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519 results on '"Diebold, Joachim"'

1. EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics

Author

Hench, Jürgen, Hultschig, Claus, Brugger, Jon, Mariani, Luigi, Guzman, Raphael, Soleman, Jehuda, Leu, Severina, Benton, Miles, Stec, Irenäus Maria, Hench, Ivana Bratic, Hoffmann, Per, Harter, Patrick, Weber, Katharina J, Albers, Anne, Thomas, Christian, Hasselblatt, Martin, Schüller, Ulrich, Restelli, Lisa, Capper, David, Hewer, Ekkehard, Diebold, Joachim, Kolenc, Danijela, Schneider, Ulf C., Rushing, Elisabeth, della Monica, Rosa, Chiariotti, Lorenzo, Sill, Martin, Schrimpf, Daniel, von Deimling, Andreas, Sahm, Felix, Kölsche, Christian, Tolnay, Markus, and Frank, Stephan

Published
2024
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3. Pathologist Computer-Aided Diagnostic Scoring of Tumor Cell Fraction: A Swiss National Study

Author

Frei, Ana Leni, Oberson, Raphaël, Baumann, Elias, Perren, Aurel, Grobholz, Rainer, Lugli, Alessandro, Dawson, Heather, Abbet, Christian, Lertxundi, Ibai, Reinhard, Stefan, Mookhoek, Aart, Feichtinger, Johann, Sarro, Rossella, Gadient, Gallus, Dommann-Scherrer, Corina, Barizzi, Jessica, Berezowska, Sabina, Glatz, Katharina, Dertinger, Susanne, Banz, Yara, Schoenegg, Rene, Rubbia-Brandt, Laura, Fleischmann, Achim, Saile, Guenter, Mainil-Varlet, Pierre, Biral, Ruggero, Giudici, Luca, Soltermann, Alex, Chaubert, Audrey Baur, Stadlmann, Sylvia, Diebold, Joachim, Egervari, Kristof, Bénière, Charles, Saro, Francesca, Janowczyk, Andrew, and Zlobec, Inti

Published
2023
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5. Drugging the catalytically inactive state of RET kinase in RET-rearranged tumors

Author

Plenker, Dennis, Riedel, Maximilian, Brägelmann, Johannes, Dammert, Marcel A, Chauhan, Rakhee, Knowles, Phillip P, Lorenz, Carina, Keul, Marina, Bührmann, Mike, Pagel, Oliver, Tischler, Verena, Scheel, Andreas H, Schütte, Daniel, Song, Yanrui, Stark, Justina, Mrugalla, Florian, Alber, Yannic, Richters, André, Engel, Julian, Leenders, Frauke, Heuckmann, Johannes M, Wolf, Jürgen, Diebold, Joachim, Pall, Georg, Peifer, Martin, Aerts, Maarten, Gevaert, Kris, Zahedi, René P, Buettner, Reinhard, Shokat, Kevan M, McDonald, Neil Q, Kast, Stefan M, Gautschi, Oliver, Thomas, Roman K, and Sos, Martin L

Subjects
Orphan Drug, Rare Diseases, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Adenocarcinoma, Adenocarcinoma of Lung, Animals, Cell Line, Tumor, Cytoskeletal Proteins, Drug Resistance, Neoplasm, Gene Rearrangement, Heterocyclic Compounds, 4 or More Rings, Humans, Imidazoles, Lung Neoplasms, Mice, Mutation, NIH 3T3 Cells, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-ret, Pyridazines, Biological Sciences, Medical and Health Sciences
Abstract

Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. We provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors, such as AD80 or ponatinib, that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells, we identify the CCDC6-RETI788N mutation and drug-induced mitogen-activated protein kinase pathway reactivation as possible mechanisms by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors.

