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  • 51. Ellingson, Benjamin M.
    et al.
    Abrey, Lauren E.
    Garcia, Josep
    Chinot, Olivier
    Wick, Wolfgang
    Saran, Frank
    Nishikawa, Ryo
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm, Stockholm, Sweden.
    Mason, Warren P.
    Harris, Robert J.
    Leu, Kevin
    Woodworth, Davis C.
    Mehta, Arnav
    Raymond, Catalina
    Chakhoyan, Ararat
    Pope, Whitney B.
    Cloughesy, Timothy F.
    Post-chemoradiation volumetric response predicts survival in newly diagnosed glioblastoma treated with radiation, temozolomide, and bevacizumab or placebo2018In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, no 11, p. 1525-1535Article in journal (Refereed)
    Abstract [en]

    Background. In the current study we used contrast-enhanced T1 subtraction maps to test whether early changes in enhancing tumor volume are prognostic for overall survival (OS) in newly diagnosed glioblastoma (GBM) patients treated with chemoradiation with or without bevacizumab (BV). Methods. Seven hundred ninety-eight patients (404 BV and 394 placebo) with newly diagnosed GBM in the AVAglio trial (NCT00943826) had baseline MRI scans available, while 337 BV-treated and 269 placebo-treated patients had > 4 MRI scans for response evaluation. The volume of contrast-enhancing tumor was quantified and used for subsequent analyses. Results. A decrease in tumor volume during chemoradiation was associated with a longer OS in the placebo group (hazard ratio [HR] = 1.578, P < 0.0001) but not BV-treated group (HR = 1.135, P = 0.4889). Results showed a higher OS in patients on the placebo arm with a sustained decrease in tumor volume using a post-chemoradiation baseline (HR = 1.692, P = 0.0005), and a trend toward longer OS was seen in BV-treated patients (HR = 1.264, P = 0.0724). Multivariable Cox regression confirmed that sustained response or stable disease was prognostic for OS (HR = 0.7509, P = 0.0127) when accounting for age (P = 0.0002), KPS (P = 0.1516), postsurgical tumor volume (P < 0.0001), O6-methylguanine-DNA methyltransferase status (P < 0.0001), and treatment type (P = 0.7637) using the post-chemoradiation baseline. Conclusions. The post-chemoradiation timepoint is a better baseline for evaluating efficacy in newly diagnosed GBM. Early progression during the maintenance phase is consequential in predicting OS, supporting the use of progression-free survival rates as a meaningful surrogate for GBM.

  • 52. Ellingson, Benjamin M.
    et al.
    Abrey, Lauren E.
    Nelson, Sarah J.
    Kaufmann, Timothy J.
    Garcia, Josep
    Chinot, Olivier
    Saran, Frank
    Nishikawa, Ryo
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm.
    Mason, Warren P.
    Wick, Wolfgang
    Butowski, Nicholas
    Ligon, Keith L.
    Gerstner, Elizabeth R.
    Colman, Howard
    de Groot, John
    Chang, Susan
    Mellinghoff, Ingo
    Young, Robert J.
    Alexander, Brian M.
    Colen, Rivka
    Taylor, Jennie W.
    Arrillaga-Romany, Isabel
    Mehta, Arnav
    Huang, Raymond Y.
    Pope, Whitney B.
    Reardon, David
    Batchelor, Tracy
    Prados, Michael
    Galanis, Evanthia
    Wen, Patrick Y.
    Cloughesy, Timothy F.
    Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma2018In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, no 9, p. 1240-1250Article in journal (Refereed)
    Abstract [en]

    Background. In the current study, we pooled imaging data in newly diagnosed glioblastoma (GBM) patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between postoperative residual enhancing tumor volume and overall survival (OS). Methods. Data from 1511 newly diagnosed GBM patients from 5 data sources were included in the current study: (i) a single institution database from UCLA (N = 398; Discovery); (ii) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N = 262 from 8 centers; Confirmation); (iii) the chemoradiation placebo arm from an international phase III trial (AVAglio; N = 394 from 120 locations in 23 countries; Validation); (iv) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N = 404 from 120 locations in 23 countries; Exploratory Set 1); and (v) an Alliance (N0874) phase I/II trial of vorinostat plus chemoradiation (N = 53; Exploratory Set 2). Postsurgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, O-6-methylguanine-DNA methyltransferase (MGMT) status, and residual tumor volume on OS. Results. A log-linear relationship was observed between postoperative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Postoperative tumor volume is a prognostic factor for OS (P < 0.01), regardless of therapy, age, and MGMT promoter methylation status. Conclusion. Postsurgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed GBM treated with chemoradiation with or without concomitant experimental therapy.

  • 53.
    Faraz, Mahmood
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herdenberg, Carl
    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.
    A protein interaction network centered on leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) regulates growth factor receptors2018In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 293, no 9, p. 3421-3435Article in journal (Refereed)
    Abstract [en]

    Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases. The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates receptor tyrosine kinases remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor α, LRIG1, and shRNAs against the identified LRIG1 interactors. The effects of the shRNAs on the ability of LRIG1 to down-regulate platelet-derived growth factor receptor α expression were evaluated. On the basis of these results, we present an LRIG1 protein interaction network with many newly identified components. The network contains the apparently functionally important LRIG1-interacting proteins RAB4A, PON2, GAL3ST1, ZBTB16, LRIG2, CNPY3, HLA-DRA, GML, CNPY4, LRRC40, and LRIG3, together with GLRX3, PTPRK, and other proteins. In silico analyses of The Cancer Genome Atlas data sets revealed consistent correlations between the expression of the transcripts encoding LRIG1 and its interactors ZBTB16 and PTPRK and inverse correlations between the transcripts encoding LRIG1 and GLRX3. We further studied the LRIG1 function–promoting paraoxonase PON2 and found that it co-localized with LRIG1 in LRIG1-transfected cells. The proposed LRIG1 protein interaction network will provide leads for future studies aiming to understand the molecular functions of LRIG1 and the regulation of growth factor signaling.

  • 54.
    Franzén, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gustafsson, H
    Sundström, S
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    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 late changes in rat parotid-gland: effects on the number of acinar-cells, potassium efflux, and amylase secretion1993In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 64, no 1, p. 93-101Article in journal (Refereed)
    Abstract [en]

    Irradiation of head- and neck cancer commonly results in oral dryness and discomfort for the patients due to salivary gland damage. The exact mechanisms behind the inherent radiosensitivity of salivary glands remain to be elucidated. In the present study, we used different in vitro secretory models and quantitative morphological characterization of rat parotid gland following fractionated unilateral irradiation to one gland on a 5-day fraction schedule (Monday-Friday) with 6 MV photons (total dose 30, 35, 40 and 45 Gy) or a two-fractions regimen in 5 days (Monday and Friday) with total dose of 24 and 32 Gy. The contralateral shielded gland served as control, and parallel analyses of irradiated and control glands were performed 180 days following the last irradiation treatment. The relative noradrenaline stimulated electrolyte secretion (rubidium-86 tracer for potassium) was decreased in the irradiated compared with control glands. The noradrenaline-stimulated exocytotic amylase release was not significantly affected by irradiation, but the gland content of amylase was decreased dose-dependently. The quantitative morphological analysis revealed a dose-dependent decline in the number of acinar cells, whereas the other parenchymal cells (intercalated, striated- and excretory duct cells) were un-, affected by the irradiation compared with control glands.

  • 55.
    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)
  • 56. 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.

  • 57.
    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.

  • 58.
    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.

  • 59. 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)
  • 60. 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.

  • 61. 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.

