, 2010年11月, 日本語, 日本化学療法学会総会, 大分, 国内会議

    口頭発表(一般)

  • 尿路感染症由来大腸菌の臨床株における薬剤排出ポンプ遺伝子の発現と各種抗菌薬耐性との関連の解析

    重村克巳, 安福富彦, 白川利朗, 木下承晧, 松本穣, 中野雄造, 田中一志, 川端眞人, 荒川創一, 藤澤正人

    第62回日本泌尿器科学会西日本総会, 2010年11月, 日本語, 日本泌尿器科学会, 鹿児島, 国内会議

    口頭発表(一般)

  • 前立腺癌患者末梢血中circulating tumor cells(CTCs)の検出法の開発

    山道深, 松岡孝幸, 川端眞人, 森下真一, 白川利朗, 藤澤正人

    第60回日本泌尿器科学会中部総会, 2010年11月, 日本語, 日本泌尿器科学会, 名古屋, 国内会議

    口頭発表(一般)

  • 尿路感染症由来緑膿菌臨床株におけるgyrA,parC遺伝子変異とキノロン系抗菌薬耐性についての検討

    松本穣, 重村克巳, 白川利朗, 安福富彦, 中野雄造, 田中一志, 武中篤, 荒川創一, 木下承皓, 川端眞人, 藤澤正人

    第19回日本腎泌尿器疾患予防医学研究会, 2010年07月, 日本語, 日本腎泌尿器疾患医学研究会, 千葉, 国内会議

    口頭発表(一般)

  • 尿路感染症由来緑膿菌臨床株におけるgyrA、parC遺伝子変異とキノロン系抗菌薬耐性の関連についての検討

    松本穣, 重村克巳, 白川利朗, 安福富彦, 中野雄造, 田中一志, 武中篤, 荒川創一, 木下承皓, 川端眞人, 藤澤正人

    第58回日本化学療法学会総会, 2010年06月, 日本語, 日本化学療法学会総会, 長崎, 国内会議

    口頭発表(一般)

  • 尿路感染症由来緑膿菌臨床株におけるgyrA、parC遺伝子変異とキノロン系抗菌薬耐性の関連についての検討

    松本穣, 重村克巳, 白川利朗, 安福富彦, 中野雄造, 田中一志, 武中篤, 荒川創一, 木下承晧, 川端眞人, 藤澤正人

    第98回日本泌尿器科学会総会, 2010年04月, 日本語, 日本泌尿器科学会, 盛岡, 国内会議

    口頭発表(一般)

  • 尿路感染症由来大腸菌の臨床株における薬剤排出ポンプ遺伝子の発現と各種抗菌薬耐性との関連の解析

    安福富彦, 重村克巳, 白川利朗, 中野雄造, 田中一志, 武中篤, 荒川創一, 木下承晧, 川端眞人, 藤澤正人

    第98回日本泌尿器科学会総会, 2010年04月, 日本語, 日本泌尿器科学会, 盛岡, 国内会議

    ポスター発表

  • 「薬剤耐性(1)」尿路感染症由来大腸菌の臨床株における薬剤排出ポンプ遺伝子の発現と各種抗菌薬耐性との関連の解析

    安福富彦, 重村克巳, 白川利朗, 中野雄造, 田中一志, 武中篤, 荒川創一, 木下承皓, 川端眞人, 藤澤正人

    第84回日本感染症学会総会・学術講演会, 2010年04月, 日本語, 日本感染症学会, 京都, 国内会議

    その他

  • ヒト膀胱癌細胞におけるCox-2阻害剤、3剤の攻腫瘍効果の比較検討

    白川利朗, ザイナル アドヒム, 松岡孝幸, 重村克巳, 丹生健一, 川端眞人, 藤澤正人

    第98回日本泌尿器科学会総会, 2010年04月, 日本語, 日本泌尿器科学会, 盛岡, 国内会議

    口頭発表(一般)

  • 尿路感染症起因大腸菌の臨床株におけるgyrA、parC遺伝子変異とフルオロキノン系抗菌薬耐性の相関についての検討

    安福富彦, 重村克巳, 白川利朗, 中野雄造, 田中一志, 武中篤, 荒川創一, 木下承晧, 原田益善, 川端眞人, 藤澤正人

    第52回日本感染症学会中日本地方会学術集会, 2009年11月, 日本語, 日本感染症学会, 名古屋, 国内会議

    口頭発表(一般)

  • 多発奇形を伴った子宮内胎児死亡の1例

    白川利朗, 牧原夏子, 天野真理子, 森本規之, 森實真由美, 山崎峰夫, 山田秀人, 北澤理子

    第121回近畿産婦人科学会学術集会, 2009年11月, 日本語, 近畿産婦人科学会, 神戸, 国内会議

    口頭発表(一般)

  • Risk factors and the mechanisms for fluoroquinolone resistance in the 156 clinically isolated Escherrichia colistrains of urinary tract infections

    Tomihiko Yasufuku, Katsumi Shigemura, Toshiro Shirakawa, Yuzo Nakano, Kazushi Tanaka, Soichi Arakawa, Shouhiro Kinoshita, Masato Kawabata, Masato Fujisawa

    第25回腎移植・血管外科研究会, 2009年11月, 英語, 尿路感染症研究会, 東京, 国内会議

    その他

  • EMERGENCE OF FLUOROQUINOLONE-RESISTANT E. COLI STRAIN AND THEIR RELATED MUTATIONS OF THE GYRA AND PARC GENES IN UTI PATIENTS IN JAPAN

    Tomihiko Yasufuku, Katsumi Shigemura, Toshiro Shirakawa, Yuzo Nakano, Kazushi Tanaka, Soichi Arakawa, Shouhiro Kinoshita, Masato Kawabata, Masato Fujisawa

    UTI研究会, 2009年11月, 英語, UTI研究会, 東京, 国際会議

    口頭発表(一般)

  • 大腸菌の臨床株におけるgyrA, parC遺伝子変異とフルオロキノロン系抗菌薬耐性の相関についての検討

    安福富彦, 重村克巳, 白川利朗, 中野雄造, 田中一志, 武中篤, 荒川創一, 木下承皓, 川端眞人, 藤澤正人

    第97回日本泌尿器科学会総会, 2009年04月, 日本語, 日本泌尿器科学会, 岡山, 国内会議

    口頭発表(一般)

  • 前立腺肥大症患者におけるシロドシンおよびナフトピジルの臨床効果に関する比較検討

    白川利朗, 原口貴裕, 松本穣, 竹田雅, 森下真一, 山道深, 源吉顕治, 原田健一, 田中一志, 武中篤, 藤澤正人

    第97回日本泌尿器科学会総会, 2009年04月, 日本語, 日本泌尿器科学会, 岡山, 国内会議

    口頭発表(一般)