Published
2017

8. PD-L1 testing of non-small cell lung cancer using different antibodies and platforms: a Swiss cross-validation study

Author

Savic, Spasenija, Berezowska, Sabina, Eppenberger-Castori, Serenella, Cathomas, Gieri, Diebold, Joachim, Fleischmann, Achim, Jochum, Wolfram, Komminoth, Paul, McKee, Thomas, Letovanec, Igor, Jasarevic, Zerina, Rössle, Matthias, Singer, Gad, von Gunten, Michael, Zettl, Andreas, Zweifel, Roland, Soltermann, Alex, and Bubendorf, Lukas

Published
2019
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9. Prospective Evaluation of Residual Breast Tissue After Skin- or Nipple-Sparing Mastectomy: Results of the SKINI-Trial

Author

Papassotiropoulos, Bärbel, Güth, Uwe, Chiesa, Federica, Rageth, Christoph, Amann, Esther, Baege, Astrid, Elfgen, Constanze, Varga, Zsuzsanna, Moskovszky, Linda, Endhardt, Katharina, Masser, Regina, Tinguely, Marianne, Farhadi, Jian, Lardi, Alessia, Dammann, Florian, Diebold, Joachim, Li, Qiyu, Dubsky, Peter, and Tausch, Christoph

Published
2019
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17. Data from Cell-Autonomous and Non–Cell-Autonomous Mechanisms of Transformation by Amplified FGFR1 in Lung Cancer

Author

Malchers, Florian, primary, Dietlein, Felix, primary, Schöttle, Jakob, primary, Lu, Xin, primary, Nogova, Lucia, primary, Albus, Kerstin, primary, Fernandez-Cuesta, Lynnette, primary, Heuckmann, Johannes M., primary, Gautschi, Oliver, primary, Diebold, Joachim, primary, Plenker, Dennis, primary, Gardizi, Masyar, primary, Scheffler, Matthias, primary, Bos, Marc, primary, Seidel, Danila, primary, Leenders, Frauke, primary, Richters, André, primary, Peifer, Martin, primary, Florin, Alexandra, primary, Mainkar, Prathama S., primary, Karre, Nagaraju, primary, Chandrasekhar, Srivari, primary, George, Julie, primary, Silling, Steffi, primary, Rauh, Daniel, primary, Zander, Thomas, primary, Ullrich, Roland T., primary, Reinhardt, H. Christian, primary, Ringeisen, Francois, primary, Büttner, Reinhard, primary, Heukamp, Lukas C., primary, Wolf, Jürgen, primary, and Thomas, Roman K., primary

Published
2023
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18. Supplementary Methods and Legends from Cell-Autonomous and Non–Cell-Autonomous Mechanisms of Transformation by Amplified FGFR1 in Lung Cancer

Author

Malchers, Florian, primary, Dietlein, Felix, primary, Schöttle, Jakob, primary, Lu, Xin, primary, Nogova, Lucia, primary, Albus, Kerstin, primary, Fernandez-Cuesta, Lynnette, primary, Heuckmann, Johannes M., primary, Gautschi, Oliver, primary, Diebold, Joachim, primary, Plenker, Dennis, primary, Gardizi, Masyar, primary, Scheffler, Matthias, primary, Bos, Marc, primary, Seidel, Danila, primary, Leenders, Frauke, primary, Richters, André, primary, Peifer, Martin, primary, Florin, Alexandra, primary, Mainkar, Prathama S., primary, Karre, Nagaraju, primary, Chandrasekhar, Srivari, primary, George, Julie, primary, Silling, Steffi, primary, Rauh, Daniel, primary, Zander, Thomas, primary, Ullrich, Roland T., primary, Reinhardt, H. Christian, primary, Ringeisen, Francois, primary, Büttner, Reinhard, primary, Heukamp, Lukas C., primary, Wolf, Jürgen, primary, and Thomas, Roman K., primary

Published
2023
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19. Supplementary Figures S1-S14 from Cell-Autonomous and Non–Cell-Autonomous Mechanisms of Transformation by Amplified FGFR1 in Lung Cancer

Author

Malchers, Florian, primary, Dietlein, Felix, primary, Schöttle, Jakob, primary, Lu, Xin, primary, Nogova, Lucia, primary, Albus, Kerstin, primary, Fernandez-Cuesta, Lynnette, primary, Heuckmann, Johannes M., primary, Gautschi, Oliver, primary, Diebold, Joachim, primary, Plenker, Dennis, primary, Gardizi, Masyar, primary, Scheffler, Matthias, primary, Bos, Marc, primary, Seidel, Danila, primary, Leenders, Frauke, primary, Richters, André, primary, Peifer, Martin, primary, Florin, Alexandra, primary, Mainkar, Prathama S., primary, Karre, Nagaraju, primary, Chandrasekhar, Srivari, primary, George, Julie, primary, Silling, Steffi, primary, Rauh, Daniel, primary, Zander, Thomas, primary, Ullrich, Roland T., primary, Reinhardt, H. Christian, primary, Ringeisen, Francois, primary, Büttner, Reinhard, primary, Heukamp, Lukas C., primary, Wolf, Jürgen, primary, and Thomas, Roman K., primary

