Hemodynamic Characteristics of Intracranial Atherosclerotic Stenosis: A Pilot Study of Contrast Enhancement Time-Density Curves Based on Regions of Interest.

OBJECTIVE: The present study aimed to analyze the hemodynamic characteristics of occluded vessels responsible for acute ischemic stroke and to diagnose the occlusion types. METHODS: Multimodal computed tomography (CT) was used to accurately identify the range of occlusion of large intracranial vessels. Regions of interest (ROI 1-3 ) were manually delineated at sites 2 mm away from the proximal, middle, and distal portions of each occlusion, generating 3 contrast enhancement time-density curves. The peak CT attenuation values, or Hounsfield units (H 1-3 ), and time-to-peak values (T 1-3 ) were extracted from each curve. H 0 and T 0 of the time-density curve, based on ROI 0 of the automatically recognized input artery, were used as the baseline values with which the odds ratios of each parameter, H 1-3/0 and T 1-3/0 , were obtained. The present study aimed to establish prediction models for intracranial atherosclerotic stenosis (ICAS) based on each ROI's time-density curve. RESULTS: Among the 33 acutely occluded intracranial vessels, 10 were found to have ICAS, whereas 23 did not, based on the diagnostic criteria. Significant differences were observed in patient sex, neutrophil-to-lymphocyte ratio upon admission, Alberta Stroke Program Early CT Score 24-48 hours after reperfusion therapy, and H 1/0 , H 3/0 , and T 3/0 between the ICAS and non-ICAS groups ( P < 0.05). The prediction model (model 3) based on the ROI 3 time-density curve showed the best performance for the diagnosis of ICAS (area under the curve, 0.944; 95% confidence interval, 0.854-1.000). The prediction models based on ROI 1 (model 1) and ROI 2 (model 2) showed moderate diagnostic performance (area under the curve, 0.817 vs 0.822, respectively). The best visualization for proximal occlusions was in the first phase (arterial phase) of multiphase CT angiography, and in the second phase (early venous phase) for distal occlusions. CONCLUSIONS: The contrast enhancement time-density curves of the ROIs at all evaluated portions of the acute ischemic stroke occlusions provided a visual display of the blood flow characteristics of the responsible vessels. The time-density curve of the ROI placed 2 mm from the distal occlusion was a combined effect of residual blood flow and collateral establishment, thus providing good performance for the diagnosis of ICAS.

Alteration of Metal Elements in Radiation Injury: Radiation-Induced Copper Accumulation Aggravates Intestinal Damage.

Ionizing radiation causes damage to a variety of tissues, especially radiation-sensitive tissues, such as the small intestine. Radiation-induced damage is caused primarily by increased oxidative stress in the body. Studies have shown that trace metal elements play an irreplaceable role in oxidative stress in humans, which may be associated with radiation-induced tissue damage. However, the alteration and functional significance of trace metal elements in radiation-induced injury is not clear. In this study, we explored the association between radiation-induced damage and 7 trace metal elements in mouse models. We found that the concentration of zinc and copper in mice serum was decreased significantly after irradiation, whereas that of nickel, manganese, vanadium, cobalt, and stannum was not changed by inductively coupled plasma mass spectrometry. The role of copper in radiation-induced intestines was characterized in detail. The concentration of copper was increased in irradiated intestine but reduced in irradiated heart. Immunohistochemistry staining showed that copper transporter protein copper transport 1 expression was upregulated in irradiated mouse intestine, suggesting its potential involvement in radiation-induced copper accumulation. At the cellular level, the addition of CuCl2 potentiated radiation-induced reactive oxygen species in intestine-derived human intestinal epithelial cell and IEC-6 cells. Moreover, the level of copper in damaged cells may be related to the severity of radiation-induced damage as evidenced by a cell viability assay. These results indicate that copper may be involved in the progression of radiation-induced tissue damage and may be a potential therapeutic target.

[The expression and significance of hnRNPD in esophageal squamous cell carcinoma cells].

