NFKBIA deletion in glioblastomas Bredel, Markus; Scholtens, Denise M; Yadav, Ajay K ...
The New England journal of medicine,
02/2011, Letnik:
364, Številka:
7
Journal Article
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Amplification and activating mutations of the epidermal growth factor receptor (EGFR) oncogene are molecular hallmarks of glioblastomas. We hypothesized that deletion of NFKBIA (encoding nuclear ...factor of κ-light polypeptide gene enhancer in B-cells inhibitor-α), an inhibitor of the EGFR-signaling pathway, promotes tumorigenesis in glioblastomas that do not have alterations of EGFR.
We analyzed 790 human glioblastomas for deletions, mutations, or expression of NFKBIA and EGFR. We studied the tumor-suppressor activity of NFKBIA in tumor-cell culture. We compared the molecular results with the outcome of glioblastoma in 570 affected persons.
NFKBIA is often deleted but not mutated in glioblastomas; most deletions occur in nonclassical subtypes of the disease. Deletion of NFKBIA and amplification of EGFR show a pattern of mutual exclusivity. Restoration of the expression of NFKBIA attenuated the malignant phenotype and increased the vulnerability to chemotherapy of cells cultured from tumors with NFKBIA deletion; it also reduced the viability of cells with EGFR amplification but not of cells with normal gene dosages of both NFKBIA and EGFR. Deletion and low expression of NFKBIA were associated with unfavorable outcomes. Patients who had tumors with NFKBIA deletion had outcomes that were similar to those in patients with tumors harboring EGFR amplification. These outcomes were poor as compared with the outcomes in patients with tumors that had normal gene dosages of NFKBIA and EGFR. A two-gene model that was based on expression of NFKBIA and O(6)-methylguanine DNA methyltransferase was strongly associated with the clinical course of the disease.
Deletion of NFKBIA has an effect that is similar to the effect of EGFR amplification in the pathogenesis of glioblastoma and is associated with comparatively short survival.
— Aluminum foils of the Stardust cometary dust collector are peppered with impact features of a wide range of sizes and shapes. By comparison to laboratory shots of known particle dimensions and ...density, using the same velocity and incidence geometry as the Stardust Wild 2 encounter, we can derive size and mass of the cometary dust grains. Using scanning electron microscopy (SEM) of foil samples (both flown on the mission and impacted in the laboratory) we have recognized a range of impact feature shapes from which we interpret particle density and internal structure. We have documented composition of crater residues, including stoichiometric material in 3 of 7 larger craters, by energy dispersive X‐ray microanalysis. Wild 2 dust grains include coarse (>10 μm) mafic silicate grains, some dominated by a single mineral species of density around 3–4 g cm−3 (such as olivine). Other grains were porous, low‐density aggregates from a few nanometers to 100 μm, with an overall density that may be lower than 1 g cm−3, containing mixtures of silicates and sulfides and possibly both alkali‐rich and mafic glass. The mineral assemblage is very similar to the most common species reported from aerogel tracks. In one large aggregate crater, the combined diverse residue composition is similar to CI chondrites. The foils are a unique collecting substrate, revealing that the most abundant Wild 2 dust grains were of sub‐micrometer size and of complex internal structure. Impact residues in Stardust foil craters will be a valuable resource for future analyses of cometary dust.
Photoemission measurements sensitive to the momentum perpendicular to the layers that make up the pnictide superconductors are able to map out a full three-dimensional superconducting gap structure.
Intracranial meningeal hemangiopericytomas in children and adolescents are prone to bleeding during surgery. CT and MR imaging may serve a role in preoperative diagnosis. The purpose of this report ...was to describe the radiologic findings in 9 pathologically proved cases of intracranial meningeal hemangiopericytomas in children and adolescents. The average duration of symptoms was short (mean, 4.0 months; median, 1.5 months). The intraoperative blood loss was large (mean, 3561 mL; median, 1000 mL). Tumors were extra-axial, irregularly multilobular, and hypervascular. Radiologically, they showed mixed attenuation on precontrast CT images, heterogeneous signal intensity on precontrast MR imaging, and marked and heterogeneous enhancement on postcontrast MR imaging. Bone erosion was sometimes present, but hyperostosis was not present. On MR imaging, multiple signal intensity voids of vessels were observed in 100% (8/8) of tumors with AVM-like signal intensity flow voids in 25% (2/8) of tumors. These results suggest that CT and MR imaging findings may be helpful for preoperative diagnosis.
