Mouse Models of Muscle-invasive Bladder Cancer: Key Considerations for Clinical Translation Based on Molecular Subtypes

Ruan, Jia‐Ling; Hsu, Jong-Wei; Browning, Richard; Stride, Eleanor; Yildiz, Yesna O.; Vojnovic, Borivoj; Kiltie, Anne E.

doi:10.1016/j.euo.2018.08.014

Cited by 7 publications

(6 citation statements)

References 51 publications

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“…The experimental models and study design should utilise the information available regarding the subtypes of the cell lines and also revisit the information available regarding the patient and the original tumour from which the cell line has been established. BCa experimental models and their molecular features have been recently reviewed by Zuiverloon et al [48] and rodent models with relevant molecular subtypes have been described by Ruan et al [49]. Here, we critically discuss the BCa experimental and preclinical models used in association with RT treatment.…”

Section: Bca Experimental Models In Rt Studiesmentioning

confidence: 95%

“…This transient state could be of importance during the invasion or the metastatic process. [49]. Abbreviations: n/a, information not available (classification have not been applied); n/c, not categorised (not coherent classification depending on the dataset used).…”

Section: Molecular Subtypesmentioning

confidence: 99%

“…We identified seven studies using syngeneic mouse models (Table 4). The three cell lines used in these studies were all chemically induced (detailed in [48]) and resemble the human basal/squamous subtype [41,49]. We noted that all of these models were heterotopic, excluding the assessment of treatment-induced bladder toxicity.…”

Section: Syngeneic Modelsmentioning

confidence: 99%

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Review of Experimental Studies to Improve Radiotherapy Response in Bladder Cancer: Comments and Perspectives

Silina

Maksut

Bernard‐Pierrot

et al. 2020

Cancers

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Bladder cancer is among the top ten most common cancer types in the world. Around 25% of all cases are muscle-invasive bladder cancer, for which the gold standard treatment in the absence of metastasis is the cystectomy. In recent years, trimodality treatment associating maximal transurethral resection and radiotherapy combined with concurrent chemotherapy is increasingly used as an organ-preserving alternative. However, the use of this treatment is still limited by the lack of biomarkers predicting tumour response and by a lack of targeted radiosensitising drugs that can improve the therapeutic index, especially by limiting side effects such as bladder fibrosis. In order to improve the bladder-preserving treatment, experimental studies addressing these main issues ought to be considered (both in vitro and in vivo studies). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, we conducted a literature search in PubMed on experimental studies investigating how to improve bladder cancer radiotherapy with different radiosensitising agents using a comprehensive search string. We made comments on experimental model selection, experimental design and results, formulating the gaps of knowledge still existing: such as the lack of reliable predictive biomarkers of tumour response to chemoradiation according to the molecular tumour subtype and lack of efficient radiosensitising agents specifically targeting bladder tumour cells. We provided guidance to improve forthcoming studies, such as taking into account molecular characteristics of the preclinical models and highlighted the value of using patient-derived xenografts as well as syngeneic models. Finally, this review could be a useful tool to set up new radiation-based combined treatments with an improved therapeutic index that is needed for bladder preservation.

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Section: Bca Experimental Models In Rt Studiesmentioning

confidence: 95%

Section: Molecular Subtypesmentioning

confidence: 99%

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Review of Experimental Studies to Improve Radiotherapy Response in Bladder Cancer: Comments and Perspectives

Silina

Maksut

Bernard‐Pierrot

et al. 2020

Cancers

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“…Multiple rat models have been established to study bladder cancer biology and treatment response in vivo 31 . Orthotopic cancer models closely resemble canonical bladder cancer development 32 and thus appear to be more suitable than heterotopic models for recapitulating the clinical HIVEC treatments.…”

Section: Introductionmentioning

confidence: 99%

A scalable hyperthermic intravesical chemotherapy (HIVEC) setup for rat models of bladder cancer

Hattum

Scutigliani

Helderman

et al. 2022

Sci Rep

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Hyperthermic intravesical chemotherapy (HIVEC)—whereby the bladder is heated to ± 43 °C during a chemotherapy instillation—can improve outcomes of non-muscle invasive bladder cancer (NMIBC) treatments. Experiments in animal models are required to explore new hyperthermia based treatments. Existing HIVEC devices are not suitable for rodents or large-scale animal trials. We present a HIVEC setup compatible with orthotopic rat models. An externally heated chemotherapeutic solution is circulated in the bladder through a double-lumen catheter with flow rates controlled using a peristaltic pump. Temperature sensors in the inflow channel, bladder and outflow channel allow temperature monitoring and adjustments in real-time. At a constant flow rate of 2.5 mL/min the system rapidly reaches the desired bladder temperature of 42–43 °C with minimal variability throughout a one-hour treatment in a rat bladder phantom, as well as in euthanised and live rats. Mean intraluminal bladder temperatures were 42.92 °C (SD = 0.15 °C), 42.45 °C (SD = 0.37 °C) and 42.52 °C (SD = 0.09 °C) in the bladder phantom, euthanised, and live rats respectively. Thermal camera measurements showed homogenous heat distributions over the bladder wall. The setup provides well-controlled thermal dose and the upscaling needed for performing large scale HIVEC experiments in rats.

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“…Conventionally used mouse models require tumors to be experimentally induced as it is uncommon for rodents to develop tumors spontaneously (Arantes- Rodrigues et al, 2013). In essence, the phenotypic and molecular heterogeneity of MIBC tumors limits the translational value of conventional rodent models to evaluate therapeutic drug efficacy, since genetically modified mouse models do not effectively mimic the biological behavior of UC in humans (Ruan et al, 2019). For example, few genetically engineered mouse models display invasive phenotypes, which is an apparent limitation when modeling aggressive cancers like MIBC (Kobayashi et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Culture and Maintenance of Urine-Derived, 3-Dimensional Canine Transitional Cell Carcinoma Organoids

Thenuwara

Mosichuk

Gabriel

et al. 2021

Preprint

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Bladder cancer is the ninth most common malignancy in the world. Transitional cell carcinoma (TCC), also referred to as urothelial carcinoma (UC) is the most common form of bladder cancer, occurring in 90% of cases. In this study, we explore urine-derived, 3-dimensional, canine TCC organoids as a possible model to study bladder TCC ex vivo. After establishing the cell lines, we subjected the 3D cells to RNA in situ hybridization (RNA-ISH) and cell viability assays. Overall, 3D cell culture from urine samples of TCC diagnosed canines expressed RNA biomarkers in a similar manner to parent tumors via RNA-ISH and showed more sensitivity to cisplatin treatment when compared to 2D human TCC cells. With further experimentation, canine TCC organoids could become an ideal model to study TCC ex vivo.

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Mouse Models of Muscle-invasive Bladder Cancer: Key Considerations for Clinical Translation Based on Molecular Subtypes

Cited by 7 publications

References 51 publications

Review of Experimental Studies to Improve Radiotherapy Response in Bladder Cancer: Comments and Perspectives

Review of Experimental Studies to Improve Radiotherapy Response in Bladder Cancer: Comments and Perspectives

A scalable hyperthermic intravesical chemotherapy (HIVEC) setup for rat models of bladder cancer

Culture and Maintenance of Urine-Derived, 3-Dimensional Canine Transitional Cell Carcinoma Organoids

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