Published
2023
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26. Overall survival and role of programmed death ligand 1 expression in patients with metastatic non-small-cell lung cancer and immunotherapy: an observational study from central Switzerland

Author

Allmann, Valentina, primary, Dyntar, Daniela, additional, Lehnick, Dirk, additional, Dressler, Marco, additional, Zeidler, Kristin, additional, Niederberger, Philipp, additional, Godau, Jeanne, additional, Diebold, Joachim, additional, and Gautschi, Oliver, additional

Published
2023
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28. 21/#810 A current perspective on endometrial carcinoma (EC) risk classification: results from an European multicentre initiative

Author

Rohner, Annika, primary, Grube, Marcel, additional, Knoll, Katharina, additional, Lum, Amy, additional, Brambs, Christine, additional, Pauly, Nina, additional, Kommoss, Felix, additional, Heublein, Sabine, additional, Battista, Marco Johannes, additional, Mittelstadt, Suzana, additional, Praetorius, Teresa, additional, Hasenburg, Annette, additional, Ataseven, Beyhan, additional, Talhouk, Aline, additional, Diebold, Joachim, additional, Zeimet, Alain-Gustave, additional, Staebler, Annette, additional, Mcalpine, Jessica, additional, and Kommoss, Stefan, additional

Published
2022
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30. miR-579-3p Controls Hepatocellular Carcinoma Formation by Regulating the Phosphoinositide 3-Kinase–Protein Kinase B Pathway in Chronically Inflamed Liver

Author

Quintavalle, Cristina, Meyer-Schaller, Nathalie, Roessler, Stephanie, Calabrese, Diego, Marone, Romina, Riedl, Tobias, Picco-Rey, Silvia, Panagiotou, Orestis A., Uzun, Sarp, Piscuoglio, Salvatore, Boldanova, Tuyana, Bian, Chaoran B., Semela, David, Jochum, Wolfram, Cathomas, Gieri, Mertz, Kirsten D., Diebold, Joachim, Mazzucchelli, Luca, Koelzer, Viktor H., Weber, Achim, Decaens, Thomas, Terracciano, Luigi M., Heikenwalder, Mathias, Hoshida, Yujin, Andersen, Jesper B., Thorgeirsson, Snorri S., Matter, Matthias S., Quintavalle, Cristina, Meyer-Schaller, Nathalie, Roessler, Stephanie, Calabrese, Diego, Marone, Romina, Riedl, Tobias, Picco-Rey, Silvia, Panagiotou, Orestis A., Uzun, Sarp, Piscuoglio, Salvatore, Boldanova, Tuyana, Bian, Chaoran B., Semela, David, Jochum, Wolfram, Cathomas, Gieri, Mertz, Kirsten D., Diebold, Joachim, Mazzucchelli, Luca, Koelzer, Viktor H., Weber, Achim, Decaens, Thomas, Terracciano, Luigi M., Heikenwalder, Mathias, Hoshida, Yujin, Andersen, Jesper B., Thorgeirsson, Snorri S., and Matter, Matthias S.

