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Engström, Mats
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Publications (10 of 17) Show all publications
Laytragoon-Lewin, N., Cederblad, L., Andersson, B.-Å., Olin, M., Nilsson, M., Rutqvist, L.-E., . . . Lewin, F. (2017). Single Nucleotide Polymorphism and Cancer Risk, Tumour Recurrence, or Survival of Head and Neck Cancer Patients. Oncology, 92, 161-169
Open this publication in new window or tab >>Single Nucleotide Polymorphism and Cancer Risk, Tumour Recurrence, or Survival of Head and Neck Cancer Patients
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2017 (English)In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 92, p. 161-169Article in journal (Refereed) Published
Abstract [en]

Objective: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients. Methods: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study. Results: Ten SNPs were associated with H&N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNFα) rs1800629 could have an influence on cancer risk, tumor recurrence as well as survival. Conclusion: Genetic variation of the TNFα rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of H&N cancer patients.

Keywords
Tumor recurrence, Survival time, Single-nucleotide polymorphisms, Head and neck cancer
National Category
Cancer and Oncology Otorhinolaryngology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-331352 (URN)10.1159/000452278 (DOI)000395366800005 ()27997918 (PubMedID)
Note

L. Cederblad, B.-Å. Andersson, and M. Olin contributed equally to this work.

Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2018-09-14Bibliographically approved
Cederblad, L., Thunberg, U., Engström, M., Castro, J., Rutqvist, L. E. & Laytragoon-Lewin, N. (2013). The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells. Nicotine & tobacco research, 15(5), 890-895
Open this publication in new window or tab >>The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells
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2013 (English)In: Nicotine & tobacco research, ISSN 1462-2203, E-ISSN 1469-994X, Vol. 15, no 5, p. 890-895Article in journal (Refereed) Published
Abstract [en]

Introduction: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Methods: Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Results: After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 mu M nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. Conclusions: Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-200343 (URN)10.1093/ntr/nts207 (DOI)000317796500004 ()
Available from: 2013-05-28 Created: 2013-05-27 Last updated: 2017-12-06Bibliographically approved
Marsk, E., Hammarstedt-Nordenvall, L., Engström, M., Jonsson, L. & Hultcrantz, M. (2013). Validation of a Swedish version of the Facial Disability Index (FDI) and the Facial Clinimetric Evaluation (FaCE) scale. Acta Oto-Laryngologica, 133(6), 662-669
Open this publication in new window or tab >>Validation of a Swedish version of the Facial Disability Index (FDI) and the Facial Clinimetric Evaluation (FaCE) scale
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2013 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 133, no 6, p. 662-669Article in journal (Refereed) Published
Abstract [en]

Conclusion: Swedish versions of the Facial Disability Index (FDI) and Facial Clinimetric Evaluation (FaCE) scale are psychometrically valid. Both questionnaires can be used for clinical studies on peripheral facial palsy patients, and provide important information on quality of life. Objectives: To translate and validate Swedish versions of the FDI and FaCE scale in patients with peripheral facial palsy. Methods: Translation of the original questionnaires followed international guidelines. Internal consistency and test-retest stability were assessed in adult patients with stable peripheral facial palsy. Facial function was examined with the Sunnybrook and House-Brackmann scales. Subjects answered the questionnaires twice with a 2-week interval. Validity was assessed by comparing FDI and FaCE scale scores to SF-36 and Sunnybrook/House-Brackmann scores. Results: Ninety-three patients were included, 53% women and 47% men, mean age 56.9 years and mean duration of palsy 51.9 months. The questionnaires showed good/excellent psychometric properties with Cronbach's alpha scores between 0.76 and 0.92. In the test-retest analysis, intra-class correlation coefficients were very good for both questionnaires with scores of 0.83-0.97. Both questionnaires showed good sensitivity to discriminate between patients with varying degrees of facial dysfunction. Moderate to strong correlation was found between the social domains in the questionnaires when compared with the equivalent domains in SF-36.

