13 results on '"Rittig, Anne H."'
Search Results
2. Prognostic miRNA classifier in early-stage mycosis fungoides: development and validation in a Danish nationwide study
- Author
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Lindahl, Lise M., Besenbacher, Søren, Rittig, Anne H., Celis, Pamela, Willerslev-Olsen, Andreas, Gjerdrum, Lise M.R., Krejsgaard, Thorbjørn, Johansen, Claus, Litman, Thomas, Woetmann, Anders, Odum, Niels, and Iversen, Lars
- Published
- 2018
- Full Text
- View/download PDF
3. Suppressed microRNA-195-5p expression in mycosis fungoides promotes tumor cell proliferation
- Author
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Rittig, Anne H., Johansen, Claus, Celis, Pamela, Odum, Niels, Litman, Thomas, Woetmann, Anders, Lindahl, Lise M., Iversen, Lars, Rittig, Anne H., Johansen, Claus, Celis, Pamela, Odum, Niels, Litman, Thomas, Woetmann, Anders, Lindahl, Lise M., and Iversen, Lars
- Abstract
Background: Several cancers, including mycosis fungoides (MF), have reported dysregulation of miR-195-5p. miR-195-5p plays a role in cell cycle regulation in several malignant diseases. Objectives: This study aimed to investigate: (a) the expression level of miR-195-5p in lesional MF skin biopsies and (b) the potential regulatory roles of miR-195-5p in MF. Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to determine miR-195-5p expression in MF skin biopsies and cell lines. The effect of miR-195-5p and ADP-ribosylation factor-like protein 2 (ARL2) on cell cycle and apoptosis was measured by flow cytometry assays. Changes in ARL2 expression were determined by RT-qPCR and Western blotting (WB). Results: We found lower expression levels of miR-195-5p in lesional skin from MF patients compared with non-lesional MF skin and skin from healthy volunteers. Additionally, miR-195-5p showed lower expression levels in the skin from patients with disease progression compared with patients with stable disease. In vitro studies showed that overexpression of miR-195-5p induced a cell cycle arrest in G0G1. Using microarray analysis, we identified several genes that were regulated after miR-195-5p overexpression. The most downregulated gene after miR-195-5p mimic transfection was ARL2. RT-qPCR and WB analyses confirmed downregulation of ARL2 following transfection with miR-195-5p mimic. Lastly, transfection with siRNA against ARL2 also induced a G0G1 arrest. Conclusion: Upregulation of miR-195-5p in MF inhibits cycle arrest by downregulation of ARL2. miR-195-5p may thus function as a tumor suppressor in MF and low miR-195-5p expression in lesional MF skin may promote disease progression.
- Published
- 2021
4. MicroRNA-106b Regulates Expression of the Tumour Suppressors p21 and TXNIP and Promotes Tumour Cell Proliferation in Mycosis Fungoides
- Author
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Lindahl, Lise M, Gluud, Maria, Emmanuel, Thomas, Thomsen, Emil A, Hu, Tengpeng, Rittig, Anne H, Celis, Pamela, Stolearenco, Veronica, Krejsgaard, Thorbjørn, Johansen, Claus, Willerslev-Olsen, Andreas, Buus, Terkild B, Woetmann, Anders, Aagaard, Lars, Geisler, Carsten, Litman, Thomas, Mikkelsen, Jacob G, Odum, Niels, Iversen, Lars, Lindahl, Lise M, Gluud, Maria, Emmanuel, Thomas, Thomsen, Emil A, Hu, Tengpeng, Rittig, Anne H, Celis, Pamela, Stolearenco, Veronica, Krejsgaard, Thorbjørn, Johansen, Claus, Willerslev-Olsen, Andreas, Buus, Terkild B, Woetmann, Anders, Aagaard, Lars, Geisler, Carsten, Litman, Thomas, Mikkelsen, Jacob G, Odum, Niels, and Iversen, Lars
- Abstract
A prognostic 3-miRNA classifier for early-stage mycosis fungoides has been developed recently, with miR-106b providing the strongest prognostic power. The aim of this study was to investigate the molecular function of miR-106b in mycosis fungoides disease progression. The cellular localization of miR-106b in mycosis fungoides skin biopsies was determined by in situ hybridization. The regulatory role of miR-106b was assessed by transient miR-106b inhibitor/mimic transfection of 2 mycosis fungoides derived cell lines, followed by quantitative real-time PCR (RT-qPCR), western blotting and a proliferation assay. MiR-106b was found to be expressed by dermal T-lymphocytes in mycosis fungoides skin lesions, and miR-106b expression increased with advancing mycosis fungoides stage. Transfection of miR-106b in 2 mycosis fungoides derived cell lines showed that miR-106b represses the tumour suppressors cyclin-dependent kinase inhibitor 1 (p21) and thioredoxin-interacting protein (TXNIP) and promotes mycosis fungoides tumour cell proliferation. In conclusion, these results substantiate that miR-106b has both a functional and prognostic role in progression of mycosis fungoides.
