Intravesical Therapy With Vinorelbine Tartrate: Antitumor Activity in Orthotopic Murine Cell Carcinoma of the Bladder

Bonfil, R. Daniel; Russo, Daniela M.; Schmilovich, A.; Garcia-Palazzo, Irma B.

doi:10.1016/s0022-5347(01)64363-5

Cited by 8 publications

(5 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This model results in efficient tumour take in multiple different cell lines, but due to the depth of tumour invasion, is not suitable for the study of intravesical therapy. Transurethral administration of cancer cells allowing for tumour deposition and seeding onto the mouse urothelium more closely reproduces nonmuscle‐invasive bladder tumours [6–16]. It is essential to emphasize that these are highly malignant and invasive urothelial carcinoma cells whose biological behaviour is not necessarily typical of noninvasive disease, but the main characteristic of the model is the lack of deeper invasion at early time‐points, which makes these tumours amenable to intravesical therapy.…”

Section: Discussionmentioning

confidence: 99%

“…One such advance, bioluminescence imaging (BLI), permits sensitive in vivo detection and quantification of cells specifically engineered to express luciferase. Although several orthotopic animal models of bladder cancer have been described [6–16], BLI offers unique advantages for easy longitudinal quantification of tumour burden in living mice. Furthermore, in contrast to end‐point weight or calliper measurements of tumours that include areas of necrosis or oedema, BLI measures only viable tumour.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A validated mouse model for orthotopic bladder cancer using transurethral tumour inoculation and bioluminescence imaging

et al. 2007

View full text Add to dashboard Cite

OBJECTIVES To describe a technique for transurethral tumour inoculation, bioluminescence imaging (BLI) and validation of this approach using ex vivo magnetic resonance imaging (MRI), as a reproducible and quantifiable model of orthotopic bladder cancer is required to enable preclinical pharmacological studies of intravesically administered anticancer agents and the use of BLI provides a sensitive method to monitor tumour growth over time. MATERIALS AND METHODS Human KU‐7 bladder tumour cells were transduced with a lentiviral construct to stably express the firefly luciferase gene. These cells were then inoculated in female nude mice by intravesical instillation. BLI was performed weekly and the mice were killed after 4 weeks. Ex vivo MRI and whole‐mount step‐sections were obtained to assess bladder tumour volume. RESULTS KU‐7 tumour cells were highly tumorigenic and were successfully inoculated in 96% of mice. After 4 weeks, all tumours were confined to the mucosa and submucosa (≤pT1). There was an excellent correlation between tumour volume and BLI for both ex vivo bladder MRI (R2 = 0.929) and end‐point histological measurements (R2 = 0.836). CONCLUSIONS We have established and validated a reliable model of orthotopic bladder cancer that can be used to evaluate various methods of intravesical therapy. BLI allows excellent longitudinal surveillance and quantification of tumour burden.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A validated mouse model for orthotopic bladder cancer using transurethral tumour inoculation and bioluminescence imaging

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Previous studies in an experimental setting showed that vinorelbine is a potent antitumoral agent in vitro and in vivo for TCC of the bladder [6,7], but this anti‐microtubule agent has not yet been used for the clinical treatment of this type of cancer. Therefore, superficial bladder cancer was considered a reasonable target to evaluate intravesical therapy with vinorelbine.…”

Section: Discussionmentioning

confidence: 99%

“…The capacity of vinorelbine to inhibit in vitro cell proliferation of MB‐49, a murine TCC of the bladder, and its invasive and cell motility abilities, were reported recently [6]. Moreover, the drug diminished both tumour incidence and volume, when administered intravesically in C57Bl/6 J mice orthotopically inoculated with MB‐49 bladder cancer cells [7].…”

