umu.sePublications
Change search
Refine search result
45678910 301 - 350 of 1274
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 301.
    Franzén, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sundström, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Gustafsson, Hans
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Littbrand, Bo
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fractionated irradiation and early changes in noradrenaline induced potassium efflux(86Rb+) in rat parotid gland1992In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 31, no 3, p. 359-364Article in journal (Refereed)
    Abstract [en]

    The effects of fractionated irradiation on the electrolyte fluid secretion from rat parotid gland were studied. Secretion was measured as noradrenaline stimulated potassium efflux in vitro with Rb-86+ as tracer for potassium. The irradiation was delivered either as a five-day schedule (total dose 20, 25, 30, 35, 40, 45 Gy) or a two-day schedule (total dose 24, 32 Gy). The noradrenaline stimulated efflux was decreased in comparison with contralateral controls 10 days after the last irradiation. The effect was dose-dependent. Based on the data available, alpha/beta ratio of the used system was calculated to about 20 Gy, which corresponds to other results regarding early radiation effects.

  • 302.
    Fridriksson, Jón O.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Folkvaljon, Yasin
    Nilsson, Per
    Robinson, David
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Ryhov Hospital, J€onk€oping, Sweden.
    Franck-Lissbrant, Ingela
    Ehdaie, Behfar
    Eastham, James A.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Camilla T.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Long-term adverse effects after curative radiotherapy and radical prostatectomy: population-based nationwide register study2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 5, p. 338-345Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to assess the risk of serious adverse effects after radiotherapy (RT) with curative intention and radical prostatectomy (RP).

    Materials and methods: Men who were diagnosed with prostate cancer between 1997 and 2012 and underwent curative treatment were selected from the Prostate Cancer data Base Sweden. For each included man, five prostate cancer-free controls, matched for birth year and county of residency, were randomly selected. In total, 12,534 men underwent RT, 24,886 underwent RP and 186,624 were controls. Adverse effects were defined according to surgical and diagnostic codes in the National Patient Registry. The relative risk (RR) of adverse effects up to 12 years after treatment was compared to controls and the risk was subsequently compared between RT and RP in multivariable analyses.

    Results: Men with intermediate- and localized high-risk cancer who underwent curative treatment had an increased risk of adverse effects during the full study period compared to controls: the RR of undergoing a procedures after RT was 2.64 [95% confidence interval (CI) 2.56–2.73] and after RP 2.05 (95% CI 2.00–2.10). The risk remained elevated 10–12 years after treatment. For all risk categories of prostate cancer, the risk of surgical procedures for urinary incontinence was higher after RP (RR 23.64, 95% CI 11.71–47.74), whereas risk of other procedures on the lower urinary tract and gastrointestinal tract or abdominal wall was higher after RT (RR 1.67, 95% CI 1.44–1.94, and RR 1.86, 95% CI 1.70–2.02, respectively).

    Conclusion: The risk of serious adverse effects after curative treatment for prostate cancer remained significantly elevated up to 12 years after treatment.

  • 303.
    Fritzson, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Axelsson, Bertil
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Association between parenteral fluids and symptoms in hospital end-of-life care: an observational study of 280 patients2015In: BMJ Supportive & Palliative Care, ISSN 2045-435X, E-ISSN 2045-4368, Vol. 5, no 2, p. 160-168Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate whether dying patients receiving parenteral fluids (PF) suffer from more or less symptoms than patients who do not receive PF. Today's evidence on how PF affects palliative patients' symptoms is very scarce. Nevertheless, 40% of the patients who die expectedly in Swedish hospitals receive PF during their last 24 h of life.

    METHODS: A historical cohort study of medical records was performed. Of the 530 patients who were reported to have died expectedly at hospital in Västerbotten county (Sweden) between 1 January 2011 and 30 June 2012, 140 cases who had received PF and 140 controls who had not received PF were identified by stratified randomisation and matched by age, sex and main disease. The groups were compared regarding documented presence of dyspnoea, respiratory secretions, anxiety, nausea and confusion during the last 24 h and the last week of life.

    RESULTS: The prevalence of documented dyspnoea in the PF groups was higher than in the non-PF groups (51% vs 22% last 24 h, p<0.0001; 70% vs 45% last 7 days, p<0.001). The proportions of patients suffering from dyspnoea increased with larger administered volume. Although our main hypothesis--that the prevalence of respiratory secretions would be higher in the PF group--was not confirmed, we found a tendency in that direction (63% vs 50% last week, p=0.072). No clinically significant differences in anxiety, nausea or confusion were found.

    CONCLUSIONS: There is an association between PF administration and increased frequency of documented dyspnoea for terminally ill patients in their last week of life.

  • 304.
    Frängsmyr, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Baranov, Vladimir
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Stendahl, Ulf
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Kjellberg, Lennart
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Cytoplasmic microvesicular form of Fas ligand in human early placenta: switching the tissue immune privilege hypothesis from cellular to vesicular level2004In: Mol Hum Reprod, ISSN 1360-9947, Vol. 11, no 1, p. 35-41Article in journal (Refereed)
  • 305. Försti, A
    et al.
    Lei, H
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Enquist, K
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Altieri, A
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hemminki, K
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Polymorphisms in the genes of the urokinase plasminogen activation system in relation to colorectal cancer.2007In: Ann Oncol, ISSN 0923-7534, Vol. 18, p. 1990-1994Article in journal (Refereed)
  • 306. Försti, Asta
    et al.
    Jin, Qianren
    Altieri, Andrea
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Wagner, Kerstin
    Enquist, Kerstin
    Grzybowska, Ewa
    Pamula, Jolanta
    Pekala, Wioletta
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Hemminki, Kari
    Polymorphisms in the KDR and POSTN genes: association with breast cancer susceptibility and prognosis.2007In: Breast Cancer Research and Treatment, ISSN 0167-6806, Vol. 101, no 1, p. 83-93Article in journal (Refereed)
    Abstract [en]

    Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke. Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting. Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke. Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.

  • 307.
    Försti, Asta
    et al.
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany / Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
    Li, Xuchen
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Wagner, Kerstin
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Altieri, Andrea
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hemminki, Kari
    Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany / Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression2010In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 49, no 3, p. 270-281Article in journal (Refereed)
    Abstract [en]

    Transforming growth factor beta1 (TGFB1) acts as a growth inhibitor of normal colonic epithelial cells, however, as a tumor promoter of colorectal cancer (CRC) cells. To explore the association between genetic polymorphisms in the TGFB1 pathway and CRC susceptibility and clinical outcome, we carried out a case-control study on a Swedish population of 308 CRC cases and 585 age- and gender-matched controls. The cases were sampled prospectively and had up to 16 years follow-up, making the study material particularly suitable for survival analysis. On the basis of their reported or predicted functional effect, nine single-nucleotide polymorphisms (TGFB1: Leu10Pro; TGFBR1: 9A/6A and IVS7G+24A; FURIN: C-229T; THBS1: T+42C; LTBP1L: C-256G; LTBP4: T-893G and Thr750Ala; BAMBI: T-779A) were selected for genotyping. We evaluated the associations between genotypes and CRC and Dukes' stage. Survival probabilities were compared between different subgroups. The observed statistically significant associations included a decreased CRC risk for TGFBR1 IVS7G+24A minor allele carriers (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.53-0.97), less aggressive tumors with Dukes' stage A+B for carriers of LTBP4 Thr750Ala and BAMBI T-779A minor alleles (OR: 0.58, 95%CI: 0.36-0.93 and OR: 0.51, 95%CI: 0.29-0.89, respectively) and worse survival for FURIN C-229T heterozygotes (hazard ratio: 1.63, 95%CI: 1.08-2.46). As this is the first study about the influence of the polymorphisms in the TGFB1 pathway on CRC progression, further studies in large independent cohorts are warranted.

