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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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Successful preparation of cancer-tissue origi-nated spheroids (CTOS) in non-muscle invasive bladder cancer. (a) Success rate of CTOS preparation from transurethrally resected specimens of bladder cancers according to clinicopathological factors. Success of preparation was defined as ≥20 CTOS in the culture dish 1 day after preparation. Pathological T stage (pT) was classified according to the 2009 TNM classification. (b) H&E staining of the original tumor (left column) and CTOS (middle column) and phase contrast image of CTOS (right column) for BC232 (upper row); high-grade (HG) and pTa tumor, and BC239 (lower row); low-grade (LG) and pTa tumor. Scale bar, 100 μm.
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fig01: Successful preparation of cancer-tissue origi-nated spheroids (CTOS) in non-muscle invasive bladder cancer. (a) Success rate of CTOS preparation from transurethrally resected specimens of bladder cancers according to clinicopathological factors. Success of preparation was defined as ≥20 CTOS in the culture dish 1 day after preparation. Pathological T stage (pT) was classified according to the 2009 TNM classification. (b) H&E staining of the original tumor (left column) and CTOS (middle column) and phase contrast image of CTOS (right column) for BC232 (upper row); high-grade (HG) and pTa tumor, and BC239 (lower row); low-grade (LG) and pTa tumor. Scale bar, 100 μm.

Mentions: We previously reported the preparation and culture of bladder cancer cells from surgically resected samples based on the CTOS method.24 Here, we focused on CTOS from TUR samples. CTOS were prepared from 176 TUR samples, including 135 from the previous study. More than 20 CTOSs were obtained from each sample; the success rate of CTOS preparation was better in NMIBC (76.2%) than in MIBC (42.1%) (Fig.1a). Low-grade (in pathological findings) and papillary (in cystoscopic appearance) types had better success rates than others. The CTOS from high-grade tumors were irregularly shaped, with a high nucleus-to-cytoplasm ratio (Fig.1b). In contrast, CTOS from low-grade tumors were round, with a low nucleus-to-cytoplasm ratio. These findings were comparable to the original tumors. There was no correlation between clinicopathological factors and CTOS growth in 14 patient samples examined (Suppl. Table S1).


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)

Successful preparation of cancer-tissue origi-nated spheroids (CTOS) in non-muscle invasive bladder cancer. (a) Success rate of CTOS preparation from transurethrally resected specimens of bladder cancers according to clinicopathological factors. Success of preparation was defined as ≥20 CTOS in the culture dish 1 day after preparation. Pathological T stage (pT) was classified according to the 2009 TNM classification. (b) H&E staining of the original tumor (left column) and CTOS (middle column) and phase contrast image of CTOS (right column) for BC232 (upper row); high-grade (HG) and pTa tumor, and BC239 (lower row); low-grade (LG) and pTa tumor. Scale bar, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Successful preparation of cancer-tissue origi-nated spheroids (CTOS) in non-muscle invasive bladder cancer. (a) Success rate of CTOS preparation from transurethrally resected specimens of bladder cancers according to clinicopathological factors. Success of preparation was defined as ≥20 CTOS in the culture dish 1 day after preparation. Pathological T stage (pT) was classified according to the 2009 TNM classification. (b) H&E staining of the original tumor (left column) and CTOS (middle column) and phase contrast image of CTOS (right column) for BC232 (upper row); high-grade (HG) and pTa tumor, and BC239 (lower row); low-grade (LG) and pTa tumor. Scale bar, 100 μm.
Mentions: We previously reported the preparation and culture of bladder cancer cells from surgically resected samples based on the CTOS method.24 Here, we focused on CTOS from TUR samples. CTOS were prepared from 176 TUR samples, including 135 from the previous study. More than 20 CTOSs were obtained from each sample; the success rate of CTOS preparation was better in NMIBC (76.2%) than in MIBC (42.1%) (Fig.1a). Low-grade (in pathological findings) and papillary (in cystoscopic appearance) types had better success rates than others. The CTOS from high-grade tumors were irregularly shaped, with a high nucleus-to-cytoplasm ratio (Fig.1b). In contrast, CTOS from low-grade tumors were round, with a low nucleus-to-cytoplasm ratio. These findings were comparable to the original tumors. There was no correlation between clinicopathological factors and CTOS growth in 14 patient samples examined (Suppl. Table S1).

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