Non-curative treatment of patients with oral tongue squamous-cell carcinoma.

PURPOSE: Late-stage OTSCC is associated with poor overall survival (OS). Non-curative treatment approach aims to improve quality of life and prolong survival of patients deemed incurable. The purpose of this study was to investigate the used non-curative treatment modalities for OTSSC and patient survival. METHODS: All patients diagnosed with OTSCC and treated with non-curative intent at the HUS Helsinki University Hospital (Helsinki, Finland) during the 12-year period of 2005-2016 were included. Survival analysis after the non-curative treatment decision was conducted using the Kaplan-Meier method in this population-based study. RESULTS: Eighty-two patients were identified. A non-curative treatment decision was made at presentation without any previous treatment in 26 patients (7% of all patients diagnosed with OTSCC during the study period). Palliative radiotherapy was administered to 24% of all patients. The average survival time after the non-curative treatment decision was 3.7 months (median 2 and range 0-26). CONCLUSIONS: Due to the short mean survival time after decision for treatment with non-curative intent, and the notable symptom burden in this patient population, a prompt initiation of all non-curative measures is warranted.

Myofibroblasts in oral potentially malignant disorders: Is it related to malignant transformation?

In oral cancer, acquisition of α-smooth muscle actin (α-SMA)-positive fibroblasts, known as myofibroblasts or carcinoma-associated fibroblasts (CAF), is an important event for progression and metastasis. However, the contribution of myofibroblasts in oral potentially malignant disorders (OPMD) remains controversial. This systematic review provides evidence that immunodetection of myofibroblasts may identify oral submucous fibrosis (OSMF) with high risk of malignant transformation, but does not represent an auxiliary tool to predict the malignant potential of leukoplakia and erythroplakia, the most common OPMD.

Extracellular vesicles from oral squamous carcinoma cells display pro- and anti-angiogenic properties.

BACKGROUND: A new intercellular communication mode established by neoplastic cells and tumor microenvironment components is based on extracellular vesicles (EVs). However, the biological effects of the EVs released by tumor cells on angiogenesis are not completely understood. Here, we aimed to understand the biological effects of EVs isolated from two cell lines of oral squamous cell carcinoma (OSCC) (SCC15 and HSC3) on endothelial cell tubulogenesis. METHODS: OSCC-derived EVs were isolated with a polymer-based precipitation method, quantified using nanoparticle tracking analysis and verified for EV markers by dot blot. Functional assays were performed to assess the angiogenic potential of the OSCC-derived EVs. RESULTS: The results showed that EVs derived from both cell lines displayed typical spherical-shaped morphology and expressed the EV markers CD63 and Annexin II. Although the average particle concentration and size were quite similar, SCC15-derived EVs promoted a pronounced tubular formation associated with significant migration and apoptosis rates of the endothelial cells, whereas EVs derived from HSC3 cells inhibited significantly endothelial cell tubulogenesis and proliferation. CONCLUSION: The findings of this study reveal that EVs derived from different OSCC cell lines by a polymer-based precipitation method promote pro- or anti-angiogenic effects.

Topical tacrolimus, triamcinolone acetonide, and placebo in oral lichen planus: a pilot randomized controlled trial.

OBJECTIVE: To carry out a double-blind randomized controlled trial (RCT) to compare the effectiveness of topical tacrolimus (TAC), triamcinolone acetonide (TRI), and placebo (PLA) in symptomatic oral lichen planus (OLP). SUBJECTS AND METHODS: A clinical score (CS, range 0-130) was developed to measure the clinical signs and symptoms of OLP. Twenty-seven OLP patients with a CS of ≥20 were randomly allocated to receive 0.1% TAC ointment (n = 11), 0.1% TRI paste (n = 7), or Orabase® paste as PLA (n = 9) for 3 weeks. If the CS dropped ≥20% (interpreted as response), the patients continued the same medication for another 3 weeks. If the CS dropped <20% or increased (non-response), the patients were switched to TAC for 6 weeks. A 6-month follow-up period ensued. The primary outcome variable was the change in CS from baseline to week 3. In primary outcome analysis, CS values between the treatment arms were compared. RESULTS: Tacrolimus and TRI were more effective (P = 0.012 and 0.031, respectively) than PLA in reducing the CS at week 3. No difference in the efficacy was noted between TAC and TRI (P = 0.997). CONCLUSIONS: This pilot RCT provides evidence for the effectiveness of TAC and TRI over PLA in the management of OLP.

