7 results on '"Pammer M"'
Search Results
2. Virus-induced senescence is driver and therapeutic target in COVID-19
- Author
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Lee, S., Yu, Y., Trimpert, J., Benthani, F., Mairhofer, M., Richter-Pechanska, P., Wyler, E., Belenki, D., Kaltenbrunner, S., Pammer, M., Kausche, L., Firsching, T.C., Dietert, K., Schotsaert, M., Martínez-Romero, C., Singh, G., Kunz, S., Niemeyer, D., Ghanem, R., Salzer, H.J.F., Paar, C., Mülleder, M., Uccellini, M., Michaelis, E.G., Khan, A., Lau, A., Schönlein, M., Habringer, A., Tomasits, J., Adler, J.M., Kimeswenger, S., Gruber, A.D., Hoetzenecker, W., Steinkellner, H., Purfuerst, B., Motz, R., Di Pierro, F., Lamprecht, B., Osterrieder, N., Landthaler, M., Drosten, C., García-Sastre, A., Langer, R., Ralser, M., Eils, R., Reimann, M., Fan, D.N.Y., and Schmitt, C.A.
- Subjects
Cancer Research ,Technology Platforms - Abstract
Derailed cytokine and immune cell networks account for organ damage and clinical severity of COVID-19. Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and accompanied by a senescence-associated secretory phenotype (SASP), composed of pro-inflammatory cytokines, extracellular matrix-active factors and pro-coagulatory mediators. COVID-19 patients displayed markers of senescence in their airway mucosa in situ and elevated serum levels of SASP factors. Mirroring COVID-19 hallmark features such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue in vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, neutrophil extracellular trap (NET) formation as well as activation of platelets and the clotting cascade in response to supernatant of VIS cells, including SARS-CoV-2-induced senescence. Senolytics such as Navitoclax and Dasatinib/Quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-driven hamster and mouse models. Our findings mark VIS as pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest senolytic targeting of virus-infected cells as a novel treatment option against SARS-CoV-2 and perhaps other viral infections.
- Published
- 2021
3. T-02-05: Bridging the gap between coagulation in experimental research and clinical hemostaseology - a modified rotational thromboelastometry assay to show the pro-coagulatory effect of senescence on human blood.
- Author
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Kausche, L. E., Mairhofer, M., Yu, Y., Wöß, C., Pammer, M., Lee, S., and Schmitt, C. A.
- Published
- 2023
- Full Text
- View/download PDF
4. Emerging Lipid Targets in Glioblastoma.
- Author
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Darwish A, Pammer M, Gallyas F Jr, Vígh L, Balogi Z, and Juhász K
- Abstract
GBM accounts for most of the fatal brain cancer cases, making it one of the deadliest tumor types. GBM is characterized by severe progression and poor prognosis with a short survival upon conventional chemo- and radiotherapy. In order to improve therapeutic efficiency, considerable efforts have been made to target various features of GBM. One of the targetable features of GBM is the rewired lipid metabolism that contributes to the tumor's aggressive growth and penetration into the surrounding brain tissue. Lipid reprogramming allows GBM to acquire survival, proliferation, and invasion benefits as well as supportive modulation of the tumor microenvironment. Several attempts have been made to find novel therapeutic approaches by exploiting the lipid metabolic reprogramming in GBM. In recent studies, various components of de novo lipogenesis, fatty acid oxidation, lipid uptake, and prostaglandin synthesis have been considered promising targets in GBM. Emerging data also suggest a significant role hence therapeutic potential of the endocannabinoid metabolic pathway in GBM. Here we review the lipid-related GBM characteristics in detail and highlight specific targets with their potential therapeutic use in novel antitumor approaches.