OBJECTIVE: To investigate the expression of heterogeneous nuclear ribonucleoprotein D (hnRNPD) in esophageal squamous cell carcinoma (ESCC) tissues and the relationship between hnRNPD expression and the clinicopathological features of ESCC, and to study the effect of down-regulated hnRNPD on the proliferation of ESCC cells and explore its potential mechanism. METHODS: The expression of hnRNPD protein in ESCC tissues and the normal paracancerous tissues were detected by immunohistochemistry. The siRNA-hnRNPD was transfected into ESCC cells and the silence effect was verified by Western blotting. MTT assay and clone formation assay were used to evaluate the proliferation of ESCC cells after down-regulation of hnRNPD genes. Cell apoptosis was examined by annexin V-phycoerythrin/7-aminoactinomycin D (annexin V-PE/7-AAD) staining and flow cytometry. RESULTS: The expression of hnRNPD protein in ESCC tissues was significantly higher than that of the normal paracancerous tissues, and the expression was closely related with neoplasm staging. Down-regulation of hnRNPD inhibited the proliferation and clonality of ESCC cells. Compared with the control group, siRNA targeting hnRNPD significantly promoted cell apoptosis. CONCLUSION: Down-regulation of hnRNPD inhibits the proliferation of ESCC cells by promoting cell apoptosis.

MG132 enhances the radiosensitivity of lung cancer cells in vitro and in vivo.

Radiotherapy is a common treatment modality for lung cancer, however, radioresistance remains a fundamental barrier to attaining the maximal efficacy. Cancer cells take advantage of the ubiquitin-proteasome system (UPS) for increased proliferation and decreased apoptotic cell death. MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal­H), a specific and selective reversible inhibitor of the 26S proteasome, has shown anticancer effect in multiple types of cancers. Previously, we have reported that MG132 enhances the anti­growth and anti-metastatic effects of irradiation in lung cancer cells. However, whether MG132 can enhance the radiosensitivity in lung cancer cells in vitro and in vivo is still unknown. In this study, we found that MG132 increased apoptosis and dicentric chromosome ratio of A549 and H1299 cells treated by irradiation. Radiation-induced NF-κB expression and IκBα phosphorylation was attenuated in MG132 plus irradiation-treated cells. The in vivo model of H1299 xenografts of nude mice showed that the tumor size of MG132 plus irradiation treated xenografts was smaller than that of irradiation, MG132 or the control group. Moreover, MG132 plus irradiation group showed significant reduced Ki67 expression. Taken together, these results demonstrate that MG132 enhances the radiosensitivity through multiple mechanisms in vitro and in vivo.

Overexpression of TOB1 confers radioprotection to bronchial epithelial cells through the MAPK/ERK pathway.

The aim of this study was to investigate the effects and mechanisms of antiproliferative transducer of erbB2, 1 (TOB1) on the radiosensitivity of the normal human bronchial epithelial cell line HBE. After exposure to different doses of irradiation or a certain dose for different time intervals, the expression of TOB1 mRNA and protein in HBE cells was determined by semi-quantitative RT-PCR and western blot analysis. Liposome-induced recombinant plasmid transfection and G418 selection were performed to establish a stably transfected TOB1-overexpressing HBE cell line. A clonogenic assay was used to determine the radiosensitivity of the HBE cells with different TOB1 expression statuses. The cell cycle distribution was detected by flow cytometry. The ionizing radiation (IR)-induced γ-H2AX foci formation was detected by immunofluorescence assay. The related mechanism was explored by western blot analysis. TOB1 expression in the HBE cells was not induced by IR, neither dose-dependently nor time-dependently. Compared to the parental or 'mock' transfected HBE cells, the radiosensitivity of HBE cells overexpressing TOB1 was significantly decreased (P<0.05). Exogenous TOB1 prevented HBE cells from apoptosis after IR, in contrast to the control cells (P<0.05), and significantly decreased the IR-induced γ-H2AX foci formation. After IR, the expression of DNA damage repair proteins such as XRCC1, MRE11, FEN1 and ATM was increased in the TOB1­overexpressing HBE cells when compared with the expression levels in the control cells. HBE/TOB1 cells presented a much higher phosphorylated ERK1/2 and phosphorylated p53 when compared with the levels in the control cell lines when receiving 6 Gy of X-rays. Notably, the increased expression of phosphorylated p53 in HBE/TOB1 cells after IR was sufficiently blocked by U0126, a specific inhibitor of MEK1/2. Different from its functions in several lung cancer cell lines, TOB1 demonstrated a radioprotective function in the immortalized normal human bronchial epithelial cell line HBE via the MAPK/ERK signaling pathway.