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1.
  • Idris, AM, et al. (författare)
  • The Swedish snus and the Sudanese toombak : are they different?
  • 1998
  • Ingår i: Oral Oncology. - 1368-8375 .- 1879-0593. ; 34:6, s. 558-566
  • Tidskriftsartikel (refereegranskat)abstract
    • In Sweden, snuff (locally known as snus), was introduced since the year 1637. Presently, Sweden has the highest per capita consumption and sale figures of snuff in the world, and the habit is becoming increasingly popular. Snus is manufactured into a dry form used in the nasal cavity and a moist form used in the oral cavity. Snus manufactured for oral use is a moist ground tobacco of Dark Kentucky or Virginia species mixed with an aqueous solution of water and other blending ingredients. This form of snuff is found in two types: (1) loose and (2) portion-bag-packed. These are the most widely used. The loose moist form (1–2 g a quid) is the most popular type consumed by 73% of the males, followed by the portion-bag-packed form (0.5–1 g a quid), consumed by 13% of the males, while 14% of the males are mixed users. The majority of snus users place the quid in the vestibular area of the upper lip, and the prevalence among persons 15 years of age or older is 15.9% among males and 0.2% among females. The pH of snus has declined from a previous range of 8–9 to a range of 7.8–8.5, moisture content ranges 35–60% and nicotine content is in the order of 5–11 mg/g dry wt tobacco-specific N-nitrosamines (TSNAs) in micrograms (N′-nitrosonornicotine: NNN 5–9; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: NNK 1–2; N′-nitrosoanatabine: NAT 2–5). In the Sudan, snuff, locally known as toombak, was introduced approximately 400 years ago. It is always processed into a loose moist form, and its use is widespread in the country. Tobacco used for manufacture of toombak is of the species Nicotiana rustica, and the fermented ground powder is mixed with an aqueous solution of sodium bicarbonate. The resultant product is moist, with a strong aroma, highly addictive and its use is widespread particularly among males. Its pH range is 8–11, moisture content ranges 6–60% and nicotine content is from 8 to 102 mg/g dry wt, and TSNAs contents in micrograms (NNN 420–1 550; NNK 620–7 870; NAT 20–290). Snus and toombak dippers develop a clinically and histologically characteristic lesion at the site of dipping. Probably due to control of the TSNAs in snus, this type of snuff is associated with a lower risk of cancer of the oral cavity (relative risk: RR 5–6-fold), whereas the risk for cancer of the oral cavity among toombak users was high (RR 7.3–73.0-fold). In conclusion, the two snuff products significantly differ in many aspects. Most notable differences are tobacco species, fermentation and ageing, nicotine and TSNAs content, pH, expression of the p53 tumour supressor gene, and keratin types 13, 14, and 19. It was, therefore, the object of the present study to highlight the oral health hazards of toombak, and to compare it with snus regarding the aforementioned differences.
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  • Skolin, Inger, et al. (författare)
  • Nutrient intake and weight development in children during chemotherapy for malignant disease
  • 1997
  • Ingår i: Oral Oncology. - 1368-8375 .- 1879-0593. ; 33:5, s. 364-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to assess the actual daily oral intake of energy, protein, fat and carbohydrate in relation to current recommendations in children with malignant disease during chemotherapy and to follow their weight development. Dietary information was collected for 21 consecutive days via 7-day recording in 14 children, aged 5-16 years. The number of days with loss of appetite, vomiting, and the number of days on anti-emetic drugs were also recorded. The average daily energy intake decreased from 91% of the recommendation of the Swedish Nutrition Recommendations (SNR), before chemotherapy to 69% after start of chemotherapy. During days spent at home, the energy intake increased to 77% of SNR. Twenty-two per cent of the total energy intake during the hospital days came from sucrose. On average, the children experienced loss of appetite on 50% of the days, vomiting on 12%, and received anti-emetic drugs on 38%. On admission, the average SD score for body weight for the whole group was -0.09. The mean weight reduction after 1 week was 0.19 SD (P = 0.05) compared to the admission weight. The weight reduction 6 weeks (n = 10) and 3 months (n = 13) after the start of chemotherapy was 0.10 SD and 0.37 SD (P = 0.04), respectively
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  • Ansell, Anna, et al. (författare)
  • Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines.
