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  • 1. Bersani, Cinzia
    et al.
    Mints, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Tertipis, Nikolaos
    Haeggblom, Linnea
    Näsman, Anders
    Romanitan, Mircea
    Dalianis, Tina
    Ramqvist, Torbjörn
    MicroRNA-155,-185 and-193b as biomarkers in human papillomavirus positive and negative tonsillar and base of tongue squamous cell carcinoma2018Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 82, s. 8-16Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 2. Bersani, Cinzia
    et al.
    Mints, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Tertipis, Nikolaos
    Haeggblom, Linnea
    Sivars, Lars
    Ährlund-Richter, Andreas
    Vlastos, Andrea
    Smedberg, Cecilia
    Grün, Nathalie
    Munck-Wikland, Eva
    Näsman, Anders
    Ramqvist, Torbjörn
    Dalianis, Tina
    A model using concomitant markers for predicting outcome in human papillomavirus positive oropharyngeal cancer2017Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 68, s. 53-59Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 3.
    Boldrup, Linda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, Philip J
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Differences in p63 expression in SCCHN tumours of different sub-sites within the oral cavity2011Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 47, nr 9, s. 861-865Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 4.
    Ebrahimi, Majid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Boldrup, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, Philip J
    Wahlin, Ylva-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral diagnostisk radiologi.
    Bourdon, Jean-Christophe
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Expression of novel p53 isoforms in oral lichen planus.2007Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 44, nr 2, s. 156-161Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 5.
    Ebrahimi, Majid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Boldrup, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wahlin, Ylva-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Pedodonti.
    Coates, Philip J
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Decreased expression of the p63 related proteins beta-catenin, E-cadherin and EGFR in oral lichen planus2007Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 44, nr 7, s. 634-638Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 6.
    Rentoft, Matilda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Laurell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Coates, Philip J
    Sjöström, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Comments on "Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples" by Saleh et al., Oral Oncol 46 (2010) 379-386.2010Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 46, nr 12, s. 891-892Artikkel i tidsskrift (Annet vitenskapelig)
  • 7.
    Skolin, I.
    et al.
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Pediatrik.
    Axelsson, K.
    Umeå universitet, Medicinsk fakultet, Omvårdnad.
    Ghannad, P.
    Umeå universitet, Medicinsk fakultet, Odontologi, Pedodonti.
    Hernell, O.
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Pediatrik.
    Wahlin, YB
    Umeå universitet, Medicinsk fakultet, Odontologi, Pedodonti.
    Nutrient intake and weight development in children during chemotherapy for malignant disease1997Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 33, nr 5, s. 364-368Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 8. Troiano, Giuseppe
    et al.
    Boldrup, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ardito, Fatima
    Gu, Xaolian
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lo Muzio, Lorenzo
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Circulating miRNAs from blood, plasma or serum as promising clinical biomarkers in oral squamous cell carcinoma: A systematic review of current findings2016Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 63, s. 30-37Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    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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