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The Belle Collaboration,
K. Negishi,
Y. Horii,
Y. Onuki,
T. Sanuki,
H. Yamamoto,
I. Adachi,
H. Aihara,
D. M. Asner,
T. Aushev, [......],
M. Watanabe,
Y. Watanabe,
E. Won,
B. D. Yabsley,
Y. Yamashita,
C. C. Zhang,
Z. P. Zhang,
V. Zhilich,
V. Zhulanov,
A. Zupanc
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ABSTRACT: We report a study of the decay $B^0\rightarrow D K^+\pi^-$ followed by
$D\rightarrow K^-\pi^+$, where $D$ indicates $D^0$ or $\bar{D}^0$. We
reconstruct the $D K^+\pi^-$ state in a phase space corresponding to $D
K^{*}(892)^0$. The CP-violating angle $\phi_3$ affects its decay rate via the
interference between $b\rightarrow u$ and $b\rightarrow c$ transitions. The
result is obtained from a 711 ${\rm fb}^{-1}$ data sample that contains 772
$\times 10^6 B\bar{B}$ pairs collected at the $\Upsilon(4S)$ resonance with the
Belle detector at the KEKB asymmetric-energy $e^+ e^-$ collider. We measure the
ratio ${\cal R}_{DK^{*0}} \equiv \Gamma(B^0\rightarrow
[K^-\pi^+]_DK^+\pi^-)/\Gamma(B^0\rightarrow [K^+\pi^-]_DK^+\pi^-)$ to be $(4.1
^{+ 5.6 + 2.8}_{- 5.0 - 1.8}) \times 10^{-2}$, and set an upper limit of ${\cal
R}_{DK^{*0}} < 0.16$ at the 95% confidence level.
05/2012;
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R Saito,
R Shirakawa,
H Nishiyama,
T Kobayashi,
M Kawato,
T Kanno,
K Nishizawa,
Y Matsui,
T Ohbayashi,
M Horiguchi,
T Nakamura,
T Ikeda,
K Yamane,
E Nakayama,
E Nakamura,
Y Toda,
T Kimura,
T Kita, O Ogawa,
H Horiuchi
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ABSTRACT: The small GTPase Ral is known to be highly activated in several human cancers, such as bladder, colon and pancreas cancers. It is reported that activated Ral is involved in cell proliferation, migration and metastasis of bladder cancer. This protein is activated by Ral guanine nucleotide exchange factors (RalGEFs) and inactivated by Ral GTPase-activating proteins (RalGAPs), the latter of which consist of heterodimers containing a catalytic α1 or α2 subunit and a common β subunit. In Ras-driven cancers, such as pancreas and colon cancers, constitutively active Ras mutant activates Ral through interaction with RalGEFs, which contain the Ras association domain. However, little is known with regard to the mechanism that governs aberrant activation of Ral in bladder cancer, in which Ras mutations are relatively infrequent. Here, we show that Ral was highly activated in invasive bladder cancer cells due to reduced expression of RalGAPα2, the dominant catalytic subunit in bladder, rather than increased expression of RalGEFs. Exogenous expression of wild-type RalGAPα2 in KU7 bladder cancer cells with invasive phenotype, but not mutant RalGAPα2-N1742K lacking RalGAP activity, resulted in attenuated cell migration in vitro and lung metastasis in vivo. Furthermore, genetic ablation of Ralgapa2 promoted tumor invasion in a chemically-induced murine bladder cancer model. Importantly, immunohistochemical analysis of human bladder cancer specimens revealed that lower expression of RalGAPα2 was associated with advanced clinical stage and poor survival of patients. Collectively, these results are highly indicative that attenuated expression of RalGAPα2 leads to disease progression of bladder cancer through enhancement of Ral activity.Oncogene advance online publication, 26 March 2012; doi:10.1038/onc.2012.101.
