Glycerol as a chemical chaperone enhances radiation-induced apoptosis in anaplastic thyroid carcinoma cells

INTRODUCTION: Anaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cells (8305c cells). To examine the effectiveness of glycerol in radiation induced lethality for anaplastic thyroid carcinoma 8305c cells, we performed colony formation assay and apoptosis analysis. RESULTS: Apoptosis was analyzed with Hoechst 33342 staining and DNA ladder formation assay. 8305c cells became radiosensitive when glycerol was added to culture medium before X-ray irradiation. Apoptosis was induced by X-rays in the presence of glycerol. However, there was little apoptosis induced by X-ray irradiation or glycerol alone. The binding activity of whole cell extracts to bax promoter region was induced by X-rays in the presence of glycerol but not by X-rays alone. CONCLUSION: These findings suggest that glycerol is effective against radiotherapy of p53-mutant thyroid carcinomas

Crystallization and evaluation of hen egg-white lysozyme crystals for protein pH titration in the crystalline state

Hen egg-white lysozyme was crystallized over a wide pH range (2.5–8.0) and the quality of the crystals was characterized. Crystallization phase diagrams at pH 2.5, 6.0 and 7.5 were determine

Radiological Evaluation of the Initial Fixation between Cortical Bone Trajectory and Conventional Pedicle Screw Technique for Lumbar Degenerative Spondylolisthesis

Study DesignRetrospective study.PurposeTo compare initial fixation using the cortical bone trajectory (CBT) technique versus conventional pedicle screws (PS) in radiographs of postsurgical lumbar degenerative spondylolisthesis.Overview of LiteratureFew reports have documented the holding strength of CBT technique for spondylolisthesis cases.MethodsFrom October 2009 to June 2014, 21 cases of degenerative spondylolisthesis were surgically treated in our institution. Ten were treated with conventional PS technique and 11 of with CBT technique. Mean lumbar lordosis and percent slippage were evaluated preoperatively, immediately after surgery, and 6 months and 1 year postoperatively using radiographs. We also investigated percent loss of slip reduction.ResultsThere were statistically significant differences between preoperative percent slippage and postoperative slippage in both PS and CBT procedures over 1 year, and both techniques showed good slip reduction. On the other hand, lumbar lordosis did not change significantly in either the PS or CBT groups over 1 year.ConclusionsCBT technique showed similarly good initial fixation compared with the PS procedure in the treatment of lumbar degenerative spondylolisthesis

Explosive nucleosynthesis in the neutrino-driven aspherical supernova explosion of a non-rotating 15M⊙M_{\odot} star with solar metallicity

We investigate explosive nucleosynthesis in a non-rotating 15$M_\odot$ star with solar metallicity that explodes by a neutrino-heating supernova (SN) mechanism aided by both standing accretion shock instability (SASI) and convection. To trigger explosions in our two-dimensional hydrodynamic simulations, we approximate the neutrino transport with a simple light-bulb scheme and systematically change the neutrino fluxes emitted from the protoneutron star. By a post-processing calculation, we evaluate abundances and masses of the SN ejecta for nuclei with the mass number $\le 70$ employing a large nuclear reaction network. Aspherical abundance distributions, which are observed in nearby core-collapse SN remnants, are obtained for the non-rotating spherically-symmetric progenitor, due to the growth of low-mode SASI. Abundance pattern of the supernova ejecta is similar to that of the solar system for models whose masses ranges (0.4-0.5) \Ms of the ejecta from the inner region (\le 10,000\km) of the precollapse core. For the models, the explosion energies and the \nuc{Ni}{56} masses are $\simeq 10^{51} \rm erg$ and (0.05-0.06) \Ms, respectively; their estimated baryonic masses of the neutron star are comparable to the ones observed in neutron-star binaries. These findings may have little uncertainty because most of the ejecta is composed by matter that is heated via the shock wave and has relatively definite abundances. The abundance ratios for Ne, Mg, Si and Fe observed in Cygnus loop are well reproduced with the SN ejecta from an inner region of the 15\Ms progenitor.Comment: 15 pages, 1 table, 17 figures, accepted for publication in Astrophyscal Journa

