Abstract
Purpose: We determined if the potentially otoprotective agent sodium thiosulfate (STS) could be given 6 h after cisplatin without diminishing the antineuroblastoma activity of cisplatin in human neuroblastoma cell lines in vitro (including cisplatin-resistant cell lines) and in neuroblastoma xenografts in vivo. Experimental Design: We determined the antineuroblastoma activity of cisplatin with or without the addition of STS at 0 or 6 h after cisplatin in six neuroblastoma cell lines, both in standard cell culture conditions (20% O 2) and in physiologic hypoxia (2% O2). Drug cytotoxicity was measured using the DIMSCAN fluorescence/digital imaging microscopy assay. In vivo studies of cisplatin combined with STS used a human neuroblastoma subcutaneous xenograft model (SMS-SAN) in athymic nu/numice. Results: A significant protection against cisplatin cytotoxicity was seen when the neuroblastoma cells were exposed to cisplatin directly combined with STS. However, when cisplatin was given first and STS exposure occurred 6 h later, no effect on cisplatin cytotoxicity was observed. In a subcutaneous neuroblastoma xenograft model in nu/nu mice, mice receiving cisplatin alone or cisplatin + STS at 6 h had significantly better progression-free survival rates (P <0.03) compared with controls or mice treated with cisplatin + STS concurrently. There was no statistically significant difference in outcomes between mice treated with cisplatin alone and the group treated with cisplatin followed by STS 6 h later (P = 0.9). Conclusion: These preclinicaldata suggest that theuse of STS 6 h after cisplatin for otoprotection is unlikely to compromise the antineuroblastoma activity of cisplatin.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 533-540 |
| Number of pages | 8 |
| Journal | Clinical Cancer Research |
| Volume | 14 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 15 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity. / Harned, Theresa M.; Kalous, Ondrej; Neuwelt, Alexander; Loera, Jason; Ji, Lingyun; Iovine, Peter; Sposto, Richard; Neuwelt, Edward; Reynolds, C. Patrick.
In: Clinical Cancer Research, Vol. 14, No. 2, 15.01.2008, p. 533-540.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity
AU - Harned, Theresa M.
AU - Kalous, Ondrej
AU - Neuwelt, Alexander
AU - Loera, Jason
AU - Ji, Lingyun
AU - Iovine, Peter
AU - Sposto, Richard
AU - Neuwelt, Edward
AU - Reynolds, C. Patrick
PY - 2008/1/15
Y1 - 2008/1/15
N2 - Purpose: We determined if the potentially otoprotective agent sodium thiosulfate (STS) could be given 6 h after cisplatin without diminishing the antineuroblastoma activity of cisplatin in human neuroblastoma cell lines in vitro (including cisplatin-resistant cell lines) and in neuroblastoma xenografts in vivo. Experimental Design: We determined the antineuroblastoma activity of cisplatin with or without the addition of STS at 0 or 6 h after cisplatin in six neuroblastoma cell lines, both in standard cell culture conditions (20% O 2) and in physiologic hypoxia (2% O2). Drug cytotoxicity was measured using the DIMSCAN fluorescence/digital imaging microscopy assay. In vivo studies of cisplatin combined with STS used a human neuroblastoma subcutaneous xenograft model (SMS-SAN) in athymic nu/numice. Results: A significant protection against cisplatin cytotoxicity was seen when the neuroblastoma cells were exposed to cisplatin directly combined with STS. However, when cisplatin was given first and STS exposure occurred 6 h later, no effect on cisplatin cytotoxicity was observed. In a subcutaneous neuroblastoma xenograft model in nu/nu mice, mice receiving cisplatin alone or cisplatin + STS at 6 h had significantly better progression-free survival rates (P <0.03) compared with controls or mice treated with cisplatin + STS concurrently. There was no statistically significant difference in outcomes between mice treated with cisplatin alone and the group treated with cisplatin followed by STS 6 h later (P = 0.9). Conclusion: These preclinicaldata suggest that theuse of STS 6 h after cisplatin for otoprotection is unlikely to compromise the antineuroblastoma activity of cisplatin.
AB - Purpose: We determined if the potentially otoprotective agent sodium thiosulfate (STS) could be given 6 h after cisplatin without diminishing the antineuroblastoma activity of cisplatin in human neuroblastoma cell lines in vitro (including cisplatin-resistant cell lines) and in neuroblastoma xenografts in vivo. Experimental Design: We determined the antineuroblastoma activity of cisplatin with or without the addition of STS at 0 or 6 h after cisplatin in six neuroblastoma cell lines, both in standard cell culture conditions (20% O 2) and in physiologic hypoxia (2% O2). Drug cytotoxicity was measured using the DIMSCAN fluorescence/digital imaging microscopy assay. In vivo studies of cisplatin combined with STS used a human neuroblastoma subcutaneous xenograft model (SMS-SAN) in athymic nu/numice. Results: A significant protection against cisplatin cytotoxicity was seen when the neuroblastoma cells were exposed to cisplatin directly combined with STS. However, when cisplatin was given first and STS exposure occurred 6 h later, no effect on cisplatin cytotoxicity was observed. In a subcutaneous neuroblastoma xenograft model in nu/nu mice, mice receiving cisplatin alone or cisplatin + STS at 6 h had significantly better progression-free survival rates (P <0.03) compared with controls or mice treated with cisplatin + STS concurrently. There was no statistically significant difference in outcomes between mice treated with cisplatin alone and the group treated with cisplatin followed by STS 6 h later (P = 0.9). Conclusion: These preclinicaldata suggest that theuse of STS 6 h after cisplatin for otoprotection is unlikely to compromise the antineuroblastoma activity of cisplatin.
UR - http://www.scopus.com/inward/record.url?scp=38949097507&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38949097507&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-06-2289
DO - 10.1158/1078-0432.CCR-06-2289
M3 - Article
C2 - 18223229
AN - SCOPUS:38949097507
VL - 14
SP - 533
EP - 540
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 2
ER -