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1. Tonsillar transcriptional profiles in atopic and non-atopic subjects

Author

Hanif, T. (Tanzeela), Ivaska, L. E. (Lotta E.), Ahmad, F. (Freed), Tan, G. (Ge), Mikola, E. (Emilia), Puhakka, T. (Tuomo), Palomares, O. (Oscar), Akdis, C. A. (Cezmi A.), Toppila-Salmi, S. (Sanna), Jartti, T. (Tuomas), Hanif, T. (Tanzeela), Ivaska, L. E. (Lotta E.), Ahmad, F. (Freed), Tan, G. (Ge), Mikola, E. (Emilia), Puhakka, T. (Tuomo), Palomares, O. (Oscar), Akdis, C. A. (Cezmi A.), Toppila-Salmi, S. (Sanna), and Jartti, T. (Tuomas)

Abstract

Background: Emerging research suggests that local lymphatic tissue such as tonsils have important role in regulating the immune responses. However, allergen sensitization-induced alterations in transcriptome of tonsils are not known. Objective: To examine the key differences in tonsillar gene expression between atopic and non-atopic subjects and further by type of sensitization. Methods: RNA-sequencing was performed on 52 tonsillar samples from atopic and non-atopic tonsillectomy patients. Sensitization to common food- and aero-allergen was defined by allergen specific IgE. Following groups were studied: (1) aero- and food-allergen sensitized (AS+FS) versus non-sensitized (NS), (2) aeroallergen-sensitized (AS) versus food-allergen sensitized (FS), (3) AS versus NS, (4) FS versus NS. Bioinformatics analysis was done using DESeq2(v3.10.2), WGCNA and GATK pipeline in R software (v3.3.1). Protein–protein interaction network was made from String database. Results: We studied 13 aeroallergen-sensitized, 6 food-allergen sensitized, 4 both food-and aero-allergen-sensitized and 29 non-sensitized tonsillectomy patients. Overall, 697 unique differentially expressed genes (DEGs) were detected in all sensitized subgroups including chemokines (CXCL2, CXCL8, CXCL10, CXCL11), IL-20RA, MUC1 and MUC20. When comparing different groups, the gene expression profiles overlapped except the AS versus FS group comparison, suggesting significantly different gene expression between the two sensitization subgroups. Furthermore, aeroallergen-sensitized subjects had more prominent immune responses compared with non-sensitized and food-allergen sensitized subjects including gene expression for IL-17 pathway and Toll-like receptor signalling pathway. Conclusion: Allergic sensitization is associated with extensive tonsillar transcriptomic alterations and changes in immune related genes and pathways. Distinct differences were found between aero-allergen and food-allergen sensitization.

Published
2023

2. The expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma

Author

Seppälä, M. (Miia), Jauhiainen, L. (Laura), Tervo, S. (Sanni), Al-Samadi, A. (Ahmed), Rautiainen, M. (Markus), Salo, T. (Tuula), Lehti, K. (Kaisa), Monni, O. (Outi), Hautaniemi, S. (Sampsa), Tynninen, O. (Olli), Mäkitie, A. (Antti), Mäkinen, L. K. (Laura K.), Paavonen, T. (Timo), Toppila-Salmi, S. (Sanna), Seppälä, M. (Miia), Jauhiainen, L. (Laura), Tervo, S. (Sanni), Al-Samadi, A. (Ahmed), Rautiainen, M. (Markus), Salo, T. (Tuula), Lehti, K. (Kaisa), Monni, O. (Outi), Hautaniemi, S. (Sampsa), Tynninen, O. (Olli), Mäkitie, A. (Antti), Mäkinen, L. K. (Laura K.), Paavonen, T. (Timo), and Toppila-Salmi, S. (Sanna)

Abstract

P-cadherin (CDH3) is a cell-to-cell adhesion molecule that regulates several cellular homeostatic processes in normal tissues. Lack of CDH3 expression is associated with aggressive behavior in oral squamous cell carcinoma (OSCC). Previous studies have shown that CDH3 is downregulated in high-grade OSCC and its reduced expression is predictive for poorer survival. The aim of this study was to evaluate the expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma (TSCC). A retrospective series of 211 TSCC and 50 lymph node samples were stained immunohistochemically with polyclonal antibody (anti-CDH3). CDH3 expression was assessed semi-quantitatively with light microscopy. Fisher’s exact test was used to compare patient and tumor characteristics, and the correlations were tested by Spearman correlation. Survival curves were drawn by the Kaplan–Meier method and analyzed by the log-rank test. Univariate and multivariate Cox regression was used to estimate the association between CDH3 expression and survival. CDH3 expression did not affect TSCC patient’s disease-specific survival or overall survival. Strong CDH3 expression in the primary tumor predicted poor disease-specific and overall survival in patients with recurrent disease. CDH3 expression in lymph nodes without metastasis was negative in all cases. CDH3 expression was positive in all lymph node metastases with extranodal extension. In contrast to previous report about the prognostic value of CDH3 in OSCC, we were not able to validate the result in TSCC.

