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  • 151.
    Sandström, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model2004In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 91, no 6, p. 1174-1180Article in journal (Refereed)
  • 152.
    Sandström, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Effects of the VEGFR inhibitor ZD6474 in combination with radiotherapy and temozolomide in an orthotopic glioma model.2008In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 88, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    AIM OF THE STUDY:

    The extensive neovascularisation of malignant glioma is mainly influenced by vascular endothelial growth factor (VEGF). The effect of ZD6474, a potent inhibitor of VEGF-receptor-2, was evaluated in combination with either radiotherapy or temozolomide.

    METHODS:

    The effects on glioma growth were investigated in the intracerebral BT4C rat glioma model. ZD6474 30 mg/kg was given alone or in combination with radiotherapy 12 Gy x 1 or with temozolomide 100 mg/kg for 3 days. Two different experiments were performed comparing ZD6474 to radiotherapy or temozolomide. For each experiment 28 animals were randomized into four groups.

    RESULTS:

    ZD6474 in combination with radiotherapy significantly decreased tumour area by 66% compared with controls whereas the combination with temozolomide decreased tumour area by 74%.

    CONCLUSIONS:

    ZD6474 in combination with two standard modalities in the treatment of malignant glioma, radiotherapy and chemotherapy, markedly decreased the growth of an intracerebral experimental glioma. These results justify further investigations of these therapies in combination.

  • 153.
    Sandström, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Sandström, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bergenheim, A. Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Expression of the proteolytic factors, tPA and uPA, PAI-1 and VEGF during malignant glioma progression1999In: International Journal of Developmental Neuroscience, ISSN 0736-5748, E-ISSN 1873-474X, Vol. 17, no 5, p. 473-481Article in journal (Refereed)
  • 154. Saran, F.
    et al.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm and Umeå University, Stockholm/Umeå.
    Mason, W.
    Wick, W.
    Nishikawa, R.
    Cloughesy, T.
    Hilton, M.
    Kerloeguen, Y.
    Chinot, O. L.
    The Addition of Bevacizumab (BEV) to Temozolomide (TMZ) and Radiation Therapy (RT) in Newly Diagnosed Glioblastoma (GBM) Improves Progression-Free Survival (PFS) Without Adding to RT Toxicity2013In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 87, no 2, Supplement S, p. S16-S16Article in journal (Other academic)
  • 155. Saran, Frank
    et al.
    Chinot, Olivier L.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Mason, Warren
    Wick, Wolfgang
    Cloughesy, Timothy
    Dhar, Sunita
    Pozzi, Emanuela
    Garcia, Josep
    Nishikawa, Ryo
    Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy2016In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 18, no 7, p. 991-1001Article in journal (Refereed)
    Abstract [en]

    Background. The proposed use of bevacizumab with radiotherapy/temozolomide for newly diagnosed glioblastoma raised potential safety concerns. Bevacizumab has been linked with stroke, bleeding events, and wound-healing complications in other tumor types; these events are of particular concern for glioblastoma (highly vascular tumors that are usually resected). Published data on the interaction of bevacizumab with radiotherapy/temozolomide are also limited. We report safety data from a phase III randomized trial (Avastin in Glioblastoma), focusing on these considerations. Methods. Eligible patients received: radiotherapy and temozolomide plus bevacizumab/placebo, 6 cycles; a 4-week treatment break; temozolomide plus bevacizumab/placebo, 6 cycles; and bevacizumab/placebo until progression. Data on adverse events (AEs) were collected throughout. Results. Bevacizumab-treated patients (n = 461) had a longer median safety follow-up time (12.3 vs 8.5 mo), and a higher proportion completed 6 cycles of maintenance temozolomide (64.6% vs 36.9%) versus placebo (n = 450). The incidences of relevant AEs (bevacizumab vs placebo, respectively) were: arterial thromboembolic events (5.9% vs 1.6%); cerebral hemorrhage (3.3% vs 2.0%); wound-healing complications (6.9% vs 4.7%); thrombocytopenia (34.1% vs 27.3%); radiotherapy-associated skin injury (8.2% vs 9.3%); alopecia (39.0% vs 36.0%); gastrointestinal perforation (including gastrointestinal abscesses and fistulae, 1.7% vs 0.4%); and radiotherapy-associated injury (0.4% vs 0.0%). Overall, 15.8% and 23.8% of bevacizumab-and placebo-treated patients had surgery (including biopsy) after progression. Within 30 days of postprogression surgery, AE incidence was 10.9% (bevacizumab) and 23.4% (placebo). Conclusion. The safety profile was consistent with that expected from radiotherapy/temozolomide plus bevacizumab. The increased AE incidence with bevacizumab did not impact patients' ability to receive standard-of-care treatment or to undergo further surgery.

