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| 2. |
- Carlsson, Hanna, 1979, et al.
(author)
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Cluster analysis of S100 gene expression and genes correlating to psoriasin (S100A7) expression at different stages of breast cancer development
- 2005
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In: Int J Oncol. ; 27:6, s. 1473-81
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Journal article (peer-reviewed)abstract
- Gene expression patterns in ductal carcinoma in situ (DCIS) and invasive and metastatic breast tumors have been determined using serial analysis of gene expression (SAGE). The purpose of this approach was to identify biologically and clinically meaningful subgroups of DCIS with a high risk of progression to invasive disease. The analyses have led to the identification of several differentially expressed genes, such as HIN-1, dermcidin and S100A7 (psoriasin). The aim of the present study was further to delineate the expression profile of S100 genes using information from 22 breast epithelial SAGE libraries. We demonstrated the down-regulation of S100A6 and S100A10 in breast cancer, irrespective of pathological stage. S100P and S100Z were both up-regulated in cancer; whereas S100A7, S100A8 and S100A9 were strongly up-regulated only in DCIS. The hierarchical clustering of S100 gene expression in these 22 libraries revealed two major groups with distinguishable S100 gene expression profiles. One of them was characterized by the high concomitant expression of S100A7, S100A8 and S100A9. Using SAGE informatics, we found 21 genes with a high positive correlation to S100A7 expression in libraries representing different categories of tissues archived at SAGE Genie, suggesting a function of psoriasin that is not tissue specific. Like S100A7, several of these genes displayed cation-binding properties. We also report the strong correlation in the breast epithelial SAGE libraries between the expression of S100A7 and genes reported as being up-regulated in DCIS, as well as in the inflammatory skin disorder, psoriasis; including RGS5, UPK1A, TMPRSS3, S100A9, p53, SCCA1, SCCA2 and KRT17.
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| 3. |
- Carlsson, Hanna, 1979, et al.
(author)
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Psoriasin (S100A7) and calgranulin-B (S100A9) induction is dependent on reactive oxygen species and is downregulated by Bcl-2 and antioxidants
- 2005
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In: Cancer Biol Ther. ; 4:9, s. 998-1005
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Journal article (peer-reviewed)abstract
- S-100 proteins are calcium-binding proteins with important growth regulatory functions. Of these proteins, psoriasin and calgranulin-B have been shown to be highly upregulated in ductal carcinoma in situ (DCIS) of the breast and in psoriasis. The purpose of this study was to further elucidate the functional relevance of the overexpression of these two S-100 proteins in psoriasis and DCIS. We report the induction of both proteins by reactive oxygen species, phorbol ester TPA, and the induction of psoriasin in response to the PI3K inhibitor wortmannin. We also demonstrate that Bcl-2 overexpression represses the induction of psoriasin and calgranulin-B under these different conditions. The same effect was obtained with the antioxidant NAC, which indicates that the suppression of psoriasin and calgranulin-B induction is mediated by the antioxidant function of Bcl-2. Furthermore, we demonstrate that overexpression of a dominant negative IKKbeta also inhibits the induction of psoriasin suggesting that the NFkappaB pathway is involved in the induction of this protein. Also, we found NFkappaB responsive DNA elements in the upstream promoter region of psoriasin. MCF10A cells with a stable retroviral overexpression of psoriasin were significantly more resistant to H2O2-induced cell death than control cells further supporting the hypothesis that these S-100 proteins may play a role in oxidative stress response.
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| 4. |
- Enerbäck, Hanna
(author)
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Caries Prevention in Patients Undergoing Orthodontic Treatment
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Background: Scientifically based guidelines to predict and prevent caries during orthodontic treatment with fixed orthodontic appliances are lacking. Aim: The overall aim of this thesis was to improve caries risk assessment before orthodontic treatment, as well as to evaluate caries risk and improve caries prevention during treatment. Patients and methods: Patients (n=270) undergoing treatment with fixed appliance at the Specialist Clinic of Orthodontics in Mölndal, Sweden, were included. Studies I, III and IV were performed with an RCT design, with the subjects being randomly assigned to one of the following groups: i. Fluoride mouth rinse (FMR) group, 0.2 % sodium fluoride (NaF) mouth rinse plus 1450 ppm F toothpaste; ii. High-fluoride toothpaste (HFT) group, 5000 ppm F; and iii. Control (CTR) group, 1450 ppm F toothpaste. In study I, the effect of orthodontic treatment and the different fluoride regimens on caries risk and caries risk factors were evaluated. Study II was performed with a prospective design that evaluated the CRA programmes and the caries indices abilities to predict the outcome of caries during treatment. In studies III and IV, the impacts of the different fluoride regimens on caries incidence (through radiographs and clinical photographs) during orthodontic treatment were evaluated. Results: The FMR and HFT groups showed an unchanged caries risk during treatment, while the caries risk increased significantly in the CTR group (p<0.0001). The DiFS index demonstrated the highest accuracy in predicting initial and manifest caries during treatment with fixed appliances, as compared to the multi-factorial CRA programmes. Radiographic analyses revealed no significant difference between the fluoride groups in terms of increased caries incidence during treatment. However, the numbers of patients with an increase of one or more white spot lesions (WSL) during orthodontic treatment were significantly higher in the CTR group than in the FMR group (p=0.0097) or HFT group (p=0.018) when the data for incisors, lateral incisors and canines were included. Conclusion: The DiFS index most-accurately predicts caries during orthodontic treatment. Furthermore, a mouth rinse or high-fluoride toothpaste can be recommended during orthodontic treatment to retain low caries risk and to reduce the numbers of WSLs in the aesthetic front.