Abstract

Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas the 10-year incidence for HCC in patients with cirrhosis is approximately 20%, many of these patients remain tumor free for their entire lives. Clarifying the mechanisms that define the various outcomes of chronic liver inflammation is a key aspect in HCC research. In addition to a wide variety of contributing factors, microRNAs (miRNAs) have also been shown to be engaged in promoting liver cancer. Therefore, we wanted to characterize miRNAs that are involved in the development of HCC, and we designed a longitudinal study with formalin-fixed and paraffin-embedded liver biopsy samples from several pathology institutes from Switzerland. We examined the miRNA expression by nCounterNanostring technology in matched nontumoral liver tissue from patients developing HCC (n = 23) before and after HCC formation in the same patient. Patients with cirrhosis (n = 26) remaining tumor free within a similar time frame served as a control cohort. Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed a down-regulation of miR-579-3p as an early step in HCC development, which was further confirmed in a validation cohort. Correlation with messenger RNA expression profiles further revealed that miR-579-3p directly attenuated phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) expression and consequently protein kinase B (AKT) and phosphorylated AKT. In vitro experiments and the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology confirmed that miR-579-3p controlled cell proliferation and cell migration of liver cancer cell lines. Conclusion: Liver tissues from patients developing HCC revealed changes in miRNA expression. miR-579-3p was identified as a novel tumor suppressor regulating phosphoinositide 3-kina

Published
2022

33. miR-579-3p Controls Hepatocellular Carcinoma Formation by Regulating the Phosphoinositide 3-Kinase-Protein Kinase B Pathway in Chronically Inflamed Liver

Author

Quintavalle, Cristina, Meyer-Schaller, Nathalie, Roessler, Stephanie, Calabrese, Diego, Marone, Romina, Riedl, Tobias, Picco-Rey, Silvia, Panagiotou, Orestis A., Uzun, Sarp, Piscuoglio, Salvatore, Boldanova, Tuyana, Bian, Chaoran B., Semela, David, Jochum, Wolfram, Cathomas, Gieri, Mertz, Kirsten D., Diebold, Joachim, Mazzucchelli, Luca, Koelzer, Viktor H., Weber, Achim, Decaens, Thomas, Terracciano, Luigi M., Heikenwalder, Mathias, Hoshida, Yujin, Andersen, Jesper B., Thorgeirsson, Snorri S., and Matter, Matthias S.

Subjects
Gene Expression Regulation, Neoplastic, Inflammation, Liver Cirrhosis, MicroRNAs, Phosphatidylinositol 3-Kinases, Carcinoma, Hepatocellular, Liver Neoplasms, Humans, Longitudinal Studies, Phosphatidylinositol 3-Kinase, Proto-Oncogene Proteins c-akt
Abstract

Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas the 10-year incidence for HCC in patients with cirrhosis is approximately 20%, many of these patients remain tumor free for their entire lives. Clarifying the mechanisms that define the various outcomes of chronic liver inflammation is a key aspect in HCC research. In addition to a wide variety of contributing factors, microRNAs (miRNAs) have also been shown to be engaged in promoting liver cancer. Therefore, we wanted to characterize miRNAs that are involved in the development of HCC, and we designed a longitudinal study with formalin-fixed and paraffin-embedded liver biopsy samples from several pathology institutes from Switzerland. We examined the miRNA expression by nCounterNanostring technology in matched nontumoral liver tissue from patients developing HCC (n = 23) before and after HCC formation in the same patient. Patients with cirrhosis (n = 26) remaining tumor free within a similar time frame served as a control cohort. Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed a down-regulation of miR-579-3p as an early step in HCC development, which was further confirmed in a validation cohort. Correlation with messenger RNA expression profiles further revealed that miR-579-3p directly attenuated phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) expression and consequently protein kinase B (AKT) and phosphorylated AKT. In vitro experiments and the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology confirmed that miR-579-3p controlled cell proliferation and cell migration of liver cancer cell lines. Conclusion: Liver tissues from patients developing HCC revealed changes in miRNA expression. miR-579-3p was identified as a novel tumor suppressor regulating phosphoinositide 3-kinase–AKT signaling at the early stages of HCC development.

Published
2021

34. miR‐579‐3p Controls Hepatocellular Carcinoma Formation by Regulating the Phosphoinositide 3‐Kinase–Protein Kinase B Pathway in Chronically Inflamed Liver

Author

Quintavalle, Cristina, primary, Meyer‐Schaller, Nathalie, additional, Roessler, Stephanie, additional, Calabrese, Diego, additional, Marone, Romina, additional, Riedl, Tobias, additional, Picco‐Rey, Silvia, additional, Panagiotou, Orestis A., additional, Uzun, Sarp, additional, Piscuoglio, Salvatore, additional, Boldanova, Tuyana, additional, Bian, Chaoran B., additional, Semela, David, additional, Jochum, Wolfram, additional, Cathomas, Gieri, additional, Mertz, Kirsten D., additional, Diebold, Joachim, additional, Mazzucchelli, Luca, additional, Koelzer, Viktor H., additional, Weber, Achim, additional, Decaens, Thomas, additional, Terracciano, Luigi M., additional, Heikenwalder, Mathias, additional, Hoshida, Yujin, additional, Andersen, Jesper B., additional, Thorgeirsson, Snorri S., additional, and Matter, Matthias S., additional

