Exposure to Vinorelbine Inhibits in Vitro Proliferation and Invasiveness of Transitional Cell Bladder Carcinoma

Bonfil, R. Daniel; Russo, Daniela M.; Schmilovich, A.

doi:10.1097/00005392-199608000-00074

Cited by 4 publications

(5 citation statements)

References 11 publications

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“…Vinorelbine has not been previously evaluated in dogs with TCC, however, it effectively inhibited tumour growth and invasion in murine TCC cells . Although not widely studied in the treatment of TCC in people, vinorelbine has been used in combination protocols for the treatment of advanced urothelial TCC with some success .…”

Section: Introductioncontrasting

confidence: 91%

Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma

Kaye

Thamm

Weishaar

et al. 2013

Vet Comparative Oncology

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The goal of this study was to evaluate the anti-tumour activity and toxicoses of vinorelbine as a palliative rescue therapy for dogs with primary urinary bladder carcinoma. Thirteen dogs refractory to prior chemotherapeutics and one dog naïve to chemotherapeutic treatment were enrolled. Vinorelbine (15 mg m(-2) IV) was administered intravenously along with concurrent oral anti-inflammatory drugs, if tolerated. A median of six doses of vinorelbine (range: 1-16) was administered. Two dogs (14%) had partial responses, and eight (57%) experienced stable disease. Subjective improvement in clinical signs was noted in 11 dogs (78%). Adverse events were mild and primarily haematological in nature. Median time to progression was 93 days (range: 20-239 days). Median survival time for all dogs was 187 days; median survival for 13 pre-treated dogs was 207 days. Vinorelbine may have utility in the management of canine primary urinary bladder carcinoma and should be evaluated in a prospective study.

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Section: Introductioncontrasting

confidence: 91%

Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma

Kaye

Thamm

Weishaar

et al. 2013

Vet Comparative Oncology

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“…The anti‐proliferative effect of vinorelbine against different human cell lines has already been established [23–25]. To verify its effect on renal cancer cell growth, A498 and 786‐O cells were treated with increasing concentrations of vinorelbine (10 nM, 100 nM, and 1μM) and cell survival was assessed with the MTT assay.…”

Section: Resultsmentioning

confidence: 99%

“…Invasion of tumour cells through the matrix of the microenvironment is an early process of metastasis. It was reported that exposure to vinorelbine inhibits in vitro invasiveness of transitional cell bladder carcinoma [23]. To determine whether vinorelbine plays an inhibitory role in the invasion of renal cancer cells, we performed a Matrigel invasion assay in the presence or absence of the drug.…”

Section: Resultsmentioning

confidence: 99%

VEGF neutralizing antibody increases the therapeutic efficacy of vinorelbine for renal cell carcinoma

Sinha

Dutta

Wang

et al. 2010

J Cellular Molecular Medi

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Renal cell carcinoma (RCC) is currently one of the most treatment-resistant malignancies and affects approximately three in 10,000 people. The impact of this disease produces about 31,000 new cases in the United States per year; and 12,000 people in the United States alone die from RCC annually. Although several treatment strategies have been investigated for RCC, this cancer continues to be a therapeutic challenge. For this reason, the aim of our study is to develop a more effective combinational therapy to treat advanced RCC. We examined the effect of vinorelbine on the signalling pathways of two human renal cancer cell lines (A498 and 786-O) and also examined the in vivo effect of vinorelbine treatment alone and vinorelbine in combination with the anti-VEGF antibody 2C3 on A498 and 786-O tumour growth in nude mice. Tumour angiogenesis was measured by vWF staining, and apoptosis was determined by the TUNEL assay. We observed a significant tumour growth inhibition when using a combinational therapy of anti-VEGF antibody 2C3 and vinorelbine in both A498 and 786-O tumour-bearing mice. The results suggest a breakthrough treatment for advanced RCC.

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“…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: 99%

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

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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.

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Exposure to Vinorelbine Inhibits in Vitro Proliferation and Invasiveness of Transitional Cell Bladder Carcinoma

Abstract: Vinorelbine proved to be an effective drug to inhibit tumor cell growth and invasion in a transitional cell bladder carcinoma model. The results obtained would justify preclinical studies to evaluate the effectiveness of VNR as a potential treatment of TCC.

Cited by 4 publications

References 11 publications

Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma

Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma

VEGF neutralizing antibody increases the therapeutic efficacy of vinorelbine for renal cell carcinoma

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

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Exposure to Vinorelbine Inhibits in Vitro Proliferation and Invasiveness of Transitional Cell Bladder Carcinoma

Abstract: Vinorelbine proved to be an effective drug to inhibit tumor cell growth and invasion in a transitional cell bladder carcinoma model. The results obtained would justify preclinical studies to evaluate the effectiveness of VNR as a potential treatment of TCC.

Cited by 4 publications

References 11 publications

Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma

Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma

VEGF neutralizing antibody increases the therapeutic efficacy of vinorelbine for renal cell carcinoma

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

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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