  • 2009
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 45:10, s. 866-871
  • Tidskriftsartikel (refereegranskat)abstract
    • Concomitant chemoradiotherapy is a common treatment for advanced head and neck squamous cell carcinomas (HNSCC). Cisplatin is the backbone of chemotherapy regimens used to treat HNSCC. Therefore, the aim of this study was to identify predictive markers for cisplatin treatment outcome in HNSCC. The intrinsic cisplatin sensitivity (ICS) was determined in a panel of tumour cell lines. From this panel, one sensitive and two resistant cell lines were selected for comparative transcript profiling using microarray analysis. The enrichment of Gene Ontology (GO) categories in sensitive versus resistant cell lines were assessed using the Gene Ontology Tree Machine bioinformatics tool. In total, 781 transcripts were found to be differentially expressed and 11 GO categories were enriched. Transcripts contributing to this enrichment were further analyzed using Ingenuity Pathway Analysis (IPA) for identification of key regulator genes. IPA recognized 20 key regulator genes of which five were differentially expressed in sensitive versus resistant cell lines. The mRNA level of these five genes was further assessed in a panel of 25 HNSCC cell lines using quantitative real-time PCR. Among these key regulators, MMP-7 and MMP-13 are implicated as potential biomarkers of ICS. Taken together, genome-wide transcriptional analysis identified single genes, GO categories as well as molecular networks that are differentially expressed in HNSCC cell lines with different ICS. Furthermore, two novel predictive biomarkers for cisplatin resistance, MMP-7 and MMP-13, were identified.
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  • Ansell, Anna, et al. (författare)
  • Polymorphism of FGFR4 in cancer development and sensitivity to cisplatin and radiation in head and neck cancer
  • 2009
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 45:1, s. 23-29
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the predisposition of the FGFR4 Gly/Arg polymorphism for development of head and neck squamous cell carcinoma (HNSCC) and, furthermore, to examine if the FGFR4 Arg(388) allele can be associated with resistance to chemo-and radiotherapy.When analysing 110 tumour biopsies a significant 1.7-fold increased risk to develop HNSCC in individuals carrying the Gly(388) allele (p = 0.026) was found. Moreover a 2-fold increased risk for mates harbouring the Gly(388) allele (p = 0.031) to develop HNSCC was detected. In 39 HNSCC cell lines the role of the Arg(388) allele for radiation and cisplatin sensitivity was investigated. Our results show no rote of the Arg(388) allele for the radiosensitivity (p = 0.996) but indicate a tendency to increased cisplatin sensitivity (p = 0.141). When screening the transmembrane and kinase domains in the FGFR4 gene a novel mutation, probably generating a truncated protein lacking exons 14-18, was found in six of eight selected cell lines.Taken together, we have here identified a marker that predicts the risk to develop HNSCC and possibly the sensitivity to cisplatin as well as a novel. mutation in the FGFR4 gene.
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10.
  • Bersani, Cinzia, et al. (författare)
  • A model using concomitant markers for predicting outcome in human papillomavirus positive oropharyngeal cancer
  • 2017
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 68, s. 53-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Head-neck cancer therapy has become intensified. With radiotherapy alone, 3-year disease-free survival (DFS) is 80% for HPV-positive TSCC/BOTSCC and better for patients with favorable characteristics, suggesting therapy could be tapered for some, decreasing side-effects. Therefore, we built a model to predict progression-free survival for patients with HPV-positive TSCC and BOTSCC. Material and methods: TSCC/BOTSCC patients treated curatively between 2000 and 2011, with HPV16 DNA/E7 mRNA positive tumors examined for CD8(+) TILs, HPV16 mRNA and HLA class I expression were included. Patients were split randomly 65/35 into training and validation sets, and LASSO regression was used to select a model in the training set, the performance of which was evaluated in the validation set. Results: 258 patients with HPV DNA/E7 mRNA positive tumors could be included, 168 and 90 patients in the respective sets. No treatment improved prognosis compared to radiotherapy alone. CD8(+) TIL counts and young age were the strongest predictors of survival, followed by T-stage <3 and presence of HPV16 E2 mRNA. The model had an area under curve (AUC) of 76%. A model where the presence of three of four of these markers defined good prognosis captured 56% of non-relapsing patients with a positive predictive value of 98% in the validation set. Furthermore, the model identified 35% of our cohort that was over-treated and could safely have received de-escalated therapy. Conclusion: CD8(+) TIL counts, age, T-stage and E2 expression could predict progression-free survival, identifying patients eligible for randomized trials with milder treatment, potentially reducing side effects without worsening prognosis.
