Survival After Curative Treatment of Muscle-Invasive Bladder Cancer

Fosså, Sophie D.; Aass, Nina; Ous, S.; Wæhre, Håkon; Ilner, Kari; Hannisdal, Einar

doi:10.3109/02841869609098521

Cited by 23 publications

(11 citation statements)

References 28 publications

(10 reference statements)

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“…The radiotherapy trial in this study included almost only patients with N » disease or locally advanced tumours (86%) in which cystectomy was not possible. The present results of radical radiotherapy alone are comparable with those achieved in other studies (22)(23)(24), and the survival time of patients selected for cystectomy is comparable with that reported from consecutive series (25,26).…”

Section: Discussionsupporting

confidence: 81%

Neoadjuvant Chemotherapy with Cisplatin and Methotrexate in Patients with Muscle-Invasive Bladder Tumours

et al. 2002

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Section: Discussionsupporting

confidence: 81%

Neoadjuvant Chemotherapy with Cisplatin and Methotrexate in Patients with Muscle-Invasive Bladder Tumours

et al. 2002

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“…However, most patients have a recurrence within the first year and in the recurrent cases, additional cisplatin combination chemotherapy provides limited benefit (1,2). Thus, over the past three decades there have been numerous trials to overcome cisplatin resistance in bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

NVP-BEZ235, a dual PI3K/mTOR inhibitor synergistically potentiates the antitumor effects of cisplatin in bladder cancer cells

Moon

Lee

et al. 2014

International Journal of Oncology

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The PI3K/Akt/mTOR pathway is a prototypic survival pathway and constitutively activated in many malignant conditions. Moreover, activation of the PI3K/Akt/mTOR pathway confers resistance to various cancer therapies and is often associated with a poor prognosis. In this study, we explored the antitumor effect of NVP-BEZ235, a dual PI3K/mTOR inhibitor in cisplatin-resistant human bladder cancer cells and its synergistic interaction with cisplatin. A human bladder cancer cell line with cisplatin resistance was exposed to escalating doses of NVP-BEZ235 alone or in combination with cisplatin and antitumor effects was determined by the CCK-8 assay. Based on a dose-response study, synergistic interaction between NVP-BEZ235 and cisplatin was evaluated by combination index (CI), three-dimensional model and clonogenic assay. The combination of NVP-BEZ235 and cisplatin caused significant synergistic antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range and reduced the IC50 of NVP-BEZ235 and cisplatin by 5.6- and 3.6-fold, respectively. Three-dimensional synergy analysis resulted in a synergy volume of 388.25 μM/ml2% indicating a strong synergistic effect of combination therapy. The combination therapy caused cell cycle arrest and caspase-dependent apoptosis. Although NVP-BEZ235 suppressed PI3K/mTOR signaling without any paradoxical induction of Akt activity, it caused MEK/ERK pathway activation. The present study demonstrated that the PI3K/mTOR dual inhibitor NVP-BEZ235 can synergistically potentiate the antitumor effects of cisplatin in cisplatin-resistant bladder cancer cells though the suppression of cell cycle progression and the survival pathway as well as induction of caspase-dependent apoptosis.

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“…Even though bladder transitional cell carcinoma is relatively chemotherapy-sensitive, the responses are usually transient and most responding diseases recur within the first year, with median survival ranging from 12 to 14 months. Thus, during the past few decades, numerous trials have been conducted to develop new treatment regimens for advanced bladder cancer [1-4]. …”

Section: Introductionmentioning

confidence: 99%

Sunitinib Malate Synergistically Potentiates Anti-Tumor Effect of Gemcitabine in Human Bladder Cancer Cells

et al. 2011

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PurposeSunitinib malate (Sutent; Pfizer, New York, NY, USA) is a highly selective multi-targeted agent and has been reported to have potent anti-tumor effects against various tumors, including renal cell carcinoma and gastrointestinal stromal tumors. In this study, we explored in vitro the anti-tumor effect and related molecular mechanisms of sunitinib malate against human bladder cancer cell lines. We also determined the synergistic anti-tumor effect between sunitinib and conventional cytotoxic drugs, cisplatin and gemcitabine, in bladder cancer cells.Materials and MethodsSix human cancer cell lines (HTB5, HTB9, T24, UMUC14, SW1710, and J82) were exposed to an escalating dose of sunitinib alone or in combination with cisplatin/gemcitabine, and the cytotoxic effect of the drugs was examined by CCK-8 assay. The synergistic effect between sunitinib and cisplatin/gemcitabine was determined by the combination index (CI) and clonogenic assay. Alterations in cell cycle (cyclin D, B1), survival (p-Akt, t-Akt), and apoptosis (Bax, Bad) regulator expression were analyzed by Western blotting.ResultsLike cisplatin and gemcitabine, sunitinib exerted a dose- and time-dependent anti-tumor effect in bladder cancer cells. However, sunitinib exhibited entirely different sensitivity profiles from cisplatin and gemcitabine. Sunitinib suppressed the expression of cyclin B1, p-Akt, and t-Akt while augmenting the expression of cyclin D and pro-apoptotic Bax and Bad in HTB5 cells. Analysis of the drug combination by the isobolic method and clonogenic assay revealed that sunitinib acts in synergy with gemcitabine in HTB5 cells.ConclusionsThese results indicate that sunitinib malate has a potent anti-tumor effect and may synergistically enhance the anti-tumor effect of gemcitabine in human bladder cancer cells.

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Survival After Curative Treatment of Muscle-Invasive Bladder Cancer

Cited by 23 publications

References 28 publications

Neoadjuvant Chemotherapy with Cisplatin and Methotrexate in Patients with Muscle-Invasive Bladder Tumours

Neoadjuvant Chemotherapy with Cisplatin and Methotrexate in Patients with Muscle-Invasive Bladder Tumours

NVP-BEZ235, a dual PI3K/mTOR inhibitor synergistically potentiates the antitumor effects of cisplatin in bladder cancer cells

Sunitinib Malate Synergistically Potentiates Anti-Tumor Effect of Gemcitabine in Human Bladder Cancer Cells

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