| 1. |
- Drakskog, Cecilia, et al.
(författare)
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Extensive qPCR analysis reveals altered gene expression in middle ear mucosa from cholesteatoma patients
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- The middle ear is a small and hard to reach compartment, limiting the amount of tissue that can be extracted and the possibilities for studying the molecular mechanisms behind diseases like cholesteatoma. In this paper 14 reference gene candidates were evaluated in the middle ear mucosa of cholesteatoma patients and two different control tissues. ACTB and GAPDH were shown to be the optimal genes for the normalisation of target gene expression when investigating middle ear mucosa in multiplex qPCR analysis. Validation of reference genes using c-MYC expression confirmed the suitability of ACTB and GAPDH as reference genes and showed an upregulation of c-MYC in middle ear mucosa during cholesteatoma. The occurrence of participants of the innate immunity, TLR2 and TLR4, were analysed in order to compare healthy middle ear mucosa to cholesteatoma. Analysis of TLR2 and TLR4 showed variable results depending on control tissue used, highlighting the importance of selecting relevant control tissue when investigating causes for disease. It is our belief that a consensus regarding reference genes and control tissue will contribute to the comparability and reproducibility of studies within the field.
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| 2. |
- Westerberg, Johanna, 1971-, et al.
(författare)
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JAK/STAT Dysregulation With SOCS1 Overexpression in Acquired Cholesteatoma-Adjacent Mucosa
- 2021
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Ingår i: Otology and Neurotology. - : Lippincott Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 42:1, s. e94-e100
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Surgery remains the gold standard in cholesteatoma treatment. However, the rate of recurrence is significant and the development of new nonsurgical treatment alternatives is warranted. One of the possible molecular pathways to target is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.OBJECTIVE: To investigate the JAK/STAT pathway in the middle ear mucosa in patients with acquired cholesteatoma compared with middle ear mucosa from healthy controls.DESIGN: Case-control study.SETTING: Linköping University Hospital, Sweden, and Karolinska Institutet, Stockholm, Sweden. Sampling period: February 2011 to December 2016.PARTICIPANTS: Middle ear mucosa from 26 patients with acquired cholesteatoma undergoing tympanoplasty and mastoidectomy, and 27 healthy controls undergoing translabyrinthine surgery for vestibular schwannoma or cochlear implantation was investigated.MAIN OUTCOMES/MEASURES: The expression of Interleukin-7 receptor alpha, JAK1, JAK2, JAK3, STAT5A, STAT5B, and suppressor of cytokine signaling-1 (SOCS1) were quantified using quantitative polymerase chain reaction. In addition, expression level of cyclin D2, transforming growth factor beta 1, thymic stromal lymphopoietin, CD3, and CD19 was evaluated.RESULTS: In cholesteatoma-adjacent mucosa, SOCS1 was significantly upregulated (p= 0.0003) compared with healthy controls, whereas STAT5B was significantly downregulated (p = 0.0006). The expression of JAK1, JAK2, JAK3, and STAT5A did not differ significantly between groups.CONCLUSIONS AND RELEVANCE: To the best of our knowledge, this is the first article reporting dysregulation of the JAK/STAT pathway in cholesteatoma-adjacent mucosa. The main finding is that important players of the aforementioned pathway are significantly altered, namely SOCS1 is upregulated and STAT5B is downregulated compared with healthy controls.
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| 3. |
- Westerberg, Johanna, 1971-
(författare)
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Middle ear cholesteatoma : Surgical outcome and aspects of the innate immunity
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cholesteatomas are bone destructive expansions of keratinizing squamous epithelium in the middle ear and temporal bone. Today, surgery is the only treatment. There are several controversies regarding cholesteatomas, including the definition, the pathogenesis and the surgical method. Intense efforts have been made searching for a comprehension of the cholesteatoma process at a cellular and molecular level. Recurrent infections and inflammation seem to be contributing factors for the cholesteatomas to expand. The innate immunity, essential to keep a healthy middle ear environment and to protect the middle ear from intruding pathogens, is therefore a matter of interest.In this thesis, results are presented from a cohort of cholesteatoma surgeries in Östergötland from a 16-year period. A group of patients also filled in a questionnaire to assess changes in health-related quality of life (HRQoL) after surgery. According to the findings in this thesis, the residual and recurrence frequencies are low, and the hearing and HRQoL are improved in the majority of cases.This thesis also presents an investigation of the innate immunity in ears with acquired cholesteatoma, in comparison with healthy controls. The expression of mRNA of toll-like receptors 2 and 4, participants of the Janus kinase/signal transducer and activator of transcription pathway, and nitric oxide synthases in middle ear mucosa, were investigated with quantitative polymerase chain reaction. An investigation of nitric oxide (NO) in the middle ear, with chemiluminescence measurements, is also presented.A derangement of the innate immune system is seen in ears with cholesteatoma, which supports the idea that the innate immunity participates in the cholesteatoma process, though the underlying mechanisms are still unclear. The suggestion of NO production in the middle ear sheds light on NOs possible participation in the healthy middle ear environment.
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