Tags:
Pathology,
oral pathology,
oral cancer,
radiation damage
Publications
-
Giglio, Daniel; Ganesh, Divya; Bhattarai, Bishwa Prakash; Søland, Tine Merete; Sundberg, Jonas & Thorsell, Annika
[Show all 9 contributors for this article]
(2026).
Biomarkers Correlating With the Development of Oral Squamous Cell Carcinoma From Leukoplakia.
Oral Diseases.
ISSN 1354-523X.
doi:
10.1111/odi.70439.
Full text in Research Archive
Show summary
Background
We assessed protein biomarkers expressed in oral leukoplakia (OL) that are associated with the risk of transformation into oral squamous cell carcinoma (OSCC).
Methods
Tissue sections of OL transforming into OSCC (leuko-ca), the corresponding OSCC and OL that did not progress to OSCC (leuko-nonca) were analyzed with global relative quantification to compare proteome profiles. Immunohistochemistry was performed to validate the expression of identified biomarkers.
Results
The top enriched biological pathways in OL transforming into OSCC within 5–26 months after diagnosis (short duration [SD]-leuko-ca) compared with leuko-nonca were pathways regulating remodeling of the extracellular matrix (ECM) and lipid and cholesterol metabolism/transport. Kininogen-1, apolipoprotein E (ApoE), collagen alpha-1 (XVIII) chain (COL18A1), sortilin, and perlecan were the most downregulated proteins, whereas EEF1D was the most upregulated in SD-leuko-ca compared with leuko-nonca. Immunohistochemistry confirmed the expression of kininogen-1, ApoE, perlecan, and EEF1D in OL and OSCC. In OSCC compared with leuko-ca, enriched biological pathways involved keratinocyte and epithelial differentiation and immune response regulation.
Conclusion
We identified biomarkers in OL that were associated with the risk of malignant transformation. Our study gives further support for the importance of the immune system, ECM remodeling, and lipoproteins and cholesterol metabolism in the progression of OL to OSCC.
-
Golnarnik, Golnaz; Nieminen, Anni I.; Søland, Tine Merete; Galtung, Hilde & Haug, Trude M.
(2026).
Differential metabolic responses to hydrogen peroxide-induced oxidative stress in parotid and submandibular gland acinar cell lines.
Biochemistry and Biophysics Reports.
46,
p. 102596–102596.
doi:
10.1016/j.bbrep.2026.102596.
Full text in Research Archive
-
Søland, Tine Merete; Ljunggren, A; Abuharb, A; Alaref, F; Kelppe, J & Reibel, J
[Show all 14 contributors for this article]
(2025).
Odontogenic tumors in Sweden, Norway, Finland, and Denmark. A multicenter study.
Journal of Oral Pathology & Medicine.
ISSN 0904-2512.
54(5),
p. 360–370.
doi:
10.1111/jop.13635.
Full text in Research Archive
Show summary
Background
Updated and comprehensive epidemiological data on odontogenic tumors are not available for the Nordic countries. The aim of the study was to retrospectively examine the prevalence and clinical and radiological characteristics of primary odontogenic tumors over a 10-year period in Sweden, Norway, Finland, and Denmark.
Methods
Primary odontogenic tumors diagnosed by oral pathologists from 2010 to 2020 at nine different diagnostic laboratories in Sweden, Norway, Finland, and Denmark were identified. Using histopathology referrals and their corresponding histopathological reports, age and sex, anatomic site, clinical and radiological findings, tentative diagnosis, histopathological diagnosis, and recurrence of the tumors were recorded. Range, mean, and median for continuous variables and frequency tabulation for discrete variables were used.
Results
In total, 1139 primary odontogenic tumors (598 in males and 540 in females) were identified during the study period, giving an annual incidence rate of 4.2/million. The mean age of all patients was 29 years. Ninety-nine percent of the tumors were benign, and the mandible was the predominant location. Odontoma, ameloblastoma, and odontogenic fibroma were the three most common tumors. The mixed epithelial and mesenchymal benign odontogenic tumors were more common at a younger age compared with the epithelial tumors and the mesenchymal tumors (mean age 22, 44, and 35 years, respectively). Information on variables other than sex, age, and tumor site was missing in most referrals.
Conclusion
The annual incidence of 4.2 cases per million indicates that odontogenic tumors are uncommon in Nordic countries. Better practices to improve the quantity and quality of clinical information in the pathology referrals are needed.
-
Juvkam, Inga; Zlygosteva, Olga; Schreurs, Olaf Joseph Franciscus; Edin, Nina Frederike Jeppesen; Galtung, Hilde & Malinen, Eirik
[Show all 7 contributors for this article]
(2025).
Regional atrophy, cellular plasticity, and regenerative potential in irradiated murine salivary glands.
Acta Oncologica.
ISSN 0284-186X.
64,
p. 927–938.
doi:
10.2340/1651-226x.2025.44012.
Full text in Research Archive
Show summary
Background and purpose: Radiotherapy of head and neck cancer may cause detrimental late side effects such as fibrosis and hyposalivation. We investigated mouse salivary glands after fractionated irradiation, with the aim to elucidate cellular plasticity and potential regeneration.
Methods: 12-week-old female C57BL/6JRj mice were irradiated with X-rays to a total dose of 66 Gy, given in 10 fractions over 5 days. The radiation field covered the oral cavity and major salivary glands. The submandibular (SMG), sublingual (SLG), and parotid glands (PG) were dissected at day 100 after finishing irradiation. Using different histological staining techniques, morphological, cellular, and molecular changes were investigated in irradiated and control SMG, SLG, and PG.
Results: Atrophy of acinar cells was observed in irradiated SMG and SLG, but not in PG. Surprisingly, the acinar atrophy was confined to one region of each irradiated gland. These atrophic regions showed distinct cellular and molecular compositions compared to non-atrophic regions and control glands. Increased expression of the ductal cell markers keratin 5 and 19 (K5 and K19), along with increased percentages of proliferating myofibroblasts, fibroblasts, leukocytes, and acinar cells (Nkcc1+) were observed in the atrophic regions compared to controls. In addition, some of the K19+ and K5+ duct-like cells also co-expressed Nkcc1.
Interpretation: Through a detailed histological assessment of the cellular and molecular changes in the major salivary glands of irradiated mice, we observed signs of cellular plasticity where ductal cells adopt an acinar cell phenotype upon irradiation. This suggests a regenerative potential of salivary glands after irradiation.
-
Haugsten, Helene Rygvold; Kristoffersen, Anne Karin; Enersen, Morten; Thiede, Bernd; Søland, Tine Merete & Haug, Trude M.
[Show all 7 contributors for this article]
(2025).
Bacterial extracellular vesicles from Porphyromonas gingivalis – proteomic profile and influence on oral fibroblasts.
Archives of Oral Biology.
ISSN 0003-9969.
181.
doi:
10.1016/j.archoralbio.2025.106424.
Full text in Research Archive
Show summary
Objectives
In this study, we aimed to explore the protein content of bacterial extracellular vesicles (bEVs) from three strains of Porphyromonas gingivalis, an anaerobic gram-negative bacterium closely associated with periodontitis. Additionally, we aimed to investigate the effects of bEV uptake on human oral fibroblasts, to better understand the role of these vesicles in the pathogenesis of periodontitis.
Design
Liquid chromatography-mass spectrometry was performed on bEVs from three strains of P. gingivalis with different virulence: ATCC 33277, A7A1–28, and W83. Three key proteins associated with virulence were validated using dot blot. Proliferation and viability of human oral fibroblasts after incubation with bEVs were assessed at different timepoints and different concentrations of bEVs.
Results
A total of 307 proteins were identified in the bEVs from the three strains of P. gingivalis. Among those were several relevant for virulence, for example gingipains, fimbriae, and peptidyl-arginine deiminase (PPAD). When oral fibroblasts were exposed to bEVs from A7A1–28 or W83, proliferation was significantly affected after 12 and 24 h at one bEV concentration. Furthermore, viability was significantly affected by bEVs from W83 at several timepoints and bEV concentrations. bEVs from ATCC 33277 did not induce any significant changes.
Conclusion
Several proteins associated with virulence were detected in bEVs from all three strains of P. gingivalis, with varying abundance. Uptake of these bEVs can influence human cells, as exemplified by changes in viability and proliferation.
-
Haugsten, Helene Rygvold; Lipka, Aleksandra Katarzyna; Kristoffersen, Anne Karin; Enersen, Morten; Nieminen, Anni & Søland, Tine Merete
[Show all 8 contributors for this article]
(2025).
Metabolic Changes in Oral Fibroblasts After Exposure to Bacterial Extracellular Vesicles From Three Strains of Porphyromonas gingivalis.
Cellular Microbiology.
ISSN 1462-5814.
2025(1).
doi:
10.1155/cmi/7515004.
Full text in Research Archive
Show summary
Aims
Porphyromonas gingivalis is a keystone pathogen in periodontitis that releases bacterial extracellular vesicles (bEVs) with a content derived from the membrane and cytosol of the bacteria itself. The bEVs are taken up by host tissue cells, such as oral fibroblasts, yet their effects on human cells remain incompletely understood.
