| 1. |
- Nielsen, S. N., et al.
(författare)
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No association between relapse hazard and thiopurine methyltransferase geno- or phenotypes in non-high risk acute lymphoblastic leukemia: a NOPHO ALL2008 sub-study
- 2021
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Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 88, s. 271-279
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Tidskriftsartikel (refereegranskat)abstract
- Purpose 6-mercaptopurine(6MP)/methotrexate maintenance therapy is essential to reduce relapse of childhood acute lymphoblastic leukemia (ALL). Common germline variants in TPMT cause low activity of thiopurine methyltransferase (TPMT) and higher 6MP metabolite (TGN) levels. Higher levels of TGNs incorporated into DNA (DNA-TG) and low TPMT activity have previously been associated with a lower relapse risk. We explored if TPMT geno- or phenotype was associated with DNA-TG levels and relapse rate in NOPHO ALL2008. Methods TPMT genotype, repeated phenotyping, and DNA-TG measurements were collected in 918 children with non-high risk ALL (NOPHO ALL2008 maintenance therapy study). Maintenance therapy started with 6MP at 50 and 75 mg/m(2) for TPMT heterozygous and wildtype patients and was adjusted to a target WBC of 1.5 - 3.0 x 10(9)/L. Results Of 918 patients, 78 (8.5%) were TPMT heterozygous and 903 had at least one TPMT measurement (total 3063). Mean TPMT activities were higher with wildtype than heterozygous TPMT (N = 752, 16.6 versus 9.6 U/mL ery., p < 0.001). The 5-year cumulative incidence of relapse was 6.4% and 6.0% for TPMT heterozygous and wildtype patients, and there was no association between genotype and relapse rate (N = 918, hazard ratio = 1.01, 95% confidence interval [CI] 0.40 - 2.54, p = 0.98). Although TPMT heterozygous patients had higher DNA-TG (N = 548, median 760.9 [interquartile range (IQR) 568.7 - 890.3] versus 492.7 [IQR 382.1 - 634.6] fmol/mu g, p < 0.001), TPMT activity was not associated with relapse rate (N = 813; hazard ratio = 0.98 per one U/mL ery. increase in TPMT activity, 95% CI 0.91 - 1.06, p = 0.67). Conclusion TPMT geno- and phenotype were not associated with relapse in non-high risk NOPHO ALL2008.
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| 2. |
- Tulstrup, M., et al.
(författare)
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Effects of germ line DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia
- 2020
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 136:10, s. 1161-1168
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Tidskriftsartikel (refereegranskat)abstract
- Methotrexate (MTX) during maintenance therapy is essential for curing acute lymphoblastic leukemia (ALL), but dosing strategies aiming at adequate treatment intensity are challenged by interindividual differences in drug disposition. To evaluate genetic factors associated with MTX metabolism, we performed a genome-wide association study in 447 ALL cases from the Nordic Society for Pediatric Haematology and Oncology ALL2008 study, validating results in an independent set of 196 patients. The intergenic single-nucleotide polymorphism rs1382539, located in a regulatory element of DHFR, was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 x 10(-8)) related to suppression of enhancer activity, whereas rs35789560 in FPGS (p.R466C, P = 5.6 x 10(-9)) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Furthermore, the FPGS variant was linked with increased relapse risk (P = .044). These findings show a genetic basis for interpatient variability in MTX response and could be used to improve future dosing algorithms.
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| 3. |
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| 4. |
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| 5. |
- Berg, T, et al.
(författare)
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Smärtans förlopp vid Bell's pares
- 2006
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Ingår i: Svensk ÖNH-tidskrift. ; 13, s. 12-13
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
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| 7. |
- Diaconu, Iulia, et al.
(författare)
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Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus
- 2012
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72:9, s. 2327-2338
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Tidskriftsartikel (refereegranskat)abstract
- Oncolytic adenovirus is an attractive platform for immunotherapy because virus replication is highly immunogenic and not subject to tolerance. Although oncolysis releases tumor epitopes and provides costimulatory danger signals, arming the virus with immunostimulatory molecules can further improve efficacy. CD40 ligand (CD40L, CD154) induces apoptosis of tumor cells and triggers several immune mechanisms, including a T-helper type 1 (TH1) response, which leads to activation of cytotoxic T cells and reduction of immunosuppression. In this study, we constructed a novel oncolytic adenovirus, Ad5/3-hTERT-E1A-hCD40L, which features a chimeric Ad5/3 capsid for enhanced tumor transduction, a human telomerase reverse transcriptase (hTERT) promoter for tumor selectivity, and human CD40L for increased efficacy. Ad5/3-hTERT-E1A-hCD40L significantly inhibited tumor growth in vivo via oncolytic and apoptotic effects, and (Ad5/3-hTERT-E1A-hCD40L)–mediated oncolysis resulted in enhanced calreticulin exposure and HMGB1 and ATP release, which were suggestive of immunogenicity. In two syngeneic mouse models, murine CD40L induced recruitment and activation of antigen-presenting cells, leading to increased interleukin-12 production in splenocytes. This effect was associated with induction of the TH1 cytokines IFN-γ, RANTES, and TNF-α. Tumors treated with Ad5/3-CMV-mCD40L also displayed an enhanced presence of macrophages and cytotoxic CD8+ T cells but not B cells. Together, our findings show that adenoviruses coding for CD40L mediate multiple antitumor effects including oncolysis, apoptosis, induction of T-cell responses, and upregulation of TH1 cytokines.
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| 8. |
- Flyvholm, M-A, et al.
(författare)
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Nordic Occupational Skin Questionnaire - NOSQ
- 2002
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Questionnaires for surveying work-related skin diseases and exposures have been designed in the Nordic Occupational Skin Questionnaire (NOSQ) project. NOSQ-2002/SHORT is a short, ready-to-use questionnaire for screening and monitoring occupational skin diseases on hands and forearms. NOSQ-2002/LONG is a longer, more in-depth questionnaire for surveying hand dermatitis and risk factors in workplaces or in a population. The Nordic Council of Ministers has the copyright to the NOSQ-2002 questionnaires. Use of the questionnaires is free of charge. The NOSQ-2002 questionnaires and their present and possible future translations cannot be used commercially. The NOSQ-2002 report includes a review of pertinent literature on questionnaire methods for skin disease studies and the NOSQ-2002/INFO version of the questionnaire including instructions and recommendations to researchers and guidelines for modification.
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| 9. |
- Gruvberger, Birgitta, et al.
(författare)
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Methyldibromoglutaronitrile
- 2003
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Ingår i: Management of positive patch test reactions. - 3540443479 ; , s. 41-41
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
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