Oncogene 03/2012; · 6.37 Impact Factor
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T Kanno,
T Kamba,
T Yamasaki,
N Shibasaki,
R Saito,
N Terada,
Y Toda,
Y Mikami,
T Inoue,
A Kanematsu,
H Nishiyama, O Ogawa,
E Nakamura
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ABSTRACT: Inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene causes both hereditary and sporadic clear-cell renal-cell carcinoma (ccRCC). Although the best-characterized function of the VHL protein (pVHL) is regulation of hypoxia-inducible factor-α (HIFα), pVHL also controls the development of pheochromocytoma through HIF-independent pathways by regulating JunB. However, it is largely unknown how these pathways contribute to the development and progression of ccRCC. In the present study, we confirmed that JunB was upregulated in VHL-defective ccRCC specimens by immunostaining. Short-hairpin RNA (shRNA)-mediated knockdown of JunB in 786-O and A498 VHL null ccRCC cells suppressed their invasiveness. In addition, JunB knockdown significantly repressed tumor growth and microvessel density in xenograft tumor assays. Conversely, forced expression of wild-type, but not dimerization-defective, JunB in a VHL-restored 786-O subclone promoted invasion in vitro and tumor growth and vessel formation in vivo. Quantitative PCR array analysis revealed that JunB regulated multiple genes relating to tumor invasion and angiogenesis such as matrix metalloproteinase-2 (MMP-2), MMP-9 and chemokine (C-C motif) ligand-2 (CCL2) in 786-O cells. JunB knockdown in these cells reduced the proteolytic activity of both MMPs in gelatin zymography and the amount of CCL2 in the culture supernatant. Moreover, shRNA-mediated knockdown of MMP-2 or inhibition of CCL2 activity with a neutralizing antibody repressed xenograft tumor growth and angiogenesis. Collectively, these results suggest that JunB promotes tumor invasiveness and enhances angiogenesis in VHL-defective ccRCCs.
Oncogene 10/2011; 31(25):3098-110. · 6.37 Impact Factor
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Annals of Oncology 03/2010; 21(6):1382-3. · 6.43 Impact Factor
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[show abstract]
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ABSTRACT: Summary Laparoscopic surgery has become a common modality in the urological field. However, a relatively high incidence of complications was reported due to the complexity of the laparoscopic approach. Herein we report the first case of retroperitoneal chylocoele following laparoscopic adrenalectomy.
07/2009; 5(4):367-368.
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ABSTRACT: To evaluate the usefulness of a quantification method using filter paper for analyzing minute voided urine of the mouse.
Voided stain on paper (VSOP) method; the correlation between area of stained spot on a filter paper and amount of applied liquid was calculated. Voiding behavior of the mice was analyzed by placing the animal above the same filter paper and recording voided time and area over 2 hr. The usefulness of the VSOP method was tested in analysis of the voiding behavior of five female 7-week-old ddY mice treated with cyclophosphamide (CPM, 150 mg/kg, intraperitoneally) and five control ones, in comparison with the histology of CPM-induced cystitis. Further, the voided volume of male and female ddY mouse ranging from 2 to 13 weeks was assessed.
There was a linear correlation between liquid volume and stained area on the filter paper (y = 16.472x - 22.411, R(2) = 0.9981). Between control mice and those with histologically proven CPM cystitis, there was a significant difference in voided volume (362.7 +/- 51.9 and 127.8 +/- 100.0 microl, < 0.001) and voiding interval (10.30 +/- 3.10 and 4.47 +/- 1.70 min, < 0.001). Voided volume of ddY mice was quantifiable from as early as 2-week old, increased along with their growth and correlated well with their body weight [(voided volume: microl) = 10.8 x (body weight: g) + 32, R(2) = 0.762].
The VSOP method is a useful tool for evaluating voiding behavior of the mouse, including those with small bladder capacity.