Methods
The aim of this study was to investigate the impact of bEVs on human oral fibroblasts. Targeted liquid chromatography–mass spectrometry was used to assess changes in the metabolome of these cells following exposure to bEVs from three strains of P. gingivalis (ATCC 33277, A7A1-28, and W83). Metabolite content of the bEVs from each strain was also characterized.
Result
Metabolomic analyses revealed both common and strain-specific metabolites in the bEVs from these strains. Additionally, pathways mainly associated with amino acid metabolism were enriched for all. Following exposure to bEVs, the fibroblasts exhibited a metabolic shift in energy metabolism. In particular, fibroblasts incubated with bEVs from ATCC 33277 had a unique profile of enriched pathways after 10 min. However, after 24 h, this profile changed and became more similar to the profile in fibroblasts incubated with bEVs from the two more pathogenic strains. Pathway analysis revealed enrichment of glycerophospholipid and butanoate metabolism for fibroblasts exposed to all the bEVs. Additionally, altered sphingolipid metabolism was observed in fibroblasts following exposure to bEVs from ATCC 33277.
Conclusion
Our findings demonstrate that bEVs derived from P. gingivalis strains can induce changes in cellular processes in fibroblasts. This suggests a role of bEVs in the pathogenesis of periodontitis.
-
Lipka, Aleksandra; Søland, Tine Merete; Nieminen, Anni I.; Sapkota, Dipak; Haug, Trude Marie & Galtung, Hilde
(2025).
The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts.
Frontiers in Molecular Biosciences.
12.
doi:
10.3389/fmolb.2025.1492282.
Full text in Research Archive
Show summary
Introduction: Oral cancer is one of the most common forms of head and neck cancers. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the oral malignancies. The molecular pathogenesis of OSCC is complex as it involves altered expression of specific genes and proteins, but also comprises changes in metabolic processes. It is suggested that extracellular vesicles (EVs) released by cancer cells may contribute to cancer development and metastasis by recruiting and changing phenotype of normal cells that surround the tumor. Methods: The aim of the project was to characterize the effect of OSCC EVs on the metabolic profile of normal oral fibroblasts (NOFs). Targeted liquid chromatography mass spectrometry metabolic profiling was performed on control cells and NOFs exposed to OSCC EVs for 24 and 48 h. Results: Analysis of detected metabolites revealed that OSCC EVs affected NOFs the most after 24 h of exposure. Among metabolites that were significantly altered at 24 h, pyruvate, ATP, UTP, coenzyme A, and dihydroxyacetone phosphate were upregulated, while fatty acids such as nervonic acid, linoleate, oleate, palmitoleic acid, and docosahexaenoic acid were downregulated. These findings were supported by Western blotting of pyruvate kinase M2 (PKM2) and aldolase, fructose-bisphosphate A (ALDOA). Conclusion: The metabolic pathways of glycolysis, citric acid cycle, and amino acid metabolism were enriched, suggesting that OSCC EVs cause phenotype switch in NOFs that may contribute to acquiring a pro-tumorigenic phenotype.
-
Golnarnik, Golnaz; Thiede, Bernd; Søland, Tine Merete; Galtung, Hilde & Haug, Trude Marie
(2025).
Hydrogen peroxide-induced oxidative stress alters protein expression in two rat salivary acinar cell lines.
Archives of Oral Biology.
ISSN 0003-9969.
175.
doi:
10.1016/j.archoralbio.2025.106254.
Full text in Research Archive
Show summary
Objectives: This study aimed to investigate the impact of hydrogen peroxide-induced oxidative stress on the protein expression profiles of submandibular and parotid acinar cells using a proteomic approach. We sought to evaluate how oxidative stress might contribute to salivary gland dysfunction and whether the two glands respond differently.<p> <p>Design: Immortalized rat parotid gland (PG) and submandibular gland (SMG) acinar epithelial cell lines were exposed to 50 µM and 150 µM hydrogen peroxide for 24 hr, followed by protein identification and quantification via liquid chromatography-mass spectrometry. Immunofluorescence microscopy and western blot analysis validated selected protein expressions, and cell viability was assessed using trypan blue exclusion assays. <p>Results: Compared to controls, histone H4 expression increased in both cell types after hydrogen peroxide exposure, whereas voltage-dependent anion-selective channel 1, keratin 7, and keratin 8 increased only in parotid gland cells. Conversely, mitochondrial aldehyde dehydrogenase and kidney isoform glutaminase were downregulated in parotid gland cells. Basal expression of mitochondrial aldehyde dehydrogenase and catalase was higher in submandibular gland cells. At higher hydrogen peroxide concentrations, antioxidant proteins expression and cell viability were greater in submandibular gland cells compared to parotid gland cells. <p>Conclusions: Our results suggest that submandibular gland acinar cells exhibit greater resistance to oxidative stress compared to parotid gland cells, potentially due to distinct antioxidant and metabolic coping strategies. Understanding these gland-specific responses may contribute to future approaches to protect salivary glands from oxidative damage under pathological conditions.
-
-
Golnarnik, Golnaz; Søland, Tine Merete; Galtung, Hilde & Haug, Trude Marie
(2024).
Hydrogen peroxide disrupts the regulatory pathway of saliva secretion in two salivary acinar rat cell lines.
Frontiers in Molecular Biosciences.
11.
doi:
10.3389/fmolb.2024.1480721.
Full text in Research Archive
Show summary
Background: Secretion of saliva is controlled by autonomic nerve signals via regulation of Ca2+-dependent ion transport across acinar cell membranes. Oxidative stress may affect this process, leading to a decrease in saliva production. This study investigates elements of the Ca2+ regulatory pathway and their vulnerability to hydrogen peroxide-induced oxidative stress.
Methods: Rat parotid and submandibular salivary gland acinar cell lines were exposed to different hydrogen peroxide concentrations to simulate oxidative stress. Cell viability and intracellular reactive oxygen species were measured, mRNA levels were assessed via RT-qPCR, and protein expression was studied using western blot and immunofluorescence microscopy.
Results: Elevated concentrations of hydrogen peroxide reduced cell viability and increased intracellular levels of reactive oxygen species and led to a decrease in cholinergic receptor muscarinic 3 and adrenoreceptor alpha 1A mRNA and protein levels in both cell lines. In parotid gland cells, both mRNA and protein levels of stromal interaction molecule 1 and Orai1 decreased with increasing concentrations of hydrogen peroxide. In contrast, in submandibular gland cells stromal interaction molecule 1 and Orai1 displayed differential mRNA and protein expression levels.
Conclusion: Our study revealed that hydrogen peroxide exposure alters rat parotid and submandibular acinar cells, increasing reactive oxygen species and reducing autonomic receptor expression. Differential mRNA and protein expression of stromal interaction molecule 1 and Orai1 highlight complex oxidative stress effects on Ca2⁺ signaling. Most likely these effects will be deleterious to salivary secretion, but some effects may be protective.
-
Hanson, Ingunn; Juvkam, Inga; Zlygosteva, Olga; Søland, Tine Merete; Galtung, Hilde & Malinen, Eirik
[Show all 7 contributors for this article]
(2024).
TGF-β3 increases the severity of radiation-induced oral mucositis and salivary gland fibrosis in a mouse model.
International Journal of Radiation Biology.
ISSN 0955-3002.
100(5),
p. 767–776.
doi:
10.1080/09553002.2024.2324476.
Full text in Research Archive
Show summary
Purpose Toxicities from head and neck (H&N) radiotherapy (RT) may affect patient quality of life and can be dose-limiting. Proteins from the transforming growth factor beta (TGF-β) family are key players in the fibrotic response. While TGF-β1 is known to be pro-fibrotic, TGF-β3 has mainly been considered anti-fibrotic. Moreover, TGF-β3 has been shown to act protective against acute toxicities after radio- and chemotherapy. In the present study, we investigated the effect of TGF-β3 treatment during fractionated H&N RT in a mouse model. Materials and methods 30 C57BL/6J mice were assigned to three treatment groups. The RT + TGF-β3 group received local fractionated H&N RT with 66 Gy over five days, combined with TGF-β3-injections at 24-hour intervals. Animals in the RT reference group received identical RT without TGF-β3 treatment. The non-irradiated control group was sham-irradiated according to the same RT schedule. In the follow-up period, body weight and symptoms of oral mucositis and lip dermatitis were monitored. Saliva was sampled at five time points. The experiment was terminated 105 d after the first RT fraction. Submandibular and sublingual glands were preserved, sectioned, and stained with Masson’s trichrome to visualize collagen. Results A subset of mice in the RT + TGF-β3 group displayed increased severity of oral mucositis and increased weight loss, resulting in a significant increase in mortality. Collagen content was significantly increased in the submandibular and sublingual glands for the surviving RT + TGF-β3 mice, compared with non-irradiated controls. In the RT reference group, collagen content was significantly increased in the submandibular gland only. Both RT groups displayed lower saliva production after treatment compared to controls. TGF-β3 treatment did not impact saliva production. Conclusions When repeatedly administered during fractionated RT at the current dose, TGF-β3 treatment increased acute H&N radiation toxicities and increased mortality. Furthermore, TGF-β3 treatment may increase the severity of radiation-induced salivary gland fibrosis.