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  • Bersani, Cinzia, et al. (författare)
  • MicroRNA-155,-185 and-193b as biomarkers in human papillomavirus positive and negative tonsillar and base of tongue squamous cell carcinoma
  • 2018
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 82, s. 8-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Three-year disease-free survival (DFS) is 80% for human papillomavirus (HPV) positive tonsillar and base of tongue cancer (TSCC/BOTSCC) treated with radiotherapy alone, and today's intensified therapy does not improve prognosis. More markers are therefore needed to more accurately identify patients with good prognosis or in need of alternative therapy. Here, microRNAs (miRs) 155, 185 and 193b were examined as potential prognostic markers in TSCC/BOTSCC.Material and methods: 168 TSCC/BOTSCC patients diagnosed 2000-2013, with known data on HPV-status, CD8(+) tumour infiltrating lymphocytes, tumour staging and survival were examined for expression of miR-155, -185 and -193b using Real-Time PCR. Associations between miR expression and patient and tumour characteristics were analysed using univariate testing and multivariate regression.Results: Tumours compared to normal tonsils showed decreased miR-155 and increased miR-193b expression. miR-155 expression was associated with HPV-positivity, low T-stage, high CD8(+) TIL counts and improved survival. miR-185 expression was associated with HPV-negativity and a tendency towards decreased survival, while miR-193b expression was associated with higher T-stage, male gender and lower CD8(+) TIL counts, but not with outcome. Upon Cox regression, miR-185 was the only miR significantly associated with survival. Combining miR-155 and miR-185 to predict outcome in HPV+ patients yielded an area under curve (AUC) of 71%.Conclusion: Increased miR-155 expression was found as a positive predictor of survival, with the effect mainly due to its association with high CD8(+) TIL numbers, while miR-185 independently associated with decreased survival. Addition of these miRs to previously validated prognostic biomarkers could improve patient stratification accuracy.
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  • Boldrup, Linda, et al. (författare)
  • Differences in p63 expression in SCCHN tumours of different sub-sites within the oral cavity
  • 2011
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 47:9, s. 861-865
  • Tidskriftsartikel (refereegranskat)abstract
    • Squamous cell carcinoma of the head and neck, SCCHN, the sixth most common cancer in the world, comprises tumours of differentanatomical sites. The overall survival is low, and there are no good prognostic or predictive markers available. The p53 homologue, p63, plays an important role in development of epithelial structures and has also been suggested to be involved in development of SCCHN. However, most studies on p63 in SCCHN have not taken into account the fact that this group of tumours is heterogeneous in terms of the particular site of origin of the cancer. Mapping and comparing p63 expression levels in tumours and corresponding clinically normal tissue in SCCHN from gingiva, tongue and tongue/floor of the mouth revealed clear differences between these regions. In normal samples from tongue and gingiva, tongue samples showed 2.5-fold higher median p63 expression and also more widespread expression compared to gingival samples. These results emphasise the importance of taking sub-site within the oral cavity into consideration in analyses of SCCHN.
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  • Ebrahimi, Majid, 1963-, et al. (författare)
  • Decreased expression of the p63 related proteins beta-catenin, E-cadherin and EGFR in oral lichen planus
  • 2007
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 44:7, s. 634-638
  • Tidskriftsartikel (refereegranskat)abstract
    • Oral lichen planus (OLP) is a chronic inflammatory disease and although classified by WHO as a premalignant condition, the risk for transformation into squamous cell carcinoma of the head and neck (SCCHN) is a matter of great controversy. The p63 gene encodes six different proteins which are required for development of ectodermally derived tissues such as oral mucosa, salivary glands, teeth and skin. p63 is highly expressed in SCCHN whereas decreased expression is seen in OLP. beta-catenin, E-cadherin and epidermal growth factor receptor (EGFR) are p63 related proteins, and abnormalities in their expression suggested they are involved in development of squamous cell carcinoma of the head and neck (SCCHN). In this study we mapped the expression of these p63 related proteins in OLP and matched normal healthy controls. Results showed decreased expression of beta-catenin, E-cadherin and EGFR in the vast majority of OLP samples compared with the normal controls. This is the first comprehensive study mapping expression of several p63- and SCCHN-related proteins in tissue from patients with OLP. Results showed a mixed expression pattern with OLP variably resembling normal as well as tumour tissue. Based on our present and previous data it cannot be judged whether OLP lesions are at an increased risk of malignant development.
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  • Ebrahimi, Majid, et al. (författare)
  • Expression of novel p53 isoforms in oral lichen planus.