  • 62.
    Hammarsten, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Häggström Rudolfsson, Stina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Inhibitory effects of castration in an orthotopic model of androgen-independent prostate cancer can be mimicked and enhanced by angiogenesis inhibition.2006In: Clinical Cancer Research, ISSN 1078-0432, Vol. 12, no 24, p. 7431-7436Article in journal (Refereed)
  • 63.
    Hammarsten, Peter
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Rudolfsson, Stina
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Inhibition of the epidermal growth factor receptor enhances castration-induced prostate involution and reduces testosterone-stimulated prostate growth in adult rats.2007In: Prostate, ISSN 0270-4137, Vol. 67, no 6, p. 573-581Article in journal (Refereed)
  • 64.
    Hedman, Håkan
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    LRIG inhibitors of growth factor signalling - double-edged swords in human cancer?2007In: Eur J Cancer, ISSN 0959-8049, Vol. 43, no 4, p. 676-682Article in journal (Refereed)
  • 65.
    Hedman, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindström, Annika K
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tot, Tibor
    Stendahl, Ulf
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hellberg, Dan
    LRIG2 in contrast to LRIG1 predicts poor survival in early-stage squamous cell carcinoma of the uterine cervix2010In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 6, p. 812-815Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises LRIG1, 2, and 3. LRIG1 negatively regulates growth factor signaling and is a proposed tumor suppressor. In early stage uterine cervical carcinoma, expression of LRIG1 is associated with good survival. Less is known about the function and expression of LRIG2; it has not been studied in cervical carcinoma, previously. MATERIALS AND METHODS: LRIG2 expression was studied by immunohistochemistry in 129 uterine cervical squamous cell carcinomas and 36 uterine cervical adenocarcinomas. Possible associations between LRIG2 immunoreactivity and patient survival were evaluated. RESULTS: In early-stage squamous cell carcinoma (stages IB-IIB), high expression of LRIG2 was associated with poor survival (Kaplan-Meier, log-rank, p=0.02). The 10-year survival rate for patients with high expression of LRIG2 was 60%, compared to 87% in patients with low expression (odds ratio 0.22, 95% CI 0.07-0.64). In multivariate analysis including the previously studied tumor suppressor LRIG1 and clinical stage, LRIG2 emerged as an independent prognostic factor (odds ratio 0.22, 95% CI 0.09-0.50). For patients with both high expression of LRIG2 and low expression of LRIG1, the 10-year survival rate was only 26% compared to 66% for the remaining study population. There was no correlation between LRIG2 expression and prognosis in the limited adenocarcinoma series. DISCUSSION AND CONCLUSION: LRIG2 appears to be a significant predictor of poor prognosis in early-stage squamous cell carcinoma of the uterine cervix. A combination of high LRIG2 expression and low LRIG1 expression identified women with a very poor prognosis.

  • 66.
    Hedman, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Guo, Dongsheng
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Is LRIG1 a tumour suppressor gene at chromosome 3p14.3?2002In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 41, no 4, p. 352-354Article in journal (Refereed)
    Abstract [en]

    The LRIG1 gene (formerly LIG-1), recently cloned by us, displays structural similarities to the Drosophila Kek I gene. Kek I encodes a cell surface protein, Kekkon-1, which inhibits epidermal growth factor receptor-mediated signalling. We localized the LRIG1 gene to chromosome band 3p14.3, a region known to be deleted in various human cancers. In the present study LRIG1 gene expression was examined in different tumour cell lines and corresponding normal tissues by real-time RT-PCR. In many tumour cell lines, LRIG1 expression appeared absent or was down regulated compared to corresponding normal tissues. The results are consistent with LRIG1 being a tumour suppressor gene in humans. However, further studies are justified to elucidate the explicit role of LRIG1 as a negative regulator of oncogenesis.

  • 67.
    Hellström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ericsson, Madelene
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Faraz, Mahmood
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Anderson, Fredrick
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm/Gotland, Stockholm, Sweden.
    Nilsson, Stefan K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cardiac hypertrophy and decreased high-density lipoprotein cholesterol in Lrig3-deficient mice2016In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 310, no 11, p. R1045-R1052Article in journal (Refereed)
    Abstract [en]

    Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure and plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice and investigated the importance of Lrig3 for heart function and plasma lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze Lrig3 expression in the hearts of wild-type and Lrig3-deficient mice. In addition, molecular, physiological, and functional parameters such as organ weights, heart rate, blood pressure, heart structure and function, gene expression in the heart, and plasma insulin, glucose, and lipid levels were evaluated. The Lrig3-deficient mice were smaller than the wild-type mice but otherwise appeared grossly normal. Lrig3 was expressed at detectable but relatively low levels in adult mouse hearts. At 9 mo of age, ad libitum-fed Lrig3-deficient mice had lower insulin levels than wildtype mice. At 12 mo of age, Lrig3-deficient mice exhibited increased blood pressure, and the Lrig3-deficient female mice displayed signs of cardiac hypertrophy as assessed by echocardiography, heart-to-body weight ratio, and expression of the cardiac hypertrophy marker gene Nppa. Additionally, Lrig3-deficient mice had reduced plasma HDL cholesterol and free glycerol. These findings in mice complement the human epidemiological results and suggest that Lrig3 may influence heart function and plasma lipid levels in mice and humans.

  • 68.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Modulation of serous salivary gland function by the sympathetic nervous system: a biochemical and ultrastructural study with special reference to β-adrenoceptor subtypes1981Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of the present investigation was to study the influence of the sympathetic nervous system and of various adrenoceptor agents on enzyme secretion and morphology in rat parotid and guinea-pig submandibular glands. Biochemical methods were combined with electron microscopical techniques.

    Two different in vitro systems were employed, batch-incubation and microperifusion, to characterize the sympathetically evoked amylase release and its correlation to cyclic AMP. By using various selective β-adrenoceptor agonists and antagonists a dominance of the β1-adrenoceptor over the β2 - in regulating amylase release - was establ ished. Continuous noradrenaline perifusion caused a rapid initial amylase discharge, closely correlated to tissue levels of cyclic AMP; no correlation between the two was observed during the later phase. Prenalterol (a β1-agonist) failed to elevate glandular cyclic AMP. This was in contrast to its potent secretagogic effect. On the other hand, terbutaline (a β2-agonist) was a weak secretagogue but markedly raised the levels of cyclic AMP. Thus, β-adrenoceptor activation may lead to release of large amounts of amylase despite minimal or no increase in cyclic AMP. Moreover, these effects seemed to be dissociated in salivary glands with regard to the β-adrenoceptor subtypes. This was further substantiated by the findings that repeated injections of prenalterol induced qualitative changes in the granule populations, similar to those caused by the non-selective β-agonist isoprenaline. Terbutaline was without effect. However, acinar cells size was increased following both prenalterol and terbutaline treatment. The data suggest that the 3-adrenergic effects on acinar cell size and granule population may be independently regulated.

    A decreased sympathetic activity of long duration was induced by neonatal or adult extirpation of the superior cervical ganlion on one side. Acinar cell size, as well as granule and amylase content was reduced 9 weeks after neonatal denervation. Ganglionectomy performed in adult animals was without significant effects.

    The secretory behaviour of neonatally denervated glands was characterized by an increased postjunctional sensitivity to 3-adrenoceptor agonists. Of special interest was the finding that neonatal denervation seemed to transform terbutaline from a partial to a full secretory agonist, thus changing its effects in the direction of those of prenalterol and noradrenaline. Moreover, increased levels of cyclic AMP as well as an enhanced response to DBcAMP were noted in the denervated glands as were intracellular changes. The denervation supersensitivity after neonatal denervation seems to differ from that observed in adult denervated glands. The results of the studies on denervated glands suggest that the sympathetic nervous system plays a fundamental role in the early maturation of the rat parotid gland as well as for the development of the β-adrenoceptor subtypes.

