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- Elliot, A, et al.
(författare)
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Incidence of IP and risk of malignant transformation in the Swedish population 1960-2010
- 2017
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Ingår i: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. - : Springer Science and Business Media LLC. - 1434-4726. ; 274:3, s. 1445-1448
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Tidskriftsartikel (refereegranskat)
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- Hammarstedt, Lilian, et al.
(författare)
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Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer
- 2006
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Ingår i: Int J Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 119:11, s. 2620-3
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Tidskriftsartikel (refereegranskat)abstract
- Smoking and alcohol are well-known etiological factors in tonsillar cancer. However, as in cervical cancer, human papillomavirus (HPV) is currently found in a sizable proportion of tonsillar cancer. Recent reports from the U.S. and Finland show an increase in the incidence of tonsillar cancer, without a parallel rise in smoking and alcohol consumption. This study investigates whether the incidence of tonsillar cancer has also changed in Sweden and whether a possible explanation of the increase is a higher proportion of HPV-positive tonsillar cancer. The incidence of tonsillar cancer between 1970 and 2002 in the Stockholm area was obtained from the Swedish Cancer Registry. In parallel, 203 pretreatment paraffin-embedded tonsillar cancer biopsies taken during 1970-2002 from patients in the Stockholm area were tested for presence of HPV DNA by PCR. The incidence of tonsillar cancer increased 2.8-fold (2.6 in men and 3.5 in women) from 1970 to 2002. During the same period, a significant increase in the proportion of HPV-positive tonsillar cancer cases was observed, as it increased 2.9-fold (p < 0.001). The distribution of HPV-positive cases was 7/30 (23.3%) in the 1970s, 12/42 (29%) in the 1980s, 48/84 (57%) in the 1990s and 32/47 (68%) during 2000-2002. We have demonstrated a highly significant and parallel increase both in the incidence of tonsillar cancer and the proportion of HPV-positive tumors. Hence, HPV may play an important role for the increased incidence of tonsillar cancer. This should definitely influence future preventive strategies as well as treatment for this type of cancer.
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- Marklund, L, et al.
(författare)
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Impact of HPV in Oropharyngeal Cancer
- 2011
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Ingår i: Journal of oncology. - : Hindawi Limited. - 1687-8469 .- 1687-8450. ; 2011, s. 509036-
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of oropharyngeal cancers has increased in the western world and Human Papilloma Virus (HPV) has been recognised as a risk factor in the last decades. During the same period the prevalence of HPV in oropharyngeal tumours has increased and HPV has been suggested responsible for the increase. The HPV-positive tumours are today recognized as a distinct subset of head and neck cancers with its own clinopathological and risk profile and have a significantly improved prognosis regardless of treatment strategy. This review summarizes current knowledge regarding human papillomavirus biology, oncogenic mechanisms, risk factors, and impact of treatment.
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- Wendt, M, et al.
(författare)
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Long-Term Survival and Recurrence in Oropharyngeal Squamous Cell Carcinoma in Relation to Subsites, HPV, and p16-Status
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Long-term survival data in relation to sub-sites, human papillomavirus (HPV), and p16INK4a (p16) for patients with oropharyngeal squamous cell carcinoma (OPSCC) is still sparse. Furthermore, reports have indicated atypical and late recurrences for patients with HPV and p16 positive OPSCC. Therefore, we assessed long-term survival and recurrence in relation to oropharyngeal subsite and HPV/p16 status. A total of 529 patients with OPSCC, diagnosed in the period 2000–2010, with known HPVDNA and p16-status, were included. HPV/p16 status and sub-sites were correlated to disease-free and overall survival (DFS and OS respectively). The overexpression of p16 (p16+) is associated with significantly better long-term OS and DFS in tonsillar and base of tongue carcinomas (TSCC/BOTSCC), but not in patients with other OPSCC. Patients with HPVDNA+/p16+ TSCC/BOTSCC presented better OS and DFS compared to those with HPVDNA−/p16− tumors, while those with HPVDNA−/p16+ cancer had an intermediate survival. Late recurrences were rare, and significantly more frequent in patients with p16− tumors, while the prognosis after relapse was poor independent of HPVDNA+/−/p16+/− status. In conclusion, patients with p16+ OPSCC do not have more late recurrences than p16−, and a clear prognostic value of p16+ was only observed in TSCC/BOTSCC. Finally, the combination of HPVDNA and p16 provided superior prognostic information compared to p16 alone in TSCC/BOTSCC.
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- Ahluwalia, T. S., et al.
(författare)
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Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- 2021
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:5, s. 393-409
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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| 35. |
- Bark, R, et al.
(författare)
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Cancer of the gingiva
- 2016
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Ingår i: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. - : Springer Science and Business Media LLC. - 1434-4726. ; 273:6, s. 1335-1345
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Tidskriftsartikel (refereegranskat)
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- D'Esposito, V., et al.