  • 2007
  • Ingår i: Oral Oncology. - : Elsevier BV. - 1368-8375 .- 1879-0593. ; 44:2, s. 156-161
  • Tidskriftsartikel (refereegranskat)abstract
    • Oral lichen planus (OLP) is a chronic inflammatory disease of unknown origin, showing little spontaneous regression. WHO classifies OLP as a premalignant condition, however, the underlying mechanisms initiating development of cancer in OLP lesions are not understood. The p53 tumour suppressor plays an important role in many tumours, and an increased expression of p53 protein has been seen in OLP lesions. Recently it was shown that the human TP53 gene encodes at least nine different isoforms. Another member of the p53 family, p63, comprises six different isoforms and plays a crucial role in the formation of oral mucosa, salivary glands, teeth and skin. It has also been suggested that p63 is involved in development of squamous cell carcinoma of the head and neck (SCCHN). In contrast to p53, a decreased expression of p63 protein has been seen in OLP lesions. In this study, we mapped the expression of five novel p53 isoforms at RNA and protein levels in OLP and matched normal controls. In the same samples we also measured levels of p63 isoforms using quantitative RT-PCR. Results showed p53 to be expressed in all OLP lesions and normal tissues. The p53beta and Delta133p53 isoforms were expressed in the majority of samples whereas the remaining three novel isoforms analysed were expressed in only a few samples. Levels of p63 isoforms were lower in OLP lesions compared with normal tissue, however, changes were not statistically significant.
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18.
  • Ekblad, Lars, et al. (författare)
  • Anti- or pro-proliferation - Conditional options for TGF-α and cetuximab in head and neck squamous cell carcinoma.
  • 2015
  • Ingår i: Oral Oncology. - : Elsevier BV. - 1879-0593 .- 1368-8375. ; 51:1, s. 46-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Cetuximab is an epidermal growth factor receptor (EGFR)-targeting drug that has shown effects in head and neck squamous cell carcinoma (HNSCC). The effects are, however, small and have mainly been proven in a subset of patients, and the cost-effectiveness has been questioned. For this reason, we need to know more about the basic mechanisms controlling the effect of EGFR signalling on tumour growth.
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  • Garvin, Stina, et al. (författare)
  • Nuclear expression of WRAP53 beta is associated with a positive response to radiotherapy and improved overall survival in patients with head and neck squamous cell carcinoma
  • 2015
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 51:1, s. 24-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Today there are no reliable predictive markers for radiotherapy response in head and neck squamous cell carcinoma (HNSCC), leading to both under-and over-treatment of patients, personal suffering, and negative socioeconomic effects. Inherited mutation in WRAP53 beta (WD40 encoding RNA Antisense to p53), a protein involved in intracellular trafficking, dramatically increases the risk of developing HNSCC. The purpose of this study was to investigate whether WRAP53 beta can predict response to radiotherapy in patients with HNSCC. Materials and methods: Tumor biopsies from patients with HNSCC classified as responders or non-responders to radiotherapy were examined for the expression of the WRAP53 beta protein and single nucleotide polymorphisms in the corresponding gene employing immunohistochemistry and allelic discrimination, respectively. In addition, the effect of RNAi-mediated downregulation of WRAP53 beta on the intrinsic radiosensitivity of two HNSCC cell lines was assed using crystal violet and clonogenic assays. Results: Nuclear expression of WRAP53 beta was significantly associated with better response to radiotherapy and improved patient survival. Downregulation of WRAP53 beta with siRNA in vitro enhanced cellular resistance to radiation. Conclusions: Our findings suggest that nuclear expression of WRAP53 beta promotes tumor cell death in response to radiotherapy and is a promising predictor of radiotherapy response in patients with HNSCC.
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  • Hakelius, Malin, et al. (författare)
  • Interleukin-1-mediated effects of normal oral keratinocytes and head and neck squamous carcinoma cells on extracellular matrix related gene expression in fibroblasts
  • 2012
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 48:12, s. 1236-1241
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The composition of tumor stroma and the activity of tumor associated fibroblasts are important for tumor growth. Interactions between carcinoma cells and fibroblasts regulate the turnover of extracellular matrix (ECM). Here, the in vitro effects of oral squamous cell carcinoma (SCC) cells (UT-SCC-30 and UT-SCC-87) on fibroblast expression of genes for ECM components and connective tissue growth factor (CTGF/CCN2), were compared to those of normal oral keratinocytes (NOK).Materials and Methods: Cocultures with fibroblasts in collagen gels and keratinocytes with the two cell types separated by a semi permeable membrane were used, and relative gene expression was measured with real-time PCR.Results: All investigated genes were regulated by NOK and the SCCs. The downregulation of pro-collagens alpha 1(I) and alpha 1(III) was more pronounced in cocultures with NOK, while the expression of CCN2 and fibronectin was downregulated by both NOK and the SCCs to a similar extent. UT-SCC-87, but not UT-SCC-30, secreted significantly more IL-1 alpha than NOK. A recombinant interleukin-1 receptor antagonist reversed many of the observed effects on fibroblast gene expression suggesting involvement of IL-1 in cocultures with NOK as well as with SCCs.Conclusion: The observed differential effects on fibroblast gene expression suggest that NOK are more antifibrotic compared to UT-SCC-30 and UT-SCC-87. These findings may contribute to a better understanding of the mechanisms behind ECM turnover in tumors. (C) 2012 Elsevier Ltd. All rights reserved.