  • EMERGENCE OF FLUOROQUINOLONE-RESISTANT E. COLI STRAIN AND THEIR RELATED MUTATIONS OF THE GYRA AND PARC GENES IN UTI PATIENTS IN JAPAN

    Tomihiko Yasufuku, Katsumi Shigemura, Toshiro Shirakawa, Yuzo Nakano, Kazushi Tanaka, Soichi Arakawa, Shouhiro Kinoshita, Masato Kawabata, Masato Fujisawa

    第104回AUA(Amerigcan Urological Association), 2009年04月, 英語, 米国泌尿器科学会, シカゴ, アメリカ, 国際会議

    ポスター発表

  • 腎臓がん患者におけるsorcinの発現低下

    中村任, 岡村昇, 後藤章暢, 白川利朗, 藤澤正人, 栄田敏之

    第67回日本癌学会, 2008年10月, 日本語, 日本癌学会, 名古屋, 国内会議

    口頭発表(一般)

  • ヒト膀胱癌細胞に対するミドカインプロモーターを組み込んだ増殖制限型アデノウイルスベクター(ADMKE1a)の有用性の検討

    白川利朗, 乃美昌司, 田中一志, 武中篤, 藤澤正人, 後藤章暢

    第46回日本癌治療学会, 2008年10月, 日本語, 日本癌治療学会, 名古屋, 国内会議

    口頭発表(一般)

  • Suppression of sorcin mRNA in patients with renal cell carcinoma

    川上 恵, 中村任, 岡村昇, 寺尾 秀治, 後藤章暢, 白川利朗, 藤澤正人, 山森 元博, 栄田敏之

    第67回日本癌学会学術総会, 2008年10月, 日本語, 日本癌学会, 名古屋, 国内会議

    ポスター発表

  • Current status of gene therapy for prostate cancer

    白川利朗

    9th International Congress on Cell Biology, 2008年10月, 英語, Korean Society for Molecular and Cellular Biology, Seoul, Korea, 国際会議

    [招待有り]

    口頭発表(招待・特別)

  • Pre-clinical studies of GMJ2.1: carrier cell-based adenoviral oncolytic virotherapy for head and neck aquamous cell carcinoma

    白川利朗

    2008 International Society for Cell and Gene Therapy of Cancer, China Conference, 2008年09月, 英語, International Society for Cell and Gene Therapy of Cancer, Shijiazhuang, China, 国際会議

    口頭発表(一般)

  • Therapeutic efficacy of midkine promoter-based conditionally replicative adenovirus vector for targetting the midkine-expressing human bladder cancer cells

    Shirakawa T, Tanaka K, Takenaka A, Kamidono S, Fujisawa M, Gotoh A

    第103回AUA(American Urological Association)annual meeting, 2008年05月, 英語, 米国泌尿器科学会, オーランド, アメリカ, 国際会議

    ポスター発表

  • 腎癌におけるSorcin発現の検討とVEGF発現に及ぼす影響

    岡村昇, 白川利朗, 中村任, 栄田敏之, 奥村勝彦, 武中篤, 藤澤正人, 後藤章暢

    第96回日本泌尿器科学会, 2008年04月, 日本語, 日本泌尿器科学会, 横浜, 国内会議

    ポスター発表

  • 感染症分野における分子疫学および分子診断の進歩について

    白川利朗

    第30回日本臨床検査専門医会総会, 2007年11月, 日本語, 日本臨床検査専門医会, 大阪, 国内会議

    口頭発表(招待・特別)

  • 腎癌におけるSorcinおよびVEGFの発現に関する検討

    岡村昇, 白川利朗, 中村任, 栄田敏之, 武中篤, 藤澤正人, 後藤章暢

    第66回日本癌学会総会, 2007年10月, 日本語, 日本癌学会, 横浜, 国内会議

    口頭発表(一般)

  • 新しい抗癌剤の臨床研究 ホルモン療法抵抗性の転移性前立腺癌の患者に対するAd-OC-TK遺伝子療法の臨床試験成績

    白川利朗, 後藤章暢, 田中一志, 武中篤, 原勲

    第66回日本癌学会総会, 2007年10月, 日本語, 日本癌学会, 横浜, 国内会議

    口頭発表(一般)

  • 骨転移を有するホルモン不応性前立腺癌に対する遺伝子治療臨床研究の長期成績

    白川利朗, 後藤章暢, 田中一志, 武中篤, 原勲, 守殿貞夫, 藤澤正人

    第45回日本癌治療学会, 2007年10月, 日本語, 日本癌治療学会, 京都, 国内会議

    シンポジウム・ワークショップパネル(公募)

  • ホルモン不応性再燃前立腺癌の治療 骨転移を有するホルモン不応性前立腺癌に対する遺伝子治療臨床研究の長期成績

    白川利朗, 後藤章暢, 田中一志, 武中篤, 原勲, 守殿貞夫, 藤澤正人

    第45回日本癌治療学会総会, 2007年10月, 日本語, 日本癌治療学会, 京都, 国内会議

    口頭発表(一般)

  • The impact and perspective on chronic kidney disease in Vietnam

    伊藤純, 川端眞人, 白川利朗

    第22回日本国際保健医療学会総会, 2007年10月, 日本語, 日本国際保健医療学会, 大阪, 国内会議

    口頭発表(一般)

  • Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer

    白川利朗, 後藤章暢, 田中一志, 武中篤, 原勲, 守殿貞夫, 藤澤正人

    第66回日本ガン学会学術総会, 2007年10月, 英語, 日本癌学会, 横浜, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • ホルミウムレーザー前立腺核出術(HoLEP)22例の臨床的検討

    大場健史, 曽我英雄, 白川利朗, 藤澤正人

    第28回日本レーザー医学会, 2007年09月, 日本語, 日本レーザー医学会, 北海道, 国内会議

    口頭発表(一般)

  • Evaluation of protein expression in human renal cell carcinoma by proteome analysis using the NBS method

    中村任, 岡村昇, 後藤章暢, 白川利朗, 藤澤正人, 栄田敏之, 奥村勝彦

    日本薬物動態学会ビジョン・シンポジウム, 2007年07月, 英語, 日本薬物動態学会, 東京, 国内会議

    ポスター発表

  • Results of a phase I/II study of Ad-OC-TK/VAL gene therapy for the patients with metastatic or local recurrent prostate cancer

    白川利朗, 後藤章暢, 田中一志, 武中篤, 原勲, 守殿貞夫, 藤澤正人

    第13回日本遺伝子治療学会, 2007年06月, 日本語, 日本遺伝子治療学会, 名古屋, 国内会議

    シンポジウム・ワークショップパネル(公募)

  • Long-term results of a phase I/II study of Ad-OC-TK/VAL gene therapy for the patients with metastatic or local recurrent prostate cancer

