Visceral-to-subcutaneous fat ratio is a possible prognostic factor for type 1 endometrial cancer

[Background] Associations have been observed between obesity defined by the body mass index (BMI) and the incidence of endometrial cancer. However, the impact of obesity on the prognosis of endometrial cancer is not yet clear. Recently, visceral fat has been considered to have a greater impact on malignant disease in obese patients than subcutaneous fat. In this study, we investigated the association between prognostic factors of type 1 and type 2 endometrial cancer and obesity parameters. [Methods] The impacts of clinical factors on the progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively in 145 primary endometrial cancer patients. The factors included age, BMI, pathological findings, Federation of Gynecology and Obstetrics (FIGO) stage, status of lymph node metastasis, and the amounts of visceral and subcutaneous fat obtained from computed tomography (CT) data. [Results] Only the visceral-to-subcutaneous fat ratio (V/S ratio) (cutoff value 0.5) corresponded to a significant difference in OS and PFS in type 1 endometrial cancer (p = 0.0080, p = 0.0053) according to the results of log-rank tests of Kaplan–Meier curves. The COX regression univariate analysis revealed that only the V/S ratio was a significant prognostic factor for PFS, but not OS (p = 0.033 and p = 0.270, respectively). [Conclusion] A V/S ratio > 0.5 is a possible factor for poor prognosis in type 1 endometrial cancer. Further research is needed to investigate the preventive and therapeutic effects of reducing visceral fat on the prognosis of this type of cancer

Atomic dynamics of the i-ScZnMg and its 1/1 approximant phase: experiment and simulation

International audienceQuasicrystals are long range ordered materials which lack translational invariance so that the study of their physical properties remains a challenging problem. In order to study the respective influence of the local order and of the long range order (periodic or quasiperiodic) on lattice dynamics, we have carried out inelastic x-ray and neutron scattering experiments on single grain samples of the Zn-Mg-Sc icosahedral quasicrystal and of the Zn-Sc periodic cubic 1/1 approximant. Besides the overall similarities and the existence of a pseudo gap in the transverse dispersion relation, marked differences are observed, the pseudo gap being larger and better defined in the approximant than in the quasicrystal. This can be qualitatively explained using the concept of pseudo Brillouin zone in the quasicrystal. These results are compared to simulations on atomic models and using oscillating pair potentials which have been fitted against ab-initio data. The simulated response function reproduces both the dispersion relation but also the observed intensity distribution in the measured spectra. The partial vibrational density of states, projected on the cluster shells, is computed from this model

Comparison of phosphorylation kinetics in DNA repair proteins after exposure to high and low LET radiations

Comparison of phosphorylation kinetics in DNA repair proteins after exposure to high and low LET radiations\nR. Okayasu (1), A. Okabe (1,2) and K. Takakura (2)(1) National Institute of Radiological Sciences, Chiba, Japan, (2) International Christian University, Tokyo, Japan ([email protected] /Fax: +81 43-251-4531 / Phone: +81 43-206-3230)\nWe irradiated plateau phase normal human fibroblasts with 2 Gy X-rays, 70 keV/um carbon (290MeV/n) and 200 keV/um iron ions (500 MeV/n) and observed the kinetics of phosphorylation in various proteins associated with DNA double strand break (DSB) repair. GammaH2AX foci, a marker for DSBs, were detected immediately after irradiation, and the peak of phosphorylation was seen 30 to 60 min post-irradiation for three kinds of radiations. Disappearance of gamma-H2AX foci was much faster for X-irradiated samples than that for heavy ion irradiated samples; the phosphorylation kinetics for carbon and iron ions are similar for gamma-H2AX foci. In contrast, phosphorylation of an NHEJ protein, DNA-PKcs (threonine 2609) was significantly delayed in carbon and iron irradiated cells when compared to X-irradiated cells. Disappearance of DNA-PKcs sites was much faster in X-irradiated samples than carbon and iron samples which showed a similar pattern as in the case of gamma-H2AX. Furthermore, in the case of ATM protein phosphorylation (serine 1981), iron irradiation alone caused a significant initial delay, but the kinetics of disappearance is similar for iron and carbon samples with much higher remaining number of foci in iron samples than those for X-rays and carbon ions. These results suggest that 1) high LET irradiation induces complex and/or severe DNA DSB damage which affects the function of DSB repair proteins, 2) Both ATM and DNA-PKcs may recognize the complexity of DSBs, but ATM may be more sensitive to detecting the complexity of DSB damage, 3) gamma-H2AX may just recognize DSBs, but not the complexity of them. Our studies also indicate that high LET radiation would be a useful tool to elucidate the complexity of initial DSB damage and the mechanism of repair on these damages.The 36th COSPAR Scientifi Assembl

ATM protein plays a critical role in repairing the complex DNA double strand breaks induced by hogh LET radiation