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| 5. |
- Enerbäck, Hanna, et al.
(author)
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Effect of a mouth rinse and a high-fluoride toothpaste on caries incidence in orthodontic patients: A randomized controlled trial
- 2022
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In: American Journal of Orthodontics and Dentofacial Orthopedics. - : Elsevier BV. - 0889-5406. ; 162:1
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Journal article (peer-reviewed)abstract
- Introduction: The objective was to evaluate the effect of a fluoride mouth rinse and a high-fluoride toothpaste on caries incidence in patients undergoing orthodontic treatment with fixed appliances. Methods: In this 3-armed, parallel-group, randomized controlled trial, patients referred to the Specialist Clinic of Orthodontics, Mölndal, Sweden, were randomly allocated to 1 of the 3 groups. (1) Fluoride mouth rinse (FMR) group: 0.2 % sodium fluoride (NaF) mouth rinse plus 1450 ppm fluoride (F) toothpaste; (2) High-fluoride tootpaste (HFT) group: 5000 ppm F toothpaste; and (3) Control (CTR) group: 1450 ppm F toothpaste. The generation of a randomization sequence was performed in blocks of 30. Inclusion criteria included patients scheduled for treatment with fixed appliances in the maxillary and mandibular arch aged 12-20 years. The primary outcome variable was the change in Decayed Initial Filled Surfaces (ΔDiFS) based on radiographs taken before and after the treatment. For statistical comparisons between groups, the Kruskal–Wallis test were used for continuous variables, whereas the Mann-Whitney U-test was used for pairwise group comparisons. Furthermore, the risk ratio (RR) and 95% confidence interval (CI) based on clinically relevant cutoffs (DiFS ≥2) were calculated to compare the increase of caries during orthodontic treatment between 2 groups. The Cochran-Mantel-Haenszel method was used to adjust RR for baseline values. Blinding was employed during the caries registration and the data analysis. Results: In total, 270 participants were randomized, with 15 patients dropping out, such that 255 patients were included in the statistical analyses. Recruitment was from October 2010 to December 2012. An increase in DiFS (≥1 DiFS) during treatment was observed in 48.3% of the FMR group, 42.0% of the HFT group, and 35.6% of the CTR group. There was no significant difference between the groups regarding increased DiFS (P = 0.17). The risk of increase in DiFS ≥2 during orthodontic treatment was 31.0% in the FMR group, 25.9% in the HFT group, and 18.4% in the CTR group. The RR for an increase of ≥2 DiFS during orthodontic treatment was 1.38 (95% CI, 0.81-2.34; P = 0.23) for FMR vs CTR, 1.21 (95% CI, 0.70-2.10; P = 0.51) for HFT vs CTR, and 0.93 (95% CI, 0.57-1.49; P = 0.76) for HFT vs FMR. Conclusions: In patients who demonstrate a low prevalence of caries and are undergoing orthodontic treatment, daily use of high-fluoride toothpaste or fluoride mouth rinse in combination with regular toothpaste does not appear to significantly alter the caries incidence compared with the use of regular toothpaste. Trial Registration: The trial was registered in the FoU i Sverige research database (http://www.fou.nu/is/sverige), with registration no. 236251. Protocol: The protocol was not published before trial commencement. Funding: Local Research and Development Board for Gothenburg and South Bohuslän (grant no. 768531); and The Swedish Patent Revenue Fund (grant number EKF-780/19).
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| 6. |
- Enerbäck, Hanna, et al.