    白川利朗, 後藤章暢, 田中一志, 武中篤, 原勲, 守殿貞夫, 藤澤正人

    第10回米国遺伝子治療学会, 2007年06月, 英語, 米国遺伝子治療学会, シアトル, アメリカ, 国際会議

    口頭発表(一般)

  • The impact and perspective on chronic kidney disease in Vietnam

    伊藤純, 藤澤正人, 川端眞人, 白川利朗

    第50回日本腎臓学会総会(第1回アジアフォーラムCKDイニシアチブ), 2007年05月, 英語, 日本腎臓学会、アジア太平洋腎臓学会、国際腎臓学会, 浜松, 国際会議

    口頭発表(一般)

  • 選択的cyclooxygenase-II(COX-2)阻害剤etodolacのヒト前立腺がん細胞株における抗腫瘍効果の検討

    重村克巳, 白川利朗, 後藤章暢, 藤澤正人

    第95回日本泌尿器科学会総会, 2007年04月, 日本語, 日本泌尿器科学会総会, 神戸, 国内会議

    口頭発表(一般)

  • マウス前立腺癌モデルに対するPETを用いたAd-OC-TK/VAL遺伝子治療効果および遺伝子導入効率の評価に関する有用性の検討

    白川利朗, 武中篤, 藤澤正人, 後藤章暢

    第95回日本泌尿器科学会総会, 2007年04月, 日本語, 日本泌尿器科学会総会, 神戸, 国内会議

    口頭発表(一般)

  • ヒト膀胱癌細胞における選択的Cox-2阻害剤、EtodolacのE-cadherin発現増強および抗腫瘍効果の検討

    白川利朗, 重村克巳, 後藤章暢, 川端眞人, 藤澤正人

    第95回日本泌尿器科学会総会, 2007年04月, 日本語, 日本泌尿器科学会, 神戸, 国内会議

    口頭発表(一般)

  • 内分泌療法抵抗性前立腺癌に対するAd-OC-TK plus Valacyclovir遺伝子治療臨床研究におけるquality of lifeの評価

    白川 利朗, 田中 一志, 武中 篤, 荒川 創一, 原 勲, 藤澤 正人

    第58回日本泌尿器科学会西日本大会, 2006年11月, 日本語, 日本泌尿器科学会, 長崎, 国内会議

    口頭発表(一般)

  • Phase I/II clinical trial of Ad-OC-TK plus VAL for the patients with metastatic or local recurrent prostate cancer: Kobe University Experience

    白川 利朗

    2006 International Society for Cell and Gene Therapy of Cancer, Japan Conference, 2006年10月, 英語, International Society for Cell and Gene Therapy of Cancer, 千葉, 国際会議

    口頭発表(一般)

  • Ad-OC-TK/VAL遺伝子治療臨床試験における肝機能障害に対する検討

    白川 利朗, 武中 篤, 原 勲, 荒川 創一, 藤澤 正人

    第44回日本癌治療学会総会, 2006年10月, 日本語, 日本癌治療学会, 東京, 国内会議

    口頭発表(一般)

  • 【18F】FDGを用いたPETによるAd-OC-TK/VAL遺伝子治療評価方法の有用性の検討

    白川 利朗, 藤澤 正人

    第65回日本癌学会学術総会, 2006年09月, 日本語, 日本癌学会, 横浜, 国内会議

    口頭発表(一般)

  • Improvement of Quality of life of patients with metastatic or local recurrent prostate cancer after Phase Ⅰ/Ⅱ clinical trial of Ad-OC-TK plus Valacyclovir.

    白川 利朗, 藤澤 正人

    第12回日本遺伝子治療学会, 2006年08月, 英語, 日本遺伝子治療学会, 東京, 国内会議

    口頭発表(一般)

  • ホルミウムレーザー前立腺核手術(HoLEP)22例の臨床的検討

    大場 健史, 曽我 英雄, 白川 利朗, 藤澤 正人

    日本レーザー医学会関西地方会, 2006年07月, 日本語, 日本レーザー医学会, 神戸, 国内会議

    口頭発表(一般)

  • Genetically engineered Bifidobacterium animalis expressing the Salmonella flagellin gene for the mucosal immunization in a mouse model

    白川 利朗, 川端 眞人

    American Society of Gene Therapy 9th annual meeting, 2006年05月, 英語, 米国遺伝子治療学会, バルチモア, 国際会議

    口頭発表(一般)

  • 視床下部下垂体精巣軸におけるNeuropeptide YおよびPancreatic polypeptideの役割

    後藤 章暢, 白川 利朗, 藤澤 正人

    第94回日本泌尿器科学会, 2006年04月, 日本語, 日本泌尿器科学会, 福岡, 国内会議

    口頭発表(一般)

  • α1遮断薬による前立腺肥大症の薬物療法についての排尿症状(IPSS)を中心とした長期薬効の検討

    白川 利朗

    第94回日本泌尿器科学会総会, 2006年04月, 日本語, 日本泌尿器科学会, 福岡, 国内会議

    ポスター発表

  • α1受容体遮断薬による前立腺肥大症の薬物療法についての排尿症状(IPSS)を中心とした長期薬効の検討

    白川 利朗, 大場 健史, 山田 裕二, 藤澤 正人

    第94回日本泌尿器科学会, 2006年04月, 日本語, 日本泌尿器科学会, 福岡, 国内会議

    口頭発表(一般)

  • ヒト膀胱癌細胞に対するミドカインプロモーターを組み込んだ増殖制限型アデノウイルスベクター(AD-MK-E1a)の有用性の検討

    白川 利朗, 後藤 章暢, 藤澤 正人

    第94回日本泌尿器科学会, 2006年04月, 日本語, 日本泌尿器科学会, 福岡, 国内会議

    口頭発表(一般)

  • 腎臓癌におけるVEGF発現量と遺伝子型

    田中 久登, 岡村 昇, 後藤 章暢, 白川 利朗, 寺尾 秀治, 山森 元博, 瀬戸 亮太, 中村 任, 栄田 敏之, 奥村 勝彦

    第26回日本臨床薬理学会年会, 2005年12月, 日本語, 日本臨床薬理学会, 別府, 国内会議

    ポスター発表

  • 腎臓癌におけるVEGF発現量と遺伝子型

    田中 久登, 岡村 昇, 後藤 章暢, 白川 利朗, 寺尾 秀治, 山森 元博, 瀬戸 亮太, 中村 任, 栄田 敏之, 奥村 勝彦

    第26回日本臨床薬理学会, 2005年12月, 日本語, 日本臨床薬理学会, 別府, 国内会議

    ポスター発表

  • 腎臓癌におけるEGFR発現量と各種遺伝子の発現相関

    徳井 健次, 岡村 昇, 後藤 章暢, 白川 利朗, 寺尾 秀治, 中村 任, 田中 久登, 八木 麻理子, 栄田 敏之, 奥村 勝彦

    第55回日本薬学会近畿支部, 2005年11月, 日本語, 日本薬学会, 西宮, 国内会議

    口頭発表(一般)

