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      1. Author :
        Jadert, C.; Petersson, J.; Massena, S.; Ahl, D.; Grapensparr, L.; Holm, L.; Lundberg, J. O.; Phillipson, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Free Radic Biol Med
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29
      12. Abstract :
        Nitric oxide (NO) generated by vascular NO synthases can exert anti-inflammatory effects, partly through its ability to decrease leukocyte recruitment. Inorganic nitrate and nitrite, from endogenous or dietary sources, have emerged as alternative substrates for NO formation in mammals. Bioactivation of nitrate is believed to require initial reduction to nitrite by oral commensal bacteria. Here we investigated the effects of inorganic nitrate and nitrite on leukocyte recruitment in microvascular inflammation and in NSAID-induced small-intestinal injury. We show that leukocyte emigration in response to the proinflammatory chemokine MIP-2 is reduced by 70% after 7days of dietary nitrate supplementation as well as by acute intravenous nitrite administration. Nitrite also reduced leukocyte adhesion to a similar extent and this effect was inhibited by the soluble guanylyl cyclase inhibitor ODQ, whereas the effect on emigrated leukocytes was not altered by this treatment. Further studies in TNF-alpha-stimulated endothelial cells revealed that nitrite dose-dependently reduced the expression of ICAM-1. In rats and mice subjected to a challenge with diclofenac, dietary nitrate prevented the increase in myeloperoxidase and P-selectin levels in small-intestinal tissue. Antiseptic mouthwash, which eliminates oral nitrate reduction, markedly blunted the protective effect of dietary nitrate on P-selectin levels. Despite attenuation of the acute immune response, the overall ability to clear an infection with Staphylococcus aureus was not suppressed by dietary nitrate as revealed by noninvasive IVIS imaging. We conclude that dietary nitrate markedly reduces leukocyte recruitment to inflammation in a process involving attenuation of P-selectin and ICAM-1 upregulation. Bioactivation of dietary nitrate requires intermediate formation of nitrite by oral nitrate-reducing bacteria and then probably further reduction to NO and other bioactive nitrogen oxides in the tissues.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22178413
      14. Call Number :
        PKI @ kd.modi @ 18
      15. Serial :
        10452
      1. Author :
        Adachi, T.; Kawakami, E.; Ishimaru, N.; Ochiya, T.; Hayashi, Y.; Ohuchi, H.; Tanihara, M.; Tanaka, E.; Noji, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Dev Growth Differ
      6. Products :
      7. Volume :
        52
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, Animals; Base Sequence; Cell Line, Tumor; Collagen/*chemistry; DNA Primers; *Gene Silencing; Mice; RNA, Small Interfering/*administration & dosage/*chemistry; Reverse Transcriptase Polymerase Chain Reaction
      12. Abstract :
        Silencing gene expression by small interfering RNAs (siRNAs) has become a powerful tool for the genetic analysis of many animals. However, the rapid degradation of siRNA and the limited duration of its action in vivo have called for an efficient delivery technology. Here, we describe that siRNA complexed with a synthetic collagen poly(Pro-Hyp-Gly) (SYCOL) is resistant to nucleases and is efficiently transferred into cells in vitro and in vivo, thereby allowing long-term gene silencing in vivo. We found that the SYCOL-mediated local application of siRNA targeting myostatin, coding a negative regulator of skeletal muscle growth, in mouse skeletal muscles, caused a marked increase in the muscle mass within a few weeks after application. Furthermore, in vivo administration of an anti-luciferase siRNA/SYCOL complex partially reduced luciferase expression in xenografted tumors in vivo. These results indicate a SYCOL-based non-viral delivery method could be a reliable simple approach to knockdown gene expression by RNAi in vivo as well as in vitro.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20874713
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10352
      1. Author :
        Close, P.; Gillard, M.; Ladang, A.; Jiang, Z.; Papuga, J.; Hawkes, N.; Nguyen, L.; Chapelle, J. P.; Bouillenne, F.; Svejstrup, J.; Fillet, M.; Chariot, A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Biol Chem
      6. Products :
      7. Volume :
        287
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, Carrier Proteins/genetics/*metabolism; Cell Line, Tumor; *Cell Movement; Gene Deletion; HEK293 Cells; Humans; Melanoma/genetics/*metabolism/pathology; Multiprotein Complexes/genetics/*metabolism; Neoplasm Invasiveness; Neoplasm Proteins/genetics/*metabolism; Proteins/genetics/*metabolism; RNA Polymerase II/genetics/metabolism
      12. Abstract :