(author)
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Effect of high-fluoride toothpaste and mouth rinse on the prevention of demineralized lesions during orthodontic treatment: a randomized controlled trial
- 2023
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In: European Journal of Orthodontics. - : Oxford University Press. - 0141-5387 .- 1460-2210. ; 45:5, s. 477-484
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Journal article (peer-reviewed)abstract
- Objective To evaluate the effect of high-fluoride mouth rinse and high-fluoride toothpaste on the development of demineralized lesions (DLs) during orthodontic treatment. Trial design Three-armed parallel-group randomized controlled trial. Methods The trial was performed with 270 adolescent orthodontic patients. Randomization was performed in blocks of 30, enrolling the patients into one of the following groups: the fluoride mouth rinse (FMR) group receiving 0.2% sodium fluoride (NaF) mouth rinse plus 1450 ppm fluoride (F) toothpaste; high-fluoride toothpaste (HFT) group receiving 5000 ppm F toothpaste; and the Control (CTR) group receiving 1450 ppm F toothpaste. Inclusion criteria were patients scheduled for treatment in both arches with fixed appliances and age between 12 and 20 years. The primary outcome variable was the proportion of participants with at least one new demineralized lesion as assessed on digital photos taken before and after treatment, analysed by a blinded clinician. The analysis included all teeth or teeth in the aesthetic zone, i.e. all central incisors, lateral incisors, and canines. A random sample of 30 participants was assessed to check intra- and inter-reliability. For pairwise comparison between groups, Fisher's non-parametric permutation test was used for continuous variables. Blinding was employed during the caries registration and data analysis. Recruitment October 2010 to December 2012 Results In total, 270 patients were randomized, of which 22 were excluded during treatment. Therefore, 248 participants were included in the study. The number of patients with an increase of & GE;1 DL, including only central- and lateral incisors and canines, during orthodontic treatment, was significantly lower in the HFT group, 51/85 60%, compared to the CTR group, 64/82 78%, RR 0.77 (CI 0.62; 0.95), P = .01 and in the FMR group, 47/81 58%, compared to the CTR group, RR 0.74 (CI 0.60; 0.92), P < .01. Conclusions To prevent demineralized lesions in the aesthetic zone, high-fluoride mouth rinse and high-fluoride toothpaste may be recommended. Limitations The protocol was not registered, and the present study did not use a double-blinded design.
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| 7. |
- Enerbäck, Hanna, et al.
(author)
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Effects of orthodontic treatment and different fluoride regimens on numbers of cariogenic bacteria and caries risk: a randomized controlled trial
- 2019
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In: European journal of orthodontics. - : Oxford University Press (OUP). - 1460-2210 .- 0141-5387. ; 41:1, s. 59-66
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Journal article (peer-reviewed)abstract
- Background: Caries is an undesirable side-effect of treatment with fixed orthodontic appliances. Therefore, it is crucial to understand how orthodontic treatment and different fluoride regimens affect caries risk and individual risk factors. Objective: To evaluate the effects of orthodontic treatment and different fluoride regimens on caries risk and caries risk factors, including cariogenic bacteria. Trial design: Three-armed, parallel group, randomized, controlled trial. Methods: Patients referred to the Specialist Clinic of Orthodontics, Mölndal Hospital, Sweden, were distributed randomly into the following groups: group I (Control group), 1450 ppm fluoride (F) toothpaste; group II, 1450 ppm F toothpaste plus 0.2 per cent sodium fluoride (NaF) mouth rinse; and group III, 5000 ppm F toothpaste. The inclusion criteria were: age 12-20 years; and bimaxillary treatment with fixed appliances. The primary outcome variables were: caries risk; and the numbers of cariogenic bacteria. Radiographs were taken before treatment to determine the caries status. Data were collected before treatment and after 1 year with a fixed appliance. The variables were compiled into a Cariogram to assess the caries risk. Comparisons were made over time within and between the groups. The generation of randomization sequence was performed in blocks of 30. Blinding was employed during the data analysis and the caries registration. Recruitment: The clinical study duration was from October 2010 to December 2012. Results: Overall, 270 patients were randomized, of which 15 were excluded from the study. Therefore, 255 patients were included in the analyses. The caries risk increased significantly during orthodontic treatment in group I (P < 0.0001), whereas groups II and III had unchanged caries risks. All the groups showed statistically significant increases in the numbers of cariogenic bacteria. Harms: No harms were reported during the trial. Conclusions: To avoid an increased risk of caries during orthodontic treatment, everyday use of high-fluoride toothpaste (5000 ppm F) or mouth rinse (0.2% NaF) in combination with ordinary toothpaste is recommended. Registration: The trial was not registered.
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| 8. |
- Enerbäck, Hanna, et al.