Infection and apoptosis associated with inflammation in periodontitis: An immunohistologic study.

OBJECTIVE: Evidence of increased apoptosis is observed in periodontitis and may be associated with destruction of the periodontal tissue caused by the increased cell death, with the release of danger signals and subsequent stimulation of the proinflammatory processes. However, the exact mechanisms associated with these processes remain unclear. This study aimed to investigate the presence of the periodontal pathogen Treponema denticola, apoptosis, high mobility group box 1 as a damage-associated molecular pattern, and several inflammatory markers in periodontitis and gingivitis subjects. MATERIALS AND METHODS: Soft tissue specimens from gingival tissues of periodontitis and gingivitis patients were used for immunohistochemical and immunofluorescence staining of T. denticola chymotrypsin-like proteinase (CTLP), apoptosis markers, high mobility group box 1, Toll-like receptor 4, inflammatory cell markers, and proinflammatory cytokines. RESULTS: Treponema denticola was detected in all periodontitis-affected tissues. This was associated with a significant increase in the number of apoptotic cells, including macrophages, alterations in the expression of high mobility group box 1 and its receptor, and increased levels of proinflammatory cytokines compared with gingivitis. CONCLUSIONS: In summary, the presence of T. denticola (especially its CTLP), apoptosis, high mobility group box 1, and inflammatory markers suggests their potential involvement in the pathogenesis of periodontitis.

Phosphorus in manure and sewage sludge more recyclable than in soluble inorganic fertilizer.

Phosphorus (P) flow from deposits through agriculture to waterways leads to eutrophication and depletion of P reserves. Therefore, P must be recycled. Low and unpredictable plant availability of P in residues is considered to be a limiting factor for recycling. We identified the determinants for the plant-availability of P in agrifood residues. We quantified P in Italian ryegrass (Lolium multiflorum) and in field soil fractions with different plant availabilities of P as a response to manure and sewage sludge with a range of P capture and hygienization treatments. P was more available in manure and in sludge, when it was captured biologically or with a moderate iron (Fe)/P (1.6), than in NPK. Increasing rate of sludge impaired P recovery and high Fe/P (9.8) prevented it. Anaerobic digestion (AD) reduced plant-availability at relevant rates. The recovery of P was increased in AD manure via composting and in AD sludge via combined acid and oxidizer. P was not available to plants in the sludge hygienized with a high calcium/P. Contrary to assumed knowledge, the recyclability of P in appropriately treated residues can be better than in NPK. The prevention of P sorption in soil by organic substances in fertilizers critically enhances the recyclability of P.

The prognostic value of histopathological grading systems in oral squamous cell carcinomas.

OBJECTIVE: This study evaluated the association of four histopathological grading systems (WHO grading system, malignancy grading of the deep invasive margins (MG), histological risk (HR) model, and tumor budding and depth of invasion (BD) model) with clinicopathological parameters and outcome of 113 oral squamous cell carcinomas to identify their roles in prognosis. METHODS: Demographic and clinical features were obtained from patients' records. Sections from all paraffin-embedded blocks were evaluated according to the four grading systems. Demographic and clinical associations were analyzed using chi-square test, and correlations between the grading systems were established with the Spearman's rank correlation test. Survival curves were performed with Kaplan-Meier method, and multivariate analysis based on Cox proportional hazard model was calculated. RESULTS: Significant associations with survival were observed for WHO grading system and BD model in the univariate analysis, but only the BD model was significantly associated with disease outcome as an independent prognostic marker. Age, tumor size, and presence of regional metastasis were also independent markers of reduced survival. CONCLUSION: A significant association between the BD model and outcome of OSCC patients was observed, indicating this new histopathological grading system as a possible prognostic tool.