Published
2021

3. The effect of fascin 1 inhibition on head and neck squamous cell carcinoma cells

Author

Wahab, A. (Awais), Hyytiäinen, A. (Aini), Wahbi, W. (Wafa), Tuomainen, K. (Katja), Tervo, S. (Sanni), Conesa-Zamora, P. (Pablo), Jauhiainen, L. (Laura), Mäkinen, L. K. (Laura K.), Paavonen, T. (Timo), Toppila-Salmi, S. (Sanna), Salem, A. (Abdelhakim), Almangush, A. (Alhadi), Salo, T. (Tuula), Al-Samadi, A. (Ahmed), Wahab, A. (Awais), Hyytiäinen, A. (Aini), Wahbi, W. (Wafa), Tuomainen, K. (Katja), Tervo, S. (Sanni), Conesa-Zamora, P. (Pablo), Jauhiainen, L. (Laura), Mäkinen, L. K. (Laura K.), Paavonen, T. (Timo), Toppila-Salmi, S. (Sanna), Salem, A. (Abdelhakim), Almangush, A. (Alhadi), Salo, T. (Tuula), and Al-Samadi, A. (Ahmed)

Abstract

Fascin 1 plays important pro-metastatic roles in head and neck carcinoma (HNSCC) migration, invasion, and metastasis. However, limited advancement in targeting metastasis remains a major obstacle in improving HNSCC patients’ survival. Therefore, we assessed the therapeutic potential of fascin 1 targeted inhibition and its potential prognostic value in HNSCC patients. Using in vitro and in vivo approaches, we investigated the effect of compound G2, a novel fascin 1 inhibitor, on HNSCC cells migration, invasion, and metastasis. High-throughput screening (HTS) was used to assess cytotoxic activity of compound G2 alone or combined with irradiation. We also evaluated the prognostic potential of fascin 1 in HNSCC patients. Interestingly, compound G2 reduced carcinoma cells migration and invasion in vitro and inhibited metastasis in vivo. Moreover, HTS revealed a modest cytotoxic activity of the compound G2 on HNSCC cell lines. Irradiation did not synergistically enhance the compound G2-mediated cytotoxic activity. Survival analyses showed that high fascin 1 immunoexpression, at the tumor invasive front, was associated with cancer-specific mortality in the advanced stages of HNSCC. Collectively, our findings suggest that fascin 1 represents a promising anti-metastatic therapeutic target and a useful prognostic marker in patients with HNSCC. Novel anti-metastatic agents could provide a valuable addition to cancer therapy.

Published
2021

4. Evaluation challenges in the validation of B7-H3 as oral tongue cancer prognosticator

Author

Sieviläinen, M. (Meri), Wirsing, A. M. (Anna Maria), Hyytiäinen, A. (Aini), Almahmoudi, R. (Rabeia), Rodrigues, P. (Priscila), Bjerkli, I.-H. (Inger-Heidi), Åström, P. (Pirjo), Toppila-Salmi, S. (Sanna), Paavonen, T. (Timo), Coletta, R. D. (Ricardo D.), Hadler-Olsen, E. (Elin), Salo, T. (Tuula), Al-Samadi, A. (Ahmed), Sieviläinen, M. (Meri), Wirsing, A. M. (Anna Maria), Hyytiäinen, A. (Aini), Almahmoudi, R. (Rabeia), Rodrigues, P. (Priscila), Bjerkli, I.-H. (Inger-Heidi), Åström, P. (Pirjo), Toppila-Salmi, S. (Sanna), Paavonen, T. (Timo), Coletta, R. D. (Ricardo D.), Hadler-Olsen, E. (Elin), Salo, T. (Tuula), and Al-Samadi, A. (Ahmed)

Abstract

B7-H3 was the only molecule identified with prognostic potential from a recent systematic review of the prognostic value of immune checkpoints in oral cancer. We aimed to validate this finding in a multicenter international cohort. We retrospectively retrieved 323 oral tongue squamous cell carcinoma (OTSCC) samples from three different countries (Brazil, Finland, and Norway) for immunostaining and scoring for B7-H3. We evaluated tumor immunogenicity by analyzing the amount of tumor-infiltrating lymphocytes and divided the tumors into immune hot and cold. To increase the reliability of the results, both digital and manual visual scoring were used. Survival curves were constructed based on the Kaplan-Meier method, and the Cox proportional hazard model was utilized for univariate and multivariate survival analysis. B7-H3 expression was not significantly associated with overall or disease-specific survival in the whole OTSCC cohort. When divided into immune hot and cold tumors, high B7-H3 expression was significantly associated with poor disease-specific and overall survival in the immune hot group, depending on the scoring method and the country of the cohort. This was achieved only in the univariate analysis. In conclusion, B7-H3 was a negative prognosticator for OTSCC patient survival in the subgroup of immune hot tumors, and was not validated as a prognosticator in the full cohort. Our findings suggest that the immune activity of the tumor should be considered when testing immune checkpoints as biomarkers.

Published
2021

5. Maternal smoking during pregnancy affects adult onset of asthma in offspring:a follow up from birth to age 46 years

Author

Toppila-Salmi, S. (Sanna), Luukkainen, A. T. (Annika T.), Xu, B. (Baizhuang), Lampi, J. (Jussi), Auvinen, J. (Juha), Dhaygude, K. (Kishor), Järvelin, M.-R. (Marjo-Riitta), and Pekkanen, J. (Juha)

Subjects
respiratory tract diseases
Abstract

Rationale: Environmental tobacco smoke (ETS) exposure increases asthma risk in children. There is limited knowledge of prenatal ETS for adult-onset asthma. Objectives: To determine the association between prenatal ETS and adult onset asthma. Measurements and main results: The questionnaire and clinical data of 5200 people, free of physician-diagnosed asthma by 31 years of age, who were included in the Northern Finland Birth Cohort 1966 Study was used. The association of maternal smoking during the last 3 months of pregnancy with onset of physician-diagnosed asthma and with lung function in adult offspring was studied using adjusted multivariate regression analyses. The cumulative incidence of physician-diagnosed asthma between the ages of 31 and 46 years was 5.1% among men and 8.8% among women. Gestational smoke exposure was associated with adult-onset asthma among offspring (adjusted OR 1.54, 95% CI 1.04–2.29), namely among offspring who reported either past non-diagnosed asthma (OR 9.63, 95% CI 2.28–40.67) or past cough with wheeze (3.21, 95% CI 1.71–6.05). A significant association was detected between gestational smoke exposure and the offspring’s forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) ratio at 31 years of age. In offspring with the haplotype rs11702779-AA of RUNX1, gestational smoke exposure was associated with adult-onset asthma (5.53, 95% CI 2.11–14.52, adjusted p-value for interaction 0.10). Conclusion: Maternal smoking during pregnancy is associated with the cumulative incidence of asthma in offspring between the ages of 31 and 46 years. The association was accentuated in offspring who at age 31, reported having past respiratory problems and/or who had haplotype rs11702779-AA. A reduction in FEV₁/FVC ratio was also observed at age 31 years in offspring with gestational smoke exposure. These results could reflect the early vulnerability of offspring’s airways to ETS and its putative long-term effects.