  • 69.
    Henriksson, Roger
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Poulsen, Hans Skovgaard
    Radiumhemmet, Karolinska Hospital, Stockholm, Sweden; Department of Oncology, Finsencenter, University Hospital, 9 Blegdamsvej, 2100 Copenhagen, Denmark.
    Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review2011In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 104, no 3, p. 639-646Article, review/survey (Refereed)
    Abstract [en]

    The maintenance of quality of life (QoL) in patients with high-grade glioma is an important endpoint during treatment, particularly in those with glioblastoma multiforme (GBM) given its dismal prognosis despite limited advances in standard therapy. It has proven difficult to identify new therapies that extend survival in patients with recurrent GBM, so one of the primary aims of new therapies is to reduce morbidity, restore or preserve neurologic functions, and the capacity to perform daily activities. Apart from temozolomide, cytotoxic chemotherapeutic agents do not appear to significantly impact response or survival, but produce toxicity that is likely to negatively impact QoL. New biological agents, such as bevacizumab, can induce a clinically meaningful proportion of durable responses among patients with recurrent GBM with an acceptable safety profile. Emerging evidence suggests that bevacizumab produces an improvement or preservation of neurocognitive function in GBM patients, suggestive of QoL improvement, in most poor-prognosis patients who would otherwise be expected to show a sudden and rapid deterioration in QoL.

  • 70.
    Henriksson, Roger
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enigma of a rapid introduction of antiangiogenic therapy with bevacizumab in glioblastoma: a new era in the treatment of malignant brain tumours?2009In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, no 1, p. 6-8Article in journal (Other academic)
  • 71.
    Henriksson, Roger
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Capala, Jacek
    Michanek, Annika
    Lindahl, Sten-Åke
    Salford, Leif G
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Blomquist, Erik
    Westlin, Jan-Erik
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Boron neutron capture therapy (BNCT) for glioblastoma multiforme.: A phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA).2008In: Radiother Oncol, ISSN 0167-8140, Vol. 88, no 2, p. 183-191Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion.

    PATIENT AND METHODS:

    This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute.

    RESULTS:

    The boron-blood concentration during irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT.

    CONCLUSION:

    Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells.

  • 72.
    Henriksson, Roger
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Fredrik
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Blomquist, Erik
    Bergström, Stefan
    Ekman, Simon
    Bergqvist, Michael
    Brain Tumors - Prognostic and Predictive Markers2009In: Histological and Serological Tumor Markers and Gene Expression and Their Clinical Usefulness in Cancers / [ed] Dan Hellberg, Hauppauge: Nova Science Publishers, Inc., 2009, p. 53-75Chapter in book (Refereed)
    Abstract [en]

    This review summarizes the status of prognostic and predictive markers in brain tumors with a focus on the most frequent tumors, gliomas. Brain tumors are a heterogeneous group of different tumors with a huge variation in outcome. Although the most common tumor, high-grade malignant glioma, still has a dismal prognosis, the last years have seen a significant improvement in the management in this tumor as well as in most other brain tumors. Age, tumor grade and KPS are still the most reliable prognostic and predictive variables available for patients with brain tumors. Although chromosome 1p/19q co-deletion and methylation status of the promoter of the MGMT gene (encoding O6-methylguanine-DNA methyl transferase) have been identified as the most promising potential predictors of response to chemotherapy in malignant gliomas, there are as yet no reliable biomarkers for tumour grading or tumour monitoring in the clinical setting.

  • 73.
    Henriksson, Roger
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Malmström, Annika
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Gertrud
    Trojanowski, Thomas
    Andreasson, Lars
    Blomquist, Erik
    Jonsborg, Sonny
    Edekling, Tomas
    Salander, Pär
    Umeå University, Faculty of Social Sciences, Department of Social Work. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    High-grade astrocytoma treated concomitantly with estramustine and radiotherapy2006In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 78, no 3, p. 321-326Article in journal (Refereed)
  • 74. Hoang-Xuan, Khe
    et al.
    Bessell, Eric
    Bromberg, Jacoline
    Hottinger, Andreas F.
    Preusser, Matthias
    Ruda, Roberta
    Schlegel, Talli
    Soussain, Carole
    Abacioglu, Ufuk
    Cassoux, Nathalie
    Deckert, Martina
    Dirven, Siemens M. F.
    Ferreri, Andres J. M.
    Graus, Francesc
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm County, Stockholm, Sweden.
    Herdinger, Ulric
    Taphoorn, Martin
    Soffietti, Riccardo
    Weller, Michael
    Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology2015In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 16, no 7, p. E322-E332Article, review/survey (Refereed)
    Abstract [en]

    The management of primary CNS lymphoma is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the very few controlled studies available. In 2013, the European Association of Neuro-Oncology created a multidisciplinary task force to establish evidence-based guidelines for immunocompetent adults with primary CNS lymphoma. In this Review, we present these guidelines, which provide consensus considerations and recommendations for diagnosis, assessment, staging, and treatment of primary CNS lymphoma. Specifically, we address aspects of care related to surgery, systemic and intrathecal chemotherapy, intensive chemotherapy with autologous stem-cell transplantation, radiotherapy, intraocular manifestations, and management of elderly patients. The guidelines should aid clinicians in their daily practice and decision making, and serve as a basis for future investigations in neuro-oncology.

  • 75. Holgersson, Georg
    et al.
    Bergqvist, Michael
    Uppsala University Hospital.
    Nyman, Jan
    Hoye, Even
    Helsing, Martin
    Friesland, Signe
    Holgersson, Margareta
    Ekberg, Lars
    Mörth, Charlotte
    Ekman, Simon
    Blystad, Thomas
    Ewers, Sven-Börje
    Löden, Britta
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Stefan
    The impact of hyperfractionated radiotherapy regimen in patients with non-small cell lung cancer2013In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 30, no 1, article id 320Article in journal (Refereed)
    Abstract [en]

    The prognosis for patients with lung cancer is poor with an average of 5-year overall survival rate of only 10-15 % taking all clinical stages together. The aim of this study was to elucidate the impact of the radiotherapy regimen on survival. Clinical data were collected from all the Swedish Oncology Departments for 1,287 patients with a diagnosed non-small cell lung cancer (NSCLC) subjected to curatively intended irradiation (>= 50 Gy) during the years 1990 to 2000. The included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Patients who did not have a histopathological diagnosis date and/or death date/last follow-up date as well as patients being surgically treated were excluded from the study (n = 592). Thus, 695 patients were included in the present study. Patients who received hyperfractionated radiotherapy (HR) had a higher local control rate compared with patients receiving conventional fractionation (CF) (38 vs. 49 % local relapse). The difference in survival between the two radiotherapy regimens was statistically significant in a univariate Cox analysis (p = 0.023) in favor of HR. This significance was, however, not retained in a multivariate Cox analysis (p = 0.56). Thus, the possible beneficial effects of hyperfractionation are still unclear and need to be further investigated in well-controlled prospective clinical trials, preferably including systemic treatment with novel drugs.

