Pathophysiology of irradiated skin and breast

Archambeau, John O.; Pezner, Richard D.; Wasserman, Todd H.

doi:10.1016/0360-3016(94)00423-i

Cited by 315 publications

(218 citation statements)

References 61 publications

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“…On the other hand, the irradiation was delivered in one acute dose, while in radiotherapy the treatment is given in fractionated doses. However, the lesions we observed were close to those observed during or after radiotherapy [10,[14][15][16] so we assume that this model could serve as a suitable experimental model for developing biomarkers for patients treated with radiotherapy.…”

Section: Spot Train Shifts In Pi After Irradiationsupporting

confidence: 70%

“…Accidental or therapeutic irradiation can cause skin injuries whose severity mainly depends on the dose received, the exposed surface and volume, and individual radiosensitivity. Depending on the level of these parameters, radiation-induced reactions of the exposed skin will gradually reach different clinical states such as erythema, dry and moist desquamations, necrosis, ulceration, and/or fibrosis in the case of very late effects [9,10]. Recent radiation accidents [11,12] have highlighted the role of damage to the cutaneous system in the prognosis and outcome of radiation-induced multiorgan failure [13].…”

Section: Introductionmentioning

confidence: 99%

“…Recent radiation accidents [11,12] have highlighted the role of damage to the cutaneous system in the prognosis and outcome of radiation-induced multiorgan failure [13]. More commonly, a variety of numerous radiation-induced skin reactions are often observed in the course of or following radiation therapy [10,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Time‐course analysis of mouse serum proteome changes following exposure of the skin to ionizing radiation

et al. 2007

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Radiation-induced lesion outcomes of normal tissues are difficult to predict. In particular, radiotherapy or local exposure to a radioactive source by accident can trigger strong injury to the skin. The finding of biomarkers is of fundamental relevance for the prediction of lesion apparition and its evolution, and for the settlement of therapeutic strategies. In order to study radiationinduced cutaneous lesions, we developed a mouse model in which the dorsal skin was selectively exposed to ionizing radiation (IR). 2-D difference gel electrophoresis (2-D DIGE) coupled with MS was used to investigate proteins altered in expression and/or PTM in serum. Proteome changes were monitored from 1 day to 1 month postirradiation, at a dose of 40 Gy, in this specific model developing reproducible clinical symptoms ranging from erythema to skin ulceration with wound healing. About 60 proteins (including some isoforms and likely post-translational variants), representing 20 different proteins, that exhibited significant and reproducible kinetic expression changes, were identified using MS and database searches. Several proteins, down-or up-regulated from day one, could prove to be good candidates to prognosticate the evolution of a skin lesion such as necrosis. In addition, we observed shifts in pI of several spot trains, revealing potential PTM changes, which could also serve as indicators of irradiation or as predictors of lesion severity.

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Section: Spot Train Shifts In Pi After Irradiationsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

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Time‐course analysis of mouse serum proteome changes following exposure of the skin to ionizing radiation

et al. 2007

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“…The three major normal tissue side-effects are cosmetic outcome, cardiac complications and pulmonary fibrosis (Coles et al, 2005). The principal long-term complications that impair cosmetics are fibrosis and induration of the breast resulting from inflammatory responses induced by radiation (Archambeau et al, 1995). The probability of observing late changes by 5 years for patients receiving radiotherapy is about 40% (Coles et al, 2005).…”

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confidence: 99%

In vitro irradiation of basement membrane enhances the invasiveness of breast cancer cells

et al. 2007

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Following removal of the primary breast tumour by conservative surgery, patients may still have additional malignant foci scattered throughout the breast. Radiation treatments are not designed to eliminate all these residual cancer cells. Rather, the radiation dose is calculated to optimise long-term results with minimal complications. In a tumour, cancer cells are surrounded by a basement membrane, which plays an important role in the regulation of gene expression. Using an invasion chamber, we have shown that irradiation before cell plating of a reconstituted basement membrane (Matrigel; Becton Dickinson, Bedford, MA, USA) increased the invasiveness of the breast cancer cells MDA-MB-231. This radiation enhancement of invasion was associated with the upregulation of the pro-invasive gene matrix metalloproteinase (MMP)-2. The expression of membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitor of metalloproteinase-2 (TIMP), which are required to activate the MMP-2, were also increased. Confirming the role of MMP-2 and MT1-MMP, radiation enhancement of cancer cell invasion was prevented by an MMP-2 inhibitor and an anti-MT1-MMP antibody. This study also demonstrated that radiation can potentially enhance the invasion ability by inducing the release of pro-invasive factors stored in the Matrigel. Conversely, no enhancement of invasiveness was observed with the low metastatic cell line MCF-7. This lack of invasiveness correlated with the absence of the MMP-2 activator MT1-MMP in the MCF-7 cells. Radiotherapy is an efficient modality to treat breast cancer which could be further improved by inhibiting the pro-invasive gene upregulated by radiation.

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“…Telangiectasiae are focal dilatations of post-capillary venules mainly, but also occasionally of the capillaries and arterioles of the subpapillary plexus (Requena and Sangueza, 1997). They occur in an atrophic dermis under a thin epidermis and present as areas of reddish discolouration (Archambeau et al, 1995). The mechanisms by which telangiectasiae develop are not fully understood but they seem to be both genetically and mechanistically predetermined.…”

Section: Discussionmentioning

confidence: 99%

Can cutaneous telangiectasiae as late normal-tissue injury predict cardiovascular disease in women receiving radiotherapy for breast cancer?

et al. 2009

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Background: Overall, ∼5% of patients show late normal-tissue damage after radiotherapy with a smaller number having a risk of radiation-induced heart disease. Although the data are conflicting, large studies have shown increased risks of cardiovascular disease (CVD) for irradiated patients compared with non-irradiated ones, or for those treated to the left breast or chest wall compared with those treated to the right. Cutaneous telangiectasiae as late normal-tissue injury have so far only been regarded as a cosmetic burden. Methods: The relationship between late normal-tissue radiation injury phenotypes in 149 irradiated breast cancer patients and the presence of cardiovascular disease were examined. Results: A statistically significant association between the presence of skin telangiectasiae and the long-term risk of CVD was shown in these patients ( P =0.017; Fisher's exact test). Interpretation: This association may represent initial evidence that telangiectasiae can be used as a marker of future radiation-induced cardiac complications. It could also suggest a common biological pathway for the development of both telangiectasiae and CVD on the basis of a genetically predisposed endothelium. To our knowledge this is the first reported study looking at this association.

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Pathophysiology of irradiated skin and breast

Cited by 315 publications

References 61 publications

Time‐course analysis of mouse serum proteome changes following exposure of the skin to ionizing radiation

Time‐course analysis of mouse serum proteome changes following exposure of the skin to ionizing radiation

In vitro irradiation of basement membrane enhances the invasiveness of breast cancer cells

Can cutaneous telangiectasiae as late normal-tissue injury predict cardiovascular disease in women receiving radiotherapy for breast cancer?

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