| 1. |
- Bark, Rusana, et al.
(författare)
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Sentinel node-assisted neck dissection in advanced oral squamous cell carcinoma - A new protocol for staging and treatment
- 2023
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Ingår i: Cancer Medicine. - : Wiley-Blackwell. - 2045-7634. ; 12:11, s. 12524-12534
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sentinel lymph node biopsy (SLNB) is used to improve the staging of and guide treatment in patients with early-stage T1-T2 N0 oral squamous cell carcinoma (OSCC). The role of sentinel nodes (SNs) and the use of SN-technique in advanced OSCC (T3-T4 and/or N+) remain to be evaluated. This study investigates the nodal drainage and the rate of positive SNs (SNs+) in all stages of OSCC.Materials and Methods: In total, 85 patients with T1-T4 OSCC diagnosed 2019-2021 were included. We used a prolonged interval between peritumoral injection of radionuclide and SPECT-CT to include all SNs.Results: Patients with advanced OSCC presented a higher proportion of contralateral lymphatic drainage and a higher rate of SN+ compared to patients with early-stage disease. T3-T4 and N+ tumors presented a tendency for a higher rate of contralateral lymphatic drainage compared to T1-T2 and N0 tumors (p = 0.1). The prevalence of positive nodes (SNs+) was higher among patients with advanced disease, T3-T4 versus T1-T2 (p = 0.0398).Conclusion: SN-assisted ND enables identification and removal of all SNs + and has the potential for more accurate staging and could possibly give prognostic advantages regarding regional recurrence for all OSCC patients, especially among those with advanced disease. The precise localization of the SNs + also suggests that a more individualized ND approach might be possible in the future even for patients with advanced OSCC.
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| 2. |
- Bogefors, Jesper, et al.
(författare)
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LEAP-2, LL-37 and RNase7 in tonsillar tissue: downregulated expression in seasonal allergic rhinitis.
- 2014
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Ingår i: Pathogens and Disease. - 2049-632X. ; 72:1, s. 55-60
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Tidskriftsartikel (refereegranskat)abstract
- In the upper airway, the production of antimicrobial peptides (AMPs) protects against bacteria, viruses and fungi. Previous investigations have revealed downregulated expression of AMPs in different manifestations of allergic disease. In this study, we examined the expression of LL-37, RNase7 and LEAP-2 in tonsillar tissue and studied a possible relation to seasonal allergic rhinitis (SAR).
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| 3. |
- 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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| 4. |
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| 6. |
- Georén, Susanna Kumlien
(författare)
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Endogenous and exogenous glucocorticoid effects in a model of allergic airway inflammation.
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Allergic asthma and rhinitis are inflammatory diseases of the airways. Allergic asthma is characterized by eosinophilic inflammation, reversible bronchoconstriction and airway hyperresponsiveness, whereas patients with rhinitis suffer from nasal inflammation, leading to rhinorrhea and nasal congestion. Glucocorticoids (GCs) are one of the major drugs for asthma and rhinitis treatment and can regulate leukocyte trafficking and mediator release. The hypothalamus pituitary-adrenal (HPA) axis regulates the secretion of endogenous GCs, and is one of the major stress effector systems in the body. The main role for the HPA-axis is to facilitate the maintenance of neuroendocrine homeostasis, both at basal and pathological conditions. An understanding of the regulation and function of the HPA axis is important for the evaluation of pathological changes and possible side effects caused by GCs. In the studies presented in this thesis we have used a mouse model to investigate the effects of endogenous GC synthesis and GC receptor inhibition, as well as acute stress, and different doses of exogenous administered GCs on inflammatory cells in different cellular compartments in allergic airway inflammation. We also investigated the effects of acute stress on the neurotrophic mediator, nerve growth factor (NGF) in the airways, during allergic inflammation. In the first study (I), we investigated the effects of endogenous GCs on eosinophilic airway inflammation. Inhibition of GC release with metyrapone (ME) induced an increase of bone marrow eosinophilia and when the ME treatment was combined with a GC receptor antagonist (RU 486) the allergen-induced bone marrow eosinophilia was further enhanced. ME treatment also induced an increase of CD4+ T lymphocytes in the nasal mucosa, both when employed as a single treatment and in combination with RU 486. In the second study (II), timing and dose-dependent effects of dexamethasone (DEX) on eosinophilic airway inflammation were studied. This study provided evidence that a low dose of DEX (1 µg/kg) evoked a stronger inhibitory effect on the eosinophilic airway inflammation, as compared to the effect of the 500 times higher pharmacological dose (500µg/kg) if given before the allergen challenge. When administered simultaneously the allergen challenge, the two doses displayed similar effects. The third study (III), was focused on the effects of timing of a short acute stress on allergic airway inflammation in upper and lower airways. Short stress applied before an allergen challenge decreased the allergen-induced eosinophilia in bronchoalveolar lavage fluid and lungs and also the inflammation in the nasal tissue. No effects on eosinophilia or inflammation were seen when stress was applied after allergen challenge or as a double stress both before and after challenge. The protective effects, seen in the mice stressed prior to the allergen challenge, were GC-dependent. In the fourth study (IV), the aim was to assess how acute stress modulated NGF levels and eosinophils in the airways during non-allergic and mild allergic conditions. We found that short stress increased the levels of NGF locally in the airways in both allergic and non-allergic mice. We also demonstrated that airway eosinophils decreased when stress was applied after allergen-challenge in a model of mild airway inflammation. The stress-evoked increase in NGF and decrease in eosinophilia in the airways were dependent on endogenous GC-synthesis, as evident from pre-treatment with ME. In summary, these results indicate that endogenous GCs may have a protective effect in both upper and lower eosinophilic airway inflammation. Our studies also demonstrate that the inhibitory effect of GCs on the allergic inflammation is timing-dependent. By the use of a GC synthesis inhibitor, we show that the inhibitory effects on the eosinophilic airway inflammation during acute stress are GC-dependent. Acute stress increased local airway NGF and this effect is mediated by endogenous GC synthesis. Thus, we also conclude that NGF may function as a mediator in the psychoneuroimmunological stress-response.
