Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures

<p>Abstract</p> <p>Background</p> <p>Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment.</p> <p>Methods</p> <p>Cells of 19 primary human liposarcoma were harvested intraoperatively and brought into cell culture. Cells were incubated with doxorubicin for 24 h, RNA was isolated and differential gene expression was analysed by the microarray technique.</p> <p>Results</p> <p>A variety of genes involved in apoptosis were up and down regulated in different samples revealing a heterogeneous expression pattern of the 19 primary tumor cell cultures in response to doxorubicin treatment. However, more than 50% of the samples showed up-regulation of pro-apoptotic genes such as <it>TRAIL Receptor2</it>, <it>CDKN1A</it>, <it>GADD45A</it>, <it>FAS</it>, <it>CD40</it>, <it>PAWR</it>, <it>NFKBIA</it>, <it>IER3</it>, <it>PSEN1</it>, <it>RIPK2</it>, and <it>CD44</it>. The anti-apoptotic genes <it>TNFAIP3</it>, <it>PEA15</it>, <it>Bcl2A1</it>, <it>NGFB</it>, and <it>BIRC3 </it>were also up-regulated. The pro-apoptotic <it>CD14</it>, <it>TIA1</it>, and <it>ITGB2 </it>were down-regulated in more than 50% of the tumor cultures after treatment with doxorubicin, as was the antiapoptotic <it>YWHAH</it>.</p> <p>Conclusion</p> <p>Despite a correlation of the number of differentially regulated genes to the tumor grading and to a lesser extent histological subtype, the expression patterns varied strongly; however, especially among high grade tumors the responses of selected apoptosis genes were similar. The predescribed low clinical response rates of low grade liposarcoma to doxorubicin correspond to our results with only little changes on gene expression level and also divergent findings concerning the up- and down-regulation of single genes in the different sarcoma samples.</p

NASA Standing Review Board Handbook

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Nanostructure, osteopontin, and mechanical properties of calcitic avian eggshell

Avian (and formerly dinosaur) eggshells form a hard, protective biomineralized chamber for embryonic growth—an evolutionary strategy that has existed for hundreds of millions of years. We show in the calcitic chicken eggshell how the mineral and organic phases organize hierarchically across different length scales and how variation in nanostructure across the shell thicknessmodifies its hardness, elastic modulus, and dissolution properties.We also show that the nanostructure changes during egg incubation, weakening the shell for chick hatching. Nanostructure and increased hardness were reproduced in synthetic calcite crystals grown in the presence of the prominent eggshell protein osteopontin. These results demonstrate the contribution of nanostructure to avian eggshell formation, mechanical properties, and dissolution.This work was supported by a grant from the Canadian Institutes of Health Research (no. MOP-142330) and the Natural Sciences and Engineering Research Council of Canada (NSERC; no. RGPIN-2016-05031) to M.D.M., an NSERC (no. RGPIN-2016-04410) Discovery grant to M.T.H., a Spanish Government grant (CGL2015-64683-P) to A.B.R.-N., an Emmy Noether research grant from the German Research Foundation (no. WO1712/3-1) to S.E.W., and an NSF grant (NSF BMAT; no. 1507736) to J.J.G. M.D.M. is a member of the Fonds de Recherche Quebec–Sante Network for Oral and Bone Health Research and the McGill Centre for Bone and Periodontal Researc

Catalyst preparation for CMOS-compatible silicon nanowire synthesis

Metallic contamination was key to the discovery of semiconductor nanowires, but today it stands in the way of their adoption by the semiconductor industry. This is because many of the metallic catalysts required for nanowire growth are not compatible with standard CMOS (complementary metal oxide semiconductor) fabrication processes. Nanowire synthesis with those metals which are CMOS compatible, such as aluminium and copper, necessitate temperatures higher than 450 C, which is the maximum temperature allowed in CMOS processing. Here, we demonstrate that the synthesis temperature of silicon nanowires using copper based catalysts is limited by catalyst preparation. We show that the appropriate catalyst can be produced by chemical means at temperatures as low as 400 C. This is achieved by oxidizing the catalyst precursor, contradicting the accepted wisdom that oxygen prevents metal-catalyzed nanowire growth. By simultaneously solving material compatibility and temperature issues, this catalyst synthesis could represent an important step towards real-world applications of semiconductor nanowires.Comment: Supplementary video can be downloaded on Nature Nanotechnology websit

The JNK Inhibitor XG-102 Protects against TNBS-Induced Colitis

The c-Jun N-terminal kinase (JNK)-inhibiting peptide D-JNKI-1, syn. XG-102 was tested for its therapeutic potential in acute inflammatory bowel disease (IBD) in mice. Rectal instillation of the chemical irritant trinitrobenzene sulfonic acid (TNBS) provoked a dramatic acute inflammation in the colon of 7–9 weeks old mice. Coincident subcutaneous application of 100 µg/kg XG-102 significantly reduced the loss of body weight, rectal bleeding and diarrhoea. After 72 h, the end of the study, the colon was removed and immuno-histochemically analysed. XG-102 significantly reduced (i) pathological changes such as ulceration or crypt deformation, (ii) immune cell pathology such as infiltration and presence of CD3- and CD68-positive cells, (iii) the production of tumor necrosis factor (TNF)-α in colon tissue cultures from TNBS-treated mice, (iv) expression of Bim, Bax, FasL, p53, and activation of caspase 3, (v) complexation of JNK2 and Bim, and (vi) expression and activation of the JNK substrate and transcription factor c-Jun. A single application of subcutaneous XG-102 was at least as effective or even better depending on the outcome parameter as the daily oral application of sulfasalazine used for treatment of IBD

Tribological behavior of a cold-sprayed Cu\u2013MoS\u2082 composite coating during dry sliding wear

Two cold spray coatings, one pure Cu and the other a Cu\u2013MoS\u2082 composite coating, were studied for their tribology performance in dry air. It was demonstrated that a small amount of MoS\u2082 (1.8 \ub1 0.99 wt%) could significantly decrease coefficient of friction (CoF) from around 0.7 (Cu coating) to 0.14\u20130.15. MoS\u2082 patches on the wear track exhibited a lower local CoF, and the main velocity accommodation mechanism was shearing MoS\u2082-containing debris. Even though the coating wear rates were high in the early sliding (8.61\u201312.8 nm/cycle in penetration depth during the first 100 cycles), slow wear (0.12\u20130.22 nm/cycle) over the subsequent sliding was observed. It was also found that the presence of MoS\u2082 helped to achieve high endurance of the first steady-state CoF. The dynamics of the process, material transfer, and phase transformation were examined using scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Raman spectroscopy. The MoS\u2082 patches developed on the wear track and the counterface served as reservoirs to replenish MoS\u2082 in the contact and became depleted with sliding. Cross-sectional microstructure revealed by electron channeling contrast imaging technique showed a layer of sliding-induced microstructure, 3\u20135 \ub5m thick for the Cu\u2013MoS\u2082 coating, and 10\u201330 \ub5m thick for the Cu coatingPeer reviewed: YesNRC publication: Ye