Histopathological characterization of a syngeneic orthotopic murine bladder cancer model

Chade, Daher C.; Andrade, P. M.; Borra, Ricardo Carneiro; Leite, Kátia R. M.; Andrade, Enrico; Villanova, Fabiola; Srougi, Miguel

doi:10.1590/s1677-55382008000200013

Cited by 26 publications

(19 citation statements)

References 19 publications

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“…The orthotopic murine model of bladder cancer was a modification of a previously described technique (25,26). In brief, female nude (nu/nu) mice at 8 to 10 weeks of age (Simonsen Laboratory) were anaesthetized with isoflurane.…”

Section: Orthotopic Model Of Bladder Cancer and Intravesical Treatmentmentioning

confidence: 99%

Intravesical Delivery of Small Activating RNA Formulated into Lipid Nanoparticles Inhibits Orthotopic Bladder Tumor Growth

et al. 2012

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Practical methods for enhancing protein production in vivo remain a challenge. RNA activation (RNAa) is emerging as one potential solution by using double-stranded RNA (dsRNA) to increase endogenous gene expression. This approach, although related to RNA interference (RNAi), facilitates a response opposite to gene silencing. Duplex dsP21-322 and its chemically modified variants are examples of RNAa-based drugs that inhibit cancer cell growth by inducing expression of tumor suppressor p21 WAF1/CIP1 (p21). In this study, we investigate the therapeutic potential of dsP21-322 in an orthotopic model of bladder cancer by formulating a 2 0 -fluoro-modified derivative (dsP21-322-2 0 F) into lipid nanoparticles (LNP) for intravesical delivery. LNP composition is based upon clinically relevant formulations used in RNAi-based therapies consisting of PEG-stabilized unilamellar liposomes built with lipid DLin-KC2-DMA. We confirm p21 induction, cell-cycle arrest, and apoptosis in vitro following treatment with LNP-formulated dsP21-322-2 0 F (LNP-dsP21-322-2 0 F) or one of its nonformulated variants. Both 2 0 -fluoro modification and LNP formulation also improve duplex stability in urine. Intravesical delivery of LNPdsP21-322-2 0 F into mouse bladder results in urothelium uptake and extends survival of mice with established orthotopic human bladder cancer. LNP-dsP21-322-2 0 F treatment also facilitates p21 activation in vivo leading to regression/disappearance of tumors in 40% of the treated mice. Our results provide preclinical proof-of-concept for a novel method to treat bladder cancer by intravesical administration of LNP-formulated RNA duplexes.

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Section: Orthotopic Model Of Bladder Cancer and Intravesical Treatmentmentioning

confidence: 99%

Intravesical Delivery of Small Activating RNA Formulated into Lipid Nanoparticles Inhibits Orthotopic Bladder Tumor Growth

et al. 2012

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“…Other agents, e.g., N-methyl-N-nitrosurea (MNU) or silver nitrate can also be used for denudation but are not as effective as acid washing (36). Mechanical damage, including electrical cauterization or epithelial abrasion can also facilitate tumor cell adhesion (19,40,58). Prolonged dwell time of tumor cells can also improve take rates (19).…”

Section: Transplantable Modelsmentioning

confidence: 99%

Current animal models of bladder cancer: Awareness of translatability (Review)

Ding

Pan

et al. 2014

Experimental and Therapeutic Medicine

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Experimental animal models are crucial in the study of biological behavior and pathological development of cancer, and evaluation of the efficacy of novel therapeutic or preventive agents. A variety of animal models that recapitulate human urothelial cell carcinoma have thus far been established and described, while models generated by novel techniques are emerging. At present a number of reviews on animal models of bladder cancer comprise the introduction of one type of method, as opposed to commenting on and comparing all classifications, with the merits of a certain method being explicit but the shortcomings not fully clarified. Thus the aim of the present study was to provide a summary of the currently available animal models of bladder cancer including transplantable (which could be divided into xenogeneic or syngeneic, heterotopic or orthotopic), carcinogen-induced and genetically engineered models in order to introduce their materials and methods and compare their merits as well as focus on the weaknesses, difficulties in operation, associated problems and translational potential of the respective models. Findings of these models would provide information for authors and clinicians to select an appropriate model or to judge relevant preclinical study findings. Pertinent detection methods are therefore briefly introduced and compared.

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“…One of them involves the use of hydrochloric acid (0.1 ml 0.1 M HCl for 15 minutes) and subsequent neutralization with alkali and extensive washing with saline (Zhang et al, 2011). Another technique involves instillation of a solution of silver nitrate (NO 3 Ag ) (Chade et al, 2008). Both forms of injury allow the generation of tumors uniformly distributed in the bladder.…”

Section: Orthotopic Tumor Growthmentioning

confidence: 99%

“…Mice with 1x10 4 or 1x10 5 MB49 cell lines, inoculated by electrocautery, present hematuria about 15 or 9 days post-inoculation, respectively (Lodillinsky et al, 2009). Inoculation of 5x10 3 cells in the bladder previously treated with NO 3 Ag generates hematuria in all mice about 7 days after tumor implantation (Chade et al, 2008). Palpation of the bladder may give an idea of the extent of the tumor, but it is difficult to carry out because the bladder is retropubic.…”

Section: Orthotopic Tumor Growthmentioning

confidence: 99%