  • Intra-muscular infjection of rb-IL-2 enhanced the antitumor effect of Ad-OC-TK plus ACV Suicide-gene therapy on murine prostate concer model

    白川 利朗, 張 竹君, 寺尾 秀治, 和田 義孝, 藤澤 正人, 後藤 章暢

    第7回泌尿器遺伝子・細胞治療研究会, 2005年11月, 日本語, 泌尿器遺伝子・細胞治療研究会, 岡山, 国内会議

    口頭発表(一般)

  • 前立腺肥大症に対するα1受容体遮断薬長期投与症例における排尿症状動態に関する検討

    白川 利朗, 寺尾 秀治, 日向 信之, 合田 上政, 大場 健史, 和田 義孝, 山田 裕二, 後藤 章暢, 岡田 弘, 藤澤 正人

    第12回日本排尿機能学会, 2005年10月, 日本語, 日本排尿機能学会, 松本, 国内会議

    口頭発表(一般)

  • 腎臓癌におけるEGFR発現量と各種遺伝子の発現相関

    徳井 健次, 岡村 昇, 後藤 章暢, 白川 利朗, 寺尾 秀治, 中村 任, 田中 久登, 八木 麻理子, 栄田 敏之, 奥村 勝彦

    第55回日本薬学会近畿支部総会・大会, 2005年10月, 日本語, 日本薬学会, 西宮, 国内会議

    ポスター発表

  • 腎臓癌におけるEGFR発現量およびゲフィチニブ感受性関連体細胞変異

    大松 秀明, 岡村 昇, 後藤 章暢, 白川 利朗, 寺尾 秀治, 中村 任, 徳井 健次, 田中 久登, 八木 麻理子, 大石 美惠, 西口 工司, 栄田 敏之, 奥村 勝彦

    第15回医療薬学会年会, 2005年10月, 日本語, 日本医療薬学会, 岡山, 国内会議

    ポスター発表

  • Multi-Functional GMP Facility for Cell and Gene Therapy, in Kobe City, Japan

    Toshiro Shirakawa

    The Williamsburg BioProcessing Conference Asia-Pacific 2nd Annual Meeting, 2005年09月, 英語, The Williamsburg BioProcessing, シンガポール, 国際会議

    [招待有り]

    口頭発表(招待・特別)

  • Real-Time PCR法を用いた腸チフスの血中細菌定量法の開発

    白川 利朗, 松本 安代, 高田 哲男, 後藤 章暢, 川端 眞人, 木下 承晧, 熊谷 俊一, 荒川 創一

    第79回日本感染症学会, 2005年04月, 日本語, 日本感染症学会, 名古屋, 国内会議

    ポスター発表

  • 2003年臨床分離MRSAにおけるバンコマイシン耐性関連遺伝子保有状況

    高田 哲男, 白川 利朗, 松本 安代, 木下 承晧, 熊谷 俊一, 後藤 章暢, 川端 眞人

    第79回日本感染症学会, 2005年04月, 日本語, 日本感染症学会, 名古屋, 国内会議

    口頭発表(一般)

  • 腎癌における各種遺伝子のmRNA発現変動及び遺伝子型

    岡村 昇, 後藤 章暢, 白川 利朗, 寺尾 秀治, 中村 任, 盛岡 正志, 徳井 健次, 田中 久登, 八木 麻理子, 栄田 敏之, 奥村 勝彦

    日本薬剤学会第20年会, 2005年03月, 日本語, 日本薬剤学会, 東京, 国内会議

    ポスター発表

  • 腎癌における各種遺伝子のmRNA発現変動及び遺伝子型

    岡村 昇, 後藤 章暢, 白川 利朗, 寺尾 秀治, 中村 任, 盛岡 正志, 徳井 健次, 田中 久登, 八木 麻理子, 栄田 敏之, 奥村 勝彦

    日本薬剤学会第20回記念大会, 2005年03月, 日本語, 日本薬剤学会, 東京, 国内会議

    口頭発表(一般)

  • 前立腺癌骨転移巣に対する遺伝子治療

    白川 利朗

    第21回神戸UGカンファレンス, 2005年, 日本語, 神戸UGカンファレンス, 神戸, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • 泌尿器科病棟における血液培養陽性例の検討

    合田 上政, 藤澤 正人, 白川 利朗, 土橋 正樹, 近藤 有, 岡田 弘, 守殿 貞夫

    第54回日本泌尿器科学会中部総会, 2004年11月, 日本語, 第54回日本泌尿器科学会中部総会, 泉佐野, 国内会議

    口頭発表(一般)

  • 前立腺癌骨転移巣に対する遺伝子治療臨床研究

    白川 利朗

    第69回日本泌尿器科学会東部総会, 2004年09月, 日本語, 日本泌尿器科学会東部総会, 東京, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • 間歇的アンドロゲン除去療法の休薬中に性交渉が可能となった前立腺癌の一例

    後藤 章暢, 白川 利朗, 原 勲, 守殿 貞夫

    第15回日本性機能学会学術総会・西部総会, 2004年09月, 日本語, 第15回日本性機能学会学術総会・西部総会, 徳島, 国内会議

    口頭発表(一般)

  • 原発巣の診断に苦慮した甲状腺癌陰嚢皮下転移の1例

    合田 上政, 白川 利朗, 後藤 章暢, 岡田 弘, 原 勲, 守殿 貞夫, 藤澤 正人

    第187回日本泌尿器科学会関西地方会, 2004年06月, 日本語, 第187回日本泌尿器科学会関西地方会, 神戸, 国内会議

    口頭発表(一般)

  • 経直腸的前立腺針生検後の感染阻止化学療法に関する検討

    寺尾 秀治, 守殿 貞夫, 後藤 章暢, 白川 利朗, 日向 信之, 合田 上政

    第52回日本化学療法学会総会, 2004年06月, 日本語, 第52回日本化学療法学会総会, 沖縄, 国内会議

    口頭発表(一般)

  • 院内感染制御における泌尿器科医の役割

    白川 利朗, 後藤 章暢, 寺尾 秀治, 日向 信之, 重村 克巳, 合田 上政, 和田 義孝, 村蒔 基次, 田中 一志, 山田 裕二, 原 勲, 守殿 貞夫

    第92回日本泌尿器科学会総会, 2004年04月, 日本語, 第92回日本泌尿器科学会総会, 大阪, 国内会議

    口頭発表(一般)

  • ヒト精巣組織におけるTRAILおよびDR4、DR5、DcR1、DcR2の発現に関する免疫組織学的検討

    合田 上政, 藤澤 正人, 白川 利朗, 寺尾 秀治, 山口 耕平, 近藤 有, 土橋 正樹, 岡田 弘, 後藤 章暢, 守殿 貞夫

    第92回日本泌尿器科学会総会, 2004年04月, 日本語, 第92回日本泌尿器科学会総会, 大阪, 国内会議

    口頭発表(一般)