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  • Huang, Junchi, et al. (författare)
  • MYB alternative promoter activity is increased in adenoid cystic carcinoma metastases and is associated with a specific gene expression signature
  • 2024
  • Ingår i: ORAL ONCOLOGY. - 1368-8375 .- 1879-0593. ; 151
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Adenoid cystic carcinoma (ACC) is a head and neck cancer with a poor long-term prognosis that shows frequent local recurrences and distant metastases. The tumors are characterized by MYB oncogene activation and are notoriously unresponsive to systemic therapies. The biological underpinnings behind therapy resistance of disseminated ACC are largely unknown. Here, we have studied the molecular and clinical significance of MYB alternative promoter (TSS2) usage in ACC metastases. Materials and methods: MYB TSS2 activity was investigated in primary tumors and metastases from 26 ACC patients using RNA-sequencing and quantitative real-time PCR analysis. Differences in global gene expression between MYB TSS2 high and low cases were studied, and pathway analyses were performed. Results: MYB TSS2 activity was significantly higher in ACC metastases than in primary tumors (median activity 15.1 vs 3.0, P = 0.0003). MYB TSS2 high ACC metastases showed a specific gene expression signature, including increased expression of multi-drug resistance genes and canonical MYB target genes, and suppression of the p53 and NOTCH pathways. Conclusions: Collectively, our findings indicate that elevated MYB TSS2 activity is associated with metastases, potential drug resistance, and augmented MYB-driven gene expression in ACC. Our study advocates the need for new therapies that specifically target MYB and drug resistance mechanisms in disseminated ACC.
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  • Jerhammar, Fredrik, et al. (författare)
  • YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer
  • 2014
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 50:9, s. 832-839
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Targeted therapy against the epidermal growth factor receptor (EGFR) only variably represents a therapeutic advance in head and neck squamous cell carcinoma (HNSCC). This study addresses the need of biomarkers of treatment response to the EGFR-targeting antibody cetuximab (Erbitux (R)). Materials and Methods: The intrinsic cetuximab sensitivity of HNSCC cell lines was assessed by a crystal violet assay. Gene copy number analysis of five resistant and five sensitive cell lines was performed using the Affymetrix SNP 6.0 platform. Quantitative real-time PCR was used for verification of selected copy number alterations and assessment of mRNA expression. The functional importance of the findings on the gene and mRNA level was investigated employing siRNA technology. The data was statistically evaluated using Mann-Whitney U-test and Spearmans correlation test. Results: Analysis of the intrinsic cetuximab sensitivity of 32 HNSCC cell lines characterized five and nine lines as cetuximab sensitive or resistant, respectively. Gene copy number analysis of five resistant versus five sensitive cell lines identified 39 amplified protein-coding genes, including YAP1, in the genomic regions 11q22.1 or 5p13-15. Assessment using qPCR verified that YAP1 amplification associated with cetuximab resistance. Amplification of YAP1 correlated to higher mRNA levels, and RNA knockdown resulted in increased cetuximab sensitivity. Assessment of several independent clinical data sets in the public domain confirmed YAP1 amplifications in multiple tumor types including HNSCC, along with highly differential expression in a subset of HNSCC patients. Conclusion: Taken together, we provide evidence that YAP1 could represent a novel biomarker gene of cetuximab resistance in HNSCC cell lines.
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  • Jonasson, Kristina, et al. (författare)
  • Squamous cell carcinoma of the mobile tongue in young adults: A Swedish head & neck cancer register (SweHNCR) population-based analysis of prognosis in relation to age and stage
  • 2023
  • Ingår i: Oral Oncology. - : Elsevier BV. - 1368-8375 .- 1879-0593. ; 144
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased incidence of squamous cell carcinoma (SCC) of the tongue has been reported in young adults (YA) in several countries since the 1980s and confirmed in later studies. The etiology is unclear, the prognosis has been debated, and conflicting results have been published. Some studies show better survival in young adults than in older patients, some worse, and others no difference. Most studies are based on selected series or include other sites in the oral cavity. The definition of "YA" is arbitrary and varies between studies. It is thus difficult to use in general conclusions.This work uses data from the population-based Swedish Head and Neck Cancer register (SweHNCR), which has > 98% coverage. SweHNCR data includes age, gender, TNM, treatment intention, treatment given, lead times, performance status, and to a lesser degree, smoking habits. The current Swedish population is around 10 million.We analyzed outcomes for 1416 patients diagnosed with SCC of the oral tongue from 2008 to 2017 using 18-39 years to define YA age because it is the range most commonly used.We found no significant difference in relative survival (a proxy for diagnosis-specific survival) between age groups of patients treated with curative intent for SCC of the oral tongue. The stage at time of diagnosis was equally distributed among the age groups. Excess mortality rate correlated mainly with stage, subsite of the tongue, performance status, and lead time to treatment.