  • 308.
    Garpebring, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Yu, Jun
    Sveriges lantbruksuniversitet, Centre of Biostochastiscs.
    Wirestam, Ronnie
    Lunds universitet, Medicinsk strålningsfysik.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Uncertainty estimation in dynamic contrast-enhanced MRI2013In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 69, no 4, p. 992-1002Article in journal (Refereed)
    Abstract [en]

    Using dynamic contrast-enhanced MRI (DCE-MRI), it is possible to estimate pharmacokinetic (PK) parameters that convey information about physiological properties, e.g., in tumors. In DCE-MRI, errors propagate in a nontrivial way to the PK parameters. We propose a method based on multivariate linear error propagation to calculate uncertainty maps for the PK parameters. Uncertainties in the PK parameters were investigated for the modified Kety model. The method was evaluated with Monte Carlo simulations and exemplified with in vivo brain tumor data. PK parameter uncertainties due to noise in dynamic data were accurately estimated. Noise with standard deviation up to 15% in the baseline signal and the baseline T1 map gave estimated uncertainties in good agreement with the Monte Carlo simulations. Good agreement was also found for up to 15% errors in the arterial input function amplitude. The method was less accurate for errors in the bolus arrival time with disagreements of 23%, 32%, and 29% for Ktrans, ve, and vp, respectively, when the standard deviation of the bolus arrival time error was 5.3 s. In conclusion, the proposed method provides efficient means for calculation of uncertainty maps, and it was applicable to a wide range of sources of uncertainty.

  • 309.
    Garpebring, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Yu, Jun
    Wirestam, Ronnie
    Radiofysik, Lunds Universitet.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Thomas, Asklund
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Uncertainty Maps in Dynamic Contrast-Enhanced MRI2012Conference paper (Refereed)
  • 310.
    Garpebring, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Yu, Jun
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Wirestam, Ronnie
    Radiofysik, Lunds Universitet.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Thomas, Asklund
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Uncertainty Maps in Dynamic Contrast-Enhanced MRI2012Conference paper (Refereed)
  • 311.
    Garpebring, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wirestam, Ronnie
    Yu, Jun
    SLU, Centre of Biostochastics.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Phase-based arterial input functions in humans applied to dynamic contrast-enhanced MRI: potential usefulness and limitations2011In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 24, no 4, p. 233-245Article in journal (Refereed)
    Abstract [en]

    Object: Phase-based arterial input functions (AIFs) provide a promising alternative to standard magnitude-based AIFs, for example, because inflow effects are avoided. The usefulness of phase-based AIFs in clinical dynamic contrast-enhanced MRI (DCE-MRI) was investigated, and relevant pitfalls and sources of uncertainty were identified.

    Materials and methods: AIFs were registered from eight human subjects on, in total, 21 occasions. AIF quality was evaluated by comparing AIFs from right and left internal carotid arteries and by assessing the reliability of blood plasma volume estimates.

    Results: Phase-based AIFs yielded an average bolus peak of 3.9 mM and a residual concentration of 0.37 mM after 3 min, (0.033 mmol/kg contrast agent injection). The average blood plasma volume was 2.7% when using the AIF peak in the estimation, but was significantly different (p < 0.0001) and less physiologically reasonable when based on the AIF tail concentration. Motion-induced phase shifts and accumulation of contrast agent in background tissue regions were identified as main sources of uncertainty.

    Conclusions: Phase-based AIFs are a feasible alternative to magnitude AIFs, but sources of errors exist, making quantification difficult, especially of the AIF tail. Improvement of the technique is feasible and also required for the phase-based AIF approach to reach its full potential.

  • 312. Georgiadis, Panagiotis
    et al.
    Gavriil, Marios
    Rantakokko, Panu
    Ladoukakis, Efthymios
    Botsivali, Maria
    Kelly, Rachel S
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Kiviranta, Hannu
    Vermeulen, Roel C H
    Späth, Florentin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hebbels, Dennie G A J
    Kleinjans, Jos C S
    de Kok, Theo M C M
    Palli, Domenico
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia2019In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 126, p. 24-36Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To characterize the impact of PCB exposure on DNA methylation in peripheral blood leucocytes and to evaluate the corresponding changes in relation to possible health effects, with a focus on B-cell lymphoma.

    METHODS: We conducted an epigenome-wide association study on 611 adults free of diagnosed disease, living in Italy and Sweden, in whom we also measured plasma concentrations of 6 PCB congeners, DDE and hexachlorobenzene.

    RESULTS: We identified 650 CpG sites whose methylation correlates strongly (FDR < 0.01) with plasma concentrations of at least one PCB congener. Stronger effects were observed in males and in Sweden. This epigenetic exposure profile shows extensive and highly statistically significant overlaps with published profiles associated with the risk of future B-cell chronic lymphocytic leukemia (CLL) as well as with clinical CLL (38 and 28 CpG sites, respectively). For all these sites, the methylation changes were in the same direction for increasing exposure and for higher disease risk or clinical disease status, suggesting an etiological link between exposure and CLL. Mediation analysis reinforced the suggestion of a causal link between exposure, changes in DNA methylation and disease. Disease connectivity analysis identified multiple additional diseases associated with differentially methylated genes, including melanoma for which an etiological link with PCB exposure is established, as well as developmental and neurological diseases for which there is corresponding epidemiological evidence. Differentially methylated genes include many homeobox genes, suggesting that PCBs target stem cells. Furthermore, numerous polycomb protein target genes were hypermethylated with increasing exposure, an effect known to constitute an early marker of carcinogenesis.

    CONCLUSIONS: This study provides mechanistic evidence in support of a link between exposure to PCBs and the etiology of CLL and underlines the utility of omic profiling in the evaluation of the potential toxicity of environmental chemicals.

  • 313. Georgiadis, Panagiotis
    et al.
    Liampa, Irene
    Hebels, Dennie G
    Krauskopf, Julian
    Chatziioannou, Aristotelis
    Valavanis, Ioannis
    de Kok, Theo M C M
    Kleinjans, Jos C S
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Spaeth, Florentin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palli, Domenico
    Vermeulen, R C H
    Vlaanderen, J
    Chadeau-Hyam, Marc
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis2017In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 18, article id 728Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance.

    RESULTS: We employed peripheral blood buffy coats of 347 apparently healthy subjects, of whom 28 were diagnosed with CLL 2.0-15.7 years after enrollment, to derive for the first time genome-wide DNA methylation, as well as gene and miRNA expression, profiles associated with the risk of future disease. After adjustment for white blood cell composition, we identified 722 differentially methylated CpG sites and 15 differentially expressed genes (Bonferroni-corrected p < 0.05) as well as 2 miRNAs (FDR < 0.05) which were associated with the risk of future CLL. The majority of these signals have also been observed in clinical CLL, suggesting the presence in prediagnostic blood of CLL-like cells. Future CLL cases who, at enrollment, had a relatively low B-cell fraction (<10%), and were therefore less likely to have been suffering from undiagnosed CLL or a precursor condition, showed profiles involving smaller numbers of the same differential signals with intensities, after adjusting for B-cell content, generally smaller than those observed in the full set of cases. A similar picture was obtained when the differential profiles of cases with time-to-diagnosis above the overall median period of 7.4 years were compared with those with shorted time-to-disease. Differentially methylated genes of major functional significance include numerous genes that encode for transcription factors, especially members of the homeobox family, while differentially expressed genes include, among others, multiple genes related to WNT signaling as well as the miRNAs miR-150-5p and miR-155-5p.