  • 前立腺癌の遺伝子治療

    白川 利朗

    COEシンポジウム 千葉大学大学院「消化器扁平上皮癌に対する最先端多戦略治療拠点形成」Cancer Gene Therapy Symposium, 2004年02月, 日本語, COEシンポジウム, 千葉, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • Process development of gene therapies in Japan

    Toshiro Shirakawa

    The williamsburg BioProcessing Conference Asia-Pacific 1st annual meeting, Sydney, Australia, 2004年, 英語, The williamsburg BioProcessing Conference Asia-Pacific 1st annual meeting, Sydney, Australia, シドニー, 国際会議

    [招待有り]

    口頭発表(招待・特別)

  • 薬剤耐性淋菌性尿道炎の分子生物学的検討およびDHPLCを用いた迅速遺伝子診断法の開発

    重村 克己, 白川 利朗, 岡田 弘, 田中 一志, 荒川 創一, 木下 承酷, 後藤 章暢, 守殿 貞夫

    ・第53回日本泌尿器科学会中部総会, 2003年11月, 日本語, 日本泌尿器科学会中部総会, 金沢, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • 放射線併用抗癌化学療法が有用であった女性尿道癌の2例

    日向 信之, 白川 利朗, 和田 義孝, 重村 克巳, 岡田 弘, 後藤 章暢, 守殿 貞夫

    第53回日本泌尿器科学会中部総会, 2003年10月, 日本語, 第53回日本泌尿器科学会中部総会, 金沢, 国内会議

    口頭発表(一般)

  • 当科における最近の腹腔鏡下手術

    重村 克巳, 白川 利朗, 岡田 弘, 田中 一志, 荒川 創一, 木下 承晧, 後藤 章暢, 守殿 貞夫

    第53回日本泌尿器科学会中部総会, 2003年10月, 日本語, 第53回日本泌尿器科学会中部総会, 金沢, 国内会議

    口頭発表(一般)

  • 前立腺癌骨転移巣に対する遺伝子治療臨床研究の現況

    合田 上政, 藤澤 正人, 土橋 正樹, 山崎 隆文, 張 竹君, 白川 利朗, 後藤 章暢, 岡田 弘, 荒川 創一, 守殿 貞夫

    第41回日本癌治療学会総会, 2003年10月, 日本語, 日本癌治療学会, 札幌, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • 精巣腫瘍晩期再発症例の臨床的検討

    後藤 章暢, 白川 利朗, 守殿 貞夫

    第53回日本泌尿器科学会中部総会, 2003年10月, 日本語, 第53回日本泌尿器科学会中部総会, 金沢, 国内会議

    口頭発表(一般)

  • 後腹膜鏡下右腎尿管全摘除術および腹腔鏡下膀胱全摘除術を併施した1症例

    白川 利朗, 岡田 弘, 後藤 章暢, 日向 信之, 和田 義孝, 守殿 貞夫, 宇治 達哉, 山本 明良

    第53回日本泌尿器科学会中部総会, 2003年10月, 日本語, 第53回日本泌尿器科学会中部総会, 金沢, 国内会議

    口頭発表(一般)

  • CD44v8-10分子遺伝子導入は膀胱癌細胞株の生物学的悪性度を亢進させる

    重村 克巳, 岡田 弘, 田中 一志, 荒川 創一, 守殿 貞夫, 白川 利朗, 後藤 章暢, 木下 承晧

    第62回日本癌学会学術総会, 2003年09月, 日本語, 第62回日本癌学会学術総会, 名古屋, 国内会議

    口頭発表(一般)

  • 放射光による微量元素分析と生命科学・医学への応用 前立腺癌細胞内の亜鉛分布状態の変化―ホルモンと亜鉛の関係

    白川 利朗, 杉村 和朗, 北村 ゆり, 敷根 俊輔, 川上 拓男, 井手 亜里, 後藤 章暢

    第14回日本微量元素学会, 2003年07月, 日本語, 日本微量元素学会, 大阪, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • 新しい迅速直接抗菌剤感受性測定装置の開発とそのUTIにおける有用性

    岡田 弘, 重村 克巳, 白川 利朗, 田中 一志, 後藤 章暢, 川端 岳, 荒川 創一, 浜口行雄, 守殿 貞夫

    第51回日本化学療法学会総会, 2003年05月, 日本語, 第51回日本化学療法学会総会, 横浜, 国内会議

    口頭発表(一般)

  • 前立腺癌に対する腹腔鏡下前立腺全摘除術の治療成績とQOL

    白川 利朗, 後藤 章暢, 日向 信之, 和田 義孝, 原 勲, 岡田 弘, 守殿 貞夫

    第91回日本泌尿器科学会総会, 2003年04月, 日本語, 第91回日本泌尿器科学会総会, 徳島, 国内会議

    口頭発表(一般)

  • CD44R1分子遺伝子導入は膀胱癌細胞株の生物学的悪性度を亢進させる

    熊野 晶文, 白川 利朗, 田中 一志, 原 勲, 川端 岳, 岡田 弘, 守殿 貞夫, 生田 繁, 藤澤 正人

    第91回日本泌尿器科学会総会, 2003年04月, 日本語, 第91回日本泌尿器科学会総会, 徳島, 国内会議

    口頭発表(一般)

所属学協会

  • アメリカ遺伝子治療学会

  • 日本癌治療学会

  • 日本癌学会

  • 日本感染症学会

  • 日本遺伝子治療学会

  • 日本泌尿器科学会

共同研究・競争的資金等の研究課題

  • 尿路感染症における網羅的薬剤耐性機構の研究

    重村 克巳, 大澤 佳代, 宮良 高維, 白川 利朗

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2019年04月01日 - 2022年03月31日

  • 膜輸送性高分子をキャリアーとした粘膜投与型ロングペプチド癌ワクチンの開発研究

    白川 利朗, 佐久間 信至

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2019年04月01日 - 2022年03月31日

  • 【AMED】腸管免疫を利用した新規経口がんワクチンの開発

    白川 利朗

    国立研究開発法人日本医療研究開発機構, 橋渡し研究戦略的推進プログラム, 2019年04月 - 2022年03月, 研究代表者

    競争的資金

  • 丹生 健一, 大月 直樹, 上原 奈津美, 白川 利朗

    日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 2016年04月01日 - 2019年03月31日

    MidkineはHeparin-binding growth factorの一種で、頭頸部扁平上皮癌を含め多くの癌で高発現しているが、成人の正常組織ではほとんど発現がみられない。この特性を活かし、今回、我々はMidkineをプロモータとしてウイルスの増殖に必要なE1A・E1B遺伝子を組み込んだ制限増殖型アデノウイルスを作成し、更に、このウイルスに頭頸部扁平上皮癌に高発現している上皮成長因子受容体Epidermal growth factor receptor (EGFR)に対するsmall interfering RNA (siRNA)の遺伝子を組み込んだ。

