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Öğe Author Response: Radiotherapy Increases aMMP-8-Levels and Neutrophil/Lymphocyte Ratio Rapidly in Head and Neck Cancer Patients: A Pilot Study(2023) Brandt, Ella; Keskin, Mutlu; Tervahartiala, Taina; Yılmaz, Mustafa; Harmankaya, İlknur; Karaçetin, Didem; İpek, Turgut; Gürsoy, Ulvi Kahraman; Rautava, Jaana; Gupta, Shipra; Hagström, Jaana; Raisanen, Ismo T.; Sorsa, Timo...Öğe Induction of collagenolytic MMP-8 and -9 tissue destruction cascade in mouth by head and neck cancer radiotherapy: a cohort study(2023) Brandt, Ella; Keskin, Mutlu; Raisanen, Ismo; Tervahartiala, Taina; Makitie, Antti; Harmankaya, İlknur; Karaçetin, Didem; Hagström, Jaana; Rautava, Jaana; Sorsa, TimoThe effect of head and neck cancer (HNC) radiotherapy (RT) on biomarkers is not known but there is a lot of potential for gaining more precise cancer treatments and less side effects. This cohort study investigated the levels and molecular forms of the matrix metalloproteinase (MMP) -8 and -9, tissue inhibitor of metalloproteinase (TIMP)-1, myeloperoxidase (MPO) and interleukin (IL)-6 in mouth-rinse samples as well as the clinical periodontal status in HNC patients (n = 21) receiving RT. Complete periodontal examinations were performed pre-RT and one month after RT. Mouth-rinse samples (pre-RT, after six weeks of RT and one month after RT) were assayed using a point-of-care-kit (PerioSafe®/ORALyzer® (Dentognostics GmbH, Jena, Germany)) for active MMP-8 and ELISA analysis for total MMP-8 and -9, MPO, TIMP-1, and IL-6 levels. Molecular forms of MMP-9 were assessed by gelatinolytic zymography and MMP-8 by western immunoblot. Significant changes were observed between the three time points in the mean levels of active and total MMP-8, active MMP-9, and IL-6. Their levels increased during the RT and decreased after the RT period. The aMMP-8 levels stayed elevated even one month after RT compared to the pre-RT. Clinical attachment loss, probing depths, and bleeding on probing were increased between pre- and post-calculations in periodontal status. Elevated inflammatory biomarker levels together with clinical recordings strongly suggest that RT eventually increases the risk to the periodontal tissue destruction by inducing the active proteolytical MMP-cascade, and especially by prolonged activity of collagenolytic aMMP-8. Eventually, the aMMP-8 point-of-care mouth-rinse test could be an easy, early detection tool for estimating the risk for periodontal damage by the destructive MMP-cascade in HNC patients with RT treatment.Öğe Radiotherapy increases aMMP-8-levels and neutrophil/lymphocyte ratio rapidly in head and neck cancer patients: a pilot study(2023) Brandt, Ella; Keskin, Mutlu; Tervahartiala, Taina; Yılmaz, Mustafa; Harmankaya, İlknur; Karaçetin, Didem; İpek, Turgut; Gürsoy, Ulvi Kahraman; Rautava, Jaana; Gupta, Shipra; Hagström, Jaana; Raisanen, Ismo T.; Sorsa, TimoRadiotherapy for head and neck carcinoma (HNC) has both curative and palliative purposes. This study investigated mouthrinse aMMP-8 levels, molecular forms of MMP-8, blood neutrophil counts and neurophil/lymphocyte ratios before and 3 weeks after HNC radiotherapy started. Thirteen HNC patients undergoing radiotherapy were included. Mouthrinse samples (before and 3 weeks after HNC radiotherapy had started) were assayed quantitatively by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) and by western immunoblot. Total neutrophil counts and neutrophil/lymphocyte ratios were evaluated in the hemogram results. Three weeks after HNC radiotherapy started, significant increases in aMMP-8 levels and neutrophil/lymphocyte ratios were observed. No significant difference was found in total neutrophil counts. Elevations of the activated and fragmented MMP-8 levels after HNC radiotherapy application were observed on western immunoblot analysis. The increase in the aMMP-8 levels and neutrophil/lymphocyte ratios indicate inflammation both locally and systemically suggesting increased risk for periodontitis due to the HNC radiotherapy.Öğe Two cheers for Crohn's disease and periodontitis: Beta-defensin-2 as an actionable target to intervene on two clinically distinct diseases(Mary Ann Liebert, Inc, 2015) Keskin, Mutlu; Zeidan-Chulia, Fares; Gürsoy, Mervi; Kononen, Eija; Rautava, Jaana; Gürsoy, Ulvi KahramanRecent advances in multi-omics approaches encompassing genomics, transcriptomics, proteomics, and metabolomics offer hitherto unprecedented insights on common complex human diseases. A unique angle pertinent for both diagnostic and therapeutic sciences involves rethinking clinically distinct diseases with a view to their shared molecular targets, interactomes, and pathophysiologies. Reflecting at a scale of disease-to-disease associations might help clinicians, public health practitioners, drug and biotechnology developers, and associated knowledge industries in the current era. This review article examines the hypothesis that "Intersecting Molecular Pathways Permit Interventions on Multiple Clinical Endpoints", thus uniquely bringing together Crohn's disease and periodontitis. Furthermore, we propose a novel connector molecular target between these two ostensibly distinct diseases at a clinical level, human beta defensin (hBD)-2, and suggest pathways by which hBD-2 can conceivably connect Crohn's disease and periodontitis by virtue of regulating the innate-immune response. We conclude by emphasizing different approaches where hBD-2 can be employed as a diagnostic and therapeutic tool to improve the quality of life of susceptible individuals and minimize the economic costs of these two major global public health problems. The strategy presented here also presents potentials for targeting of multiple diseases through a unique "nodal molecular target" that "speaks to" multiple clinical endpoints.