    CONCLUSIONS: Our findings demonstrate the presence in prediagnostic blood of future CLL patients, more than 10 years before diagnosis, of CLL-like cells which evolve as preclinical disease progresses, and point to early molecular alterations with a pathogenetic potential.

  • 314.
    Ghasimi, Soma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Genotype-phenotype studies in brain tumors2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Meningioma and glioma are the most common primary brain tumors, but their etiologies are largely unknown. Although meningioma is usually benign, their intracranial location can lead to lethal consequences, and despite progress in surgery, radiotherapy, and chemotherapy the prognosis for patients with glioma remains poor. The only well-established environmental risk factor for meningioma and glioma is ionizing radiation. Evidence for inherited predisposition to meningioma and glioma is provided by a number of rare inherited syndromes where collectively these diseases account for only a small proportion of the twofold increased risk of brain tumors seen in first-degree relatives for meningioma and glioma patients. It is very possible that much of the excess familial risk is a consequence of co-inheritance of multiple low-risk genetic variations. With this in mind, the aims of the studies in this thesis were to discover genetic risk variants influencing the probability of acquiring the disease and to identify the association between risk variants on the tumor phenotype.

    To identify genetic variants influencing meningioma risk, a comprehensive tagging of the selected genes in a case-control study was performed. We identified nine risk variants in

    EGF, ERBB2, and LRIG2 genes. However, these findings could not be confirmed in another larger independent dataset. In addition, the study identified a correlation between LRIG2 protein expression and ER status when analyzed with different parameters. In a separate study with a larger sample of meningioma patients, the same correlation between LRIG2 and ER status was observed.

    To explore the potential association between reported germline risk variants and somatic genetic events, matched tumor and blood samples from glioma patients were analyzed by SNP array. The results identified correlations between

    EGFR gene variants and somatic aberrations within the EGFR locus and CDKN2A/B locus. To further study the relationship between germline risk variants and tumor phenotype, the same patient material was used and analyzed by three different techniques: SNP array, IHC, and FISH. The results revealed EGFR risk variants effecting copy number variation of the EGFR gene and the expression of the IDH1 and p53. Further comparison between different techniques such as SNP array and FISH analysis revealed the difficulty in achieving consistent results with different techniques.

    To summarize, the glioma studies show a link between genotype and phenotype where genetic risk variants in the

    EGFR gene were found to be associated with specific somatic aberrations. These associations are biologically interesting because EGFR is involved in multiple cellular processes. Additional studies of the direct functional role of these observations need to be conducted to elucidate the molecular mechanisms underlying the identified association between germline gene variants and somatic aberrations. For the meningioma studies, no significant risk variants influencing the disease were found but a correlation between LRIG2 and ER status was observed. This result suggests a potential role for the LRIG protein in the pathogenesis of meningioma, but more studies are needed to confirm this hypothesizes.

  • 315.
    Ghasimi, Soma
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Haapasalo, H.
    Eray, M.
    Korhonen, K.
    Brannstrom, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Immunohistochemical analysis of LRIG proteins in meningiomas: correlation between estrogen receptor status and LRIG expression2012In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 14, no Suppl 3, p. 69-69Article in journal (Other academic)
  • 316.
    Ghasimi, Soma
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Haapasalo, H
    Eray, M
    Dobbins, S
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ahlbom, A
    Auvinen, A
    Collatz-Laier, H
    Feychting, M
    Johansen, C
    Kiuru, A
    Houlston, R
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Genetic variants in EGF, EGFR, ERBB2, LRIG2, LRIG3 and meningioma riskManuscript (preprint) (Other academic)
  • 317.
    Ghasimi, Soma
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Dahlin, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Genetic risk variants in the EGFR regions are associated with copy number variation in the EGFR gene as well as IDH1, and p53 protein expressionManuscript (preprint) (Other academic)
  • 318.
    Ghasimi, Soma
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Dahlin, Anna M.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Genetic risk variants in the CDKN2A/B, RTEL1 and EGFR genes are associated with somatic biomarkers in glioma2016In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 127, no 3, p. 483-492Article in journal (Refereed)
    Abstract [en]

    During the last years, genome wide association studies have discovered common germline genetic variants associated with specific glioma subtypes. We aimed to study the association between these germline risk variants and tumor phenotypes, including copy number aberrations and protein expression. A total of 91 glioma patients were included. Thirteen well known genetic risk variants in TERT, EGFR, CCDC26, CDKN2A, CDKN2B, PHLDB1, TP53, and RTEL1 were selected for investigation of possible correlations with the glioma somatic markers: EGFR amplification, 1p/19q codeletion and protein expression of p53, Ki-67, and mutated IDH1. The CDKN2A/B risk variant, rs4977756, and the CDKN2B risk variant, rs1412829 were inversely associated (p = 0.049 and p = 0.002, respectively) with absence of a mutated IDH1, i.e., the majority of patients homozygous for the risk allele showed no or low expression of mutated IDH1. The RTEL1 risk variant, rs6010620 was associated (p = 0.013) with not having 1p/19q codeletion, i.e., the majority of patients homozygous for the risk allele did not show 1p/19q codeletion. In addition, the EGFR risk variant rs17172430 and the CDKN2B risk variant rs1412829, both showed a trend for association (p = 0.055 and p = 0.051, respectively) with increased EGFR copy number, i.e., the majority of patients homozygote for the risk alleles showed chromosomal gain or amplification of EGFR. Our findings indicate that CDKN2A/B risk genotypes are associated with primary glioblastoma without IDH mutation, and that there is an inverse association between RTEL1 risk genotypes and 1p/19q codeletion, suggesting that these genetic variants have a molecular impact on the genesis of high graded brain tumors. Further experimental studies are needed to delineate the functional mechanism of the association between genotype and somatic genetic aberrations.

  • 319. Ghez, D.
    et al.
    Fortpied, C.
    Mounier, N.
    Carde, P.
    Perrot, A.
    Khaled, H.
    Amorim, S.
    Ramadan, S.
    Bras, F. L.
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herbaux, C.
    Marolleau, J-P
    Nicolas-Virelezier, E.
    Casasnovas, O.
    Stamatoullas-Bastard, A.
    Ferme, C.
    First-line escalated BEACOPP does not hinder stem cell collection and transplantation strategy in patients with relapsed/refractory Hodgkin's lymphoma2017In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, no 2, p. 310-312Article in journal (Refereed)
  • 320. Ghez, D.
    et al.
    Fortpied, C.
    Mounier, N.
    Carde, P.
    Perrot, A.
    Khaled, H.
    Amorim, S.
    Ramadan, S.
    Le Bras, F.
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herbaux, C.
    Marolleau, J. P.
    Nicolas-Virelizier, E.
    Casasnovas, O.
    Stamatoullas-Bastard, A.
    Ferme, C.
    STEM CELL COLLECTION AFTER FAILURE OF UPFRONT ABVD OR BEACOPP IN PATIENTS WITH HIGH RISK ADVANCED STAGE III-IV HODGKIN'S LYMPHOMA2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no S5, p. 50-50, article id P091Article in journal (Refereed)
  • 321. Gholiha, Alex
    et al.
    Fransson, Greger
    Fürst, Carl Johan
    Heedman, Per-Anders
    Lundström, Staffan
    Axelsson, Bertil
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stora luckor i journaler vid vård i livets slutskede: Journaluppgifter saknas för data inrapporterade till Palliativregistret2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 16-17, p. 918-921Article in journal (Refereed)
    Abstract [sv]

    Dokumentation av vårdåtgärder och bedömningar är väsentlig för en optimal pal­lia­tiv vård.

    I denna studie har vi jämfört åtgärder som inrapporterats till Svenska palliativregistret i samband med dödsfall med den befintliga journaldokumentationen.

