Article Figures & Data
Figures
- Fig. 1.
Six representative neuroblastoma cell lines (SMS-KCNR, CHLA-15, SMS-SAN, CHLA-122, CHLA-20, and CHLA-42). The survival fraction for cells treated with cisplatin (2 μg/mL) + STS at hour 0 was significantly increased for six of six cell lines (SMS-SAN, CHLA-122, CHLA-15, CHLA-20, CHLA-42, and SMS-KCNR) in 20% oxygen. The survival fraction for cells treated with cisplatin + STS at 6 h was not significantly increased compared with cisplatin alone in five of six cell lines at the highest dose level of cisplatin (2 μg/mL; CHLA-122, CHLA-15, CHLA-20, CHLA-42, and SMS-KCNR). Two-sided P values were determined by likelihood ratio tests for the ratio of survival fractions for cisplatin + STS at hour 0 or hour 6 compared with cisplatin alone. A P < 0.05 was considered significant.
- Fig. 2.
The same six representative neuroblastoma cell lines (SMS-KCNR, CHLA-15, SMS-SAN, CHLA-122, CHLA-20, and CHLA-42) were also studied in conditions of physiologic hypoxia found in bone marrow (2% oxygen). Again, STS given 6 h after cisplatin did not significantly increase the survival fraction compared with cisplatin alone in five of six cell lines (CHLA-122, CHLA-15, CHLA-20, CHLA-42, and SMS-KCNR), whereas STS given simultaneously with cisplatin did increase the survival fraction compared with cisplatin alone in 2% O2 in five of six cell lines (SMS-SAN, CHLA-122, CHLA-15, CHLA-42, and SMS-KCNR). Two-sided P values were determined by likelihood ratio tests for the ratio of survival fractions for cisplatin + STS at hour 0 or hour 6 compared with cisplatin alone. A P < 0.05 was considered significant.
- Fig. 3.
STS given 0 or 6 h after etoposide did not affect etoposide cytotoxicity. In two representative neuroblastoma cell lines (CHLA-15 and SMS-SAN) STS given 0 or 6 h after etoposide did not affect the survival fraction for cells treated with etoposide.
- Fig. 4.
Exposure to STS at the same time as carboplatin decreased carboplatin cytotoxicity in two representative neuroblastoma cell lines (CHLA-15 and SMS-SAN), whereas exposure to STS 6 h after carboplatin did not protect from cytotoxicity.
- Fig. 5.
A, effect of STS and cisplatin on subcutaneous human neuroblastoma xenograft growth. Nude mice were inoculated s.c. with 3.2 × 107 SMS-SAN neuroblastoma cells and were treated as (a) no treatment (n = 5), (b) cisplatin (4 mg/kg i.p. × 4 d; n = 6), (c) cisplatin (4 mg/kg/d × 4 d) + STS (3.5 g/kg/d i.p. × 4 d immediately after cisplatin; n = 6), and (d) cisplatin (4mg/kg/d i.p. × 4 d) + STS (3.5 g/kg/d i.p × 4 d at 6 h after cisplatin; n = 6). Tumor volumes were measured twice per week. B, the time to tumor progression (tumor volume of >600 mm3 or last measurement taken) was determined. The probability of progression-free survival for the four treatment groups was determined using the permutated log-rank test. STS given 6 h after cisplatin daily for 4 d did not significantly (P = 0.9) affect cisplatin antitumor activity in SMS-SAN xenografts in nu/nu mice compared with cisplatin alone. However, STS given simultaneously with cisplatin daily for 4 d significantly (P = 0.03) protected tumors from cisplatin.
Volume 14, Issue 2