Published
2020

6. Next-generation care pathways for allergic rhinitis and asthma multimorbidity: A model for multimorbid non-communicable diseases—Meeting Report (Part 1)

Author

Bousquet, J. (Jean), Pham-Thi, N. (Nhân), Bedbrook, A. (Anna), Agache, I. (Ioana), Annesi-Maesano, I. (Isabella), Ansotegui, I.J. (I.), Anto, J.M. (Josep), Bachert, C. (Claus), Benveniste, S. (Samuel), Bewick, M. (Mike), Billo, N. (Nils), Bosnic-Anticevich, S. (Sinthia), Bosse, I. (Isabelle), Brusselle, G.G. (Guy), Calderon, M. (Moises), Canonica, G. (Gwalter), Caraballo, L.R. (L.), Cardona, D. (Doris), Carriazo, A.M. (Ana Maria), Cash, E. (Eugene), Cecchi, L. (Lorenzo), Chu, D.K. (Derek K.), Colgan, E. (Elaine), Costa, E. (Elisio), Cruz, A.A. (Alvaro), Czarlewski, W. (Wienczyslawa), Durham, S.R. (Stephen), Ebisawa, M. (Motohiro), Erhola, M. (Marina), Fauquert, J.-L. (Jean-Luc), Fokkens, W.J. (Wytske), Fonseca, J.A. (Joao A.), Guldemond, N. (Nick), Iinuma, T. (Tomohisa), Illario, M. (Maddalena), Klimek, L. (Ludger), Kuna, P. (Piotr), Kvedariene, V. (Violeta), Larenas-Linneman, D. (Désirée), Laune, D. (Daniel), Le, L.T.T. (Lan T.T.), Lourenço, O. (Olga), Malva, J.O. (Joao O.), Marien, G. (Gert), Menditto, E. (Enrica), Mullol, J. (Joaquim), Münter, L. (Lars), Okamoto, Y. (Yoshitaka), Onorato, G.L. (Gabrielle L.), Papadopoulos, N., Perala, M. (Maritta), Pfaar, O. (Oliver), Phillips, A. (Abigail), Phillips, J. (Jim), Pinnock, H. (Hilary), Portejoie, F. (Fabienne), Quinones-Delgado, P. (Pablo), Rolland, C. (Christine), Rodts, U. (Ulysse), Samolinski, B. (Boleslaw), Sanchez-Borges, M. (Mario), Schünemann, H.J. (Holger), Shamji, M. (Mohamed), Somekh, D. (David), Togias, A., Toppila-Salmi, S. (Sanna), Tsiligianni, I.G. (Ioanna G), Usmani, O. (Omar), Walker, S. (Samantha), Wallace, D. (D.), Valiulis, A. (Arunas), Van Der Kleij, R.M. (Rianne Mjj), Ventura, M.T. (Maria Teresa), Williams, S. (Sian), Yorgancioglu, A. (Arzu), Zuberbier, T. (Torsten), Bousquet, J. (Jean), Pham-Thi, N. (Nhân), Bedbrook, A. (Anna), Agache, I. (Ioana), Annesi-Maesano, I. (Isabella), Ansotegui, I.J. (I.), Anto, J.M. (Josep), Bachert, C. (Claus), Benveniste, S. (Samuel), Bewick, M. (Mike), Billo, N. (Nils), Bosnic-Anticevich, S. (Sinthia), Bosse, I. (Isabelle), Brusselle, G.G. (Guy), Calderon, M. (Moises), Canonica, G. (Gwalter), Caraballo, L.R. (L.), Cardona, D. (Doris), Carriazo, A.M. (Ana Maria), Cash, E. (Eugene), Cecchi, L. (Lorenzo), Chu, D.K. (Derek K.), Colgan, E. (Elaine), Costa, E. (Elisio), Cruz, A.A. (Alvaro), Czarlewski, W. (Wienczyslawa), Durham, S.R. (Stephen), Ebisawa, M. (Motohiro), Erhola, M. (Marina), Fauquert, J.-L. (Jean-Luc), Fokkens, W.J. (Wytske), Fonseca, J.A. (Joao A.), Guldemond, N. (Nick), Iinuma, T. (Tomohisa), Illario, M. (Maddalena), Klimek, L. (Ludger), Kuna, P. (Piotr), Kvedariene, V. (Violeta), Larenas-Linneman, D. (Désirée), Laune, D. (Daniel), Le, L.T.T. (Lan T.T.), Lourenço, O. (Olga), Malva, J.O. (Joao O.), Marien, G. (Gert), Menditto, E. (Enrica), Mullol, J. (Joaquim), Münter, L. (Lars), Okamoto, Y. (Yoshitaka), Onorato, G.L. (Gabrielle L.), Papadopoulos, N., Perala, M. (Maritta), Pfaar, O. (Oliver), Phillips, A. (Abigail), Phillips, J. (Jim), Pinnock, H. (Hilary), Portejoie, F. (Fabienne), Quinones-Delgado, P. (Pablo), Rolland, C. (Christine), Rodts, U. (Ulysse), Samolinski, B. (Boleslaw), Sanchez-Borges, M. (Mario), Schünemann, H.J. (Holger), Shamji, M. (Mohamed), Somekh, D. (David), Togias, A., Toppila-Salmi, S. (Sanna), Tsiligianni, I.G. (Ioanna G), Usmani, O. (Omar), Walker, S. (Samantha), Wallace, D. (D.), Valiulis, A. (Arunas), Van Der Kleij, R.M. (Rianne Mjj), Ventura, M.T. (Maria Teresa), Williams, S. (Sian), Yorgancioglu, A. (Arzu), and Zuberbier, T. (Torsten)