- Published
- 2024
- Full Text
- View/download PDF
5. Virus-induced senescence is a driver and therapeutic target in COVID-19.
- Author
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Lee S, Yu Y, Trimpert J, Benthani F, Mairhofer M, Richter-Pechanska P, Wyler E, Belenki D, Kaltenbrunner S, Pammer M, Kausche L, Firsching TC, Dietert K, Schotsaert M, Martínez-Romero C, Singh G, Kunz S, Niemeyer D, Ghanem R, Salzer HJF, Paar C, Mülleder M, Uccellini M, Michaelis EG, Khan A, Lau A, Schönlein M, Habringer A, Tomasits J, Adler JM, Kimeswenger S, Gruber AD, Hoetzenecker W, Steinkellner H, Purfürst B, Motz R, Di Pierro F, Lamprecht B, Osterrieder N, Landthaler M, Drosten C, García-Sastre A, Langer R, Ralser M, Eils R, Reimann M, Fan DNY, and Schmitt CA
- Subjects
- Aniline Compounds pharmacology, Aniline Compounds therapeutic use, Animals, COVID-19 complications, Cell Line, Cricetinae, Dasatinib pharmacology, Dasatinib therapeutic use, Disease Models, Animal, Female, Humans, Male, Mice, Quercetin pharmacology, Quercetin therapeutic use, SARS-CoV-2 drug effects, Sulfonamides pharmacology, Sulfonamides therapeutic use, Thrombosis complications, Thrombosis immunology, Thrombosis metabolism, COVID-19 pathology, COVID-19 virology, Cellular Senescence drug effects, Molecular Targeted Therapy, SARS-CoV-2 pathogenicity, COVID-19 Drug Treatment
- Abstract
Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs.
1-4 ). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators5-7 . Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue1,8,9 . Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2021
- Full Text
- View/download PDF
6. Humoral and cellular immune responses in SARS-CoV-2 mRNA-vaccinated patients with cancer.
- Author
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Mairhofer M, Kausche L, Kaltenbrunner S, Ghanem R, Stegemann M, Klein K, Pammer M, Rauscher I, Salzer HJF, Doppler S, Habringer A, Paar C, Kimeswenger S, Hoetzenecker W, Lamprecht B, Lee S, and Schmitt CA
- Subjects
- Humans, Immunity, Cellular, RNA, Messenger genetics, SARS-CoV-2, COVID-19, Neoplasms genetics
- Published
- 2021
- Full Text
- View/download PDF
7. "As Needed" nonvitamin K antagonist oral anticoagulants for infrequent atrial fibrillation episodes following atrial fibrillation ablation guided by diligent pulse monitoring: A feasibility study.
- Author
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Zado ES, Pammer M, Parham T, Lin D, Frankel DS, Dixit S, and Marchlinski FE
- Subjects
- Administration, Oral, Aged, Anticoagulants adverse effects, Atrial Fibrillation complications, Atrial Fibrillation diagnosis, Atrial Fibrillation physiopathology, Clinical Decision-Making, Drug Administration Schedule, Feasibility Studies, Female, Humans, Male, Middle Aged, Patient Compliance, Patient Preference, Patient Selection, Recurrence, Risk Assessment, Risk Factors, Stroke diagnosis, Stroke etiology, Time Factors, Treatment Outcome, Anticoagulants administration & dosage, Atrial Fibrillation therapy, Catheter Ablation adverse effects, Heart Rate drug effects, Stroke prevention & control
- Abstract
Introduction: After atrial fibrillation (AF) ablation, oral anticoagulation (OAC) is recommended if stroke risk as assessed by CHA
2 DS2 -VASc score is high. However, patients without AF are often reluctant to take daily OAC. We describe outcome using as needed nonvitamin K antagonist (NOACs) guided by pulse monitoring to detect AF following successful ablation., Methods and Results: We identified 99 patients (84% male, age 64 ± 8 years), CHA2 DS2 -VASc score greater than or equal to 1 in men and greater than or equal to 2 in women (median 2, range 1-6), capable of pulse assessment twice daily and no AF on extended monitoring after AF ablation. All patients were instructed to start NOAC if AF >1 hour or recurrent shorter episodes. Duration of NOAC use after restart was typically 2 to 4 weeks. After 30 ± 14 months (total 244 patient-years), 22 patients (22%) transitioned to daily NOAC because of noncompliance with pulse assessment or patient preference (six patients) or because of suspected or documented AF episode(s) in 16 (16%) patients. Of the remaining 77 (78%), 14 (14%) used NOACs but did not transition back to daily use, most (10 patients) with single use (seven patients) or non-AF rhythm (three patients) documented. There was only one thromboembolic event (0.4%/yr of follow-up) in patient without AF and one mild bleeding event (epistaxis)., Conclusion: The use of as needed NOACs when AF is suspected with pulse monitoring is effective and safe to maintain low risk of stroke and bleeding after successful ablation. Transition back to daily NOAC use should be anticipated in about one quarter of patients., (© 2019 Wiley Periodicals, Inc.)- Published
- 2019
- Full Text
- View/download PDF
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