| 1. |
- Ahlén Bergman, Emma, et al.
(författare)
-
Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
- 2018
-
Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
|
|
| 2. |
- Gordon, Daniela, et al.
(författare)
-
Sentinel Node Location in Trunk and Extremity Melanomas: Uncommon or Multiple Lymph Drainage Does Not Affect Survival
- 2014
-
Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 21:11, s. 3386-3394
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with cutaneous melanoma (CM) on the trunk have a worse prognosis than those with extremity CM. One reason could be multiple or uncommon (outside axilla or groin) sentinel node locations (SNLs). We identified 859 patients who underwent sentinel node biopsy for trunk (n = 465) or extremity (n = 394) CM in three Swedish healthcare regions from 2000 to 2008. We collected patient, tumor, and sentinel node characteristics through clinical registers and medical records. We investigated the distribution of SNLs in a logistic regression model, and risk of overall and melanoma-specific death through 2011 in a multivariable Cox regression model. Trunk CM was associated with multiple SNLs (31 vs. 7 %; odds ratio [OR] 7.1; 95 % confidence interval [CI] 4.6-11.5; p < 0.001) but not uncommon SNLs (8 vs. 7 %; OR 1.1; 95 % CI 0.6-1.9; p = 0.75) compared with extremity CM. The increased risk of melanoma-specific death was confirmed for trunk CM (hazard ratio [HR] 1.9; 95 % CI 1.3-2.9; p = 0.003), especially on the upper back (HR 2.3; 95 % CI 1.4-3.6; p < 0.001) compared with extremity CM. Uncommon SNLs (HR 0.5; 95 % CI 0.2-1.4; p = 0.21) or multiple SNLs (HR 1.1; 95 % CI 0.4-2.9; p = 0.81) were not associated with melanoma-specific death compared with those with common/single SNL. Trunk melanomas were associated with multiple lymph drainage, but the worse prognosis of trunk melanomas could not be explained by the increased frequency of multiple or uncommon SNLs.
|
|
| 3. |
- Lacson, John Charles A., et al.
(författare)
-
Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families
- 2021
-
Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. Methods: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. Results: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. Conclusions: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.
|
|
| 4. |
- Taylor, Nicholas J, et al.
(författare)
-
Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT
- 2019
-
Ingår i: Journal of the American Academy of Dermatology. - : Elsevier BV. - 0190-9622 .- 1097-6787. ; 81:2, s. 386-394
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of melanoma families and whether performance improvements can be achieved.METHODS: 2,116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CI) along with net reclassification indices (NRI) as performance metrics.RESULTS: MELPREDICT performed well (AUC=0.752; 95%CI: 0.730, 0.775), and GenoMELPREDICT performance was similar (AUC=0.748; 95% CI: 0.726, 0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (p<0.0001) in GenoMELPREDICT (AUC=0.772; 95%CI: 0.750, 0.793; NRI=0.40). Including phenotypic risk factors did not improve performance.CONCLUSION: The MELPREDICT model functioned well in a global dataset of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in counselling these patients towards genetic testing or cancer risk counselling.
|
|
| 5. |
- Taylor, Nicholas J., et al.
(författare)
-
Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families
- 2017
-
Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 137:12, s. 2606-2612
-
Tidskriftsartikel (refereegranskat)abstract
- Germline mutations in CDKN2A are frequently identified among melanoma kindreds and are associated with increased atypical nevus counts. However, a clear relationship between pathogenic CDKN2A mutation carriage and other nevus phenotypes including counts of common acquired nevi has not yet been established. Using data from GenoMEL, we investigated the relationships between CDKN2A mutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families. Compared with individuals without a pathogenic mutation, those who carried one had an overall higher prevalence of atypical (odds ratio = 1.64; 95% confidence interval = 1.18–2.28) nevi but not 2-mm nevi (odds ratio = 1.06; 95% confidence interval = 0.92–1.21) or 5-mm nevi (odds ratio = 1.26; 95% confidence interval = 0.94–1.70). Stratification by case status showed more pronounced positive associations among non-case family members, who were nearly three times (odds ratio = 2.91; 95% confidence interval = 1.75–4.82) as likely to exhibit nevus counts at or above the median in all three nevus categories simultaneously when harboring a pathogenic mutation (vs. not harboring one). Our results support the hypothesis that unidentified nevogenic genes are co-inherited with CDKN2A and may influence carcinogenesis.
|
|
| 6. |
- Ytreberg, Agnes, et al.
(författare)
-
God havsmiljö 2020 : Marin strategi för Nordsjön och Östersjön Del 3: Övervakningsprogram
- 2014
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Havsmiljöförordningens övergripande mål är att upprätthålla eller uppnå en god miljöstatus i de svenska förvaltningsområdena Nordsjön och Östersjön till år 2020. En av uppgifterna i den första förvaltningsperioden är att fastställa övervakningsprogram.God miljöstatus baseras på ett ramverk av så kallade deskriptorer som anges i havsmiljödirektivet, det vill säga det EU-direktiv som i Sverige genomförs genom havsmiljöförordningen. Deskriptorerna beskriver god miljöstatus på en övergripande nivå för elva temaområden. Till varje deskriptor hör en rad kriterier som anger vad som ska ingå i en bedömning av miljöstatus. Utifrån de elva deskriptorerna har Sverige fastställt 13 övervakningsprogram. Sex program utgår ifrån olika biodiversitetsteman som berörs av en upp till tre deskriptorer, medan de övriga sju programmen utgår ifrån de deskriptorer som är mer inriktade mot belastning och miljöförändring.För varje program har ett antal underprogram föreslagits baserat på den nuvarande övervakningen och/eller planerad övervakning. Övervakning som ingår i programmen ska vara pågående och data ska vara tillgängliga. I programmen ingår nationell och regional miljöövervakning inklusive verksamhetsutövares recipientkontroll. Dessutom ingår annan typ av datainsamling som till exempel inventeringar av tumlare och uppgifter om omfattningen av mänskliga aktiviteter som orsakar belastning och miljöförändringar. Enligt havsmiljödirektivet ska övervakningen fånga upp tillstånd och miljöförändringar, belastning och omfattning av aktiviteterna som orsakar belastningen samt effekter av åtgärder. Eftersom nästa steg i havsförvaltningscykeln är att fastställa åtgärdsprogram kommer övervakning för att följa upp åtgärder att läggas till övervakningsprogrammen först under nästa förvaltningscykel.I beskrivningarna av programmen framgår hur den nuvarande övervakningen motsvarar de krav som ställs på dataunderlag genom havsmiljödirektivets bilaga III samt genom deskriptorer, kriterier, indikatorer och beslutade miljökvalitetsnormer. I dagens övervakning saknas bland annat tillräcklig övervakning för uppföljning av livsmiljöers tillstånd och utbredning. För marint avfall, buller och främmande arter saknas nationellt samordnad övervakning, men det görs regionala insatser och ett antal projekt har genomförts eller påbörjats för att öka kunskapen om hur övervakning bäst ska utformas. För de program som har pågående övervakning beskrivs utvecklingsbehoven för att förbättra underlaget för de återkommande tillståndsbedömningarna.Övervakningsprogrammet som fastställs under 2014 utgör således inte ett fast program för kunskapsinhämtning. Bristerna kommer att beaktas i det fortsatta genomförandet av havsmiljöförordningen där utveckling av indikatorer och övervakning kommer att ske kontinuerligt.
|
|
