Baeyens, Ans

Francies, Flavia

Poole, Jeanet

Slabbert, Jacobus

Wainwright, Rosalind

English

Ghent University Academic Bibliography

S547                                                                                     ESTRO 36  _______________________________________________________________________________________________		due to impairing of the phenotypic plasticity that causes cells to adopt stem cell and pro-migratory characteristics. Further mechanistic studies are focusing on alterations to stem cell subpopulations after radiation and superadded notch inhibition.  PO-0991  Chromosomal radiosensitivity and genomic instability of Fanconi anaemia patients in South Africa F.Z. Francies1, R. Wainwright2, J. Poole2, J. Slabbert3, A. Baeyens4 1Univ. of Witwatersrand, Radiation Sciences, Johannesburg, South Africa 2Univ. of Witwatersrand, Paediatrics, Johannesburg, South Africa 3iThemba LABS, Radiation Biophysics, Cape Town, South Africa 4Ghent University, Basic Medical Sciences, Ghent, Belgium  Purpose or Objective  Fanconi anaemia (FA) is an autosomal recessive disorder characterised by defects in DNA repair associated with chromosomal instability. FA cells exhibit cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC). The clinical manifestations include congenital and developmental abnormalities and haematological defects. It has previously been shown that FA patients undergoing radiotherapy display increased clinical radiosensitivity by exhibiting adverse normal tissues side-effects. Evidence suggests that FA patients are chromosomally radiosensitive to ionising radiation, however, with very limited data.  The aim of this study is to investigate chr omosomal radiosensitivity and genomic instability of hom ozygous and heterozygous carriers of FA mutations compared to healthy individuals using the micronucleus (MN) assays. Material and Methods  For the G0 MN assay, heparinised blood in culture medium was irradiated at 0Gy (Baseline), 2Gy and 4Gy followed by the immediate stimulation of lymphocytes using phytohaemagglutinin (PHA). Cytochalasin B was added 23 hours later to inhibit cytoplasmic division. Cells were harvested 70 hours post irradiation. The S/G2 MN assay is a modified version of the G0 MN assay. To initiate the assay, the cultures are stimulated with PHA and then irradiated with the same radiation doses 72 hours after stimulation. To detect DNA damage in the S/G2 phase of the cell cycle, the cells were harvested 8 hours post irradiation.  The third assay is similar to the G0 MN assay except the cell damage is induced using MMC. Subsequent to harvest, all slides were prepared and stained with acridine orange and micronuclei were scored using a fluorescent microscope.  Results  When compared to parents and healthy controls, spontaneously occurring micronuclei are significantly higher in FA patients indicating genomic instability. A similar trend is noticed in the micronuclei frequency of irradiated FA cells signifying chromosomal radiosensitivity. This sensitivity is evidently pronounced in the S/G2 phase. Elevated chromosomal damage was also detected with MMC treatment in the FA patients. Conclusion  Chromosomal radiosensitivity and genomic instability of FA mutation carriers are notably higher when compared to healthy individuals.   PO-0992  Low-dose whole lung irradiation plus Re-188-liposome eliminates lung metastasis of esophageal cancer Y.J. Chen1, S.Y. Liu2, H.C. Tai1, T.W. Lee3, C.H. Chang3 1Mackay Memorial Hospital, Department of Radiation Oncology, Taipei, Taiwan 2Mackay Memorial Hospital, Department of Medical Research, Taipei, Taiwan 3Institute of Nuclear Energy Research, Isotope Application Division, Taoyuan, Taiwan  Purpose or Objective  External beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by isotopes can control tumors systemically. Rhenium 188 (188Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy with biodistribution profiles preferential to tumors. We designed a unique combinatory treatment and examined its effects on lung metastasis from esophageal cancer, a malignancy with poor prognosis.  Material and Methods  Human esophageal cancer BE-3 cells with luciferase gene for optical imaging were injected into tail vein of nude mice to induce lung metastasis. The radiochemical purity of 188Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT (NanoSPECT/CT PLUS, Mediso, Alsotorokvesz, Budapest, Hungary) showed that lung metastatic lesion could uptake the 188Re-liposome. For biodistribution, the radioactivity of 188Re-liposome was detected by Auto-Gamma counter (Packard Cobra II, Canberra, Germany), and the uptake of 188Re-liposome in each organ was expressed as the percentage of injected dose per gram of tissue (% ID/g). Low-dose whole lung EBRT with 3 consecutive daily fractions of 1 Gy was delivered by linear accelerator with 6-MV photon (Clinac iX, Varian Medical Systems, USA) followed by intravenous 188Re-liposome (250 µCi) administration 2-h after last teletherapy. Flow cytometry was used to estimate the amount of myeloid derived suppressor cells and macrophages. Results  The combination of EBRT and 188Re-liposome inhibited tumor burden of lung metastasis faster and better than each treatment alone (Figure 1 and 2). Combination treatment did no cause additive adverse effects on white blood cell counts, body weight, or liver and renal functions. EBRT significantly reduced the uptake of 188Re-liposome in lung, kidney, bone marrow and blood. In spleen, 188Re-liposome administration declined the amount of myeloid derived suppressor cells and increased the amount of M1 and M2 macrophages.   Figure 1. The therapeutic efficacy of 188Re-liposome 

Chromosomal radiosensitivity and genomic instability of Fanconi anaemia patients in South Africa

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Chromosomal radiosensitivity and genomic instability of Fanconi anaemia patients in South Africa

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