  • 76. Holgersson, Georg
    et al.
    Bergstrom, Stefan
    Bergqvist, Michael
    Nyman, Jan
    Hoye, Even
    Helsing, Martin
    Friesland, Signe
    Holgersson, Margareta
    Birath, Elisabet
    Ekrnan, Simon
    Blystad, Thomas
    Ewers, Sven-Borje
    Morth, Charlotte
    Loden, Britta
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Swedish Lung Cancer Radiation Study Group: Predictive value of histology for radiotherapy response in patients with non-small cell lung cancer2011In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, no 16, p. 2415-2421Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the potential predictive value of histology in non-small cell lung cancer (NSCLC) treated with curatively intended radiotherapy. In a collaborative effort among all the Swedish Oncology Departments, clinical data were collected for 1146 patients with a diagnosed non-small cell lung cancer subjected to curatively intended irradiation (>= 50 Gy) during the years 1990 to 2000. The included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Only patients who did not have a histological diagnosis date and death date/last follow-up date were excluded (n = 141). Among the 1146 patients with non-small cell carcinoma eligible for analysis, 919 were diagnosed with either adenocarcinoma (n = 323) or squamous cell carcinoma (n = 596) and included in this study. The median survival for the 919 patients was 14.8 months, while the 5-year survival rate was 9.5%. Patients with adenocarcinoma had a significantly better overall survival compared with patients with squamous cell carcinoma (p = 0.0062, log-rank test). When comparing different stages, this survival benefit was most pronounced for stages IIA-IIB (p<0.0001, log-rank test). The difference in survival between the two histological groups was statistically significant in a univariate Cox analysis (p = 0.0063) as well as in two multivariate Cox analyses including demographic and treatment variables (p = 0.037 and p = 0.048, respectively). In this large population based retrospective study we describe for the first time that patients with adenocarcinoma have a better survival after curatively intended radiation therapy in comparison with squamous cell carcinoma patients, particularly those with clinical stages IIA-IIB. (C) 2011 Elsevier Ltd. All rights reserved.

  • 77.
    Holgersson, Georg
    et al.
    Institutionen för Immunologi, Genitik och Patologi Umeå Universitet /Centrum för forskning och utveckling Region Gävleborg.
    Bergström, Stefan
    Institutionen för Immunologi, Genitik och Patologi Umeå Universitet /Centrum för forskning och utveckling Region Gävleborg.
    Hallqvist, Anders
    Institutionen för Onkologi, Sahlgrenska Universitetssjukhuset.
    Liv, Per
    Centrum för forskning och utveckling Region Gävleborg.
    Nilsson, R. Jonas A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Centrum för forskning och utveckling, Uppsala Universitet / Region Gävleborg, Gävle sjukhus, Gävle, Sverige.
    Willén, Linda
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Centrum för forskning och utveckling, Uppsala Universitet / Region Gävleborg, Gävle sjukhus, Gävle, Sverige.
    Nyman, Jan
    Institutionen för Onkologi, Sahlgrenska Universitetssjukhuset.
    Ekman, Simon
    Institutionen för Onkologi, Karolinska Universitetssjukhuset.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergqvist, Michael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Centrum för forskning och utveckling Region Gävleborg.
    The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy2017In: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317, Vol. 64, no 6, p. 909-915Article in journal (Refereed)
    Abstract [en]

    Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109 /L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109 /L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting

  • 78. Holgersson, Georg
    et al.
    Bergström, Stefan
    Liv, Per
    Nilsson, Jonas
    Edlund, Per
    Blomberg, Carl
    Nyman, Jan
    Friesland, Signe
    Ekman, Simon
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergqvist, Michael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Center for Research and Development, Uppsala University, Gävle Hospital, Gävle, Sweden ; Department of Oncology, Gävle Hospital, Gävle, Sweden.
    Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 10, p. 5491-5497Article in journal (Refereed)
    Abstract [en]

    Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC).

    Patients and Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (>= 50 Gy) in Sweden during the time period 1990 to 2000.

    Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical-and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17).

    Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.

  • 79. Holgersson, Georg
    et al.
    Hoye, Even
    Bergqvist, Michael
    Ekman, Simon
    Nyman, Jan
    Helsing, Martin
    Friesland, Signe
    Holgersson, Margareta
    Ekberg, Lars
    Blystad, Thomas
    Ewers, Sven-Börje
    Mörth, Charlotte
    Löden, Britta
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Stefan
    Swedish Lung Cancer Radiation Study Group: Predictive value of age at diagnosis for radiotherapy response in patients with non-small cell lung cancer2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 6, p. 759-767Article in journal (Refereed)
    Abstract [en]

    Introduction. The aim of the present study was to investigate the impact of age at diagnosis on prognosis in patients treated with curatively intended radiotherapy for NSCLC. Material and methods. This is a joint effort among all the Swedish Oncology Departments that includes all identified patients with a diagnosed non-small cell lung cancer that have been subjected to curatively intended irradiation (>= 50 Gy) treated during 1990 to 2000. Included patients had a histopathological/cytological diagnosis date as well as a death date or a last follow-up date. The following variables were studied in relation to overall and disease-specific survival: age, gender, histopathology, time period, smoking status, stage and treatment. Results. The median overall survival of all 1146 included patients was 14.7 months, while the five-year overall survival rate was 9.5%. Younger patients (<55 years), presented with a more advanced clinical stage but had yet a significantly better overall survival compared with patients in the age groups 55-64 years (p = 0.035) and 65-74 years (p = 0.0097) in a multivariate Cox regression analysis. The overall survival of patients aged >= 75 years was comparable to those aged <55 years. Conclusion. In this large retrospective study we describe that patients younger than 55 years treated with curatively intended radiotherapy for NSCLC have a better overall survival than patients aged 55-64 and 65-74 years and that younger patients seem to benefit more from the addition of surgery and/or chemotherapy to radiotherapy. Due to the exploratory nature of the study, these results should be confirmed in future prospective trials.

  • 80. Holgersson, Georg
    et al.
    Sandelin, Martin
    Hoye, Even
    Bergström, Stefan
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ekman, Simon
    Nyman, Jan
    Helsing, Martin
    Friesland, Signe
    Brodin, Ola
    Holgersson, Margareta
    Lamberg Lundström, Kristina
    Janson, Christer
    Ekberg, Lars
    Mörth, Charlotte
    Blystad, Thomas
    Ewers, Sven-Börje
    Löden, Britta
    Bergqvist, Michael
    The Value of Induction Chemotherapy for Survival in Patients with Non-small Cell Lung Cancer Treated with Radiotherapy2012In: Anticancer research, ISSN 1791-7530, Vol. 32, no 4, p. 1339-1346Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to retrospectively investigate the impact of induction chemotherapy on treatment outcome in patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC).

    Patients and Methods: Patients with a diagnosed NSCLC that have been subjected to curatively intended irradiation (≥50 Gy) and treated in an oncology department in Sweden during the years 1990-2000 were included in the study. Operated patients and patients having received concomitant chemotherapy were excluded. The included patients were localised by a manual search of all the oncology departments' medical records and radiation charts.

    Results: Patients treated with induction chemotherapy (n=79) had a significantly better overall survival compared with patients treated with radiotherapy alone (p=0.0097) in a univariate Cox regression analysis. A platinum/taxane combination produced the greatest survival benefit; hazard ratio=0.49 (95% confidence interval=0.31 to 0.75).

    Conclusion: We found that patients treated with induction chemotherapy in addition to radiotherapy for NSCLC have a better overall survival than patients treated with radiotherapy alone and that the best results are achieved using a platinum/taxane combination.