(author)
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Validation of caries risk assessment methods in orthodontic patients
- 2020
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In: American Journal of Orthodontics and Dentofacial Orthopedics. - : Elsevier BV. - 0889-5406. ; 158
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Journal article (peer-reviewed)abstract
- Introduction: Dental caries is an undesirable side effect of orthodontic treatment with fixed appliances. Caries lesions can result in long-term esthetic disturbance, costly interventions, and even interrupted treatment. Therefore, it is crucial to assess accurately both a patient's caries risk before treatment and their suitability for orthodontic treatment. This study aimed to evaluate the validity of 5 caries risk assessment methods for predicting caries outcome during orthodontic treatment: Cariogram, Caries Management by Risk Assessment (CAMBRA), R2, decayed filled teeth (DFT), and decayed initial filled surfaces (DiFS). Methods: A prospective longitudinal clinical study of 270 adolescents who were referred to the Specialist Clinic for Orthodontics, Mölndal Hospital, Sweden for treatment with fixed orthodontic appliances. The following data were collected before treatment: plaque index, radiographs to determine caries prevalence (DFT, DiFS), photographs to determine white-spot lesions, saliva samples (Streptococcus mutans and Lactobacilli), and responses to a questionnaire (regarding diet and oral hygiene). The variables were compiled to assess caries risk according to Cariogram, CAMBRA, and R2. Radiographs were also taken posttreatment to assess caries incidence. The caries outcomes after treatment were analyzed and compared with the caries risk, assessed by the caries risk assessment methods at baseline. Results: DiFS proved to be the most reliable method for predicting caries during orthodontic treatment, presenting the highest area under the receiver operating characteristic curve for both manifest caries (0.77) and initial caries (0.71). Conclusions: The DiFS prevalence index was demonstrated to be useful in identifying patients who are at risk for developing manifest and initial caries during orthodontic treatment. © 2020
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| 9. |
- Krop, I., et al.
(author)
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A putative role for psoriasin in breast tumor progression
- 2005
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In: Cancer Research. ; 65:24, s. 11326-34
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Journal article (peer-reviewed)abstract
- Psoriasin (S100A7) was identifi;ed as a gene highly expressed in psoriatic keratinocytes and highly and more frequently expressed in ductal carcinoma in situ (DCIS) than in invasive breast carcinomas (IBC), suggesting a potential role in tumor progression. Psoriasin expression is associated with poor prognostic factors in both DCIS and IBC. Several putative functions have been proposed for psoriasin in various disease types, but none of these can fully explain its involvement in breast tumor progression. Here, we show that down-regulation of endogenous psoriasin expression via stable short hairpin RNAs in a human IBC cell line (MDA-MB-468) increases cell migration and invasion without influencing cell proliferation and survival in vitro but inhibits tumor growth in vivo. These seemingly paradoxical results are potentially explained by the dramatic up-regulation and down-regulation of matrix metalloproteinase-13 and vascular endothelial growth factor (VEGF), respectively, observed in cells with decreased psoriasin levels compared with controls. Correlating with this, high psoriasin expression in human IBC is associated with increased angiogenesis and worse clinical outcome, and psoriasin mRNA levels are coordinately regulated with VEGF and other genes related to hypoxia and mitochondrial reactive oxygen species (ROS). Based on these results, we propose that psoriasin may play a role in breast tumor progression by promoting angiogenesis and enhancing the selection for cells that overcome its anti-invasive function. This hypothesis may explain why psoriasin expression is highest in high-grade and/or estrogen receptor-negative tumors, as these are associated with increased hypoxia and ROS, a setting in which the angiogenic effects of psoriasin are most important.
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| 10. |
- Martinsson, Hanna, et al.
(author)
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Expression patterns of S100A7 (psoriasin) and S100A9 (calgranulin-B) in keratinocyte differentiation
- 2005
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In: Exp Dermatol. ; 14:3, s. 161-8
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Journal article (peer-reviewed)abstract
- S100 proteins are involved in many biological processes. S100A7 and S100A9 have been shown to be markedly upregulated both in ductal carcinoma in situ of the breast and in psoriasis. We have examined the relationship between keratinocyte differentiation and the expression of the two proteins. Using Western blot analysis and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), both S100A7 and S100A9 were shown to be induced in normal primary keratinocytes (HEKn), when differentiation was promoted by high extracellular calcium, loss of contact with extracellular matrix and confluent conditions, as previously reported for S100A7 in mammary epithelial cells. Differentiation was confirmed by using RT-PCR for the differentiation marker keratin-1. Using immunohistochemistry with monoclonal antibodies, we compared the expression of the two proteins in a spectrum of conditions of dysregulated keratinocyte differentiation. We found a strikingly similar distribution of the proteins. Their expression correlated with the degree of keratinocyte differentiation. They were both absent in undifferentiated basalioma and strongly expressed in carcinoma in situ, as well as in keratoacanthoma and differentiated squamous cell carcinoma. In normal epithelium, they were expressed in the superficial, differentiated region of the epithelium rather than in the basal region. These findings support the hypothesis that these two S100 proteins are involved in keratinocyte differentiation.
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