Published
2019
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7. Next-generation care pathways for allergic rhinitis and asthma multimorbidity: A model for multimorbid non-communicable diseases—Meeting Report (Part 2)

Author

Bousquet, J. (Jean), Pham-Thi, N. (Nhân), Bedbrook, A. (Anna), Agache, I. (Ioana), Annesi-Maesano, I. (Isabella), Ansotegui, I.J. (I.), Anto, J.M. (Josep), Bachert, C. (Claus), Benveniste, S. (Samuel), Bewick, M. (Mike), Billo, N. (Nils), Bosnic-Anticevich, S. (Sinthia), Bosse, I. (Isabelle), Brusselle, G.G. (Guy), Calderon, M. (Moises), Canonica, G. (Gwalter), Caraballo, L.R. (L.), Cardona, D. (Doris), Carriazo, A.M. (Ana Maria), Cash, E. (Eugene), Cecchi, L. (Lorenzo), Chu, D.K. (Derek K.), Colgan, E. (Elaine), Costa, E. (Elisio), Cruz, A.A. (Alvaro), Czarlewski, W. (Wienczyslawa), Durham, S.R. (Stephen), Ebisawa, M. (Motohiro), Erhola, M. (Marina), Fauquert, J.-L. (Jean-Luc), Fokkens, W.J. (Wytske), Fonseca, J.A. (Joao A.), Guldemond, N. (Nick), Iinuma, T. (Tomohisa), Illario, M. (Maddalena), Klimek, L. (Ludger), Kuna, P. (Piotr), Kvedariene, V. (Violeta), Larenas-Linneman, D. (Désirée), Laune, D. (Daniel), Le, L.T.T. (Lan T.T.), Lourenço, O. (Olga), Malva, J.O. (Joao O.), Marien, G. (Gert), Menditto, E. (Enrica), Mullol, J. (Joaquim), Münter, L. (Lars), Okamoto, Y. (Yoshitaka), Onorato, G.L. (Gabrielle L.), Papadopoulos, N., Perala, M. (Maritta), Pfaar, O. (Oliver), Phillips, A. (Abigail), Phillips, J. (Jim), Pinnock, H. (Hilary), Portejoie, F. (Fabienne), Quinones-Delgado, P. (Pablo), Rolland, C. (Christine), Rodts, U. (Ulysse), Samolinski, B. (Boleslaw), Sanchez-Borges, M. (Mario), Schünemann, H.J. (Holger), Shamji, M. (Mohamed), Somekh, D. (David), Togias, A., Toppila-Salmi, S. (Sanna), Tsiligianni, I.G. (Ioanna G), Usmani, O. (Omar), Walker, S. (Samantha), Wallace, D. (D.), Valiulis, A. (Arunas), Van Der Kleij, R.M. (Rianne Mjj), Ventura, M.T. (Maria Teresa), Williams, S. (Sian), Yorgancioglu, A. (Arzu), Zuberbier, T. (Torsten), Bousquet, J. (Jean), Pham-Thi, N. (Nhân), Bedbrook, A. (Anna), Agache, I. (Ioana), Annesi-Maesano, I. (Isabella), Ansotegui, I.J. (I.), Anto, J.M. (Josep), Bachert, C. (Claus), Benveniste, S. (Samuel), Bewick, M. (Mike), Billo, N. (Nils), Bosnic-Anticevich, S. (Sinthia), Bosse, I. (Isabelle), Brusselle, G.G. (Guy), Calderon, M. (Moises), Canonica, G. (Gwalter), Caraballo, L.R. (L.), Cardona, D. (Doris), Carriazo, A.M. (Ana Maria), Cash, E. (Eugene), Cecchi, L. (Lorenzo), Chu, D.K. (Derek K.), Colgan, E. (Elaine), Costa, E. (Elisio), Cruz, A.A. (Alvaro), Czarlewski, W. (Wienczyslawa), Durham, S.R. (Stephen), Ebisawa, M. (Motohiro), Erhola, M. (Marina), Fauquert, J.-L. (Jean-Luc), Fokkens, W.J. (Wytske), Fonseca, J.A. (Joao A.), Guldemond, N. (Nick), Iinuma, T. (Tomohisa), Illario, M. (Maddalena), Klimek, L. (Ludger), Kuna, P. (Piotr), Kvedariene, V. (Violeta), Larenas-Linneman, D. (Désirée), Laune, D. (Daniel), Le, L.T.T. (Lan T.T.), Lourenço, O. (Olga), Malva, J.O. (Joao O.), Marien, G. (Gert), Menditto, E. (Enrica), Mullol, J. (Joaquim), Münter, L. (Lars), Okamoto, Y. (Yoshitaka), Onorato, G.L. (Gabrielle L.), Papadopoulos, N., Perala, M. (Maritta), Pfaar, O. (Oliver), Phillips, A. (Abigail), Phillips, J. (Jim), Pinnock, H. (Hilary), Portejoie, F. (Fabienne), Quinones-Delgado, P. (Pablo), Rolland, C. (Christine), Rodts, U. (Ulysse), Samolinski, B. (Boleslaw), Sanchez-Borges, M. (Mario), Schünemann, H.J. (Holger), Shamji, M. (Mohamed), Somekh, D. (David), Togias, A., Toppila-Salmi, S. (Sanna), Tsiligianni, I.G. (Ioanna G), Usmani, O. (Omar), Walker, S. (Samantha), Wallace, D. (D.), Valiulis, A. (Arunas), Van Der Kleij, R.M. (Rianne Mjj), Ventura, M.T. (Maria Teresa), Williams, S. (Sian), Yorgancioglu, A. (Arzu), and Zuberbier, T. (Torsten)

