Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Hypoxia has been associated with poor local tumour control and relapse in many cancer sites, including carcinoma of the prostate. This translational study tests whether breathing carbogen gas improves the oxygenation of human prostate carcinoma xenografts in mice and in human patients with prostate...

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Vydané v:	British journal of cancer Ročník 100; číslo 4; s. 644 - 648
Hlavní autori:	Alonzi, R, Padhani, A R, Maxwell, R J, Taylor, N J, Stirling, J J, Wilson, J I, d′Arcy, J A, Collins, D J, Saunders, M I, Hoskin, P J
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 24.02.2009 Nature Publishing Group
Predmet:	Aged Animals Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Carbon Dioxide - blood Carbon Dioxide - metabolism Cell Hypoxia Cell Line, Tumor Drug Resistance Epidemiology Human subjects Humans Hypoxia Magnetic Resonance Imaging Male Medical prognosis Medical research Medical sciences Mice Middle Aged Molecular Medicine Neoplasm Transplantation - diagnostic imaging Nephrology. Urinary tract diseases Oncology Oxygen - blood Oxygen - metabolism Oxygen Inhalation Therapy Prostate cancer Prostatic Neoplasms - diagnostic imaging Prostatic Neoplasms - metabolism Prostatic Neoplasms - therapy Radiation therapy Radiography Translational Therapeutics Transplantation, Heterologous Tumors Tumors of the urinary system Urinary tract. Prostate gland United Kingdom > UK hypoxia prostate cancer magnetic resonance imaging BOLD carbogen Prostate disease Transplantation Heterotransplantation Cancerology Surgery Graft Male genital diseases Human Oxygen Urinary system disease Rodentia Malignant tumor Nuclear magnetic resonance imaging Genetic translation Vertebrata Mammalia Treatment Mouse Animal Medical imagery Hypoxia Oxygenation Prostate cancer Cancer
ISSN:	0007-0920, 1532-1827, 1532-1827
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Shrnutí:	Hypoxia has been associated with poor local tumour control and relapse in many cancer sites, including carcinoma of the prostate. This translational study tests whether breathing carbogen gas improves the oxygenation of human prostate carcinoma xenografts in mice and in human patients with prostate cancer. A total of 23 DU145 tumour-bearing mice, 17 PC3 tumour-bearing mice and 17 human patients with prostate cancer were investigated. Intrinsic susceptibility-weighted MRI was performed before and during a period of carbogen gas breathing. Quantitative R 2 * pixel maps were produced for each tumour and at each time point and changes in R 2 * induced by carbogen were determined. There was a mean reduction in R 2 * of 6.4% ( P =0.003) for DU145 xenografts and 5.8% ( P =0.007) for PC3 xenografts. In all, 14 human subjects were evaluable; 64% had reductions in tumour R 2 * during carbogen inhalation with a mean reduction of 21.6% ( P =0.0005). Decreases in prostate tumour R 2 * in both animal models and human patients as a result of carbogen inhalation suggests the presence of significant hypoxia. The finding that carbogen gas breathing improves prostate tumour oxygenation provides a rationale for testing the radiosensitising effects of combining carbogen gas breathing with radiotherapy in prostate cancer patients.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0007-0920 1532-1827 1532-1827
DOI:	10.1038/sj.bjc.6604903