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High-dose chemotherapeutics of intravesical chemotherapy rapidly induce mitochondrial dysfunction in bladder cancer-derived spheroids.

Yoshida T, Okuyama H, Nakayama M, Endo H, Nonomura N, Nishimura K, Inoue M - Cancer Sci. (2014)

Bottom Line: Two hours after exposure to MMC, the mitochondrial membrane potential decreased and the mitochondria were fragmented, while plasma membrane integrity was maintained.ATP levels rapidly decreased in CTOS after exposure to EPI or MMC.In the CTOS prepared directly from 19 surgical specimens exposed to EPI and MMC, the decrease of ATP levels varied among patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.

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Individual responses of primary cancer-tissue originated spheroids (CTOS) to high-dose chemotherapeutic agents. (a) Clinicopathological characteristics of 19 primary specimens of bladder cancer. (b) Bar plot shows ATP levels in CTOS after 2 h exposure to epirubicin (EPI) or mitomycin C (MMC) (1 mg/mL). (c) Each dot represents ATP levels after 2 h exposure to EPI or MMC in CTOS prepared from each case. R2 = 0.000822 (linear regression analysis).
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fig06: Individual responses of primary cancer-tissue originated spheroids (CTOS) to high-dose chemotherapeutic agents. (a) Clinicopathological characteristics of 19 primary specimens of bladder cancer. (b) Bar plot shows ATP levels in CTOS after 2 h exposure to epirubicin (EPI) or mitomycin C (MMC) (1 mg/mL). (c) Each dot represents ATP levels after 2 h exposure to EPI or MMC in CTOS prepared from each case. R2 = 0.000822 (linear regression analysis).

Mentions: We used CTOS prepared from primary patient samples to assess individual responses by measuring ATP levels after exposure to high-dose chemotherapy. Figure6a shows the clinicopathological characteristics of 19 patients from whom CTOS were prepared. The decrease of ATP levels varied among CTOS derived from 19 surgical specimens; it ranged from 22.5% to 83.1% in EPI-treated and from 16.9% to 88.4% in MMC-treated CTOS (Fig.6b). The mean reduction of ATP among 19 cases was 47.7% when treated with EPI and 50.6% when treated with MMC; the between-treatment difference was not statistically significant. No association was observed between clinicopathological factors and ATP decrease. There was no correlation in the ATP values between MMC and EPI after 2 h exposure to high-dose chemotherapeutics (Fig.6c), although it should be noted that one drug tended to have better effects than the other in some patients. The treatment protocols after TUR are too diverse and the number of patient samples is too small in this study to assess the correlation between the recurrence rate and the ATP decrease.


High-dose chemotherapeutics of intravesical chemotherapy rapidly induce mitochondrial dysfunction in bladder cancer-derived spheroids.

Yoshida T, Okuyama H, Nakayama M, Endo H, Nonomura N, Nishimura K, Inoue M - Cancer Sci. (2014)

Individual responses of primary cancer-tissue originated spheroids (CTOS) to high-dose chemotherapeutic agents. (a) Clinicopathological characteristics of 19 primary specimens of bladder cancer. (b) Bar plot shows ATP levels in CTOS after 2 h exposure to epirubicin (EPI) or mitomycin C (MMC) (1 mg/mL). (c) Each dot represents ATP levels after 2 h exposure to EPI or MMC in CTOS prepared from each case. R2 = 0.000822 (linear regression analysis).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317779&req=5

fig06: Individual responses of primary cancer-tissue originated spheroids (CTOS) to high-dose chemotherapeutic agents. (a) Clinicopathological characteristics of 19 primary specimens of bladder cancer. (b) Bar plot shows ATP levels in CTOS after 2 h exposure to epirubicin (EPI) or mitomycin C (MMC) (1 mg/mL). (c) Each dot represents ATP levels after 2 h exposure to EPI or MMC in CTOS prepared from each case. R2 = 0.000822 (linear regression analysis).
Mentions: We used CTOS prepared from primary patient samples to assess individual responses by measuring ATP levels after exposure to high-dose chemotherapy. Figure6a shows the clinicopathological characteristics of 19 patients from whom CTOS were prepared. The decrease of ATP levels varied among CTOS derived from 19 surgical specimens; it ranged from 22.5% to 83.1% in EPI-treated and from 16.9% to 88.4% in MMC-treated CTOS (Fig.6b). The mean reduction of ATP among 19 cases was 47.7% when treated with EPI and 50.6% when treated with MMC; the between-treatment difference was not statistically significant. No association was observed between clinicopathological factors and ATP decrease. There was no correlation in the ATP values between MMC and EPI after 2 h exposure to high-dose chemotherapeutics (Fig.6c), although it should be noted that one drug tended to have better effects than the other in some patients. The treatment protocols after TUR are too diverse and the number of patient samples is too small in this study to assess the correlation between the recurrence rate and the ATP decrease.

Bottom Line: Two hours after exposure to MMC, the mitochondrial membrane potential decreased and the mitochondria were fragmented, while plasma membrane integrity was maintained.ATP levels rapidly decreased in CTOS after exposure to EPI or MMC.In the CTOS prepared directly from 19 surgical specimens exposed to EPI and MMC, the decrease of ATP levels varied among patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.

Show MeSH
Related in: MedlinePlus