Normal human and ataxia telangiectasia (AT) homozygote fibroblasts were irradiated with 2 Gy X-rays, 70 keV/um carbon (290MeV/n) and 200 keV/um iron ions (500MeV/n) at plateau phase cultures, and the kinetics of phosphorylation in various proteins associated with DNA double strand break (DSB) repair were compared. In normal cells, peaks of GammaH2AX foci formation were observed 30 to 60 min post-irradiation for three kinds of radiations, and the disappearance of gamma-H2AX foci was much faster for X-irradiated samples than that for samples irradiated with heavy ions. In AT cells, on the other hand, the peaks of gamma-H2AX phosphorylation for carbon and iron samples were delayed for one to two hours when compared to that for X-rays. The phosphorylation of DNA-PKcs (at threonine 2609) in normal cells was significantly delayed in carbon and iron irradiated cells when compared to X-irradiated cells. Disappearance of DNA-PKcs sites in normal cells was much faster in X-irradiated samples than carbon and iron samples as in the case of gamma-H2AX. However, we were not able to detect DNA-PKcs phosphorylation signals in AT cells irradiated with high LET heavy ions, although DNA-PKcs foci were observed with AT cells irradiated with X-rays. Moreover, in the case of ATM protein phosphorylation (serine 1981) in normal cells, iron irradiation alone caused a significant initial delay, but the kinetics of disappearance is similar for iron and carbon samples with much higher number of remaining foci in iron samples than those for X-rays and carbon ions. \nThese results indicate that 1) high LET irradiation induces complex and/or severe DNA DSB damage which affects the functions of crucial DSB repair proteins, 2) Both ATM and DNA-PKcs may recognize the complexity of DSBs, and 3) ATM may be critical in repairing the complex form of DSB damage such as the one induced by high LET radiation.Radiation Research Society 53rd Annual Meetin

Radiation-induced apoptosis of chiken lymphocyte B-cell line DT40

12th International Congress of Radiation Researc

Comparison of the Kinetics of Radiation-Induced Apoptosis in DT40 Cells Irradiated with Low and High Doses of X Rays

In this study, we attempted to clarify the influence of the DNA repair genes RAD54 and KU70, components of the homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways, respectively, on apoptosis induced by 1 Gy (low-dose) and 5 Gy (high-dose) irradiation. All experiments were performed using chicken B-lymphocyte DT40 cells and the DNA repair-deficient cell lines KU70-/-, RAD54-/- and KU70-/-/ RAD54-/-. Morphological changes were detected by fluorescence methods, and the sub-G1 fraction and the activated caspases in DT40 cells were analyzed by flow cytometry. Irradiation with 1 Gy significantly increased the level of apoptosis in cells with the defective DNA repair genes, with the maximum apoptosis occurring in double mutant cells, KU70-/-/RAD54-/-, demonstrating that 1 Gy is enough to induce apoptosis in DNA repair-deficient DT40 cells, and that KU70 and RAD54 must have almost the same role in low-dose radiation-induced apoptosis. After 5 Gy, fast induction of apoptosis, within 2 h, was seen in both wild-type cells and RAD54-/- cells, indicating that functional KU70 must be important for the rescue of the cells from the induction of fast apoptosis

The autophosphorylation of DNA-PKcs in irradiated human cells.

We used an antibody to DNA-PKcs phosphorylated at threonine 2609(T2609) to study the status of autophosphorylation of DNA-PKcs, which is one of the key proteins for Non Homologous End Joining(NHEJ). The number of foci of T2609 induced by X rays in normal human fibroblast cells (HFLIII) and Ligase IV deficient cells (180BR) were counted under fluorescent microscope. DNA-PKcs was autophosphorylated 10 minutes after irradiation and the number of foci reached the peak at 1hour after irradiation in both cell lines. Although the number of foci were gradually reduced and returned to almost the background levels after 24 hours, the remaining number of foci in 180BR cells was much higher than that in normal cells. To investigate the interaction with other proteins, the colocalization of T2609 was studied with phosphorylated ATM at serine 1981(S1981) and gamma H2AX. The focus of T2609 was formed over nucleus and did not correspond with the sites of S1981 and gamma H2AX foci. However the foci of T2609 were accumulated and almost all of them were colocalized with S1981 and gamma H2AX 4 hours after irradiation. In unirradiated cells, gamma H2AX and S1981 foci were not formed at the sites of T2609 foci, although there were some foci of phosphorylated DNA-PKcs.After high LET carbon ion(70keV/um) irradiation, the peak for the number of T2609 foci appearance was significantly delayed in HFLIII and 180BR when compared with X-irradiated cells. This delay was more distinct in irradiated 180BR cells. These results indicate both DNA-PKcs and ATM may function at DSB sites simultaneously. Besides, DNA-PKcs should be phosphorylated not at the sites of DSB. Therefore, the phosphorylation of DNA-PKcs should have not only repair function but also other functions. The results from experiments using high LET heavy ion irradiation are also presented.第５２回 Radiation Research Society annual meetin

CHARACTERISTIC STUDIES OF NON-HOMOLOGOUS END JOINING IN HUMAN CELLS IRRADIATED WITH HIGH LET RADIATION

We studied the repair process of G0 or G1 phase normal (HFL III) and non homologous end joining (NHEJ) deficient human fibroblasts (180 BR) exposed to X-rays and high LET carbon ions (70 keV per micro m) using a modified fusion-based premature chromosome condensation (PCC) technique. We have succeeded in increasing the sensitivity of the PCC method by adding a potent DNA double strand break repair inhibitor, wortmannin, during the incubation period of this assay. With x-ray exposure (2 Gy or less), the rejoining of G1 chromosome breaks in 180BR cells are significantly slower and less efficient than that in normal cells. On the other hand, the difference in rejoining kinetics between 180 BR and normal cells with high LET carbon exposure is much smaller than that with x-ray exposure. These results seem to reflect the radiation cell survival responses using the same cell lines. We also studied the auto-phosphorylation status of DNA dependent protein kinase catalytic subunit (DNA-PKcs) protein in cells exposed to high and low LET radiation. Our immuno-staining results using an antibody to detect an auto-phosphorylation site of DNA-PKcs further reveal the difficulty in NHEJ for cells exposed to high LET radiation. The peak time for the auto-phosphorylation in x-irradiated normal human cells is one hour post-irradiation, but the peak in the same cells irradiated with high LET carbon beams shifted to two hours post-irradiation, reflecting much slower NHEJ processing associated with the high LET radiation. These data help understand the mechanism underlying the biological effect induced by heavy ion particles in the space environment.35th COSPAR Scientific Asembl