  • 81. Holgersson, Georg
    et al.
    Sandelin, Martin
    Hoye, Even
    Bergström, Stefan
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ekman, Simon
    Nyman, Jan
    Helsing, Martin
    Friesland, Signe
    Holgersson, Margareta
    Lamberg Lundström, Kristina
    Janson, Christer
    Birath, Elisabet
    Mörth, Charlotte
    Blystad, Thomas
    Ewers, Sven-Börje
    Löden, Britta
    Bergqvist, Michael
    Swedish lung cancer radiation study group: the prognostic value of anaemia, thrombocytosis and leukocytosis at time of diagnosis in patients with non-small cell lung cancer2012In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 29, no 5, p. 3176-3182Article in journal (Refereed)
    Abstract [en]

    There is a need to improve the prognostic and predictive indicators in non-small cell lung cancer (NSCLC). At present, the main focus is on genetic predictive markers while the prognostic value of the standard blood variables related to haematopoiesis has been subjected to relatively limited attention. To study the prognostic potential of haemoglobin (Hgb), platelet (Plt) and white blood cell (WBC) levels at time of diagnosis in NSCLC patients, 835 NSCLC patients, stage I-IV, who received radiotherapy with curative intention (> 50 Gy), were included in the study. WBC, Plt, Hgb, gender, age at diagnosis, stage, surgery and first-line chemotherapy were studied in relation to overall survival. For patients with Hgb < 110 g/L and Hgb a parts per thousand yen 110 g/L), the median survival was 11.2 and 14.5 months, respectively (p = 0.0032). For WBC > 9.0 x 10(9)/L and < 9.0 x 10(9)/L, the median survival was 11.6 and 15.4 months, respectively (p < 0.0001). For Plt > 350 x 10(9)/L and < 350 x 10(9)/L, the median survival was 11.2 and 14.9 months, respectively (p < 0.0001). The median survival in patients with pathological results in all three markers was half of that in patients with normal levels of all three markers (8.0 and 16.0 months, respectively (p < 0.0001). The level of the three studied haematological biomarkers corresponds significantly to outcome in NSCLC. These results indicate that standard haematological variables may be used as guidance for the clinician in the decision-making regarding treatment intensity and patient information.

  • 82.
    Holmlund, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Haapasalo, Hannu
    Yi, Wei
    Raheem, Olayinka
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bragge, Helena
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cytoplasmic LRIG2 expression is associated with poor oligodendroglioma patient survival.2009In: Neuropathology (Kyoto. 1993), ISSN 0919-6544, E-ISSN 1440-1789, Vol. 29, no 3, p. 242-247Article in journal (Refereed)
    Abstract [en]

    The three leucine-rich repeats and immunoglobulin-like domains (LRIG) genes encode integral membrane proteins. Of these, LRIG1 negatively regulates growth factor signaling and is implicated as a tumor suppressor in certain malignancies. In astrocytic tumors, the subcellular distribution of LRIG proteins is associated with specific clinicopathological features and patient survival. The role of LRIG proteins in oligodendroglioma has not previously been studied. Here we used immunohistochemistry to analyze the expression of the LRIG proteins in 63 oligodendroglial tumors, and evaluated possible associations between LRIG protein expression and clinicopathological parameters. Notably, cytoplasmic LRIG2 expression was found to be an independent prognostic factor associated with poor oligodendroglioma patient survival. This is the first report of an LRIG protein showing a negative effect on survival, suggesting that LRIG2 might have a function different from that of LRIG1, and possibly contributing to the etiology of oligodendroglioma.

  • 83.
    Holmlund, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Guo, Dongsheng
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Starefeldt, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Characterization and tissue-specific expression of human LRIG22004In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 332, p. 35-43Article in journal (Refereed)
    Abstract [en]

    We have recently identified and cloned the human LRIG1 gene (formerly LIG1). LRIG1 is a predicted integral membrane protein with a domain organization reminiscent of the Drosophila epidermal growth factor (EGF)-receptor antagonist Kekkon-1. We have searched for additional members of the human LRIG family and identified LRIG2 (KIAA0806). The LRIG2 gene was localized to chromosome 1p13 and had an open reading frame of 1065 amino acids. The LRIG2 protein was predicted to have the same domain organization as LRIG1 with a signal peptide, an extracellular part containing15 leucine-rich repeats and three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail. The LRIG2 amino acid sequence was 47% identical to human LRIG1 and mouse Lrig1 (also known as Lig-1). Northern blotting and RT-PCR revealed LRIG2 transcripts in all tissues analyzed. Quantitative real-time RT-PCR showed the most prominent RNA expression in skin, uterus, ovary, kidney, brain, small intestine, adrenal gland, and stomach. Immunoblotting of COS-7 cell lysates demonstrated that heterologously expressed human LRIG2 had an apparent molecular weight of 132 kDa under reducing gel-running conditions. N-glycosidase F treatment resulted in a reduction of the apparent molecular weight to 107 kDa, showing that LRIG2 was a glycoprotein carrying N-linked oligosaccharides. Cell surface biotinylation experiments and confocal fluorescence laser microscopy demonstrated expression of LRIG2 both at the cell surface and in the cytoplasm. LRIG2 was detected in tissue lysates from stomach, prostate, lung, and fetal brain by immunoblotting. In conclusion, LRIG2 was found to be a glycoprotein which was encoded by a gene on human chromosome 1p13 and its mRNA was present in all tissues analyzed.