    Genom slumpmässigt urval deltog totalt 14 registeraktiva vårdenheter representerande de fem vanligaste enhetstyperna. De tio senaste dödsfallen på varje enhet grans­kades med fokus på vårdinnehållet sista veckan i livet.

    Bristfällig journaldokumentation noterades i stor utsträckning (8–76 procent).

    Behovet av tydliga sökord är stort för att såväl läkares som sjuksköterskors journaldokumentation ska kunna leva upp till modern standard vad gäller palliativa vårdinsatser i livets slutskede.

  • 322. Gillanders, Elizabeth M
    et al.
    Xu, Jianfeng
    Chang, Bao-li
    Lange, Ethan M
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Bailey-Wilson, Joan E
    Baffoe-Bonnie, Agnes
    Jones, MaryPat
    Gildea, Derek
    Riedesel, Erica
    Albertus, Julie
    Isaacs, Sarah D
    Wiley, Kathleen E
    Mohai, Caroline E
    Matikainen, Mika P
    Tammela, Teuvo L J
    Zheng, S Lilly
    Brown, W Mark
    Rökman, Annika
    Carpten, John D
    Meyers, Deborah A
    Walsh, Patrick C
    Schleutker, Johanna
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Cooney, Kathleen A
    Isaacs, William B
    Trent, Jeffrey M
    Combined genome-wide scan for prostate cancer susceptibility genes2004In: J Natl Cancer Inst, ISSN 1460-2105, Vol. 96, no 16, p. 1240-1247Article in journal (Refereed)
  • 323. Glimelius, Bengt
    et al.
    Ask, Anders
    Bjelkengren, Göran
    Björk-Eriksson, Thomas
    Blomquist, Erik
    Johansson, Bengt
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Number of patients potentially eligible for proton therapy2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 836-849Article in journal (Refereed)
    Abstract [en]

    A group of Swedish radiation oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy in a facility where one of the principal aims is to facilitate randomized and other studies in which the advantage of protons can be shown and the magnitude of the differences compared with optimally administered conventional radiation treatment, also including intensity-modulated radiation therapy (IMRT) and brachytherapy, can be shown. The estimations have been based on current statistics of tumour incidence in Sweden, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours together with information on normal tissue complication rates. In Sweden, it is assessed that between 2200 and 2500 patients annually are eligible for proton beam therapy, and that for these patients the potential therapeutic benefit is so great as to justify the additional expense of proton therapy. This constitutes between 14- 15% of all irradiated patients annually.

  • 324. Glimelius, Bengt
    et al.
    Dahl, Olav
    Cedermark, Björn
    Jakobsen, Anders
    Bentzen, Sören M
    Starkhammar, Hans
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Hultborn, Ragnar
    Albertsson, Maria
    Påhlman, Lars
    Tveit, Kjell-Magne
    Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group2005In: Acta Oncology, ISSN 0284-186X, Vol. 44, no 8, p. 904-912Article in journal (Refereed)
  • 325. Glimelius, Bengt
    et al.
    Myklebust, Tor Age
    Lundqvist, Kristina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibe, Arne
    Guren, Marianne G.
    Two countries - Two treatment strategies for rectal cancer2016In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 121, no 3, p. 357-363Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Trials in rectal cancer have shown that radiotherapy (RT) decreases local recurrence rates, whereas the effects on survival are uncertain. Swedish and Norwegian oncologists have had different treatment recommendations. The aim was to evaluate local recurrence rates and survival in the two countries.

    Patients and methods: Between 1995 and 2012 rectal cancer patients registered in Sweden and Norway were analyzed, presenting population-based “real world” data.

    Results: Totally 29,029 Swedish and 15,456 Norwegian patients were analyzed. Resection for cure was performed in two-thirds of the patients. RT was given to 49% of Swedish patients, mainly short-course RT and to 26% of Norwegian patients, predominantly chemoradiotherapy (CRT). In Sweden, the proportion irradiated was stable whereas in Norway, an increase from 10% to 40% was seen. Local 5-year recurrence rates were initially higher in Norway (12%) than in Sweden (8%), whereas they were equally low (4%) during the latter time. No survival differences were seen, however, survival improved with time in both countries.

    Conclusions: Two entirely different approaches to preoperative therapy resulted in similar survival with initially higher local recurrence rates in Norway, but similarly low rates in later years. This raises questions about optimal RT rates and regimens.

  • 326. Goldbrunner, Roland
    et al.
    Minniti, Giuseppe
    Preusser, Matthias
    Jenkinson, Michael D.
    Sallabanda, Kita
    Houdart, Emmanuel
    von Deimling, Andreas
    Stavrinou, Pantelis
    Lefranc, Florence
    Lund-Johansen, Morten
    Moyal, Elizabeth Cohen-Jonathan
    Brandsma, Dieta
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre Stockholm, Stockholm, Sweden.
    Soffietti, Riccardo
    Weller, Michael
    EANO guidelines for the diagnosis and treatment of meningiomas2016In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 17, no 9, p. E383-E391Article, review/survey (Refereed)
    Abstract [en]

    Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.

  • 327. Gontero, Paolo
    et al.
    Sylvester, Richard
    Pisano, Francesca
    Joniau, Steven
    Eeckt, Kathy Vander
    Serretta, Vincenzo
    Larre, Stephane
    Di Stasi, Savino
    Van Rhijn, Bas
    Witjes, Alfred J.
    Grotenhuis, Anne J.
    Kiemeney, Lambertus A.
    Colombo, Renzo
    Briganti, Alberto
    Babjuk, Marek
    Malmström, Per-Uno
    Oderda, Marco
    Irani, Jacques
    Malats, Nuria
    Baniel, Jack
    Mano, Roy
    Cai, Tommaso
    Cha, Eugene K.
    Ardelt, Peter
    Varkarakis, John
    Bartoletti, Riccardo
    Spahn, Martin
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Frea, Bruno
    Soukup, Viktor
    Xylinas, Evanguelos
    Dalbagni, Guido
    Karnes, R. Jeffrey
    Shariat, Shahrokh F.
    Palou, Joan
    Prognostic Factors and Risk Groups in T1G3 Non-Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guerin: Results of a Retrospective Multicenter Study of 2451 Patients2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, no 1, p. 74-82Article in journal (Refereed)
    Abstract [en]

    Background: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective: To assess prognostic factors in patients who received bacillus Calmette Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >= 70 yr, size >= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >= 70 yr with tumor size >= 3 cm and 13% otherwise. Conclusions: T1G3 patients >= 70 yr with tumors >= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >= 70 yr, tumor size >= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

  • 328. Granfors, Torvald
    et al.
    Modig, Hans
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Damber, Jan-Erik
    Tomic, Radisa
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Long-term followup of a randomized study of locally advanced prostate cancer treated with combined orchiectomy and external radiotherapy versus radiotherapy alone.2006In: J Urol, ISSN 0022-5347, Vol. 176, no 2, p. 544-7Article in journal (Refereed)
  • 329.
    Granholm, Susanne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henning, Petra
    Lindholm, Catharina
    Lerner, Ulf H.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Osteoclast progenitor cells present in significant amounts in mouse calvarial osteoblast isolations and osteoclastogenesis increased by BMP-22013In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 52, no 1, p. 83-92Article in journal (Refereed)
    Abstract [en]