Neurourology and Urodynamics 06/2008; 27(6):548-52. · 2.96 Impact Factor
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ABSTRACT: To improve conventional chemotherapeutic efficacy, a combination use of traditional medicines is effective but detailed mechanisms have been rarely elucidated. In the this study, we attempted to clarify how triptolide (PG490), an oxygenated diterpene derived from a Chinese herb, enhances the cisplatin (CDDP)-induced cytotoxicity in urothelial cancer cells. Our results showed that a combined CDDP/triptolide therapy induced apoptosis in urothelial cancer cell lines with wild-type p53, but not in those with mutant-type p53 or normal human urothelium. As the mechanism, triptolide suppressed CDDP-induced p53 transcriptional activity, leading to p21 attenuation, which promoted apoptosis via the activation of c-Jun N-terminal kinase (JNK) and Bax. We further demonstrated that the functional regulation of p53 by triptolide was mediated by an intranuclear association of p53 with glycogen synthase kinase-3beta (GSK3beta), which was inactivated by protein kinase C (PKC). This modulation of the PKC-GSK3beta axis by triptolide was observed in a cancer-specific manner. A mouse xenograft model also showed that a combined CDDP/triptolide therapy completely suppressed tumor growth without any side effects. We expect that cancer-specific enhancement of CDDP-induced cytotoxicity with triptolide may effectively overcome the resistance to a CDDP-based conventional chemotherapy as a treatment for urothelial cancer.
Oncogene 05/2008; 27(33):4603-14. · 6.37 Impact Factor
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H Kawanishi,
T Takahashi,
M Ito,
Y Matsui,
J Watanabe,
N Ito,
T Kamoto,
T Kadowaki,
G Tsujimoto,
I Imoto,
J Inazawa,
H Nishiyama, O Ogawa
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ABSTRACT: The purpose of this study was to investigate the accumulation of genetic alterations during metachronous and/or synchronous development of multifocal low-grade superficial urothelial tumours in the same patient, by using array-based comparative genomic hybridisation (array-CGH) and FGFR mutation analysis. We analysed 24 tumours (pTa-1 G1-2) from five patients. We had previously identified a clonal relationship among the tumours of each patient by microsatellite analysis. This time, unsupervised hierarchical cluster analysis revealed that the tumours from each patient were clustered together independently of the tumours from the other patients. All of the tumours from a single patient showed a set of 2-7 identical regional or whole-arm chromosomal changes. In addition, several individual alterations were also found. Cladistic diagrams revealed that the accumulation of genetic alterations could not be explained by a linear model, and the existence of a hypothetical precursor cell was assumed in four patients. In some cases, FGFR mutation seemed to occur later during multifocal tumour development. Taken together, these findings suggest that low-grade superficial urothelial tumours accumulate minor genetic alterations during multifocal development, although these tumours are genetically stable.
British Journal of Cancer 08/2007; 97(2):260-6. · 5.04 Impact Factor
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K Yoshimura,
T Kamoto,
E Nakamura,
T Segawa,
T Kamba,
T Takahashi,
H Nishiyama,
N Ito,
K Takayama,
T Mizowaki,
M Mitsumori,
M Hiraoka, O Ogawa
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ABSTRACT: We compared health-related quality-of-life (HRQL) after intensity-modulated radiotherapy (IMRT) with statuses obtained after old and new protocols of three-dimensional conformal radiation therapy (3DCRT) for localized prostate cancer. We measured the general and disease specific HRQL using the MOS 36-Item Health Survey (SF-36), and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI), respectively. IMRT resulted in similar profiles of general and disease-specific HRQL to two other methods within the first year after treatment. Moreover, IMRT gave rise to comparable urinary, intestinal and sexual side effects despite the high dose of radiation applied.
Prostate Cancer and Prostatic Diseases 02/2007; 10(3):288-92. · 2.42 Impact Factor
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ABSTRACT: 3-3'-Methylene-bis [4-hydroxycoumarin] (dicoumarol), an inhibitor of NADPH:quinone oxidoreductase 1, has been reported to possess potential antineoplastic effects and the ability to abrogate p53 protein. In the present study, we investigated the cytotoxic effects of dicoumarol in combination with cisplatin (CDDP), using four bladder (RT112, 253J, J82 and UMUC3) and two prostate (LNCap and PC3) cancer cell lines. Single treatment with 100 microM dicoumarol suppressed cell proliferation but did not induce apoptosis at 24 h in all cell lines examined. On the other hand, pretreatment with dicoumarol enhanced cytotoxicity of CDDP in three cell lines with wild type of p53 (RT112, 253J and LNCap), but not in three other cell lines with mutant p53 or in RT112 stable transfectants with a dominant-negative mutant of p53. In RT112 and LNCap, CDDP induced p53 and p21 expression, while pretreatment of dicoumarol suppressed induction of p53/p21 and resulted in sequential activation of c-Jun N-terminal kinase (JNK) in a time-dependent manner. Furthermore, inhibition of JNK, using SP600125, completely suppressed activity of caspases and poly-(ADP-ribose) polymerase cleavage, leading to suppression of enhancement of CDDP-mediated apoptosis by dicoumarol. These results suggested that dicoumarol could enhance cytotoxicity of CDDP in urogenital cancer cells with wild-type p53 through the p53/p21/JNK pathways.