Keywords
Facial palsy, Bell's palsy, quality of life, SF-36, translation, Cronbach's alpha, intra-class correlation, House-Brackmann, Sunnybrook
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-202345 (URN)10.3109/00016489.2013.766924 (DOI)000319011800016 ()
Available from: 2013-06-24 Created: 2013-06-24 Last updated: 2017-12-06Bibliographically approved
Axelsson, S., Berg, T., Jonsson, L., Engström, M., Kanerva, M. & Stjernquist-Desatnik, A. (2012). Bell's palsy: the effect of prednisolone and/or valaciclovir versus placebo in relation to baseline severity in a randomised controlled trial. Clinical Otolaryngology, 37(4), 283-290
Open this publication in new window or tab >>Bell's palsy: the effect of prednisolone and/or valaciclovir versus placebo in relation to baseline severity in a randomised controlled trial
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2012 (English)In: Clinical Otolaryngology, ISSN 1749-4478, E-ISSN 1365-2273, Vol. 37, no 4, p. 283-290Article in journal (Refereed) Published
Abstract [en]

Objectives: To evaluate the treatment effect of prednisolone and/or valaciclovir in Bells palsy patients with different baseline severity of palsy.

Design: Patient data were collected from the Scandinavian Bells Palsy Study, a prospective, randomised, double-blind, placebo-controlled, multi-centre trial.

Setting: Sixteen otorhinolaryngological centres in Sweden and one in Finland.

Participants: Altogether, 829 patients aged 1875 years were treated within 72 h of palsy onset. Patients were randomly assigned to treatment with prednisolone plus placebo (n = 210), valaciclovir plus placebo (n = 207), prednisolone plus valaciclovir (n = 206), placebo plus placebo (n = 206). Follow-up was 12 months.

Main outcome measures: Facial function was assessed using the Sunnybrook grading scale at baseline and at 12 months. Complete recovery was defined as Sunnybrook score = 100.

Results: All patients, regardless of baseline severity, showed significantly higher complete recovery rates if treated with prednisolone compared with no prednisolone. In patients with severe palsy, recovery at 12 months was 51% with prednisolone treatment versus 31% without prednisolone (P = 0.02). Corresponding results were 68%versus 51% (P = 0.004) for moderate, and 83%versus 73% (P = 0.02) for mild palsy. In patient groups with moderate and mild palsy at baseline, significantly fewer prednisolone-treated patients had synkinesis at 12 months (P = 0.04 and P < 0.0001, respectively). For patients with severe palsy at baseline, prednisolone versus no prednisolone made no significant difference regarding synkinesis at 12 months. Valaciclovir did not add any significant effect to prednisolone regarding recovery rate or synkinesis at 12 months.

Conclusion: Prednisolone treatment resulted in higher complete recovery rates, regardless of severity at baseline. Prednisolone treatment should be considered in all patients irrespective of degree of palsy.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-182541 (URN)10.1111/j.1749-4486.2012.02526.x (DOI)000308040800004 ()
Available from: 2012-10-11 Created: 2012-10-11 Last updated: 2017-12-07Bibliographically approved
Marsk, E., Bylund, N., Jonsson, L., Hammarstedt, L., Engström, M., Hadziosmanovic, N., . . . Hultcrantz, M. (2012). Prediction of nonrecovery in Bell's palsy using sunnybrook grading. The Laryngoscope, 122(4), 901-906
Open this publication in new window or tab >>Prediction of nonrecovery in Bell's palsy using sunnybrook grading
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2012 (English)In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 122, no 4, p. 901-906Article in journal (Refereed) Published
Abstract [en]

Objectives/Hypothesis: To develop a clinical prognostic model to identify Bell's palsy patients with risk for nonrecovery at 12 months.

Study Design: Data from a prospective, randomized, double-blind, placebo-controlled, multicenter study.

Methods: There were 829 patients with Bell's palsy randomized in a factorial fashion to treatment with prednisolone or no prednisolone. Facial function was assessed with the Sunnybrook grading scale. Univariate and multivariate logistic regression analyses at different time points were used to identify factors predicting nonrecovery, defined as Sunnybrook < 70 at 12 months. Variables studied were age, gender, time to inclusion, prednisolone treatment, side of palsy, pain at inclusion, and Sunnybrook scores. Factors of predictable significance were used to construct prognostic models at baseline, days 11 to 17, and at 1 month. Receiver operating characteristics curves were created to test the predictive capacity of the models.

Results: At baseline, treatment with prednisolone or no prednisolone (P = .0005), age (P = .04) and the Sunnybrook score (P = .0002) were significant factors for predicting nonrecovery. The receiver operating characteristics area under the curve at baseline for these three variables was 0.74 (sensitivity 0.83, specificity 0.57). At days 11 to 17 and at 1 month, the Sunnybrook score was the only significant predictive variable. The respective areas under the curves for the Sunnybrook score at these time points were 0.83 (sensitivity 0.81, specificity 0.75) and 0.94 (sensitivity 0.91, specificity 0.85).

