| 1. |
- Moskovszky, Linda, et al.
(författare)
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Analysis of giant cell tumour of bone cells for Noonan syndrome/Cherubism-related mutations.
- 2012
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 1600-0714 .- 0904-2512.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Giant cell tumour of bone (GCTB) is an osteolytic tumour which contains numerous osteoclast-like giant cells and a proliferation of mononuclear stromal cells (MSC). Giant cell-rich osteolytic lesions can also develop in the jaw bones in Noonan syndrome, a cherubism-like developmental abnormality that is transmitted in an autosomal dominant fashion, often because of mutation in the PTPN11 or BRAF genes. Methods: We screened GCTBs for mutations in PTPN11 and BRAF to determine whether GCTBs develop through alterations of genes involved in Noonan syndrome. MSC were isolated from 10 GCTBs. Results: Chromosome banding analysis of these cells revealed telomeric associations (tas) in 7 of the 10 cases. Thus, the cultured cells expressed a cytogenetic abnormality typically found in short-term cultures from GCTBs. Sequencing of DNA extracted from the seven GCTB-derived MSC cultures displaying tas did not identify any mutation in PTPN11 or in exons 9-15 of BRAF. Conclusion: Our findings indicate that the molecular pathways involved in GCTB development are different from those causing Noonan syndrome. The method for isolating and culturing GCTB stromal cells described in this study generated a population of MSC that contained tas, indicating that it is useful for obtaining stromal cells from GCTB and other giant cell-rich lesions, such as giant cell reparative granuloma, for genetic and other studies.
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| 2. |
- Abtahi, Jahan, et al.
(författare)
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Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone
- 2012
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley and Sons. - 0904-2512 .- 1600-0714. ; 41:6, s. 494-499
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Tidskriftsartikel (refereegranskat)abstract
- J Oral Pathol Med (2012) 41: 494499 Background: Bisphosphonate-related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate-related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis. Material and methods: Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 mu g/kg per day alendronate; Groups III and IV, 200 mu g/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups IIII. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH). Results: All animals in the alendronate plus dexamethasone groups developed large ONJ-like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups. Conclusion: Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ-like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.
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| 3. |
- Danielsson, Karin, et al.
(författare)
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Altered expression of miR-21, miR-125b, and miR-203 indicates a role for these microRNAs in oral lichen planus
- 2012
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 41:1, s. 90-95
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oral lichen planus (OLP), which is a chronic inflammatory disease of the oral mucosa with unknown etiology, affects about 2% of the population. MicroRNAs are small non-coding RNAs involved in normal processes such as development and differentiation as well as progression of human diseases. The aim of this study was to investigate the expression of miR-21, miR-125b, and miR-203 and to compare RNA levels of their potential targets, the tumor suppressor p53 and its relative p63, both known to be deregulated in OLP. Methods: In biopsies from 20 patients with OLP and 20 age- and sex-matched healthy controls, epithelium was laser dissected and analyzed for the expression of miR-21, miR-125b, miR-203, p53, and p63 using qRT/PCR. Results: Increased expression of miR-21 and miR-203, decreased expression of miR-125, and down-regulation of p53 and ΔNp63 RNA were seen in OLP compared to normal oral mucosa. When comparing microRNA expression to levels of p53 and p63 RNA, a significant negative correlation was seen between ΔNp63 and miR-203 and between miR-21 and p53, respectively. Conclusion: Results indicate a role for the studied microRNAs in changes seen in OLP.
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| 4. |
- Danielsson, Karin, et al.
(författare)
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Increased expression of Smad proteins, and in particular Smad3, in oral lichen planus compared to normal oral mucosa
- 2010
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 39:9, s. 639-644
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Tidskriftsartikel (refereegranskat)abstract
- Backgound: Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa which the World Health Organisation (WHO) considers a premalignant condition. One step in malignant development is so called epithelial mesenchymal transition (EMT), a process whereby epithelial cells acquire mesenchymal characteristics. EMT occurs during embryogenesis and wound healing but also in some human diseases such as cancer and fibrosis. A factor known to induce EMT is transforming growth factor-beta (TGF-beta), which uses the Smad proteins as mediators for its signalling. TGF-beta is also often over-expressed in squamous cell carcinoma of the head and neck (SCCHN). Methods: In the present study we mapped expression of Smad proteins in OLP lesions by immunohistochemistry, and compared to expression in normal and sensitive oral mucosa. The latter group of patients had developed SCCHN after shorter or longer periods of diffuse oral symptoms. The aim was to see if there were any signs of EMT related changes in the OLP lesions, as judged by changes in the TGF-beta pathway. Conclusion: Changes in the TGF-beta pathway related to EMT are seen in the very earliest stages of oral malignancy and become more severe as lesions progress.
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| 5. |
- Ebrahimi, Majid, 1963-, et al.
(författare)
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Decreased expression of p63 in oral lichen planus and graft-vs.-host disease associated with oral inflammation.
- 2006
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 35:1, s. 46-50
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oral lichen planus (OLP) and graft-vs.-host disease (GVHD) are conditions with increased risk of malignant transformation to squamous cell carcinoma of the head and neck (SCCHN). The p63 gene encodes six different proteins and is expressed at high levels in SCCHN. METHODS: Biopsies from patients diagnosed with OLP and GVHD were analysed for p63 protein expression using antibodies distinguishing between the major isoforms expressed in normal epithelia, in parallel with biopsies from normal buccal mucosa and SCCHN. RESULTS: In OLP and GVHD a decreased expression of all p63 isoforms was seen, while expression of p53 protein was upregulated, compared with normal mucosa. In SCCHN, p63 was abundantly expressed and some tumours showed strong p53 staining, suggestive of p53 mutation. CONCLUSIONS: Decreased p63 and increased p53 expression in OLP and GVHD indicates a coordinated action of these two related proteins to protect the oral mucosae from the damaging effects of underlying inflammation. In SCCHN disruption of the TP53 gene and overrepresentation of certain p63 isoforms
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| 6. |
- Ebrahimi, Majid, et al.
(författare)
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Detection of antibodies against p63 and p73 isoforms in sera from patients diagnosed with oral lichen planus.
- 2007
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 36:2, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oral lichen planus (OLP) is a chronic inflammatory disease of oral mucosa. Despite numerous publications and intense research, the etiology of OLP is still unknown, however, autoimmunity as a possible causative factor has been discussed. Methods: In the present study sera from 20 patients clinically and histologically diagnosed with OLP were analyzed for antibodies directed toward p53, p63, and p73 using Western blot. Results: Sera from two patients reacted with all six p63 isoforms, and one also with p73. The strongest reaction was noted against the TAp63beta protein, which is the most potent transactivator of all p63 proteins and is implicated in the differentiation of stratified epithelia. Conclusions: This is the first demonstration of antibodies directed against all p63 and some p73 isoforms in sera from patients diagnosed with OLP.