We examined the occurrence of seasonal hypoxia (O
2<2
mg
l
−1) in the bottom waters of four river-dominated ocean margins (off the Changjiang, Mississippi, Pearl and Rhône Rivers) and compared the ...processes leading to the depletion of oxygen. Consumption of oxygen in bottom waters is linked to biological oxygen demand fueled by organic matter from primary production in the nutrient-rich river plume and perhaps terrigenous inputs. Hypoxia occurs when this consumption exceeds replenishment by diffusion, turbulent mixing or lateral advection of oxygenated water. The margins off the Mississippi and Changjiang are affected the most by summer hypoxia, while the margins off the Rhône and the Pearl rivers systems are less affected, although nutrient concentrations in the river water are very similar in the four systems. Spring and summer primary production is high overall for the shelves adjacent to the Mississippi, Changjiang and Pearl (1–10
g C
m
−2
d
−1), and lower off the Rhône River (<1
g C
m
−2
d
−1), which could be one of the reasons of the absence of hypoxia on the Rhône shelf. The residence time of the bottom water is also related to the occurrence of hypoxia, with the Mississippi margin showing a long residence time and frequent occurrences of hypoxia during summer over very large spatial scales, whereas the East China Sea (ECS)/Changjiang displays hypoxia less regularly due to a shorter residence time of the bottom water. Physical stratification plays an important role with both the Changjiang and Mississippi shelf showing strong thermohaline stratification during summer over extended periods of time, whereas summer stratification is less prominent for the Pearl and Rhône partly due to the wind effect on mixing. The shape of the shelf is the last important factor since hypoxia occurs at intermediate depths (between 5 and 50
m) on broad shelves (Gulf of Mexico and ECS). Shallow estuaries with low residence time such as the Pearl River estuary during the summer wet season when mixing and flushing are dominant features, or deeper shelves, such as the Gulf of Lion off the Rhône show little or no hypoxia.
The aim of this study is to explore the regulatory mechanism of circRNA UBAP2 (circUBAP2) in colorectal cancer (CRC).
The expression levels of circUBAP2, miR-199a, and VEGFA in tissues and cell lines ...were detected by RT-qPCR. The cell proliferation was examined by CCK-8 and colony formation assays. The migration and invasion abilities were evaluated by wound healing and transwell assays, respectively. Bioinformatics analysis and Luciferase activity assay were applied to determine the interaction between genes.
The expression of circUBAP2 was upregulated in CRC tissues and cell lines, and depletion of circUBAP2 suppressed the cell proliferation, migration, and invasion of CRC. Furthermore, miR-199a inhibitor abrogated the suppressive effect of circUBAP2 knockdown on CRC progression. Vascular endothelial growth factor A (VEGFA) was identified as a downstream target gene of miR-199a, and overexpression of VEGFA rescued the tumor phenotypes attenuated by circUBAP2 knockdown or miR-199a overexpression.
Our findings demonstrated that circUBAP2 facilitated CRC progression by sponging miR-199a to upregulate VEGFA. These findings implied that circUBAP2 may be a potential therapeutic biomarker for CRC.
The E12-14-012 experiment, performed in Jefferson Lab Hall A, has collected exclusive electron-scattering data (e,e'p) in parallel kinematics using natural argon and natural titanium targets. In this ...study we report the first results of the analysis of the data set corresponding to beam energy 2222 GeV, electron scattering angle 21.5° , and proton emission angle –50° . The differential cross sections, measured with ≈4% uncertainty, have been studied as a function of missing energy and missing momentum, and compared to the results of Monte Carlo simulations, obtained from a model based on the distorted-wave impulse approximation.
The East China Sea (ECS) and the South China Sea (SCS) are two major marginal seas of the North Pacific with distinct seasonal variations of primary productivity. Based upon field observations ...covering both the ECS and the northern SCS (NSCS) during December 2008–January 2009, we examined southward long-range transport of nutrients from the ECS to the northeastern SCS (NESCS) carried by the China Coastal Current (CCC) driven by the prevailing northeast monsoon in wintertime. These escaped nutrients from the ECS shelf, where primary production (PP) was limited in winter, might however refuel the PP on the NESCS shelf at lower latitude, where the water temperature remained favorable, but river-sourced nutrients were limited. By combining the field observation of nitrate+nitrite (NO3+NO2, DIN) with our best estimate of volume transport of the CCC, we derived a first-order estimate for DIN flux of 1430 ± 1024 mol s−1. Under the assumption that DIN was the limiting nutrient, such southward DIN transport would have stimulated 8.84 ± 6.33 × 1011 gC of new production (NP), accounting for 33–74% of the NP or 14–22% of PP in winter on the NESCS shelf shallower than 100 m.
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