Conclusions: Sunnybrook grading at 1 month most accurately predicts nonrecovery at 12 months in Bell's palsy.

Keywords
Facial palsy, facial paralysis, facial nerve, prognosis, multivariate analysis, receiver operating characteristics, area under the curve, Level of Evidence: 1b
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-173334 (URN)10.1002/lary.23210 (DOI)000301714800039 ()
Available from: 2012-04-24 Created: 2012-04-23 Last updated: 2017-12-07Bibliographically approved
Berg, T., Bylund, N., Marsk, E., Jonsson, L., Kanerva, M., Hultcrantz, M. & Engström, M. (2012). The Effect of Prednisolone on Sequelae in Bell's Palsy. Archives of Otolaryngology - Head & Neck Surgery, 138(5), 443-447
Open this publication in new window or tab >>The Effect of Prednisolone on Sequelae in Bell's Palsy
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2012 (English)In: Archives of Otolaryngology - Head & Neck Surgery, ISSN 0886-4470, E-ISSN 1538-361X, Vol. 138, no 5, p. 443-447Article in journal (Refereed) Published
Abstract [en]

Objective: To study whether prednisolone reduces sequelae in Bell's palsy. Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial with 12 months of follow-up. Setting: Seventeen referral centers. Patients: In all, 829 patients aged 18 to 75 years. Interventions: Randomization within 72 hours in a factorial fashion to placebo plus placebo (n=206); prednisolone, 60 mg/d for 5 days, with the dosage then tapered for 5 days, plus placebo (n=210); valacyclovir hydrochloride, 1000 mg 3 times daily for 7 days, plus placebo (n=207); or prednisolone plus valacyclovir (n=206). Main Outcome Measures: Facial function at 12 months assessed with the Sunnybrook and House-Brackmann grading systems. Results: In 184 of the 829 patients, the Sunnybrook score was less than 90 at 12 months; 71 had been treated with prednisolone and 113 had not (P<.001). In 98 patients, the Sunnybrook score was less than 70; 33 had received prednisolone and 65 had not (P<.001). The difference between patients who received prednisolone and who did not in House-Brackmann gradings higher than I and higher than II was also significant (P<.001 and P=.01, respectively). No significant difference was found between patients who received prednisolone and those who did not in Sunnybrook scores less than 50 (P=.10) or House-Brackmann grades higher than III (P=.80). Synkinesis was assessed with the Sunnybrook score in 743 patients. Ninety-six patients had a synkinesis score more than 2, of whom 33 had received prednisolone and 63 had not (P=.001). Sixty patients had a synkinesis score more than 4, of whom 22 had received prednisolone and 38 had not (P=.005). Conclusion: Prednisolone significantly reduces mild and moderate sequelae in Bell's palsy.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-177629 (URN)000305415100001 ()
Available from: 2012-07-17 Created: 2012-07-17 Last updated: 2017-12-07Bibliographically approved
Cheng, J., Engström, M., Ekberg, T., Nestor, M., Anniko, M. & Tolmachev, V. (2010). The use of closo-dodecaborate-containing linker improves targeting of HNSCC xenografts with radioiodinated chimeric monoclonal antibody U36. Molecular Medicine Reports, 3(1), 155-160
Open this publication in new window or tab >>The use of closo-dodecaborate-containing linker improves targeting of HNSCC xenografts with radioiodinated chimeric monoclonal antibody U36
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2010 (English)In: Molecular Medicine Reports, ISSN 1791-2997, Vol. 3, no 1, p. 155-160Article in journal (Refereed) Published
Abstract [en]

Radionuclide imaging of head and neck squamous cell carcinoma (HNSCC) using monoclonal antibodies (MAbs) has the potential to contribute to improved diagnosis and staging, thereby making more effective treatment possible. Chimeric monoclonal antibody U36 (cMAb U36), specific to CD44v6 antigen. is a candidate for the targeting of HNSCC. The aim of this study was to compare the influence of indirect iodination via closo-dodecaborate-based linker (DABI) with the influence of direct radioiodination on the biodistribution of the chimeric anti-CD44v6 antibody U36. The study was performed using nude mice bearing UT-SCC7 HNSCC xenografts using the paired-label method. The biodistribution of cMAb U36 labelled directly with I-131 and using DABI with I-125 was compared in the same animals. The influence of DABI on the tumour-to-organ ratio was evaluated. For both conjugates, radioactivity uptake in blood and organs decreased with time, except in tumours and the thyroid. DABI-labelled cMAb U36 was characterised by fast blood clearance and an elevated uptake in the liver and spleen. The use of DABI enabled a 1.5 to 2-fold improvement in the tumour-to-blood and tumour-to-organ ratios in comparison with direct radioiodination, with the exception of the liver and spleen. These results indicate that DABI is a promising linker for the coupling of radioiodine to HNSCC-targeting antibodies.