Published
2022
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35. Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients

Author

Michels, Sebastian, Scheel, Andreas Hans, Scheffler, Matthias, Schultheis, Anne Maria, Gautschi, Oliver, Aebersold, Franziska, Diebold, Joachim, Pall, Georg, Rothschild, Sacha, Bubendorf, Lukas, Hartmann, Wolfgang, Heukamp, Lukas, Schildhaus, Hans-Ulrich, Fassunke, Jana, Ihle, Michaela Angelika, Künstlinger, Helen, Heydt, Carina, Fischer, Rieke, Nogovà, Lucia, Mattonet, Christian, Hein, Rebecca, Adams, Anne, Gerigk, Ulrich, Schulte, Wolfgang, Lüders, Heike, Grohé, Christian, Graeven, Ullrich, Müller-Naendrup, Clemens, Draube, Andreas, Kambartel, Karl-Otto, Krüger, Stefan, Schulze-Olden, Susanne, Serke, Monika, Engel-Riedel, Walburga, Kaminsky, Britta, Randerath, Winfried, Merkelbach-Bruse, Sabine, Büttner, Reinhard, and Wolf, Jürgen

Published
2016
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37. Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF Cohort

Author

Gautschi, Oliver, Milia, Julie, Cabarrou, Bastien, Bluthgen, Marie-Virginia, Besse, Benjamin, Smit, Egbert F, Wolf, Juergen, Peters, Solange, Früh, Martin, Koeberle, Dieter, Oulkhouir, Youssouf, Schuler, Martin, Curioni-Fontecedro, Alessandra, Huret, Benjamin, Kerjouan, Mallorie, Michels, Sebastian, Pall, Georg, Rothschild, Sacha, Schmid-Bindert, Gerald, Scheffler, Matthias, Veillon, Rémi, Wannesson, Luciano, Diebold, Joachim, Zalcman, Gérard, Filleron, Thomas, and Mazières, Julien

Published
2015
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45. Comment on: Wieser et al. Ovarian cancer in Switzerland: incidence and treatment according to hospital registry data. Swiss Med Wkly.2018;148:w14647

Author

Feller, Anita, Bopp, Matthias, Lorez, Matthias, Zellweger, Ulrich, Adam, Martin, Curjuric, Ivan, Staehelin, Katharina, Perren, Aurel, Bergeron, Yvan, Rapiti, Elisabetta, Mousavi, Mohsen, Diebold, Joachim, Dyntar, Daniela, Bulliard, Jean-Luc, Maspoli Conconi, Manuela, Bordoni, Andrea, Konzelmann, Isabelle, Wagner, Ulrich, Rohrmann, Sabine, Feller, Anita, Bopp, Matthias, Lorez, Matthias, Zellweger, Ulrich, Adam, Martin, Curjuric, Ivan, Staehelin, Katharina, Perren, Aurel, Bergeron, Yvan, Rapiti, Elisabetta, Mousavi, Mohsen, Diebold, Joachim, Dyntar, Daniela, Bulliard, Jean-Luc, Maspoli Conconi, Manuela, Bordoni, Andrea, Konzelmann, Isabelle, Wagner, Ulrich, and Rohrmann, Sabine

Published
2020

46. Gene deletion of MK2 inhibits TNF-[alpha] and IL-6 and protects against cerulein-induced pancreatitis

Author

Tietz, Anne Barbara, Malo, Antje, Diebold, Joachim, Kotlyarov, Alexey, Herbst, Andreas, Kolligs, Frank T., Brandt-Nedelev, Barbara, Halangk, Walter, Gaestel, Matthias, Goke, Burkhard, and Schafer, Claus

Subjects
Cytokines -- Properties, Cytokines -- Research, Gene expression -- Analysis, Pancreatitis -- Causes of, Biological sciences
Abstract