Published
2019
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8. Next-generation ARIA care pathways for rhinitis and asthma: A model for multimorbid chronic diseases

Author

Bousquet, J.J. (J. Jean), Schünemann, H.J. (Holger), Togias, A., Erhola, M. (Marina), Hellings, P.W. (Peter), Zuberbier, T. (Torsten), Agache, I. (Ioana), Ansotegui, I.J. (I.), Anto, J.M. (Josep), Bachert, C. (Claus), Becker, S. (Sven), Bedolla-Barajas, M. (Martin), Bewick, M. (Michael), Bosnic-Anticevich, S. (Sinthia), Bosse, I. (Isabelle), Boulet, L.P., Bourrez, J.M. (Jean Marc), Brusselle, G.G. (Guy), Chavannes, N.H. (Nicolas), Costa, E. (Elisio), Cruz, A.A. (Alvaro), Czarlewski, W. (Wienczyslawa), Fokkens, W.J. (Wytske), Fonseca, J.A. (Joao A.), Gaga, M. (Mina), Haahtela, T. (Tari), Illario, M. (Maddalena), Klimek, L. (Ludger), Kuna, P. (Piotr), Kvedariene, V. (Violeta), Le, L.T., Larenas-Linnemann, D. (Désirée), Laune, D. (Daniel), Lourenço, O.M. (Olga M.), Menditto, E. (Enrica), Mullol, J. (Joaquin), Okamoto, Y. (Yashitaka), Papadopoulos, N., Pham-Thi, N. (Nhân), Picard, R. (Robert), Pinnock, H. (Hilary), Roche, N. (Nicolas), Roller-Wirnsberger, R.E. (Regina E.), Rolland, C. (Christine), Samolinski, B. (Boleslaw), Sheikh, A. (Aziz), Toppila-Salmi, S. (Sanna), Tsiligianni, I.G. (Ioanna G), Valiulis, A. (Arunas), Valovirta, E. (Erkka), Vasankari, T. (Tuula), Ventura, M.-T. (Maria-Teresa), Walker, S. (Samantha), Williams, S. (Sian), Akdis, C.A. (Cezmi A.), Annesi-Maesano, I. (Isabella), Arnavielhe, S. (Sylvie), Basagaña, X. (Xavier), Bateman, E.D. (Eric), Bedbrook, A. (Anna), Bennoor, K.S. (K.), Benveniste, S. (Samuel), Bergmann, K.-C. (Karl-Christian), Bialek, S. (Slawomir), Billo, N. (Nils), Bindslev-Jensen, C. (Carsten), Bjermer, L. (Leif), Blain, H. (Hubert), Bonini, M. (Matteo), Bonniaud, P. (Philippe), Bouchard, J. (Jacques), Briedis, V. (Vitalis), Brightling, C.E. (Christofer E.), Brozek, J., Buhl, R. (Roland), Buonaiuto, R. (Roland), Canonica, G.W. (Giorgo W.), Cardona, D. (Doris), Carriazo, A.M. (Ana M.), Carr, W.W. (Warner), Cartier, C. (Christine), Casale, T.B. (Thomas), Cecchi, L. (Lorenzo), Cepeda Sarabia, A.M. (Alfonso M.), Chkhartishvili, E. (Eka), Chu, D.K. (Derek K.), Cingi, C. (Cemal), Colgan, E. (Elaine), De Sousa, J.C. (Jaime Correia), Courbis, A.L. (Anne Lise), Custovic, A. (Adnan), Cvetkosvki, B. (Biljana), Damato, G. (Gennaro), Da Silva, J. (Jane), Dantas, C. (Carina), Dokic, D. (D.), Dauvilliers, Y. (Yves), Dedeu, A. (Antoni), De Feo, G. (Giulia), Devillier, P. (Philippe), Di Capua, S. (Stefania), Dykewickz, M. (Marc), Dubakiene, R. (R.), Ebisawa, M. (Motohiro), El-Gamal, Y. (Y.), Eller, E. (Esben), Emuzyte, R., Farrell, J. (John), Fink-Wagner, A. (Antjie), Fiocchi, A. (Alessandro), Fontaine, J.F. (Jean F.), Gemicioǧlu, B. (Bilun), Schmid-Grendelmeir, P. (Peter), Gamkrelidze, A. (Amiran), Garcia-Aymerich, J. (Judith), Gomez, M. (Maximiliano), Diaz, S.G. (Sandra González), Gotua, M. (M.), Guldemond, N. (Nick), Guzmán, M.A. (M.), Hajjam, J. (Jawad), O'Hourihane, J.B. (John B.), Humbert, M. (Marc), Iaccarino, G. (Guido), Ierodiakonou, D. (Despo), Ivancevich, J.C. (Juan), Joos, G.F. (Guy), Jung, K.-S. (Ki-Suck), Jutel, M. (M.), Kaidashev, I. (Igor), Kalayci, O. (Omer), Kardas, P. (Przemyslaw), Keil, M. (Mark), Khaitov, M. (Mussa), Khaltaev, N., Kleine-Tebbe, J. (Jörg), Kowalski, M.L., Kritikos, V. (Vicky), Kull, C.A. (Christian), Leonardini, L. (Lisa), Lieberman, A.P. (Andrew), Lipworth, B., Lødrup Carlsen, K.C. (K. C.), Loureiro, C.C. (Claudia C.), Louis, R. (Renaud), Mair, A. (Alpana), Marien, G. (Gert), Mahboub, B., Malva, J. (Joao), Manning, P. (Patrick), De Manuel Keenoy, E. (Esteban), Marshall, G.D., Masjedi, M.R. (Mohamed R.), Maspero, J.F. (Jorge F.), Mathieu-Dupas, E. (Eve), Matricardi, P.M. (Poalo M.), Melén, E. (Eric), Melo-Gomes, E. (Elisabete), Meltzer, E.O., Mercier, J. (Jacques), Miculinic, N. (Neven), Mihaltan, F. (Florin), Milenkovic, B. (Branislava), Moda, G. (Giuliana), Mogica-Martinez, M.