Oncogene 05/2006; 25(17):2500-8. · 6.37 Impact Factor
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ABSTRACT: Clinical application of anticancer agents has been often hampered by toxicity against normal cells, so the achievement of their cancer-specific action is still one of the major challenges to be addressed. Previously, we reported that arsenic trioxide (As2O3) could be a promising new drug against not only leukemia but also solid tumors. The cytotoxicity of As2O3 occurred through the generation of reactive oxygen species (ROS), thus inhibiting radical scavenging systems would enhance the therapeutic efficacy of As2O3 provided that normal cells were relatively resistant to such a measure. Here, we report that the combination therapy of As2O3 with L-buthionine-sulfoximine (BSO), which inhibits a critical step in glutathione synthesis, effectively enhanced in vitro growth inhibition effect of As2O3 on all 11 investigated cell lines arising from prostate, breast, lung, colon, cervix, bladder, and kidney cancers, compared with As2O3 treatment alone. Furthermore, this combination enhanced cytotoxicity to cell lines from prostate cancer with less toxicity to those from normal prostate. In vitro cytotoxic assay using ROS-related compounds demonstrated that hydrogen peroxide (H2O2) is a major cytotoxic mediator among ROS molecules. Biochemical analysis showed that combined use of As2O3 and BSO blocked H2O2-scavenging systems including glutathione, catalase, and glutathione peroxidase, and that the degree of this blockade was well correlated with intracellular ROS levels and sensitivity to this treatment. Finally, the effectiveness of the combination therapy of As2O3 with BSO was demonstrated with an orthotopic model of prostate cancer metastasis. We propose that the combination therapy of As2O3 with BSO is a valid means of blockade of H2O2-scavenging system, and that the combination of a ROS-generating agent with an inhibitor of major scavenging systems is effective in terms of both efficacy and selectivity. Furthermore, because the effective doses of both compounds are within clinically achievable range, this report will lead to immediate benefit for the development of a new cancer therapy.
Cell Death and Differentiation 08/2004; 11(7):737-46. · 8.85 Impact Factor
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ABSTRACT: Arsenic trioxide (As2O3) induces clinical remission in acute promyelocytic leukemic patients and apoptosis in various tumor cells in vitro. To develop As2O3-based combination chemotherapy for renal cell carcinoma (RCC), we investigated the cytotoxic effects of As2O3 in combination with chemotherapeutic agents or L-buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor. Cytotoxicity and synergy were assessed by the MTT assay and isobolographic analysis, respectively. Apoptosis was monitored by Hoechst 33342 staining, flow cytometrical analysis, and DNA fragmentation assay. Treatment of ACHN cells with As2O3 in combination with adriamycin, vinblastine, or 5-fluorouracil induced an antagonistic effect. However, combination treatment with As2O3 and BSO resulted in a synergistic cytotoxic effect. Synergy was also obtained in Caki-1, Caki-2, NC65 cells and freshly derived RCC cells from 6 patients. Simultaneous treatment of ACHN cells with As2O3 and BSO caused significantly more cytotoxicity than the As2O3 first BSO second or the reverse treatment. We further explored the mechanisms underlying this synergistic effect and found that the synergistic cytotoxicity of As2O3 and BSO was realized by inducing apoptosis. This combination markedly decreased intracellular GSH content and GSH-S-transferase (GST) activity. However, neither the intracellular GSH nor GST was decreased by As2O3 with adriamycin, vinblastine, or 5-fluorouracil. Furthermore, the GSH-increasing agents N-acetylcysteine and lipoic acid significantly inhibited the combined cytotoxicity of As2O3 and BSO. These findings indicate that BSO sensitizes RCC cells to As2O3-induced apoptosis through the down-regulation of the intracellular GSH redox system, suggesting the potential application of a combination of As2O3 and BSO for the treatment of RCC.