  • 84. Jacobs, Kevin B
    et al.
    Yeager, Meredith
    Zhou, Weiyin
    Wacholder, Sholom
    Wang, Zhaoming
    Rodriguez-Santiago, Benjamin
    Hutchinson, Amy
    Deng, Xiang
    Liu, Chenwei
    Horner, Marie-Josephe
    Cullen, Michael
    Epstein, Caroline G
    Burdett, Laurie
    Dean, Michael C
    Chatterjee, Nilanjan
    Sampson, Joshua
    Chung, Charles C
    Kovaks, Joseph
    Gapstur, Susan M
    Stevens, Victoria L
    Teras, Lauren T
    Gaudet, Mia M
    Albanes, Demetrius
    Weinstein, Stephanie J
    Virtamo, Jarmo
    Taylor, Philip R
    Freedman, Neal D
    Abnet, Christian C
    Goldstein, Alisa M
    Hu, Nan
    Yu, Kai
    Yuan, Jian-Min
    Liao, Linda
    Ding, Ti
    Qiao, You-Lin
    Gao, Yu-Tang
    Koh, Woon-Puay
    Xiang, Yong-Bing
    Tang, Ze-Zhong
    Fan, Jin-Hu
    Aldrich, Melinda C
    Amos, Christopher
    Blot, William J
    Bock, Cathryn H
    Gillanders, Elizabeth M
    Harris, Curtis C
    Haiman, Christopher A
    Henderson, Brian E
    Kolonel, Laurence N
    Le Marchand, Loic
    McNeill, Lorna H
    Rybicki, Benjamin A
    Schwartz, Ann G
    Signorello, Lisa B
    Spitz, Margaret R
    Wiencke, John K
    Wrensch, Margaret
    Wu, Xifeng
    Zanetti, Krista A
    Ziegler, Regina G
    Figueroa, Jonine D
    Garcia-Closas, Montserrat
    Malats, Nuria
    Marenne, Gaelle
    Prokunina-Olsson, Ludmila
    Baris, Dalsu
    Schwenn, Molly
    Johnson, Alison
    Landi, Maria Teresa
    Goldin, Lynn
    Consonni, Dario
    Bertazzi, Pier Alberto
    Rotunno, Melissa
    Rajaraman, Preetha
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Freeman, Laura E Beane
    Berg, Christine D
    Buring, Julie E
    Butler, Mary A
    Carreon, Tania
    Feychting, Maria
    Ahlbom, Anders
    Gaziano, J Michael
    Giles, Graham G
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hankinson, Susan E
    Hartge, Patricia
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Inskip, Peter D
    Johansen, Christoffer
    Landgren, Annelie
    McKean-Cowdin, Roberta
    Michaud, Dominique S
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Peters, Ulrike
    Ruder, Avima M
    Sesso, Howard D
    Severi, Gianluca
    Shu, Xiao-Ou
    Visvanathan, Kala
    White, Emily
    Wolk, Alicja
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Silverman, Debra T
    Kogevinas, Manolis
    Gonzalez, Juan R
    Villa, Olaya
    Li, Donghui
    Duell, Eric J
    Risch, Harvey A
    Olson, Sara H
    Kooperberg, Charles
    Wolpin, Brian M
    Jiao, Li
    Hassan, Manal
    Wheeler, William
    Arslan, Alan A
    Bueno-de-Mesquita, H Bas
    Fuchs, Charles S
    Gallinger, Steven
    Gross, Myron D
    Holly, Elizabeth A
    Klein, Alison P
    Lacroix, Andrea
    Mandelson, Margaret T
    Petersen, Gloria
    Boutron-Ruault, Marie-Christine
    Bracci, Paige M
    Canzian, Federico
    Chang, Kenneth
    Cotterchio, Michelle
    Giovannucci, Edward L
    Goggins, Michael
    Bolton, Judith A Hoffman
    Jenab, Mazda
    Khaw, Kay-Tee
    Krogh, Vittorio
    Kurtz, Robert C
    McWilliams, Robert R
    Mendelsohn, Julie B
    Rabe, Kari G
    Riboli, Elio
    Tjønneland, Anne
    Tobias, Geoffrey S
    Trichopoulos, Dimitrios
    Elena, Joanne W
    Yu, Herbert
    Amundadottir, Laufey
    Stolzenberg-Solomon, Rachael Z
    Kraft, Peter
    Schumacher, Fredrick
    Stram, Daniel
    Savage, Sharon A
    Mirabello, Lisa
    Andrulis, Irene L
    Wunder, Jay S
    García, Ana Patiño
    Sierrasesúmaga, Luis
    Barkauskas, Donald A
    Gorlick, Richard G
    Purdue, Mark
    Chow, Wong-Ho
    Moore, Lee E
    Schwartz, Kendra L
    Davis, Faith G
    Hsing, Ann W
    Berndt, Sonja I
    Black, Amanda
    Wentzensen, Nicolas
    Brinton, Louise A
    Lissowska, Jolanta
    Peplonska, Beata
    McGlynn, Katherine A
    Cook, Michael B
    Graubard, Barry I
    Kratz, Christian P
    Greene, Mark H
    Erickson, Ralph L
    Hunter, David J
    Thomas, Gilles
    Hoover, Robert N
    Real, Francisco X
    Fraumeni, Joseph F
    Caporaso, Neil E
    Tucker, Margaret
    Rothman, Nathaniel
    Pérez-Jurado, Luis A
    Chanock, Stephen J
    Detectable clonal mosaicism and its relationship to aging and cancer.2012In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, no 6, p. 651-658Article in journal (Refereed)
    Abstract [en]

    In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.

  • 85.
    Janson, Veronica
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Klinisk kemi.
    Andersson, Britta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Behnam-Motlagh, Parviz
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Engström, Karl-Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Klinisk kemi.
    Acquisition of Cisplatin-resistance in Malignant Mesothelioma Cells Abrogates Na,K(+),2Cl(-;)-cotransport Activity and Cisplatin-induced Early Membrane Blebbing.2008In: Cell Physiol Biochem, ISSN 1421-9778, Vol. 22, no 1-4, p. 45-56Article in journal (Refereed)
    Abstract [en]

    AIMS:

    Resistance mechanisms are important limiting factors in the treatment of solid malignancies with cis-diamminedichloroplatinum(II) (cisplatin). To gain further understanding of the effects of acquired cisplatin-resistance, we compared a human malignant pleural mesothelioma cell line (p31) to a sub-line (p31res1.2) with acquired cisplatin-resistance.

    METHODS AND RESULTS:

    The role of Na(+),K(+),2Cl(-)-cotransport (NKCC1) activity in cisplatin-induced morphological changes and acquired cisplatin-resistance was investigated in a time-resolved manner. Acquisition of cisplatin-resistance resulted in markedly reduced NKCC1 activity, absence of cisplatin-induced early membrane blebbing, and increased basal caspase-3 activity. At equitoxic cisplatin concentrations, P31res1.2 cells had a faster activation of caspase-3 than P31 cells, but the end-stage cytotoxicity and number of cells with DNA fragmentation was similar. Bumetanide inhibition of NKCC1 activity in P31 cells repressed cisplatin-induced early-phase membrane blebbing but did not increase P31 cell resistance to cisplatin.

    CONCLUSIONS:

    Together, these results suggest that active NKCC1 was necessary for cisplatin-induced early membrane blebbing of P31 cells, but not for cisplatin-resistance. Thus, acquisition of cisplatin-resistance can affect mechanisms that have profound effects on cisplatin-induced morphological changes but are not necessary for the subsequent progression to apoptosis.

  • 86.
    Janson, Veronica
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Behnam-Motlagh, Parviz
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hörstedt, Per
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Phase-contrast microscopy studies of early Cisplatin-induced morphological changes of malignant mesothelioma cells and the correspondence to induced apoptosis2008In: Experimental Lung Research, ISSN 0190-2148, E-ISSN 1521-0499, Vol. 34, no 2, p. 49-67Article in journal (Refereed)
    Abstract [en]

    Cisplatin treatment efficacy of malignant pleural mesothelioma (MPM) is aggravated by resistance and adverse effects. In P31 MPM cells, cisplatin induces morphological changes and apoptosis. To determine if very early (10 minutes) morphological responses corresponded to apoptosis-induction, cisplatin effects on P31 morphology were examined with phase-contrast microscopy (PCM), scanning electron microscopy (SEM), and flow cytometry (fluorescence-activated cell sorting [FACS]), and compared to apoptosis-induction over time. Increased membrane protrusions were identified with PCM and SEM, but these were not consistent with the induction of apoptosis. The authors concluded that very early morphological changes can be determined with PCM in MPM, but they did not convincingly correspond to apoptosis induction.

  • 87. Jin, Qianren
    et al.
    Hemminki, Kari
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Grzybowska, Ewa
    Klaes, Rüdinger
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Chen, Bowang
    Pamula, Jolanta
    Pekala, Wioletta
    Zientek, Helena
    Rogozinska-Szczepka, Jadwiga
    Utracka-Hutka, Beata
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Försti, Asta
    Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis2005In: Clinical Cancer Research, ISSN 1078-0432, Vol. 11, no 10, p. 3647-3653Article in journal (Refereed)
  • 88.
    Johansson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Periodontology.
    Behnam Motlagh, Parviz
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Adenylate cyclase toxin from Bordetella pertussis enhances cisplatin-induced apoptosis to lung cancer cells in vitro.2006In: Oncology Research, ISSN 0965-0407, E-ISSN 1555-3906, Vol. 15, no 9, p. 423-430Article in journal (Refereed)
    Abstract [en]

    The present study examined the possibility to enhance lung cancer cell cytotoxicity and apoptosis of the anticancer drug cisplatin by exposure with adenylate cyclase (AC) toxin from Bordetella pertussis. A malignant mesothelioma cell line (P31) and a small-cell lung cancer cell line (U1690) were exposed to increasing concentrations of cisplatin and AC toxin, alone or in combination. Cytotoxicity was determined by a fluorescein-based assay and apoptosis by flow cytometry quantification of annexin V binding. Caspase-3, -8, and -9 activities were measured by enzyme activity assays. The cytotoxicity of AC toxin was time and dose dependent with an LD50 value at 72 h of 3 and 7 mg/L for P31 cells and U1690 cells, respectively. Cisplatin showed a similar time- and dose-dependent cytotoxicity, which was increased in the presence of a low toxic concentration (1 mg/L) of AC toxin. Furthermore, cisplatin caused a dose-dependent increase of annexin V binding cells of both cell lines after 24-h incubation, which was also enhanced in combination with AC toxin. AC toxin (1 mg/L) increased cisplatin-induced caspase-3, -8, and -9 activities in U1690 cells. Only minor increases of caspase-8 and -9 were noted for P31 cells. The present results, together with the knowledge that bacterial toxins decrease side effects of traditional cancer treatment, suggest a possibility to use them to enhance the therapeutic effect of cancer chemotherapy with reduced clinical adverse effects.