-D. (Maria-Dolores), Mohammad, Y., Montefort, S. (Steve), Monti, R. (Ricardo), Morais-Almeida, M. (Mario), Mösges, R. (Ralph), Münter, L. (Lars), Muraro, A. (Antonella), Murray, R. (Ruth), Naclerio, R., Napoli, L. (Luigi), Namazova-Baranova, L. (Leila), Neffen, H. (Hugo), Nekam, K. (Kristoff), Neou, A. (A.), Novellino, E. (Enrico), Nyembue, D. (Dieudonné), O'Hehir, R. (Robin), Ohta, K., Okubo, K. (Kimi), Onorato, G. (Gabrielle), Ouedraogo, S., Pali-Schöll, I. (I.), Palkonen, S. (Susanna), Panzner, P. (P.), Park, H.-S. (Hae-Sim), Pépin, J.-L. (Jean-Louis), Pereira, A.-M. (Ana-Maria), Pfaar, O. (Oliver), Paulino, E. (Ema), Phillips, J. (Jim), Plavec, D. (Davor), Popov, T.A. (Ted A.), Portejoie, F. (Fabienne), Price, D. (David), Prokopakis, E.P. (Emmanuel P.), Pugin, B. (Benoit), Raciborski, F. (Filip), Rajabian-Söderlund, R. (Rojin), Reitsma, S. (Sietze), Rodo, X. (Xavier), Romano, A., Rosario, N. (Nelson), Rottem, M. (Menahenm), Ryan, D. (Dermot), Salimäki, J. (Johanna), Sanchez-Borges, M.M. (Mario M.), Sisul, J.C. (J.), Solé, D. (Dirceu), Somekh, D. (David), Sooronbaev, T. (Talant), Sova, M. (Milan), Spranger, O., Stellato, C. (Cristina), Stelmach, R. (Rafael), Ulrik, C.S., Thibaudon, M. (Michel), To, T. (Teresa), Todo Bom, A., Tomazic, P.V. (Peter V.), Valero, A.A. (Antonio A.), Valenta, R. (Rudolph), Valentin-Rostan, M. (Marylin), Van Der Kleij, R.M. (Rianne Mjj), Vandenplas, O. (Olivier), Vezzani, G. (Giorgio), Viart, F. (Frédéric), Viegi, G., Wallace, D. (D.), Wagenmann, M. (Martin), Wang, D.Y. (De Y.), Waserman, S. (Susan), Wickman, M. (Magnus), Williams, D., Wong, G. (G.), Wroczynski, P. (Piotr), Yiallouros, P.K. (P.), Yorgancioglu, A. (Arzu), Yusuf, O.M. (Osman), Zar, H.J. (Heahter J.), Zeng, S. (Stéphane), Zernotti, M., Zhang, L. (Luo), Zhong, N.S. (Nan S.), Zidarn, M. (Mihaela), Bousquet, J.J. (J. Jean), Schünemann, H.J. (Holger), Togias, A., Erhola, M. (Marina), Hellings, P.W. (Peter), Zuberbier, T. (Torsten), Agache, I. (Ioana), Ansotegui, I.J. (I.), Anto, J.M. (Josep), Bachert, C. (Claus), Becker, S. (Sven), Bedolla-Barajas, M. (Martin), Bewick, M. (Michael), Bosnic-Anticevich, S. (Sinthia), Bosse, I. (Isabelle), Boulet, L.P., Bourrez, J.M. (Jean Marc), Brusselle, G.G. (Guy), Chavannes, N.H. (Nicolas), Costa, E. (Elisio), Cruz, A.A. (Alvaro), Czarlewski, W. (Wienczyslawa), Fokkens, W.J. (Wytske), Fonseca, J.A. (Joao A.), Gaga, M. (Mina), Haahtela, T. (Tari), Illario, M. (Maddalena), Klimek, L. (Ludger), Kuna, P. (Piotr), Kvedariene, V. (Violeta), Le, L.T., Larenas-Linnemann, D. (Désirée), Laune, D. (Daniel), Lourenço, O.M. (Olga M.), Menditto, E. (Enrica), Mullol, J. (Joaquin), Okamoto, Y. (Yashitaka), Papadopoulos, N., Pham-Thi, N. (Nhân), Picard, R. (Robert), Pinnock, H. (Hilary), Roche, N. (Nicolas), Roller-Wirnsberger, R.E. (Regina E.), Rolland, C. (Christine), Samolinski, B. (Boleslaw), Sheikh, A. (Aziz), Toppila-Salmi, S. (Sanna), Tsiligianni, I.G. (Ioanna G), Valiulis, A. (Arunas), Valovirta, E. (Erkka), Vasankari, T. (Tuula), Ventura, M.-T. (Maria-Teresa), Walker, S. (Samantha), Williams, S. (Sian), Akdis, C.A. (Cezmi A.), Annesi-Maesano, I. (Isabella), Arnavielhe, S. (Sylvie), Basagaña, X. (Xavier), Bateman, E.D. (Eric), Bedbrook, A. (Anna), Bennoor, K.S. (K.), Benveniste, S. (Samuel), Bergmann, K.