-
Rykkelid, Anne Marit; Sinha, Priyanshu Manojkumar; Folefac, Charlemagne Asonganyi; Horsman, Michael R.; Sørensen, Brita Singers & Søland, Tine Merete
[Show all 9 contributors for this article]
(2024).
Combination of proton- or X-irradiation with anti-PDL1 immunotherapy in two murine oral cancers.
Scientific Reports.
14(1).
doi:
10.1038/s41598-024-62272-z.
Full text in Research Archive
Show summary
Combining radiation therapy with immunotherapy is a strategy to improve both treatments. The purpose of this study was to compare responses for two syngeneic head and neck cancer (HNC) tumor models in mice following X-ray or proton irradiation with or without immune checkpoint inhibition (ICI). MOC1 (immunogenic) and MOC2 (less immunogenic) tumors were inoculated in the right hind leg of each mouse (C57BL/6J, n = 398). Mice were injected with anti-PDL1 (10 mg/kg, twice weekly for 2 weeks), and tumors were treated with single-dose irradiation (5–30 Gy) with X-rays or protons. MOC2 tumors grew faster and were more radioresistant than MOC1 tumors, and all mice with MOC2 tumors developed metastases. Irradiation reduced the tumor volume in a dose-dependent manner. ICI alone reduced the tumor volume for MOC1 with 20% compared to controls, while no reduction was seen for MOC2. For MOC1, there was a clear treatment synergy when combining irradiation with ICI for radiation doses above 5 Gy and there was a tendency for X-rays being slightly more biologically effective compared to protons. For MOC2, there was a tendency of protons being more effective than X-rays, but both radiation types showed a small synergy when combined with ICI. Although the responses and magnitudes of the therapeutic effect varied, the optimal radiation dose for maximal synergy appeared to be in the order of 10–15 Gy, regardless of tumor model.
-
-
Søland, Tine Merete; Lipka, Aleksandra Katarzyna; Ruus, Ann-Kristin; Molværsmyr, Ann-Kristin; Galtung, Hilde & Haug, Trude Marie
(2024).
Extracellular vesicles from cancer cell lines of different origins drive the phenotype of normal oral fibroblasts in a CAF-like direction.
Frontiers in Oncology.
14.
doi:
10.3389/fonc.2024.1456346.
Full text in Research Archive
Show summary
Introduction: Normal oral fibroblasts (NOFs) are located in the connective tissue of the oral mucosa. The NOFs play an important role in wound healing, tumor progression, and metastasis. They are subjected to influence by external and internal stimuli, among them extracellular vesicles (EVs), that are considered as important players in cell to cell communication, especially in carcinogenesis and metastatic processes. During tumorigenesis, stromal NOFs may undergo activation into cancer-associated fibroblasts (CAFs) that modify their phenotype to provide pro-oncogenic signals that in turn facilitate tumor initiation, progression, and metastasis. The aim of the study was to reveal the effect of EVs derived from local (oral squamous cell carcinoma – OSCC) and distant (pancreatic adenocarcinoma – PDAC; malignant melanoma brain metastasis – MBM) cancer origin on NOFs and their possible change into a CAF-like direction. Methods: The effect of each of the cancer EV types on NOFs proliferation, viability, and migration was tested. Also, changes in gene expression of the well-established CAF biomarkers ACTA2, FAP, PDGFR, and two putative CAF biomarkers, the Ca2+- activated ion channels ANO1 and KCNMA, were studied. Results: Obtained results indicate that NOFs receive and process signals transmitted by EVs originating from both OSCC, PDAC, and MBM. The fibroblast response was dependent on EV origin and concentration, and duration of EV exposure. Conclusion: The present results indicate that the molecular cargo of the EVs direct NOFs towards a pro-tumorigenic phenotype.
-
Juvkam, Inga; Zlygosteva, Olga; Sitarz, Mateusz; Sørensen, Brita Singers; Aass, Hans Christian & Edin, Nina Frederike Jeppesen
[Show all 9 contributors for this article]
(2024).
Proton- compared to X-irradiation leads to more acinar atrophy and greater hyposalivation accompanied by a differential cytokine response.
Scientific Reports.
14:22311(1),
p. 1–12.
doi:
10.1038/s41598-024-73110-7.
Full text in Research Archive
Show summary
Proton therapy gives less dose to healthy tissue compared to conventional X-ray therapy, but systematic comparisons of normal tissue responses are lacking. The aim of this study was to investigate late tissue responses in the salivary glands following proton- or X-irradiation of the head and neck in mice. Moreover, we aimed at investigating molecular responses by monitoring the cytokine levels in serum and saliva. Female C57BL/6J mice underwent local fractionated irradiation with protons or X-rays to the maximally tolerated acute level. Saliva and serum were collected before and at different time points after irradiation to assess salivary gland function and cytokine expression. To study late responses in the major salivary glands, histological analyses were performed on tissues collected at day 105 after onset of irradiation. Saliva volume after proton and X-irradiation was significantly lower than for controls and remained reduced at all time points after irradiation. Protons caused reduced saliva production and fewer acinar cells in the submandibular glands compared to X-rays at day 105. X-rays induced a stronger inflammatory cytokine response in saliva compared to protons. This work supports previous preclinical findings and indicate that the relative biological effectiveness of protons in normal tissue might be higher than the commonly used value of 1.1.
-
Juvkam, Inga Solgård; Zlygosteva, Olga; Sitarz, Mateusz; Thiede, Bernd; Sørensen, Brita Singers & Malinen, Eirik
[Show all 9 contributors for this article]
(2023).
Proton Compared to X-Irradiation Induces Different Protein Profiles in Oral Cancer Cells and Their Derived Extracellular Vesicles.
International Journal of Molecular Sciences.
ISSN 1661-6596.
24(23),
p. 1–17.
doi:
10.3390/ijms242316983.
Full text in Research Archive
Show summary
Extracellular vesicles (EVs) are membrane-bound particles released from cells, and their cargo can alter the function of recipient cells. EVs from X-irradiated cells have been shown to play a likely role in non-targeted effects. However, EVs derived from proton irradiated cells have not yet been studied. We aimed to investigate the proteome of EVs and their cell of origin after proton or X-irradiation. The EVs were derived from a human oral squamous cell carcinoma (OSCC) cell line exposed to 0, 4, or 8 Gy from either protons or X-rays. The EVs and irradiated OSCC cells underwent liquid chromatography–mass spectrometry for protein identification. Interestingly, we found different protein profiles both in the EVs and in the OSCC cells after proton irradiation compared to X-irradiation. In the EVs, we found that protons cause a downregulation of proteins involved in cell growth and DNA damage response compared to X-rays. In the OSCC cells, proton and X-irradiation induced dissimilar cell death pathways and distinct DNA damage repair systems. These results are of potential importance for understanding how non-targeted effects in normal tissue can be limited and for future implementation of proton therapy in the clinic.
-
Haugsten, Helene Rygvold; Kristoffersen, Anne Karin; Haug, Trude Marie; Søland, Tine Merete; Øvstebø, Reidun & Aass, Hans Christian
[Show all 8 contributors for this article]
(2023).
Isolation, characterization, and fibroblast uptake of bacterial extracellular vesicles from Porphyromonas gingivalis strains.
MicrobiologyOpen.
12(5).
doi:
10.1002/mbo3.1388.
Full text in Research Archive
Show summary
Periodontitis is an inflammatory condition caused by bacteria and represents a serious health problem worldwide as the inflammation damages the supporting tissues of the teeth and may predispose to systemic diseases. Porphyromonas gingivalis is considered a keystone periodontal pathogen that releases bacterial extracellular vesicles (bEVs) containing virulence factors, such as gingipains, that may contribute to the pathogenesis of periodontitis. This study aimed to isolate and characterize bEVs from three strains of P. gingivalis, investigate putative bEV uptake into human oral fibroblasts, and determine the gingipain activity of the bEVs. bEVs from three bacterial strains, ATCC 33277, A7A1-28, and W83, were isolated through ultrafiltration and size-exclusion chromatography. Vesicle size distribution was measured by nano-tracking analysis (NTA). Transmission electron microscopy was used for bEV visualization. Flow cytometry was used to detect bEVs and gingipain activity was measured with an enzyme assay using a substrate specific for arg-gingipain. The uptake of bEVs into oral fibroblasts was visualized using confocal microscopy. NTA showed bEV concentrations from 108 to 1011 particles/mL and bEV diameters from 42 to 356 nm. TEM pictures demonstrated vesicle-like structures. bEV-gingipains were detected both by flow cytometry and enzyme assay. Fibroblasts incubated with bEVs labeled with fluorescent dye displayed intracellular localization consistent with bEV internalization. In conclusion, bEVs from P. gingivalis were successfully isolated and characterized, and their uptake into human oral fibroblasts was documented. The bEVs displayed active gingipains demonstrating their origin from P. gingivalis and the potential role of bEVs in periodontitis.
