Successful treatment of invasive aspergillosis in chronic granulomatous disease by bone marrow transplantation, granulocyte colony-stimulating factor-mobilized granulocytes, and liposomal amphotericin-B.

In this study, we sought to explore the merit of proteomic profiling strategies in patients with cancer before and during radiotherapy in an effort to discover clinical biomarkers of radiation exposure. Patients with a diagnosis of cancer provided informed consent for enrollment on a study permitting the collection of serum immediately before and during a course of radiation therapy. High-resolution surface-enhanced laser desorption and ionization-time of flight (SELDI-TOF) mass spectrometry (MS) was used to generate high-throughput proteomic profiles of unfractionated serum samples using an immobilized metal ion-affinity chromatography nickel-affinity chip surface. Resultant proteomic profiles were analyzed for unique biomarker signatures using supervised classification techniques. MS-based protein identification was then done on pooled sera in an effort to begin to identify specific protein fragments that are altered with radiation exposure. Sixty-eight patients with a wide range of diagnoses and radiation treatment plans provided serum samples both before and during ionizing radiation exposure. Computer-based analyses of the SELDI protein spectra could distinguish unexposed from radiation-exposed patient samples with 91% to 100% sensitivity and 97% to 100% specificity using various classifier models. The method also showed an ability to distinguish high from low dose-volume levels of exposure with a sensitivity of 83% to 100% and specificity of 91% to 100%. Using direct identity techniques of albumin-bound peptides, known to underpin the SELDI-TOF fingerprints, 23 protein fragments/peptides were uniquely detected in the radiation exposure group, including an interleukin-6 precursor protein. The composition of proteins in serum seems to change with ionizing radiation exposure. Proteomic analysis for the discovery of clinical biomarkers of radiation exposure warrants further study.

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Discovering clinical biomarkers of ionizing radiation exposure with serum proteomic analysis.

Analysis of MIR-18 results for physical and biological dosimetry: radiation shielding effectiveness in LEO.

Altered apoptotic profiles in irradiated patients with incrased toxicity

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

An assay for biological dosimetry based on the induction of apoptosis in human T-lymphocytes is de- scribed. Radiation-induced apoptosis was assessed by flow cytometric identification of cells displaying apoptosis-as- sociated DNA condensation. CD4 and CD8 T-lymphocytes were analysed. They were recognized on the basis of their cell-surface antigens. Four parameters were measured for both cell types: cell size, granularity, antigen immunoflu- orescence and DNA content. Apoptosis was quantified as the fraction of CD4-, or CD8-positive cells with a charac- teristic reduction of cell size and DNA content. At doses below 1 Gy, levels of radiation-induced apoptosis in- creased for up to 5 days after irradiation. Optimal dose dis- crimination was observed 4 days after irradiation, at which time the dose-response curves were linear, with a slope of 8% ± 0.5% per 0.1 Gy. In controlled, dose-response ex- periments the lowest dose level at which the radiation- induced apoptosis frequency was still significantly above control was 0.05 Gy. After 5 days post-irradiation incuba- tion, intra- and interdonor variations were measured and found to be similar; thus, apoptotic levels depend more on the dose than on the donor. The results demonstrate the po- tential of this assay as a biological dosimeter.

Biological dosimetry: the potential use of radiation-induced apoptosis in human T-lymphocytes ORIGINAL PAPER

An assay for biological dosimetry based on the induction of apoptosis in human T-lymphocytes is described. Radiation-induced apoptosis was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation. CD4 and CD8 T-lymphocytes were analysed. They were recognized on the basis of their cell-surface antigens. Four parameters were measured for both cell types: cell size, granularity, antigen immunofluorescence and DNA content. Apoptosis was quantified as the fraction of CD4-, or CD8-positive cells with a characteristic reduction of cell size and DNA content. At doses below 1 Gy, levels of radiation-induced apoptosis increased for up to 5 days after irradiation. Optimal dose discrimination was observed 4 days after irradiation, at which time the dose-response curves were linear, with a slope of 8% ± 0.5% per 0.1 Gy. In controlled, dose-response experiments the lowest dose level at which the radiation-induced apoptosis frequency was still significantly above control was 0.05 Gy. After 5 days post-irradiation incubation, intra- and interdonor variations were measured and found to be similar; thus, apoptotic levels depend more on the dose than on the donor. The results demonstrate the potential of this assay as a biological dosimeter.

R. Menz

Papers

Biological dosimetry: the potential use of radiation-induced apoptosis in human T-lymphocytes ORIGINAL PAPER

Biological dosimetry: the potential use of radiation-induced apoptosis in human T-lymphocytes.