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| 7. |
- Hylander, Terese, et al.
(författare)
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Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double-blind placebo-controlled trial.
- 2016
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Allergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases. We and others have previously demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, this has recently been disputed. The aim of this study was therefore to expand our previous trial, further assessing the safety and efficacy of ILIT.
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| 8. |
- Larsson, Olivia, et al.
(författare)
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Substance P represents a novel first-line defense mechanism in the nose
- 2018
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 141:1, s. 3-136
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuropeptides, such as substance P (SP), have long been seen as mediators of widespread continuous airway inflammation, a process known as neurogenic inflammation. However, this has been difficult to demonstrate clinically, suggesting an alternative role for these signaling molecules. Objectives: We sought to examine the role of SP in nasal infection by assessing the release of SP in response to viral stimulation and characterizing the effects of SP on innate immunity, with the latter reflected in changes in local Toll-like receptor (TLR) expression. Methods: The distribution of SP and TLRs in the nasal mucosa and local airway neurons was assessed with immunohistochemistry. The TLR7 agonists R-837 and R-848 were used to mimic a viral insult in the upper airways represented by primary human nasal epithelial cells (HNECs) and murine nasal epithelial cells (MNECs) and isolated murine trigeminal ganglial neurons. SP release from HNECs, MNECs, and trigeminal ganglial neurons was quantified with EIA. The effects of SP on TLR expression on HNECs were determined by using flow cytometry and confocal microscopy. Results: SP was released from the sensory neurons, MNECs, and HNECs within 15 minutes of local TLR7 stimulation. Subsequently, stimulation with SP induced upregulation of TLR expression in HNECs within 30 minutes through induction of TLR movement within HNECs. Upregulation of TLR expression was not evident when cells were treated with the neurokinin 1 receptor antagonist aprepitant before SP stimulation. Conclusions: This highlights a novel role for sensory neuropeptides as acute and local mediators of pathogen-driven inflammation, rapidly priming innate immune defenses in the airway.
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| 9. |
- Larsson, Olivia, et al.
(författare)
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The SP‐TLR axis, which locally primes the nasal mucosa, is impeded in patients with allergic rhinitis
- 2021
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Ingår i: Clinical and Translational Allergy. - Oxford, United kingdom : John Wiley & Sons. - 2045-7022. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSubstance P (SP) and toll-like receptors (TLRs) contribute to airway disease, particularly during viral infection. We recently demonstrated that SP can act as an initial response to viral stimuli in the upper airway by upregulating TLRs in the nasal epithelia (the SP-TLR axis). Patients with allergic rhinitis (AR) suffer from prolonged airway infections. The aim of the present study was to examine if patients with AR exhibit a disturbance in the SP-TLR axis.MethodHuman nasal biopsies and human nasal epithelial cells (HNEC) from healthy volunteers and patients with AR were cultured in the presence of SP. Epithelial expression of TLR4, neutral endopeptidase (NEP) and neurokinin 1 (NK1) were evaluated with flow cytometry and/or quantitative polymerase chain reaction after 30 min to 24 h. The effect of SP on nasal lipopolysaccharide-induced interleukin-8 (IL-8) release was investigated.ResultsSP stimulation of tissue from healthy volunteers resulted in a transient increase of the TLR4 expression, whereas stimulation of AR patient-derived material led to a delayed and prolonged upregulation of TLR4. NEP expression in HNEC was lower in AR than healthy controls whereas NK1 receptor expression was increased. SP pretreatment increased TLR4-dependent IL-8 expression in healthy controls, but not in AR.ConclusionsSP-induced regulation of TLR4 in the human nasal mucosa is disturbed in AR. An altered SP-mediated innate immune response may contribute to the dysfunctional and often prolonged responses to infection in AR.
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| 10. |
- Piersiala, Krzysztof, et al.
(författare)
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Regulatory B cells producing IL-10 are increased in human tumor draining lymph nodes
- 2023
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 153:4, s. 854-866
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of different immune cell subsets, especially T cells, in anti-tumor immune response is well established. In contrast to T cells, the anti-tumor contribution of B cells has been scarcely investigated. B-cells are often overlooked, even though they are important players in a fully integrated immune response and constitute a substantial fraction of tumor draining lymph nodes (TDLNs) known also as Sentinel Nodes. In this project, samples including TDLNs, non-TDLNs (nTDLNs) and metastatic lymph nodes from 21 patients with oral squamous cell carcinoma were analyzed by flow cytometry. TDLNs were characterized by a significantly higher proportion of B cells compared with nTDLNs (P = .0127). TDLNs-associated B cells contained high percentages of naive B cells, in contrary to nTDLNs which contained significantly higher percentages of memory B cells. Patients having metastases in TDLNs showed a significantly higher presence of immunosuppressive B regulatory cells compared with metastasis-free patients (P = .0008). Elevated levels of regulatory B cells in TDLNs were associated with the advancement of the disease. B cells in TDLNs were characterized by significantly higher expression of an immunosuppressive cytokine-IL-10 compared with nTDLNs (P = .0077). Our data indicate that B cells in human TDLNs differ from B cells in nTDLNs and exhibit more naive and immunosuppressive phenotypes. We identified a high accumulation of regulatory B cells within TDLNs which may be a potential obstacle in achieving response to novel cancer immunotherapies (ICIs) in head and neck cancer.
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