[Nutraceuticals in the combat against oral cancer].

Head and neck squamous cell carcinoma (HNSCC), the eighth most common cancer worldwide, accounts for approximately 600,000 new cases per year. The mobile tongue is the most common site for oral cancer and is associated with a poorer survival than other HNSCC sites. Standard therapeutic strategies have failed to significantly improve survival rates that have remained around 50% over the past four decades. In the last decade intense investigations on oral cancer highlighted the mandatory role of the tumor microenvironment (TME), in addition to the genetic aberrations and molecular biology changes within the cancer cells. Furthermore, the molecular crosstalk between cancer cells and TME components (i.e., cancer-associated fibroblasts, inflammatory pro-tumorigenic cells, etc.) has a crucial role in growth, invasion, spread and metastases of the cancer cells and consequently leads to poor prognosis. Recent studies suggest that plant-derived dietary agents nutraceuticals, especially curcumin and green tea, have the advantage to combat both malignant cells and TME components, unlike standard anti-cancer protocols that target only cancer cells. However, due to a very low bioavailability, nutraceuticals do not currently constitute an integral part of these protocols. Ongoing developments in nanotechnology for improved delivery are expected to overcome their challenging pharmacokinetics.

Toll-like receptor 5 (TLR5) expression is a novel predictive marker for recurrence and survival in squamous cell carcinoma of the tongue.

BACKGROUND: Toll-like receptor 5 (TLR5) is an immune receptor recognising bacterial flagellin. Activation of TLR5 results in cancer invasion and cytokine release. As certain bacteria have been linked to oral cancer, we wanted to study TLR5 expression in oral tongue squamous cell carcinoma (OTSCC). METHODS: Samples from 119 patients with OTSCC were obtained, including 101 samples of adjacent normal lingual mucosa. The TLR5 histoscore (0-300) was assessed semiquantitatively by immunohistochemistry in a blinded manner. RESULTS: Toll-like receptor 5 was expressed in 84 normal epithelia and 118 cancer samples. Expression of TLR5 was increased in cancer when compared with normal lingual epithelium (median histoscore 15 vs 135). In cancer, higher TLR5 was associated with age of >70 years at the time of diagnosis, female gender and disease recurrence. No association between TLR5 expression and tumour grade, stage or treatment was found. In multivariate analysis, TLR5 was an independent predictor of cancer mortality (hazard ratio (HR) 3.587, 95% confidence interval (CI) (1.632-7.882)) and disease recurrence (HR 4.455, 95% CI (2.168-9.158)). CONCLUSION: Toll-like receptor 5 has a previously undescribed role in the pathophysiology of OTSCC and might represent a link between bacteria and cancer. It could be a useful marker for predicting recurrence or survival of OTSCC patients.

The expression and role of Lysyl oxidase (LOX) in dentinogenesis.

AIM: To establish whether eliminating Lysyl oxidase (LOX) gene would affect dentine formation. METHODOLOGY: Newborn wild-type (wt) and homo- and heterozygous LOX knock-out (Lox(-/-) and Lox(+/-) , respectively) mice were used to study developing tooth morphology and dentine formation. Collagen aggregation in the developing dentine was examined histochemically with picrosirius red (PSR) staining followed by polarized microscopy. Because Lox(-/-) die at birth, adult wt and Lox(+/-) mouse tooth morphologies were examined with FESEM. Human odontoblasts and pulp tissue were used to study the expression of LOX and its isoenzymes with Affymetrix cDNA microarray. RESULTS: No differences between Lox(-/-) , Lox(+/-) and wt mice developing tooth morphology were seen by light microscopy. Histochemically, however, teeth in wt mice demonstrated yellow-orange and orange-red polarization colours with PSR staining, indicating thick and more densely packed collagen fibres, whilst in Lox(-/-) and Lox(+/-) mice, most of the polarization colours were green to green-yellow, indicating thinner, less aggregated collagen fibres. Fully developed teeth did not show any differences between Lox(+/-) and wt mice with FESEM. Human odontoblasts expressed LOX and three of four of its isoenzymes. CONCLUSIONS: The data indicate that LOX is not essential in dentinogenesis, even though LOX deletion may affect dentine matrix collagen thickness and packing. The absence of functional LOX may be compensated by LOX isoenzymes.