-
Toközlü, Burcu; Sapkota, Dipak; Vallenari, Evan Michael; Schreurs, Olaf Joseph Franciscus & Søland, Tine Merete
(2023).
Cortactin expression in a Norwegian cohort of human papilloma virus negative oral squamous cell carcinomas of the mobile tongue.
European Journal of Oral Sciences.
ISSN 0909-8836.
doi:
10.1111/eos.12925.
Full text in Research Archive
-
Zlygosteva, Olga; Juvkam, Inga; Arous, Delmon; Sitarz, Mateusz; Sørensen, Brita Singers & Ankjærgaard, Christina
[Show all 11 contributors for this article]
(2023).
Acute normal tissue responses in a murine model following fractionated irradiation of the head and neck with protons or X-rays.
Acta Oncologica.
ISSN 0284-186X.
doi:
10.1080/0284186X.2023.2254481.
Full text in Research Archive
Show summary
Background The purpose of this study was to investigate acute normal tissue responses in the head and neck region following proton- or X-irradiation of a murine model. Materials and methods Female C57BL/6J mice were irradiated with protons (25 or 60 MeV) or X-rays (100 kV). The radiation field covered the oral cavity and the major salivary glands. For protons, two different treatment plans were used, either with the Bragg Peak in the middle of the mouse (BP) or outside the mouse (transmission mode; TM). Delivered physical doses were 41, 45, and 65 Gy given in 6, 7, and 10 fractions for BP, TM, and X-rays, respectively. Alanine dosimetry was used to assess delivered doses. Oral mucositis and dermatitis were scored using CTC v.2.0-based tables. Saliva was collected at baseline, right after end of irradiation, and at day 35. Results The measured dose distribution for protons (TM) and X-rays was very similar. Oral mucositis appeared earlier, had a higher score and was found in a higher percentage of mice after proton irradiation compared to X-irradiation. Dermatitis, on the other hand, had a similar appearance after protons and X-rays. Compared to controls, saliva production was lower right after termination of proton- and X-irradiation. The BP group demonstrated saliva recovery compared to the TM and X-ray group at day 35. Conclusion With lower delivered doses, proton irradiation resulted in similar skin reactions and increased oral mucositis compared to X-irradiation. This indicates that the relative biological effectiveness of protons for acute tissue responses in the mouse head and neck is greater than the clinical standard of 1.1. Thus, there is a need for further investigations of the biological effect of protons in normal tissues.
-
Zlygosteva, Olga; Juvkam, Inga; Aass, Hans Christian; Galtung, Hilde; Søland, Tine Merete & Malinen, Eirik
[Show all 7 contributors for this article]
(2023).
Cytokine Levels in Saliva Are Associated with Salivary Gland Fibrosis and Hyposalivation in Mice after Fractionated Radiotherapy of the Head and Neck.
International Journal of Molecular Sciences.
ISSN 1661-6596.
24(20).
doi:
10.3390/ijms242015218.
Full text in Research Archive
Show summary
Cytokines are mediators of inflammation that could lead to fibrosis. The aim was to monitor cytokine levels in saliva and serum after locally fractionated radiotherapy of the head and neck in mice and investigate associations with salivary gland fibrosis and hyposalivation. C57BL/6 mice were randomized to sham or X-ray irradiation of 66 Gy in 10 fractions over 5 days. Blood and saliva were collected on days −7, 5, 35, 80, and 105 following cytokine analysis. The harvested submandibular salivary gland was assessed for the presence of fibrosis. Decision tree regression analysis was used to investigate whether cytokine levels could predict late endpoints in terms of hyposalivation or fibrosis. Significant formation of fibrosis in gland tissue and reduced saliva production was found after irradiation. The pro-inflammatory cytokines IL-1α, TNF, TIMP1, G-CSF, KC, and MIP-1α showed increased levels in saliva in irradiated mice and a strong correlation with late endpoints. The decision tree analysis largely separated controls from irradiated animals, with IL-1α being the strongest predictor. Pro-inflammatory cytokines in saliva, but not in serum, were associated with late endpoints. This indicates that cytokine expression in saliva is a good biomarker for local salivary gland damage with IL-1α as the strongest single predictor.
-
Søland, Tine Merete; Solhaug, Maren Bråten; Bjerkli, Inger-Heidi; Schreurs, Olaf Joseph Franciscus & Sapkota, Dipak
(2022).
The prognostic role of combining Krüppel-like factor 4 score and grade of inflammation in a Norwegian cohort of oral tongue squamous cell carcinomas.
European Journal of Oral Sciences.
ISSN 0909-8836.
p. 1–11.
doi:
10.1111/eos.12866.
Full text in Research Archive
Show summary
Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor involved in inflammation, cancer development, and progression. However, the relationship between KLF4, inflammation, and prognosis in oral cancer is not fully understood. KLF4 expression levels were examined in a multicenter cohort of 128 oral squamous cell carcinoma (OSCC) specimens from the tongue (OTSCC) using immunohistochemistry. In two external KLF4 mRNA datasets (The Cancer Genome Atlas/The Genotype-Tissue Expression Portal), lower KLF4 mRNA expression was found in OSCC and head and neck squamous cell carcinomas (HNSCC) than in control oral epithelium. These data indicate that down-regulation of KLF4 mRNA is linked to OSCC/HNSCC progression. Using Cox-multivariate analysis, a significantly favorable 5-year disease-specific survival rate was observed for a subgroup of patients with a combination of high levels of KLF4 expression and inflammation. OSCC cell lines exposed to IFN-γ showed a significant upregulation of nuclear KLF4 expression, indicating a link between inflammation and KLF4 expression in OSCC. Overall, the current data suggest a functional link between KLF4 and inflammation. The combination of high KLF4 nuclear expression and marked/moderate stromal inflammation might be useful as a favorable prognostic marker for a subgroup of OTSCC patients.
-
Sofizadeh, Narmin; Bjerkehagen, Bodil; Solheim, Tore Torsteinson; Sapkota, Dipak & Søland, Tine Merete
(2022).
The spectrum and frequency of histopathological diagnosis of oral diseases in Oslo: Implications to oral pathology syllabus.
European journal of dental education.
ISSN 1396-5883.
00,
p. 1–7.
doi:
10.1111/eje.12808.
Full text in Research Archive
Show summary
Introduction To assure knowledge and skills in diagnostic work of oral diseases a continuously updated curriculum is essential. The first aim of the present study was to evaluate the spectrum and frequency of oral histopathological diagnoses signed out by oral pathologists at the Department of Pathology, Oslo University Hospital (OUS), Norway during a two-year period. The second aim was to compare the spectrum of histopathological diagnoses with the content of the current syllabus in oral pathology at the Faculty of Dentistry, University of Oslo (UiO). Materials and Methods In this retrospective cross-sectional study, all histological diagnosis signed out during 2015 and 2016 were included. All histopathological reports were analysed with regard to clinical information and histopathological diagnosis. The spectrum of histopathological diagnoses was compared to the diagnoses presented in lectures and courses for dental and dental hygienist students at UiO. Results Three thousand four hundred and two histopathological reports (47% males and 53% females) were included. The diagnoses were categorised into eight disease groups and the three most frequent disease groups were cysts, benign tumours/reactive lesions, and white, red, ulcerative and vesiculobullous lesions. The lateral periodontal cyst was more frequent than expected. Conclusions We conclude that a minor revision of the syllabus is needed, although the most frequent oral conditions presented in this study are well covered in the oral pathology teaching in Oslo. A more clinical related teaching approach should be considered by categorising oral diseases according to, for example location and age groups.
-
Juvkam, Inga; Zlygosteva, Olga; Arous, Delmon; Galtung, Hilde; Malinen, Eirik & Søland, Tine Merete
[Show all 7 contributors for this article]
(2022).
A preclinical model to investigate normal tissue damage following fractionated radiotherapy to the head and neck.
Journal of radiation research.
ISSN 0449-3060.
p. 1–9.
doi:
10.1093/jrr/rrac066.
Full text in Research Archive
Show summary
Abstract Radiotherapy (RT) of head and neck (H&N) cancer is known to cause both early- and late-occurring toxicities. To better appraise normal tissue responses and their dependence on treatment parameters such as radiation field and type, as well as dose and fractionation scheme, a preclinical model with relevant endpoints is required. 12-week old female C57BL/6 J mice were irradiated with 100 or 180 kV X-rays to total doses ranging from 30 to 85 Gy, given in 10 fractions over 5 days. The radiation field covered the oral cavity, swallowing structures and salivary glands. Monte Carlo simulations were employed to estimate tissue dose distribution. The follow-up period was 35 days, in order to study the early radiation-induced effects. Baseline and post irradiation investigations included macroscopic and microscopic examinations of the skin, lips, salivary glands and oral mucosa. Saliva sampling was performed to assess the salivary gland function following radiation exposure. A dose dependent radiation dermatitis in the skin was observed for doses above 30 Gy. Oral mucositis in the tongue appeared as ulcerations on the ventral surface of the tongue for doses of 75–85 Gy. The irradiated mice showed significantly reduced saliva production compared to controls. In summary, a preclinical model to investigate a broad panel of normal tissue responses following fractionated irradiation of the H&N region was established. The optimal dose to study early radiation-induced effects was found to be around 75 Gy, as this was the highest tolerated dose that gave acute effects similar to that observed in cancer patients.
