Orthotopic Mouse Models of Urothelial Cancer

Jäger, Wolfgang; Moskalev, Igor; Raven, Peter A.; Goriki, Akihiro; Bidnur, Samir; Black, Peter C.

doi:10.1007/978-1-4939-7234-0_15

Cited by 9 publications

(8 citation statements)

References 36 publications

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“…Peter Black (University of British Columbia) presented opportunities to join forces and leverage Canadian strengths in bladder cancer translational research. He noted Canadian research capabilities, including advanced in vivo modelling, 5 genomics infrastructure, 6,7 liquid biopsy programs, 8 expertise in tumor immunology, [9][10][11][12][13][14] and epigenetics, 15 and established biospecimen repositories, 16 as well as a strong track record of linking these translational resources with investigatorinitiated trials. 17,18 The growth in bladder cancer research in Canada is clearly evident from pioneering new research findings and a growing cohort of Canadian researchers with a natural inclination to collaborate.…”

Section: Setting the Stagementioning

confidence: 99%

Assembling a network to promote translational bladder cancer research in Canada

Koti

Berman

Lange

et al. 2020

CUAJ

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Bladder cancer research has historically lagged behind efforts in other disease sites with substantial underfunding relative to the heavy morbidity and mortality suffered by patients. Alongside increasing advocacy however, more recent advances in our understanding of the molecular biology of bladder cancer has ushered in a period of renaissance with exciting prospects for novel, precise diagnostics and therapeutics. Given significant and diverse assets within the research community across Canada, an inaugural translational research forum was convened to identify research gaps and strengths, and to formalize investigational themes that would be apposite for multi-institutional collaboration. The virtual meeting brought together a multi-disciplinary network of genitourinary cancer researchers, including clinicians and basic scientists, and entailed detailed environmental scans of the Canadian clinical and translational research landscape as well as selected “elevator pitches” of potential research themes. The results of these discussions are detailed herein and have provided the impetus to formalize the Canadian Bladder Cancer Research Network (CBCRN). Working groups have been created to focus future multi-institutional collaborations in four inter-related initiatives: biomarker development, epigenetic targeting, immuno-oncology and the microbiome.

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Section: Setting the Stagementioning

confidence: 99%

Assembling a network to promote translational bladder cancer research in Canada

Koti

Berman

Lange

et al. 2020

CUAJ

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“…To assess the efficacy of Gli ASO treatment in vivo we utilized the murine intravesical orthotopic human BCa (mio-hBC) model that is summarized in Figure 7 (Jager et al, 2018;Raven et al, 2018). All animal procedures were performed according to the guidelines of the Canadian Council on Animal Care.…”

Section: In Vivo Assessment Of Gli Asosmentioning

confidence: 99%

Inhibition of GLI2 with antisense‐oligonucleotides: A potential therapy for the treatment of bladder cancer

Raven

Lysakowski

Tan

et al. 2019

Journal Cellular Physiology

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The sonic hedgehog (SHH) signaling pathway plays an integral role in the maintenance and progression of bladder cancer (BCa) and SHH inhibition may be an efficacious strategy for BCa treatment. We assessed an in-house human BCa tissue microarray and found that the SHH transcription factors, GLI1 and GLI2, were increased in disease progression. A panel of BCa cell lines show that two invasive lines, UM-UC-3 and 253J-BV, both express these transcription factors but UM-UC-3 produces more SHH ligand and is less responsive in viability to pathway stimulation by recombinant human SHH or smoothened agonist, and less responsive to inhibitors including the smoothened inhibitors cyclopamine and SANT-1. In contrast, 253J-BV was highly responsive to these manipulations. We utilized a GLI1 and GLI2 antisense oligonucleotide (ASO) to bypass pathway mechanics and target the transcription factors directly. UM-UC-3 decreased in viability due to both ASOs but 253J-BV was only affected by GLI2 ASO. We utilized the murine intravesical orthotopic human BCa (mio-hBC) model for the establishment of noninvasive BCa and treated tumors with GLI2 ASO. Tumor size, growth rate, and GLI2 messenger RNA and protein expression were decreased. These results suggest that GLI2 ASO may be a promising new targeted therapy for BCa.

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“…Orthotopic models, which result from transplantation of cancer cells to the bladder, are closest to this ideal model 4 . To date, four methods for development of orthotopic bladder cancer models have been reported 7,8 . After our failed attempt to develop a patient‐derived xenograft model of bladder cancer using the direct intramural injection of cancer cells, one of the most widely used methods, we aimed to evaluate the validity of our approach.…”

Section: Introductionmentioning

confidence: 99%

“…4 To date, four methods for development of orthotopic bladder cancer models have been reported. 7,8 After our failed attempt to develop a patient-derived xenograft model of bladder cancer using the direct intramural injection of cancer cells, one of the most widely used methods, we aimed to evaluate the validity of our approach. We therefore utilized a cancer cell line with 100% tumor take rate to evaluate the efficacy and success rate of the direct intramural injection technique, via histopathological assessment, in developing orthotopic bladder cancer models.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of direct intramural injection to the bladder wall as a method for developing orthotopic tumor models

Bitaraf

Muhammadnejad

Azimzadeh

et al. 2022

Anim Models and Exp Med

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Background: Bladder cancer poses a great burden on society and its high rate of recurrence and treatment failure necessitates use of appropriate animal models to study its pathogenesis and test novel treatments. Orthotopic models are superior to other types since they provide a normal microenvironment. Four methods are described for developing bladder cancer models inside the animal's bladder. Direct intramural injection is one of these methods and is widely used. However, its efficacy in model development has not yet been studied. We aimed to evaluate the efficacy and success rate of the direct intramural injection method of developing an orthotopic model for the study of bladder cancer.Method: Tumor cell lines were prepared in four microtubes. Aliquots of 200 × 10 3 cells were injected through a 27 gauge needle into the ventral wall of the bladders of 4 male and 4 female BALB/c mice following a midline 1 cm laparotomy incision. In addition, 1 million cells from each microtube were injected into the flanks of control mice.To prevent infection and alleviate pain, 5 mg/kg enrofloxacin and 2.5 mg/kg flunixin meglumine, respectively, were injected subcutaneously. Results:Tumors formed in all mice, resulting in 100% take rate and zero post-operation mortality. Surgery time was ≤15 min per mouse. In two mice, tumors were found in the peritoneal space as well. Conclusion:Direct intramural injection is a rapid, reliable, and reproducible method for developing orthotopic models of bladder cancer. It can be done on both male and female mice and only requires readily available surgical tools. However, needle track can result in cell spillage and peritoneal tumors.

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Orthotopic Mouse Models of Urothelial Cancer

Cited by 9 publications

References 36 publications

Assembling a network to promote translational bladder cancer research in Canada

Assembling a network to promote translational bladder cancer research in Canada

Inhibition of GLI2 with antisense‐oligonucleotides: A potential therapy for the treatment of bladder cancer

Evaluation of direct intramural injection to the bladder wall as a method for developing orthotopic tumor models

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