BackgroundCycling and chronic tumor hypoxia are involved in tumor development and growth. However, the impact of cycling hypoxia and its molecular mechanism on glioblastoma multiforme (GBM) progression remain unclear.MethodologyGlioblastoma cell lines, GBM8401 and U87, and their xenografts were exposed to cycling hypoxic stress in vitro and in vivo. Reactive oxygen species (ROS) production in glioblastoma cells and xenografts was assayed by in vitro ROS analysis and in vivo molecular imaging studies. NADPH oxidase subunit 4 (Nox4) RNAi-knockdown technology was utilized to study the role of Nox4 in cycling hypoxia-mediated ROS production and tumor progression. Furthermore, glioblastoma cells were stably transfected with a retroviral vector bearing a dual reporter gene cassette that allowed for dynamic monitoring of HIF-1 signal transduction and tumor cell growth in vitro and in vivo, using optical and nuclear imaging. Tempol, an antioxidant compound, was used to investigate the impact of ROS on cycling hypoxia-mediated HIF-1 activation and tumor progression.Principal FindingsGlioblastoma cells and xenografts were compared under cycling hypoxic and normoxic conditions; upregulation of NOX4 expression and ROS levels were observed under cycling hypoxia in glioblastoma cells and xenografts, concomitant with increased tumor cell growth in vitro and in vivo. However, knockdown of Nox4 inhibited these effects. Moreover, in vivo molecular imaging studies demonstrated that Tempol is a good antioxidant compound for inhibiting cycling hypoxia-mediated ROS production, HIF-1 activation, and tumor growth. Immunofluorescence imaging and flow cytometric analysis for NOX4, HIF-1 activation, and Hoechst 3342 in glioblastoma also revealed high localized NOX4 expression predominantly in potentially cycling hypoxic areas with HIF-1 activation and blood perfusion within the endogenous solid tumor microenvironment.ConclusionsCycling hypoxia-induced ROS via Nox4 is a critical aspect of cancer biology to consider for therapeutic targeting of cycling hypoxia-promoted HIF-1 activation and tumor progression in GBM.

The survival rate of dental implants is markedly influenced by the quality of the bone into which they are placed. The purpose of this study was to determine the trabecular bone density at potential dental implant sites in different regions of the Chinese jawbone using computed tomography (CT) images. One hundred and fifty-four potential implant sites (15 in the anterior mandible, 47 in the anterior maxilla, 55 in the posterior mandible, and 37 in the posterior maxilla) were selected from the jawbones of 62 humans. The data were subjected to statistical analysis to determine any correlation between bone density (in Hounsfield units, HU) and jawbone region using the Kruskal-Wallis test. The bone densities in the four regions decreased in the following order: anterior mandible (530 +/- 161 HU, mean +/- s.d.) approximately equal anterior maxilla (516 +/- 132 HU) > posterior mandible (359 +/- 150 HU) approximately equal posterior maxilla (332 +/- 136 HU). The CT data demonstrate that trabecular bone density varies markedly with potential implant site in the anterior and posterior regions of the maxilla and mandible. These findings may provide the clinician with guidelines for dental implant surgical procedures (i.e., to determine whether a one-stage or a two-stage protocol is required).

Recent studies have shown unique clinicoradiologic characteristics in patients with hemiballism-hemichorea (HB-HC) caused by non-ketotic hyperglycemia; however, there is still a limited number of patients being reported. We report 7 patients (3 males and 4 females) with this type of dyskinesia, whose ages ranged from 60 to 84 years. Brain CT of these patients showed hyperdensity in the contralateral striatum, corresponding with MRI studies that showed an increased signal intensity on T1-weighted images and a decreased signal on T2-weighted images. After metabolic control had been achieved, the hyperkinetic state of these patients abruptly ceased. Follow-up neuroimaging studies in 2 patients documentied complete resolution of the striatal hyperintensity on brain CT and MRI after 3 months and 6 months, respectively. A review of patients with HB-HC caused by non-ketotic hyperglycemia reported formerly and in the present study shows that the dyskinesia tends to occur in aged diabetic patients. The age of patients with dyskinesia secondary to cerebral infarction is generelly much lower. We also found that 86% (30 out of 35 cases) patients reported with HB-HC caused by non-ketotic hyperglycemia were Asians. The prognosis of the dyskinesia was excellent, and the radiological abnormalities are completely reversible.