    Enzymatically released cells from neonatal mouse calvarial bones are frequently used as primary mouse osteoblasts for in vitro studies. We, here, report that although these cells lack mRNA expression of the osteoclastic genes Calcr, Acp5 and Mmp-9 at early time points after their isolation, these transcripts are gradually upregulated when the calvarial osteoblast cultures are differentiated to more mature osteoblasts in long term cultures. Similarly, Calcr, Acp5, Mmp-9, as well as Rank and Nfatc1 mRNA expressions are robustly increased when the osteoblast cultures were induced to differentiate by treatment with bone morphogenetic protein (BMP-2). The increased Calcr mRNA resulted in functionally active calcitonin receptors. Enhanced osteoblastic differentiation was associated with increased Rankl mRNA expression and decreased Opg and Cfs1 mRNA expression. Treatment of the osteoblastic cells with BMP-2 or RANKL, either on plastic dishes or bone slices, resulted in the formation of multinucleated tartrate-resistant acid phosphatase positive cells, which were able to excavate resorption pits and release CTX from the bones. In contrast, increased osteoblastic differentiation induced by BMP-2 in the mouse calvarial osteoblastic cell line MC3T3-E1 was not associated with increased mRNA expression of Calcr, Acp5, Rank, c-Fms or Oscar. Interestingly, Ctsk mRNA was increased during osteoblastic differentiation in both mouse calvarial osteoblast cultures and in MC3T3-E1 cultures. Also osteoblasts isolated from mouse long bones by outgrowth from explant cultures were contaminated with osteoclast progenitors able to differentiate into bone resorbing osteoclasts. These data indicate that mouse calvarial osteoblast cultures contain osteoclast progenitor cells, which will be differentiated along the osteoclastic lineage during osteoblastic differentiation. Moreover, the data show that BMP-2 not only stimulates osteoblastic differentiation but can also induce osteoclastogenesis through increased RANKL.

  • 330.
    Gray, Sarah
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Appetite and hunger in advanced cancer patients - a descriptive pilot study2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 331. Gray, Sarah
    et al.
    Axelsson, Bertil
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Östersunds sjukhus.
    The prevalence of deranged C-reactive protein and albumin in patients with incurable cancer approaching death2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 3, article id e0193693Article in journal (Refereed)
    Abstract [en]

    Introduction Amongst patients with incurable cancer approaching death, cachexia is common and associated with adverse outcomes. The term cachexia lacks a universally accepted definition and there is no consensus regarding which variables are to be measured. Furthermore, an elevated C-reactive protein is a common clinical challenge in this patient group. This study aims to add to the ongoing discussion regarding the definition of cancer cachexia and to study the role of C-reactive protein and s-albumin in this context.

    Material and methods A 1-year cohort, consisting of 155 cancer patients enrolled in a specialized palliative home care team in the city of Ostersund, Sweden, that were deceased during the year of 2015 was studied. Laboratory measures were studied within 0-30 and 31-60 days prior to death. C-reactive protein >10 mg/L and coinciding s-albumin <30 g/L was referred to as "laboratory cachexia". Also, the number of days from the first found "laboratory cachexia" until death was noted.

    Results The prevalence of "laboratory cachexia" was 85% 0-30 days prior to death compared to 66% 31-60 days prior to death (p<0.01). The majority of patients (75%) had an onset of "laboratory cachexia" within 0-120 days prior to death, with a median of 47 days. The median values for C-reactive protein and s-albumin within 0-30 days prior to death were 84mg/L and 23g/L respectively.

    Discussion Could markedly deranged values of C-reactive protein and s-albumin, such as found in this study, signal a relatively short remaining survival time in patients with incurable cancer and no clinical signs of ongoing infection? The role of "laboratory cachexia" in this context as well as the cut off values for the laboratory measures included may be further discussed.

  • 332.
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Prostate cancer: epidemiological studies1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Prostate cancer is a large and increasing medical problem both in Sweden and in the rest of the developed world, with about 300.000 new cases diagnosed world wide annually. Despite the high incidence of this disease, little is known about the aetiology of prostate cancer. The aim of this study was to try to understand more about the natural history and to find possible a etiological risk factors for this tumour.

    In a population based study of prostate cancer cases in northern Sweden it was found that the large increase in prostate cancer during the last two decades was mainly caused by well (Gl) and moderately (G2) differentiated tumours. However, the incidence of poorly differentiated (G3) tumours remained unchanged. The introduction of new diagnostic methods is the most plausible explanation for the increase of these low grade tumours.

    The relative survival in prostate cancer was found to be independent of patient age at diagnosis, indicating that tumour proliferation and the aggressiveness of this disease is equal in all ages. However, due to the increasing occurrence of concurrent diseases with growing age the number of lost years caused by prostate cancer decreases dramatically in older age groups. The overall cause specific mortality for prostate cancer was found to be around 50%. In accordance with most other cancer tumours, the annual mortality rate decreased with longer survival also for prostate cancer patients.

    In a study from the Swedish Twin Register it was found that the proband concordance rates for prostate cancer were 4,5 time greater among monozygotic compared to dizygotic twins. In a large nation-wide cohort study of men who had a father with prostate cancer, the overall standardised incidence ratio (SIR) was 1.70 for prostate cancer. Younger age at diagnosis among the fathers were associated with an increased risk among sons. This cohort study and the twin study indicates that both inherited and familial factors are of importance in a subgroup of prostate cancer patients.

    In a prospective case-control study, both a high body mass index (BMI) and a high food intake were found to be independent risk factors for prostate cancer. Both BMI and a high food intake might be indicators of a high fat diet, which so far is the most consistent exogenous risk factor for prostate cancer. The use of tobacco or alcoholic beverages were not associated with prostate cancer risk.

  • 333.
    Grönlund, Christer
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Östlund, Nils
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Stefan J
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Spatio-temporal processing of surface EMG signals from the sternocleidomastoideus muscle to assess effects of radiotherapy on motor unit conduction velocity and firing rate: a pilot study2008In: Biomedical Signal Processing and Control, ISSN 1746-8094, Vol. 3, no 2, p. 163-168Article in journal (Refereed)
    Abstract [en]

    Radiation therapy causes both muscle and nerve tissue damage. However, the evolution and mechanisms of these damages are not fully understood. Information on the state of active muscle fibres and motoneurons can be obtained by measuring sEMG signals and calculating the conduction velocity (CV) and firing rate of individual motor units, respectively. The aim of this pilot study was to evaluate if the multi-channel surface EMG (sEMG) technique could be applied to the sternocleidomastoideus muscle (SCM) of radiotherapy patients, and to assess if the CV and firing rate are altered as a consequence of the radiation.

    Surface EMG signals were recorded from the radiated and healthy SCM muscles of 10 subjects, while subjects performed isometric rotation of the head. CV and firing rate were calculated using two recently proposed methods based on spatio-temporal processing of the sEMG signals. The multi-channel sEMG technique was successfully applied to the SCM muscle and CV and firing rates were obtained. The measurements were fast and simple and comfortable for the patients. Sufficient data quality was obtained from both sides of seven and four subjects for the CV and firing rate analysis, respectively. No differences in CV or firing rate were found between the radiated and non-radiated sides (p = 0.13 and p = 0.20, respectively). Firing rate and CV were also obtained from a myokymic discharge pattern. It was found that the CV decreased significantly (p = 0.01) during the bursts.

  • 334. Grövdal, Michael
    et al.
    Karimi, Mohsen
    Khan, Rasheed
    Aggerholm, Anni
    Antunovic, Petar
    Astermark, Jan
    Bernell, Per
    Engström, Lena-Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kjeldsen, Lars
    Linder, Olle
    Nilsson, Lars
    Olsson, Anna
    Holm, Mette S
    Tangen, Jon M
    Wallvik, Jonas
    Oberg, Gunnar
    Hokland, Peter
    Jacobsen, Sten E
    Porwit, Anna
    Hellström-Lindberg, Eva
    Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy2010In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 150, no 3, p. 293-302Article in journal (Refereed)
    Abstract [en]

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.

