Optimizing intravesical mitomycin C therapy in non-muscle-invasive bladder cancer

Zargar, Homayoun; Aning, Jonathan; Ischia, Joseph; So, Alan; Black, Peter C.

doi:10.1038/nrurol.2014.52

Cited by 55 publications

(49 citation statements)

References 75 publications

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“…13,14). Treatment for NMIBC tumors involves transurethral resection, followed by the instillation of chemotherapeutic agents (mitomycin) or an immunostimulatory agent, Bacillus Calmette Guerin, to delay recurrence, and periodical cystoscopic surveillance (15,16). Bladder-confined muscle-invasive tumors are treated by radical cystectomy with platinum-based chemotherapy, which results in approximately 50% survival for 5 years; the remaining 50% of patients develop metastatic disease and only approximately 5% of these survive for 5 years (17,18).…”

Section: Introductionmentioning

confidence: 99%

Activating Transcription Factor 3 Expression as a Marker of Response to the Histone Deacetylase Inhibitor Pracinostat

Sooraj

Cain

et al. 2016

Molecular Cancer Therapeutics

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Improved treatment strategies are required for bladder cancer due to frequent recurrence of low-grade tumors and poor survival rate from high-grade tumors with current therapies. Histone deacetylase inhibitors (HDACi), approved as single agents for specific lymphomas, have shown promising preclinical results in solid tumors but could benefit from identification of biomarkers for response. Loss of activating transcription factor 3 (ATF3) expression is a feature of bladder tumor progression and correlates with poor survival. We investigated the utility of measuring ATF3 expression as a marker of response to the HDACi pracinostat in bladder cancer models. Pracinostat treatment of bladder cancer cell lines reactivated the expression of ATF3, correlating with significant alteration in proliferative, migratory, and anchoragedependent growth capacities. Pracinostat also induced growth arrest at the G 0 -G 1 cell-cycle phase, coincident with the activation of tumor suppressor genes. In mouse xenograft bladder cancer models, pracinostat treatment significantly reduced tumor volumes compared with controls, accompanied by reexpression of ATF3 in nonproliferating cells from early to late stage of therapy and in parallel induced antiangiogenesis and apoptosis. Importantly, cells in which ATF3 expression was depleted were less sensitive to pracinostat treatment in vitro, exhibiting significantly higher proliferative and migratory properties. In vivo, control xenograft tumors were significantly more responsive to treatment than ATF3 knockdown xenografts. Thus, reactivation of ATF3 is an important factor in determining sensitivity to pracinostat treatment, both in vitro and in vivo, and could serve as a potential biomarker of response and provide a rationale for therapeutic utility in HDACi-mediated treatments for bladder cancer.

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Section: Introductionmentioning

confidence: 99%

Activating Transcription Factor 3 Expression as a Marker of Response to the Histone Deacetylase Inhibitor Pracinostat

Sooraj

Cain

et al. 2016

Molecular Cancer Therapeutics

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“…This allows an increased MMC uptake. Additionally, MMC is more effective at higher temperatures, resulting in a synergistic effect [7]. Another suggested mechanism is that hyperthermia activates an immune response, by mimicking fever.…”

Section: Chemohyperthermia Principlesmentioning

confidence: 99%

Chemohyperthermia in non-muscle-invasive bladder cancer: An overview of the literature and recommendations

Liem

Crezee

Rosette

et al. 2016

International Journal of Hyperthermia

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Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high risk of recurrence for the present standard treatment of transurethral resection of the bladder (TURB) followed by intravesical instillation of Mitomycin-C (MMC) or bacillus Calmette-Gu erin (BCG). To decrease this high recurrence rate, alternative treatments are studied. Intravesical MMC combined with hyperthermia could be an interesting alternative active treatment for intermediate-and high-risk NMIBC, and has been investigated in the past years. Hyperthermia, raising tumour temperatures to 40-44 C, can be achieved with several hyperthermia systems, based on three different techniques: 1) intravesical microwave induced heating, 2) conductive heating, and 3) loco-regional, using external radiofrequency antennas. In this review an overview is given of the available hyperthermia systems and the reported outcomes. Future directions are discussed. Optimal implementation of a combined regimen of MMC and hyperthermia requires further clinical trials to identify patients who will benefit most from this treatment, to optimise treatment schedules and to compare the efficacy of different hyperthermia devices. ARTICLE HISTORY

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“…However, its clinical effectiveness is limited bythe occurrence of resistance to MMC (12)(13)(14). To overcome this treatment resistance, MMC is often combined with other agents to increase MMC chemotherapy sensitivity (15).…”

Section: Introductionmentioning

confidence: 99%

Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82 human bladder cancer cells

Zhang

Chen²,

Dong³

et al. 2018

Oncol Lett

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Abstract. The occurrence of resistance to mitomycin C (MMC) often limits its clinical effectiveness. Combination therapy thus is employed to overcome this treatment resistance. The present study aimed to establish a novel J82 bladder cancer cell line so as to study the effect of inhibition of aquaporin 1 (AQP-1) on chemotherapy sensitivity of J82 bladder cancer cells. A novel J82 bladder cancer cell line whose expression of AQP-1 is inhibited was established through transfection of J82 cells with newly constructed recombinant plasmid. The resulting cell line was designated J82-short hairpin (sh)AQP1 and was subjected to further analyses together with J82 cell line. Reverse transcription-polymerase chain reaction was used to quantify the expression of AQP-1mRNA in the cells; cell viability was analyzed with MTT assay and apoptosis was measured by flow cytometry. The expression of cell proliferation and cell apoptosis-associated proteins, proliferating cell nuclear antigen (PCNA), B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax) and caspase-3, were detected by Western blot. A statistically significant decrease in the transcription and expression of AQP1 was observed in the J82-shAQP1 cells as compared with J82 cells. J82-shAQP1 cells treated by MMC, also had a lower cell viability than J82 cells treated by MMC and showed enhanced apoptosis. Western blot analysis revealed J82-shAQP1 cells treated by MMC had less expression of PCNA, lower bcl-2/Bax ratio and more expression of caspase-3 as compared with the J82 cells treated by MMC. Selective inhibition of AQP-1 enhanced MMC chemotherapy sensitivity of J82 bladder cancer cells, suggesting combination of AQP-1 inhibition with MMC treatment as a promising treatment strategy to overcome bladder cancer treatment resistance.

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Optimizing intravesical mitomycin C therapy in non-muscle-invasive bladder cancer

Cited by 55 publications

References 75 publications

Activating Transcription Factor 3 Expression as a Marker of Response to the Histone Deacetylase Inhibitor Pracinostat

Activating Transcription Factor 3 Expression as a Marker of Response to the Histone Deacetylase Inhibitor Pracinostat

Chemohyperthermia in non-muscle-invasive bladder cancer: An overview of the literature and recommendations

Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82 human bladder cancer cells

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