  • 89.
    Johansson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Periodontology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Behnam Motlagh, Parviz
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Verotoxin-1 Induction of Apoptosis in Gb3-Expressing Human Glioma Cell Lines2006In: Cancer Biology & Therapy, ISSN 1538-4047, E-ISSN 1555-8576, Vol. 5, no 9, p. 1211-1217Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to examine the cytotoxicity and mechanism of apoptosis induction of verotoxin-1 (VT-1) in human glioma cell lines. VT-1 is a member of the shiga-toxin family expressed by some serotypes of Escherichia coli and Shigella dysenteriae. Shiga-toxins have been shown to induce apoptosis by binding to its membrane receptor Gb3. The human glioma cell lines SF-767, U-343 MG, and U-251 MG were studied together with BT4C, a rat glioma cell line. Cells were first screened for Gb3 expression by flow cytometry. Fluorescein diacetate was used to determine cell viability after VT-1 and irradiation exposure and apoptosis was studied by TUNEL staining, a mitochondrial membrane potential assay, and caspase activity assays. SF-767 and U-343 MG cells were found to express Gb3 and were also sensitive to VT-1-induced cytotoxicity, whereas nonGb3-expressing U-251 MG and BT4C glioma cells were not. VT-1 depolarized the mitochondrial membrane and activated caspase-9 and -3 of SF-767 and U-343 MG cells. VT-1 exposure for 72 h resulted in approx. 60 and 90% TUNEL-stained cells, respectively. D, L-Threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) an inhibitor of glucosylceramide synthesis was used to block Gb3 synthesis. Two mumol/L PPMP for 72 h abolished SF-767 and U-343 MG expression of Gb3 and made the cells completely resistant to VT-1 induced apoptosis. Key components of MAP kinase signalling pathways that control BAX and mitochondrial function were investigated. VT-1 induced JNK phosphorylation in both cell lines, suggesting that survival signal pathways were overruled by VT-1-induced JNK activation leading to mitochondrial depolarization, caspase-9 activation and apoptosis. Immunohistochemistry of cryostat section from glioma biopsies demonstrated expression of Gb3 was in the vascular endothelial cells as well as tumor cells, but not in astrocytes. The high specificity and apoptosis inducing properties of verotoxin-1 indicates that the toxin may be a potential anti-neoplastic agent for Gb3-expressing gliomas.

  • 90. Johansson, Fredrik
    et al.
    Ekman, Simon
    Blomquist, Erik
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergstrom, Stefan
    Bergqvist, Michael
    A Review of Dose-dense Temozolomide Alone and in Combination with Bevacizumab in Patients with First Relapse of Glioblastoma2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 9, p. 4001-4006Article, review/survey (Refereed)
    Abstract [en]

    Treatment of patients with glioblastoma improved dramatically when concomitant and adjuvant temozolomide was added to external radiation therapy. The addition of this new treatment schedule as well as the improvements in individually-tailored radiation treatment, has resulted in a larger proportion of patients being fit for further treatment after first relapse. One of the most interesting combinations that have started to become part of the therapeutic arsenal in the daily clinic is dose-dense temozolomide in combination with bevacizumab. We reviewed and compiled the literature concerning the present topic based on a search of the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) for the years between 1995 and 2011. The clinical studies that have been performed are small and divergent, making it difficult to grade the scientific evidence for the combinatorial treatment of dose-dense temozolomide and bevacizumab. However, the available studies and the experience we have at our departments suggest that this combination is of interest for glioblastoma patients experiencing first relapse. More randomized clinical trials are needed in order to establish the standard of treatment at first relapse in patients with glioblastoma.

  • 91.
    Johansson, Mikael
    et al.
    Departments of Oncology, University Hospital, Umeå, Sweden.
    Bergenheim, A. Tommy
    Departments of Oncology, University Hospital, Umea, Sweden. Neurosurgery, University Hospital, Umeå, Sweden.
    Henriksson, Roger
    Departments of Oncology, University Hospital, Umea, Sweden.
    Koskinen, Lars-Owe D.
    Neurosurgery, University Hospital, Umeå, Sweden.
    Vallbo, Christina
    Departments of Oncology, University Hospital, Umea, Sweden.
    Widmark, Anders
    Departments of Oncology, University Hospital, Umea, Sweden.
    Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model.1997In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 41, no 1, p. 237-244Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed.

    METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated.

    RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight.

    CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.

  • 92.
    Karlsson, Terese
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Induction of apoptosis in resistant glioma cells by synthetic caspase-activation2004In: J Neurooncol, ISSN 0167-594X, Vol. 66, no 1-2, p. 71-79Article in journal (Refereed)
  • 93.
    Karlsson, Terese
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kvarnbrink, Samuel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Botling, J
    Micke, P
    Johansson, Mikael
    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.
    LMO7 interacts with LRIG proteins, and is a negative prognostic marker in lung cancerManuscript (preprint) (Other academic)
  • 94.
    Karlsson, Terese
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kvarnbrink, Samuel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Botling, Johan
    Micke, Patrick
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease2018In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 125, p. 174-184Article in journal (Refereed)
    Abstract [en]

    Objectives: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises the integral membrane proteins LRIG1, LRIG2 and LRIG3. LRIG1 is frequently down-regulated in human cancer, and high levels of LRIG1 in tumor tissue are associated with favorable clinical outcomes in several tumor types including non-small cell lung cancer (NSCLC). Mechanistically, LRIG1 negatively regulates receptor tyrosine kinases and functions as a tumor suppressor. However, the details of the molecular mechanisms involved are poorly understood, and even less is known about the functions of LRIG2 and LRIG3. The aim of this study was to further elucidate the functions and molecular interactions of the LRIG proteins.

    Materials and methods: A yeast two-hybrid screen was performed using a cytosolic LRIG3 peptide as bait. In transfected human cells, co-immunoprecipitation and co-localization experiments were performed. Proximity ligation assay was performed to investigate interactions between endogenously expressed proteins. Expression levels of LMO7 and LIMCH1 in normal and malignant lung tissue were investigated using qRT-PCR and through in silico analyses of public data sets. Finally, a clinical cohort comprising 355 surgically treated NSCLC cases was immunostained for LMO7.

    Results: In the yeast two-hybrid screen, the two paralogous proteins LMO7 and LIMCH1 were identified as interaction partners to LRIG3. LMO7 and LIMCH1 co-localized and co-immunoprecipitated with both LRIG1 and LRIG3. Endogenously expressed LMO7 was in close proximity of both LRIG1 and LRIG3. LMO7 and LIMCH1 were highly expressed in normal lung tissue and down-regulated in malignant lung tissue. LMO7 immunoreactivity was shown to be a negative prognostic factor in LRIG1 positive tumors, predicting poor patient survival.