Keywords
nude mice, chimeric monoclonal antibody U36, head and neck squamous cell carcinoma, tumour transplantation, tumour targeting
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-127366 (URN)10.3892/mmr_00000233 (DOI)000272753700023 ()
Available from: 2010-07-13 Created: 2010-07-13 Last updated: 2015-02-27Bibliographically approved
Cederblad, L., Johansson, S., Enblad, G., Engström, M. & Blomquist, E. (2009). Cancer of the parotid gland; long-term follow-up: A single centre experience on recurrence and survival. Acta Oncologica, 48(4), 549-555
Open this publication in new window or tab >>Cancer of the parotid gland; long-term follow-up: A single centre experience on recurrence and survival
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2009 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, no 4, p. 549-555Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival.

PATIENTS AND METHODS:

At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16-89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64-66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume.

RESULTS:

The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3-5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s.

CONCLUSIONS:

Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-105426 (URN)10.1080/02841860802680419 (DOI)000265272900009 ()19140053 (PubMedID)
Available from: 2009-06-03 Created: 2009-06-03 Last updated: 2017-12-13Bibliographically approved
Björck, M., Bergqvist, D. & Engström, M. (2009). Glomustumörer, en kärlkirurgisk utmaning som kräver ett multidisciplinärt samarbete. Svensk Kirurgi, 67(3 Suppl.), 35
Open this publication in new window or tab >>Glomustumörer, en kärlkirurgisk utmaning som kräver ett multidisciplinärt samarbete
2009 (Swedish)In: Svensk Kirurgi, ISSN 0346-847X, Vol. 67, no 3 Suppl., p. 35-Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-112690 (URN)
Available from: 2010-01-19 Created: 2010-01-19 Last updated: 2017-12-12Bibliographically approved
Botling, J., Edlund, K., Segersten, U., Tahmasebpoor, S., Engström, M., Sundström, M., . . . Micke, P. (2009). Impact of thawing on RNA integrity and gene expression analysis in fresh frozen tissue. Diagnostic molecular pathology (Print), 18(1), 44-52
Open this publication in new window or tab >>Impact of thawing on RNA integrity and gene expression analysis in fresh frozen tissue
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2009 (English)In: Diagnostic molecular pathology (Print), ISSN 1052-9551, E-ISSN 1533-4066, Vol. 18, no 1, p. 44-52Article in journal (Refereed) Published
Abstract [en]

Biobanks of fresh, unfixed human tissue represent a valuable source for gene expression analysis in translational research and molecular pathology. The aim of this study was to evaluate the impact of thawing on RNA integrity and gene expression in fresh frozen tissue specimens. Portions of snap frozen tonsil tissue, unfixed or immersed in RNAlater, were thawed at room temperature for 0 minute, 5 minutes, 30 minutes, 45 minutes, 1 hour, 3 hours, 6 hours, and 16 hours before RNA extraction. Additionally, tonsil tissue underwent repetitive freezing and thawing cycles. RNA integrity was analyzed by microchip gel electrophoresis and gene expression by quantitative real-time polymerase chain reaction for selected genes (FOS, TGFB1, HIF1A, BCL2, and PCNA). Minimal RNA degradation was detected after 30 minutes of thawing in unfixed samples. This degradation was accompanied by relevant changes in gene expression for FOS and BCL2 at 45 minutes. Modified primer design or the use of different housekeeping genes could not rectify the changes for FOS. Repetitive thawing cycles had similar effects on RNA integrity. The incubation of the tissue in RNAlater efficiently prevented RNA degradation. In conclusion, degradation of RNA in frozen tissue occurs first after several minutes of thawing. Already minimal decrease in RNA quality may result in significant changes in gene expression patterns in clinical tissue samples.

Keywords
RNA degradation, gene expression, RNA quality, biobank, thawing
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-112901 (URN)10.1097/PDM.0b013e3181857e92 (DOI)000263781000006 ()19214109 (PubMedID)
Available from: 2010-01-22 Created: 2010-01-22 Last updated: 2018-02-01Bibliographically approved
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