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  • Niméus, Emma, et al. (författare)
  • Amplification of the cyclin D1 gene is associated with tumour subsite, DNA non-diploidy and high S-phase fraction in squamous cell carcinoma of the head and neck
  • 2004
  • Ingår i: Oral Oncology. - : Elsevier BV. - 1879-0593 .- 1368-8375. ; 40:6, s. 624-629
  • Tidskriftsartikel (refereegranskat)abstract
    • Amplification of CCND1 (cyclin D1 gene) in squamous cell carcinoma of the head and neck (SCCHN) is correlated to poor prognosis. The purpose of this study was to investigate whether CCND1 amplification is related to different subsites and also to DNA ploidy status and S-phase fraction (SPF). Biopsies from 67 patients with SCCHN were analysed for CCND1 amplification by fluorescence in situ hybridisation (FISH) and for ploidy status and SPF by flow cytometry (FCM). Twenty-one of 67 tumours (31%) showed CCND1 amplification and the frequencies differed significantly between different subsites (p = 0.01). Tumours from hypopharynx, larynx and oropharynx showed higher rates of amplification as compared to tumours from oral cavity and epipharynx. CCND1 amplification was also associated to DNA non-diploidy and high SPF (p = 0.002 and p = 0.002, respectively). In conclusion, the rate of CCND1 amplification differed between different subsites in SCCHN and was also associated to a more aggressive tumour phenotype, as defined by DNA non-diploidy and high SPF.
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  • Persson, Karolina, et al. (författare)
  • Pain management with popliteal block for fibular graft harvesting in head and neck reconstruction; a randomised double-blind placebo-controlled study
  • 2022
  • Ingår i: Oral Oncology. - : Elsevier BV. - 1879-0593 .- 1368-8375. ; 128, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Curative treatment for locally advanced head and neck tumours often includes reconstructive surgery using a microvascular free flap. Effective recuperation is essential but may be impeded by postoperative donor site pain. The aim of this study was to evaluate the effects of a continuous popliteal block on postoperative pain after fibular graft harvesting.MATERIAL AND METHODS: In this randomized double-blind placebo-controlled study adult patients scheduled for reconstructive head and neck surgery with a microvascular free fibular graft received an indwelling popliteal nerve block catheter and were randomized to receive continuous levobupivacaine/ropivacaine or placebo during the first postoperative week. Primary outcome was postoperative extremity pain assessed using the numerated rating scale (NRS). Secondary outcomes included opioid consumption.RESULTS: In total 24 patients were included. The median (median, IQR [range]) postoperative extremity NRS scores was lower in the local anaesthetic (LA) group (2, 0-3 [0-10]) compared to the placebo group (2, 1-4 [0-10]), p = 0.008. The LA group also experienced fewer episodes of breakthrough pain, defined as NRS ≥ 4 (17% vs 33% of observations), p = 0.009. Furthermore, median (median, IQR [range]) opioid consumption the first postoperative week was lower in the LA group (109 mg, 74-134 [19-611]) compared to the placebo group (202 mg, 135-241 [78-749]), p = 0.010. No complications attributed to the blocks were observed.CONCLUSION: Continuous popliteal block significantly reduced postoperative extremity pain and opioid consumption in patients undergoing fibular graft harvesting for head and neck reconstructive surgery.
