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The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours.
We have studied the influence of the peripheral vasodilator hydralazine (HDZ) on the vasculature and blood perfusion of two members of a series of subcutaneous murine adenocarcinomata of the colon (MAC tumours), and the influence of HDZ on the efficacy and/or toxicity of TCNU and melphalan. The fluo...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1992
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977797/ https://www.ncbi.nlm.nih.gov/pubmed/1503906 |
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author | Quinn, P. K. Bibby, M. C. Cox, J. A. Crawford, S. M. |
author_facet | Quinn, P. K. Bibby, M. C. Cox, J. A. Crawford, S. M. |
author_sort | Quinn, P. K. |
collection | PubMed |
description | We have studied the influence of the peripheral vasodilator hydralazine (HDZ) on the vasculature and blood perfusion of two members of a series of subcutaneous murine adenocarcinomata of the colon (MAC tumours), and the influence of HDZ on the efficacy and/or toxicity of TCNU and melphalan. The fluorescent DNA stain Hoechst 33342, showed that HDZ caused a shutdown of tumour vasculature, related in magnitude to both dose and tumour differentiation state; 10 mg kg-1 caused an 80% vascular shutdown of well differentiated MAC 26 tumours, but only a 50% shutdown of the poorly differentiated MAC 15A tumours. 2.5 mg kg-1 was ineffective. The blood perfusion marker 99mTc-HMPAO showed that the normal perfusion of MAC tumours was consistently markedly less than that of lung, liver or kidneys (4-5% of lung perfusion). HDZ (10 mg kg-1) decreased MAC 26 perfusion by 63%, and that of MAC 15A by 20%. Again, 2.5 mg kg-1) was ineffective. Use of in vivo to in vitro clonogenic assays showed that HDZ (10 mg kg-1) potentiated the efficacy of melphalan (1-10 mg kg-1 i.p.) by a factor of 2.1, and increased the efficacy of TCNU (1-10 mg kg-1 i.v., factor = 1.7) when given 10 or 15 min respectively after dosing. However, the addition of HDZ increased the acute bone marrow toxicity of melphalan, but not that of TCNU. The clinical relevance of these results is discussed. IMAGES: |
format | Text |
id | pubmed-1977797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1992 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-19777972009-09-10 The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours. Quinn, P. K. Bibby, M. C. Cox, J. A. Crawford, S. M. Br J Cancer Research Article We have studied the influence of the peripheral vasodilator hydralazine (HDZ) on the vasculature and blood perfusion of two members of a series of subcutaneous murine adenocarcinomata of the colon (MAC tumours), and the influence of HDZ on the efficacy and/or toxicity of TCNU and melphalan. The fluorescent DNA stain Hoechst 33342, showed that HDZ caused a shutdown of tumour vasculature, related in magnitude to both dose and tumour differentiation state; 10 mg kg-1 caused an 80% vascular shutdown of well differentiated MAC 26 tumours, but only a 50% shutdown of the poorly differentiated MAC 15A tumours. 2.5 mg kg-1 was ineffective. The blood perfusion marker 99mTc-HMPAO showed that the normal perfusion of MAC tumours was consistently markedly less than that of lung, liver or kidneys (4-5% of lung perfusion). HDZ (10 mg kg-1) decreased MAC 26 perfusion by 63%, and that of MAC 15A by 20%. Again, 2.5 mg kg-1) was ineffective. Use of in vivo to in vitro clonogenic assays showed that HDZ (10 mg kg-1) potentiated the efficacy of melphalan (1-10 mg kg-1 i.p.) by a factor of 2.1, and increased the efficacy of TCNU (1-10 mg kg-1 i.v., factor = 1.7) when given 10 or 15 min respectively after dosing. However, the addition of HDZ increased the acute bone marrow toxicity of melphalan, but not that of TCNU. The clinical relevance of these results is discussed. IMAGES: Nature Publishing Group 1992-08 /pmc/articles/PMC1977797/ /pubmed/1503906 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Quinn, P. K. Bibby, M. C. Cox, J. A. Crawford, S. M. The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours. |
title | The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours. |
title_full | The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours. |
title_fullStr | The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours. |
title_full_unstemmed | The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours. |
title_short | The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours. |
title_sort | influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of mac tumours. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977797/ https://www.ncbi.nlm.nih.gov/pubmed/1503906 |
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