International Journal of Oncology 07/2004; 24(6):1489-97. · 2.40 Impact Factor
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ABSTRACT: Methods: The Japanese version (version 1.2) of the UCLA PCI was developed through a process of translation, back-translation, and
refinement after interviewing patients. Reliability and validity were examined for 125 Japanese patients with localized prostate
cancer. The patients simultaneously responded to the Japanese version of the RAND 36-Item Health Survey (SF-36) and five representative
questions from the International Index of Erectile Function (IIEF).
Results: Internal consistency reliability was very high for both urinary and sexual function scales, and lower for bowel function.
The test-retest reliability of the urinary and sexual function scales and the urinary bother scales was stable, while that
of the bowel function and bother scales was relatively unstable. Sexual function scores did not correlate highly with sexual
bother scores. Furthermore, poor sexual function and bother had little association with the SF-36 scores. Missing data as
to urinary and bowel function/bother scales were minimal (0.8%–2.4%), while those for sexual function and bother were relatively
high (4.8%–11.2%).
Conclusions: The results of this pilot study, together with the previous American study, suggest ethnic or cultural difference in how
impaired sexual function is integrated into overall QOL. A future cross-cultural comparative study using the UCLA PCI and
SF-36 will provide useful information about the influence of cultural or ethnic differences on health-related QOL in prostate
cancer patients.
International Journal of Clinical Oncology 09/2002; 7(5):0306-0311. · 1.41 Impact Factor
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ABSTRACT: To retrospectively analyse the secretor status in women with acute uncomplicated pyelonephritis, as non-secretors of histo-blood group antigens are reportedly at risk of recurrent urinary tract infections (UTIs).
The study included 245 women who had been diagnosed as having acute uncomplicated pyelonephritis in affiliated hospitals over the past 5 years. All women were sent antiseptic swabs, to collect saliva, and a questionnaire to survey their past UTI episodes and menstrual status. Responses with written informed consent were obtained from 106 women (median age 50.5 years, range 17-85). The secretor status was determined using the haemagglutination inhibition assay from the saliva on the swabs.
Forty-four (41%) of the women were non-secretors, a significantly higher frequency than in the (control) Japanese population (217 of 960, 22.6%; P< 0.001). The incidence of non-secretors was significantly higher (P < 0.01) in premenopausal (26 of 46, 57%) than in postmenopausal women (18 of 60, 30%).
These results suggest that non-secretor status is associated with a genetic susceptibility to acute uncomplicated pyelonephritis, especially in premenopausal women.
BJU International 07/2002; 89(9):851-4. · 2.84 Impact Factor
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ABSTRACT: FUBI (failure of ureteric bud invasion) is a highly inbred strain of mouse with a high spontaneous incidence of uni- or bilateral renal agenesis (60%). Bilateral renal agenesis is lethal within 2 days after birth. The primary defect of FUBI is failure of the ureteric bud to penetrate into the metanephric mesenchyme at around embryonic day 11, resulting in apoptosis of metanephric cells and leading to renal agenesis on the affected side. The metanephros seemed to be normal because co-culturing of the FUBI metanephros with homologous spinal cord induced differentiation of the rudiment, but co-culturing with the homologous ureteric bud frequently did not. Genetic analysis revealed that more than two genes were involved in this malformation and we mapped one of the modifier loci, fubi1, on chromosome 2, at approximately 65 cM from the centromere. In this region, there are two possible candidate genes, Wilms' tumor 1 and formin, that play important roles in kidney development. Some of formin mutants shared a similar phenotype with FUBI; however, there was no difference in the expression of formin in embryonic kidneys between FUBI and control NFS/N mice. Studies of fubi1 congenic mice indicated that interaction of two or more loci is essential for the FUBI phenotype.