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| 7. |
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| 8. |
- Ebrahimi, Majid, et al.
(författare)
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Oral lichen planus and the p53 family : what do we know?
- 2011
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 40:4, s. 281-285
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Tidskriftsartikel (refereegranskat)abstract
- J Oral Pathol Med (2010) Oral lichen planus (OLP) is a relatively common chronic disease of the oral mucosa for which the aetiopathogenesis is not fully understood. It mainly affects middle aged and elderly. The finding of autoantibodies against p63, a member of the p53 family, is a strong indication of autoimmunity as a causative or contributing factor. The WHO classified OLP as a potentially malignant disorder, but still there is an ongoing debate in the literature on this subject. The TP53 gene encodes a tumour suppressor protein that is involved in induction of cell-cycle arrest or apoptosis of DNA-damaged cells. The p63 gene encodes six different proteins that are crucial for formation of the oral mucosa and skin. The coordinated stabilization of p53 and decreased expression of p63 seen in OLP cause induction of apoptosis enabling removal of DNA-damaged cells. In view of the complexity of cancerogenesis, no firm statement can at present be made about the relevance of the observed relationship between p53 and p63 and the possible malignant transformation of OLP.
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| 9. |
- Ebrahimi, Majid, et al.
(författare)
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The use of a novel ELISA method for detection of antibodies against p63 in sera from patients diagnosed with oral and/or genital and skin lichen planus.
- 2010
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714.
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Tidskriftsartikel (refereegranskat)abstract
- Lichen planus is a chronic inflammatory disease of mucosa and skin affecting approximately 1-2% of the adult population. Autoimmunity has been implicated in the etiology of this disease, and recently we detected antibodies directed against all six p63 isoforms in sera from 2 out of 20 patients diagnosed with oral lichen planus (OLP) using Western blot analysis. Here we have developed an ELISA method for screening sera for presence of autoantibodies directed against p63. Using the same sera as previously analysed, we show that the optical density ratios for sera from the two patients with known autoantibodies was considerably higher compared to mean optical density ratios for all samples as well as controls analysed. Applying this novel ELISA technique for screening of sera from an additional group of 46 patients with oral and/or genital or skin lichen and 43 matched controls, we detected another three patients with autoantibodies against the p63 proteins. These data are discussed together with the observation that all five patients with detectable p63 autoantibodies from our two studies had clinically severe disease symptoms.
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| 10. |
- Farnebo, Lovisa, et al.
(författare)
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Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines
- 2011
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley and sons. - 0904-2512 .- 1600-0714. ; 40:10, s. 739-746
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines. METHODS: The expression of epidermal growth factor receptor, survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse. RESULTS: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (r=0.36, p=0.02). The combination of survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r=0.553, p<0.001). CONCLUSION: These data indicate that the intrinsic radiosensitivity of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.
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| 11. |
- Flink, Håkan, et al.
(författare)
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Effect of oral iron supplementation on unstimulated salivary flow rate : a randomized, double-blind, placebo-controlled trial
- 2006
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 35:9, s. 540-547
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Tidskriftsartikel (refereegranskat)abstract
- Background: No treatment is known to permanently increase salivary flow in patients with hyposalivation. The objective of this study was to investigate the effect of iron supplementation on salivary flow rate. Methods: A double-blind, randomized, placebo-controlled trial was carried out on 50 individuals with a low unstimulated whole salivary flow rate and low serum ferritin. Half the individuals received 60 mg iron orally twice a day for 3 months, while the other half received placebo. Results: No statistically significant difference was found between the groups after treatment for the unstimulated flow rate and in the subjective assessments of oral dryness. The serum ferritin values increased significantly in the iron group but not in the placebo group. Conclusions: Oral supplementation with iron for 3 months has no effect on salivary flow rate among individuals with hyposalivation and low serum ferritin values.
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| 12. |
- Hedner, E, et al.
(författare)
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Primary herpes simplex virus (type 1) infection delays healing of oral excisional and extraction wounds in the rat
- 1990
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 19:10, s. 471-476
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Tidskriftsartikel (refereegranskat)abstract
- The effect of acute herpes simplex virus type 1 (HSV-1) infection on the healing process of intraoral wounds and tooth extraction sockets in the rat was studied. A standardized size of the buccal mucosa was excised and molars were extracted and a HSV-1 suspension was topically applied. The virus infected wounds were clinically characterized by erythema and swelling and histologically by heavy inflammation cell infiltrate and abscesses during the first week. The acute HSV-1 infection was found to significantly delay healing of both types of wounds by 3 days. Antiviral treatment with acyclovir (ACV) decreased the degree of inflammation and improved healing of the infected wounds. The present results indicate a delayed and disturbed healing of wounds in the oral cavity in the presence of HSV-1. The findings may have a clinical significance for primary or latent HSV-1 infections in conjunction with surgical intervention in the oral cavity.
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| 13. |
- Hedner, E, et al.
(författare)
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Recrudescence of herpes simplex virus type 1 in latently infected rats after trauma to oral tissues
- 1993
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 22:5, s. 214-220
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Tidskriftsartikel (refereegranskat)abstract
- Tooth extraction in rats was used to trigger a latent HSV-1 infection. HSV-1 was inoculated unilaterally in the rat palates. Eight weeks later two molars were removed bilaterally. The trigeminal ganglia were co-cultivated and HSV-1 was isolated from 63% of the ganglia on the infected sides but from only 11% on control sides. The immune response pattern was analysed by immunoblotting of rat serum, and strong reactivity to HSV-1 specific cell polypeptides and glycoproteins (ICP6, gC, pgC, gD) was seen after reactivation. The extraction sockets were histopathologically evaluated and showed healing on the infected side in 26% compared to 63% in contralateral control sockets. The effect of acyclovir (ACV) treatment was elucidated and was found to influence the subsequent development of antibodies and to promote healing of the sockets. Vesiculation in intra- and subepithelial tissue was present on the infected side in 58% but in only 12% of ACV-treated animals. The present study in rats has shown that a latent HSV-1 infection can be established and reactivated by tooth extraction. Reactivation resulted in delayed healing of sockets on the latently infected side but not on the contralateral control side. HSV-1 reactivation was demonstrated serologically by immunoblotting. Healing was significantly promoted by administration of ACV, which also supports the contention that HSV-1 interferes with the healing process.
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| 14. |
- Hirsch, Jan M, et al.