- Published
- 2020
5. Suppressed microRNA‐195‐5p expression in mycosis fungoides promotes tumor cell proliferation
- Author
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Rittig, Anne H., primary, Johansen, Claus, additional, Celis, Pamela, additional, Odum, Niels, additional, Litman, Thomas, additional, Woetmann, Anders, additional, Lindahl, Lise M., additional, and Iversen, Lars, additional
- Published
- 2020
- Full Text
- View/download PDF
6. Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma
- Author
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Lindahl, Lise M, Willerslev-Olsen, Andreas, Gjerdrum, Lise M R, Nielsen, Pia R, Blümel, Edda, Rittig, Anne H, Celis, Pamela, Herpers, Bjorn, Becker, Jürgen C, Stausbøl-Grøn, Birgitte, Wasik, Mariusz A, Gluud, Maria, Fredholm, Simon, Buus, Terkild B, Johansen, Claus, Nastasi, Claudia, Peiffer, Lukas, Kubat, Linda, Bzorek, Michael, Eriksen, Jens O, Krejsgaard, Thorbjørn, Bonefeld, Charlotte M, Geisler, Carsten, Mustelin, Tomas, Langhoff, Erik, Givskov, Michael, Woetmann, Anders, Kilian, Mogens, Litman, Thomas, Iversen, Lars, Odum, Niels, Lindahl, Lise M, Willerslev-Olsen, Andreas, Gjerdrum, Lise M R, Nielsen, Pia R, Blümel, Edda, Rittig, Anne H, Celis, Pamela, Herpers, Bjorn, Becker, Jürgen C, Stausbøl-Grøn, Birgitte, Wasik, Mariusz A, Gluud, Maria, Fredholm, Simon, Buus, Terkild B, Johansen, Claus, Nastasi, Claudia, Peiffer, Lukas, Kubat, Linda, Bzorek, Michael, Eriksen, Jens O, Krejsgaard, Thorbjørn, Bonefeld, Charlotte M, Geisler, Carsten, Mustelin, Tomas, Langhoff, Erik, Givskov, Michael, Woetmann, Anders, Kilian, Mogens, Litman, Thomas, Iversen, Lars, and Odum, Niels
- Abstract
It has been proposed that CD4 T cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T cell lymphoma (CTCL). In this prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in eight patients with advanced stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In six out of eight patients, a malignant T cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global mRNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of IL-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.
- Published
- 2019
7. Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma
- Author
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Lindahl, Lise M., primary, Willerslev-Olsen, Andreas, additional, Gjerdrum, Lise M.R., additional, Nielsen, Pia R., additional, Blümel, Edda, additional, Rittig, Anne H., additional, Celis, Pamela, additional, Herpers, Bjorn, additional, Becker, Jürgen C., additional, Stausbøl-Grøn, Birgitte, additional, Wasik, Mariusz A., additional, Gluud, Maria, additional, Fredholm, Simon, additional, Buus, Terkild B., additional, Johansen, Claus, additional, Nastasi, Claudia, additional, Peiffer, Lukas, additional, Kubat, Linda, additional, Bzorek, Michael, additional, Eriksen, Jens O., additional, Krejsgaard, Thorbjørn, additional, Bonefeld, Charlotte M., additional, Geisler, Carsten, additional, Mustelin, Tomas, additional, Langhoff, Erik, additional, Givskov, Michael, additional, Woetmann, Anders, additional, Kilian, Mogens, additional, Litman, Thomas, additional, Iversen, Lars, additional, and Odum, Niels, additional
- Published
- 2019
- Full Text
- View/download PDF
8. Prognostic miRNA classifier in early-stage mycosis fungoides:development and validation in a Danish nationwide study
- Author
-
Lindahl, Lise M, Besenbacher, Søren, Rittig, Anne H, Celis, Pamela, Willerslev-Olsen, Andreas, Gjerdrum, Lise M R, Krejsgaard, Thorbjørn, Johansen, Claus, Litman, Thomas, Woetmann, Anders, Odum, Niels, Iversen, Lars, Lindahl, Lise M, Besenbacher, Søren, Rittig, Anne H, Celis, Pamela, Willerslev-Olsen, Andreas, Gjerdrum, Lise M R, Krejsgaard, Thorbjørn, Johansen, Claus, Litman, Thomas, Woetmann, Anders, Odum, Niels, and Iversen, Lars
- Abstract
Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma. The disease often takes an indolent course, but in approximately one-third of the patients, the disease progresses to an aggressive malignancy with a poor prognosis. At the time of diagnosis, it is impossible to predict which patients develop severe disease and are in need of aggressive treatment. Accordingly, we investigated the prognostic potential of microRNAs (miRNAs) at the time of diagnosis in MF. Using a quantitative reverse transcription polymerase chain reaction platform, we analyzed miRNA expression in diagnostic skin biopsies from 154 Danish patients with early-stage MF. The patients were subdivided into a discovery cohort (n = 82) and an independent validation cohort (n = 72). The miRNA classifier was built using a LASSO (least absolute shrinkage and selection operator) Cox regression to predict progression-free survival (PFS). We developed a 3-miRNA classifier, based on miR-106b-5p, miR-148a-3p, and miR-338-3p, which successfully separated patients into high-risk and low-risk groups of disease progression. PFS was significantly different between these groups in both the discovery cohort and the validation cohort. The classifier was stronger than existing clinical prognostic factors and remained a strong independent prognostic tool after stratification and adjustment for these factors. Importantly, patients in the high-risk group had a significantly reduced overall survival. The 3-miRNA classifier is an effective tool to predict disease progression of early-stage MF at the time of diagnosis. The classifier adds significant prognostic value to existing clinical prognostic factors and may facilitate more individualized treatment of these patients.
- Published
- 2018
9. Prognostic miRNA classifier in early-stage mycosis fungoides: Development and validation in a Danish nationwide study
- Author
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Lindahl, Lise M., primary, Besenbacher, Søren, additional, Rittig, Anne H., additional, Celis, Pamela, additional, Willerslev-Olsen, Andreas, additional, Gjerdrum, Lise M.R., additional, Krejsgaard, Thorbjørn, additional, Johansen, Claus, additional, Litman, Thomas, additional, Woetmann, Anders, additional, Odum, Niels, additional, and Iversen, Lars, additional
- Published
- 2018
- Full Text
- View/download PDF
10. Protein phosphatase 2Cδ/Wip1 regulates phospho-p90RSK2 activity in lesional psoriatic skin
- Author
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Rasmussen, Mads K, primary, Nielsen, Jakob, additional, Kjellerup, Rasmus B, additional, Andersen, Stine M, additional, Rittig, Anne H, additional, Johansen, Claus, additional, Iversen, Lars, additional, and Gesser, Borbala, additional
- Published
- 2017
- Full Text
- View/download PDF
11. Protein phosphatase 2Cδ/Wip1 regulates phospho-p90RSK2 activity in lesional psoriatic skin
- Author
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Rasmussen,Mads K, Nielsen,Jakob, Kjellerup,Rasmus B, Andersen,Stine M, Rittig,Anne H, Johansen,Claus, Iversen,Lars, Gesser,Borbala, Rasmussen,Mads K, Nielsen,Jakob, Kjellerup,Rasmus B, Andersen,Stine M, Rittig,Anne H, Johansen,Claus, Iversen,Lars, and Gesser,Borbala
- Abstract
Mads K Rasmussen, Jakob Nielsen, Rasmus B Kjellerup, Stine M Andersen, Anne H Rittig, Claus Johansen, Lars Iversen, Borbala Gesser Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark Objectives: P90 ribosomal S6 kinase (RSK) 1 and 2 are serine/threonine protein kinases believed to mediate proliferation and apoptosis via the extracellular signal-regulated kinases (ERK1/2) signaling pathway. Macrophage migration inhibitory factor (MIF) and epidermal growth factor (EGF) are activators of this pathway and are elevated in the serum of patients with psoriasis compared with healthy controls. Studies on COS-7 cell cultures have shown that protein phosphatase 2Cδ (PP2Cδ) decreases the activity of RSK2 following EGF stimulation. We therefore hypothesize that PP2Cδ regulates RSK2 activity in psoriasis. Methods: In paired biopsies from nonlesional (NL) and lesional (L) skins, we analyzed the level of RSK1, 2 phosphorylation and the expression of PP2Cδ isoforms, integrin-linked kinase-associated serine/threonine phosphatase (ILKAP) and wild-type p53-induced phosphatase 1 (Wip1) by Western blotting, immunofluorescence and coimmunoprecipitation with monoclonal antibody for RSK2. The induction of Wip1 by MIF or EGF was studied in cultured normal human keratinocytes.Results: The protein level of RSK1, 2 phosphorylated at T573/T577 was significantly increased in L compared with NL psoriatic skin, while phosphorylation at S380/S386 was reduced in L compared with NL psoriatic skin when assayed by Western blotting and immunofluorescence microscopy. ILKAP expression was significantly higher in L than in NL skin, whereas Wip1 was expressed in similar amounts but showed increased coimmunoprecipitation with RSK2 in L compared with NL psoriatic skin. In cultured normal human keratinocytes stimulated with MIF, Wip1 phosphorylation and Wip1 expression were increased after 2
