Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer

Nogawa, Masaki; Yuasa, Takeshi; Kimura, Shinya; Tanaka, Motoyoshi; Kuroda, Junya; Satô, Kiyoshi; Yokota, Asumi; Segawa, Hajime; Toda, Yoshinobu; Kageyama, Susumu; Tokura, Y.; Okada, Yusaku; Maekawa, Taira

doi:10.1172/jci23043

Cited by 165 publications

(59 citation statements)

References 29 publications

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“…16 Cationic liposomes were successfully used to deliver siRNA after intravesical administration in the murine bladder. 17 The current study supports the use of cationic liposomes as an OND carrier.…”

Section: Discussionsupporting

confidence: 78%

Down-Regulation of Nerve Growth Factor Expression in the Bladder by Antisense Oligonucleotides as New Treatment for Overactive Bladder

et al. 2013

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Purpose Nerve growth factor over expression in the bladder has a role in overactive bladder symptoms via the mediation of functional changes in bladder afferent pathways. We studied whether blocking nerve growth factor over expression in bladder urothelium by a sequence specific gene silencing mechanism would suppress bladder overactivity and chemokine expression induced by acetic acid. Materials and Methods Female Sprague-Dawley® rats anesthetized with isoflurane were instilled with 0.5 ml saline, scrambled or TYE™ 563 labeled antisense oligonucleotide targeting nerve growth factor (12 μM) alone or complexed with cationic liposomes for 30 minutes. The efficacy of nerve growth factor antisense treatments for acetic acid induced bladder overactivity was assessed by cystometry. Bladder nerve growth factor expression levels and cellular distribution were quantified by immunofluorescence staining and enzyme-linked immunosorbent assay. Effects on bladder chemokine expression were measured by Luminex® xMAP® analysis. Results Liposomes were needed for bladder uptake of oligonucleotide, as seen by the absence of bright red TYE 563 fluorescence in rats instilled with oligonucleotide alone. At 24 hours after liposome-oligonucleotide treatment baseline bladder activity during saline infusion was indistinct in the sham and antisense treated groups with a mean ± SEM intercontraction interval of 348 ± 55 and 390 ± 120 seconds, respectively. Acetic acid induced bladder overactivity was shown by a decrease in the intercontraction interval to a mean of 33.2% ± 4.0% of baseline in sham treated rats. However, the reduction was blunted to a mean of 75.8% ± 3.4% of baseline in rats treated with liposomal antisense oligonucleotide (p <0.05). Acetic acid induced increased nerve growth factor in the urothelium of sham treated rats, which was decreased by antisense treatment, as shown by enzyme-linked immunosorbent assay and reduced nerve growth factor immunoreactivity in the urothelium. Increased nerve growth factor in bladder tissue was associated with sICAM-1, sE-selectin, CXCL-10 and 1, leptin, MCP-1 and vascular endothelial growth factor over expression, which was significantly decreased by nerve growth factor antisense treatment (p <0.01). Conclusions Acetic acid induced bladder overactivity is associated with nerve growth factor over expression in the urothelium and with chemokine up-regulation. Treatment with liposomal antisense suppresses bladder overactivity, and nerve growth factor and chemokine expression. Local suppression of nerve growth factor in the bladder could be an attractive approach for overactive bladder. It would avoid the systemic side effects that may be associated with nonspecific blockade of nerve growth factor expression.

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Section: Discussionsupporting

confidence: 78%

Down-Regulation of Nerve Growth Factor Expression in the Bladder by Antisense Oligonucleotides as New Treatment for Overactive Bladder

et al. 2013

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“…On the other hand, it has previously been reported that gene silencing induced by siRNA/DNA is likely to be less effective than that induced by its unmodified counterparts, because siRNA/DNA exhibits weaker activity for formation of am RNA-induced silencing complex [13,51]. Considering these facts, we adopted a multiple siRNA/ DNA injection protocol (in the present study, thrice, at days 0, 7, and 14) as described elsewhere [51,52].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of KIF23 suppresses glioma proliferation