(författare)
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A clinical, histomorphological and histochemical study on snuff-induced lesions of varying severity
- 1982
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 11:5, s. 387-398
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Tidskriftsartikel (refereegranskat)abstract
- The oral lesions in 50 habitual snuff-dippers were graded on a four-point scale. The patients' tobacco and drinking habits were studied by means of a questionnaire. From each patient a biopsy was taken for histomorphological and histochemical analysis. A correlation between snuff habits and the clinical degrees was found, as well as between the snuff habits and certain superficial and deeply located cell changes. The incidence of keratinized lesions, sialadenitis and slight dysplasia (based on subjective evaluation under a light microscope) was higher than previously reported. Presence of dysplastic changes could not be predicted by means of the parameters which characterise the snuff habit or from the clinical grade. The histomorphological and histochemical results were interpreted as showing that the mucosa react to snuff inducing hyperplasia in the basal cell layers. In the surface layer indications of lethal damage were found. The overall stromal reaction to snuff was weak. However, the salivary glands and excretory ducts exhibited degenerative changes which were found to be more severe than the pathological changes in the surface epithelium.
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| 15. |
- Hirsch, Jan M, et al.
(författare)
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Effect of long-term application of snuff on the oral mucosa : an experimental study in the rat
- 1983
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 12:3, s. 187-198
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Tidskriftsartikel (refereegranskat)abstract
- The long-term effect of snuff exposure was studied in Sprague-Dawley rats using a surgically-created test canal in the lower lip to retain snuff. The rats received standard snuff (n = 42) and highly alkaline snuff (n = 10) for 9-22 months, whereupon they were killed. Untreated rats with identical test canals (n = 15) served as controls. A complete post-mortem examination was performed. One rat exposed to standard snuff for 9 months developed a squamous cell carcinoma of the oral cavity. However, exposure to standard snuff usually resulted in a mild to moderate hyperplasia of the epithelium, hyperorthokeratosis and acanthosis. Rats exposed to snuff for 18-22 months showed vacuolated cells penetrating deeper into the epithelium with hyperplastic and atrophic lesions. In a few rats, severe dysplastic changes developed in the crevicular epithelium. Rats exposed to alkaline snuff differed little from the first group except that there was focally atrophic and ulcerated epithelium and less fibrosis. Pathological findings outside the oral cavity were rare. Squamous cell hyperplasia of the forestomach was found in rats exposed to snuff for 18-22 months, possibly caused by ingested snuff. In conclusion, this study has shown that exposure of rats to snuff for 10-16 hours per day 5 days a week for most of their life-span resulted in lesions mainly restricted to the epithelium and the underlying connective tissue of the surgically created test canal.
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| 16. |
- Hirsch, Jan M, et al.
(författare)
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The reversibility of the snuff-induced lesion : an experimental study in the rat
- 1986
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 15:10, s. 540-543
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Tidskriftsartikel (refereegranskat)abstract
- Snuff lesions were induced in 30 rats. Ten of the snuff-exposed rats were killed immediately after 13 months snuff exposure, as were the 10 control animals. Ten rats were killed 1 month and 10 rats 4 months after the snuff administration had ceased. The rats exposed to snuff for 13 months exhibited hyperplastic, hyperorthokeratotic epithelium with focal mild atypia, focal ulcerations and marked subepithelial fibrosis. These changes were markedly reduced or absent in rats exposed to snuff and killed after a snuff-free interval of 1 or 4 months. Similar differences between the test-groups were seen in the epithelium lining the gingival sulcus of the lower incisors. This area seems to be more sensitive to chemical exposure than the oral mucosa proper as more severe microscopical changes were seen here. Snuff exposure results in the development of a hyperplastic, reactive, reversible lesion of the oral mucosa, suggesting that snuff predominantly has promoting activity when administered for a relatively short interval of time.
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| 17. |
- Jalouli, Jamshid, et al.
(författare)
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Presence of human papilloma virus, herpes simplex virus and Epstein-Barr virus DNA in oral biopsies from Sudanese patients with regard to toombak use
- 2010
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 39:8, s. 599-604
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Tidskriftsartikel (refereegranskat)abstract
- J Oral Pathol Med (2010) Using PCR/DNA sequencing, we investigated the prevalence of human papillomavirus (HPV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) DNA in brush biopsies obtained from 150 users of Sudanese snuff (toombak) and 25 non-users of toombak in formalin-fixed paraffin-embedded tissue samples obtained from 31 patients with oral dysplasias (25 toombak users and 6 non-users), and from 217 patients with oral cancers (145 toombak users and 72 non-users). In the brush tissue samples from toombak users, HPV was detected in 60 (40%), HSV in 44 (29%) and EBV in 97 (65%) of the samples. The corresponding figures for the 25 samples from non-users were 17 (68%) positive for HPV, 6 (24%) positive for HSV and 21 (84%) for EBV. The formalin-fixed samples with oral dysplasias were all negative for HPV. In the 145 oral cancer samples from toombak users, HPV was detected in 39 (27%), HSV in 15 (10%) and EBV in 53 (37%) of the samples. The corresponding figures for the samples from non-users were 15 (21%) positive for HPV, 5 (7%) for HSV and 16 (22%) for EBV. These findings illustrate that prevalence of HSV, HPV and EBV infections are common and may influence oral health and cancer development. It is not obvious that cancer risk is increased in infected toombak users. These observations warrant further studies involving toombak-associated oral lesions, to uncover the possible mechanisms of these viral infections in the development of oral cancer, and the influence of toombak on these viruses.
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| 18. |
- Jedlinski, Adam, et al.
(författare)
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EGFR status and EGFR ligand expression influence the treatment response of head and neck cancer cell lines
- 2013
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley and Sons. - 0904-2512 .- 1600-0714. ; 42:1, s. 26-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: Combination treatment (chemoradiotherapy) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems. A high level of epidermal growth factor receptor (EGFR) has been associated with a more aggressive phenotype as well as decreased responsiveness to radio- or chemotherapy. We examined the role of EGFR status and EGFR ligand expression for the treatment response. Methods: Intrinsic sensitivity to radiotherapy, cisplatin, and cetuximab treatments was investigated in 25 HNSCC cell lines. EGFR gene copy number, mRNA and protein expression, EGFR and Akt phosphorylation status, and mRNA expression of the EGFR ligands were analyzed using quantitative PCR and ELISA and assessed for their impact on treatment sensitivity. Results: Different treatment modalities yielded great diversity in outcome; of note, cetuximab treatment stimulated growth in one cell line. When treatments were combined primarily additive effects were observed. While radioresistance tended to be associated with a high level of phosphorylated EGFR (pEGFR; P = 0.09), cetuximab-resistant cells had low levels of pEGFR (P = 0.13). The three most cetuximab-sensitive cell lines had high EGFR gene copy numbers. Furthermore, cetuximab treatment response was significantly correlated with epiregulin mRNA expression (r = -0.408, P = 0.043). Cisplatin-resistant tumor cells expressed significantly lower levels of EGFR protein (P = 0.04) compared to cisplatin-sensitive cells and tended to have lower levels of phosphorylated Akt (pAkt; P = 0.13) and lower expression levels of amphiregulin (P = 0.18). Conclusions: Epidermal growth factor receptor status and ligand expression influence the treatment sensitivity of HNSCC cells and may be useful as predictive markers.