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  • Prgomet, Zdenka, et al. (författare)
  • Wnt5a stimulates migration and invasion in OSCC
  • 2013
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 49, s. S115-S116
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: Wnt5a is the most important Wnt protein activating the non-canonical Wnt pathway. It regulates proliferation, differentiation, migration, adhesion and polarity of the cell. Clinical studies have shown that Wnt5a could act as a prognostic marker in various cancers. It seems that Wnt5a acts both as a tumor suppressor (breast, thyroid, colon and livercancer) and as a tumor promotor (malignant melanoma, pancreatic and gastric cancer). In oral squamous cell carcinoma (OSCC) a number of Wnt and Frizzled genes are expressed, mostly Wnt5a and Frizzled-5 but the role of Wnt5a has not yet been thoroughly elucidated. The aim of this study is to evaluate the role of Wnt5a in oral OSCC and its influence on the cell proliferation, migration and invasion. Material and methods: The protein content of Wnt5a in two OSCC cell lines (SCC25 and SCC9) was determined by Western blotting. The influence of rWnt5a and two Wnt5a-derived hexapeptides: Foxy5 (an agonist that mimics Wnt5a activity) and Box5 (an antagonist that inhibits Wnt5a) on the migration and proliferation in OSCC cell lines was studied by a scratch assay and BrdU. Invasion influenced by rWnt5a was studied using Boyden chambers. Results: Both cell lines express Wnt5a. Dose–response curves of rWnt5a in SCC9 and SCC25 indicate that Wnt5a increases migration with statistically significant effective concentration at 0.4 μg/ml but has no effect on the proliferation of the two cell lines. To confirm this we used Foxy5 and Box5. Foxy5 increases migration with statistically significant effective concentration at 150 μM while Box5 inhibits Wnt5a effect on the migration. Foxy5 and Box5 have no influence on proliferation. Invasion was increased by rWnt5a. Conclusions: The results demonstrate that Wnt5a increases migration and invasion but has no influence on proliferation in OSCC cell lines.
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  • Sasaki, Yutaka, et al. (författare)
  • The anti-tumour effect of cisplatin and ifosfamide on xenografted squamous cell carcinoma of the head and neck is schedule-dependent.
  • 2012
  • Ingår i: Oral Oncology. - : Elsevier BV. - 1879-0593 .- 1368-8375. ; 48, s. 61-66
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of chemotherapy (CHX) in squamous cell carcinoma of the head and neck (SCCHN) has been expanding. Although combination chemotherapy regimens regularly produce significantly high response rates, meta-analyses show little benefit regarding final outcome. One way to improve induction CHX is to improve drug combinations and schedules for CHX. Cisplatin (CDDP) is one of the most active drugs in the treatment of patients with SCCHN, and it is used in most combinations. Ifosfamide (IFO) is another agent that has shown activity in the treatment of patients with SCCHN. A poorly differentiated squamous cell carcinoma xenografted to nude mice was used. CDDP (2.5mg/kg) and IFO (100mg/kg) as single bolus doses induced significant retardation of tumour growth. Single drug administration was compared with CDDP given before IFO and IFO given before CDDP. Mean specific growth delay (SGD) for untreated controls was 0. For CDDP as single drug it was 1.50, for IFO as single drug it was 0.79, for CDDP given 4h before IFO it was 1.79, and for IFO given 4h before CDDP it was 2.90. Maximum toxicity, calculated as change in median weight at day 7, was less than 10%. The efficacy and toxicity of CDDP and IFO is schedule-dependent, with IFO given before CDDP being more effective than CDDP given before IFO. This is in contrast to most schedules used clinically. The toxicities were comparable. The number of combinations of drugs with respect to order and time interval is of a magnitude that would not be possible to test clinically. In the pursuit of more efficient combinations, the importance of order and schedule of drugs and also the potential of xenografted SSCHN are underestimated.
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43.
  • Troiano, Giuseppe, et al. (författare)
  • Circulating miRNAs from blood, plasma or serum as promising clinical biomarkers in oral squamous cell carcinoma : A systematic review of current findings
  • 2016
  • Ingår i: Oral Oncology. - : Elsevier BV. - 1368-8375 .- 1879-0593. ; 63, s. 30-37
  • Forskningsöversikt (refereegranskat)abstract
    • The purpose of this systematic review was to summarize current findings on the use of circulating miRNAs from blood, serum and plasma as cancer biomarkers in patients with oral squamous cell carcinoma. Studies were gathered after searching four different electronic databases: PUBMED, SCOPUS, Cochrane Library and Web of Science. Additional search was carried out through cross check on bibliography of selected articles. After the selection process made by two of the authors, 16 articles met the inclusion criteria and were included in the review. Results showed that circulating miRNAs from blood, serum or plasma represent promising candidates as cancer biomarkers in patients suffering from oral cancer. The possibility to predict recurrences and metastases through follow-up quantification of candidate miRNAs represents another potential feature to be addressed in future studies. However, methodological standardization and uniform sampling is needed to increase the power and accuracy of results. 
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44.