Inflammatory effects contribute to the pathogenesis of pancreatitis. Clearly, proinflammatory cytokines like TNF-[alpha] and IL-6 are involved in this process and the associated systemic complications. The MAPKAPK-2 (MK2) signaling pathway is involved in cytokine gene expression. Therefore, we hypothesized that blockade of this pathway inhibits the expression of proinflammatory cytokines and thereby protects against pancreatitis. To investigate this, we used an in vivo mouse model with a homozygous deletion of the MK2 gene. Pancreatitis was induced by injection of cerulein. The severity was determined by measuring serum lipase, pancreatic trypsin activation, pancreatic edema, and morphological changes by quantitative scoring of histological sections. Systemic inflammation was evaluated by measuring myeloperoxidase activity in lung tissue. Serum levels of TNF-[alpha] and IL-6 were measured using an ELISA, and mRNA levels were identified using RT-PCR and subsequent quantitative PCR analysis. Pancreatitis in animals with deletion of the MK2 gene is less severe and accompanied with reduced serum levels of TNF-[alpha] and IL-6. Pancreatic mRNA levels revealed a fourfold reduction of IL-6 mRNA expression in MK2 -/- mice. Effects were associated with suppression of pancreatic trypsin activity and reduced acinar cell injury. In summary, these data show that gene deletion of MK2 ameliorates cerulein-induced pancreatitis. TNF-[alpha] and IL-6 signaling is mediated by the MK2 pathway and therefore crucial for the regulatory inflammatory processes. TNF-[alpha] expression is supposably regulated by a posttranscriptional mechanism, whereas IL-6 expression is most likely regulated by transcriptional effects. cytokines; MAPKAP kinase; actin cytoskeleton; inflammation

Published
2006

49. IL-28A and IL-29 mediate antiproliferative and antiviral signals in intestinal epithelial cells and murine CMV infection increases colonic IL-28A expression

Author

Brand, Stephan, Beigel, Florian, Olszak, Torsten, Zitzmann, Kathrin, Eichhorst, Soren T., Otte, Jan-Michel, Diebold, Joachim, Diepolder, Helmut, Adler, Barbara, Auernhammer, Christoph J., Goke, Burkhard, and Dambacher, Julia

Subjects
Cytokines -- Physiological aspects, Cytomegalovirus infections -- Chemical properties, Cytomegalovirus infections -- Physiological aspects, Epithelial cells -- Chemical properties, Epithelial cells -- Physiological aspects, Biological sciences
Abstract

Human cytomegalovirus virus (CMV) is a major cause of morbidity and mortality in immunocompromised individuals. Recently, a novel group of cytokines [interleukin (IL)-28A/B and IL-29, also termed interferon (IFN)-[lambda]s] has been described. Here, we demonstrate that intestinal epithelial cell (IEC) lines as well as murine and human colonic tissue express the IFN-[lambda] receptor subunits IL-28R and IL-10R2. IL-28A and IL-29 binding to their receptor complex activates ERK-1/2 and stress-activated protein kinase/c-Jun N[H.sub.2]-terminal kinase MAPKs and Akt, resulting in increased IL-8 protein expression. IFN-[lambda] also induce phosphorylation of signal transducer and activator of transcription 1 and significantly increase mRNA expression of suppressor of cytokine signaling 3 and the antiviral proteins myxovirus resistance A and 2',5'-oligoadenylate synthetase. These signals result in an up to 83% reduction of cells positive for human CMV immediate-early protein after human CMV infection. In mice, IL-28A mRNA expression is upregulated after infection with murine CMV in vivo. Both IL-28A and IL-29 significantly decrease cell proliferation but have no effect on Fas-induced apoptosis. In conclusion, IECs express functional receptors for IFN-[lambda]s, which mediate antiviral and antiproliferative signals in IECs, suggesting a potential for therapeutic use in certain viral infections and as (antiproliferative) anticancer therapy. interleukin-10-like cytokines; interferon-[lambda]; interleukin-28A; interleukin-29; suppressor of cytokine signaling 3; signal transducer and activator of transcription 1; cytomegalovirus; human cytomegalovirus; murine cytomegalovirus

Published
2005

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