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| 19. |
- Kragelund, C, et al.
(författare)
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Scandinavian fellowship for oral pathology and oral medicine : statement on oral pathology and oral medicine in the European dental curriculum
- 2010
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 39:10, s. 800-801
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: For many years, dentists have migrated between the Scandinavian countries without an intentionally harmonized dental education. The free movement of the workforce in the European Union has clarified that a certain degree of standardization or harmonization of the European higher education acts, including the dental education, is required. As a result of the Bologna process, the Association for Dental Education in Europe and the thematic network DentEd have generated guidelines in the document 'Profile and Competences for the European Dentist' (PCD). This document is meant to act as the leading source in revisions of dental curricula throughout Europe converging towards a European Dental Curriculum. In order to render the best conditions for future curriculum revisions providing the best quality dentist we feel obliged to analyse and comment the outlines of oral pathology and oral medicine in the PCD.METHODS: The representatives agreed upon definitions of oral pathology and oral medicine, and competences in oral pathology and oral medicine that a contemporary European dentist should master. The competences directly related to oral pathology and oral medicine were identified, within the PCD.RESULTS: The subject representatives suggested eighteen additions and two rewordings of the PCD, which all were substantiated by thorough argumentation.PERSPECTIVES: Hopefully, this contribution will find support in future revisions of the PCD in order to secure the best quality dental education.
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| 20. |
- Larsson, P A, et al.
(författare)
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Snuff tumorigenesis : effects of long-term snuff administration after initiation with 4-nitroquinoline-N-oxide and herpes simplex virus type 1
- 1989
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 18:4, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- The tumor promoting effects of snuff was studied in Lewis rats initiated with 4-nitroquinoline-N-oxide (4-NQO) and Sprague Dawley rats repeatedly inoculated with herpes simplex virus type 1 (HSV-1). The test substances were administered in a surgically created canal in the lower lips of the rats. There were 15 rats in each test group and 10 rats in the control group. In the groups treated with 4-NQO and 4-NQO + snuff, 8 and 12 tumors (5 and 9 malignant) were found, respectively. In the group subjected to HSV-1 only, 3 tumors were found (2 malignant), in the group subjected to snuff only, 4 tumors were found (3 malignant) and in the group subjected to the combination of HSV-1 and snuff, 13 tumors were found (7 malignant). In the control group only one malignancy was found. The study did not show any promoting effects of snuff in the oral cavity after initiation with 4-NQO. Neither was there any increase in the number of oral tumors in rats treated with HSV-1 and snuff. However, there was a marked increase in the number of malignant tumors outside the oral cavity in the group treated with HSV-1 and snuff, underlining the importance of interactions between these two agents in the development of malignant lesions.
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| 21. |
- Larsson, Åke, et al.
(författare)
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A Case of Multiple AOT-like Jawbone Lesions in a Young Patient - a New Odontogenic Entity?
- 2003
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 32:1, s. 55-62
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We assessed the immunohistochemical profile of an unusual case of multiple similarly looking tumors in the jawbone of a young patient. Histologically, the tumors exhibited features of adenomatoid odontogenic tumor (AOT) and adenomatoid dentinoma but showed no resemblance to any other defined odontogenic tumor entities. They expressed high amounts of cytokeratin (CK) 8 and 14 together with some Vimentin. A small rim of peripheral cells showed CK 5, 17, and 19 reactivity. Also, these lesions expressed some bcl-2 as well as p53 and Ki67. Histologically and immunohistochemically, the unusual multiple lesions differed in details from a simultaneously examined group of 24 classical AOT cases, suggesting that they may represent a hitherto less well-defined odontogenic tumor entity.
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| 22. |
- Lundqvist, Lotta, et al.
(författare)
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The importance of stromal inflammation in squamous cell carcinoma of the tongue
- 2012
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley-Blackwell. - 0904-2512 .- 1600-0714. ; 41:5, s. 379-383
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Tidskriftsartikel (refereegranskat)abstract
- Background: Histological risk assessment evaluating worst pattern of tumour invasion (WPOI), and lymphocytic response (LR), has previously been shown to be of prognostic significance in squamous cell carcinomas of the head and neck (SCCHN). SCCHN is a heterogeneous group of tumours including tumours located in the oral cavity, of which the majority is located in the tongue. Methods: Haematoxylin/eosin-stained slides from diagnostic biopsies from 94 cases of SCC on the tongue were evaluated for WPOI and LR. Within the inflammatory infiltrate, the percentage of eosinophilic granulocytes was also estimated. Results were correlated with clinical data such as response to treatment and recurrence. Results: For WPOI the majority of patients, 84%, showed small invasive tumours islands with a size <15 cells (grade 4). No correlation with survival, response to treatment or recurrence was seen for WPOI. More than half of the patients showed a dense lymphocytic infiltrate, a factor that was significantly correlated with complete response to radio therapy. Of the patients with dense lymphoid infiltrate, the majority, 63%, did not either have a recurrence. No significant correlation with recurrence, response to treatment or any other factor was seen for presence of eosinophils. Conclusions: Data clearly showed that tongue tumours have a split invasive growth pattern and an intense inflammatory response at the tumour interface. Results also indicated that evaluation of the intensity of the inflammatory infiltrate at the tumour interface in tongue SCC could provide information of potential importance for choice of treatment and prognosis.
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| 23. |
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| 24. |
- Nylander, Elisabet, et al.
(författare)
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Changes in miRNA expression in sera and correlation to duration of disease in patients with multifocal mucosal lichen planus.
- 2012
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 41:1, s. 86-89
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mucosal lichen planus is a severe variant of lichen planus, Lichen planus (LP), which in many ways affect patients' lives. The aetiology is not fully understood, and there is no treatment clearing the disease once and for all. Oral LP has by the WHO been classified as a precancerous lesion. Micro-RNAs, miRNAs, are non-coding, small single-stranded RNAs involved in biological processes like apoptosis, proliferation, differentiation, metastasis, angiogenesis and immune response. Methods and Results: In sera from 30 patients with multifocal mucosal LP, 15 miRNAs were identified as significantly differentially expressed compared with controls. The three most up-regulated miRNAs are all connected to oral squamous cell carcinoma or epithelial carcinoma in general. Discussion: Even if no specific LP-associated miRNA profile was found, data clearly indicate that miRNAs could play a role in the earlier phases of lichen planus.