        The Elongator complex is composed of 6 subunits (Elp1-Elp6) and promotes RNAPII transcript elongation through histone acetylation in the nucleus as well as tRNA modification in the cytoplasm. This acetyltransferase complex directly or indirectly regulates numerous biological processes ranging from exocytosis and resistance to heat shock in yeast to cell migration and neuronal differentiation in higher eukaryotes. The identity of human ELP1 through ELP4 has been reported but human ELP5 and ELP6 have remained uncharacterized. Here, we report that DERP6 (ELP5) and C3ORF75 (ELP6) encode these subunits of human Elongator. We further investigated the importance and function of these two subunits by a combination of biochemical analysis and cellular assays. Our results show that DERP6/ELP5 is required for the integrity of Elongator and directly connects ELP3 to ELP4. Importantly, the migration and tumorigenicity of melanoma-derived cells are significantly decreased upon Elongator depletion through ELP1 or ELP3. Strikingly, DERP6/ELP5 and C3ORF75/ELP6-depleted melanoma cells have similar defects, further supporting the idea that DERP6/ELP5 and C3ORF75/ELP6 are essential for Elongator function. Together, our data identify DERP6/ELP5 and C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of melanoma cells, as integral subunits of Elongator.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22854966
      14. Call Number :
        PKI @ kd.modi @ 20
      15. Serial :
        10530
      1. Author :
        Clapper, M. L.; Hensley, H. H.; Chang, W. C.; Devarajan, K.; Nguyen, M. T.; Cooper, H. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Neoplasia
      6. Products :
      7. Volume :
        13
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MMPSense, IVIS, Adenoma/diagnosis/*enzymology/pathology; Animals; Colorectal Neoplasms/diagnosis/*enzymology/pathology; Disease Models, Animal; Female; *Fluorescent Dyes/administration & dosage/diagnostic use; Male; Matrix Metalloproteinases/*metabolism; Mice; Mice, Inbred C57BL; Molecular Imaging
      12. Abstract :
        A significant proportion of colorectal adenomas, in particular those that lack an elevated growth component, continue to escape detection during endoscopic surveillance. Elevation of the activity of matrix metalloproteinases (MMPs), a large family of zinc endopeptidases, in adenomas serves as a biomarker of early tumorigenesis. The goal of this study was to assess the feasibility of using a newly developed near-infrared bioactivatable probe (MMPSense 680) that reports the activity of a broad array of MMP isoforms to detect early colorectal adenomas. Adenomatous polyposis coli (Apc)(+/Min-FCCC) mice that spontaneously develop multiple colorectal adenomas were injected with MMPSense 680, and the colons were imaged in an IVIS Spectrum system ex vivo. Image analyses were correlated with histopathologic findings for all regions of interest (ROIs). The biochemical basis of fluorescent signal was investigated by immunohistochemical staining of MMP-7 and -9. A strong correlation (Kendall = 0.80) was observed between a positive signal and the presence of pathologically confirmed colonic adenomas; 92.9% of the 350 ROIs evaluated were classified correctly. The correlation between two independent observers was 0.87. MMP-7 expression was localized to epithelial cells of adenomas and microadenomas, whereas staining of MMP-9 was found in infiltrating polymorphonuclear leukocytes within the adenomas. MMPSense 680 identifies colorectal adenomas, both polypoid and nonpolypoid, in Apc(+/Min-FCCC) mice with high specificity. Use of this fluorescent probe in combination with colonoscopy could aid in preventing colorectal neoplasias by providing new opportunities for early detection and therapeutic intervention.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21847360
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10459
      1. Author :
        Comenge, J.; Sotelo, C.; Romero, F.; Gallego, O.; Barnadas, A.; Parada, T. G.; Dominguez, F.; Puntes, V. F.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8, A549-luc, IVIS, Bioware
      12. Abstract :
        Nanoparticles (NPs) have emerged as a potential tool to improve cancer treatment. Among the proposed uses in imaging and therapy, their use as a drug delivery scaffold has been extensively highlighted. However, there are still some controversial points which need a deeper understanding before clinical application can occur. Here the use of gold nanoparticles (AuNPs) to detoxify the antitumoral agent cisplatin, linked to a nanoparticle via a pH-sensitive coordination bond for endosomal release, is presented. The NP conjugate design has important effects on pharmacokinetics, conjugate evolution and biodistribution and results in an absence of observed toxicity. Besides, AuNPs present unique opportunities as drug delivery scaffolds due to their size and surface tunability. Here we show that cisplatin-induced toxicity is clearly reduced without affecting the therapeutic benefits in mice models. The NPs not only act as carriers, but also protect the drug from deactivation by plasma proteins until conjugates are internalized in cells and cisplatin is released. Additionally, the possibility to track the drug (Pt) and vehicle (Au) separately as a function of organ and time enables a better understanding of how nanocarriers are processed by the organism.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23082177
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10522