-C. (Karl-Christian), Bialek, S. (Slawomir), Billo, N. (Nils), Bindslev-Jensen, C. (Carsten), Bjermer, L. (Leif), Blain, H. (Hubert), Bonini, M. (Matteo), Bonniaud, P. (Philippe), Bouchard, J. (Jacques), Briedis, V. (Vitalis), Brightling, C.E. (Christofer E.), Brozek, J., Buhl, R. (Roland), Buonaiuto, R. (Roland), Canonica, G.W. (Giorgo W.), Cardona, D. (Doris), Carriazo, A.M. (Ana M.), Carr, W.W. (Warner), Cartier, C. (Christine), Casale, T.B. (Thomas), Cecchi, L. (Lorenzo), Cepeda Sarabia, A.M. (Alfonso M.), Chkhartishvili, E. (Eka), Chu, D.K. (Derek K.), Cingi, C. (Cemal), Colgan, E. (Elaine), De Sousa, J.C. (Jaime Correia), Courbis, A.L. (Anne Lise), Custovic, A. (Adnan), Cvetkosvki, B. (Biljana), Damato, G. (Gennaro), Da Silva, J. (Jane), Dantas, C. (Carina), Dokic, D. (D.), Dauvilliers, Y. (Yves), Dedeu, A. (Antoni), De Feo, G. (Giulia), Devillier, P. (Philippe), Di Capua, S. (Stefania), Dykewickz, M. (Marc), Dubakiene, R. (R.), Ebisawa, M. (Motohiro), El-Gamal, Y. (Y.), Eller, E. (Esben), Emuzyte, R., Farrell, J. (John), Fink-Wagner, A. (Antjie), Fiocchi, A. (Alessandro), Fontaine, J.F. (Jean F.), Gemicioǧlu, B. (Bilun), Schmid-Grendelmeir, P. (Peter), Gamkrelidze, A. (Amiran), Garcia-Aymerich, J. (Judith), Gomez, M. (Maximiliano), Diaz, S.G. (Sandra González), Gotua, M. (M.), Guldemond, N. (Nick), Guzmán, M.A. (M.), Hajjam, J. (Jawad), O'Hourihane, J.B. (John B.), Humbert, M. (Marc), Iaccarino, G. (Guido), Ierodiakonou, D. (Despo), Ivancevich, J.C. (Juan), Joos, G.F. (Guy), Jung, K.-S. (Ki-Suck), Jutel, M. (M.), Kaidashev, I. (Igor), Kalayci, O. (Omer), Kardas, P. (Przemyslaw), Keil, M. (Mark), Khaitov, M. (Mussa), Khaltaev, N., Kleine-Tebbe, J. (Jörg), Kowalski, M.L., Kritikos, V. (Vicky), Kull, C.A. (Christian), Leonardini, L. (Lisa), Lieberman, A.P. (Andrew), Lipworth, B., Lødrup Carlsen, K.C. (K. C.), Loureiro, C.C. (Claudia C.), Louis, R. (Renaud), Mair, A. (Alpana), Marien, G. (Gert), Mahboub, B., Malva, J. (Joao), Manning, P. (Patrick), De Manuel Keenoy, E. (Esteban), Marshall, G.D., Masjedi, M.R. (Mohamed R.), Maspero, J.F. (Jorge F.), Mathieu-Dupas, E. (Eve), Matricardi, P.M. (Poalo M.), Melén, E. (Eric), Melo-Gomes, E. (Elisabete), Meltzer, E.O., Mercier, J. (Jacques), Miculinic, N. (Neven), Mihaltan, F. (Florin), Milenkovic, B. (Branislava), Moda, G. (Giuliana), Mogica-Martinez, M.-D. (Maria-Dolores), Mohammad, Y., Montefort, S. (Steve), Monti, R. (Ricardo), Morais-Almeida, M. (Mario), Mösges, R. (Ralph), Münter, L. (Lars), Muraro, A. (Antonella), Murray, R. (Ruth), Naclerio, R., Napoli, L. (Luigi), Namazova-Baranova, L. (Leila), Neffen, H. (Hugo), Nekam, K. (Kristoff), Neou, A. (A.), Novellino, E. (Enrico), Nyembue, D. (Dieudonné), O'Hehir, R. (Robin), Ohta, K., Okubo, K. (Kimi), Onorato, G. (Gabrielle), Ouedraogo, S., Pali-Schöll, I. (I.), Palkonen, S. (Susanna), Panzner, P. (P.), Park, H.-S. (Hae-Sim), Pépin, J.-L. (Jean-Louis), Pereira, A.-M. (Ana-Maria), Pfaar, O. (Oliver), Paulino, E. (Ema), Phillips, J. (Jim), Plavec, D. (Davor), Popov, T.A. (Ted A.), Portejoie, F. (Fabienne), Price, D. (David), Prokopakis, E.P. (Emmanuel P.), Pugin, B. (Benoit), Raciborski, F. (Filip), Rajabian-Söderlund, R. (Rojin), Reitsma, S. (Sietze), Rodo, X. (Xavier), Romano, A., Rosario, N. (Nelson), Rottem, M. (Menahenm), Ryan, D. (Dermot), Salimäki, J. (Johanna), Sanchez-Borges, M.M. (Mario M.), Sisul, J.C. (J.), Solé, D. (Dirceu), Somekh, D. (David), Sooronbaev, T. (Talant), Sova, M. (Milan), Spranger, O., Stellato, C. (Cristina), Stelmach, R. (Rafael), Ulrik, C.S., Thibaudon, M. (Michel), To, T. (Teresa), Todo Bom, A., Tomazic, P.V. (Peter V.), Valero, A.A. (Antonio A.), Valenta, R. (Rudolph), Valentin-Rostan, M. (Marylin), Van Der Kleij, R.M. (Rianne Mjj), Vandenplas, O. (Olivier), Vezzani, G. (Giorgio), Viart, F. (Frédéric), Viegi, G., Wallace, D. (D.), Wagenmann, M. (Martin), Wang, D.Y. (De Y.), Waserman, S. (Susan), Wickman, M. (Magnus), Williams, D., Wong, G. (G.), Wroczynski, P. (Piotr), Yiallouros, P.K. (P.), Yorgancioglu, A. (Arzu), Yusuf, O.M. (Osman), Zar, H.J. (Heahter J.), Zeng, S. (Stéphane), Zernotti, M., Zhang, L. (Luo), Zhong, N.S. (Nan S.), and Zidarn, M. (Mihaela)