  • 335. Gubanski, Michael
    et al.
    Johnsson, Anders
    Fernebro, Eva
    Kadar, Lianna
    Karlberg, Ingegerd
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Flygare, Petra
    Berglund, Ake
    Glimelius, Bengt
    Lind, Pehr A.
    Randomized phase II study of sequential docetaxel and irinotecan with 5-fluorouracil/folinic acid (leucovorin) in patients with advanced gastric cancer: the GATAC trial2010In: Gastric Cancer, ISSN 1436-3291, E-ISSN 1436-3305, Vol. 13, no 3, p. 155-161Article in journal (Refereed)
    Abstract [en]

    Background. The optimal chemotherapy in patients with advanced gastric carcinoma (GC) is yet to be determined. We compared sequential administration of docetaxel and irinotecan, both in combination with infused 5-fluorouracil/leucovorin (5-Fu/Lv), and randomly assigned patients to start with either of the two. Methods. Patients with previously untreated locally advanced or metastatic GC and with measurable lesions (response evaluation criteria in solid tumors; RECIST) were randomly assigned to start with docetaxel 45 m (arm T) or irinotecan 180 mg/m(2) (arm C) with bolus/44-h infusion of 5-Fu/Lv (day 1 every 2 weeks). After four courses, there was a pre-scheduled crossover to the alternative regimen for four additional courses. Results. Eighty-one patients were randomized and 78 started treatment. Complete and partial responses were seen in 31 (40%) patients after 8 weeks and in 32 (41%) after 16 weeks, with similar results in both study arms. The median overall survival (OS) was 11.5 and 10.6 months in arms T and C, respectively (P = 0.3). The two schedules were feasible and did not differ in the overall rate of severe adverse events (SAEs). Conclusion. This is the first randomized comparison of two of the newer cytostatic drugs in GC therapy. No differences favoring either arm T or arm C were found with respect to response rate, OS, or toxicity. The median OS of 11 months indicates that sequential administration of the two combinations is effective and is similar to triple combinations. Thus, comparable efficacy to platinum combinations appears to be obtained with newer, less toxic regimens when given sequentially.

  • 336. Guida, Florence
    et al.
    Sun, Nan
    Bantis, Leonidas E.
    Muller, David C.
    Li, Peng
    Taguchi, Ayumu
    Dhillon, Dilsher
    Kundnani, Deepali L.
    Patel, Nikul J.
    Yan, Qingxiang
    Byrnes, Graham
    Moons, Karel G. M.
    Tjonneland, Anne
    Panico, Salvatore
    Agnoli, Claudia
    Vineis, Paolo
    Palli, Domenico
    Bueno-de-Mesquita, Bas
    Peeters, Petra H.
    Agudo, Antonio
    Huerta, Jose M.
    Dorronsoro, Miren
    Rodriguez Barranco, Miguel
    Ardanaz, Eva
    Travis, Ruth C.
    Byme, Karl Smith
    Boeing, Heiner
    Steffen, Annika
    Kaaks, Rudolf
    Huesing, Anika
    Trichopoulou, Antonia
    Lagiou, Pagona
    La Vecchia, Carlo
    Severi, Gianluca
    Boutron-Ruault, Marie-Christine
    Sandanger, Torkjel M.
    Weiderpass, Elisabete
    Nost, Therese H.
    Tsilidis, Kostas
    Riboli, Elio
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Goodman, Gary E.
    Feng, Ziding
    Brennan, Paul
    Johansson, Mattias
    Hanash, Samir M.
    Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins2018In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 4, no 10, article id e182078Article in journal (Refereed)
    Abstract [en]

    Importance  There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases.

    Objective  To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria.

    Design, Setting, and Participants  Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS).

    Main Outcomes and Measures  Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity).

    Results  In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P = .003 for difference in AUC). At an overall specificity of 0.83, based on the US Preventive Services Task Force screening criteria, the sensitivity of the integrated risk prediction (biomarker) model was 0.63 compared with 0.43 for the smoking model. Conversely, at an overall sensitivity of 0.42, based on the US Preventive Services Task Force screening criteria, the integrated risk prediction model yielded a specificity of 0.95 compared with 0.86 for the smoking model.

    Conclusions and Relevance  This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.

  • 337. Gunnlaugsson, Adalsteinn
    et al.
    Kjellen, Elisabeth
    Hagberg, Oskar
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Change in prostate volume during extreme hypo-fractionation analysed with MRI2014In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 9, p. 22-Article in journal (Refereed)
    Abstract [en]

    Background: Hypo-fractionated external beam radiotherapy with narrow CTV-PTV margins is increasingly applied for prostate cancer. This demands a precise target definition and knowledge on target location and extension during treatment. It is unclear how increase in fraction size affects changes in prostate volume during treatment. Our aim was to study prostate volume changes during extreme hypo-fractionation (7 x 6.1 Gy) by using sequential MRIs. Methods: Twenty patients treated with extreme hypo-fractionation were recruited from an on-going prospective randomized phase III trial. An MRI scan was done before start of treatment, at mid treatment and at the end of radiotherapy. The prostate was delineated at each MRI and the volume and maximum extension in left-right, anterior-posterior and cranial-caudal directions were measured. Results: There was a significant increase in mean prostate volume (14%) at mid treatment as compared to baseline. The prostate volume remained enlarged (9%) at the end of radiotherapy. Prostate swelling was most pronounced in the anterior-posterior and cranial-caudal directions. Conclusions: Extreme hypo-fractionation induced a significant prostate swelling during treatment that was still present at the time of last treatment fraction. Our results indicate that prostate swelling is an important factor to take into account when applying treatment margins during short extreme hypo-fractionation, and that tight margins should be applied with caution.

  • 338.
    Guo, Dongsheng
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    The Identification and Characterisation of LRIG Gene Family and Its Expression in Astrocytic Tumours2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Gliomas are the most common primary brain tumours, and their capacity to invade surrounding normal brain prevents complete removal of the tumour. Malignant glioma has still a poor prognosis. However, with the rapid development of molecular biology our understanding about glioma has increased dramatically. Among known growth factors, EGF and its receptor are frequently amplified and over expressed in malignant glioma. Therefore, it is of interest to find approaches to hamper the activity of EGF/EGFR. The aim of this thesis was to identify and characterize human analogues to a recently identified gene in Drosophilia, kekkon-1, which negatively regulates the activity of Drosophilia EGF receptor.

    In the first part, we set up a quantitative real-time RT-PCR assay, which showed good linearity, reproducibility and uniformity. We analyzed the expression of the most commonly used reference genes, and showed that 18S was the most reliable endogenous reference gene in this study.

    In the second part, we cloned, identified, and sequenced a gene family, which we named leucine-rich repeats and immunoglobulin–like domains family (LRIG). The LRIG gene family had three vertebrate paralogs and one homolog in ascidiacea. The proteins encoded by human LRIG genes shared an overall structure with a signal peptide, 15 tandems leucine-rich repeats with N- and C- terminal flanking regions followed by 3 immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail. Northern blot showed the mRNA sizes to be 5.5 kb for LRIG1, 4.8 kb for LRIG2, and 5.1 kb for LRIG3. LRIG1-3 mRNAs were detected in all human and mouse tissues analyzed, however, at various levels. FISH and BLAST analysis showed that LRIG1 was located at 3p14, LRIG2 at 1q13, and LRIG3 at 12q13. LRIG1 was shown to be down-regulated in several cancer cell lines and proposed to be a tumour suppressor gene.