American Journal Of Pathology 01/2002; 159(6):2347-53. · 4.89 Impact Factor
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ABSTRACT: A total of 321 uropathogenic Escherichia coli (UPEC) strains and 12 strains of E. coli isolated from stool samples of healthy individuals, which were previously shown to be positive in colony hybridization test using the usp (encoding for the uropathogenic-specific protein) DNA probe, were examined by PCR amplification to determine the size of the usp gene and the pathogenicity island (PI). Three types of size variation were observed for the usp gene and four types for the PI. Sequencing analysis of the PIs from seven representative strains (six UPEC and one from a normal healthy individual) revealed that the usp genes can be classified into two groups, each having different sequences in the 3'-terminal region. The peptides encoded by the three open reading frames (ORFs) downstream of usp had identical 23 amino acid residues in the C-terminal region. The subregion encoding these small ORFs has a mosaic structure constituted of six segments. The positions of these segments vary from strain to strain, and in some strains, two to four segments are deleted. This indicates that rearrangements occur frequently in this region and the mosaic arrangement apparently contributes to the size variation observed in the PCR examination of the usp genes and PIs.
FEMS Microbiology Letters 12/2001; 205(1):71-6. · 2.04 Impact Factor
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ABSTRACT: Environmental factors act in concert with individual susceptibility to cause most human cancers. The modulation of these environmental factors by host susceptibility has rarely been evaluated. Recently, the molecular epidemiology of human cancer has been extended to a study clarifying individual variation and gene-environmental interactions by integrating molecular biology, in vitro and in vivo laboratory models, biochemistry and epidemiology to infer individual cancer risk. This article briefly reviews genetic polymorphisms frequently used in molecular epidemiological studies and shows, as an example, a possible association between the genetic polymorphisms of CYP17 genes and prostate cancer risk.
Hinyokika kiyo. Acta urologica Japonica 12/2001; 47(11):833-6.
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Nippon rinsho. Japanese journal of clinical medicine 12/2001; 59 Suppl 7:364-72.
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ABSTRACT: Vascular endothelial growth factor (VEGF)-related factors are believed to regulate angiogenesis, an essential event in the growth of solid tumors. In this study, we investigated the expression of VEGF-related factor genes (VEGF, VEGF-B, and VEGF-C) and their receptor genes (VEGFR-1 and VEGFR-2) in renal cell carcinoma (RCC). There were significant differences in the expression level of VEGF, VEGFR-1 and VEGFR-2 between RCC and the corresponding normal renal tissue. The expression level of VEGF in the tumor tissue significantly correlated with those of VEGFR-1 and VEGFR-2. Expression levels VEGF-B and VEGF-C genes were not significantly different between RCC and normal renal tissue. A moderate to high protein expression for VEGF, VEGFR-1, and VEGFR-2 was observed in both the tumor cells and the endothelial cells, whereas the protein expression was low for VEGF-B and VEGF-C. The present results suggested that VEGF and its receptors VEGFR-1 and VEGFR-2 cooperates to play a crucial role in the angiogenesis of RCC, while VEGF-B and VEGFR-C may not. Furthermore, since VEGFR-1 and VEGFR-2 proteins were expressed in the tumor cells as well as in the endothelial cells, these receptors may also be responsible for the progression of RCC.
The Tohoku Journal of Experimental Medicine 11/2001; 195(2):101-13. · 1.24 Impact Factor
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ABSTRACT: A 72-year-old man had undergone surgical castration for metastatic prostate cancer (stage D2, the PSA value was 4,300 ng/ml) in September, 1997. He was well clinically for 16 months with undetected level of PSA. However, he presented with general malaise and gross hematuria in May, 1999. After admission to our hospital his condition rapidly deteriorated and he died one week later with respiratory failure. Autopsy revealed extensive involvement of the prostate and bladder by solid tumor with multiple metastases in lungs, liver, spleen, kidneys and bone. Histological examination revealed pure small cell carcinoma of the prostate.
Hinyokika kiyo. Acta urologica Japonica 09/2001; 47(8):591-3.