Abstract

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhi-nitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.

Published
2019
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9. Immune checkpoints indoleamine 2,3‐dioxygenase 1 and programmed death‐ligand 1 in oral mucosal dysplasia

Author

Sieviläinen, M. (Meri), Passador‐Santos, F. (Fabricio), Almahmoudi, R. (Rabeia), Christopher, S. (Solomon), Siponen, M. (Maria), Toppila‐Salmi, S. (Sanna), Salo, T. (Tuula), Al‐Samadi, A. (Ahmed), Sieviläinen, M. (Meri), Passador‐Santos, F. (Fabricio), Almahmoudi, R. (Rabeia), Christopher, S. (Solomon), Siponen, M. (Maria), Toppila‐Salmi, S. (Sanna), Salo, T. (Tuula), and Al‐Samadi, A. (Ahmed)

Abstract

Background: Oral mucosal dysplasia is a histologic feature of potentially malignant disorders that is associated with the risk of transformation to carcinoma. Dysplastic cells use many strategies during their transformation to cancer, including escape from the immune mediated destruction. We hypothesized that adaptive immunity is inhibited by activation of distinct immune checkpoint molecules, such as indoleamine 2,3‐dioxygenase 1 (IDO1) and programmed death‐ligand 1 (PD‐L1). Methods: We collected 63 oral dysplasia samples from 47 patients. Nine biopsies from alveolar mucosa were taken during wisdom teeth extractions were used as healthy controls. Tissue samples were stained and scored for IDO1 and PD‐L1. Additionally, dysplasia grades and inflammatory cell infiltration were evaluated. Eight patients were followed up to 36 months to evaluate dysplasia progression, inflammation, and immune checkpoint molecules expression. Results: Dysplastic epithelium had significantly lower IDO1 expression than that of healthy controls. PD‐L1 positive cells in the lamina propria were mainly in dysplastic samples and seldom in healthy controls. Dysplasia grade was associated negatively with epithelium IDO1 and positively with IDO1 and PD‐L1 expression in the lamina propria. There was a positive association between dysplasia grade and level of inflammatory cell infiltration. During follow‐up, dysplasia grade, inflammatory cell infiltration, and the immune checkpoint expression fluctuated over time. Conclusions: Immune checkpoint molecules IDO1 and PD‐L1 are modulated during oral epithelial dysplastic changes, and their expression is associated with inflammatory cell infiltration in the lamina propria. As immune checkpoint molecules expression fluctuates over time, these molecules are not useful as biomarkers for oral mucosal dysplasia progression.

Published
2018

10. Extracellular interleukin‐17F has a protective effect in oral tongue squamous cell carcinoma

Author

Almahmoudi, R. (Rabeia), Salem, A. (Abdelhakim), Sieviläinen, M. (Meri), Sundquist, E. (Elias), Almangush, A. (Alhadi), Toppila-Salmi, S. (Sanna), Paavonen, T. (Timo), Salo, T. (Tuula), Al-Samadi, A. (Ahmed), Almahmoudi, R. (Rabeia), Salem, A. (Abdelhakim), Sieviläinen, M. (Meri), Sundquist, E. (Elias), Almangush, A. (Alhadi), Toppila-Salmi, S. (Sanna), Paavonen, T. (Timo), Salo, T. (Tuula), and Al-Samadi, A. (Ahmed)

Abstract

Background: Oral tongue squamous cell carcinoma (SCC) is characterized by early metastasis and poor prognosis. Interleukin‐17F (IL‐17F) plays a protective role in many tumors. However, IL‐17F expression in oral tongue SCC tissue has not been investigated. Methods: Immunostaining of 83 oral tongue SCC specimens and blinded‐scoring were used to map IL‐17F expression, location, and distribution. Survival curves were constructed according to Kaplan‐Meier method. The Cox proportional hazard model was applied for univariate and multivariate survival analyses. Results: Mast cells are the major source of IL‐17F in oral tongue SCC. In multivariate analysis, only the extracellular mast cell‐derived IL‐17F at the tumor invasion front was associated with better disease‐specific survival in patients with all‐stages and early‐stages of oral tongue SCC. Conclusion: Extracellular mast cell‐derived IL‐17F is antitumorigenic in oral tongue SCC. It separates patients with early‐stage disease who are at high risk from patients who are at low risk. Furthermore, when analyzing tentative prognostic molecules, we conclude that in addition to the staining intensity, attention must be paid to the cellular source, distribution, and location of the molecule.

Published
2018

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