Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity

Theresa M. Harned, Ondrej Kalous, Alexander Neuwelt, Jason Loera, Lingyun Ji, Peter Iovine, Richard Sposto, Edward Neuwelt, C. Patrick Reynolds

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)533-540
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number2
DOIs
StatePublished - Jan 15 2008
Externally publishedYes

Fingerprint

Cisplatin
Neuroblastoma
Heterografts
sodium thiosulfate
Cell Line
Optical Imaging
Disease-Free Survival
Microscopy
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Harned, T. M., Kalous, O., Neuwelt, A., Loera, J., Ji, L., Iovine, P., ... Reynolds, C. P. (2008). Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity. Clinical Cancer Research, 14(2), 533-540. https://doi.org/10.1158/1078-0432.CCR-06-2289

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 journalArticle

Harned, TM, Kalous, O, Neuwelt, A, Loera, J, Ji, L, Iovine, P, Sposto, R, Neuwelt, E & Reynolds, CP 2008, 'Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity', Clinical Cancer Research, vol. 14, no. 2, pp. 533-540. https://doi.org/10.1158/1078-0432.CCR-06-2289
Harned, Theresa M. ; Kalous, Ondrej ; Neuwelt, Alexander ; Loera, Jason ; Ji, Lingyun ; Iovine, Peter ; Sposto, Richard ; Neuwelt, Edward ; Reynolds, C. Patrick. / Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 2. pp. 533-540.
@article{5e5b4b0259f24d58b1ffad9c2aad4d25,
title = "Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity",
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.",
author = "Harned, {Theresa M.} and Ondrej Kalous and Alexander Neuwelt and Jason Loera and Lingyun Ji and Peter Iovine and Richard Sposto and Edward Neuwelt and Reynolds, {C. Patrick}",
year = "2008",
month = "1",
day = "15",
doi = "10.1158/1078-0432.CCR-06-2289",
language = "English (US)",
volume = "14",
pages = "533--540",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

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

VL - 14

SP - 533

EP - 540

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 2

ER -