- Published
- 2017
12. Suppressed microRNA-195-5p expression in mycosis fungoides promotes tumor cell proliferation.
- Author
-
Rittig AH, Johansen C, Celis P, Odum N, Litman T, Woetmann A, Lindahl LM, and Iversen L
- Subjects
- Apoptosis genetics, Cell Cycle Checkpoints genetics, Cell Line, Tumor, Disease Progression, Down-Regulation, Gene Expression Regulation, Neoplastic, Humans, Mycosis Fungoides pathology, Skin Neoplasms pathology, Cell Proliferation genetics, GTP-Binding Proteins genetics, MicroRNAs metabolism, Mycosis Fungoides genetics, Skin Neoplasms genetics
- Abstract
Background: Several cancers, including mycosis fungoides (MF), have reported dysregulation of miR-195-5p. miR-195-5p plays a role in cell cycle regulation in several malignant diseases., Objectives: This study aimed to investigate: (a) the expression level of miR-195-5p in lesional MF skin biopsies and (b) the potential regulatory roles of miR-195-5p in MF., Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to determine miR-195-5p expression in MF skin biopsies and cell lines. The effect of miR-195-5p and ADP-ribosylation factor-like protein 2 (ARL2) on cell cycle and apoptosis was measured by flow cytometry assays. Changes in ARL2 expression were determined by RT-qPCR and Western blotting (WB)., Results: We found lower expression levels of miR-195-5p in lesional skin from MF patients compared with non-lesional MF skin and skin from healthy volunteers. Additionally, miR-195-5p showed lower expression levels in the skin from patients with disease progression compared with patients with stable disease. In vitro studies showed that overexpression of miR-195-5p induced a cell cycle arrest in G0G1. Using microarray analysis, we identified several genes that were regulated after miR-195-5p overexpression. The most downregulated gene after miR-195-5p mimic transfection was ARL2. RT-qPCR and WB analyses confirmed downregulation of ARL2 following transfection with miR-195-5p mimic. Lastly, transfection with siRNA against ARL2 also induced a G0G1 arrest., Conclusion: Upregulation of miR-195-5p in MF inhibits cycle arrest by downregulation of ARL2. miR-195-5p may thus function as a tumor suppressor in MF and low miR-195-5p expression in lesional MF skin may promote disease progression., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
13. MicroRNA-106b Regulates Expression of the Tumour Suppressors p21 and TXNIP and Promotes Tumour Cell Proliferation in Mycosis Fungoides.
- Author
-
Lindahl LM, Gluud M, Emmanuel T, Thomsen EA, Hu T, Rittig AH, Celis P, Stolearenco V, Krejsgaard T, Johansen C, Willerslev-Olsen A, Buus TB, Woetmann A, Aagaard L, Geisler C, Litman T, Mikkelsen JG, Odum N, and Iversen L
- Subjects
- Carrier Proteins, Cell Proliferation, Humans, Prognosis, MicroRNAs genetics, Mycosis Fungoides genetics, Skin Neoplasms genetics
- Abstract
A prognostic 3-miRNA classifier for early-stage mycosis fungoides has been developed recently, with miR-106b providing the strongest prognostic power. The aim of this study was to investigate the molecular function of miR-106b in mycosis fungoides disease progression. The cellular localization of miR-106b in mycosis fungoides skin biopsies was determined by in situ hybridization. The regulatory role of miR-106b was assessed by transient miR-106b inhibitor/mimic transfection of 2 mycosis fungoides derived cell lines, followed by quantitative real-time PCR (RT-qPCR), western blotting and a proliferation assay. MiR-106b was found to be expressed by dermal T-lymphocytes in mycosis fungoides skin lesions, and miR-106b expression increased with advancing mycosis fungoides stage. Transfection of miR-106b in 2 mycosis fungoides derived cell lines showed that miR-106b represses the tumour suppressors cyclin-dependent kinase inhibitor 1 (p21) and thioredoxin-interacting protein (TXNIP) and promotes mycosis fungoides tumour cell proliferation. In conclusion, these results substantiate that miR-106b has both a functional and prognostic role in progression of mycosis fungoides.
- Published
- 2020
- Full Text
- View/download PDF
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