Scandinavian Fellowship for Oral Pathology and Oral Medicine: guidelines for oral pathology and oral medicine in the dental curriculum.

In Scandinavia, as in many European countries, most patients consult their general dentist once a year or more. This gives the dentist a unique opportunity and an obligation to make an early diagnosis of oral diseases, which is beneficial for both the patient and the society. Thus, the dentist must have knowledge of clinical symptoms, local and systemic signs and clinical differential diagnoses to make an accurate diagnosis. The dentist must be competent in selecting appropriate diagnostic tests, for example, tissue biopsy and microbiological samples, and conducting them correctly, as well as in interpreting test results and taking appropriate action accordingly. Furthermore, the dentist must be aware of diseases demanding multidisciplinary cooperation and be able to recognise his/her professional limitation, and to refer to other specialists when required. The dental curriculum changes over time as new approaches, treatments and diagnostic possibilities develop. Likewise, the role of the dentist in the community changes and may vary in different countries. As members of the Scandinavian Fellowship for Oral Pathology and Oral Medicine and subject representatives of oral pathology and oral medicine, we feel obliged to contribute to the discussion of how the guidelines of the dental curriculum support the highest possible standards of dental education. This article is meant to delineate a reasonable standard of oral pathology and oral medicine in the European dental curriculum and to guide subject representatives in curriculum development and planning. We have created an advisory topic list in oral pathology and oral medicine.

Reduced expression of lipopolysaccharide-induced CXC chemokine in Porphyromonas gingivalis-induced experimental periodontitis in matrix metalloproteinase-8 null mice.

BACKGROUND AND OBJECTIVE: Matrix metalloproteinase-8 (MMP-8) is a central mediator in chronic periodontitis. Recently developed MMP-8-deficient mice show an impaired polymorphonuclear neutrophil response and more severe alveolar bone loss in Porphyromonas gingivalis-induced experimental periodontitis. The main mediators involved in neutrophil and monocyte/macrophage recruitment and in bone loss include lipopolysaccharide-induced CXC chemokine (LIX/CXCL5), stromal-derived factor-1/CXC chemokine ligand 12 (SDF1/CXCL12) and RANKL. Therefore, the aim of this study was to characterize the expression of LIX/CXCL5, SDF1/CXCL12 and RANKL in Porphyromonas gingivalis-induced experimental periodontitis in MMP-8⁻/⁻ (knockout) and wild-type mice. MATERIAL AND METHODS: MMP-8 null and WT P. gingivalis-infected and uninfected mice were included. Histopathological changes were assessed and LIX/CXCL5, SDF1/CXCL12 and RANKL were immunodetected and quantified. RESULTS: Typical histopathological features of chronic periodontitis were seen in P. gingivalis-infected groups. LIX/CXCL5 expression was restricted to the gingival papilla in all four groups. Significantly lower expression of LIX/CXCL5 was seen in the knockout group compared with the wild-type infected group (p < 0.05). SDF1/CXCL12 and RANKL expression was mainly localized to the alveolar crest, including inflammatory leukocytes, vascular endothelium, osteoblasts and osteoclasts. Significant increases of SDF1/CXCL12 and RANKL were seen in both knockout and wild-type P. gingivalis-infected groups compared with uninfected groups (p < 0.05). CONCLUSION: RANKL and SDF1/CXCL12 are up-regulated in P. gingivalis-induced periodontitis and they appear to be associated with the pathogenesis of the disease. MMP-8 is associated with a reduced expression of LIX/CXCL5 in the P. gingivalis-induced experimental periodontitis model.

Toll-like receptor 9 ligands enhance mesenchymal stem cell invasion and expression of matrix metalloprotease-13.