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| 25. |
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| 26. |
- Ryott, M, et al.
(författare)
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Cyclooxygenase-2 expression in oral tongue squamous cell carcinoma
- 2011
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Ingår i: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. - : Wiley. - 1600-0714. ; 40:5, s. 385-389
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Tidskriftsartikel (refereegranskat)
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| 27. |
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| 28. |
- Sundelin, Kaarina, et al.
(författare)
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Effects of cisplatin, interferon-alpha and 13-cis retinoic acid on the expression of Fas (CD95), intercellular adhesion molecule-1 (ICAM-1) and epidermal growth factor receptor (EGFR) in oral cancer cell lines
- 2007
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Ingår i: Journal of Oral Pathology & Medicine. - : Blackwell Publishing. - 0904-2512 .- 1600-0714. ; 36:3, s. 177-183
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies showed that many chemotherapeutic agents can induce immuno-suppression at therapeutic drug concentrations whereas low drug doses induce immuno-augmentation.Methods: The effect of low-dose cisplatin, interferon-alpha, and 13-cis retinoic acid on receptors involved in immune-mediated apoptosis (Fas/CD95), cell growth (epidermal growth factor receptor) and lymphocyte adhesion (intercellular adhesion molecule-1) was investigated in two oral cancer cell lines (UT-SCC-20A and UT-SCC-24A). Different methods for cell preparation were studied: mechanical and enzymatic detachment, and culture on chamber slides. Receptor expression was investigated using immunohistochemical staining. The amount of soluble and cell-bound Fas was determined with the ELISA technique, and the functional relevance of Fas expression, apoptosis induction, was analyzed.Results: Cisplatin enhanced cytoplasm and membrane staining for Fas in both cell lines. After cisplatin treatment, the amount of soluble Fas was increased in UT-SCC-20A cultures, but no effect was observed in the UT-SCC-24A cell line. Apoptosis, measured as enhanced caspase-3 activity, was induced by an agonistic Fas antibody (CH11) after cisplatin treatment in UT-SCC-24A cells.Conclusions: Low-dose cisplatin treatment enhanced Fas expression in both cell lines and increased susceptibility to apoptosis in one of them.
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| 29. |
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| 30. |
- Ansell, Anna, et al.
(författare)
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Epidermal growth factor is a biomarker for poor cetuximab response in tongue cancer cells
- 2016
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley-Blackwell. - 0904-2512 .- 1600-0714. ; 45:1, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidermal growth factor receptor (EGFR) is a target for treatment in tongue cancer. Here, EGFR ligands were evaluated for their potential uses as predictive biomarkers of cetuximab treatment response.Methods: In three tongue cancer cell lines the influences of epidermal growth factor (EGF), amphiregulin (AR), and epiregulin (EPR) on tumour cell proliferation and cetuximab response were evaluated by the addition of recombinant human (rh) proteins or the siRNA-mediated downregulation of endogenous ligand production.Results: EGF or AR downregulation suppressed the proliferation of all investigated cell lines. Furthermore, all cell lines displayed increased cetuximab resistance upon the addition of rhEGF, whereas EGF silencing resulted in an improved cetuximab response in one cell line.Conclusions: Our data suggest that EGF and AR are critical components of the EGFR signalling network required for full proliferative potential. Moreover, EGF is a potential predictive biomarker of poor cetuximab response and a possible treatment target.
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| 31. |
- Boldrup, Linda, et al.
(författare)
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Low potential of circulating interleukin 1 receptor antagonist as a prediction marker for squamous cell carcinoma of the head and neck
- 2021
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 50:8, s. 785-794
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating markers are attractive molecules for prognosis and management of cancer that allow sequential monitoring of patients during and after treatment. Based on previous protein profiling data, circulating interleukin 1 receptor antagonist (IL-1Ra) was evaluated as a potential diagnostic and prognostic marker for squamous cell carcinomas of the head and neck (SCCHN). In this study, we aimed at confirming the clinical relevance of plasma IL-1Ra in SCCHN and exploring its potential as a prediction marker for SCCHN.Methods: Plasma from 87 patients with SCCHN, control plasma from 28 healthy individuals and pre-diagnostic plasma from 44 patients with squamous cell carcinoma of the oral tongue (SCCOT) and 88 matched controls were analysed with IL-1Ra electrochemiluminescence immunoassays from mesoscale diagnostics.Results: Plasma IL-1Ra was found to be up-regulated in patients with oral tongue, gingiva and base of tongue tumours compared to healthy individuals (p < 0.01). IL-1Ra levels positively correlated with tumour size (p < 0.01) and body mass index (p = 0.013). Comparing pre-diagnostic plasma to the matched controls, similar IL1-Ra levels were seen (p = 0.05).Conclusion: The anti-inflammatory cytokine IL-1Ra could be a diagnostic marker for SCCHN, whereas its potential as a cancer prediction marker was not supported by our data.
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| 32. |
- Chrcanovic, Bruno, et al.
(författare)
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Adenomatoid odontogenic tumor : an updated analysis of the cases reported in the literature
- 2019
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 48:1, s. 10-16
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Forskningsöversikt (refereegranskat)abstract
- Purpose. To review the clinical and radiographic features of the available data published on adenomatoid odontogenic tumor (AOT) with special emphasis on the comparison of its variants. Methods. An electronic search was undertaken in July/2018. Eligibility criteria included publications having enough clinical/radiological/histological information to confirm the diagnosis. Results. 436 publications reporting 1558 cases were included, of which 739 follicular, 247 extrafollicular, and 30 peripheral AOTs. Impacted canine is associated with follicular AOTs in almost 70% of the cases. AOTs were more prevalent in females, in the second decade of life, in maxillae, in anterior region of the jaws, and most are asymptomatic, with a considerable number of lesions presenting cortical bone perforation. Most of the lesions were treated by enucleation. Some cases of recurrence were reported in the literature, but only one was well documented. No difference was found when comparing the clinical/radiological features of the follicular, extrafollicular and peripheral variants. Conclusions. AOT variants do not show distinctive clinical radiological features. Recurrence of AOT is very rare, which justify its conservative management.
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| 33. |
- Chrcanovic, Bruno, et al.