  • Zhu, Ling, et al. (författare)
  • Sensory recovery and oral health-related quality of life following tongue reconstruction using non-innervated radial forearm free flaps
  • 2021
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 121
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: This study aimed to monitor the recovery of somatosensory function and oral health-related quality of life after tongue reconstruction using a non-innervated radial forearm free flap (RFFF).METHODS: Twenty patients (9 men, age: 42-67 years) underwent tongue reconstruction with non-innervated RFFFs, and twenty age- and sex-matched controls were included in this study. Quantitative sensory testing (QST), including cold, warm, and mechanical detection thresholds (CDT, WDT, MDT); cold, heat, and mechanical pain thresholds (CPT, HPT, MPT); and static two-point, sharp/blunt, and direction discrimination (S2-PD, S/BD, DD) were determined 9 months and 18 months after surgery on the surgical (9 M, 18 M) and contralateral sides (9Mc, 18Mc). Oral Health Impact Profile-49 (OHIP-49) was used to determine the oral-related quality of life of participants.RESULTS: All parameters showed significantly lower sensitivity at 9 M and 18 M (p < 0.001) compared to those for the controls and the contralateral side, except for DD (p = 0.101). In addition, the parameters showed a significant decrease in sensitivity for 9Mc and 18Mc (p ≤ 0.043) compared to those for the controls, except for MPT, HPT, S/SD, and DD (p ≥ 0.453). Findings on WDT, MPT, S2-PD, and DD (p ≤ 0.046) indicated significantly higher somatosensory function at 18 M than that at 9 M. MDT and MPT (p ≤ 0.038) showed significantly higher sensitivity at 18Mc than at 9Mc. Scores for all dimensions of OHIP-49 were significantly higher in patients (decrease in quality of life, p ≤ 0.002) than in controls, except for physical discomfort (p = 0.51). However, the scores were significantly higher at 18 M than at 9 M (p ≤ 0.011), except for handicap (p = 0.36). Postoperative chemotherapy was significantly correlated with impaired thermal sensitivity of the flaps (WDT, p = 0.049).CONCLUSION: The present findings showed significant impairment in somatosensory function on both the surgical and contralateral sides of patients with RFFFs. However, a significant increase in somatosensory function was observed on both sides over time. Somatosensory disturbances observed after surgery were associated with poor oral health-related quality of life.
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45.
  • Zupancic, Mark, et al. (författare)
  • Human papillomavirus (HPV) load is higher in HPVDNA/p16 positive than in HPVDNA positive/p16 negative oropharyngeal squamous cell carcinoma but does not differ significantly between various subsites or correlate to survival
  • 2024
  • Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 151
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivePatients with human papillomavirus DNA positive (HPVDNA+) and p16ink4a overexpressing (p16+) oropharyngeal squamous cell carcinoma (OPSCC), especially those with cancer in the tonsillar and base of tongue subsites as compared to other OPSCC subsites have a better outcome than those with only HPVDNA+ or only p16+ cancer. Likewise having a high viral load has been suggested to be a positive prognostic factor. We therefore hypothesized, that HPV viral load could vary depending on OPSCC subsite, as well as with regard to whether the cancer was HPVDNA+ and p16+, or only HPVDNA+, or only p16+ and that this affected outcome.Material and methodsTo address these issues HPV viral load was determined by HPV digital droplet (dd) PCR in tumor biopsies with previously known HPVDNA/p16 status from 270 OPSCC patients diagnosed 2000–2016 in Stockholm, Sweden. More specifically, of these patients 235 had HPVDNA+/p16+, 10 had HPVDNA+/p16-, 13 had HPVDNA-/p16+ and 12 had HPVDNA-/p16- cancer.ResultsWe found that HPVDNA+/p16+ OPSCC had a significantly higher viral load than HPVDNA+/p16- OPSCC. Moreover, there was a tendency for a higher viral load in the tonsillar and base of tongue OPSCC subsites compared to the other subsites and for a low viral load to correlate to a better clinical outcome but none of these tendencies reached statistical significance.ConclusionTo conclude, the mean viral load in HPVDNA+/p16+ OPSCC was higher than in HPVDNA+/p16- OPSCC, but there was no statistically significant difference in viral load depending on OPSCC subsite or on clinical outcome.
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46.
  • Öhman, Jenny, et al. (författare)
  • Oral and lip cancer in solid organ transplant patients--a cohort study from a Swedish Transplant Centre.
  • 2015
  • Ingår i: Oral oncology. - : Elsevier BV. - 1879-0593 .- 1368-8375. ; 51:2, s. 146-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous large studies have shown that solid organ transplant (SOT) patients have an increased risk of developing malignancies. Few studies have compared the prognosis for SOT patients who develop cancer with that of non-transplanted cancer patients. In this study we have investigated the increased risk of oral and lip cancer in SOT patients and also compared the relative survival between SOT patients and non-SOT patients with oral and lip cancer.
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