  • 大月 直樹, 丹生 健一, 白川 利朗

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2016年04月01日 - 2019年03月31日

    頭頸部癌において活性化しているサイトカインシグナル伝達系のひとつであるJAK/STATシグナル経路はサイトカインシグナル阻害分子(SOCS)により抑制される。アデノウイルスベクターを用いてSOCS遺伝子を頭頸部癌細胞株に導入することにより、SOCSの発現が認められ、腫瘍細胞の増殖が抑制されることが示された。

  • 重村 克巳

    学術研究助成基金助成金/基盤研究(C), 2016年04月 - 2019年03月

    競争的資金

  • 腸管免疫を利用した新規経口がんワクチンの開発

    白川 利朗

    AMED, 橋渡し研究戦略的推進プログラム:シーズB, 2017年04月 - 2018年03月, 研究代表者

    競争的資金

  • 大澤 佳代

    学術研究助成基金助成金/基盤研究(C), 2015年04月 - 2018年03月

    競争的資金

  • 白川 利朗, 片山 高嶺, 堀田 博

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2014年04月 - 2017年03月, 研究代表者

    現在、世界中で約1億7千万人のHCVキャリアーが存在し、インターフェロンや抗ウイルス薬によりC型慢性肝炎の治療成績は向上したが、その根治率は未だ満足のいくものではない。現在までに我々は、ビフィズス菌の表層にHCVのNS3タンパクをディスプレイした新しいC型慢性肝炎経口ワクチンを作製し、マウス実験モデルにて細胞性免疫の誘導を確認している。今回の研究では本ワクチンを用いた新規C型慢性肝炎治療法の開発研究として、NS3タンパク発現マウス腫瘍モデルを用いてインターフェロン併用療法との相乗効果を確認した。

    競争的資金

  • 【AMED】染色体性薬剤耐性遺伝子を保持する薬剤耐性菌の分子疫学的解析

    白川 利朗

    国立研究開発法人日本医療研究開発機構, 医療分野国際科学技術共同研究開発推進事業 戦略的国際共同研究プログラム(ベトナム・インドネシア), 2017年, 研究代表者

    競争的資金

  • 大月 直樹

    学術研究助成基金助成金/基盤研究(C), 2013年04月 - 2016年03月

    競争的資金

  • 悪性胸膜中皮腫に対する新規治療法の開発及び実用化に関する研究

    白川 利朗

    革新的がん医療実用化研究事業, 2016年, 研究代表者

    競争的資金

  • 大澤 佳代

    科学研究費補助金/基盤研究(C), 2012年04月 - 2015年03月

    競争的資金

  • 白川 利朗, 堀田 博, 片山 高嶺, 片山 高嶺

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2011年 - 2013年, 研究代表者

    現在、世界中で約1億7千万人のHCVキャリアーが存在し、インターフェロンや抗ウイルス薬によりC型慢性肝炎の治療成績は向上したものの、その根治率は未だ満足のいくものではない。HCVウイルスの排除にはHCV非構造タンパクNS3に対する細胞性免疫が大きな役割を果たしていることが報告されている。今回、我々は、プロバイオティクスであるビフィズス菌の表層に、HCVのNS3タンパクのCD4およびCD8エピトープを複数含んだポリペプチドをディスプレイした新しいC型慢性肝炎経口ワクチンを作製し、マウスを用いた動物実験により、本ワクチンがNS3特異的細胞性免疫を誘導できることを確認した。

    競争的資金

  • 丹生 健一, 大月 直樹

    日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 2009年 - 2011年

    頭頸部癌に対しては、手術療法と放射線療法、化学療法を組み合わせた様々な集学的治療法が試みられている。しかし、多くが5年生存率30%前後の予後不良な進行癌であり、新たな治療法の確立が望まれる。本研究では、癌特異的に高発現するミドカインのプロモーター下にウイルスの自己増殖に必要な遺伝子を導入したアデノウイルスベクターを作成した。この基本ベクターに、抗腫瘍効果が期待できるEGFRとVEGFのsiRNAを発現するユニットを導入し、制限増殖型かつ抗腫瘍効果を併せ持つアデノウイルスベクターを作成した。

  • 白川 利朗, 片山 高嶺

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2008年 - 2010年

    近年、腸管での粘膜免疫の誘導が感染予防に対して大きな役割を果たすことが期待されており、生きた腸内細菌、プロバイオティクスを、抗原タンパク遺伝子のキャリアーとして応用した経口ワクチンの開発が研究されている。今回、我々は代表的なプロバイオティクスであるビフィズス菌を応用した経口ワクチンの研究開発を実施し、病原体の抗原を表層ディスプレイするビフィズス菌の開発に成功し、そのワクチン効果をネズミ・チフスモデルで確認した。

  • 癌細胞ワクチンによるオンコリティック・アデノウイルスの新規ドラッグデリバリー

    白川 利朗

    2010年, 研究代表者

    競争的資金

  • 大月 直樹

    科学研究費補助金/基盤研究(C), 2008年

    競争的資金

  • 遺伝子・タンパク質発現解析に基づく腎癌治療薬の創薬ターゲットの探索

    奥村 勝彦, 栄田 敏之, 後藤 章暢, 白川 利朗, 岡村 昇, 中村 任

    日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 2004年 - 2005年

    腎臓癌は、外科的療法が一般的に行われるが、化学療法や放射線療法の奏功率が他の癌に比べて著しく低いこと、有用な診断マーカーが存在しないことが問題となっている。そこで抗癌剤に対する耐性メカニズムの解明や新規創薬ターゲット診断マーカーの探索を目指して、摘出腎癌における癌部・非癌部のトランスクリプトーム・プロテオーム解析を行った。 昨年度、癌部において多剤耐性に関わるSorcinの発現量が低下していることを明らかにしたが、癌細胞増殖における役割をRNA干渉の手法により検討した。すなわち、腎臓癌細胞Caki-1において、SorcinをsiRNAによってノックダウンさせると、癌の増殖、進展に重要な役割を果たしている血管内皮増殖因子(vascular endothelial growth factor ; VEGF)の発現が誘導されることが明らかとなった。したがって、Sorcinの低下によりVEGFの発現が誘導されることにより、癌の増殖が促進されることが示唆された。 腎臓癌の癌部・非癌部におけるタンパク発現の網羅的な解析を目的として、それぞれの試料を^<12>Cおよび^<13>Cをそれぞれ6原子持つ2-Nitorobenzenesulfonyl chlorideにて修飾した後、MALDI-TOF/Msに解析した。質量差6Daのピークの高さにより、癌部で発現の上昇あるいは低下しているタンパクを検出し、同定した。その結果、これまで腎臓癌で発現上昇が認められているタンパクに加えて、未知のタンパクも同定することができた。

