Spelling suggestions: "subject:"colon aancer."" "subject:"colon 7cancer.""
231 |
Defective IL-23/IL-17 Axis Protects p47phox−/− Mice from Colon CancerRichter, Cornelia, Herrero San Juan, Martina, Weigmann, Benno, Bergis, Dominik, Dauber, Katrin, Muder, Michael H., Baretton, Gustavo B., Pfeilschifter, Josef Martin, Bonig, Halvard, Brenner, Sebastian, Radeke, Heinfried H. 19 July 2017 (has links) (PDF)
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model. Initially, we found that IL-12−/− mice developed less severe colitis but are highly susceptible to colon cancer. By contrast, p47phox−/− mice showed lower tumor scores and fewer high grade tumors than wild-type (WT) littermates. Treatment with toll-like receptor 9 ligand CpG2216 significantly enhanced colitis in p47phox−/− mice, whereas tumor growth was simultaneously reduced. In tumor tissue of p47phox−/− mice, the IL-23/IL-17 axis was crucially hampered. IL-23p19 protein expression in tumor tissue correlated with tumor stage. Reconstitution of WT mice with IL-23p19−/− bone marrow protected these mice from colon cancer, whereas transplantation of WT hematopoiesis into IL-23p19−/− mice increased the susceptibility to tumor growth. Our study strengthens the divergent role of IL-12 and IL-23 in colon cancer development. With the characterization of p47phox as a novel modulator of both cytokines our investigation introduces a promising new target for antitumor strategies.
|
232 |
Defective IL-23/IL-17 Axis Protects p47phox−/− Mice from Colon CancerRichter, Cornelia, Herrero San Juan, Martina, Weigmann, Benno, Bergis, Dominik, Dauber, Katrin, Muder, Michael H., Baretton, Gustavo B., Pfeilschifter, Josef Martin, Bonig, Halvard, Brenner, Sebastian, Radeke, Heinfried H. 19 July 2017 (has links)
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model. Initially, we found that IL-12−/− mice developed less severe colitis but are highly susceptible to colon cancer. By contrast, p47phox−/− mice showed lower tumor scores and fewer high grade tumors than wild-type (WT) littermates. Treatment with toll-like receptor 9 ligand CpG2216 significantly enhanced colitis in p47phox−/− mice, whereas tumor growth was simultaneously reduced. In tumor tissue of p47phox−/− mice, the IL-23/IL-17 axis was crucially hampered. IL-23p19 protein expression in tumor tissue correlated with tumor stage. Reconstitution of WT mice with IL-23p19−/− bone marrow protected these mice from colon cancer, whereas transplantation of WT hematopoiesis into IL-23p19−/− mice increased the susceptibility to tumor growth. Our study strengthens the divergent role of IL-12 and IL-23 in colon cancer development. With the characterization of p47phox as a novel modulator of both cytokines our investigation introduces a promising new target for antitumor strategies.
|
233 |
High Field <sup>1</sup>H Nuclear Magnetic Resonance (NMR) Spectroscopy Based Metabolomics and Complex Mixture Analysis by Multidimensional NMR and Liquid Chromatography-Mass Spectrometry (LC-MS)Paudel, Liladhar 02 August 2012 (has links)
No description available.
|
234 |
Optimization of differential ion mobility and segmented ion fractionation to improve proteome coverageWu, Zhaoguan 09 1900 (has links)
La sensibilité et la profondeur de l'analyse protéomique sont limitées par les ions isobares et les interférences qui entravent l'identification des peptides de faible abondance. Lorsque nous analysons des échantillons de grande complexité, une séparation extensive de l'échantillon est souvent nécessaire pour étendre la couverture protéomique. Ces dernières années, la spectrométrie de mobilité ionique à forme d'onde asymétrique à haut champ (FAIMS) a gagné en popularité dans le domaine de la protéomique pour sa capacité à séparer les ions isobares, à améliorer la capacité de pic et la sensibilité de la spectrométrie de masse (MS). Nous rapportons ici l'intégration d'un appareil FAIMS Pro™ à un Q-Exactive HF™ ainsi qu'un spectromètre de masse Orbitrap Exploris 480™. Des expériences protéomiques sur des digestions d'extraits protéiques issues de cellules Hela à l'aide d'un spectromètre de masse avec FAIMS ont amélioré le rapport signal sur bruit (S/N) et réduit les ions interférents, ce qui a entraîné une augmentation du taux d'identification des peptides de plus de 42 %. FAIMS est également combiné avec le fractionnement ionique segmenté (SIFT), qui utilise tour à tour une fenêtre de 100 ~ 300 m/z au lieu de la large plage traditionnelle (700 ~ 800 m/z), augmentant ainsi la profondeur de la couverture protéomique tout en réduisant la proportion de spectres MS/MS chimériques de 50% à 27%. Dans l'analyse quantitative, nous démontrons l'application de FAIMS pour améliorer les mesures quantitatives lorsque le marquage peptidique isobare est utilisé. Par rapport aux expériences LC-MS/MS conventionnelles, la combinaison des expériences FAIMS et SIFT réalisées sur un modèle à deux protéomes a montré une amélioration de 65 % de la précision des mesures quantitatives. Les digestions tryptiques d'extraits protéiques de différentes lignées cellulaires du cancer colorectal ont été utilisées pour l'évaluation de stratégie combinée FAIMS et SIFT sur un spectromètre de masse Orbitrap Exploris 480™ offre un gain d'identification de 70 % par rapport à l'approche conventionnelle et combinée aux données transcriptomiques elle facilite l’identification de variants protéiques. / The sensitivity and depth of proteomic analysis in mass spectrometry (MS) is limited by isobaric
ions and interferences that hinder the identification of low-abundance peptides. For high
complexity samples, extensive separation is often required to expand proteomic coverage. In
recent years, high-field asymmetric waveform ion mobility spectrometry (FAIMS) has gained
popularity in the field of proteomics for its ability to resolve confounding ions, improve peak
capacity, and sensitivity. This thesis presents the integration of a FAIMS Pro™ interface with
electrical and gas embedded connections to a Q-Exactive HF™ as well as an Orbitrap Exploris
480™ mass spectrometer. Proteomic experiments on tryptic digests of HeLa cell line using a
FAIMS integrated mass spectrometer improved signal-to-noise ratio (S/N) and reduced the
occurrence of interfering ions. This enabled a 42% increase in peptide identification rate. Also,
FAIMS was combined with segmented ion fractionation (SIFT), which in turn scans with windows
of 100~300 m/z width instead of the traditional width (700~800 m/z), further increasing the depth
of proteome coverage by a reducing from 50% to 27% in terms of MS/MS chimeric spectra
numbers. The application of FAIMS gain improvement on quantitative measurements with TMT
labeling method is presented. Compared to conventional LC-MS/MS tests, the combination of
FAIMS and SIFT experiments showed a improvement by 65% in quantitative accuracy when
performed on a human-yeast two-proteome model. As an application of the method, the tryptic
digests from different colorectal cancer cell lines were used for the evaluation. FAIMS-SIFTcombined strategy on an Orbitrap Exploris 480™ mass spectrometer provides a 70% gain in
identification compared to the conventional LC-MS/MS approach for the same sample amount
and instrument time. This enhanced sensitivity facilitates single amino acid mutations confirmed
by RNAseq analyses.
|
Page generated in 0.0422 seconds