Human mesenchymal stem cells (hMSCs) are multipotent cells that are found in the bone marrow. Inflammation and tissue damage mobilize MSCs and induce their migration towards the damaged site through mechanisms that are not well defined. Toll-like receptor-9 (TLR9) is a cellular receptor for microbial and vertebrate DNA. Stimulation of TLR9 induces inflammatory and invasive responses in TLR9-expressing cells. We studied here the expression of TLR9 in human MSCs and the effects of synthetic TLR9-agonists on their invasion. Constitutive expression of TLR9 was detected in human MSCs but the expression was suppressed when MSCs were induced to differentiate into osteoblasts. Using standard invasion assays and a novel organotypic culture model based on human myoma tissue, we discovered that stimulation with the TLR9 agonistic, CpG oligonucleotides increased the invasion capacity of undifferentiated MSCs. Simultaneously, an increase in MMP-13 synthesis and activity was detected in the CpG-activated MSCs. Addition of anti-MMP-13 antibody significantly diminished the CpG-induced hMSC invasion. We conclude that treatment with TLR9-ligands increases MSC invasiveness, and this process is at least partially MMP-13-mediated.

Can orthotic insoles prevent lower limb overuse injuries? A randomized-controlled trial of 228 subjects.

Lower limb overuse injuries are common among people who are exposed to physical stress. Orthotic shoe insoles are widely used to prevent lower limb overuse injuries. Here, we conducted a randomized-controlled study to examine whether the use of orthotic insoles prevents lower limb overuse injuries. Participants (n=228) were randomly assigned to use (n=73) or not to use (n=147) orthotic insoles. The insoles were molded to the shape of the foot to provide support during physical activity. The main outcome measure in the present study was the physician-diagnosed lower limb overuse injury. Thirty-four (46.6%) subjects in the insole group were diagnosed with a lower limb overuse injury compared with 56 (38.1%) in the control group (P=0.29) during the 6-month study period. When body mass index and the results of a 12-min running test and muscle strength were adjusted in a Cox's regression model, the hazard ratio for lower limb overuse injury in the insole group was 1.3 (95% confidence intervals: 0.8-2.1) compared with the control group. Use of orthotic insoles was not associated with a decrease in lower limb overuse injuries. Our findings suggest that routine use of orthotic insoles does not prevent physical-stress-related lower limb injuries in healthy young male adults.

MMP8 increases tongue carcinoma cell-cell adhesion and diminishes migration via cleavage of anti-adhesive FXYD5.

Matrix metalloproteinases (MMPs) modify bioactive factors via selective processing or degradation resulting in tumour-promoting or tumour-suppressive effects, such as those by MMP8 in various cancers. We mapped the substrates of MMP8 to elucidate its previously shown tumour-protective role in oral tongue squamous cell carcinoma (OTSCC). MMP8 overexpressing (+) HSC-3 cells, previously demonstrated to have reduced migration and invasion, showed enhanced cell-cell adhesion. By analysing the secretomes of MMP8 + and control cells with terminal amine isotopic labelling of substrates (TAILS) coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS), we identified 36 potential substrates of MMP8, including FXYD domain-containing ion transport regulator 5 (FXYD5). An anti-adhesive glycoprotein FXYD5 has been previously shown to predict poor survival in OTSCC. Cleavage of FXYD5 by MMP8 was confirmed using recombinant proteins. Furthermore, we detected a loss of FXYD5 levels on cell membrane of MMP8 + cells, which was rescued by inhibition of the proteolytic activity of MMP8. Silencing (si) FXYD5 increased the cell-cell adhesion of control but not that of MMP8 + cells. siFXYD5 diminished the viability and motility of HSC-3 cells independent of MMP8 and similar effects were seen in another tongue cancer cell line, SCC-25. FXYD5 is a novel substrate of MMP8 and reducing FXYD5 levels either with siRNA or cleavage by MMP8 increases cell adhesion leading to reduced motility. FXYD5 being a known prognostic factor in OTSCC, our findings strengthen its potential as a therapeutic target.

Elevated MMP-8 and decreased myeloperoxidase concentrations associate significantly with the risk for peripheral atherosclerosis disease and abdominal aortic aneurysm.