    In the third part, we analysed the expression of LRIG gene family in human astrocytic tumours. LRIG1-3 mRNAs were detected in all human glioma cell lines, in primary tumour tissues and control-matched normal brain tissues, at various levels. Subcellular localizations of LRIG1-GFP fusion proteins were visualized in nuclear, perinuclear, and cytoplasmic compartment. According to the predicted protein sequences, short peptides were synthesized and used to raise antibodies in rabbits. The antibodies were used for immunohistochemical analysis of LRIG1-3 in 404 human astrocytic tumours in a tissue micro array. The pattern of immunoreactivity of LRIG1-3 was heterogeneous with staining in nuclear, perinuclear and cytoplasmic compartment of positive tumour cells. Perinuclear staining of LRIG1-3 displayed a significant inverse correlation with WHO grade and especially positive LRIG3 perinuclear and cytoplasmic staining correlated with a low proliferation index. The LRIGs correlated with survival, and LRIG3 perinuclear staining was in addition to tumour grade an independent prognostic factor. The results suggest that LRIGs may play a role in normal tissue, and may be of importance in the pathogenesis and prognosis of tumours. The exact function of LRIG1-3 remains to be established.

  • 339.
    Guo, Dongsheng
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    The LRIG gene family has three vertebrate paralogs widely expressed in human and mouse tissues and a homolog in ascidiacea2004In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 84, no 1, p. 157-165Article in journal (Refereed)
    Abstract [en]

    Human LRIG1 (formerly LIG1), human LRIG2, and mouse Lrig1 (also known as Lig-1) encode integral membrane proteins. The human genes are located at chromosomes 3p14 and 1p13, which are regions frequently deleted in human cancers. We have searched for additional members of the LRIG family and by molecular cloning identified human LRIG3 and its mouse ortholog Lrig3. Human LRIG3 is located at chromosome 12q13. In silico analysis of public databases revealed a mouse Lrig2 mRNA, three LRIG homologs in the puffer fish Fugu rubripes, and one LRIG homolog in the ascidian tunicate Ciona intestinalis. The human and mouse LRIG polypeptides have the same predicted domain organization: a signal peptide, 15 tandem leucine-rich repeats with cysteine-rich N- and C-flanking domains, three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail. The extracellular part—especially the IgC2.2 domain, the transmembrane domain, and the membrane-proximal part of the cytoplasmic tail—are the most conserved regions. Northern blot analysis and real-time RT-PCR revealed that the three LRIG paralogs are widely expressed in human and mouse tissues. In conclusion, the LRIG gene family was found to have three widely expressed mammalian paralogs, corresponding orthologs in fish, and a homolog in Ascidiacea.

  • 340.
    Guo, Dongsheng
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Haapasalo, Hannu
    Raheem, Olayinka
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors2006In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 111, no 3, p. 238-346Article in journal (Refereed)
    Abstract [en]

    We have previously characterized three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3 and proposed that they may act as suppressors of tumor growth. The LRIG1 transmembrane protein antagonizes the activity of epidermal growth factor receptor family receptor tyrosine kinases. In this study, we evaluated the mRNA expression level of LRIG1-3 in human glioma cell lines and control-matched glioma tissues, characterized the sub-cellular localization of an LRIG3–GFP fusion protein, and analyzed the relationship between sub-cellular localization of LRIG1-3 and clinical parameters in 404 astrocytic tumors by immunohistochemistry. LRIG1-3 mRNA was detected in all human glioma cell lines and matched glioma samples, with large differences in the expression levels. Ectopically expressed LRIG3–GFP localized to perinuclear and cytoplasmic compartments, and to the cell surface of transfected glioma cells. Perinuclear staining of LRIG1-3 was associated with low WHO grade and better survival of the patients. Perinuclear staining of LRIG3 was associated with a lower proliferation index and was in addition to tumor grade, an independent prognostic factor. Furthermore, within the groups of grade III and grade IV tumors, perinuclear staining of LRIG3 significantly correlated with better survival. These results indicate that expression and sub-cellular localization of LRIG1-3 might be of importance in the pathogenesis and prognosis of astrocytic tumors.

  • 341. Gur, Gal
    et al.
    Rubin, Chanan
    Katz, Menachem
    Amit, Ido
    Citri, Ami
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Amariglio, Ninette
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Rechavi, Gideon
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Wides, Ron
    Yarden, Yosef
    LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation2004In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 23, no 16, p. 3270-3281Article in journal (Refereed)
  • 342.
    Gustafsson, Sofia
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Ghasimi, Soma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Popova, Dina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Krzemien, J
    Wallenius, Anders
    Jacobsson, Stig OP
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    The effects of cannabinoids on the viability and differentiation of neurons derived from retinoic acid-induced  P19 embryonal carcinoma cellsManuscript (preprint) (Other academic)
    Abstract [en]

    Cannabinoids and cannabinoid receptors play an important role in development and differentiation of the nervous system, but the mechanisms behind that role have not been fully elucidated. We have examined the effects of synthetic and endogenous cannabinoids and related polyunsaturated fatty acids upon mouse embryonal carcinoma P19 stem cell viability - before, during and after retinoic acid (RA)-induced neural differentiation. Experiments were also performed to investigate whether the cannabinoids affect the differentiation of P19-derived neurons by measuring the development and growth of neurites and intracellular acetylcholinesterase activity.

    Both synthetic and endogenous cannabinoids as well as related fatty acids produced a concentration-dependent decrease in undifferentiated P19 cell viability, but induction of the neural pathway reduced the sensitivity to the cytotoxic effects, and in differentiated neurons anandamide and related fatty acids showed no cytotoxicity. However, synthetic cannabinoids such as HU 210, HU 211 and WIN 55,212-2 produced cytotoxicity in both undifferentiated and differentiated cells, but there was a right-shifted concentration-effect curve in RA-induced cells and differentiated neurons compared with the undifferentiated cells.

    HU 210 produced a time- and concentration-dependent decrease in cell number, percentage of cells expressing neurites, number of neurites per cell and neurite length. Statistically significant inhibition was seen at a concentration of 1 µM to 3 µM, and this was confirmed by the measurement of intracellular acetylcholinesterase activity, an enzyme that is dramatically increased during the differentiation process, where HU 210 significantly decreased the activity after six and nine days of exposure. However, these effects of HU 210 could only be observed in the same concentration range as those affecting neuronal viability. Anandamide, on the other hand, had modest effect on measured markers of neuronal differentiation but decreased the fraction of neurite expressing cells and neurite length after nine days of exposure at a concentration ≥ 10 µM. No effect on the acetylcholinesterase activity was observed.

    It is concluded that cannabinoids and related fatty acids have cytotoxic effects in undifferentiated P19 embryonal carcinoma cells, but induction of the neuronal pathway reduces the sensitivity to the cytotoxic effects. The synthetic cannabinoids are more potent than the endogenous cannabinoids and fatty acids in causing cytotoxicity in differentiated neurons, but the CB-induced decrease in neurite formation and acetylcholinesterase activity in RA-induced P19-derived neurons occurs only at concentrations that cause measurable neuronal cell death. 

  • 343. Gustavsson, Anders
    et al.
    Svensson, Mikael
    Jacobi, Frank
    Allgulander, Christer
    Alonso, Jordi
    Beghi, Ettore
    Dodel, Richard
    Ekman, Mattias
    Faravelli, Carlo
    Fratiglioni, Laura
    Gannon, Brenda
    Jones, David Hilton
    Jennum, Poul
    Jordanova, Albena
    Jönsson, Linus
    Karampampa, Korinna
    Knapp, Martin
    Kobelt, Gisela
    Kurth, Tobias
    Lieb, Roselind
    Linde, Mattias
    Ljungcrantz, Christina
    Maercker, Andreas
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Moscarelli, Massimo
    Musayev, Amir
    Norwood, Fiona
    Preisig, Martin
    Pugliatti, Maura
    Rehm, Juergen
    Salvador-Carulla, Luis
    Schlehofer, Brigitte
    Simon, Roland
    Steinhausen, Hans-Christoph
    Stovner, Lars Jacob
    Vallat, Jean-Michel
    Van den Bergh, Peter
    van Os, Jim
    Vos, Pieter
    Xu, Weili
    Wittchen, Hans-Ulrich
    Jönsson, Bengt
    Olesen, Jes
    Cost of disorders of the brain in Europe 20102011In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 21, no 10, p. 718-779Article in journal (Refereed)
    Abstract [en]

    Background: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, ofan increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.