White matter microstructural alterations in patients with neuropathic pain after spinal cord injury: a diffusion tensor imaging study

BackgroundThrough contrastive analysis, we aimed to identify the white matter brain regions that show microstructural changes in patients with neuropathic pain (NP) after spinal cord injury (SCI).MethodsWe categorized patients with SCI into NP (n = 30) and non-NP (n = 15) groups. We extracted diffusion tensor maps of fractional anisotropy (FA) and mean (MD), axial (AD), and radial (RD) diffusivity. A randomization-based method in tract-based spatial statistics was used to perform voxel-wise group comparisons among the FA, MD, AD, and RD for nonparametric permutation tests.ResultsAtlas-based analysis located significantly different regions (p < 0.05) in the appointed brain atlas. Compared to the non-NP group, the NP group showed higher FA in the posterior body and splenium of the corpus callosum and higher AD in the corpus callosum, internal capsule, corona radiata, posterior thalamic radiation, sagittal stratum, external capsule, cingulum, fornix/stria terminalis, superior longitudinal fasciculus, and uncinate fasciculus.ConclusionThe results demonstrated that compared with the non-NP group, NP pathogenesis after SCI was potentially related to higher values in FA that are associated with microstructural changes in the posterior body and splenium of the corpus callosum, which could be regarded as central sensitization or network hyperexcitability

Clear Zone Formation around Screws in the Early Postoperative Stages after Posterior Lumbar Fusion Using the Cortical Bone Trajectory Technique

Study DesignRetrospective study.PurposeTo evaluate the initial fixation using the cortical bone trajectory (CBT) technique for posterior lumbar fusion through assessment of the clear zones around the screws and the risk factors involved.Overview of LiteraturePostoperative radiolucent zones (clear zones) are an indicator of poor conventional pedicle screw fixation.MethodsBetween January 2013 and April 2014, 19 patients (8 men and 11 women) underwent posterior lumbar interbody fusion or posterior lumbar fusion using the CBT technique. A total of 109 screws were used for evaluation with measurement of the maximum insertional torque of last two screw rotations. Clear zone-positivity on plain radiographs was investigated 6 months after surgery. The relation between intraoperative insertional torque and clear zone-positivity was investigated by one-way analysis of variance. In addition, the correlation between clear zone-positivity and gender, age (75 years old), or operative stabilization level (3 vertebral levels) was evaluated using the chi-square test.ResultsClear zones were observed around six screws (5.50%) in five patients (26.3%). The mean insertional torque (4.00±2.09 inlbs) of clear zone-positive screws was lower than that of clear zone-negative screws (8.12±0.50 in-lbs), but the difference was not significant. There was a significant correlation between clear zone-positivity and operative level of stabilization.ConclusionsThe low incidence of clear zone-positive screws indicates good initial fixation using the CBT technique. Multilevel fusions may be risk factors for clear zone generation

Genomic dissection of the Vibrio cholerae O-serogroup global reference strains: reassessing our view of diversity and plasticity between two chromosomes

Approximately 200 O-serogroups of Vibrio cholerae have already been identified; however, only 2 serogroups, O1 and O139, are strongly related to pandemic cholera. The study of non-O1 and non-O139 strains has hitherto been limited. Nevertheless, there are other clinically and epidemiologically important serogroups causing outbreaks with cholera-like disease. Here, we report a comprehensive genome analysis of the whole set of V. cholerae O-serogroup reference strains to provide an overview of this important bacterial pathogen. It revealed structural diversity of the O-antigen biosynthesis gene clusters located at specific loci on chromosome 1 and 16 pairs of strains with almost identical O-antigen biosynthetic gene clusters but differing in serological patterns. This might be due to the presence of O-antigen biosynthesis-related genes at secondary loci on chromosome 2

p53 変異型ヒト口腔がん細胞における高LET 放射線によるp53 非依存Akt 生存シグナルの抑制

Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G(2)/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp53 bearing cancer cells.博士（医学）・甲第598号・平成25年3月15日Copyright © 2012 Elsevier Inc. All rights reserve