et al. 2011

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To identify therapeutic molecular targets for glioma, we performed modified serological identification of antigens by recombinant complementary DNA (cDNA) expression cloning using sera from a mouse glioma model. Two clones, kinesin family member 23 (Kif23) and structural maintenance of chromosomes 4 (Smc4), were identified as antigens through immunological reaction with sera from mice harboring synergic GL261 mouse glioma and intratumoral inoculation with a mutant herpes simplex virus. The human Kif23 homolog KIF23 is a nuclear protein that localizes to the interzone of mitotic spindles, acting as a plus-end-directed motor enzyme that moves antiparallel microtubules in vitro. Expression analysis revealed a higher level of KIF23 expression in glioma tissues than in normal brain tissue. The introduction of small interfering RNA (siRNA) targeting KIF23 into two different glioma cell lines, U87MG and SF126, downregulated KIF23 expression, which significantly suppressed glioma cell proliferation in vitro. KIF23 siRNA-treated glioma cells exhibited larger cell bodies with two or more nuclei compared with control cells. In vivo analysis using mouse xenograft showed that KIF23 siRNA/DNA chimera-treated tumors were significantly smaller than tumors treated with control siRNA/DNA chimera. Taken together, our results indicate that downregulation of KIF23 decreases proliferation of glioma cells and that KIF23 may be a novel therapeutic target in malignant glioma.

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“…15,23,25–28 UM-UC3 and UC14 have been used with varying success. 25,29,30 Anecdotally we can report that UM-UC3 at one point in our hands was KU7 (and therefore HeLa; true UM-UC3 clones are readily available), and MGHU3 has been shown to be the myeloma cell line KMS-18 (data not shown), so that a certain degree of skepticism is necessary for historical papers unless cell line authentication is described. The loss of KU7 as a model for testing intravesical drug delivery has left a significant gap in our modeling ability.…”

Section: Discussionmentioning

confidence: 90%

Hiding in Plain View: Genetic Profiling Reveals Decades Old Cross Contamination of Bladder Cancer Cell Line KU7 with HeLa

et al. 2013

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Purpose KU7 is a popular urothelial carcinoma cell line that was isolated from the bladder of a patient at the Keio University (KU) in 1980. It has subsequently been widely used in laboratories around the world. Here we describe how routine cell line authentication has revealed that KU7 was cross-contaminated almost 30 years ago with HeLa, a cervical carcinoma cell line. Materials and Methods Presumed KU7 clones dating from 1984 to 1999 were provided by MD Anderson Cancer Center (MDACC), the Vancouver Prostate Centre (VPC), Kyoto University, Tokyo Medical University and KU, and HeLa was purchased from the ATCC. Genomic DNA was isolated and short tandem repeat (STR) analysis was performed by the Characterized Cell Line Core Facility at MDACC, the Fragment Analysis Facility at Johns Hopkins University and the RIKEN Bioresource Center (Japan). Comparative genomic hybridization (CGH) was performed on the Agilent platform at the VPC. Results The STR profile of all KU7 clones was an exact match with HeLa. The CGH of all samples revealed an abundance of shared chromosomal aberrations. Slight differences in some genomic areas are explained by genomic drift occurring in different KU7 clones separated by many years. Conclusions Our analysis identified that a cross-contamination of KU7 with HeLa occurred prior to 1984 at the source institution. All KU7 clones in the urologic literature should be considered HeLa and the experimental results should be viewed in this light. Our results emphasize the need to authenticate cell lines in oncologic research.

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Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer

Cited by 165 publications

References 29 publications

Down-Regulation of Nerve Growth Factor Expression in the Bladder by Antisense Oligonucleotides as New Treatment for Overactive Bladder

Down-Regulation of Nerve Growth Factor Expression in the Bladder by Antisense Oligonucleotides as New Treatment for Overactive Bladder

Downregulation of KIF23 suppresses glioma proliferation

Hiding in Plain View: Genetic Profiling Reveals Decades Old Cross Contamination of Bladder Cancer Cell Line KU7 with HeLa

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