  • 増殖型アデノウイルスベクターおよびキャリアー細胞を用いた膀胱癌に対する遺伝子治療

    白川 利朗

    日本学術振興会, 科学研究費助成事業 若手研究(B), 若手研究(B), 神戸大学, 2004年 - 2005年

    膀胱壁筋層に浸潤する膀胱癌の約50%は、すでに癌の微小転移を有しており、1年以内に臨床上、明らかな転移巣を呈するといわれている。近年の医学の進歩、特に多剤併用抗癌化学療法の確立にも関わらず、それらの患者のほとんどは2年以内に死亡する。現在、遺伝子治療を代表とする分子標的療法が大きな注目を集めているが、膀胱癌を対象としたそれらの新しい治療法の開発も切望されるところである。 従来の非増殖型ウイルスベクターについては、その遺伝子導入効率において限界が指摘されており、癌細胞においてのみ複製される腫瘍特異的な増殖型ウイルスベクターが盛んに研究されている。本研究で用いる増殖型ウイルスベクターはウイルスの複製に必要な遺伝子、E1aを腫瘍特異的プロモーターにより制御し、腫瘍内でのみ増殖可能としたアデノウイルスベクターである。 Cox-2はサイトカインや発癌プロモーターなどの刺激により、マクロファージ、血管内皮細胞、癌細胞などにおいて誘導され、炎症反応、血管新生、発癌などに関与すると言われ、膀胱癌や大腸癌など多くのヒト癌細胞での発現増強が確認されている。我々はCox-2プロモーターを組み込んだ増殖型アデノウイルスベクター、AdE3-cox-2-327を既に作製した。本ベクターはCox-2を強発現する膀胱癌などの癌細胞においてのみ増殖可能であり、癌細胞内で複製を繰り返すことにより細胞融解を引き起こし癌細胞を特異的に殺傷する。 平成16年度、われわれはAdE3-cox-2-327の膀胱癌に対する抗癌作用をIn vitro, In vivo双方で確認した。また平成17年度、AdE2-cox-2-327をキャリアー細胞、A549細胞に感染させヒト膀胱癌細胞KK47を接種して作成したマウスの皮下腫瘍に直接、投与することにより抗腫瘍効果が高まることを確認した。

  • 前立腺癌転移巣に対する臓器特異性プロモーターを用いた遺伝子治療臨床研究

    守殿 貞夫, 後藤 章暢, 前田 盛, 杉村 和朗, 松尾 雅文, 白川 利朗

    日本学術振興会, 科学研究費助成事業 基盤研究(A), 基盤研究(A), 神戸大学, 2002年 - 2005年

    「背景」進行性前立腺癌の治療法として内分泌療法が確立しているが、その50%以上が2年以内に抵抗性となり前立腺癌患者の生存率およびQOLに多大な影響を与えている。現在、内分泌療法抵抗性前立腺癌に対する有効な治療法は確立されていない。また前立腺癌は頻回に骨転移をきたす悪性腫瘍の一つであり、我々は内分泌療法抵抗性の進行性前立腺癌、特に骨転移巣に対する新たな治療法の確立を目指し、遺伝子治療臨床研究を開始した。「方法」内分泌療法抵抗性前立腺癌の骨転移、リンパ節転移及び、局所再発例に対し、単純ヘルペスウイルスのチミジンキナーゼ(Herpes Simplex Virus-Thymidine Kinase,(HSV-TK)遺伝子を,臓器特異性オステオカルシン(Osteocalcin : OC)プロモーターにより制御発現させるアデノウイルスベクター(Ad-OC-TK)を単独で癌転移巣又は局所再発巣に局所内投与し、その後プロドラッグであるバラシクロビルを経口投与する。OCプロモーターは、骨芽細胞で機能する臓器特異的プロモーターで,前立腺癌の原発巣および転移巣においても高いプロモーター活性が認められている。OCプロモーターによって発現するHSV-TK酵素はバラシクロビルをリン酸化することによって、OC-HSV-TK遺伝子が導入された癌細胞のDNA合成を阻害する。「結果」低用量3例(Ad-OC-TK:2.5×10^9pfu×2回)、高用量3例(2.5×10^<10>pfu×2回)の合計6症例に本治療を施行した。内2症例は局所再発巣、他4症例は骨転移巣を治療部位に選択した。いずれの症例においても重篤な副作用は認めなかった。また骨転移巣を治療部位とした低用量症例1例において、本治療単独で著明な血清PSA値の低下(治療前341.7ng/ml、治療後208日目7.7ng/ml)とCT画像所見の改善を認めた。「結論」内分泌療法抵抗性進行性前立腺癌、6症例に対し遺伝子治療臨床研究を行った。全ての症例において急性期の重篤な副作用は認めず、一部の症例で抗腫瘍効果を認めた。本遺伝子治療法は、今後、更なる症例を重ね研究を進めるに値する治療法であると考えられた。

  • 守殿 貞夫

    科学研究費補助金/基盤研究(A), 2005年

    競争的資金

  • 後藤 章暢

    科学研究費補助金/基盤研究(B), 2005年

    競争的資金

  • 福田 秀樹

    科学研究費補助金/萌芽研究, 2005年

    競争的資金

  • 遺伝子治療による、膀胱癌の放射線および抗癌剤の感受性増強効果の研究

    白川 利朗

    日本学術振興会, 科学研究費助成事業 若手研究(B), 若手研究(B), 神戸大学, 2002年 - 2003年

    膀胱壁筋層に浸潤した膀胱癌に対する治療法の、現在における第一選択は膀胱全摘出術である。尿路変更術の進歩などにより、膀胱全摘出術を受ける患者さんの術後のQOL(Quality of Life)は著しく改善されたが、膀胱機能の温存やさらなるQOLの向上を目指して、現在、様々な膀胱温存療法が検討されている。アメリカにおいて行われた大規模な臨床試験では、著しい局所浸潤、または全身状態の不良などで手術不可能な症例、あるいは患者さん自身が膀胱を摘出することを拒否した症例に対して、経尿道的膀胱腫瘍切除術、放射線療法、および抗癌化学療法の三者併用による膀胱温存療法が施行され、病期によっては膀胱全摘出術と同等の治療成績が確認された。本研究では、これらの三者併用療法に加えて、p53遺伝子や自殺遺伝子の導入による遺伝子治療をさらに併用し、膀胱癌の放射線や抗癌剤に対する感受性を増強することによる、進行性膀胱癌に対する膀胱温存根治療法の実現の可能性を検討した。 最初に種々のP53遺伝子の変異を持つ膀胱癌細胞と持たない膀胱癌細胞での放射線感受性を検討した。結果、正常のP53遺伝子を持つ膀胱癌細胞では、放射線照射によりP53依存性の細胞死を顕著に認めたが、P53遺伝子に変異を持つ膀胱癌細胞では認められず放射線感受性も比較的低かった。以上の結果よりP53遺伝子治療と放射線療法の併用療法の可能性が示唆された。 次にアデノウイルスベクターを用いたCD/5-FC遺伝子治療と放射線療法の併用療法の膀胱癌に対する有用性をヒト膀胱癌細胞株、KK47細胞を用いて検討した。結果、本併用療法は細胞培養系、および動物実験双方において相乗的な抗癌作用を示した。本研究により膀胱癌に対する遺伝子治療と放射線療法の併用療法の可能性が示唆された。

  • 前立腺癌の放射線治療・遺伝子治療併用療法に関する基礎的研究

    副島 俊典, 丸田 力, 白川 利朗, 後藤 章暢, 杉村 和朗, 佐々木 良平, 副島 俊典, 山田 和成

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2000年 - 2002年

    p53遺伝子変異は前立腺癌を含め、乳癌、肺癌、大腸癌などの多くの悪性疾患において最も高頻度に認められ、放射線治療や他の抗癌剤治療効果の多くは正常のp53遺伝子の機能に高度に依存していることからもその生物学的特性に大きな関心が寄せられている。しかし、遺伝子治療単独で癌を制御することは困難であり、集学的治療に組み込んだ治療法の開発が必須である。そこで我々はアデノウイルスベクターp53遺伝子(Ad5CMV-p53)を用いた遺伝子導入と放射線照射との併用効果について、p53遺伝子に異なる種類の変異を持つヒト前立腺癌細胞におけるin vitroでの実験を行った。放射線照射単独ではp53発現量はほとんど変化しなかったのに対し、遺伝子導入併用群では著明に上昇した。その下流に位置しアポトーシスおよび細胞周期を制御する遺伝子であるBax、p21の発現量も併用群において増強されていた。アポトーシスの定量的評価では、放射線照射単独ではほとんど観察されなかったが、遺伝子導入を行うことによりアポトーシスの頻度は劇的な増加が見られた。また、細胞周期解析にて放射線照射単独ではG2期停止の割合が増加し、遺伝子導入単独ではG1期停止が増加していた。併用群においてはG1停止、G2期停止共に単独治療群よりも増加していることが観察された。これらから、p53遺伝子の導入により、アポトーシス・細胞周期停止の双方の経路を介した細胞死・増殖抑制効果が活性化され、放射線照射の効果を増強することが解り、これらの結果は細胞のコロニー増殖能に反映されていた。また、放射線照射によりp53遺伝子の導入効率が上昇することを見出し、この点も併用効果を高める一因であることが判明した。現在、in vivoにおける導入効率の更なる改善手段を検討中であり、臨床応用への基盤とするための研究を進めている。

  • ヒト精巣腫瘍細胞特異性プロモーターを応用した精巣腫瘍遺伝子治療法の開発

    後藤 章暢, 守殿 貞夫, 白川 利朗

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2000年 - 2002年

    癌に対する遺伝子治療の最も基本的な問題の一つとして、対象とする遺伝子をいかに癌細胞に特異的に効率良く発現させるかということがある。近年、癌細胞特異的に活性化される臓器特異性プロモーターを用いた癌遺伝子治療法の基礎研究、および臨床試験が盛んにおこなわれているが、特に臓器特異性プロモーターと自殺遺伝子を組み合わせた治療法が注目を集めている。本研究では、化学療法抵抗性の進行性精巣腫瘍患者の約7割以上で血清・-HCG(ヒト絨毛性ゴナドトロピン)の上昇を認めることから、・-HCGのプロモーターを臓器特異性プロモーターとして応用した遺伝子治療法の開発とその有用性を研究目標とした。我々は・-HCGプロモーターとして729塩基対のDNAサイズを選択する予定であるが、他にも様々なサイズの・-HCGプロモーターのDNAをクローニングし、精巣腫瘍細胞における、それぞれのプロモーター活性を測定し、精巣腫瘍に対する遺伝子治療に最も適した・-HCGプロモーターのサイズの決定を試みた。結果的にクローニングした729塩基対の・-HCGプロモーターDNAの特異性が最も優れており、それをルシフェレース遺伝子に組み込んだプラスミドベクターに挿入した。そのプラスミドベクターを様々な細胞(絨毛癌細胞(JAR)、胎児性癌細胞(NEC8、NEC14)、前立腺癌細胞(PC-3、DU145)、膀胱癌細胞(WH))に遺伝子導入して、ルシフェレース活性を測定し、・-HCGプロモーターの細胞特異的活性を確認した。結果は・-HCGを産生する絨毛癌細胞(JAR)、胎児性癌細胞(NEC8、NEC14)にのみ高レベルのプロモーター活性を認めた。これらの研究成果よりAd-・-HCG-TK・を作製し、同様な実験にて絨毛癌細胞(JAR)、胎児性癌細胞(NEC8、NEC14)細胞株のみに特異的に抗腫瘍性が確認された。他の正常組織には細胞障害作用は認められなかった。次に自己増殖複製可能なアデノウイルスベクター、Replication Competent Adenovirusを用いる遺伝子治療の開発を検討するため、・-HCGプロモーターで制御されるE1A遺伝子を組み込んだReplication Competent Adenovirusを作製した。現在、自殺遺伝子を用いた遺伝子治療との比較検討を行う予定で、本ベクターを用いた治療実験をin Vitro、in Vivo双方で行いヒト精巣腫瘍に対する最も優れた遺伝子治療法の検討を行っている。

産業財産権

  • 免疫原性ポリペプチド表層発現ビフィズス菌(米国)

    白川 利朗, 堀田 博, 片山 高嶺

    14/768508, 2015年08月18日, 大学長, 9925259, 2018年03月27日

    特許権

  • 免疫原性ポリペプチド表層発現ビフィズス菌

    白川 利朗, 堀田 博, 片山 高嶺

    特願2015-501435, 2014年02月14日, 大学長, 特許6213969, 2017年09月29日

    特許権

  • 腫瘍免疫誘導剤

    白川 利朗, 斎藤 彩, 松岡 孝幸

    特願2011-508225, 2010年03月29日, 大学長, 特許5582542, 2014年07月25日

    特許権

  • ビフィズス菌表層提示融合タンパク質発現遺伝子

    白川 利朗, 山本 さくら

    特願2011-531985, 2010年09月17日, 大学長, 特許5561681, 2014年06月20日

    特許権

  • 経口ワクチン

    白川 利朗, 川端 眞人, 高田 哲男, 谷口 道子, 岡本 明子

    特願2009-505269, 2008年03月19日, 大学長, 特許5187642, 2013年02月01日

    特許権