(författare)
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Ameloblastic fibroma and ameloblastic fibrosarcoma : a systematic review
- 2018
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 47:4, s. 315-325
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Forskningsöversikt (refereegranskat)abstract
- Purpose. To integrate the available data published to date on ameloblastic fibromas (AF) and ameloblastic fibrosarcomas (AFS) into a comprehensive analysis of their clinical/radiologic features. Methods. An electronic search was undertaken in July/2017. Eligibility criteria included publications having enough clinical, radiological and histological information to confirm a definite diagnosis. Results. 244 publications (279 central AF tumours, 10 peripheral AF, 103 AFS) were included. AF and AFS differed significantly with regard to the occurrence of patients’ mean age, bone expansion, cortical bone perforation and lesion size. Recurrence rates were: central AF (19.2%), peripheral AF (12.5%), AFS (all lesions, 35%), primary (de novo) AFS (28.8%), secondary AFS (occurring after an AF, 50%). Larger lesions and older patients were more often treated by surgical resections for central AF. Segmental resection resulted in the lowest rate of recurrence for most of the lesion types. AFS treated by segmental resection had a 70.5% lower probability to recur (OR 0.295; p=0.049) than marginal resection. 21.3% of the AFS-patients died due to complications related to the lesion. Conclusions. Very long follow-up is recommended for AF lesions, due to the risk of recurrence and malignant change into AFS. Segmental resection is the most recommended therapy for AFS.
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| 34. |
- Chrcanovic, Bruno, et al.
(författare)
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Central giant cell lesion of the jaws : an updated analysis of 2270 cases reported in the literature
- 2018
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 47:8, s. 731-739
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Forskningsöversikt (refereegranskat)abstract
- Purpose. To review all available data published on central giant cell lesion (CGCL) of the jaws into a comprehensive analysis of its clinical/radiologic features, with emphasis on the predictive factors associated with its recurrence. Methods. Electronic search undertaken in 5 databases (February/2018), looking for publications reporting cases of CGCLs. Results. 365 publications were included, comprising 2270 lesions. CGCLs were more prevalent in women and in the mandible, being usually asymptomatic. Cortical bone perforation occurred in 50% of the cases. Marginal/segmental resection were more often performed in larger lesions, and drug therapy was more frequent in small lesions. Recurrence was reported in 232/1316 cases (17.6%). The recurrence rate of the aggressive lesions (22.8%) after surgical treatment was higher than non-aggressive lesions (7.8%). Four out of five CGCLs showed partial/total regression with pharmacological treatment. Aggressive lesions showed worse response to corticosteroids than non-aggressive lesions. For the lesions submitted to surgery as the first treatment, curettage, enucleation or marginal resection in relation to segmental resection, aggressive lesions, cortical bone perforation, and tooth root resorption were associated with increased recurrence rate. Recurrence related to combination of surgical/pharmacological treatment could not be evaluated due to the variety of protocols. Conclusions. Aggressive CGCLs recur more often than the non-aggressive ones. Despite sometimes showing poor response to corticosteroid injection or surgical curettage, a combination of both treatment strategies should be considered in these aggressive cases in order to reduce morbidities associated with radical surgery. The best protocol to manage aggressive and non-aggressive lesions remains to be determined.
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| 35. |
- Chrcanovic, Bruno, et al.
(författare)
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Clinical factors associated with the recurrence of central giant cell lesions.
- 2019
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 48:9, s. 799-802
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Tidskriftsartikel (refereegranskat)abstract
- Central giant cell lesion of the jaws (CGCLJ) is a destructive condition that shows a varied and unpredictable biological behaviour. In the present study, we aimed to evaluate factors associated with the recurrence of CGCLJ. Based on the data of a previous systematic review of 2,270 CGCLJ, we used the multiple imputation to deal with the missing data. The dependent variable was the recurrence after the first treatment (yes/no). The dichotomic covariates were sex, upper or lower jaw location, size (up to or larger than 4 cm), pain, cortical bone perforation (yes/no), locularity (uni-/multilocular), tooth displacement (yes/no), treatment type (curettage or enucleation) and root resorption (yes/no). The final logistic model indicated that the tumours associated with tooth displacement, root resorption, and treated with curettage had a more significant chance of recurrence. In conclusion, our study suggests that tooth displacement, root resorption, and the type of treatment are potentially useful in the future construction of an algorithm for patient's treatment. This article is protected by copyright. All rights reserved.
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| 36. |
- Chrcanovic, Bruno, et al.
(författare)
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Peripheral giant cell granuloma : an updated analysis of 2824 cases reported in the literature
- 2018
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 47:5, s. 454-459
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Forskningsöversikt (refereegranskat)abstract
- Objective. To integrate the available data published on peripheral giant cell granuloma (PGCG) into a comprehensive analysis of its clinical/radiologic features. Materials and Methods. An electronic search was undertaken in January/2018 in 5 databases, looking for publications reporting cases of PGCGs. Probability of recurrence was calculated for some variables. Results. 165 publications were included, 2824 lesions identified. PGCGs were slightly more prevalent in women and more prevalent in mandibles, usually asymptomatic, and presenting erosion of the subjacent bone in almost 1/3 of cases. Additional curettage (2.8%) or peripheral osteotomy (0%) after excision presented lower recurrence rates in comparison to excision alone (16%). Excision followed by curettage decreases the probability of recurrence by 85% in comparison to excision alone. Other factors (age, lesion size, follow-up, gender, location, clinical symptoms, bone erosion) seem to do not influence the probability of recurrence. Conclusions. As surgical excision alone shows a considerable recurrence rate, excision followed by an additional therapy - curettage or peripheral osteotomy - should be the first choice of treatment of PGCG.
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| 37. |
- Chrcanovic, Bruno Ramos, DDS, MSc, PhD, et al.
(författare)
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Comparison of survival outcomes between ameloblastic carcinoma and metastasizing ameloblastoma : a systematic review
- 2022
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 51:7, s. 603-610
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate and compare the demographic data, occurrence of recurrence and metastasis, and survival prognosis between ameloblastic carcinoma and metastasizing ameloblastoma, based on appropriate and currently accepted eligible diagnostic criteria, in a systematic review of the literature.METHODS: An electronic search was undertaken, last updated in December 2021. Eligibility criteria included publications having enough clinicopathological information to confirm the diagnosis of these tumors.RESULTS: Seventy-seven publications reporting 85 ameloblastic carcinomas and 43 metastasizing ameloblastomas were included. Both tumors were more frequent in mandible and showed different clinical profiles regarding patients' sex and age. There was no difference in the estimated cumulative survival between patients diagnosed with these tumors. Metastases mainly affected the lungs, followed by cervical lymph nodes. The mean time between the first metastasis and the last follow-up was higher for metastasizing ameloblastoma (p=0.021). Additionally, metastasizing ameloblastoma patients remained alive longer than ameloblastic carcinoma patients after the first metastasis diagnosis (p=0.041). Considering only the cases that metastasized, a higher ratio of ameloblastic carcinoma patients died in comparison to metastasizing ameloblastoma patients (p=0.003). The occurrence of recurrence was associated with a conservative primary treatment with both ameloblastic carcinoma (p<0.001) and metastasizing ameloblastoma tumors (p=0.017). Multiple recurrent events were associated with conservative primary therapies with metastasizing ameloblastoma (p<0.001) but not with ameloblastic carcinoma (p=0.121).CONCLUSIONS: In addition to some demographic differences, ameloblastic carcinomas that metastasize present a worse prognosis than metastasizing ameloblastoma. As conservative procedures are associated with multiple recurrent events, this treatment modality should be avoided for both tumors. This article is protected by copyright. All rights reserved.
