The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy

S. J. Lunt; C. Cawthorne; M. Ali; B. A. Telfer; M. Babur; A. Smigova; P. J. Julyan; P. M. Price; I. J. Stratford; W. D. Bloomer; M. V. Papadopoulou; K. J. Williams

doi:10.1038/sj.bjc.6605753

The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy

S. J. Lunt, C. Cawthorne, M. Ali, B. A. Telfer, M. Babur, A. Smigova, P. J. Julyan, P. M. Price, I. J. Stratford, W. D. Bloomer, M. V. Papadopoulou, K. J. Williams

Research output: Contribution to journal › Article › peer-review

Abstract

Background:Metastases cause most cancer-related deaths. We investigated the use of hypoxia-selective cytotoxins as adjuvants to radiotherapy in the control of metastatic tumour growth.Methods:The NLCQ-1, RB6145 and tirapazamine were assessed against the spontaneously metastasising KHT model. Subcutaneous KHT tumours (250mm3) were irradiated with 25Gy (single fraction) to control primary growth. Equitoxic drug treatments (NLCQ-1 (10mgkg-1) once daily; RB6145 (75mgkg-1) and tirapazamine (13mgkg-1) twice daily) were administered 3-6 days post-radiotherapy when hypoxic cells were evident in lung micrometastases. Mice were culled when 50 of controls exhibited detrimental signs of lung metastases.Results:In total, 95 of control mice presented with lung disease. This was significantly reduced by NLCQ-1 (33; P0.0002) and RB6145 (60; P0.02). Semi-quantitative grading of lung disease revealed a significant improvement with all treatments, with NLCQ-1 proving most efficacious (median grades: control, 4; NLCQ, 0 (P

Original language	English
Pages (from-to)	201-208
Number of pages	7
Journal	British Journal of Cancer
Volume	103
Issue number	2
DOIs	https://doi.org/10.1038/sj.bjc.6605753
Publication status	Published - 13 Jul 2010

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Lunt, S. J., Cawthorne, C., Ali, M., Telfer, B. A., Babur, M., Smigova, A., Julyan, P. J., Price, P. M., Stratford, I. J., Bloomer, W. D., Papadopoulou, M. V., & Williams, K. J. (2010). The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy. British Journal of Cancer, 103(2), 201-208. https://doi.org/10.1038/sj.bjc.6605753

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title = "The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy",

abstract = "Background:Metastases cause most cancer-related deaths. We investigated the use of hypoxia-selective cytotoxins as adjuvants to radiotherapy in the control of metastatic tumour growth.Methods:The NLCQ-1, RB6145 and tirapazamine were assessed against the spontaneously metastasising KHT model. Subcutaneous KHT tumours (250mm3) were irradiated with 25Gy (single fraction) to control primary growth. Equitoxic drug treatments (NLCQ-1 (10mgkg-1) once daily; RB6145 (75mgkg-1) and tirapazamine (13mgkg-1) twice daily) were administered 3-6 days post-radiotherapy when hypoxic cells were evident in lung micrometastases. Mice were culled when 50 of controls exhibited detrimental signs of lung metastases.Results:In total, 95 of control mice presented with lung disease. This was significantly reduced by NLCQ-1 (33; P0.0002) and RB6145 (60; P0.02). Semi-quantitative grading of lung disease revealed a significant improvement with all treatments, with NLCQ-1 proving most efficacious (median grades: control, 4; NLCQ, 0 (P",

author = "Lunt, {S. J.} and C. Cawthorne and M. Ali and Telfer, {B. A.} and M. Babur and A. Smigova and Julyan, {P. J.} and Price, {P. M.} and Stratford, {I. J.} and Bloomer, {W. D.} and Papadopoulou, {M. V.} and Williams, {K. J.}",

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Lunt, SJ, Cawthorne, C, Ali, M, Telfer, BA, Babur, M, Smigova, A, Julyan, PJ, Price, PM, Stratford, IJ, Bloomer, WD, Papadopoulou, MV & Williams, KJ 2010, 'The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy', British Journal of Cancer, vol. 103, no. 2, pp. 201-208. https://doi.org/10.1038/sj.bjc.6605753

TY - JOUR

T1 - The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy

AU - Lunt, S. J.

AU - Cawthorne, C.

AU - Ali, M.

AU - Telfer, B. A.

AU - Babur, M.

AU - Smigova, A.

AU - Julyan, P. J.

AU - Price, P. M.

AU - Stratford, I. J.

AU - Bloomer, W. D.

AU - Papadopoulou, M. V.

AU - Williams, K. J.

PY - 2010/7/13

Y1 - 2010/7/13

N2 - Background:Metastases cause most cancer-related deaths. We investigated the use of hypoxia-selective cytotoxins as adjuvants to radiotherapy in the control of metastatic tumour growth.Methods:The NLCQ-1, RB6145 and tirapazamine were assessed against the spontaneously metastasising KHT model. Subcutaneous KHT tumours (250mm3) were irradiated with 25Gy (single fraction) to control primary growth. Equitoxic drug treatments (NLCQ-1 (10mgkg-1) once daily; RB6145 (75mgkg-1) and tirapazamine (13mgkg-1) twice daily) were administered 3-6 days post-radiotherapy when hypoxic cells were evident in lung micrometastases. Mice were culled when 50 of controls exhibited detrimental signs of lung metastases.Results:In total, 95 of control mice presented with lung disease. This was significantly reduced by NLCQ-1 (33; P0.0002) and RB6145 (60; P0.02). Semi-quantitative grading of lung disease revealed a significant improvement with all treatments, with NLCQ-1 proving most efficacious (median grades: control, 4; NLCQ, 0 (P

AB - Background:Metastases cause most cancer-related deaths. We investigated the use of hypoxia-selective cytotoxins as adjuvants to radiotherapy in the control of metastatic tumour growth.Methods:The NLCQ-1, RB6145 and tirapazamine were assessed against the spontaneously metastasising KHT model. Subcutaneous KHT tumours (250mm3) were irradiated with 25Gy (single fraction) to control primary growth. Equitoxic drug treatments (NLCQ-1 (10mgkg-1) once daily; RB6145 (75mgkg-1) and tirapazamine (13mgkg-1) twice daily) were administered 3-6 days post-radiotherapy when hypoxic cells were evident in lung micrometastases. Mice were culled when 50 of controls exhibited detrimental signs of lung metastases.Results:In total, 95 of control mice presented with lung disease. This was significantly reduced by NLCQ-1 (33; P0.0002) and RB6145 (60; P0.02). Semi-quantitative grading of lung disease revealed a significant improvement with all treatments, with NLCQ-1 proving most efficacious (median grades: control, 4; NLCQ, 0 (P

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DO - 10.1038/sj.bjc.6605753

M3 - Article

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SN - 0007-0920

VL - 103

SP - 201

EP - 208

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

ER -

The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy

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