(författare)
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Adipocyte-released insulin-like growth factor-1 is regulated by glucose and fatty acids and controls breast cancer cell growth in vitro
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:10, s. 2811-2822
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes and obesity are associated with increased risk of site-specific cancers. We have investigated whether metabolic alterations at the level of adipose-derived differentiating cells may affect specific phenotypes of breast cancer cells. Growth profiles of breast cancer cell lines were evaluated in co-cultures with differentiated adipocytes or their precursor cells and upon treatment with adipocyte conditioned media. Production and release of cytokines and growth factors were assessed by real-time RT-PCR and multiplex-based ELISA assays. Co-cultures with either differentiated mouse 3T3-L1 or human mammary adipocytes increased viability of MCF-7 cells to a greater extent, when compared with their undifferentiated precursors. Adipocytes cultured in 25 mmol/l glucose were twofold more effective in promoting cell growth, compared with those grown in 5.5 mmol/l glucose, and activated mitogenic pathways in MCF-7 cells. Growth-promoting action was also enhanced when adipocytes were incubated in the presence of palmitate or oleate. Interestingly, 3T3-L1 and human adipocytes released higher amounts of keratinocyte-derived chemokine/IL-8, the protein 'regulated upon activation, normally T expressed, and secreted' (RANTES), and IGF-1, compared with their precursor cells. Their levels were reduced upon incubation with low glucose and enhanced by fatty acids. Moreover, both undifferentiated cells and differentiated adipocytes from obese individuals displayed about twofold higher IGF-1 release and MCF-7 cell growth induction than lean individuals. Finally, inhibition of the IGF-1 pathway almost completely prevented the growth-promoting effect of adipocytes on breast cancer cells. IGF-1 release by adipocytes is regulated by glucose and fatty acids and may contribute to the control of cancer cell growth in obese individuals.
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- Hribal, M. L., et al.
(författare)
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Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B
- 2011
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 54:4, s. 795-802
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry. METHODS: Sample 1 comprised 845 non-diabetic offspring of type 2 diabetes patients recruited in five European centres participating in the EUGENE2 study. Samples 2 and 3 comprised, respectively, 864 and 524 Italian non-diabetic participants. All individuals underwent an OGTT. Screening for the rs10811661 polymorphism was performed using a TaqMan allelic discrimination assay. RESULTS: The rs10811661 polymorphism did not show a significant association with age, BMI and insulin sensitivity. Participants carrying the TT genotype showed a significant reduction in insulin release, measured by an OGTT-derived index, compared with carriers of the C allele, in the three samples. When these results were pooled with those of three published studies, and meta-analysed with a random-effects model, the T allele was significantly associated with reduced insulin secretion (-35.09 [95% CI 14.68-55.52], p = 0.0008 for CC+CT vs TT; and -29.45 [95% CI 9.51-49.38], p = 0.0038, for the additive model). In addition, in our three samples, participants carrying the TT genotype exhibited an increased risk for impaired glucose tolerance (IGT) compared with carriers of the C allele (OR 1.55 [95% CI 1.20-1.95] for the meta-analysis of the three samples). CONCLUSIONS/INTERPRETATION: Our data, together with the meta-analysis of previously published studies, show that the rs10811661 polymorphism is associated with impaired insulin release and IGT, suggesting that this variant may contribute to type 2 diabetes by affecting beta cell function.
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| 42. |
- Makitie, AA, et al.
(författare)
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Head and neck cancer management in the Nordic countries: an effort to harmonize treatment
- 2017
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Ingår i: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. - : Springer Science and Business Media LLC. - 1434-4726. ; 274:5, s. 2363-2365
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Mulder, Skander, et al.
(författare)
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A metabolomics-based molecular pathway analysis of how the sodium-glucose co-transporter-2 inhibitor dapagliflozin may slow kidney function decline in patients with diabetes
- 2020
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Ingår i: Diabetes, obesity and metabolism. - : WILEY. - 1462-8902 .- 1463-1326. ; 22:7, s. 1157-1166
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate which metabolic pathways are targeted by the sodium-glucose co-transporter-2 inhibitor dapagliflozin to explore the molecular processes involved in its renal protective effects. Methods An unbiased mass spectrometry plasma metabolomics assay was performed on baseline and follow-up (week 12) samples from the EFFECT II trial in patients with type 2 diabetes with non-alcoholic fatty liver disease receiving dapagliflozin 10 mg/day (n = 19) or placebo (n = 6). Transcriptomic signatures from tubular compartments were identified from kidney biopsies collected from patients with diabetic kidney disease (DKD) (n = 17) and healthy controls (n = 30) from the European Renal cDNA Biobank. Serum metabolites that significantly changed after 12 weeks of dapagliflozin were mapped to a metabolite-protein interaction network. These proteins were then linked with intra-renal transcripts that were associated with DKD or estimated glomerular filtration rate (eGFR). The impacted metabolites and their protein-coding transcripts were analysed for enriched pathways. Results Of all measured (n = 812) metabolites, 108 changed (P < 0.05) during dapagliflozin treatment and 74 could be linked to 367 unique proteins/genes. Intra-renal mRNA expression analysis of the genes encoding the metabolite-associated proteins using kidney biopsies resulted in 105 genes that were significantly associated with eGFR in patients with DKD, and 135 genes that were differentially expressed between patients with DKD and controls. The combination of metabolites and transcripts identified four enriched pathways that were affected by dapagliflozin and associated with eGFR: glycine degradation (mitochondrial function), TCA cycle II (energy metabolism), L-carnitine biosynthesis (energy metabolism) and superpathway of citrulline metabolism (nitric oxide synthase and endothelial function). Conclusion The observed molecular pathways targeted by dapagliflozin and associated with DKD suggest that modifying molecular processes related to energy metabolism, mitochondrial function and endothelial function may contribute to its renal protective effect.
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- Yore, M. M., et al.
(författare)
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Discovery of a Class of Endogenous Mammalian Lipids with Anti-Diabetic and Anti-inflammatory Effects
- 2014
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 159:2, s. 318-332
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Tidskriftsartikel (refereegranskat)abstract
- Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice. FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g., palmitic-acid-9-hydroxy-stearic-acid, 9-PAHSA). PAHSAs are synthesized in vivo and regulated by fasting and high-fat feeding. PAHSA levels correlate highly with insulin sensitivity and are reduced in adipose tissue and serum of insulin-resistant humans. PAHSA administration in mice lowers ambient glycemia and improves glucose tolerance while stimulating GLP-1 and insulin secretion. PAHSAs also reduce adipose tissue inflammation. In adipocytes, PAHSAs signal through GPR120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes.
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