-
Solheim, Tore Torsteinson; Wilberg, Petter & Søland, Tine Merete
(2022).
Lokalisert juvenil spongiotisk gingival hyperplasi: En relativt ny sykdomsenhet.
Norsk tannlegeforening Tidende.
doi:
10.56373/2022-9-5.
Full text in Research Archive
-
Pandey, Sushma; Søland, Tine Merete; Bjerkli, Inger-Heidi; Sand, Lars Peter; Petersen, Fernanda Cristina & Costea, Daniela Elena
[Show all 8 contributors for this article]
(2021).
Combined loss of expression of involucrin and cytokeratin 13 is associated with poor prognosis in squamous cell carcinoma of mobile tongue.
Head and Neck.
ISSN 1043-3074.
43(11),
p. 3374–3385.
doi:
10.1002/hed.26826.
Full text in Research Archive
Show summary
Background This study aimed to evaluate the prognostic significance of expression levels of involucrin (IVL), cytokeratin (CK)-10 and -13 at different intratumor sites (tumor center and invading area) of oral tongue squamous cell carcinoma (OTSCC). Methods IVL, CK13 and CK10 expression levels were examined in a multicenter cohort of 146 OTSCCs using immunohistochemistry. External mRNA datasets were used for expression analysis and/or to validate survival associations. Results External transcriptomic datasets showed downregulation of IVL and KRT13 in oral malignancies including OTSCC as compared to normal controls. The combined loss of IVL and CK13 expression at the invading core but not at the center core was significantly associated with poor differentiation and reduced 5-year overall survival. Multivariate Cox analysis confirmed the loss of CK13 and IVL expression to be an independent prognostic factor. Transcriptomic dataset corroborated immunohistochemistry results. Conclusions Combined expression levlels of IVL and CK13 might be useful as prognostic biomarkers in OTSCC.
-
Golburean, Olga; Hagen, Maria Helene; Uncuta, Diana; Tighineanu, Marcela; Manrikyan, Gayane & Vardanian, Izabella
[Show all 17 contributors for this article]
(2021).
Knowledge, opinions, and practices related to oral cancer prevention and oral mucosal examination among dentists in Moldova, Belarus and Armenia: a multi-country cross-sectional study.
BMC Oral Health.
21.
doi:
10.1186/s12903-021-02011-2.
Full text in Research Archive
Show summary
Introduction Moldova, Belarus, and Armenia are post-Soviet countries with a high rate of heavy smokers and a relatively high age-standardized incidence of oral cancer. However, to our knowledge, there is lack of available information on dentists’ knowledge on prevention of oral cancer in the countries in question. Accordingly, this study aimed to assess the knowledge, opinions, and practices related to oral cancer prevention and oral mucosal examination among dentists in Moldova, Belarus, and Armenia. Methods This was a multi-country, cross-sectional study based on a self-administered questionnaire. A structured questionnaire was distributed to 3534 dentists (797 in Chisinau, Moldova, 1349 in Minsk, Belarus, and 1388 in Yerevan, Armenia). Dentists' knowledge about risk factors for oral cancer development and its clinical picture, current practices and opinions with regard to oral mucosal screening and oral cancer prevention, and their consistency to perform oral mucosal examination were assessed. A knowledge score ranging from 0 to 14 points was generated based on each dentist’s answer to the questionnaire. Results A total of 1316 dentists responded, achieving an overall response rate of 37.2% (34.5% in Moldova; 52.3% in Belarus; 24.2% in Armenia). Most dentists in the three countries correctly identified tobacco (83.8–98.2%) and prior oral cancer lesions (84.0–96.3%) as risk factors for oral cancer. Most dentists correctly identified leukoplakia as a lesion with malignant potential (68.7% in Moldova; 88.5% in Belarus; 69.9% in Armenia), while erythroplakia was identified by much fewer in all three countries. Less than 52% of dentists identified the tongue, rim of tongue, and floor of mouth as the most common sites for oral cancer. The mean knowledge score for all countries combined was 7.5 ± 2.7. The most commonly reported barriers to perform oral mucosal examination were lack of training, knowledge, and experience. Conclusions This study highlights the need for improved oral cancer-related education and training on oral mucosal examination for dentists in Moldova, Belarus, and Armenia. Such skills are essential to enhance oral cancer prevention and to improve the prognostic outcome by early detection.
-
Sapkota, Dipak; Sharma, Sunita; Søland, Tine Merete; Braz-Silva, Paulo & Teh, Muy-Teck
(2021).
Expression profile of SARS-CoV-2 cellular entry proteins in normal oral mucosa and oral squamous cell carcinoma.
Clinical and Experimental Dental Research.
p. 1–6.
doi:
10.1002/cre2.510.
Full text in Research Archive
Show summary
Objective Besides angiotensin converting enzyme 2 (ACE2), an active involvement of proteases (FURIN and/or TMPRSS2) is important for cellular entry of SARS-CoV-2. Therefore, a simultaneous expression profiling of entry proteins in a tissue might provide a better risk assessment of SARS-CoV-2 infection as compared to individual proteins. In an attempt to understand the relative susceptibility of oral squamous cell carcinoma (OSCC) lesions as compared to the normal oral mucosa (NOM) for SARS-CoV-2 attachment/entry, this study examined the mRNA and protein expression profiles of ACE2, FURIN, and TMPRSS2 in the corresponding tissues using public transcriptomic and proteomics datasets. Methods and methods Public transcriptomic and proteomics datasets (the Cancer Genome Atlas (TCGA)/the Genotype-Tissue Expression (GTEx), the Human Protein Atlas (HPA), and two independent microarray datasets) were used to examine the expression profiles of ACE2, TMPRSS2 and FURIN in NOM and OSCC. Results ACE2, TMPRSS2, and FURIN mRNAs were detected in NOM, however, at lower levels as compared to other body tissues. Except for moderate up-regulation of FURIN, expression levels of ACE2 and TMPRSS2 mRNA were unchanged/down-regulated in OSCC as compared to the NOM. Conclusions These results indicate that NOM may serve as a possible site for SARS-CoV-2 attachment, however, to a lesser extent as compared to organs with higher expression levels of the SARS-CoV-2 entry proteins. However, the evidence is lacking to suggest that expression status of entry proteins predisposes OSCC lesions to additional risk for SARS-CoV-2 attachment/entry as compared to NOM.
-
Bjerkli, Inger-Heidi; Hadler-Olsen, Elin Synnøve; Nginamau, Elisabeth Sivy; Laurvik, Helene; Søland, Tine Merete & Costea, Daniela Elena
[Show all 8 contributors for this article]
(2020).
A combined histo-score based on tumor differentiation and lymphocytic infiltrate is a robust prognostic marker for mobile tongue cancer.
Virchows Archiv.
ISSN 0945-6317.
477(477),
p. 865–872.
doi:
10.1007/s00428-020-02875-9.
Full text in Research Archive
Show summary
We wanted to evaluate the prognostic value of common histopathological variables in a large cohort of patients with cancer in the mobile tongue as such information can be important for treatment stratification of the individual patient, especially for patients with low-stage disease. In addition, we wanted to investigate whether an alternative scoring model with fewer options would compromise the prognostic value. One hundred fifty patients with oral tongue squamous cell carcinomas that were treated in curative intent and with available HE-stained tumor sections were included. We reclassified all tumors and performed univariate and multivariate survival analyses of histopathological and clinical variables. For the complete cohort, lymph node status, grade of differentiation, perineural infiltration, and lymphocytic infiltration were independent prognosticators. In the low-stage disease group, independent prognostic factors were tumor size, grade of differentiation, and lymphocytic infiltrate. For patients with low-stage disease, a histo-score combining the scores for tumor differentiation and lymphocytic infiltrate identified a group of patients with particularly low survival, as patients with moderately or poorly differentiated tumors and little lymphocytic infiltrate had a less favorable 5-year survival outcome than patients in the high-stage disease group. This study shows that a histo-score combining tumor differentiation and lymphocytic infiltration should be given special consideration in treatment planning. Our results also illustrate that many variables can be scored with fewer options than previously suggested to increase their reproducibility, and still maintain their prognostic value.
-
-
Guerreiro, Eduarda Mazagão; Øvstebø, Reidun; Thiede, Bernd; Costea, Daniela Elena; Søland, Tine Merete & Galtung, Hilde
(2020).
Cancer cell line-specific protein profiles in extracellular vesicles identified by proteomics.
PLOS ONE.
15(9),
p. 1–20.
doi:
10.1371/journal.pone.0238591.