Matrix metalloproteinases are responsible for degradation and remodelling of extracellular matrix and exert important roles in initiation and progression of inflammatory diseases. We aimed to examine the role of Matrix metalloproteinases (MMPs) and their regulators in degenerative arterial diseases. Serum samples were collected from patients with arterial disease (n = 126), who underwent surgery because of symptomatic aorto-occlusive disease (AOD, n = 18), carotid artery stenosis (n = 67) or abdominal arotic aneurysm (n = 41). Serum MMP-1, MMP-8, MMP-13, TIMP-1, myeloperoxidase (MPO) and neutrophil elastase (HNE) concentrations were determined by ELISA, and the molar ratio of MMP-8 and TIMP-1 was calculated. To get reference values, the determinations were done on samples of healthy blood donors (n = 100). In univariate analyses, the patients had higher MMP-8 (P < 0.001), TIMP-1 (P = 0.045), and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.001) when compared with the blood donors. All three subgroups had higher MMP-8 (P < 0.001) and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.01, except AOD) levels when compared with the references. In multiple logistic regression analyses, the male gender (P < 0.01), age (P < 0.001), elevated MMP-8 (P < 0.001) and decreased MPO (P < 0.001) concentrations associated significantly with the risk for arterial disease, and provided an area under curve (AUC) of 0.97 in the Receiver operating characteristics analyses. In multiple linear regression analyses, HNE correlated with both MMP-8 (P < 0.001) and MPO (P = 0.008) concentrations. Combination of high MMP-8 and low MPO level in serum eventually reflecting selectively modified neutrophil degranulation may indicate increased risk for arterial disease.

Gingival crevicular fluid can degrade Emdogain and inhibit Emdogain-induced proliferation of periodontal ligament fibroblasts.

BACKGROUND AND OBJECTIVE: Emdogain (EMD), consisting mostly of amelogenin, is used in periodontal therapy to regenerate lost connective tissue. Emdogain is applied onto periodontally affected root surfaces, where it becomes exposed to proteolytic enzymes. In this study, we aimed to find out whether gingival crevicular fluid or matrix metalloproteinases (MMPs) could degrade EMD, and whether this degradation has consequences for in vitro cell proliferation. MATERIAL AND METHODS: We studied the effects of 156 gingival crevicular fluid samples collected from subjects with different stages of periodontal disease and from healthy control subjects and the effects of MMP-1, -2, -8, -9, -13 and -14 on the degradation of EMD using EMD-embedded zymography. The effects of gingival crevicular fluid with or without EMD and the effects of amelogenin on the proliferation of cultured periodontal ligament fibroblasts were studied by cell proliferation enzyme-linked immunosorbent assay kit. RESULTS: Degradation of Emdogain induced by gingival crevicular fluid was greater in samples from all stages of periodontal diseases compared with healthy control samples. Of the MMPs studied, only MMP-2 and MMP-8 showed limited EMD-degrading activities. One hundred micrograms per millilitre of EMD increased proliferation of periodontal ligament fibroblasts on average by 24% (confidence interval 0.60-0.64) and at 200 microg/mL by 30% (confidence interval 0.62-0.68) compared with control fibroblasts (confidence interval 0.48-0.52). However, gingival crevicular fluid (10 microg/mL) together with 100 microg/mL EMD induced the proliferation only by 6% (confidence interval 0.51-0.55) and with 200 microg/mL EMD by 12% (confidence interval 0.54-0.58). Amelogenin at 200 microg/mL decreased the proliferation of periodontal ligament fibroblasts by 54% (confidence interval 0.22-0.25). CONCLUSION: We suggest that diseased gingival crevicular fluid containing various proteases leads to degradation of EMD and decreased proliferation of periodontal ligament fibroblasts.

Scandinavian Fellowship for Oral Pathology and Oral Medicine: statement on oral pathology and oral medicine in the European Dental Curriculum.

