Correlation between the pre-RT IL-6 and TGF-β1 plasma levels, respectively, and the IL-6 and TGF-β1 staining intensity of the corresponding tumour biopsies (grade 1–4) (IL-6: no grade 4 samples).

<p>For both cytokines, statistically significant correlations were found between the amount of pre-RT plasma levels and the staining intensity of the corresponding tumour biopsies.</p

TNF-α, IL-1β, IL-6 and TGF-β1 plasma levels at the onset of radiation pneumonitis (mean values), depicted separately for patients with moderate (grade I/II) (n = 14) and severe lung toxicity (grade III/IV) (n = 7).

<p>Error bars represent SEs of the means. Gray-shaded area indicates the normal range of the cytokine plasma levels.</p

Correlation between the tumour response (CR = complete remission; PR = partial remission; NC = no change; PD = progressive disease) and the IL-6 and TGF-β1 plasma levels assessed at the same time-points during follow-up.

<p>For both cytokines, statistically significant correlations were observed between the tumour response categories and IL-6 and TGF-β1 plasma levels.</p

Time courses of TNF-α, IL-1β, IL-6 and TGF-β1 plasma levels (mean values) before (0), during (1–6 weeks) and after radiotherapy (1–9 months), depicted separately for patients <i>with</i> (n = 21) and <i>without</i> radiation pneumonitis (n = 31).

<p>Error bars represent SEs of the means. Gray-shaded area indicates the normal range of the cytokine plasma levels.</p

Correlations between the IL-6 and TGF-β1 ratios and the incidence of radiation pneumonitis.

<p>For every patient, the ratios of the plasma levels at the end of radiotherapy (end-RT) and before RT (pre-RT) are plotted logarithmically (base 10): relative values >imply an increase (supposed high risk for RP), values <1 imply a decrease of the plasma levels at the end of RT (supposed low risk for RP). The ratios were plotted separately for the patients without radiation pneumonitis (grade 0) (n = 31), and with moderate (grade I/II) (n = 14) and severe (grade III/IV) (n = 7) lung toxicity.</p

Electron microscopy analysis of the mucosa and tumor obtained from the Fanconi patient.

<p>TEM micrographs of double-labeling of pKu70 (10-nm beads) and p53BP1 (6-nm beads) at different magnifications (boxed regions are shown at higher magnifications in the following images). Co-localization of pKu70 and 53BP1 in electron-dense regions, reflecting actively processed DSBs in heterochromatin.</p

Light microscopy analysis of the skin and tumor obtained from the Fanconi patient.

<p>Immunohistochemical staining of RAD51 and 53BP1 (diaminobenzidine, brown) in atrophic and dysplastic epidermis as well as tumor specimens derived from the Fanconi patient. Compared with healthy control epidermis moderately or considerably increased RAD51 and 53BP1 expression in the proliferating zone attached to the basement membrane. Immunfluorescence staining of 53BP1 (green) reveals discrete nuclear foci in the proliferating cells of the epidermis, with increasing foci levels during tumor development. Original magnification, x600.</p

DNA damage foci in blood lymphocytes.

<p>Immunofluorescence double staining of 53BP1 (green) and pATM (red) in blood lymphocytes of healthy individuals (ATM^+/+) and ATM^−/− homozygotes, analysed 24 h after irradiation with 2Gy compared to un-irradiated control. Deoxyribonucleic acid was counterstained with 4′,6-diamidino-2-phenylindole (blue), and images were merged to determine co-localization (yellow). Original magnification, x600.</p

Foci kinetics measured in blood lymphocytes.

<p>Double-strand break repair kinetics of ATM^−/− homozygotes, AMT^+/− heterozygotes (A), and tumor-children (B) compared to healthy control-children (ATM^+/+) evaluated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time-points after irradiation. GRJN developing grade-4 toxicities during multimodality treatment for medulloblastoma and SBNE with FA suffering relapsing squamous cell carcinomas of the oral cavity revealed impaired DSB repair capacities. * significant difference to healthy control-children (p≤0.05).</p

Characteristics of the children with tumors.

<p>Abbreviations: TMZ: Temodal, CCNU: Lomustin, VP-16: Etoposid, MTX: Methotrexat, IFO: Ifosfamid, DOX: Doxorubicin, CPM: Cyclophosphamid, CDDP: Cisplatin, DACT: Actinomycin-D, TOPO: Topotecan, DNR: Daunorubicin, DTIC: Dacarbacin, CBDCA: Carboplatin, IDA: Idarubicin, ADR: Adriamycin, TRO: Trofosfamid, EPI: Epirubicin.</p