Full text in Research Archive
Show summary
Extracellular vesicles (EVs), are important for intercellular communication in both physiological and pathological processes. To explore the potential of cancer derived EVs as disease biomarkers for diagnosis, monitoring, and treatment decision, it is necessary to thoroughly characterize their biomolecular content. The aim of the study was to characterize and compare the protein content of EVs derived from three different cancer cell lines in search of a specific molecular signature, with emphasis on proteins related to the carcinogenic process. Oral squamous cell carcinoma (OSCC), pancreatic ductal adenocarcinoma (PDAC) and melanoma brain metastasis cell lines were cultured in CELLine AD1000 flasks. EVs were isolated by ultrafiltration and size-exclusion chromatography and characterized. Next, the isolated EVs underwent liquid chromatography-mass spectrometry (LC-MS) analysis for protein identification. Functional enrichment analysis was performed for a more general overview of the biological processes involved. More than 600 different proteins were identified in EVs from each particular cell line. Here, 14%, 10%, and 24% of the identified proteins were unique in OSCC, PDAC, and melanoma vesicles, respectively. A specific protein profile was discovered for each cell line, e.g., EGFR in OSCC, Muc5AC in PDAC, and FN1 in melanoma vesicles. Nevertheless, 25% of all the identified proteins were common to all cell lines. Functional enrichment analysis linked the proteins in each data set to biological processes such as “biological adhesion”, “cell motility”, and “cellular component biogenesis”. EV proteomics discovered cancer-specific protein profiles, with proteins involved in processes promoting tumor progression. In addition, the biological processes associated to the melanoma-derived EVs were distinct from the ones linked to the EVs isolated from OSCC and PDAC. The malignancy specific biomolecular cues in EVs may have potential applications as diagnostic biomarkers and in therapy.
-
Bjerkli, Inger-Heidi; Laurvik, Helene; Nginamau, Elisabeth Sivy; Søland, Tine Merete; Costea, Daniela Elena & Hov, Håkon
[Show all 9 contributors for this article]
(2020).
Tumor budding score predicts lymph node status in oral tongue squamous cell carcinoma and should be included in the pathology report.
PLOS ONE.
15:e0239783(9),
p. 1–13.
doi:
10.1371/journal.pone.0239783.
Full text in Research Archive
Show summary
Background The majority of oral cavity cancers arise in the oral tongue. The aim of this study was to evaluate the prognostic value of tumor budding in oral tongue squamous cell carcinoma, both as a separate variable and in combination with depth of invasion. We also assessed the prognostic impact of the 8th edition of the American Joint Committee on Cancer’s TNM classification (TNM8), where depth of invasion (DOI) supplements diameter in the tumor size (T) categorization. Methods Patients diagnosed with primary oral tongue squamous cell carcinoma were evaluated retrospectively. Spearman bivariate correlation analyses with bootstrapping were used to identify correlation between variables. Prognostic value of clinical and histopathological variables was assessed by Log rank and Cox regression analyses with bootstrapping using 5-year disease specific survival as outcome. The significance level for the hypothesis test was 0.05. Results One-hundred and fifty patients had available material for microscopic evaluation on Hematoxylin and Eosin-stained slides and were included in the analyses. Reclassification of tumors according to TNM8 caused a shift towards a higher T status compared to the previous classification. The tumor budding score was associated with lymph node metastases where 23% of the patients with low-budding tumors had lymph node metastases, compared with 43% of those with high-budding tumors. T-status, lymph node status, tumor budding, depth of invasion, and the combined tumor budding/depth of invasion score were all significantly associated with survival in univariate analyses. In multivariate analyses only N-status was an independent prognosticator of survival. Conclusion Reclassification according to TNM8 shifted many tumors to a higher T-status, and also increased the prognostic value of the T-status. This supports the implementation of depth of invasion to the T-categorization in TNM8. Tumor budding correlated with lymph node metastases and survival. Therefore, information on tumor budding can aid clinicians in treatment planning and should be included in pathology reports of oral tongue squamous cell carcinomas.
-
Steigen, Sonja Eriksson; Søland, Tine Merete; Nginamau, Elisabeth Sivy; Laurvik, Helene; Costea, Daniela Elena & Johannessen, Anne Christine
[Show all 10 contributors for this article]
(2020).
Grading of oral squamous cell carcinomas – Intra and interrater agreeability: Simpler is better?
Journal of Oral Pathology & Medicine.
ISSN 0904-2512.
49,
p. 630–635.
doi:
10.1111/jop.12990.
Full text in Research Archive
Show summary
Background: Numerous studies have been presented on histological grading of oral squamous cell carcinomas (OSCC) for predicting survival, but uncertainty of their usefulness rises due to discordances of results. A scoring system should be robust and well validated, and intra‐ and interrater agreement can be used as a tool to visualize the strength of reproducibility. Methods: Here, we present an intra‐ and inter‐observer study on evaluation of OSCC using some of the most common histopathological parameters. The observers were from different Norwegian university hospitals, and calibration to ensure accuracy was first performed. Percentage of the agreement was calculated for the score made by the individual observer at different times, as well as between pairs of observers. Results: The evaluation made by the same observer at two different time points (intrarater) correlated better than observations made by different participants (interrater). In an attempt to increase the rate of agreement, many of the parameters were either dichotomized into simply low‐ and high grade, or to a three‐tier system when more than three options in the original design. This increased the concurrence with 15.4% for the intrarater and with 23% for the interrater comparisons. Conclusion: High agreement for histopathological parameters can be difficult to obtain on hematoxylin and eosin staining in scoring systems with many options. A simpler system might be more advantageous to achieve higher degree of reproducibility.
-
Skaare, Anne B; Szyszko, Ewa Alicja; Herlofson, Bente Brokstad & Søland, Tine Merete
(2020).
Orofacial granulomatosis: a questionnaire study among Norwegian dental clinicians.
European Archives of Paediatric Dentistry.
ISSN 1818-6300.
21(5),
p. 557–564.
doi:
10.1007/s40368-020-00511-3.
Full text in Research Archive
-
Søland, Tine Merete; Bjerkli, Inger-Heidi; Georgsen, Jeanette B; Schreurs, Olaf Joseph Franciscus; Jebsen, Peter Wilhelm & Laurvik, Helene
[Show all 7 contributors for this article]
(2020).
High-risk human papilloma virus was not detected in a Norwegian cohort of oral squamous cell carcinoma of the mobile tongue.
Clinical and Experimental Dental Research.
7(1),
p. 70–77.
doi:
10.1002/cre2.342.
Full text in Research Archive
Show summary
Abstract
Objectives: The presence of and the causative role of high-risk human papilloma
virus (HPV) is a subject of controversy in oral squamous cell carcinoma (OSCC). The
disagreement can be related to the misclassification of OSCC as oropharyngeal squamous
cell carcinoma and/or lack of standard detection methods. This study aimed to
examine the presence of transcriptionally active high-risk HPV in a homogenous Norwegian
cohort of primary and second primary OSCC of the mobile tongue (oral
tongue squamous cell carcinoma—OTSCC).
Methods: Tissue microarrays containing formalin-fixed and paraffin-embedded cores
of 146 OTSCC from the anterior 2/3 of the tongue (n = 128 primary and
n = 18 second primary) from a multicentric Norwegian cohort were examined for the
presence of high-risk HPV by DNA- and RNA-in situ hybridization (ISH) assays and
p16 immunohistochemistry.
Results: Transcriptionally active HPV (E6/E7 mRNA) was not identified in any of the
OTSCC specimens. In parallel, no tumors were positive for HPV by DNA ISH.
Although, 61 (42%) OTSCC demonstrated p16 positivity with varying staining intensity
and subcellular localization, only two cases demonstrated strong and uniform
p16-staining (both cytoplasmic and nuclear) in >70% of cancer cells. The absence of
transcriptionally active high-risk HPV in this cohort of OTSCC indicates that high-risk
HPV is an unlikely causative factor in the present material.
-
Guerreiro, Eduarda; Vestad, Beate; Steffensen, Lilly Alice; Aass, Hans Christian Dalsbotten; Saeed, Muhammad & Øvstebø, Reidun
[Show all 9 contributors for this article]
(2018).
Efficient extracellular vesicle isolation by combining cell media modifications, ultrafiltration, and size-exclusion chromatography.
PLOS ONE.
13:e0204276(9),
p. 1–17.
doi:
10.1371/journal.pone.0204276.
Full text in Research Archive
Show summary
Extracellular vesicles (EVs) are a heterogeneous population of biological particles released by cells. They represent an attractive source of potential biomarkers for early detection of diseases such as cancer. However, it is critical that sufficient amounts of EVs can be isolated and purified in a robust and reproducible manner. Several isolation methods that seem to produce distinct populations of vesicles exist, making data comparability difficult. While some methods induce cellular stress that may affect both the quantity and function of the EVs produced, others involve expensive reagents or equipment unavailable for many laboratories. Thus, there is a need for a standardized, feasible and cost-effective method for isolation of EVs from cell culture supernatants. Here we present the most common obstacles in the production and isolation of small EVs, and we suggest a combination of relatively simple strategies to avoid these. Three distinct cell lines were used (human oral squamous cell carcinoma (PE/CA-PJ49/E10)), pancreatic adenocarcinoma (BxPC3), and a human melanoma brain metastasis (H3). The addition of 1% exosome-depleted FBS to Advanced culture media enabled for reduced presence of contaminating bovine EVs while still ensuring an acceptable cell proliferation and low cellular stress. Cells were gradually adapted to these new media. Furthermore, using the Integra CELLine AD1000 culture flask we increased the number of cells and thereby EVs in 3D-culture. A combination of ultrafiltration with different molecular weight cut-offs and size-exclusion chromatography was further used for the isolation of a heterogeneous population of small EVs with low protein contamination. The EVs were characterized by nanoparticle tracking analysis, immunoaffinity capture, flow cytometry, Western blot and transmission electron microscopy. We successfully isolated a significant amount of small EVs compatible with exosomes from three distinct cell lines in order to demonstrate reproducibility with cell lines of different origin. The EVs were characterized as CD9 positive with a size between 60–140 nm. We conclude that this new combination of methods is a robust and improved strategy for the isolation of EVs, and in particular small EVs compatible with exosomes, from cell culture media without the use of specialized equipment such as an ultracentrifuge.
-
Søland, Tine Merete & Brusevold, Ingvild Johnsen
(2014).
Prognostiske markører i kreftsvulster fra munnhulen – quo vadis?
Den norske tannlegeforenings Tidende.
ISSN 0029-2303.
p. 364–368.
Full text in Research Archive
Show summary
Plateepitelkarsinom i munnhulen er en alvorlig sykdom. Ca. 40
prosent av pasientene dør innen fem år etter at diagnosen er
stilt, men på diagnosetidspunktet kan vi ikke forutsi hvilke. To
prognosesystemer brukes i dag: TNM-systemet i klinikken og histologisk
gradering (WHO). Verktøyene kan si noe om prognose
for en gruppe pasienter, men er ikke gode nok til å forutsi prognosen
for den enkelte pasient. Mange forskningsgrupper, inkludert
vår egen, har prøvd å finne bedre prognostiske markører
uten å lykkes. Problemet er ikke spesifikt for munnhulekreft, men
gjelder de fleste krefttyper. Vi ønsker å plukke ut pasienter med
en forventet dårlig prognose fordi de vil trenge en annen
behandling og oppfølging enn pasienter med forventet god
prognose. I denne artikkelen presenterer vi funn fra vår oversiktsartikkel
i Histopathology (2013) (1). Vi har gått igjennom
172 artikler, publisert i perioden 2006–2012, som beskriver
molekylære prognostiske studier basert på immunhistokjemi
i orale plateepitelkarsinom. Konklusjonen er at det fortsatt ikke
finnes noen optimale prognostiske molekylære markører for
orale plateepitelkarsinomer. Dette skyldes at det generelt ikke
finnes noen form for standardisering av hverken studiene eller
metodene. Dermed er ikke studier og resultater reproduserbare.
I tillegg er ofte pasientutvalget for lite til at man kan trekke
generelle konklusjoner.
-
Søland, Tine Merete; Skarstein, Kathrine; Johannessen, Anne Christine & Solheim, Tore
(2014).
Biopsier i odontologisk praksis - håndtering og innsendelse.
Den norske tannlegeforenings Tidende.
ISSN 0029-2303.
124(9),
p. 734–738.
Full text in Research Archive
-
Søland, Tine Merete & Brusevold, Ingvild Johnsen
(2013).
Prognostic molecular markers in cancer - quo vadis?
Histopathology.
ISSN 0309-0167.
63(3),
p. 297–308.
doi:
10.1111/his.12184.
Full text in Research Archive
Show summary
Despite the tremendous number of studies of prognostic molecular markers in cancer, only a few such markers have entered clinical practise. The lack of clinical prognostic markers clearly reflects limitations in or an inappropriate approach to prognostic studies. This situation should be of great concern for the research community, clinicians and patients. In the present review, we evaluate immunohistochemical prognostic marker studies in oral squamous cell carcinomas (OSCC) from 2006 to 2012. We comment upon general issues such as study design, assay methods and statistical methods, applicable to prognostic marker studies irrespective of cancer type. The three most frequently studied markers in OSCC are reviewed. Our analysis revealed that most new molecular markers are reported only once. To draw conclusions of clinical relevance based on the few markers that appeared in more than one study was problematic due to between-study heterogeneity. Currently, much valuable tissue material, time and money are wasted on irrelevant studies.
-
-
-
Brusevold, Ingvild Johnsen; Husvik, Camilla; Schreurs, Olav Joseph F; Schenck, Karl; Bryne, Magne & Søland, Tine Merete
(2010).
Induction of invasion in an organotypic oral cancer model by CoCl2, a hypoxia mimetic.
European Journal of Oral Sciences.
ISSN 0909-8836.
118(2),
p. 168–176.
Full text in Research Archive
-
Kolltveit, Kristin Melkevik; Schreurs, Olav Joseph F; Østrem, Janet M; Søland, Tine Merete; Khuu, Cuong & Berge, Tone
[Show all 11 contributors for this article]
(2010).
Expression of the T-cell-specific adapter protein in oral epithelium.
European Journal of Oral Sciences.
ISSN 0909-8836.
118(2),
p. 159–167.
Full text in Research Archive
Show summary
The multifunctional T-cell-specific adapter protein (TSAd) was originally described in T cells but is also expressed in epithelial cells from the respiratory tract and in endothelium. In this study, we found expression of TSAd messenger RNA (mRNA) and protein in both human and murine oral mucosal epithelium as well as in human primary oral keratinocyte cell cultures. In TSAd(-/-) mice, the mucosa and skin appeared macroscopically normal, but severe disturbances were observed in the fine structures of the basal membrane and intercellular epithelial spaces upon analysis using transmission electron microscopy. Oral epithelial cells from TSAd(-/-) mice displayed decreased migration compared with cells from wild-type mice, whereas overexpression of TSAd in a human epithelial cell line resulted in impaired proliferation. This study is the first to show that TSAd is expressed in normal oral mucosa, that it is important for the normal ultrastructural morphology of the epithelium and the basal membrane, and that it is involved in the migration and proliferation of oral keratinocytes.
-
Brusevold, Ingvild Johnsen; Søland, Tine Merete; Khuu, Cuong; Christoffersen, Thoralf & Bryne, Magne
(2010).
Nuclear and cytoplasmic expression of Met in oral squamous cell carcinoma and in an organotypic oral cancer model.
European Journal of Oral Sciences.
ISSN 0909-8836.
118(4),
p. 342–349.
Full text in Research Archive
-
-
Søland, Tine Merete; Brusevold, Ingvild Johnsen; Koppang, Hanna Strømme; Schenck, Karl & Bryne, Magne
(2008).
Nerve growth factor receptor (p75NTR) and pattern of invasion predict poor prognosis in oral squamous cell carcinoma.
Histopathology.
ISSN 0309-0167.
53,
p. 62–72.
doi:
10.1111/j.1365-2559.2008.03063.x.
Full text in Research Archive
View all works in NVA
-
-
Rykkelid, Anne Marit; Sinha, Priyanshu Manojkumar; Folefac, Charlemagne Asonganyi; Horsman, Michael R.; Sørensen, Brita Singers & Søland, Tine Merete
[Show all 9 contributors for this article]
(2024).
Correction to: Combination of proton- or X-irradiation with anti-PDL1 immunotherapy in two murine oral cancers (Scientific Reports, (2024), 14, 1, (11569), 10.1038/s41598-024-62272-z).
Scientific Reports.
14(1).
doi:
10.1038/s41598-024-66148-0.
Full text in Research Archive
-
Bhattarai, Bishwa Prakash; Søland, Tine Merete; Schreurs, Olaf Joseph Franciscus; Hasséus, Bengt & Sapkota, Dipak
(2024).
Expression of Cell Cycle Regulating Proteins in Oral Leukoplakia.
Full text in Research Archive
-
-
-
-
Søland, Tine Merete; Wilberg, Petter; Pham, Maria H & Solheim, Tore Torsteinson
(2022).
Lokalisert juvenil spongiotisk gingival hyperplasi:
En relativt ny sykdomsenhet.
NTFs Tidende.
131(9).
Full text in Research Archive
-
Søland, Tine Merete; Andersen, Eivind; Tingberg, Marianne; Farran, Mirna; Haugstvedt, Åse & Solheim, Tore Torsteinson
(2022).
Oral syfilis er en sykdom som tannleger bør kjenne til.
Den norske tannlegeforenings Tidende.
ISSN 0029-2303.
132(5).
doi:
10.56373/2022-5-6.
Full text in Research Archive
-
Søland, Tine Merete; Wilberg, Petter; Pham, Maria & Solheim, Tore Torsteinson
(2022).
Lokalisert juvenil spongiotisk gingival hyperplasi: En relativt ny sykdomsenhet.
Norsk tannlegeforening Tidende.
doi:
10.56373/2022-9-5.
Full text in Research Archive
-
-
Skaare, Anne B; Herlofson, Bente Brokstad & Søland, Tine Merete
(2020).