BACKGROUND: For many years, dentists have migrated between the Scandinavian countries without an intentionally harmonized dental education. The free movement of the workforce in the European Union has clarified that a certain degree of standardization or harmonization of the European higher education acts, including the dental education, is required. As a result of the Bologna process, the Association for Dental Education in Europe and the thematic network DentEd have generated guidelines in the document 'Profile and Competences for the European Dentist' (PCD). This document is meant to act as the leading source in revisions of dental curricula throughout Europe converging towards a European Dental Curriculum. In order to render the best conditions for future curriculum revisions providing the best quality dentist we feel obliged to analyse and comment the outlines of oral pathology and oral medicine in the PCD. METHODS: The representatives agreed upon definitions of oral pathology and oral medicine, and competences in oral pathology and oral medicine that a contemporary European dentist should master. The competences directly related to oral pathology and oral medicine were identified, within the PCD. RESULTS: The subject representatives suggested eighteen additions and two rewordings of the PCD, which all were substantiated by thorough argumentation. PERSPECTIVES: Hopefully, this contribution will find support in future revisions of the PCD in order to secure the best quality dental education.

Tranexamic acid can inhibit tongue squamous cell carcinoma invasion in vitro.

OBJECTIVES: Tranexamic acid (TA) is an inhibitor of plasminogen activation commonly used in surgery. Plasmin, the end product of plasminogen activation, degrades fibrin in the thrombus, leading to thrombolysis. However, plasmin is also associated with progression of several cancers and with cancer-associated matrix metalloproteinase-9 (MMP-9) activation. As the gelatinases MMP-2 and -9 are involved in cancer progression, several antigelatinolytic drugs have been developed as potential anticancer therapeutics. We previously developed gelatinases targeting peptide CTT1 capable of inhibiting carcinoma growth. STUDY DESIGN: The effects of TA and CTT1 on tongue carcinoma aggressiveness were evaluated in an in vitro assay of human HSC-3 and SCC-25 cells. MATERIALS AND METHODS: The cells were cultured with or without TA and CTT1 and their proMMP-9 production and activation were analysed with Western immunoblotting and gelatin zymography. Their effects on tongue carcinoma invasion were analysed in a Matrigel assay. RESULTS: Tranexamic acid alone and in combination with CTT1 can inhibit tongue SCC invasion in vitro, at least partially explained by its property of reducing the plasmin-mediated activation of proMMP-9. CONCLUSIONS: These data suggest that patients undergoing surgical therapy for large oral malignancies may cobenefit from prolonged TA therapy, because of its antithrombolytic and antitumour properties.

Development and validation of a psychometric scale for assessing healthcare professionals' knowledge in radiation protection.

INTRODUCTION: Healthcare professionals must sufficiently understand ionising radiation and the associated protection measures to avoid unnecessarily exposing patients and staff to ionising radiation. Hence, a proper safety culture is important to lowering health risks. The development and establishment of an instrument that can indicate healthcare professionals' understanding/knowledge of radiation protection concepts can greatly contribute to a good safety culture. The purpose of the present study was to develop and psychometrically test the Healthcare Professional Knowledge of Radiation Protection (HPKRP) self-evaluation scale, which was designed to measure the knowledge level of radiation protection by healthcare professionals working with ionising radiation in a clinical environment. METHODS: The presented research employed a cross-sectional study design. Data were collected from eight Finnish hospitals in 2017. A total of 252 eligible nurses responded to the newly developed HPKRP scale. The face and content validity were tested with the Content Validity Index (CVI). Explorative factor analysis was used to test construct validity, whereas reliability was tested with Cronbach's alpha. RESULTS: Overall S-CVI for the HPKRP scale was 0.83. Exploratory factor analysis revealed a three-factor model for the HcPCRP scale containing 33 items. The first factor was defined by Radiation physics and principles of radiation usage, the second factor by Radiation protection, and the third factor by Guidelines of safe ionising radiation usage. These three factors explained 72% of the total variance. Cronbach's alpha coefficient for the scale ranged from 0.93 to 0.96. CONCLUSION: The results provide strong evidence for the validity and reliability of the HPKRP scale. Additionally, educators can use the scale to evaluate healthcare students' understanding in radiation safety before and after education.