    Aims: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.

    Methods: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders),dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis,neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27 + Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.

    Results: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.

    Discussion: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.

    Recommendations: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.

  • 344. Gustavsson, Anders
    et al.
    Svensson, Mikael
    Jacobi, Frank
    Allgulander, Christer
    Alonso, Jordi
    Beghi, Ettore
    Dodel, Richard
    Ekman, Mattias
    Faravelli, Carlo
    Fratiglioni, Laura
    Gannon, Brenda
    Jones, David Hilton
    Jennum, Pout
    Jordanova, Albena
    Jonsson, Linus
    Karampampa, Korinna
    Knapp, Martin
    Kobelt, Gisela
    Kurth, Tobias
    Lieb, Roselind
    Linde, Mattias
    Ljungcrantz, Christina
    Maercker, Andreas
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Moscarelli, Massimo
    Musayev, Amir
    Norwood, Fiona
    Preisig, Martin
    Pugliatti, Maura
    Rehm, Juergen
    Salvador-Carulla, Luis
    Schlehofer, Brigitte
    Simon, Roland
    Steinhausen, Hans-Christoph
    Stovner, Lars Jacob
    Vallat, Jean-Michel
    Van den Bergh, Peter
    van Os, Jim
    Vos, Pieter E
    Xu, Weili
    Wittchen, Hans-Ulrich
    Jonsson, Bengt
    Olesen, Jes
    Corrigendum to “Cost of disorders of the brain in Europe 2010” [Eur. Neuropsychopharmacol. 21 (2011) 718–779]2012In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no 3, p. 237-238Article in journal (Refereed)
  • 345.
    Gylling, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schneede, Jørn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Häggstrom, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ulvik, Arve
    Ueland, Per M.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Vitamin B-6 and colorectal cancer risk: a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status2017In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 105, no 4, p. 897-904Article in journal (Refereed)
    Abstract [en]

    Background: Higher plasma concentrations of the vitamin B-6 marker pyridoxal 5#-phosphate (PLP) have been associated with reduced colorectal cancer (CRC) risk. Inflammatory processes, including vitamin B-6 catabolism, could explain such findings. Objective: We investigated 3 biomarkers of vitamin B-6 status in relation to CRC risk. Design: This was a prospective case-control study of 613 CRC cases and 1190 matched controls nested within the Northern Sweden Health and Disease Study (n = 114,679). Participants were followed from 1985 to 2009, and the median follow-up from baseline to CRC diagnosis was 8.2 y. PLP, pyridoxal, pyridoxic acid (PA), 3-hydroxykynurenine, and xanthurenic acids (XAs) were measured in plasma with the use of liquid chromatography-tandem mass spectrometry. We calculated relative and absolute risks of CRC for PLP and the ratios 3-hydroxykynurenine: XA (HK: XA), an inverse marker of functional vitamin B-6 status, and PA:(PLP + pyridoxal) (PAr), a marker of inflammation and oxidative stress and an inverse marker of vitamin B-6 status. Results: Plasma PLP concentrations were associated with a reduced CRC risk for the third compared with the first quartile and for PLP sufficiency compared with deficiency [OR: 0.60 (95% CI: 0.44, 0.81) and OR: 0.55 (95% CI: 0.37, 0.81), respectively]. HK: XA and PAr were both associated with increased CRC risk [OR: 1.48 (95% CI: 1.08, 2.02) and OR: 1.50 (95% CI: 1.10, 2.04), respectively] for the fourth compared with the first quartile. For HK: XA and PAr, the findings were mainly observed in study participants with,10.5 y of follow-up between sampling and diagnosis. Conclusions: Vitamin B-6 deficiency as measured by plasma PLP is associated with a clear increase in CRC risk. Furthermore, our analyses of novel markers of functional vitamin B-6 status and vitamin B-6-associated oxidative stress and inflammation suggest a role in tumor progression rather than initiation.

  • 346.
    Gylling, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ulvik, Arve
    Bevital AS, Laboratory building, Bergen, Norway.
    Ueland, Per Magne
    Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
    Midttun, Øivind
    Bevital AS, Laboratory building, Bergen, Norway.
    Schneede, Jørn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 68p. 947-956Article in journal (Other academic)
    Abstract [en]

    Background: One-carbon metabolism biomarker are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs.

    Objective: We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk.

    Design: The relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1211 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5´-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression.

    Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).

    Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.

  • 347. Göhler, S.
    et al.
    Da Silva Filho, M. I.
    Johansson, R.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Enquist-Olsson, K.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Henriksson, R.
    Hemminki, K.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, A.
    Functional germline variants in driver genes of breast cancer2014In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, p. S233-S233Article in journal (Other academic)
  • 348. Göhler, Stella
    et al.
    Da Silva Filho, Miguel Inacio
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist-Olsson, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Cancer Center Stockholm Gotland, 10239 Stockholm, Sweden.
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Functional germline variants in driver genes of breast cancer2017In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 28, no 4, p. 259-271Article in journal (Refereed)
    Abstract [en]

    Purpose Germline mutations in tumour suppressor genes cause various cancers. These genes are also somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic breast tumours. Methods After excluding the well-characterized breast cancer (BC) genes, we screened 15 novel genes consistently classified as BC driver genes in next-generation sequencing approaches for single nucleotide polymorphisms (SNPs). Altogether 40 SNPs located in the core promoter, 5'- and 3'-UTR or which were nonsynonymous SNPs were genotyped in 782 Swedish incident BC cases and 1,559 matched controls. After statistical analyses, further evaluations related to functional prediction and signatures of selection were performed. Results TBX3 was associated with BC risk (rs2242442: OR = 0.76, 95% CI 0.64-0.92, dominant model) and with less aggressive tumour characteristics. An association with BC survival and aggressive tumour characteristics was detected for the genes ATR (rs2227928: HR = 1.63; 95% CI 1.00-2.64, dominant model), RUNX1 (rs17227210: HR = 3.50, 95% CI 1.42-8.61, recessive model) and TTN (rs2303838: HR = 2.36; 95% CI 1.04-5.39; rs2042996: HR = 2.28; 95% CI 1.19-4.37, recessive model). According to the experimental ENCODE data all these SNPs themselves or SNPs in high linkage disequilibrium with them (r (2) ae<yen> 0.80) were located in regulatory regions. RUNX1 and TTN showed also several signatures of positive selection. Conclusion The study gave evidence that germline variants in BC driver genes may have impact on BC risk and/or survival. Future studies could discover further germline variants in known or so far unknown driver genes which contribute to cancer development.

  • 349. Göhler, Stella
    et al.
    Da Silva Filho, Miguel Inacio
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist-Olsson, Kerstin
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Cancer Center Stockholm Gotland, Stockholm, Sweden .
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population2016In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 142, no 1, p. 273-276Article in journal (Refereed)
    Abstract [en]

    Purpose: The C -> T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a similar to 29. 5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk. Methods: We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC. Results: No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50-0.96, dominant model). Conclusion: The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.

  • 350.
    Haider, Zahra
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Noren-Nyström, Ulrika
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Epigenetic and genetic distinctions between T-cell acute lymphoblastic leukemia and lymphomaManuscript (preprint) (Other academic)
45678910 301 - 350 of 1274
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf