scholarly journals Low MSH2 protein levels identify muscle-invasive bladder cancer resistant to cisplatin

2018 ◽  
Author(s):  
Andrew Goodspeed ◽  
Annie Jean ◽  
James C. Costello
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cisplatin Resistance ◽  
Bladder Cancer Cell ◽  
Muscle Invasive Bladder Cancer ◽  
Protein Levels ◽  
Msh2 Protein ◽  
Muscle Invasive

AbstractBackgroundThe response to first-line, platinum-based treatment of muscle-invasive bladder cancer has not improved in three decades.ObjectiveThe objective of this study is to identify genes that predict cisplatin resistance in bladder cancer.DesignWe performed a whole-genome, CRISPR-based screen in a bladder cancer cell line treated with cisplatin to identify genes that mediate response to cisplatin. Targeted validation was performed in vitro across two bladder cancer cell lines. The top gene candidate was validated in a publicly available bladder cancer dataset containing 340 bladder cancer patients with treatment, protein, and survival information.Results and limitationsThe cisplatin resistance screen suggested the mismatch repair pathway through the loss of MSH2 and MLH1 contribute to cisplatin resistance. Bladder cancer cells depleted of MSH2 are resistant to cisplatin in vitro, in part due to a reduction in apoptosis. These cells maintain sensitivity to the cisplatin-analog, oxaliplatin. Bladder tumors with low protein levels of MSH2 have poorer overall survival when treated with cisplatin- or carboplatin-based therapy.ConclusionsWe generated in vitro and clinical support that bladder cancer cell lines and tumors with low levels of MSH2 are more resistant to cisplatin-based therapy. Further studies are warranted to determine the ability of MSH2 protein levels to serve as a prospective biomarker of chemotherapy response in bladder cancer.Patient summaryWe report the first evidence that the protein level of MSH2 may contribute to chemotherapy resistance observed in bladder cancer. MSH2 levels has the potential to serve as a biomarker of treatment response.

Synthesis, Characterization, and Biological Activity of Anthraquinone-Substituted Imidazolium Salts for the Treatment of Bladder Cancer

2020 ◽  
Vol 6 (4) ◽  
pp. 471-479
Author(s):  
Michael L. Stromyer ◽  
David J. Weader ◽  
Uttam Satyal ◽  
Philip H. Abbosh ◽  
Wiley J. Youngs
Keyword(s):  
Bladder Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
High Grade ◽  
Imidazolium Salts ◽  
Muscle Invasive Bladder Cancer ◽  
Imidazolium Salt ◽  
Muscle Invasive

BACKGROUND: Bladder cancer is one of the most common types of cancer diagnosed each year, and more than half of patients have non-muscle invasive bladder cancer (NMIBC). The standard of care for patients with high-grade NMIBC is Bacillus Calmette-Guerin (BCG). Unfortunately, multiple BCG shortages have limited access to this treatment. Available alternatives using intravesical administration of chemotherapy have some efficacy, but lack prospective validation and long-term outcomes. Development of novel intravesical therapies may provide more active alternatives to BCG for patients with high-grade NMIBC. OBJECTIVE: To develop an optimal imidazolium salt for the intravesical treatment of NMIBC and determine preliminary in vitro activity of anthraquinone-substituted imidazolium salts. METHODS: The development of the anthraquinone-substituted imidazolium salts was undertaken in an attempt to increase the potency of this class of compounds by incorporating the quinone functional group observed in the chemotherapeutics doxorubicin, valrubicin, and mitomycin. All compounds were characterized by 1H and 13C NMR spectroscopy and infrared spectroscopy. Furthermore, these imidazolium salts were tested for in vitro cytotoxicity by the Developmental Therapeutics Program (DTP) on the NCI-60 human tumor cell line screening. Additional in vitro testing was performed against diverse bladder cancer cell lines (RT112, TCCSUP, J82, and UMUC13) using CellTiter-Glo® assays and colony-forming assays. RESULTS: The NCI-60 cell line screening indicated that compound 7 had the highest activity and was concluded to be the optimal compound for further study. Using CellTiter-Glo® assays on bladder cancer cell lines, 50% growth inhibitory concentration (IC50) values were determined to range from 32–50μM after an exposure of 1 h, for compound 7. Further evaluation of the compound by colony-forming assays showed the complete inhibition of growth at 10 days post a 100μM dose of compound 7 for 1 h. CONCLUSIONS: The most active lipophilic anthraquinone imidazolium salt, compound 7, could be a viable treatment for non-muscle invasive bladder cancer as it exhibits a cell-killing effect at a 1 h time period and completely inhibits cancer regrowth in colony-forming assays.

scholarly journals Protein expression profile related to cisplatin resistance in bladder cancer cell lines detected by two-dimensional gel electrophoresis

2015 ◽  
Vol 36 (4) ◽  
pp. 253-261 ◽  
Author(s):  
Yoshinori TAOKA ◽  
Kazumasa MATSUMOTO ◽  
Kazuya OHASHI ◽  
Satoru MINAMIDA ◽  
Masahiro HAGIWARA ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Protein Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Expression Profile ◽  
Cisplatin Resistance ◽  
Cancer Cell Lines ◽  
Bladder Cancer Cell ◽  
Two Dimensional ◽  
Protein Expression Profile

scholarly journals In vitro Assessment of Intra-operative and Post-operative Environment in Reducing Bladder Cancer Recurrence

2021 ◽  
Author(s):  
Ryan Tsz-Hei TSE ◽  
Hongda ZHAO ◽  
Christine Yim-Ping WONG ◽  
Angel Wing-Yan KONG ◽  
Ronald Cheong-Kin CHAN ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Recurrence Rate ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Recurrence ◽  
Bladder Cancer Cell ◽  
Sterile Water ◽  
Cytotoxic Effects ◽  
Bladder Cancer Recurrence

Abstract Urinary bladder cancer is a common cancer worldwide. Currently, the modality of treating and monitoring bladder cancer is wide. Nonetheless, the high recurrence rate of non-muscle-invasive bladder cancer after surgical resection is still unsatisfactory. Hereby, our study demonstrated whether the intra-operative and post-operative environments will affect bladder cancer recurrence utilizing in vitro cell line model. Bladder cancer cell lines were submerged in four different irrigating fluids for assessing their tumorigenic properties. Our results showed that sterile water performed the best in terms of the magnitude of cytotoxicity to cell lines. Besides, we also investigated cytotoxic effects of the four irrigating agents as well as mitomycin C (MMC) in normothermic and hyperthermic conditions. We observed that sterile water and MMC had an increased cytotoxic effects to bladder cancer cell lines in hyperthermic conditions. Altogether, our results could be translated into clinical practice in the future by manipulating the intra-operative and post-operative conditions in order to lower the chance of residual cancer cell reimplant onto the bladder, which in turns, reducing the recurrence rate of bladder cancers.

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