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| 38. |
- Chrcanovic, Bruno, et al.
(författare)
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Some methodological issues on the review of pathologic lesions and conditions
- 2019
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 48:3, s. 260-261
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Tidskriftsartikel (refereegranskat)abstract
- There are many pathologic conditions which occur in the maxillofacial region. Some are rare with only isolated case reports in the literature. In order to get a general picture of such lesions, it is common practice to gather information described in the literature, analyze the data, and write systematic reviews. The review of pathologic lesions and conditions is of great importance because it provides information that can improve the diagnostic accuracy and could help pathologists and surgeons to make informed decisions and refine the treatment plan to optimize the clinical outcome. With systematic reviews there are, however, the issues of missing data, wrong diagnosis, lack of histopathological information, and lack of follow-up.
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| 39. |
- Ernberg, M, et al.
(författare)
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Experimental muscle pain and music, do they interact?
- 2020
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Ingår i: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. - : Wiley. - 1600-0714. ; 49:6, s. 522-528
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Tidskriftsartikel (refereegranskat)
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| 40. |
- Gu, Xiaolian, 1976-, et al.
(författare)
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Copy number variation : A prognostic marker for young patients with squamous cell carcinoma of the oral tongue
- 2019
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 48:1, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- Background The incidence of squamous cell carcinoma of the oral tongue (SCCOT) is increasing in people under age 40. There is an urgent need to identify prognostic markers that help identify young SCCOT patients with poor prognosis in order to select these for individualized treatment. Materials and methods To identify genetic markers that can serve as prognostic markers for young SCCOT patients, we first investigated four young (<= 40 years) and five elderly patients (>= 50 years) using global RNA sequencing and whole-exome sequencing. Next, we combined our data with data on SCCOT from the cancer genome atlas (TCGA), giving a total of 16 young and 104 elderly, to explore the correlations between genomic variations and clinical outcomes. Results In agreement with previous studies, we found that SCCOT from young and elderly patients was transcriptomically and also genomically similar with no significant differences regarding cancer driver genes, germline predisposition genes, or the burden of somatic single nucleotide variations (SNVs). However, a disparate copy number variation (CNV) was found in young patients with distinct clinical outcome. Combined with data from TCGA, we found that the overall survival was significantly better in young patients with low-CNV (n = 5) compared to high-CNV (n = 11) burden (P = 0.044). Conclusions Copy number variation burden is a useful single prognostic marker for SCCOT from young, but not elderly, patients. CNV burden thus holds promise to form an important contribution when selecting suitable treatment protocols for young patients with SCCOT.
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| 41. |
- Gu, Xiaolian, 1976-, et al.
(författare)
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Early detection of squamous cell carcinoma of the oral tongue using multidimensional plasma protein analysis and interpretable machine learning
- 2023
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 52:7, s. 637-643
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interpretable machine learning (ML) for early detection of cancer has the potential to improve risk assessment and early intervention.Methods: Data from 261 proteins related to inflammation and/or tumor processes in 123 blood samples collected from healthy persons, but of whom a sub-group later developed squamous cell carcinoma of the oral tongue (SCCOT), were analyzed. Samples from people who developed SCCOT within less than 5 years were classified as tumor-to-be and all other samples as tumor-free. The optimal ML algorithm for feature selection was identified and feature importance computed by the SHapley Additive exPlanations (SHAP) method. Five popular ML algorithms (AdaBoost, Artificial neural networks [ANNs], Decision Tree [DT], eXtreme Gradient Boosting [XGBoost], and Support Vector Machine [SVM]) were applied to establish prediction models, and decisions of the optimal models were interpreted by SHAP.Results: Using the 22 selected features, the SVM prediction model showed the best performance (sensitivity = 0.867, specificity = 0.859, balanced accuracy = 0.863, area under the receiver operating characteristic curve [ROC-AUC] = 0.924). SHAP analysis revealed that the 22 features rendered varying person-specific impacts on model decision and the top three contributors to prediction were Interleukin 10 (IL10), TNF Receptor Associated Factor 2 (TRAF2), and Kallikrein Related Peptidase 12 (KLK12).Conclusion: Using multidimensional plasma protein analysis and interpretable ML, we outline a systematic approach for early detection of SCCOT before the appearance of clinical signs.
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| 42. |
- Hirsch, Jan, et al.
(författare)
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A paradigm shift in the prevention and diagnosis of oral squamous cell carcinoma
- 2023
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 52:9, s. 826-833
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oral squamous cell carcinoma (OSCC) is a widespread disease with only 50%-60% 5-year survival. Individuals with potentially malignant precursor lesions are at high risk.Methods: Survival could be increased by effective, affordable, and simple screening methods, along with a shift from incisional tissue biopsies to non-invasive brush biopsies for cytology diagnosis, which are easy to perform in primary care. Along with the explainable, fast, and objective artificial intelligence characterisation of cells through deep learning, an easy-to-use, rapid, and cost-effective methodology for finding high-risk lesions is achievable. The collection of cytology samples offers the further opportunity of explorative genomic analysis.Results: Our prospective multicentre study of patients with leukoplakia yields a vast number of oral keratinocytes. In addition to cytopathological analysis, whole-slide imaging and the training of deep neural networks, samples are analysed according to a single-cell RNA sequencing protocol, enabling mapping of the entire keratinocyte transcriptome. Mapping the changes in the genetic profile, based on mRNA expression, facilitates the identification of biomarkers that predict cancer transformation.Conclusion: This position paper highlights non-invasive methods for identifying patients with oral mucosal lesions at risk of malignant transformation. Reliable non-invasive methods for screening at-risk individuals bring the early diagnosis of OSCC within reach. The use of biomarkers to decide on a targeted therapy is most likely to improve the outcome. With the large-scale collection of samples following patients over time, combined with genomic analysis and modern machine-learning-based approaches for finding patterns in data, this path holds great promise.
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| 43. |
- Jedlinski, Adam, 1978-, et al.
(författare)
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Cetuximab sensitivity of head and neck squamous cell carcinoma xenografts is associated with treatment-induced reduction in EGFR, pEGFR, and pSrc.