    Conclusion: These findings suggest that LMO7 and LIMCH1 physically interact with LRIG proteins and that expression of LMO7 is of clinical importance in NSCLC.

  • 95.
    Karlsson, Terese
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kvarnbrink, Samuel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Botling, Johan
    Micke, Patrick
    Johansson, Mikael
    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.
    Interactions between LRIG proteins and LMO7 and the expression of LMO7 in human lung cancer.2013In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 73, no 8: suppl 1, p. 5315-Article in journal (Refereed)
  • 96.
    Karlsson, Terese
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Mark, Elisabeth B
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Redistribution of LRIG proteins in psoriasis2008In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 128, no 5, p. 1192-1195Article in journal (Refereed)
    Abstract [en]

    The human leucine-rich repeats and immunoglobulin-like domains (LRIG) family is composed of three members, LRIG1, -2, and -3, which are all expressed in human skin. LRIG1 negatively regulates growth factor signaling and is involved in the regulation of epidermal stem cell quiescence. Ablation of Lrig1 in mice results in psoriasiform epidermal hyperplasia. Hence, the LRIG proteins may be important for epidermal homeostasis and in psoriasis. Therefore, we analyzed the LRIG mRNA levels and the cellular and subcellular distribution of LRIG proteins in normal and psoriatic skin. The mRNA levels of LRIG1, -2, and -3 were not significantly different in psoriatic epidermis compared to clinically normal epidermis from the same patient. Immunohistochemistry showed that all three LRIG proteins were expressed in unique and specific patterns both in normal and psoriatic skin. Intriguingly, in psoriatic epidermis, the LRIG protein expression patterns were altered compared to normal skin. These results indicate that the LRIG proteins may have a role in epidermal homeostasis and psoriasis.

  • 97. Kiesel, Barbara
    et al.
    Thome, Carina M.
    Weiss, Tobias
    Jakola, Asgeir
    Darlix, Amelie
    Pellerino, Alessia
    Furtner, Julia
    Kerschbaumer, Johannes
    Weller, Michael
    Pilkington, Geoffrey
    Moyal, Elizabeth Cohen-Jonathan
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Watts, Colin
    Ruda, Roberta
    Reifenberger, Guido
    Oberg, Ingela
    Honnorat, Jerome
    Wick, Wolfgang
    Preusser, Matthias
    Widhalm, Georg
    Berghoff, Anna
    PERIOPERATIVE IMAGING OF BRAIN METASTASES: A EUROPEAN ASSOCIATION OF NEURO-ONCOLOGY (EANO) YOUNGSTERS SURVEY2018In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, p. 59-59Article in journal (Other academic)
    Abstract [en]

    BACKGROUND

    Neurosurgical resection is an important treatment option in the multimodal therapy of brain metastases (BM). Perioperative imaging is established in primary brain tumors to assess the extent of resection. However, structured guidelines on the use of perioperative imaging for BM patients are so far missing.

    METHODS

    The European Association of Neuro-Oncology (EANO) Youngsters committee designed a comprehensive questionnaire on the use of perioperative imaging. The survey was distributed to physicians with neuro-oncologic focus via the EANO and the European Association of Neurosurgical Societies (EANS) network.

    RESULTS

    120 physicians from non-European countries and European countries responded to the survey. 76/120 neurosurgeons, 18/120 radiation oncologists and 17/120 neurologists participated. 89/120 participants worked at academic hospitals and 39/40 participants worked in high patient volume centers as defined by >50 BM cases per year. Local standard operating procedures for perioperative imaging were applied by 94/120 physicians. The preferred preoperative imaging method represented MRI for 112/120 (93.3%) participants. Postsurgical imaging was routinely performed by 106/120 physicians. 77/120 participants indicated MRI as the preferred postoperative imaging method, however, only 71/120 performed postoperative MRI imaging within 72 hours after resection. No correlation of postsurgical MRI and localization at an academic hospital (58/79 [73.4%] vs. 19/27 [70.4%], p>0.05) or patient volume (49/71 [69%] vs 25/40 [62.5%], p>0.05) was evident. The most frequently indicated reason for postsurgical imaging was the assessment of extent of resection as participants indicated to adjust the radiotherapy plan or even considered re-surgery to achieve complete resection. CONCLUSIONS: This EANO survey indicates that preoperative MRI is the preferred imaging technique for the majority of physicians, whereas a high variability of postoperative neuroimaging routines including CT and MRI was observed. International guidelines for perioperative imaging with special focus on postoperative MRI are warranted in order to optimize perioperative treatment modalities for BM patients.

  • 98. Kitahara, Cari M
    et al.
    Wang, Sophia S
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wang, Zhaoming
    Braganza, Melissa
    Inskip, Peter D
    Albanes, Demetrius
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Beane Freeman, Laura E
    Buring, Julie E
    Carreón, Tania
    Feychting, Maria
    Gapstur, Susan M
    Gaziano, J Michael
    Giles, Graham G
    Hallmans, Goran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hankinson, Susan E
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hsing, Ann W
    Johansen, Christoffer
    Linet, Martha S
    McKean-Cowdin, Roberta
    Michaud, Dominique S
    Peters, Ulrike
    Purdue, Mark P
    Rothman, Nathaniel
    Ruder, Avima M
    Sesso, Howard D
    Severi, Gianluca
    Shu, Xiao-Ou
    Stevens, Victoria L
    Visvanathan, Kala
    Waters, Martha A
    White, Emily
    Wolk, Alicja
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Hoover, Robert
    Fraumeni, Joseph F
    Chatterjee, Nilanjan
    Yeager, Meredith
    Chanock, Stephen J
    Hartge, Patricia
    Rajaraman, Preetha
    Association between adult height, genetic susceptibility and risk of glioma.2012In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 41, no 4, p. 1075-1085Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub-types, and investigated effect modification by genetic susceptibility to the disease. METHODS: We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case-control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for glioma and glioma sub-types were estimated using logistic regression models stratified by sex and adjusted for birth cohort and study. Pooled ORs were additionally estimated after stratifying the models according to seven recently identified glioma-related genetic variants. RESULTS: Among men, we found a positive association between height and glioma risk (≥190 vs 170-174 cm, pooled OR = 1.70, 95% CI: 1.11-2.61; P-trend = 0.01), which was slightly stronger after restricting to cases with glioblastoma (pooled OR = 1.99, 95% CI: 1.17-3.38; P-trend = 0.02). Among women, these associations were less clear (≥175 vs 160-164 cm, pooled OR for glioma = 1.06, 95% CI: 0.70-1.62; P-trend = 0.22; pooled OR for glioblastoma = 1.36, 95% CI: 0.77-2.39; P-trend = 0.04). In general, we did not observe evidence of effect modification by glioma-related genotypes on the association between height and glioma risk. CONCLUSION: An association of taller adult stature with glioma, particularly for men and stronger for glioblastoma, should be investigated further to clarify the role of environmental and genetic determinants of height in the etiology of this disease.

  • 99.
    Kvarnbrink, Samuel
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Terese
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Forssell, Joakim
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Edlund, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Faraz, Mahmood
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Botling, J
    Feng, Mao
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindquist, David
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Micke, P
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    LRIG1 is a prognostic biomarker and tumor suppressor in non-small cell lung cancerManuscript (preprint) (Other academic)
  • 100. Le Rhun, E.
    et al.
    Weller, M.
    Brandsma, D.
    Van den Bent, M.
    de Azambuja, E.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center, Stockholm.
    Boulanger, T.
    Peters, S.
    Watts, C.
    Wick, W.
    Wesseling, P.
    Ruda, R.
    Preusser, M.
    EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, p. 84-99Article in journal (Refereed)
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