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内木 拓ナイキ タク

所属部署医学研究科腎・泌尿器科学分野
職名講師
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Last Updated :2020/05/28

研究者基本情報

基本情報

    科研費研究者番号:50551272

学位

  • 医学博士, 名古屋市立大学院

研究活動情報

研究分野

  • ライフサイエンス, 病態医化学
  • ライフサイエンス, 泌尿器科学

論文

  • Cotinine, a major nicotine metabolite, induces cell proliferation on urothelium in vitro and in vivo., Shugo Suzuki, Samuel M Cohen, Lora L Arnold, Karen L Pennington, Hiroyuki Kato, Taku Naiki, Aya Naiki-Ito, Yoriko Yamashita, Satoru Takahashi, Toxicology, 429, 152325 - 152325,   2020年01月15日, 査読有り, Tobacco smoking is a major risk factor for human cancers including urinary bladder carcinoma. In a previous study, nicotine enhanced rat urinary bladder carcinogenesis using a rat urinary bladder two-stage carcinogenesis model. In the present study, nicotine metabolites (cotinine, trans-3'-hydroxy cotinine and N'-nitrosonornicotine) were evaluated in a cell proliferation assay using urinary bladder urothelial cell lines. Cotinine (0.1 to 1 mM) induced the highest cell proliferation compared to the others, including nicotine, in three bladder cancer cell lines (RT4, T24 and UMUC3 cells). By Western blot, cotinine induced phosphorylation of Stat3 and expression of cyclin D1 in UMUC3 cells. The cell proliferation induced by cotinine was blocked by inhibitors of nicotinic receptors (10 nM SR16584 or 10 μM methyllycaconitine citrate) and Stat3 (100 nM stattic). In an in vivo study, cotinine (13, 40 and 120 ppm) in drinking water also induced cell proliferation and simple hyperplasia in urinary bladder and renal pelvis urothelium of rats, but to a lesser degree compared to nicotine (40 ppm). Cytotoxicity detected by scanning electron microscopy and apoptosis in the bladder urothelium were induced by nicotine but not cotinine. These data suggest that cotinine is able to induce urothelial cell proliferation both in vitro and in vivo, and high urinary concentrations may enhance urothelial carcinogenesis.
  • Recruitment of miR-8080 by luteolin inhibits androgen receptor splice variant 7 expression in castration-resistant prostate cancer., Aya Naiki-Ito, Taku Naiki, Hiroyuki Kato, Keitaro Iida, Toshiki Etani, Yuko Nagayasu, Shugo Suzuki, Yoriko Yamashita, Shingo Inaguma, Masaya Onishi, Yasuhito Tanaka, Takahiro Yasui, Satoru Takahashi, Carcinogenesis,   2019年12月05日, 査読有り, A need exists for seeking effective treatments for castration-resistant prostate cancer (CRPC) in response to its emergence following androgen deprivation therapy as a major clinical problem. In the present study, we investigated the chemopreventive and chemotherapeutic potential of luteolin, a flavonoid with antioxidative properties, on prostate cancer, including CRPC. Luteolin inhibited the progression of rat prostate carcinogenesis by induction of apoptosis in a transgenic rat for adenocarcinoma of prostate (TRAP) model. Luteolin decreased cell proliferation in a dose-dependent manner and induced apoptosis with the activation of caspases 3 and 7 in both rat (PCai1, established from a TRAP prostate tumor) and human (22Rv1) CRPC cells. Dietary luteolin also suppressed tumor growth via an increase in apoptosis and inhibition of angiogenesis in PCai1 and 22Rv1 xenografts implanted in castrated nude mice. We also focused on androgen receptor splice variant 7 (AR-V7), which contributes to cell proliferation and therapeutic resistance in CRPC. Luteolin dramatically suppressed AR-V7 protein expression in 22Rv1 cells in vitro and ex vivo. Microarray analysis identified MiR-8080, which contains a possible target sequence for AR-V7 3'-UTR, as a gene upregulated by luteolin. MiR-8080 transfection decreased the AR-V7 expression level and the induction of apoptosis in 22Rv1 cells. Furthermore, miR-8080 knockdown canceled luteolin decreasing AR-V7 and the cell growth of 22Rv1. MiR-8080 induced by luteolin intake enhanced the therapeutic effect of enzalutamide on 22Rv1 xenografts under castration conditions. These results indicate luteolin inhibits CRPC by AR-V7 suppression through miR-8080, highlighting luteolin and miR-8080 as promising therapeutic agents for this disease.
  • Prognostic significance of hyponatremia induced by systemic chemotherapy in a hospital-based propensity score-matched analysis., Sugiyama Y, Naiki T, Tasaki Y, Kondo Y, Kataoka T, Etani T, Iida K, Nozaki S, Ando R, Osaga S, Yasui T, Kimura K, International journal of clinical oncology,   2019年12月, 査読有り
  • Skeletal Muscle Mass Reduction Velocity as a Simple Prognostic Indicator for Patients with Metastatic Urothelial Carcinoma Receiving Second-Line Chemotherapy., Nagai T, Naiki T, Iida K, Nozaki S, Etani T, Sugiyama Y, Ando R, Yanase T, Chaya R, Moritoki Y, Kobayashi D, Akita H, Okamura T, Yasui T, Asian Pacific journal of cancer prevention : APJCP, 20, (10) 2995 - 3000,   2019年10月, 査読有り
  • Rare case of Richter syndrome with testicular involvement successfully obtained good prognosis with rapid operation and immunochemotherapy, Kengo Kawase, Taku Naiki, Aya Naiki-Ito, Masamitsu Yanada, Yosuke Ikegami, Yuya Ota, Tatsuya Hattori, Nayuka Matsuyama, Takashi Hamakawa, Tetsuji Maruyama, Takahiro Yasui, IJU Case Reports, 2, (4) ,   2019年07月, 査読有り
  • Complete surgical removal of multiple tumor lesions in malignant pheochromocytomas produces a good prognosis, Satoshi Nozaki, Taku Naiki, Yoshinobu Moritoki, Shuzo Hamamoto, Toshiki Etani, Keitaro Iida, Rei Unno, Atsushi Okada, Noriyasu Kawai, Takahiro Yasui, IJU Case Reports,   2019年05月, 査読有り
  • NCL1, A Highly Selective Lysine-Specific Demethylase 1 Inhibitor, Suppresses Castration-Resistant Prostate Cancer Growth via Regulation of Apoptosis and Autophagy., Toshiki Etani, Taku Naiki, Aya Naiki-Ito, Takayoshi Suzuki, Keitaro Iida, Satoshi Nozaki, Hiroyuki Kato, Yuko Nagayasu, Shugo Suzuki, Noriyasu Kawai, Takahiro Yasui, Satoru Takahashi, Journal of clinical medicine, 8, (4) ,   2019年03月31日, 査読有り, Recent studies have shown that epigenetic alterations lead to oncogenic activation, thus indicating that these are therapeutic targets. Herein, we analyzed the efficacy and therapeutic potential of our developed histone lysine demethylase 1 (LSD1) inhibitor, NCL1, in castration-resistant prostate cancer (CRPC). The CRPC cell lines 22Rv1, PC3, and PCai1CS were treated with NCL1, and LSD1 expression and cell viability were assessed. The epigenetic effects and mechanisms of NCL1 were also evaluated. CRPC cells showed strong LSD1 expression, and cell viability was decreased by NCL1 in a dose-dependent manner. Chromatin immunoprecipitation analysis indicated that NCL1 induced histone H3 lysine 9 dimethylation accumulation at promoters of P21. As shown by Western blot and flow cytometry analyses, NCL1 also dose-dependently induced caspase-dependent apoptosis. The stimulation of autophagy was observed in NCL1-treated 22Rv1 cells by transmission electron microscopy and LysoTracker analysis. Furthermore, WST-8 assay revealed that the anti-tumor effect of NCL1 was reinforced when autophagy was inhibited by chloroquine in 22Rv1 cells. Combination index analysis revealed that a concurrent use of these drugs had a synergistic effect. In ex vivo analysis, castrated nude mice were injected subcutaneously with PCai1 cells and intraperitoneally with NCL1. Tumor volume was found to be reduced with no adverse effects in NCL1-treated mice compared with controls. Finally, immunohistochemical analysis using consecutive human specimens in pre- and post-androgen deprivation therapy demonstrated that LSD1 expression levels in CRPC, including neuroendocrine differentiation cases, were very high, and identical to levels observed in previously examined prostate biopsy specimens. NCL1 effectively suppressed prostate cancer growth in vitro and ex vivo without adverse events via the regulation of apoptosis and autophagy, suggesting that NCL1 is a potential therapeutic agent for CRPC.
  • Laparoscopic radical surgery produces a good prognosis in an elderly patient with small Wilms’ tumor, Yuya Ota, Taku Naiki, Motoo Nakagawa, Aya Naiki-Ito, Shuzo Hamamoto, Toshiki Etani, Keitaro Iida, Satoshi Nozaki, Ryosuke Ando, Noriyasu Kawai, Takahiro Yasui, IJU Case Reports,   2019年03月, 査読有り
  • Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis, Cancer Management and Research,   2018年09月, 査読有り
  • Efficacy of tapentadol for first-line opioid-resistant neuropathic pain in Japan., Sugiyama Y, Kataoka T, Tasaki Y, Kondo Y, Sato N, Naiki T, Sakamoto N, Akechi T, Kimura K, Japanese journal of clinical oncology, 48, (4) 362 - 366,   2018年04月, 査読有り
  • GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis., Taku Naiki, Aya Naiki-Ito, Keitaro Iida, Toshiki Etani, Hiroyuki Kato, Shugo Suzuki, Yoriko Yamashita, Noriyasu Kawai, Takahiro Yasui, Satoru Takahashi, Oncotarget, 9, (22) 15847 - 15859,   2018年03月23日, 査読有り, Herein, we elucidated the molecular mechanisms and therapeutic potential of glutathione peroxidase 2 (GPX2) in bladder cancer. GPX2 expression gradually increased during progression from normal to papillary or nodular hyperplasia (PNHP) and urothelial carcinoma (UC) in a rat N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis model. GPX2 overexpression was more marked in UC with squamous differentiation (SqD) than in pure UC. Clinical intraepithelial lesions of papillary UC and invasive UC with SqD also had strong GPX2 expression in human radical cystectomy specimens. In addition, prognostic analysis using transurethral specimens revealed that low expression level of GPX2 predicted poor prognosis in patients with pure UC. Further, UC cell lines, BC31 and RT4, cultured in vitro also overexpressed GPX2. Knock-down of GPX2 induced significant inhibition of intracellular reactive oxygen species (ROS) production, in addition to significant growth inhibition and increased apoptosis with activation of caspase 3 or 7 in both BC31 and RT4 cells. Interestingly, tumor growth of BC31 cells subcutaneously transplanted in nude mice was significantly caused the induction of apoptosis, as well as inhibition of angiogenesis and SqD by GPX2 down-regulation. Our findings demonstrated that GPX2 plays an important role in bladder carcinogenesis through the regulation of apoptosis against intracellular ROS, and may be considered as a novel biomarker or therapeutic target in bladder cancer.
  • Urothelial carcinoma of the urinary bladder in a 12-year-old girl: A case report with immunohistological analysis and a review of the literature., Kato T, Mizuno K, Naiki T, Nishio H, Iida K, Moritoki Y, Ando R, Okada A, Yasui T, Hayashi Y, Urology case reports, 17, 29 - 31,   2018年03月, 査読有り
  • Early detection of prostate carcinogens by immunohistochemistry of HMGB2., Shugo Suzuki, Hiroyuki Kato, Satoshi Fuji, Taku Naiki, Aya Naiki-Ito, Yoriko Yamashita, Satoru Takahashi, The Journal of toxicological sciences, 43, (6) 359 - 367,   2018年, 査読有り, Screening prostatic carcinogens is time-consuming due to the time needed to induce preneoplastic and neoplastic lesions. To overcome this, we investigated alternative molecular markers for detection of prostatic carcinogens in a short period in rats. After treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), expression of high-mobility group protein B2 (HMGB2) was up-regulated in rat ventral prostate. To evaluate the applicability of HMGB2 in the early detection of carcinogenicity of chemicals using animal models, we examined HMGB2 expression in prostate of rats. Six-week-old male F344 rats were gavaged for four weeks with a total of eight individual chemicals, divided into two categories based on prostate carcinogenicity. Animals were sacrificed at the end of the study and HMGB2 immunohistochemistry was performed. HMGB2 expression in least one prostate lobe was significantly increased by all four prostate carcinogens compared with the controls. In contrast, the four chemicals that were not carcinogenic in the prostate did not cause HMGB2 up-regulation. Additionally, high HMGB2 expression in neoplastic lesions in both rat and human was detected. Therefore HMGB2 expression may be a good screening tool for the identification of potential of prostate carcinogens.
  • Investigation of tolerability and quality of life for carboplatin-based chemotherapy in an elderly urothelial carcinoma patient undergoing hemodialysis: a case report., Kondo M, Naiki T, Hotta Y, Yamamoto Y, Sugiyama Y, Yasui T, Kimura K, Journal of pharmaceutical health care and sciences, 4,   2018年, 査読有り
  • Complete remission of metastatic pheochromocytoma in 123I-metaiodobenzylguanidine scintigraphy after a single session of 131I-metaiodobenzylguanidine therapy: a case report., Sugino T, Ando R, Unno R, Iida K, Naiki T, Hamamoto S, Mizuno K, Okada A, Umemoto Y, Kawai N, Tozawa K, Hayashi Y, Inaki A, Kayano D, Kinuya S, Yasui T, BMC research notes, 10, (1) ,   2017年12月, 査読有り
  • Transcatheter Arterial Embolization for Renal Angiomyolipoma Using a Micro-balloon Catheter and a Mixture of Ethanol and Lipiodol, Yusuke Sawada, Masashi Shimohira, Takuya Hashizume, Ryoji Sobue, Soichiro Mori, Motoo Nakagawa, Yoshiyuki Ozawa, Taku Naiki, Takashi Nagai, Takahiro Yasui, Yuta Shibamoto, CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, 40, (12) 1933 - 1939,   2017年12月, 査読有り, To evaluate the efficacy and safety of transcatheter arterial embolization (TAE) for renal angiomyolipoma (AML) using a micro-balloon catheter and a mixture of ethanol and lipiodol. Twelve consecutive patients with 15 AMLs, 9 females and 3 males, with a median age of 44 years (range, 11-81), underwent this procedure between 2011 and 2016. In all procedures, a micro-balloon catheter was advanced to the feeding artery of the AML and TAE was performed with a mixture of ethanol and lipiodol under balloon inflation. We reviewed medical records and images, and evaluated the technical success rate, clinical success rate, and complications. Technical success was defined as completion of TAE using the micro-balloon catheter and the mixture of ethanol and lipiodol. Clinical success was defined as reduction of tumor size on CT, which was performed before and after TAE. In 14 of 15 AMLs, the micro-balloon catheter could be advanced to the feeding artery, and TAE was performed successfully. Thus, the technical success rate was 93%. Among these 14 AMLs of 11 patients, 13 AMLs of 10 patients could be followed and tumor shrinkage was confirmed in all. Thus, the clinical success rate was 100%. Four patients had mild symptoms after TAE; the minor complication rate was 33% (4/12), and the major complication rate was 0%. TAE for renal AML using the micro-balloon catheter and mixture of ethanol and lipiodol appears to be effective and safe.
  • A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma., Naiki T, Iida K, Kawai N, Etani T, Ando R, Nagai T, Tanaka Y, Hamamoto S, Hamakawa T, Akita H, Sugiyama Y, Yasui T, Journal of rural medicine : JRM, 12, (2) 105 - 111,   2017年11月, 査読有り
  • A New Navigation System of Renal Puncture for Endoscopic Combined Intrarenal Surgery: Real-time Virtual Sonography-guided Renal Access, Shuzo Hamamoto, Rei Unno, Kazumi Taguchi, Ryosuke Ando, Takashi Hamakawa, Taku Naiki, Shinsuke Okada, Takaaki Inoue, Atsushi Okada, Kenjiro Kohri, Takahiro Yasui, UROLOGY, 109, 44 - 50,   2017年11月, 査読有り, OBJECTIVE To evaluate the clinical utility of a new navigation technique for percutaneous renal puncture using real-time virtual sonography (RVS) during endoscopic combined intrarenal surgery. MATERIALS AND METHODS Thirty consecutive patients who underwent endoscopic combined intrarenal surgery for renal calculi, between April 2014 and July 2015, were divided into the RVS-guided puncture (RVS; n = 15) group and the ultrasonography-guided puncture (US; n = 15) group. In the RVS group, renal puncture was repeated until precise piercing of a papilla was achieved under direct endoscopic vision, using the RVS system to synchronize the real-time US image with the preoperative computed tomography image. In the US group, renal puncture was performed under US guidance only. In both groups, 2 urologists worked simultaneously to fragment the renal calculi after inserting the miniature percutaneous tract. The mean sizes of the renal calculi in the RVS and the US group were 33.5 and 30.5 mm, respectively. RESULTS A lower mean number of puncture attempts until renal access through the calyx was needed for the RVS compared with the US group (1.6 vs 3.4 times, respectively; P=.001). The RVS group had a lower mean postoperative hemoglobin decrease (0.93 vs 1.39 g/dL, respectively; P=.04), but with no between-group differences with regard to operative time, tubeless rate, and stone-free rate. None of the patients in the RVS group experienced postoperative complications of a Clavien score >= 2, with 3 patients experiencing such complications in the US group. CONCLUSION RVS-guided renal puncture was effective, with a lower incidence of bleeding-related complications compared with US-guided puncture. (C) 2017 Elsevier Inc.
  • Antimicrobial susceptibility of pathogens in acute uncomplicated cystitis cases in the urology department of a community hospital in Japan: Comparison with treatment outcome and hospital-wide antibiogram, Toshiki Etani, Taku Naiki, Sachiyo Yamaguchi, Saori Mori, Takashi Nagai, Keitaro Iida, Ryosuke Ando, Noriyasu Kawai, Keiichi Tozawa, Tohru Mogami, Takahiro Yasui, JOURNAL OF INFECTION AND CHEMOTHERAPY, 23, (10) 692 - 697,   2017年10月, 査読有り, We hypothesized that cases of uncomplicated cystitis treated in a Urology Department would display higher antimicrobial susceptibility than those reported by the hospital antibiogram. This would suggest narrow spectrum antibiotics could still be an effective treatment for uncomplicated cystitis despite this era of antimicrobial resistance. The objective of this study was thus to evaluate the rates of antimicrobial susceptibility of isolates cultured from uncomplicated cystitis cases that presented to the Urology Department of a community hospital in Japan. We evaluated the efficacy of cefaclor, a narrow spectrum antibiotic, for uncomplicated cystitis. We further compared the rates of antimicrobial susceptibility of isolates from uncomplicated cystitis cases to those reported in a hospital-wide antibiogram. A retrospective chart review was performed of patients diagnosed with uncomplicated cystitis in the Urology Department. The patients were mainly treated orally by cefaclor at 750 mg/day for seven days. Significantly greater susceptibilities to cefazolin (87.0% vs 65.7%), trimethoprim-sulfamethoxazole (89.4% vs 79.1%) and levofloxacin (84.6% vs 66.9%) were observed in a cystitis antibiogram for Escherichia coli compared with a hospital-wide antibiogram. The clinical efficacy of cefaclor for acute cystitis was also demonstrated. The greater susceptibility of Escherichia coli to antimicrobials observed in this study supports the hypothesis that antimicrobial susceptibility rates in uncomplicated cystitis cases that present to the Urology Department would be greater than those reported in the hospital antibiogram. Therefore, uncomplicated acute cystitis can be treated by narrow spectrum antibiotics such as cefaclor even in this "antimicrobial resistance era''. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
  • Syndrome of Inappropriate Secretion of Antidiuretic Hormone Caused by Carboplatin After Switching from Cisplatin in a Metastatic Urethral Cancer Patient., Sugiyama Y, Naiki T, Kondo M, Iida K, Kondo Y, Tasaki Y, Kataoka T, Hotta A, Yasui T, Kimura K, Urology case reports, 12, 17 - 19,   2017年05月, 査読有り
  • Two-year-old girl with impacted ureteral stone successfully treated with a single session of combined percutaneous nephrostomy and ureteroscopy, Teruaki Sugino, Shuzo Hamamoto, Rei Unno, Yoshinobu Moritoki, Takashi Hamakawa, Taku Naiki, Ryosuke Ando, Atsushi Okada, Takahiro Yasui, INTERNATIONAL JOURNAL OF UROLOGY, 24, (4) 326 - 329,   2017年04月, 査読有り, Impacted stones frequently cause changes in the ureter, including edema of the ureteral wall, stone embedding in the ureteral mucosa or ureteral bending, which often preclude spontaneous passing of the stone and increase the risk of complications during surgery. When stone impaction is suspected preoperatively, management should be adapted accordingly. However, surgical treatment strategies remain controversial in pediatric patients because of the scarcity of cases reported. We describe the case of a 2-year-old girl with a right impacted ureteral stone who presented with gross hematuria and pyuria, but no metabolic risk factors or hematological abnormalities. Ureteroscopy was carried out in the presence of a percutaneous nephrostomy catheter. At the 7-month follow up, hydronephrosis had improved from grade 3 to grade 1, and the ureter was free from residual or recurrent stones. No complications were noted. We believe that percutaneous nephrostomy before the lithotripsy facilitates treatment for impacted stones in pediatric patients.
  • Determinants of health-related quality of life for patients after urinary lithotripsy: ureteroscopic vs. shock wave lithotripsy., Hamamoto S, Unno R, Taguchi K, Naiki T, Ando R, Okada A, Inoue T, Okada S, AbdelRazek M, Kohri K, Yasui T, SMART Study Group, Urolithiasis,   2017年03月, 査読有り
  • A Case of Delayed Radiation Myelopathy of the Thoracic Vertebrae Following Low Dose Radiation Therapy for Metastatic Renal Cell Carcinoma., Nozaki S, Naiki T, Hamamoto S, Ando R, Iida K, Kawai N, Mizuno K, Okada A, Umemoto Y, Yasui T, Urology case reports, 11, 66 - 68,   2017年02月, 査読有り
  • Metastatic urothelial carcinoma with glandular differentiation that confirmed the response by autopsy specimen to second-line mFOLFOX6 (Fluorouracil, Oxaliplatin, and Leucovorin) plus bevacizumab chemotherapy, Naiki, T., Etani, T., Naiki-Ito, A., Fujii, K., Ando, R., Iida, K., Nagai, T., Sugiyama, Y., Nakagawa, M., Kawai, N., Yasui, T., Case Reports in Oncology, 10, (3) 1057 - 1064,   2017年, 査読有り
  • Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers, Kazumi Taguchi, Shuzo Hamamoto, Atsushi Okada, Rei Unno, Hideyuki Kamisawa, Taku Naiki, Ryosuke Ando, Kentaro Mizuno, Noriyasu Kawai, Keiichi Tozawa, Kenjiro Kohri, Takahiro Yasui, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 28, (1) 333 - 347,   2017年01月, 査読有り, Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (>2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogenactivated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.
  • Therapeutic results in elderly patients with prostate cancer: chronological comparison in a single community hospital., Okamura T, Akita H, Yamada K, Kobayashi D, Hirose Y, Kobayashi T, Tanaka Y, Naiki T, Yasui T, Journal of rural medicine : JRM, 11, (2) 59 - 62,   2016年12月, 査読有り
  • M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development, Kazumi Taguchi, Atsushi Okada, Shuzo Hamamoto, Rei Unno, Yoshinobu Moritoki, Ryosuke Ando, Kentaro Mizuno, Keiichi Tozawa, Kenjiro Kohri, Takahiro Yasui, SCIENTIFIC REPORTS, 6,   2016年10月, 査読有り, In our previous report, M2-macrophage (M phi s) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; however, the role of M phi s-related-cytokines and chemokines that affect kidney stone formation remains unknown. Here, we investigated the role of M1/M2s in crystal development by using in vitro and in vivo approaches. The crystal phagocytic rate of bone marrow-derived M2M phi s was higher than that of bone marrow-derived M phi s and M1M phi s and increased on co-culture with renal tubular cells (RTCs). However, the amount of crystal attachment on RTCs reduced on co-culture with M2M phi s In six hyperoxaluric C57BL/6J mice, M1M phi transfusion and induction by LPS and IFN-gamma facilitated renal crystal formation, whereas M2M phi transfusion and induction by IL-4 and IL-13 suppressed renal crystal formation compared with the control. These M2M phi treatments reduced the expression of crystal-related genes, such as osteopontin and CD44, whereas M1M phi treatment increased the expression of pro-inflammatory and adhesion-related genes such as IL-6, inducible NOS, TNF-alpha, C3, and VCAM-1. The expression of M2M phi-related genes was lower whereas that of M1M phi-related genes was higher in papillary tissue of CaOx stone formers. Overall, our results suggest that renal crystal development is facilitated by M1M phi s, but suppressed by M2M phi s.
  • Usefulness of early vascular phase images from contrast-enhanced ultrasonography using Sonazoid for the diagnosis of hypovascular hepatocellular carcinoma, Hideki Hayashi, Yoichi Nishigaki, Eiichi Tomita, Chiaki Watanabe, Satoshi Watanabe, Naoki Watanabe, Yusuke Suzuki, Tomohiro Kato, Takafumi Naiki, HEPATOLOGY RESEARCH, 46, (6) 497 - 504,   2016年05月, 査読有り, Aim: This study aimed to evaluate the usefulness of early vascular phase images produced by contrast-enhanced ultrasonography (CE-US) with Sonazoid for the diagnosis of hypovascular hepatocellular carcinoma (HCC). Methods: Four hundred and seventeen patients with 674 hepatic nodules were evaluated using CE-US with Sonazoid between January 2007 and March 2010. Retrospective analysis was conducted on 49 histologically confirmed nodules showing hypovascularity relative to the surrounding liver tissue in the early vascular phase and no enhancement defect in the Kupffer phase of CE-US with Sonazoid. These nodules were classified according to early vascular phase image enhancement patterns as types I (largest avascular; avascular as a whole), II (second avascular; partially avascular), III (smallest avascular; not avascular, but faintly hypovascular relative to the surrounding liver) and IV (hypovascular as a whole with vessel-like structures passing inside nodules). Results: Among the 49 nodules, types I, II, III and IV were identified in 19 (38.8%), nine (18.4%), 15 (30.6%) and six (12.2%) cases, respectively. The proportion of tumorous nodules (well-differentiated HCC and high-grade dysplastic nodules) significantly decreased with a reduction of the avascular area (68.4% in the type I, 55.6% in the type II and 33.3% in the type III nodules; P<0.05). All nodules demonstrating the type IV enhancement pattern were non-tumorous. Conclusion: Based on the size of avascular area in the early vascular phase of CE-US with Sonazoid, we can predict the malignant potential of the nodules. CE-US with Sonazoid is very useful for evaluation of hypovascular hepatic nodules.
  • Inflammatory Myofibroblastic Tumor of the Urinary Bladder: A Case Report, Etani, T., Naiki, T., Nagai, T., Iida, K., Ando, R., Naiki-Ito, A., Kawai, N., Tozawa, K., Mizuno, K., Okada, A., Mogami, T., Yasui, T., Case Reports in Oncology, 9, (2) 464 - 469,   2016年, 査読有り
  • NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect, Etani T, Suzuki T, Naiki T, Naiki-Ito A, Ando R, Iida K, Kawai N, Tozawa K, Miyata N, Kohri K, Takahashi S, Oncotarget, 6, (5) 2865 - 2878,   2015年, 査読有り
  • Novel Closing Method Using Subcutaneous Continuous Drain for Preventing Surgical Site Infections in Radical Cystectomy, Yasuhiko Hirose, Taku Naiki, Ryosuke Ando, Akihiro Nakane, Toshiki Etani, Keitaro Iida, Hidetoshi Akita, Takehiko Okamura, Kenjiro Kohri, ISRN Urology, 2014,   2014年, 査読有り
  • Are there Time-period-related Differences in the Prophylactic Effects of Bacille Calmette-Guérin Intravesical Instillation Therapy in Japan?, Takehiko Okamura, Ryosuke Ando, Hidetoshi Akita, Yoshihiro Hashimoto, Yutaka Iwase, Taku Naiki, Noriyasu Kawai, Keiichi Tozawa, Kenjiro Kohri, Asian Pacific Journal of Cancer Prevention, 13, (9) 4357 - 4361,   2012年, 査読有り, Takehiko Okamura, Ryosuke Ando, Hidetoshi Akita, Yoshihiro Hashimoto, Yutaka Iwase, Taku Naiki, Noriyasu Kawai, Keiichi Tozawa, Kenjiro Kohri, 2012, 'Are there Time-period-related Differences in the Prophylactic Effects of Bacille Calmette-Guérin Intravesical Instillation Therapy in Japan?', <i>Asian Pacific Journal of Cancer Prevention</i>, vol. 13, no. 9
  • Are there Time-period-related Differences in the Prophylactic Effects of Bacille Calmette-Guérin Intravesical Instillation Therapy in Japan?, Takehiko Okamura, Ryosuke Ando, Hidetoshi Akita, Yoshihiro Hashimoto, Yutaka Iwase, Taku Naiki, Noriyasu Kawai, Keiichi Tozawa, Kenjiro Kohri, Asian Pacific Journal of Cancer Prevention, 13, (9) 4357 - 4361,   2012年, 査読有り, Takehiko Okamura, Ryosuke Ando, Hidetoshi Akita, Yoshihiro Hashimoto, Yutaka Iwase, Taku Naiki, Noriyasu Kawai, Keiichi Tozawa, Kenjiro Kohri, 2012, 'Are there Time-period-related Differences in the Prophylactic Effects of Bacille Calmette-Guérin Intravesical Instillation Therapy in Japan?', <i>Asian Pacific Journal of Cancer Prevention</i>, vol. 13, no. 9
  • Giant Retroperitoneal Mucinous Tumor Supportively Diagnosed as a Dedifferentiated Liposarcoma by Fluorescence In Situ Hybridization of MDM2 Gene., Naiki T, Hamamoto S, Kawai N, Naiki-Ito A, Kojima Y, Yasui T, Tozawa K, Kohri K, ISRN Urology, 2011, (3) ,   2011年, 査読有り, Taku Naiki, Shuzo Hamamoto, Noriyasu Kawai, Aya Naiki-Ito, Yoshiyuki Kojima, Takahiro Yasui, Keiichi Tozawa, Kenjiro Kohri, 2011, 'Giant Retroperitoneal Mucinous Tumor Supportively Diagnosed as a Dedifferentiated Liposarcoma by Fluorescence In Situ Hybridization of MDM2 Gene', <i>ISRN Urology</i>, vol. 2011, no. 3
  • Preoperative Prediction of Neurovascular Bundle Involvement of Localized Prostate Cancer by Combined T2 and Diffusion-weighted Imaging of Magnetic Resonance Imaging, Number of Positive Biopsy Cores, and Gleason Score, Taku Naiki, Takehiko Okamura, Daisuke Nagata, Yuji Mori, Noriyasu Kawai, Kumiko Ogawa, Hidetoshi Akita, Yoshihiro Hashimoto, Keiichi Tozawa, Kenjiro Kohri, ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 12, (4) 909 - 913,   2011年, 査読有り, Because recovery of erectile function and avoidance of positive surgical margins are important but competing outcomes with prostate cancer therapy, the decision to preserve or resect a neurovascular bundle (NVB) during laparoscopic radical prostatectomy (LRP) should be firmly based on information concerning the presence and location of extracapsular extension. In the current retrospective study, the propriety of actual decisions was assessed using preoperative magnetic resonance imaging (MRI), combining T2-weighted imaging (T2WI) with diffusion-weighted imaging (DWI), the apparent diffusion coefficient (ADC), numbers of positive biopsy cores, tumor volume and the Gleason score. MRI before prostate biopsy was performed in 35 patients who underwent LRP for clinically localized prostate cancer. A single radiologist retrospectively assessed whether the tumor localization, capsular penetration, seminal vesicle invasion, NVB involvement, and MRI findings correlated with the postoperative histological results. With the postoperative specimens, 83 lesions demonstrated a Gleason score of 6 or more. Using T2WI with and without DWI and ADC, 39 and 27 of 54 lesions were correctly identified, respectively, the difference being significant. For cancers in the transitional zone, using a threshold Gleason score of 3 or greater, sensitivity was also significantly higher for T2+DWI+ADC than for T2WI alone. Of 35 patients, using all available clinical information (biopsy results including Gleason score, tumor location, percentage of positive biopsy cores, and the percentage of tumor-involved core tissue), we found that the preoperative and postoperative staging were concordant in 25 cases. There is no universal consensus for nerve-sparing LRP; therefore, we performed an additional analysis using simplified clinically defined selection criteria (PSA level >15ng/mL, cT2, less than two positive biopsy scores in the unilateral lobe and less than 30% tumor volume, and a Gleason score of 6). Using this criteria, we selected 12 of 35 patients, and the detection rate of NVB involvement by MRI combined T2WI + DWI + ADC maps was 100% in their 30 lesions, and therefore we consider it safe to perform nerve-sparing LRP using our criteria. Our findings suggest that NVB can be safely preserved in patients with low-grade tumors using simplified clinically defined selection criteria to determine margin involvement.
  • Implications of Greater Short-term PSA Recurrence with Laparoscopic as Compared to Retropubic Radical Prostatectomy for Japanese Clinically localized Prostate Carcinomas, Hidetoshi Akita, Takehiko Okamura, Ryosuke Ando, Daisuke Nagata, Hiromichi Naruyama, Yasuyuki Yamada, Taku Naiki, Takahiro Yasui, Keiichi Tozawa, Kenjiro Kohri, ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 12, (11) 2959 - 2961,   2011年, 査読有り, Purpose: There is ongoing discussion as to the necessity for certain surgical procedures being limited to high through-put institutions. To cast light on this question regarding use of open as compared to laparoscopic radical prostatectomy (LRP) the present study was conducted focusing on biochemical (PSA) recurrence-free survival of Japanese patients with clinically localized prostate carcinomas. Materials and Methods: From April 2004 to December 2010 we identified 579 patients undergoing LRP (n=245) and retropubic radical prostatectomy (RRP) (n=334) who did not undergo immediate adjuvant therapy (radiation and/or hormonal) and whose PSA levels were lower than 25 ng/ml. Preoperative prostate specific antigen (PSA) level, clinical stage, biopsy Gleason score and pathological features were assessed and Kaplan-Meier estimates of biochemical recurrence (BCR)-free survival were compared. A Cox regression model analysis was performed to determine predictors of biochemical recurrence. Results: Median follow up was 35 months(2- 115). On univariate analysis the LRP group had a slightly lower pathological T stage (p<0.001), higher biopsy Gleason score (p<0.001), but much more organ confined disease (p=0.001) than the RRP group. BCR-free survival did not significantly differ between LRP and RRP groups with preoperative PSA <6, clinical stage T1c, T2a, pathological stage T3 or more, biopsy Gleason score of 8 or more, pathological Gleason score of 6 or less and 8 or more, extra-capsular extension and negative surgical margin. The 3-year BCR-free survival rates were 91.0%(RRP) and 82.2%(LRP) (p<0.001). Conclusion: We conclude that in general LRP may be associated with a less positive outcome than BCR for resection of low risk prostate cancers. Therefore indications for LRP should be very carefully monitored.
  • Evaluation of the Outcome of Laparoscopic Radical Prostatectomy by a Single Surgeon: Experience with an Initial 30 Cases, Hidetoshi Akita, Takehiko Okamura, Taku Naiki, Daisuke Nagata, Keiichi Tozawa, Kenjiro Kohri, Journal of Rural Medicine, 5, (1) 134 - 139,   2010年, 査読有り, Hidetoshi Akita, Takehiko Okamura, Taku Naiki, Daisuke Nagata, Keiichi Tozawa, Kenjiro Kohri, 2010, 'Evaluation of the Outcome of Laparoscopic Radical Prostatectomy by a Single Surgeon: Experience with an Initial 30 Cases', <i>Journal of Rural Medicine</i>, vol. 5, no. 1, pp. 134-139
  • Risk Factors for Surgical Site Infection (SSI) after Urological Surgery: Incisional and Deep-organ/space Experience at Anjo Hospital, Jun Sawai, Takehiko Okamura, Taku Naiki, Yasuhiro Hijikata, Hideyuki Oe, Masashi Sawa, Miyuki Hyodo, Rie Inatomi, Masami Okudaira, Atsushi Naito, Kazuhisa Inuzuka, Journal of Rural Medicine, 4, (2) 59 - 63,   2009年, 査読有り, Jun Sawai, Takehiko Okamura, Taku Naiki, Yasuhiro Hijikata, Hideyuki Oe, Masashi Sawa, Miyuki Hyodo, Rie Inatomi, Masami Okudaira, Atsushi Naito, Kazuhisa Inuzuka, 2009, 'Risk Factors for Surgical Site Infection (SSI) after Urological Surgery: Incisional and Deep-organ/space Experience at Anjo Hospital', <i>Journal of Rural Medicine</i>, vol. 4, no. 2, pp. 59-63
  • Advantages of second line estramustine for overall survival of hormone-refractory prostate cancer (HRPC) patients, Naiki T, Okamura T, Kawai N, Sakagami H, Yamada Y, Fujita K, Akita H, Hashimoto Y, Tozawa K, Kohri K, Asian Pacific Journal of Cancer Prevention, 10, (1) 71 - 74,   2009年, 査読有り
  • Carcinosarcoma of the Urinary Bladder with Rapid Growth: A Case Report, Taku Naiki, Noriyasu Kawai, Daisuke Nagata, Yutaka Andoh, Hideyuki Kamisawa, Toshiki Katoh, Hidetoshi Akita, Takehiko Okamura, Journal of Rural Medicine, 4, (1) 27 - 31,   2009年, 査読有り, Taku Naiki, Noriyasu Kawai, Daisuke Nagata, Yutaka Andoh, Hideyuki Kamisawa, Toshiki Katoh, Hidetoshi Akita, Takehiko Okamura, 2009, 'Carcinosarcoma of the Urinary Bladder with Rapid Growth: A Case Report', <i>Journal of Rural Medicine</i>, vol. 4, no. 1, pp. 27-31
  • Severe Hemolytic Uremic Syndrome Associated with Cisplatin-based Chemotherapy for Advanced Bladder Cancer, Taku Naiki, Satoshi Ishikawa, Hideyuki Kamisawa, Toshiki Kato, Hidetoshi Akita, Takehiko Okamura, Journal of Rural Medicine, 3, (2) 37 - 40,   2008年, 査読有り, Taku Naiki, Satoshi Ishikawa, Hideyuki Kamisawa, Toshiki Kato, Hidetoshi Akita, Takehiko Okamura, 2008, 'Severe Hemolytic Uremic Syndrome Associated with Cisplatin-based Chemotherapy for Advanced Bladder Cancer', <i>Journal of Rural Medicine</i>, vol. 3, no. 2, pp. 37-40
  • HEAT THERAPY WITH CATIONIC LIPOSOME MIGHT SUPPRESS THE PROLIFERATION OF PROSTATE CANCER IN BONE MICROENVIRONMENT VIA THE REDUCTION OF TGF-β LEVEL IN BONE MICROENVIRONMENT, Noriyasu Kawai, Mitsuru Futakuchi, Taku Naiki, Yoshihiro Hashimoto, Keiichi Tozawa, Kenjiro Kohri, The Journal of Urology, 179, (4) 420 - 421,   2008年, 査読有り, Noriyasu Kawai, Mitsuru Futakuchi, Taku Naiki, Yoshihiro Hashimoto, Keiichi Tozawa, Kenjiro Kohri, 2008, 'HEAT THERAPY WITH CATIONIC LIPOSOME MIGHT SUPPRESS THE PROLIFERATION OF PROSTATE CANCER IN BONE MICROENVIRONMENT VIA THE REDUCTION OF TGF-β LEVEL IN BONE MICROENVIRONMENT', <i>The Journal of Urology</i>, vol. 179, no. 4, pp. 420-421
  • Congenital narrowing of the bulbar urethra with enuresis, Naiki T, Kojima Y, Hayase M, Maruyama T, Hayashi Y, Kohri K, Japanese Journal of Clinical Urology, 59, (10) 775 - 778,   2005年, 査読有り

MISC

  • Early abiraterone acetate treatment is beneficial in Japanese castration-resistant prostate cancer after failure of primary combined androgen blockade, Takashi Nagai, Takashi Nagai, Taku Naiki, Keitaro Iida, Toshiki Etani, Ryosuke Ando, Shuzo Hamamoto, Yosuke Sugiyama, Hidetoshi Akita, Hiroki Kubota, Yoshihiro Hashimoto, Noriyasu Kawai, Takahiro Yasui, Prostate International,   2017年01月01日, © 2017. Background: Development of novel agents targeting the androgen axis has led to improved overall survival in castration-resistant prostate cancer (CRPC). This study aimed to investigate the optimal timing of treatment with one such agent, abiraterone acetate (AA), in Japanese patients. Materials and methods: Between July 2014 and February 2016, 106 CRPC patients were administered AA in Nagoya City University Hospital, Nagoya, Japan and in four affiliated hospitals following failure of primary combined androgen blockade (CAB). Of these, records of 69 patients treated before chemotherapy were retrospectively analyzed. Patients were divided into two AA treatment groups: (1) first- or second-line after diagnosis of CRPC, designated the Early Group, and (2) third-line onwards, designated the Deferred Group. Prostate-specific antigen (PSA) response rate, ≥ 50% PSA decline rate with treatment, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 was used to classify adverse events. Results: In 24 patients in the Early Group and 45 patients in the Deferred Group, no significant differences in baseline parameters were observed between groups. PSA response rate, ≥ 50% PSA decline rate and PFS (but not OS) were significantly better in the Early Group than in the Deferred Group. Serum aspartate aminotransferase/alanine aminotransferase elevations were the most common Grade 3 treatment-related toxicities, and were clinically manageable. In subgroup analyses of the Early Group, comparison of first-line AA with second-line AA after flutamide treatment showed no changes in PSA response rate, PFS, or OS. Conclusion: This study suggests improved favorable outcomes of first- or second-line AA treatment in Japanese chemotherapy-naïve CRPC patients after failed CAB; statistical confirmation of such improvement was evident for PFS, but not OS. In addition, early AA treatment exhibited an acceptable safety profile.
  • Hemiscrotal agenesis: Pathogenesis and management strategies, Hidenori Nishio, Kentaro Mizuno, Yoshinobu Moritoki, Hideyuki Kamisawa, Taku Naiki, Satoshi Kurokawa, Akihiro Nakane, Atsushi Okada, Takahiro Yasui, Yutaro Hayashi, INTERNATIONAL JOURNAL OF UROLOGY, 23, (6) 523 - 526,   2016年06月, Hemiscrotal agenesis is among the rarest anomalies in scrotal development disorders. As it has only been reported in three cases, the clinical manifestations remain unclear. We report a case of hemiscrotal agenesis with ipsilateral cryptorchidism. Based on the thermal assessment of the scrotum, concurrent scrotoplasty and orchiopexy were carried out, and the scrotoplasty improved the thermal environment of the fixed left testis. Furthermore, the low expression of androgen receptor and steroid-5-alpha-reductase, alpha polypeptide 2 in the affected side of the scrotum likely resulted in the characteristics of absent scrotal rugae, and pigmentation on histological and biological analyses. For future fertility, we believe that scrotoplasty should be considered as a management option for hemiscrotal agenesis.
  • Nonpalpable testicular pure seminoma with elevated serum alpha-fetoprotein presenting with retroperitoneal metastasis: A case report, Shoichiro Iwatsuki, Taku Naiki, Noriyasu Kawai, Toshiki Etani, Keitaro Iida, Ryosuke Ando, Takashi Nagai, Atsushi Okada, Keiichi Tozawa, Yosuke Sugiyama, Takahiro Yasui, Journal of Medical Case Reports, 10,   2016年05月05日, © 2016 Iwatsuki et al. Background: Patients with a primary pure seminoma in the testis who have elevated serum alpha-fetoprotein are rare and should be treated as patients with nonseminomatous germ cell tumors. However, nonpalpable testicular tumors in this condition have never been reported. We describe a case of nonpalpable pure testicular seminoma with elevated serum alpha-fetoprotein presenting retroperitoneal metastasis. Case presentation: A 29-year-old Asian man was referred to our hospital with right flank pain. Computed tomography showed a mass located between his aorta and inferior vena cava, but a testicular tumor was not detected. His serum levels of lactate dehydrogenase, alpha-fetoprotein, and DUPAN-2 were high. Although no tumor or nodule was palpable in his testis, ultrasonography revealed multiple low echoic lesions in his right testicular parenchyma. He was diagnosed with right testicular cancer with retroperitoneal lymph node metastasis and underwent right high orchiectomy. A pathological examination revealed pure seminoma and no nonseminomatous components were found in the specimen. Three courses of induction systemic chemotherapy (cisplatin, etoposide, and bleomycin) normalized his serum alpha-fetoprotein and DUPAN-2 levels. Three additional courses of chemotherapy (etoposide and bleomycin) were performed, and treatment was completed with laparoscopic retroperitoneal lymph node dissection. Pathology of the dissected specimen showed fibrous and necrotic tissue with no viable cells. He is alive without recurrence 54 months after orchiectomy. Conclusions: We report a case of pure testicular seminoma with elevated serum alpha-fetoprotein and DUPAN-2 presenting retroperitoneal metastasis. We recommend an ultrasound examination of bilateral testes when large retroperitoneal tumors are detected in young men, even if a mass is not palpable in the scrotum.
  • Bacillus Calmette-Guerin therapy after the second transurethral resection significantly decreases recurrence in patients with new onset high-grade T1 bladder cancer, Keitaro Iida, Taku Naiki, Noriyasu Kawai, Toshiki Etani, Ryosuke Ando, Yosuke Ikegami, Takehiko Okamura, Hiroki Kubota, Atsushi Okada, Kenjiro Kohri, Takahiro Yasui, BMC UROLOGY, 16,   2016年02月, Background: The purpose of this study was to assess the efficacy of Bacillus Calmette-Guerin (BCG) therapy after a second transurethral resection (TUR) in new onset high-grade T1 bladder cancer. Methods: From January 2008 to September 2013, 207 patients with new onset high-grade T1 bladder cancer after an initial TUR were treated at our university and at affiliated hospitals. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors for intravesical recurrence were analyzed. Results: Among a total of 207 patients, 42 patients were treated with BCG therapy following a second TUR (group 1), 23 were treated with second TUR alone (group 2), 72 were treated with BCG alone (group 3), and 70 were treated without a second TUR or BCG. The median patients' age was 72.0 years, and the median follow-up period was 33.5 months. The second TUR revealed that 34 patients (52 %) had residual cancer. Between groups 1 and 2 and groups 1 and 3, the differences in RFS were statistically significant (p = 0.002 and 0.045, respectively). In addition, BCG therapy was the most significant factor to predict RFS after the second TUR. Among the 31 patients whose pathology of the second TUR was pT0, only 1 of 12 patients (8 %) in group 1 and 11 of 19 patients (58 %) in group 2 had a recurrence. Conclusions: BCG instillation following a second TUR decreases intravesical recurrence, even if the pathology of the second TUR is pT0.
  • Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder, Takashi Nagai, Taku Naiki, Noriyasu Kawai, Keitaro Iida, Toshiki Etani, Ryosuke Ando, Shuzo Hamamoto, Yosuke Sugiyama, Atsushi Okada, Kentaro Mizuno, Yukihiro Umemoto, Takahiro Yasui, Case Reports in Oncology, 9,   2016年01月01日, © 2016 The Author(s). Published by S. Karger AG, Basel. Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB) is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC) values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB.
  • Connexin 32 dysfunction promotes ethanol-related hepatocarcinogenesis via activation of Dusp1-Erk axis, Kato, H., Naiki-Ito, A., Naiki, T., Suzuki, S., Yamashita, Y., Sato, S., Sagawa, H., Kato, A., Kuno, T., Takahashi, S., Oncotarget, 7, (2) 2009 - 2021,   2016年, There is abundant epidemiological evidence that heavy alcohol intake contributes to hepatocellular carcinoma (HCC) development. Previous reports indicated that connexin 32 (Cx32), which is a major hepatocyte gap junction protein, is downregulated in chronic liver disease and has a protective role in hepatocarcinogenesis. However, functions of Cx32 in alcohol-related hepatocarcinogenesis have not been clarified. To evaluate them, 9-week-old Cx32 dominant negative transgenic (Tg) rats and their wild-type (Wt) littermates were given 1 % or 5 % ethanol (EtOH) or water ad libitum, for 16 weeks after an intraperitoneal injection of diethylnitrosamine (200 mg/kg). EtOH significantly increased the incidence and multiplicity of HCC and total tumors in a dose-dependent manner in Tg rats, but not in Wt rats. Although the number and area of glutathione S-transferase placental form (GST-P) positive foci were not significantly different between the groups, EtOH increased the Ki-67 labeling indices in GST-P positive foci only in Tg rats. EtOH up-regulated phosphorylated Erk1/2 with decrease of the Erk1/2 inhibitor, dual specificity protein phosphatase 1 (Dusp1) in whole livers of Tg and Wt rats. Immunofluorescence staining and quantitative RT-PCR revealed that EtOH significantly increased nucleolar localization of phosphorylated Erk1/2 and contrastingly reduced Dusp1 protein and mRNA expression in GST-P positive foci and HCC of Tg rats as compared to those of Wt rats. These findings suggest that Cx32 dysfunction like in chronic liver disease promoted EtOH-associated hepatocarcinogenesis through dysregulation of Erk-Dusp1 signaling.
  • Connexin 32 and luteolin play protective roles in non-alcoholic steatohepatitis development and its related hepatocarcinogenesis in rats., Sagawa H, Naiki-Ito A, Kato H, Naiki T, Yamashita Y, Suzuki S, Sato S, Shiomi K, Kato A, Kuno T, Matsuo Y, Kimura M, Takeyama H, Takahashi S, Carcinogenesis, 36,   2015年12月, © The Author 2015. Non-alcoholic steatohepatitis (NASH) has the potential to lead to the development of cirrhosis and hepatocellular carcinoma (HCC). Connexin (Cx) 32, a hepatocyte gap-junction protein, plays a preventive role in hepatocarcinogenesis. However, the precise contribution of Cx32 in the development of NASH has not been established. In this study, we aimed to clarify the role of Cx32 and the chemopreventive effect of luteolin, an antioxidant flavonoid, on the progression of NASH and NASH-related hepatocarcinogenesis. Cx32 dominant negative transgenic (Cx32ΔTg) and wild-type (Wt) rats at 10 weeks of age were given diethylnitrosamine and fed methionine-choline-deficient diet (MCDD) or MCDD with luteolin for 12 weeks. MCDD induced steatohepatitis and fibrosis along with increased inflammatory cytokine expression and reactive oxygen species in the liver. These effects were more severe in Cx32ΔTg rats as compared with Wt rats, and significantly suppressed by luteolin in both genotypes. Concerning NASH-related hepatocarcinogenesis, the number of glutathione S-transferase placental form (GST-P)-positive foci was greater in Cx32ΔTg versus Wt rats, and significantly reduced by luteolin in Cx32ΔTg rats. Microarray analysis identified brain expressed, X-linked 1 (Bex1) as an upregulated gene in Cx32ΔTg rat liver. Quantitative RT-PCR and in situ hybridization revealed that increased Bex1 mRNA was localized in GST-P-positive foci in Cx32ΔTg rats, and the expression level was significantly decreased by luteolin. Moreover, Bex1 knockdown resulted in significant growth inhibition of the rat HCC cell lines. These results show that Cx32 and luteolin have suppressive roles in inflammation, fibrosis and hepatocarcinogenesis during NASH progression, suggesting a potential therapeutic application for NASH.
  • NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect., Etani T, Suzuki T, Naiki T, Naiki-Ito A, Ando R, Iida K, Kawai N, Tozawa K, Miyata N, Kohri K, Takahashi S, Oncotarget, 6,   2015年02月, Herein, we investigated therapeutic potential of a novel histone lysine demethylase 1 (LSD1) inhibitor, NCL1, in prostate cancer. Hormone-sensitive prostate cancer cells, (LNCaP) and castration resistant cancer cells (PC3 and PCai1) were treated with NCL1, and LSD1 expression and cell viability were assessed. Prostate cancer cells showed strong LSD1 expression, and cell viability was decreased by NCL1. ChIP analysis showed that NCL1 induced H3K9me2 accumulation at the promoters of androgen-responsive genes. NCL1 also induced G1 cell cycle arrest and apoptosis. In addition, autophagosomes and autolysosomes were induced by NCL1 treatment in LNCaP. Furthermore, LC3-II expression was significantly increased by NCL1 and chloroquine. In mice injected subcutaneously with PCai1 and intraperitoneally with NCL1, tumor volume was reduced with no adverse effects in NCL1-treated mice. Finally, LSD1 expression in human cancer specimens was significantly higher than that in normal prostate glands. In conclusion, NCL1 effectively suppressed prostate cancer growth without adverse events. We suggest that NCL1 is a potential therapeutic agent for hormone-resistant prostate cancer.
  • Proinflammatory and metabolic changes facilitate renal crystal deposition in an obese mouse model of metabolic syndrome, Kazumi Taguchi, Atsushi Okada, Shuzo Hamamoto, Shoichiro Iwatsuki, Taku Naiki, Ryosuke Ando, Kentaro Mizuno, Keiichi Tozawa, Kenjiro Kohri, Takahiro Yasui, Journal of Urology, 194,   2015年01月01日, © 2015 American Urological Association Education and Research, Inc. Purpose To clarify metabolic syndrome induced stone formation mechanisms we investigated the metabolic and immunohistochemical characteristics associated with renal crystal deposition using a model of mice with metabolic syndrome administered a high fat diet and ethylene glycol. Materials and Methods Ob/Ob mice with Leptin gene deficiencies and metabolic syndrome related characteristics were compared with wild heterozygous lean mice. Four study groups were fed standard food and water (control group), a high fat diet and normal water (high fat diet group), 1% ethylene glycol and standard food (ethylene glycol group) or a high fat diet and 1% ethylene glycol (high fat diet plus ethylene glycol group). Blood, urine and kidney samples were taken after 14 days. Results Ob/Ob mice in the high fat diet plus ethylene glycol group showed diffuse renal crystal depositions. Lean and Ob/Ob mice in the high fat diet plus ethylene glycol group showed significant excretion of urinary calcium oxalate crystals. Ob/Ob mice had significant hypercalciuria, hyperphosphaturia and hyperlipidemia, massive lipid fragments in tubular lumina and fat droplets in renal tubular cells. Ob/Ob mice in the high fat diet plus ethylene glycol group had markedly increased expression of osteopontin, monocyte chemoattractant protein-1, interleukin-6 and tumor necrosis factor-α. In Ob/Ob mice the number of proinflammatory macrophages was considerably elevated. Conclusions We induced renal crystal deposition in mice with metabolic syndrome using a high fat diet and ethylene glycol. Increases in luminal mineral and lipid density, and proinflammatory adipocytokines and macrophages facilitated renal crystal formation in mice with metabolic syndrome.
  • A Case of Renal Primitive Neuroectodermal Tumor Confirmed by Fluorescence in situ Hybridization., Etani T, Naiki T, Ando R, Iida K, Naiki-Ito A, Takahashi S, Kobayashi D, Kawai N, Tozawa K, Yasui T, Kohri K, Case Reports in Oncology, 8,   2015年, © 2015 S. Karger AG, Basel. Primitive neuroectodermal tumor (PNET) is a member of the Ewing's sarcoma family of tumors (ESFT). We report a case of PNET in a 66-year-old male who presented with a large solid tumor within the parenchyma of the middle pole of the left kidney with metastases to the left adrenal gland and right ischium. A fine-needle biopsy was performed and showed a small round cell tumor. Results of immunohistochemical staining suggested this tumor belonged to ESFT. Preoperative VDC-IE (combined vincristine, doxorubicin and cyclophosphamide followed by another combination of ifosfamide and etoposide) chemotherapy and left radical nephrectomy and adrenalectomy were performed. The histopathological findings of the resected tumor were similar to those in the biopsy specimen, but the results of AE1/AE3 were different. For the diagnosis, fluorescence in situ hybridization was performed. Split signals of the EWSR1 gene were detected, and transmission electron microscopy showed neuroendocrine granules and microtubules. The final diagnosis of this tumor was PNET of the kidney.
  • Laparoscopic versus open radical cystectomy for patients older than 75 years: A single-center comparative analysis, Takahiro Yasui, Keiichi Tozawa, Ryosuke Ando, Takashi Hamakawa, Shoichiro Iwatsuki, Kazumi Taguchi, Daichi Kobayashi, Taku Naiki, Kentaro Mizuno, Atsushi Okada, Yukihiro Umemoto, Noriyasu Kawai, Shoichi Sasaki, Yutaro Hayashi, Kenjiro Kohri, Asian Pacific Journal of Cancer Prevention, 16,   2015年01月01日, Background: To explore the safety, efficacy, and oncological outcome of 3-port laparoscopic radical cystectomy (LRC) compared to open radical cystectomy (ORC) in patients older than 75 years. Materials and Methods: From June 2010 to July 2014, we analyzed 16 radical cystectomies in patients older than 75 years (LRC group=8; ORC group=8). Demographic parameters, operative variables, and perioperative outcome in the 2 groups were retrospectively collected, analyzed, and compared. Results: Patients in both groups had comparable preoperative characteristics. A significantly longer operating time (476 vs. 303 min, P=0.0002) and less estimated blood loss (627 vs. 2,106 mL, P=0.021) were observed in the LRC group compared to the ORC group. Infection and ileus were the most common early complications after surgery. Patients who underwent ORC suffered from more postoperative infection (22.2% vs. 0.0%, P=0.054) and ileus (25.0% vs. 12.5%, P=0.521) than the LRC group, but the difference was not significant. Conclusions: Judging from this initial trial, 3-port LRC can be safely carried out in elderly patients. We suggest 3-port LRC as the primary intervention to treat muscle-invasive or high-risk nonmuscle-invasive bladder cancer in elderly patients with an otherwise relatively long life expectancy.
  • MRI findings of inverted urothelial papilloma of the bladder, Mitsuru Takeuchi, Kohei Sasaguri, Taku Naiki, Akihito Mitsumori, Hirotoshi Ito, Junko Takahama, Kaori Yamada, Nagaaki Marugami, Takahiro Tsuboyama, Yoshihiro Okumura, Yoshimitstu Ohgiya, Noriyasu Kawai, Kenjiro Kohri, Yuta Shibamoto, American Journal of Roentgenology, 205,   2015年01月01日, © American Roentgen Ray Society. OBJECTIVE. The objective of this study was to characterize MRI findings of inverted urothelial papilloma of the bladder. MATERIALS AND METHODS. Data pertaining to 16 patients with 18 pathologically proven inverted urothelial papillomas of the bladder who had undergone MRI were retrospectively collected from seven institutions. The shape and surface characteristics of the tumors were evaluated using T2-weighted MR images. In addition, the signal intensity of inverted urothelial papillomas was visually assessed on T1-weighted, T2-weighted, and DW images and on early and delayed phase contrast-enhanced images. RESULTS. The shape of the 18 inverted urothelial papillomas of the bladder was classified as polypoid with a stalk for 16 tumors (89%) and polypoid without a stalk for two tumors (11%). All stalks were surrounded by urine in the bladder. A total of 15 of the tumor surfaces (83%) were nonpapillary and three (17%) were papillary. All 12 of the inverted urothelial papillomas for which evaluable T1-weighted images were available were isointense with the bladder wall. The lesions had a slightly higher signal intensity than the bladder wall in 15 of the patients (83%) and showed isointensity with the bladder wall in three patients (17%). A total of three patients (17%) had tiny hyperintense foci noted on T2-weighted images. All 16 of the inverted urothelial papillomas examined by DWI had very high signal intensity. All 13 of the lesions for which early phase images were obtained using dynamic contrast-enhanced MRI showed strong enhancement. When compared with early phase images, delayed phase images of the same 13 lesions showed that enhancement was stronger in two lesions (15%), similar in six lesions (46%), and weaker in five lesions (38%). CONCLUSION. On MRI, the typical appearance of inverted urothelial papillomas of the bladder is a polypoid shape with a nonpapillary surface and a thin short stalk surrounded by urine. Cystic foci are also occasionally seen within the tumor.
  • MRI for differentiation of renal cell carcinoma with sarcomatoid component from other renal tumor types, Mitsuru Takeuchi, Tatsuya Kawai, Tomohiro Suzuki, Taku Naiki, Noriyasu Kawai, Yukio Fujiyoshi, Hiroshi Inagaki, Kenjiro Kohri, Masaki Hara, Yuta Shibamoto, Abdominal Imaging, 40,   2015年01月01日, © 2014, Springer Science+Business Media New York. Purpose: To investigate the usefulness of MRI for detection of sarcomatoid renal cell carcinoma (SRCC) components within RCC and differentiation from other renal tumors. Methods: Two observers independently interpreted T2-weighted images of 10 patients with pathologically confirmed RCCs with SRCC and 131 with non-SRCC renal tumors, with special reference to conspicuously low signal intensity (SI) areas (T2LIA) compared to the renal cortex. SRCC probability was classified as (1) definitely non-SRCC, no T2LIA; (2) probably non-SRCC, < 1 cm T2LIA; (3) low probability of SRCC, homogeneous tumor with 1–3 cm T2LIA; (4) probably SRCC, heterogeneous tumor with 1–3 cm T2LIA; and (5) definitely SRCC, > 3 cm T2LIA, multiple > 1 cm T2LIAs, or showing disruption of the pseudocapsule. The observers used chemical shift imaging to exclude the area representing hemorrhage or hemosiderin deposition from T2LIA. Scores of 4/5 were regarded as positive for evaluating the accuracy and area under the receiver operating characteristic curve. The SI ratio of the lowest SI in the tumor to that of the renal cortex in the 1 and ≥2 score groups was compared using Mann-Whitney’s U test. Results: Sensitivity, specificity, accuracy, and positive and negative predictive values were 90%, 95%, 94%, 56%, and 99%, respectively, and area under the receiver operating characteristic curve was 0.93. The mean SI ratio of the lowest SI in the tumor to that of the renal cortex was significantly lower in the ≥2 score group (0.58) than in the 1 score group (1.36). Conclusions: MRI predicted RCC with SRCC with a moderate positive predictive value and a high negative predictive value.
  • GPX2 overexpression is involved in cell proliferation and prognosis of castration-resistant prostate cancer., Naiki T, Naiki-Ito A, Asamoto M, Kawai N, Tozawa K, Etani T, Sato S, Suzuki S, Shirai T, Kohri K, Takahashi S, Carcinogenesis, 35,   2014年09月, There is a need for exploration of new therapeutic strategies that target distinct molecular mechanisms of castration-resistant prostate cancer (CRPC) because its emergence following androgen deprivation therapy is a major clinical problem. In this report, we investigated the role of glutathione peroxidase 2 (GPX2) in CRPC. GPX2 expression was analyzed in rat and human CRPC cells. Next, we determined the proliferation rate and level of reactive oxygen species (ROS) in GPX2-small interfering RNA (siRNA)-transfected CRPC cells. For in vivo analysis, siRNA-transfected cells were subcutaneously implanted into normal and castrated nude mice. Further, immunohistochemical and prognostic analyses of GPX2 were performed using human specimens. Silencing of GPX2 caused significant growth inhibition and increased intracellular ROS in both rat (PCai1) and human (PC3) CRPC cells. Flow cytometry and western blot analyses revealed that the decrease in proliferation rate of the GPX2-silenced cells was due to cyclin B1-dependent G 2 /M arrest. Furthermore, knockdown of Gpx2 inhibited tumor growth of PCai1 cells in castrated mice. Immunohistochemical analyses indicated that expression of GPX2 was significantly higher in residual cancer foci after neoadjuvant hormonal therapy than in hormone naive cancer foci. Moreover, patients with high GPX2 expression in biopsy specimen had significantly lower prostate-specific antigen recurrence-free survival and overall survival than those with no GPX2 expression. These findings suggest that GPX2 is a prognostic marker in CRPC and affects proliferation of prostate cancer under androgen depletion partially through protection against ROS signaling. © The Author 2014. Published by Oxford University Press. All rights reserved.
  • Colony-Stimulating Factor-1 Signaling Suppresses Renal Crystal Formation, Kazumi Taguchi, Atsushi Okada, Hiroshi Kitamura, Takahiro Yasui, Taku Naiki, Shuzo Hamamoto, Ryosuke Ando, Kentaro Mizuno, Noriyasu Kawai, Keiichi Tozawa, Kenichi Asano, Masato Tanaka, Ichiro Miyoshi, Kenjiro Kohri, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 25, (8) 1680 - 1697,   2014年08月, We recently reported evidence suggesting that migrating macrophages (M phi s) eliminate renal crystals in hyperoxaluric mice. M phi s can be inflammatory (M1) or anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates polarization to the M2M phi phenotype. M2M phi s promote renal tissue repair and regeneration, but it is not clear whether these cells are involved in suppressing renal crystal formation. We investigated the role of M2M phi s in renal crystal formation during hyperoxaluria using CSF-1-deficient mice, which lack M2M phi s. Compared with wild-type mice, CSF-1-deficient mice had significantly higher amounts of renal calcium oxalate crystal deposition. Treatment with recombinant human CSF-1 increased the expression of M2-related genes and markedly decreased the number of renal crystals in both CSF-1-deficient and wild-type mice. Flow cytometry of sorted renal M phi s showed that CSF-1 deficiency resulted in a smaller population of CD11b(+)F4/80(+)CD163(+)CD206(hi) cells, which represent M2-like M phi s. Additionally, transfusion of M2M phi s into CSF-1 deficient mice suppressed renal crystal deposition. In vitro phagocytosis assays with calcium oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2-polarized M phi s than M1-polarized M phi s or renal tubular cells. Gene array profiling showed that CSF-1 deficiency resulted in disordered M2- and stone-related gene expressions. Collectively, our results provide compelling evidence for a suppressive role of CSF-1 signaling in renal crystal formation.
  • Gemcitabine and docetaxel, an effective second-line chemotherapy for lung metastasis of urothelial carcinoma, Taku Naiki, Noriyasu Kawai, Yoshihiro Hashimoto, Takehiko Okamura, Ryosuke Ando, Takahiro Yasui, Atsushi Okada, Toshiki Etani, Keiichi Tozawa, Kenjiro Kohri, INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 19, (3) 516 - 522,   2014年06月, The objective of this study was to evaluate the efficacy of a gemcitabine and docetaxel (GD) combination as a second-line treatment for patients with metastatic urothelial carcinoma (UC) after failure of first-line treatment with platinum-based chemotherapy. From June 2006 to January 2012, 38 patients with metastatic UC previously treated with platinum-based chemotherapy received GD therapy. This consisted of gemcitabine 800 mg/m(2) and docetaxel 40 mg/m(2) on days 1 and 8 of each 21-day cycle as second-line chemotherapy. All the patients were evaluated for toxicity and assessed every cycle by imaging. We analyzed the efficacy of GD as second-line chemotherapy in the follow-up study. The median number of GD treatment cycles was 4 (range 2-9); the objective response rate was 47.4 %; and the median progression-free survival and median overall survival were 4.1 and 10.8 months, respectively. Univariate and multivariate analyses on the GD treated group showed that the existence of lung metastases was the only prognostic factor for tumor response. Grade 3 treatment-related toxicity included neutropenia (31.6 %) and thrombocytopenia (15.8 %), and only one patient with grade 4 toxicity had thrombocytopenia (2.6 %). The GD regimen as second-line chemotherapy was especially effective for lung metastatic UC and yielded favorable results in patients whose first-line platinum-based chemotherapy had failed. Given the safety and benefit profile seen in this study, a large prospective study is warranted to consider the potential utility of GD chemotherapy as a second-line for UC.
  • Curcumin-loaded PLGA Nanoparticles Conjugated with Anti-P-glycoprotein Antibody to Overcome Multidrug Resistance, Wanisa Punfa, Shugo Suzuki, Pornsiri Pitchakarn, Supachai Yodkeeree, Taku Naiki, Satoru Takahashi, Pornngarm Limtrakul, ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 15, (21) 9249 - 9258,   2014年, Background: The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur-NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrug-resistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo. Materials and Methods: First, we determined the MDR-reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions. Results: The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions. Conclusions: Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.
  • Metastasectomy as optimal treatment for late relapsing solitary brain metastasis from testicular germ cell tumor: A case report, Keitaro Iida, Taku Naiki, Noriyasu Kawai, Ryosuke Ando, Toshiki Etani, Keiichi Tozawa, Kenjiro Kohr, BMC Research Notes, 7,   2014年01月01日, © 2014 Iida et al. Background: Management of late relapse of a testicular germ cell tumor is difficult because few cases have been reported and the tumors are intractable to chemotherapy. Here we present a case with a single brain metastasis from late relapse of a testicular germ cell tumor. This is the first report of a brain metastasis that was treated successfully only by surgery. Case presentation: A 19-year-old Japanese man presented with breathing difficulties and left testis enlargement and he was diagnosed with a yolk sac tumor following a left orchiectomy. At the time of diagnosis, multiple lung metastases were apparent on computed tomography, and serum alpha-fetoprotein level was elevated to 10,245 ng/ml. The patient received three postoperative courses of bleomycin, etoposide and cisplatin and etoposide and cisplatin respectively and a complete response was obtained. Four years after surgery, the patient was admitted to the hospital due to a sudden seizure. High alpha-fetoprotein levels (539 ng/ml) were evident and magnetic resonance imaging suggested a 45-mm single brain tumor in the right parietal lobe, for which surgery was performed. The pathological diagnosis was yolk sac tumor. The alpha-fetoprotein level remained normal at 2 months after operation. There was no recurrence 24 months post-operation. Conclusion: Chemoresistance and late neurotoxicity are concerns in treating brain metastasis with chemotherapy or cerebral radiotherapy. Surgery is believed to be the optimal treatment choice if the size of the brain metastasis is larger than 35-mm and the late relapse area is surgically accessible.
  • MR Imaging of Urinary Bladder Cancer for T-Staging: A Review and a Pictorial Essay of Diffusion-Weighted Imaging, Mitsuru Takeuchi, Shigeru Sasaki, Taku Naiki, Noriyasu Kawai, Kenjiro Kohri, Masaki Hara, Yuta Shibamoto, JOURNAL OF MAGNETIC RESONANCE IMAGING, 38, (6) 1299 - 1309,   2013年12月, Treatment decisions for bladder cancer patients are mainly based on the depth of bladder wall invasion by the tumor. In this article, we review the conventional MRI and exhibit a recently emerged diffusion-weighted imaging (DWI) of urinary bladder cancer for T-staging. We discuss limitations of conventional MRI, scanning protocols of DWI, normal pelvic findings on DWI, determination of T-stage using DWI, and pitfalls of DWI. DWI provides high contrast between bladder cancer and background tissue because the cancer shows markedly high SI. DWI has high sensitivity for detecting the stalk seen in stage Ta or T1. An inflammatory change or fibrosis surrounding the tumor mimics the invasion of bladder cancer on T2-weighted imaging or enhanced MRI and could lead to over-staging, but DWI could differentiate them clearly because these benign changes do not show high SI on DWI. DWI is also useful for detecting ureteral, urethral, and prostatic extension by means of the urethra. DWI provides more accurate information on the extent of bladder cancer and contributes to determination of the treatment strategy.
  • Feasibility of a novel extraperitoneal two-port laparoendoscopic approach for radical prostatectomy: An initial study, Akihiro Nakane, Hidetoshi Akita, Takehiko Okamura, Ryosuke Ando, Takahiro Kobayashi, Taku Naiki, Takahiro Yasui, Kenjiro Kohri, International Journal of Urology, 20,   2013年07月01日, The aim of this study was to describe the surgical technique and to report the early outcomes of an original extraperitoneal two-port laparoendoscopic approach for radical prostatectomy. A total of 22 consecutive patients diagnosed with early-stage prostate cancer (cT1c, cT2N0) were operated on and included in this analysis. A multichannel port with three 5-mm trocars, providing easier instrument handling, was inserted extraperitoneally through a 2.5-cm lower umbilical "U" incision. An additional 12-mm port was inserted into the left fossa to allow an adequate working angle to facilitate the most critical steps of the surgical procedures. The operation was successfully completed in all patients; one patient required an additional 5-mm port to control bleeding. The median operation time was 259min (range 207-453min), and the fluid loss, including urine and blood, was 946mL (range 257-1821mL). The median Foley catheter indwelling period was 6days (range 3-11days) after surgery. No intraoperative complications occurred. Judging from this initial trial, this procedure can be safely carried out if the surgeon is familiar with conventional five-port laparoscopic radical prostatectomy. © 2012 The Japanese Urological Association.
  • MRI findings of granulomatous prostatitis developing after intravesical Bacillus Calmette-Guérin therapy, T. Suzuki, M. Takeuchi, T. Naiki, N. Kawai, K. Kohri, M. Hara, Y. Shibamoto, Clinical Radiology, 68, (6) 595 - 599,   2013年06月, Aim: To evaluate magnetic resonance imaging (MRI) findings of granulomatous prostatitis (GP) developing after intravesical Bacillus Calmette-Guérin (BCG) therapy. Materials and methods: Ten patients with pathologically proven GP underwent prostatic MRI. Lesion shape and signal intensity (SI) were evaluated on T2-weighted (T2WI), T1WI, and diffusion-weighted imaging (DWI). Results: Polygonal nodular lesions with notches, diffuse lesions, and cystic lesions with mural nodules were seen in two, six, and one patients, respectively. The remaining patient had a diffuse and cystic lesion. All diffuse lesions showed higher SI than muscle on T1WI and higher SI than the normal peripheral zone (PZ) on DWI. On T2WI, six of seven diffuse lesions showed a slightly lower SI than bone marrow and the remaining one lesion was iso-intense. All nodular lesions showed a low SI similar to muscle on T2WI and were iso-intense to muscle on T1WI. On DWI, two each of the four nodular lesions showed slightly lower SI and slightly higher SI than the normal PZ, respectively. All contents within the cyst and mural nodules showed markedly high and low SI on T2WI, respectively. On DWI, all fluids within cysts showed markedly high SI. One each of the mural nodules showed slightly higher SI and slightly lower SI than the normal PZ on DWI. Conclusion: Three main MRI patterns of GP were identified: diffuse, nodular, and cystic with mural nodule; among them, the diffuse type was the most common. Cystic lesions with mural nodules could accompany the lesion. © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
  • Thermotherapy using magnetic cationic liposomes powerfully suppresses prostate cancer bone metastasis in a novel rat model, Daichi Kobayashi, Noriyasu Kawai, Shinya Sato, Taku Naiki, Kenji Yamada, Takahiro Yasui, Keiichi Tozawa, Takeshi Kobayashi, Satoru Takahashi, Kenjiro Kohri, PROSTATE, 73, (9) 913 - 922,   2013年06月, BACKGROUND Bone metastasis is a serious problem for individuals with prostate cancer, and the effects of the anticancer drug docetaxel (DTX) are insufficient. We therefore examined the therapeutic potential of magnetic cationic liposomes (MCL) in a novel rat model that allows the evaluation of tumor immunity. The effects of MCL thermotherapy were compared with those of DTX as a conventional therapy for the treatment of bone metastatic prostate cancer. METHODS Prostate tumor tissues were transplanted into the femurs of model rats divided into four groups: control, MCL, DTX, and MCL+DTX. Tumors were injected with MCL, and alternating magnetic field (AMF) irradiation was performed three times a week. Tumor proliferation and bone destruction were evaluated by proliferating cell nuclear antigen positivity, computed tomography, and CD68-positive cell number, while tumor immunity was evaluated by heat shock protein (HSP) 70 expression and CD8-positive lymphocyte number. RESULTS We successfully established a novel femur metastasis model of prostate cancer, and demonstrated that tumor proliferation and bone destruction in the MCL and MCL+DTX groups were significantly suppressed compared with control and DTX groups. MCL thermotherapy concurrently induced necrosis and apoptosis. The expression of HSP70 in the MCL and MCL+DTX groups was also significantly increased, and tumor immunity was enhanced through the induction of CD8-positive lymphocytes. CONCLUSION MCL thermotherapy was clearly more effective than DTX in treating bone metastatic prostate cancer. A combination of MCL thermotherapy and DTX therefore deserves consideration as a novel treatment for this disease. Prostate 73: 913922, 2013. (c) 2013 Wiley Periodicals, Inc.
  • Neoadjuvant hormonal therapy is a feasible option in laparoscopic radical prostatectomy, Taku Naiki, Noriyasu Kawai, Takehiko Okamura, Daisuke Nagata, Yoshiyuki Kojima, Hidetoshi Akita, Takahiro Yasui, Keiichi Tozawa, Kenjiro Kohri, BMC UROLOGY, 12,   2012年12月, Background: Few reports can be found in the literature with respect to the impact of neoadjuvant hormonal therapy (NHT) on operative parameters on laparoscopic radical prostatectomy (LRP) in a large study. The aim of this study was to evaluate the safety and efficacy of NHT prior to LRP for locally confined prostate cancer. Methods: From January 2004 to September 2009, 342 patients undergoing LRP were analyzed, specifically comparing 72 patients who received NHT to 270 who did not. All patients were in clinical stage T2 and nerve sparing LRP were not included. Results: The mean patient age, preoperative prostate specific antigen (PSA), clinical stage, and biopsy Gleason grade were similar for the NHT and the non-NHT LRP groups. The median blood loss and the median operative time were also similar. There were no differences in the intraoperative complication rate of rectum injury, blood transfusion, and open surgery conversion. The positive surgical margin rate was significantly improved in NHT patients. Moreover, PSA recurrence within two years was significantly less in long-term NHT than in non-NHT patients. Conclusions: LRP was shown as a safe and efficacious procedure in patients who have received NHT. Perioperative morbidity of NHT patients undergoing LRP appears equivalent to non-NHT patients, with lower positive surgical margin, and PSA recurrence rate.
  • Single monthly bacillus Calmette-Guérin intravesical instillation is effective maintenance therapy to prevent recurrence in Japanese patients with non-muscle-invasive bladder cancer, Takehiko Okamura, Hidetoshi Akita, Ryosuke Ando, Yosuke Ikegami, Taku Naiki, Noriyasu Kawai, Keiichi Tozawa, Kenjiro Kohri, International Journal of Clinical Oncology, 17, (5) 477 - 481,   2012年10月, Background A series of bacillus Calmette-Guérin (BCG) bladder instillations is the gold standard therapy to prevent recurrence after transurethral resection of bladder tumor (TUR-Bt) of non-muscle-invasive bladder cancer (NMIBC). However, in some cases the outcome is not optimal with the standard 6- to 8-week protocol and therefore interest has focused on additional maintenance therapy. The present study was conducted to assess the utility of single monthly intravesical instillation treatments for up to 1 year in Japanese patients. Methods: A total of 75 stage Ta and T1 patients who had undergone TUR-Bt were retrospectively evaluated, all first receiving 80 mg BCG (Tokyo 172 strain) given once a week, 6-8 times, for primary prophylaxis. Comparison was then made of groups with (group A, 48 patients) and without (group B, 27 patients) additional maintenance BCG therapy given once a month 6-8 times. Results: Recurrence-free survival rates at 5 years in groups A and B were 83.0 and 51.9% (P = 0.006), despite the greater proportion of T1 patients and the longer followup period in the group A patients. Significant protection against recurrence persisted on multivariate analysis with adjustment for age, stage, grade, and tumor number. Conclusions: These findings indicate maintenance BCG therapy of single intravesical instillations given once a month with our protocol to be definitely effective for prophylactic use, especially in stage Ta patients. Further evaluation of parameters such as the continuance period and dose protocol is warranted. © Japan Society of Clinical Oncology 2011.
  • Unilateral testicular seminoma with simultaneous contralateral torsion: A case report, Kazumi Taguchil, Takahiro Yasui, Taku Naiki, Yukihiro Umemoto, Yoshiyuki Kojima, Noriyasu Kawai, Keiichi Tozawa, Yutaro Hayashi, Kenjiro Kohri, Journal of Medical Case Reports, 6,   2012年08月27日, Introduction. Testicular germ cell tumors are the most common malignancies in men. Testicular torsion is also a scrotal phenomenon seen in adolescence and adulthood. The co-occurrence of these two scrotal disorders is extremely rare. Case presentation. A 28-year-old East Asian man presented at our hospital with painless bilateral scrotal swelling. Both scrotal ultrasonography and computed tomography findings showed bilateral testicular tumors, and magnetic resonance imaging demonstrated a lack of enhancement in his right testis, indicating a hemorrhagic infarction and a left testicular tumor. After a bilateral orchiectomy, the intraoperative and histopathological findings revealed a left seminoma with a complicating contralateral testicular torsion that had developed with hemorrhagic infarction. Conclusion: Testicular germ cell tumor with contralateral torsion is extremely rare. We could differentiate this case from bilateral testicular tumors appropriately using magnetic resonance imaging, and suggest that magnetic resonance imaging examination may be necessary to diagnose bilateral testicular masses. © 2012 Taguchi et al.; licensee BioMed Central Ltd.
  • Age-dependent carcinogenic susceptibility in rat liver is related to potential of gap junctional intercellular communication., Naiki-Ito A, Kato H, Asamoto M, Naiki T, Shirai T, Toxicologic Pathology, 40,   2012年07月, Connexin 32 (Cx32) is a major gap junction protein in the liver. The authors previously demonstrated that transgenic rats carrying a dominant negative mutant of Cx32 (Cx32ΔTg) have much decreased capacity for gap junctional intercellular communication (GJIC) and increased susceptibility to diethylnitrosamine (DEN)–induced hepatocarcinogenesis as compared to littermate wild-type (wt) rats. To evaluate the age-dependent susceptibility to DEN-induced hepatocarcinogenesis and alteration of GJIC function, male Cx32ΔTg and wt rats at 10, 30, or 85 weeks old were given a single intraperitoneal administration of DEN (40 mg/rat) and sacrificed 12 weeks later. The number and area of glutathione S-transferase placental form (GST-P)–positive preneoplastic foci were significantly increased in the liver of 10- and 30-wk-old Cx32ΔTg rats compared with age-matched wt. However, in the 85-wk-old rats, both Cx32ΔTg and wt rats had similarly large number and area of GST-P-positive foci, and the difference was not significant. Interestingly, function of hepatic GJIC was reduced and protein and mRNA expression of Cx32 were decreased with aging in wt rats. These results suggest that a decline of hepatic intercellular communication through gap junction results in increased susceptibility to DEN-induced hepatocarcinogenesis in aged rats. © 2012, SAGE Publications. All rights reserved.
  • Pelvic solitary fibrous tumor originally diagnosed as prostatic in origin, Ryosuke Ando, Daichi Kobayashi, Taku Naiki, Noriyasu Kawai, Shoichi Sasaki, Kenjiro Kohri, CLINICAL IMAGING, 36, (3) 243 - 245,   2012年05月, A 71-year-old man was referred to our hospital because of intermittent urine stream and postmicturition dribbling. Magnetic resonance imaging (MRI) results suggested the mass to be a malignant mesenchymal tumor arising from the left lobe of the prostate, on the basis of the presence of a beak sign. Radical prostatectomy and partial rectal excision with subsequent colostomy were performed. Contrary to preoperative MRI, no prostate involvement was found on histologic examination. Histopathologic and immunohistochemical findings showed typical characteristics of solitary fibrous tumors. The patient's postoperative course was uneventful. He showed no signs of recurrence and metastasis at 2-year follow-up. (C) 2012 Elsevier Inc. All rights reserved.
  • Organ specific Gst-pi expression of the metastatic androgen independent prostate cancer cells in nude mice., Naiki T, Asamoto M, Toyoda-Hokaiwado N, Naiki-Ito A, Tozawa K, Kohri K, Takahashi S, Shirai T, Prostate, 72,   2012年04月, Background: Elucidating the mechanisms of metastasis in prostate cancer, particularly to the bone, is a major issue for treatment of this malignancy. We previously reported that an androgen-independent variant had higher expression of glutathione S-transferase pi (Gst-pi) compared with a parent androgen-dependent transplantable rat prostate carcinoma which was established from the transgenic rat for adenocarcinoma of the prostate (TRAP). METHODS A new cell line, PCai1, was established from the androgen-independent tumor and investigated its metastatic potential in nude mice. The tumorigenesis of PCai1 cells in vivo was studied by subcutaneous transplantations into nude mice. The growth in the microenvironment of the prostate was studied by orthotopic transplantation of PCai1 cells into nude mice. The metastatic potential of PCai1 cells was studied by tail vein injections. Effects of Gst-pi knocked down were analysis in PCai1 cells. Results: PCai1 frequently formed metastatic lesions in the lung and lymph nodes after orthotopic implantation in the prostate. Intravenous injections of PCai1, metastasis to lung and bone were obvious. PCai1 had strong expression for Gst-pi, therefore we tried knocked down Gst-pi. Gst-pi-siRNA in vitro significantly suppressed cell proliferation rate. In addition, high levels of intracellular reactive oxygen species (ROS) were recognized in the Gst-pi knockout. Conclusions: Gst-pi expression of the prostate cancers are dependent on metastatic site, and that Gst-pi has an important role in adapting prostate cancer for growth and metastasis involving an alteration of ROS signals. © 2011 Wiley Periodicals,Inc.
  • Are there time-period-related differences in the prophylactic effects of bacille calmette-guérin intravesical instillation therapy in Japan?, Takehiko Okamura, Ryosuke Ando, Hidetoshi Akita, Yoshihiro Hashimoto, Yutaka Iwase, Taku Naiki, Noriyasu Kawai, Keiichi Tozawa, Kenjiro Kohri, Asian Pacific Journal of Cancer Prevention, 13, (9) 4357 - 4361,   2012年, Objective: The guidelines on indications for prophylactic use of Bacille Calmette-Guérin (BCG) against non-muscle-invasive bladder cancer (NMIBC) have changed over the years. In order to assess the impact on outcome, the present retrospective comparison of BCG efficacy by time period with Japanese patients was conducted. Patients and Methods: A total of 146 cases of NMIBC treated with BCG since February 1985 were retrospectively evaluated. All patients received 80 mg of BCG (Tokyo 172 strain) six to eight times a week for prophylactic use. Comparison was made among three historical groups (Group A: 1980's, 39 cases; Group B: 1990's, 61 cases; Group C: 2000's, 46 cases). Results: In total, recurrence was seen in 55 of the 146 cases (37.7%), and progression in 14 (9.6%), 1 patient dying of cancer. These overall results were similar to those outlined in previous reports. However, the outcomes of this time-period-based analysis indicated a tendency for a shorter time to recurrence in patients after 2000, although a log-rank test showed no significance (P=0.229). Seven of the cases featuring progression (i.e., half of all such cases) were among the 46 Group C patients (15.2%). Excluding these progressive cases, there was no significant difference among the remaining 132 patients in the three groups. Conclusion: This study results revealed a tendency for a lower non-recurrence rate after 2000 in our series. This could stem from a number of factors, including changes in BCG indication criteria and the evolution of histopathological diagnostic criteria.
  • Implications of Greater Short-term PSA Recurrence with Laparoscopic as Compared to Retropubic Radical Prostatectomy for Japanese Clinically localized Prostate Carcinomas, Hidetoshi Akita, Takehiko Okamura, Ryosuke Ando, Daisuke Nagata, Hiromichi Naruyama, Yasuyuki Yamada, Taku Naiki, Takahiro Yasui, Keiichi Tozawa, Kenjiro Kohri, ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 12, (11) 2959 - 2961,   2011年, Purpose: There is ongoing discussion as to the necessity for certain surgical procedures being limited to high through-put institutions. To cast light on this question regarding use of open as compared to laparoscopic radical prostatectomy (LRP) the present study was conducted focusing on biochemical (PSA) recurrence-free survival of Japanese patients with clinically localized prostate carcinomas. Materials and Methods: From April 2004 to December 2010 we identified 579 patients undergoing LRP (n=245) and retropubic radical prostatectomy (RRP) (n=334) who did not undergo immediate adjuvant therapy (radiation and/or hormonal) and whose PSA levels were lower than 25 ng/ml. Preoperative prostate specific antigen (PSA) level, clinical stage, biopsy Gleason score and pathological features were assessed and Kaplan-Meier estimates of biochemical recurrence (BCR)-free survival were compared. A Cox regression model analysis was performed to determine predictors of biochemical recurrence. Results: Median follow up was 35 months(2- 115). On univariate analysis the LRP group had a slightly lower pathological T stage (p<0.001), higher biopsy Gleason score (p<0.001), but much more organ confined disease (p=0.001) than the RRP group. BCR-free survival did not significantly differ between LRP and RRP groups with preoperative PSA <6, clinical stage T1c, T2a, pathological stage T3 or more, biopsy Gleason score of 8 or more, pathological Gleason score of 6 or less and 8 or more, extra-capsular extension and negative surgical margin. The 3-year BCR-free survival rates were 91.0%(RRP) and 82.2%(LRP) (p<0.001). Conclusion: We conclude that in general LRP may be associated with a less positive outcome than BCR for resection of low risk prostate cancers. Therefore indications for LRP should be very carefully monitored.
  • Preoperative Prediction of Neurovascular Bundle Involvement of Localized Prostate Cancer by Combined T2 and Diffusion-weighted Imaging of Magnetic Resonance Imaging, Number of Positive Biopsy Cores, and Gleason Score, Taku Naiki, Takehiko Okamura, Daisuke Nagata, Yuji Mori, Noriyasu Kawai, Kumiko Ogawa, Hidetoshi Akita, Yoshihiro Hashimoto, Keiichi Tozawa, Kenjiro Kohri, ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 12, (4) 909 - 913,   2011年, Because recovery of erectile function and avoidance of positive surgical margins are important but competing outcomes with prostate cancer therapy, the decision to preserve or resect a neurovascular bundle (NVB) during laparoscopic radical prostatectomy (LRP) should be firmly based on information concerning the presence and location of extracapsular extension. In the current retrospective study, the propriety of actual decisions was assessed using preoperative magnetic resonance imaging (MRI), combining T2-weighted imaging (T2WI) with diffusion-weighted imaging (DWI), the apparent diffusion coefficient (ADC), numbers of positive biopsy cores, tumor volume and the Gleason score. MRI before prostate biopsy was performed in 35 patients who underwent LRP for clinically localized prostate cancer. A single radiologist retrospectively assessed whether the tumor localization, capsular penetration, seminal vesicle invasion, NVB involvement, and MRI findings correlated with the postoperative histological results. With the postoperative specimens, 83 lesions demonstrated a Gleason score of 6 or more. Using T2WI with and without DWI and ADC, 39 and 27 of 54 lesions were correctly identified, respectively, the difference being significant. For cancers in the transitional zone, using a threshold Gleason score of 3 or greater, sensitivity was also significantly higher for T2+DWI+ADC than for T2WI alone. Of 35 patients, using all available clinical information (biopsy results including Gleason score, tumor location, percentage of positive biopsy cores, and the percentage of tumor-involved core tissue), we found that the preoperative and postoperative staging were concordant in 25 cases. There is no universal consensus for nerve-sparing LRP; therefore, we performed an additional analysis using simplified clinically defined selection criteria (PSA level >15ng/mL, cT2, less than two positive biopsy scores in the unilateral lobe and less than 30% tumor volume, and a Gleason score of 6). Using this criteria, we selected 12 of 35 patients, and the detection rate of NVB involvement by MRI combined T2WI + DWI + ADC maps was 100% in their 30 lesions, and therefore we consider it safe to perform nerve-sparing LRP using our criteria. Our findings suggest that NVB can be safely preserved in patients with low-grade tumors using simplified clinically defined selection criteria to determine margin involvement.
  • Gap junction dysfunction reduces acetaminophen hepatotoxicity with impact on apoptotic signaling and connexin 43 protein induction in rat., Naiki-Ito A, Asamoto M, Naiki T, Ogawa K, Takahashi S, Sato S, Shirai T, Toxicologic Pathology, 38,   2010年02月, Acetaminophen (APAP) is a widely used antipyretic and analgesic agent. However, overdosing and sometimes even a recommended dose can lead to serious and conceivably fatal liver toxicity. Therefore, it is important to clarify understand mechanisms of hepatotoxicity induced by APAP. Gap junctions, formed by connexin, have important roles in maintenance of tissue homeostasis and control of cell growth and differentiation. In the liver, Cx32 is a major gap junction protein whose expression is known to gradually decrease with chronic liver disease progression. In the present study, acute hepatotoxic effects of APAP were found to be reduced in Cx32 dominant negative transgenic rats lacking normal gap junctional intercellular communication in the liver. In littermate wild-type rats, the injured centrilobular hepatocytes were positive for TUNEL staining and featured elevated expre ssion of cleaved caspase-3 and Cx43, which is not expressed in normal hepatocytes. These results suggest that APAP hepatotoxicity involves apoptosis, and induction of Cx43 expression may play an important role in the apoptotic signaling. Moreover, gap junctional functions of Cx32 can play important roles in removing damaged hepatocytes by apoptosis for liver tissue homeostasis. Copyright © 2010 by The Author(s).
  • Tranilast suppresses prostate cancer growth and osteoclast differentiation in vivo and in vitro., Sato S, Takahashi S, Asamoto M, Naiki T, Naiki-Ito A, Asai K, Shirai T, Prostate, 70,   2010年02月, BACKGROUND. In bone metastatic sites, prostate cancer cells proliferate on interacting with osteoclasts. Tranilast, which is used for an antiallergic drug, has been shown to inhibit growth of several cancers and stromal cells. The present study was conducted to assess suppressive effects of Tranilast on prostate cancer growth and osteoclast differentiation in vivo and in vitro. METHODS. In vivo, rat prostate cancer tissue was transplanted onto cranial bones of F344 rats and Tranilast was given for 9 days at doses of 0, 200, or 400 mg/kg/day. In vitro, human prostate cancer cell lines, LNCaP, PC3, and DU145, the rat prostate cancer cell line, PLS-10, and rat bone marrow cells were similarly treated with the agent. RESULTS. In vivo, tumor volumes were significantly decreased in the high dose group. While cell proliferation did not appear to be affected, apoptosis was induced and tumor necrosis was apparent. Cranial bone defects were decreased in the high dose group. In vitro, cell proliferation rates of all four cell lines were reduced by Tranilast and increased apoptosis was observed in LNCaP and PLS-10. In addition, Tranilast significantly reduced osteoclast differentiation of rat bone marrow cells. Western blot analysis of PLS-10 and LNCaP revealed that phospho-GSK3b was up-regulated and phospho-Akt was down-regulated. CONCLUSIONS. Tranilast here suppressed rat prostate cancer growth and osteoclast differentiation. Growth of human prostate cancer cells was also inhibited. Thus, this agent deserves consideration as a candidate for conventional therapy of bone metastatic prostate cancer. © 2009 Wiley-Liss, Inc.
  • Advantages of second line estramustine for overall survival of hormone-refractory prostate cancer (HRPC) patients, Taku Naiki, Takehiko Okamura, Noriyasu Kawai, Hiroshi Sakagami, Yasuyuki Yamada, Keiji Fujita, Hidetoshi Akita, Yoshihiro Hashimoto, Keiichi Tozawa, Kenjiro Kohri, Asian Pacific Journal of Cancer Prevention, 10,   2009年01月01日, There is no effective standard therapy for the treatment of hormone refractory prostate cancer (HRPC), and treatments vary among different medical institutions with efforts to improve results. The present retrospective investigation was performed to assess the outcomes of second line, third line, and fourth line therapies. A total of 142 patients with HRPC were treated at Nagoya City University Hospital and its affiliate hospitals during the 10 years between October 1996 and August 2006. Patient background and treatments given after hormone refractory phase were determined, with especial attention to 50% or greater decrease rates of serum PSA levels and other variables with three common regimens based on: estramustine phosphate (EMP); diethylstilbestrol diphosphate (DES); and dexamethasone (DEX). With second line therapy for HRPC, the response rate was highest with EMP, whereas best outcomes were apparent with DES as a third line or fourth line therapy. However, overall survival for all cases and particularly with those having a poorly differentiated lesion, was best with EMP in any time period. Although there is no generally established optimal treatment for HRPC, our analysis supports the efficacy of EMP based on second line therapy response rates and optimal prognosis with longer term use.
  • Testicular metastasis from an extramedullary plasmacytoma, Hideyuki Kamisawa, Hidetoshi Akita, Taku Naiki, Toshiki Kato, Takehiko Okamura, International Journal of Clinical Oncology, 13,   2008年10月01日, Plasmacytoma is a blood disease featuring the proliferation of abnormal plasmacytes accompanied by the production of monoclonal immunoglobulins. It usually arises in the medulla; thus, extramedullary plasmacytoma is rare, and metastatic testicular tumors are also infrequent. In this report, we present a case of testicular metastasis from an extramedullary plasmacytoma involving the nasopharynx, with good control being achieved by surgery (left high inguinal orchiectomy) and vincristine, adriamycin, and dexamethasone (VAD) chemotherapy. © 2008 Japan Society of Clinical Oncology.
  • Effect of heat therapy using magnetic nanoparticles conjugated with cationic liposomes on prostate tumor in bone, Noriyasu Kawai, Noriyasu Kawai, Mitsuru Futakuchi, Tatsuro Yoshida, Akira Ito, Shinya Sato, Taku Naiki, Hiroyuki Honda, Tomoyuki Shirai, Kenjiro Kohri, Prostate, 68,   2008年05月15日, BACKGROUND. We have developed magnetite nanoparticles conjugated with cationic liposomes (MCLs) to induce intracellular hyperthermia with exposure to an alternating magnetic field (AMF). We have previously demonstrated the hyperthermic effect of MCLs against certain types of malignant tumor cells in vivo. Here, we examine the effects of MCL + AMF heat therapy on prostate cancer tissue in a bone microenvironment and on bone destruction in a rat model. MATERIALS AND METHODS. Rat prostate cancer nodules were transplanted onto the calvaria of 6-week-old F344 male rats. MCLs were injected into the tumor which reached 7 mm in diameter, and then the animals were exposed to repeated AMF irradiation. The distribution of MCL, tumor necrosis, cell proliferation, and bone destruction in the bone microenvironment were evaluated. RESULTS. MCL + AMF heat therapy suppressed tumor growth on the calvaria, and histologically, the induction of a necrotic mass was observed around magnetic particles in the tumor. The bone destruction index, which indicates the degree of osteolysis associated with prostate tumor growth in the bone microenvironment, was 34.8% in the MCL group and 67.2% in the control group with significant difference. However, almost half of rats were dead in this experiment. CONCLUSION. MCL + AMF heat therapy suppressed tumor proliferation in the bone microenvironment, in addition to bone destruction. However, this method may exhibit side effects for central nerve system. If MCL are specifically taken into the prostate cancer cells in the bone microenvironment, this method may be useful for the treatment of bone metastatic lesions of prostate cancer. © 2008 Wiley-Liss, Inc.
  • Congenital narrowing of the bulbar urethra with enuresis, Taku Naiki, Yoshiyuki Kojima, Masa Hayase, Tetsuji Maruyama, Yutaro Hayashi, Kenjiro Kohri, Japanese Journal of Clinical Urology, 59,   2005年11月03日, An 11 year-old boy with congenital narrowing of the bulbar urethra presented complaining innate diurnal and nocturnal enuresis. The frequency volume chart revealed that the functional bladder volume was low for his age, and judging from nocturnal urine volume with its specific gravity, we regarded his symptoms caused by detrusor overactivity. A voiding cystgram revealed remarkable dilation of the posterior urethra, with narrowing of the bulbar urethra. Cystmetry revealed uninhibited contraction of the bladder. Under the suspected diagnosis of overactive bladder caused by lower urinary tract stricture, patient underwent transurethral incision of the urethra. After surgery, uroflometric findings were improved, and uninhibited contraction disappeared, and enuresis became controllable. At present, he has no sign of recurrence, and has no need of additional medication.


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