- 2017
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 46:9, s. 717-724
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aims of this study were to validate in vitro drug sensitivity testing of head and neck squamous cell carcinoma (HNSCC) cell lines in an in vivo xenograft model and to identify treatment-induced changes in the epidermal growth factor receptor (EGFR) signaling pathway that could be used as markers for cetuximab treatment response.MATERIALS AND METHODS: The in vitro and in vivo cetuximab sensitivity of two HNSCC cell lines, UT-SCC-14 and UT-SCC-45, was assessed using a crystal violet assay and xenografts in nude mice, respectively. The expression of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Src (pSrc), and Ki-67 was investigated by immunohistochemistry. To verify these results, the in vitro expression of EGFR and pEGFR was analyzed with ELISA in a panel of 10 HNSCC cell lines.RESULTS: A close correlation was found between in vitro and in vivo cetuximab sensitivity data in the two investigated HNSCC cell lines. In treatment sensitive UT-SCC-14 xenografts, there was a decrease in EGFR, pEGFR, and pSrc upon cetuximab treatment. Interestingly, in insensitive UT-SCC-45 xenografts, an increased expression of these three proteins was found. The change in EGFR and pEGFR expression in vivo was confirmed in cetuximab-sensitive and cetuximab-insensitive HNSCC cell lines using ELISA.CONCLUSION: High sensitivity to cetuximab was strongly associated with a treatment-induced reduction in pEGFR both in vivo and in vitro in a panel of HNSCC cell lines, suggesting that EGFR and pEGFR dynamics could be used as a predictive biomarker for cetuximab treatment response.
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| 44. |
- Johansson, Ann-Charlotte, et al.
(författare)
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The relationship between EMT, CD44(high)/EGFR(low) phenotype, and treatment response in head and neck cancer cell lines
- 2016
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Ingår i: Journal of Oral Pathology & Medicine. - : WILEY-BLACKWELL. - 0904-2512 .- 1600-0714. ; 45:9, s. 640-646
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHead and neck squamous cell carcinoma (HNSCC) tumors are often therapy resistant and may originate from cancer stem cells or tumor cells with an epithelial-to-mesenchymal transition (EMT) phenotype. The aim of this study was to characterize HNSCC cell lines with regard to EMT profile and to investigate the influence of EMT on the response to treatment. MethodsmRNA expression of the EMT-associated genes CDH1 (E-cadherin), CDH2 (N-cadherin), FOXC2, TWIST1, VIM (vimentin), and FN1 (fibronectin) was determined using quantitative real-time PCR. Cell morphology and migration were investigated by phase-contrast microscopy and Boyden chamber assay, respectively. The cell surface expression of CD44 and epidermal growth factor receptor (EGFR) was examined by flow cytometry. The response to radiotherapy, cetuximab, and dasatinib was assessed by crystal violet staining. ResultsA total of 25 cell lines investigated differed greatly with regard to EMT phenotype. Cell lines with an EMT expression profile showed a mesenchymal morphology and a high migratory capacity. In addition, they exhibited a high cell surface expression of CD44 and a low expression of EGFR, a pattern previously associated with stemness. When the EMT inducer transforming growth factor- (TGF-) was added to non-EMT cells, changes in treatment responses were observed. Moreover, the expression of TWIST1 was found to correlate with radioresistance. ConclusionsThe data presented in this report suggest that EMT is associated with a CD44(high)/EGFR(low) phenotype and possibly negative impact on radiotherapy response in HNSCC cell lines.
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| 45. |
- Jäwert, Fredrik, et al.
(författare)
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Recurrent copy number alterations involving EGFR, CDKN2A, and CCND1 in oral premalignant lesions
- 2022
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 51:6, s. 546-552
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Tidskriftsartikel (refereegranskat)abstract
- Background A major challenge in the management of patients with oral leukoplakia is the difficulty to identify patients at high risk of developing oral squamous cell carcinoma. Our knowledge about genomic alterations in oral leukoplakia, and in particular those that progress to oral squamous cell carcinoma, is scarce and there are no useful biomarkers that can predict the risk of malignant transformation. Methods Using a novel, custom-made tissue microarray including 28 high-risk oral leukoplakias and the corresponding oral squamous cell carcinomas from 14 cases that progressed to cancer, we assayed copy number alterations involving the oral squamous cell carcinoma driver genes CDKN2A, CCND1, EGFR, and MYC by fluorescence in situ hybridization. The copy number alterationss were correlated with clinicopathological data from all patients. Results Copy number alterations were identified in 14/24 oral leukoplakias, analyzable for one or more of the oral squamous cell carcinoma driver genes. EGFR was the most frequently altered gene in oral leukoplakias with amplification/gain in 43.5% followed by loss of CDKN2A (26.1%), gains of CCND1 (26.1%), and MYC (8.3%). Losses of CDKN2A were more common in oral leukoplakias progressing to oral squamous cell carcinoma compared to those that did not. Copy number alterations were more common in oral squamous cell carcinomas than in oral leukoplakias. Conclusions Our findings demonstrate that copy number alterations involving the oral squamous cell carcinoma drivers CDKN2A, EGFR, and CCND1 occur in oral leukoplakias and suggest a possible role for these genes in the development and/or progression of subsets of oral leukoplakias.
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| 46. |
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| 47. |
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| 48. |
- Loljung, Lotta, et al.
(författare)
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High expression of p63 is correlated to poor prognosis in squamous cell carcinoma of the tongue
- 2014
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 43:1, s. 14-19
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Tidskriftsartikel (refereegranskat)abstract
- Backgroundp63 proteins are important in formation of the oral mucosa. Normal oral mucosa shows a balance between the six protein isoforms, whereas an imbalance between them is seen in squamous cell carcinomas (SCC). There is controversy over the clinical impact of p63 in SCC, which may relate to different expression in different areas. In addition, p63 isoforms can act as p53-like molecules (TAp63) or can inhibit p53 functions (Np63) and expression of these isoforms varies in different tumours. Here, we chose to concentrate on the most common intra-oral sub-site, SCC of the mobile tongue. MethodsTotal p63, Np63 and TAp63 were analysed separately using immunohistochemistry. The percentage of cells and intensity of expression of different isoforms of p63 was evaluated using a quick score method and correlated with clinical data in a group of 87 patients with tongue SCC. ResultsAll tumours expressed p63 in at least 60% of the cells when using two different antibodies detecting all 6 isoforms. p63 expression correlated significantly with 2-year survival (P=0.018), with fewer patients surviving 2years if their tumours expressed p63 with strong intensity in at least 80% of the cells (quick score 18). Looking at 5-year survival, this was even more emphasized. Np63 was expressed in all tumours, whereas expression of TAp63 was seen only in 59/87 patients, usually at very low levels. ConclusionsBased on the present data, we recommend using expression of p63 as an additional factor contributing prognostic information in analysis of SCC in the tongue.
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