Orofacial granulomatose og Crohns sykdom – et klinisk kasus og en litteraturgjennomgang.
Den norske tannlegeforenings Tidende.
ISSN 0029-2303.
130(11),
p. 914–920.
Full text in Research Archive
-
Søland, Tine Merete; Andersen, Eivind & Solheim, Tore
(2019).
Sår i munnhulen som ikke vil tilhele kan være traumatisk ulcerativt granulom med stromal eosinofili (TUGSE).
Den norske tannlegeforenings Tidende.
ISSN 0029-2303.
129,
p. 1008–1013.
Full text in Research Archive
-
-
Frettem, Åshild Kvammen; Edin, Nina Frederike J; Galtung, Hilde & Søland, Tine Merete
(2016).
Tumour associated Aquaporin-3 and hypoxia in an oral squamous cell carcinoma cell line.
Full text in Research Archive
-
Guerreiro, Eduarda; Vestad, Beate; Øvstebø, Reidun; Søland, Tine Merete & Galtung, Hilde
(2016).
Isolation of extracellular vesicles - towards understanding vesicles signaling pathway in oral squamous cell carcinoma cells.
Full text in Research Archive
-
Søland, Tine Merete; Frafjord, Roshi & Solheim, Tore
(2016).
Et tilfelle av sentralt ossifiserende fibrom.
Den norske tannlegeforenings Tidende.
ISSN 0029-2303.
116(10),
p. 780–782.
Full text in Research Archive
-
Søland, Tine Merete; Kjølle, Gry Karina & Solheim, Tore
(2016).
Oral melanotisk flekk - en kasuistikk.
Den norske tannlegeforenings Tidende.
ISSN 0029-2303.
p. 294–296.
Full text in Research Archive
-
Guerreiro, Eduarda; Vestad, Beate; Øvstebø, Reidun; Galtung, Hilde & Søland, Tine Merete
(2016).
Extracellular vesicles from oral squamous cell carcinoma cells in culture: isolation and characterization.
Full text in Research Archive
-
Guerreiro, Eduarda; Vestad, Beate; Øvstebø, Reidun; Galtung, Hilde & Søland, Tine Merete
(2016).
Extracellular vesicles from oral squamous cell carcinoma cells in culture: isolation and characterization.
Journal of Extracellular Vesicles.
Full text in Research Archive
-
Sletten, Elisabeth; Soleng, Kristina A; Søland, Tine Merete; Fløisand, Yngve & Herlofson, Bente Brokstad
(2015).
Kronisk oral transplantat-mot-vert sykdom,
en utfordring også for tannhelsepersonell?
Full text in Research Archive
-
Frettem, Åshild Kvammen; Ulekleiv, Camilla Husvik; Søland, Tine Merete & Galtung, Hilde
(2014).
The effect of hypoxia on aquaporin 3 expression and cell volume regulation in oral squamous cell carcinomas.
Acta Physiologica.
ISSN 1748-1708.
Full text in Research Archive
-
Frettem, Åshild Kvammen; Ulekleiv, Camilla Husvik; Søland, Tine Merete & Galtung, Hilde
(2014).
The effect of hypoxia on aquaporin 3 expression and cell volume regulation in oral squamous cell carcinomas.
Full text in Research Archive
-
Søland, Tine Merete; Ulekleiv, Camilla Husvik & Galtung, Hilde
(2014).
Hypoxia influences aquaporin 3 and migration in oral squamous cell carcinoma.
Full text in Research Archive
-
Brusevold, Ingvild Johnsen; Husvik, Camilla; Schreurs, Olav Joseph F; Schenck, Karl; Bryne, Magne & Søland, Tine Merete
(2010).
Induction of invasion in an organotypic oral cancer model by cobalt chloride, a hypoxia mimetic.
European Journal of Cancer.
ISSN 0959-8049.
8(5),
p. 149–149.
Full text in Research Archive
-
Brusevold, Ingvild Johnsen; Husvik, Camilla; Schreurs, Olav Joseph F; Schenck, Karl; Bryne, Magne & Søland, Tine Merete
(2010).
Induction of invasion in an organotypic oral cancer model by cobalt chloride, a hypoxia mimetic.
Full text in Research Archive
-
Brusevold, Ingvild Johnsen; Søland, Tine Merete; Khuu, Cuong; Christoffersen, Thoralf & Bryne, Magne
(2009).
Nuclear Met and p-p38 in oral squamous cell carcinoma and organotypic oral cancer model.
Full text in Research Archive
-
Brusevold, Ingvild Johnsen; Søland, Tine Merete; Khuu, Cuong; Christoffersen, Thoralf & Bryne, Magne
(2009).
Nuclear c-Met and p-p38 in oral sqamous cell carcinoma and organotypic oral cancer model.
Full text in Research Archive
-
Brusevold, Ingvild Johnsen; Søland, Tine Merete; Khuu, Cuong; Christoffersen, Thoralf & Bryne, Magne
(2008).
C-Met and p-p38 in oral cancer.
Full text in Research Archive
-
Søland, Tine Merete; Brusevold, Ingvild Johnsen; Koppang, Hanna Strømme; Schenck, Karl & Bryne, Magne
(2008).
p75NTR and pattern of invasion predict poor prognosis in oral squamous cell carcinomas.
Full text in Research Archive
-
Brusevold, Ingvild Johnsen; Søland, Tine Merete; Khuu, Cuong; Christoffersen, Thoralf & Bryne, Magne
(2008).
Nuclear c-Met and p-p38 at the invasive front of oral squamous cell carcinoma (OSCC.
Full text in Research Archive
-
Søland, Tine Merete; Brusevold, Ingvild Johnsen; Husvik, Camilla; Schreurs, Olav Joseph F; Schenck, Karl & Bryne, Magne
(2008).
Manipulation of invasion in a 3D-co-culture organotypic oral cancer model.
Full text in Research Archive
-
-
Brusevold, Ingvild Johnsen; Søland, Tine Merete; Khuu, Cuong & Bryne, Magne
(2008).
Nuclear c-Met and p-p38 at the invasive front of oral squamous cell carcinomas.
European Journal of Cancer.
ISSN 0959-8049.
6,
p. 76–76.
Full text in Research Archive
-
Søland, Tine Merete; Brusevold, Ingvild Johnsen; Koppang, Hanna Strømme; Schenck, Karl & Bryne, Magne
(2008).
p75NTR and pattern of invasion predict poor prognosis in oral squamous cell carcinomas.
European Journal of Cancer.
ISSN 0959-8049.
6,
p. 76–76.
Full text in Research Archive
-
-
Brusevold, Ingvild Johnsen; Søland, Tine Merete; Husvik, Camilla; Khuu, Cuong & Bryne, Magne
(2007).
Nerve growth factor receptor (p75 NTR) in an organotypic oral cancer model.
Full text in Research Archive
-
Brusevold, Ingvild Johnsen; Søland, Tine Merete; Husvik, Camilla; Khuu, Cuong & Bryne, Magne
(2007).
Nerve growth factor receptor (p75 NTR) in an organotypic oral cancer model.
Full text in Research Archive
-
-
Brusevold, Ingvild Johnsen; Søland, Tine Merete & Bryne, Magne
(2006).
Hepatocyte growth factor receptor in oral cancer.
Full text in Research Archive
-
-
-
-
-
-
-
Bryne, Magne; Søland, Tine Merete; Husvik, Camilla & Sudbø, Jon
(2004).
Concomitance of COX-2 up-regulation and genomic instability in precancers: a rationale for targeted use of coxibs to prevent oral cancer.
Full text in Research Archive
-
-
Søland, Tine Merete; Schreurs, Olav Joseph F; Husvik, Camilla; Koppang, Hanna Strømme & Bryne, Magne
(2003).
Selective COX-2 up-regulation in DNA aneuploid oral precancers; an opportunity for targeted preventive treatment of oral cancer.
Full text in Research Archive
-
Aase, Steinar Torbjørn; Koppang, Hanna Strømme & Søland, Tine Merete
(2003).
Oral Pathology in Norwegian Hospitals.
Full text in Research Archive
-
Bryne, Magne; Husvik, Camilla; Søland, Tine Merete; Kolltveit, Kristin Melkevik & Sudbø, Jon
(2003).
The invasion of malignant oral keratinocytes is inhibited by a COX-2 inhibitor.
Full text in Research Archive
-
Husvik, Camilla; Søland, Tine Merete; Kolltveit, Kristin Melkevik; Sudbø, Jon & Bryne, Magne
(2003).
Effect of COX-2 inhibitors on proliferation, invasion and migration of cell lines from oral squamous cell carcinoma.
Full text in Research Archive
-
Søland, Tine Merete; Sudbø, Jon; Schreurs, Olav Joseph F; Husvik, Camilla; Koppang, Hanna Strømme & Bryne, Magne
(2003).
Selective COX-2 up-regulation in DNA aneuploid oral precancers: an opportunity for targeted preventive treatment of oral cancers?
Full text in Research Archive
-
-
View all works in NVA
Published
Nov. 10, 2010 1:35 PM
- Last modified
Jan. 12, 2024 12:34 PM
