Radiation and the microenvironment - Tumorigenesis and therapy
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA. Nature reviews. Cancer
(Impact Factor: 37.4).
12/2005; 5(11):867-75. DOI: 10.1038/nrc1735
Radiation rapidly and persistently alters the soluble and insoluble components of the tissue microenvironment. This affects the cell phenotype, tissue composition and the physical interactions and signalling between cells. These alterations in the microenvironment can contribute to carcinogenesis and alter the tissue response to anticancer therapy. Examples of these responses and their implications are discussed with a view to therapeutic intervention.
Available from: Ammar Almayah
- "The microenvironment in which a genetically altered cell resides also plays several important roles. It can suppress the expression of malignant cell characteristics, promote cell division, or increase the mutation rate . Radiation has proven to be valuable in the study of cell–cell communication, such as that which occurs within the microenvironment , and may include signals passed between normal cells, from normal to malignant cells or vice versa, or between malignant cells. "
Available from: Per Karlsson
- "TGFˇwas identified as a critical signal, accelerating carcinogenesis. Such cellular and tissue responses to ionizing radiation can have non-targeted effects on non-irradiated cells, such as induction of genomic instability . Since the mechanisms and timing of breast cancer development are complex and not well understood, most efforts to develop mechanistic cancer models including GI concentrated on colon cancer , including additional pathways for genomic instability     . "
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ABSTRACT: The cohort of 17,200 female Swedish hemangioma patients, who had been exposed to ionizing radiation because of skin hemangioma, was analyzed for breast cancer incidence with descriptive excess relative risk models and mechanistic models of carcinogenesis. The dosimetry system has recently been updated, leading to substantially reduced doses for the most highly exposed part of the Stockholm cohort. The follow-up includes persons until December 2009 with 877 breast cancer cases. All models agree on the risk estimates. The excess relative and excess absolute risk at the age of 50 years are 0.48Gy(-1) (95% CI 0.28; 0.69) and 10.4 [Formula: see text] (95% CI 6.1; 14.4), respectively. These risk estimates are about a factor of 2 higher than previous analyses of this cohort as a consequence of the re-evaluation of the dosimetry system. Explicit models incorporating effects of genomic instability were developed and applied to the hemangioma cohort. It was found that a radiation-induced transition towards genomic instability was highly significant. The models indicate that the main effect of radiation-induced genomic instability is to increase the rate of transition of non-initiated cells to initiated cells with a proliferative advantage. The magnitude of such an acceleration cannot be inferred from epidemiological data alone, but must be complemented by radiobiological measurements.
Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Available from: Johan Spetz
- "activation of cytokines, growth factors and chemokines can induce persistent remodelling of the extracellular matrix, affecting the overall response of the tissue . "
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The kidneys are the dose-limiting organ in some radionuclide therapy regimens. However, the biological impact of internal exposure from radionuclides is still not fully understood. The aim of this study was to examine the effects of dose rate and time after i.v. injection of 177LuCl3 on changes in transcriptional patterns in mouse kidney tissue.
To investigate the effect of dose rate, female Balb/c nude mice were i.v. injected with 11, 5.6, 1.6, 0.8, 0.30, and 0 MBq of 177LuCl3, and killed at 3, 6, 24, 48, 168, and 24 hours after injection, respectively. Furthermore, the effect of time after onset of exposure was analysed using mice injected with 0.26, 2.4, and 8.2 MBq of 177LuCl3, and killed at 45, 90, and 140 days after injection. Global transcription patterns of irradiated kidney cortex and medulla were assessed and enriched biological processes were determined from the regulated gene sets using Gene Ontology terms.
The average dose rates investigated were 1.6, 0.84, 0.23, 0.11 and 0.028 mGy/min, with an absorbed dose of 0.3 Gy. At 45, 90 and 140 days, the absorbed doses were estimated to 0.3, 3, and 10 Gy. In general, the number of differentially regulated transcripts increased with time after injection, and decreased with absorbed dose for both kidney cortex and medulla. Differentially regulated transcripts were predominantly involved in metabolic and stress response-related processes dependent on dose rate, as well as transcripts associated with metabolic and cellular integrity at later time points.
The observed transcriptional response in kidney tissue was diverse due to difference in absorbed dose, dose rate and time after exposure. Nevertheless, several transcripts were significantly regulated in all groups despite differences in exposure parameters, which may indicate potential biomarkers for exposure of kidney tissue.
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