Section: Introductionmentioning

confidence: 98%

Immunohistochemical analysis of Ki‐67, p21^waf1/cip1 and apoptosis in marker lesions from patients with superficial bladder tumours treated with vinorelbine intravesical therapy in a preliminary phase I trial

et al. 2001

View full text Add to dashboard Cite

Objective To investigate Waf1/Cip1 expression and apoptosis, before and after treatment, in tumour biopsies obtained from patients with super®cial bladder cancer who underwent vinorelbine intravesical therapy. Patients and methods Twenty patients with high-risk super®cial bladder cancer (including one or more of the following parameters: tumour diameter >3 cm, histological grade 3, or multicentric tumours) were treated 1±6 times (weekly) with intravesical vinorelbine (50 mg/mL) instillations. Transurethral tumour marker biopsies were obtained one week before the ®rst instillation of the drug and one week after the last. The biopsies were immunostained for Ki-67 and p21 Waf1/Cip1 with monoclonal antibodies, on tissue sections derived from paraf®n-embedded samples obtained before and after vinorelbine treatments. In addition, apoptosis was determined using a terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labelling (TUNEL) technique. Results There were no signi®cant differences in the cell proliferation marker Ki-67 in biopsies taken before or after treatment. However, p21 Waf1/Cip1 showed signi®-cantly higher expression in biopsies obtained after vinorelbine treatment, with median (range) values of 40 (20±90)% before and 70 (50±80)% after (P<0.001, paired nonparametric Wilcoxon test). The apoptotic index was signi®cantly higher after vinorelbine therapy, with median (range) values of 0.89 (0.06±3.8)% before and 2.25 (0.17±18.7)% after treatment (P<0.001, paired nonparametric Wilcoxon test). Despite the brief treatment and few patients there was a clinical response in nine patients, together with low toxicity in all. Conclusion The intravesical treatment of tumours with vinorelbine affects p21 Waf1/Cip1 expression without blocking cell proliferation, although increasing apoptosis. The preliminary results suggest that vinorelbine may be useful for treating super®cial bladder tumours, and thus a phase II study is warranted.

show abstract

“…Hierzu gehören Valrubicin [1], Gemcitabine [12] und Vinorelbin [5]. Hierzu gehören Valrubicin [1], Gemcitabine [12] und Vinorelbin [5].…”

Section: Neue Substanzenunclassified

Topische Therapie beim oberflächlichen Harnblasenkarzinom

1999

View full text Add to dashboard Cite

Intravesical Therapy With Vinorelbine Tartrate: Antitumor Activity in Orthotopic Murine Cell Carcinoma of the Bladder

Cited by 8 publications

References 13 publications

A validated mouse model for orthotopic bladder cancer using transurethral tumour inoculation and bioluminescence imaging

A validated mouse model for orthotopic bladder cancer using transurethral tumour inoculation and bioluminescence imaging

Immunohistochemical analysis of Ki‐67, p21^waf1/cip1 and apoptosis in marker lesions from patients with superficial bladder tumours treated with vinorelbine intravesical therapy in a preliminary phase I trial

Topische Therapie beim oberflächlichen Harnblasenkarzinom

Contact Info

Product

Resources

About

Intravesical Therapy With Vinorelbine Tartrate: Antitumor Activity in Orthotopic Murine Cell Carcinoma of the Bladder

Cited by 8 publications

References 13 publications

A validated mouse model for orthotopic bladder cancer using transurethral tumour inoculation and bioluminescence imaging

A validated mouse model for orthotopic bladder cancer using transurethral tumour inoculation and bioluminescence imaging

Immunohistochemical analysis of Ki‐67, p21waf1/cip1 and apoptosis in marker lesions from patients with superficial bladder tumours treated with vinorelbine intravesical therapy in a preliminary phase I trial

Topische Therapie beim oberflächlichen Harnblasenkarzinom

Contact Info

Product

Resources

About

Immunohistochemical analysis of Ki‐67, p21^waf1/cip1 and apoptosis in marker lesions from patients with superficial bladder tumours treated with vinorelbine intravesical therapy in a preliminary phase I trial