  • 156. Saran, Frank
    et al.
    Chinot, Olivier L.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Reg Canc Ctr Stockholm,.
    Mason, Warren
    Wick, Wolfgang
    Nishikawa, Ryo
    Dahr, Sunita
    Hilton, Magalie
    Garcia, Josep
    Cloughesy, Timothy
    SAFETY RESULTS FROM AVAglio, A PHASE III RANDOMIZED STUDY OF BEVACIZUMAB (BEV) PLUS STANDARD COMBINATION TEMOZOLOMIDE (TMZ) AND RADIOTHERAPY (RT) IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM)2013In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 15, no Supplement: 3, p. 127-128Article in journal (Other academic)
  • 157. Schwartzbaum, Judith A
    et al.
    Ahlbom, Anders
    Lönn, Stefan
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Wigertz, Annette
    Auvinen, Anssi
    Brookes, Anthony J
    Collatz Christensen, Helle
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Johansen, Christoffer
    Salminen, Tina
    Schoemaker, Minouk J
    Swerdlow, Anthony J
    Debinski, Waldemar
    Feychting, Maria
    An International Case-Control Study of Interleukin-4R{alpha}, Interleukin-13, and Cyclooxygenase-2 Polymorphisms and Glioblastoma Risk.2007In: Cancer Epidemiol Biomarkers Prev, ISSN 1055-9965, Vol. 16, no 11, p. 2448-2454Article in journal (Refereed)
  • 158. Schwartzbaum, Judith A
    et al.
    Ahlbom, Anders
    Lönn, Stefan
    Warholm, Margareta
    Rannug, Agneta
    Auvinen, Anssi
    Collatz Christensen, Helle
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Johansen, Christoffer
    Lindholm, Carita
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Salminen, Tiina
    Schoemaker, Minouk J
    Swerdlow, Anthony J
    Feychting, Maria
    An international case-control study of glutathione transferase and functionally related polymorphisms and risk of primary adult brain tumors.2007In: Cancer Epidemiology Biomarkers Prevention, ISSN 1055-9965, Vol. 16, no 3, p. 559-565Article in journal (Refereed)
  • 159. Schwartzbaum, Judith
    et al.
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Lönn, Stefan
    Brookes, Anthony J
    Doss, Hani
    Debinski, Waldemar
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Feychting, Maria
    Polymorphisms associated with asthma are inversely related to glioblastoma multiforme2005In: Cancer Research, ISSN 0008-5472, Vol. 65, no 14, p. 6459-6465Article in journal (Refereed)
  • 160. Sharp, Lena
    et al.
    Westman, Bodil
    Olofsson, Anna
    Leppänen, Arja
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre, Stockholm-Gotland, Stockholm, Sweden.
    Access to supportive care during and after cancer treatment and the impact of socioeconomic factors2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 10, p. 1303-1310Article in journal (Refereed)
    Abstract [en]

    Background: Sweden's national cancer strategy points out several areas of cancer care that need improvements. Among them the need for supportive care resources to be accessible through the entire cancer trajectory and the reduction of socioeconomic inequalities. The aim of this study was to compare the patient-reported access to supportive care in the Stockholm-Gotland region between patients diagnosed in 2014 and 2016. The aim was also to describe how socioeconomic and other demographic factors impact access to supportive care.

    Material and methods: All patients with gynaecological, head and neck, haematological and upper gastrointestinal cancers diagnosed in the Stockholm-Gotland regions were identified through the Swedish Cancer Registries. Data were collected via a questionnaire on demographic, socioeconomic factors and patients' perception (n=1872) of access to supportive care. Data were summarized using descriptive statistics and logistic regression was used for relevant variables.

    Results: Access to some supportive care resources, such as contact nurses (CNs) and individual written care plans (IWCPs) had significantly improved from 2014 to 2016. The proportion of patients that had received information about patient advocacy groups (PAGs) had also improved but remained on a relatively low level (29 and 35%, respectively). The proportion of patients being refereed to palliative care (PC) did not change between 2014 and 2016. In total, 10% of the patients reported to having received information on second medical opinion (SMO). Patients that had undergone multimodality cancer treatment were more likely to report access to supportive care, and those with lower education levels were more likely to have access to CNs and IWCPs.

    Conclusion: Access to some of the supportive care resources have shown improvements in the Stockholm-Gotland region but further efforts are required, especially regarding access to PC, information about PAGs and SMOs.

  • 161. Shete, Sanjay
    et al.
    Hosking, Fay J
    Robertson, Lindsay B
    Dobbins, Sara E
    Sanson, Marc
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Simon, Matthias
    Marie, Yannick
    Boisselier, Blandine
    Delattre, Jean-Yves
    Hoang-Xuan, Khe
    El Hallani, Soufiane
    Idbaih, Ahmed
    Zelenika, Diana
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Schramm, Johannes
    Linnebank, Michael
    Hemminki, Kari
    Kumar, Rajiv
    Hepworth, Sarah J
    Price, Amy
    Armstrong, Georgina
    Liu, Yanhong
    Gu, Xiangjun
    Yu, Robert
    Lau, Ching
    Schoemaker, Minouk
    Muir, Kenneth
    Swerdlow, Anthony
    Lathrop, Mark
    Bondy, Melissa
    Houlston, Richard S
    Genome-wide association study identifies five susceptibility loci for glioma.2009In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Nature genetics, ISSN 1546-1718, Vol. 41, no 8, p. 899-904Article in journal (Refereed)
    Abstract [en]

    To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 x 10(-17)), 8q24.21 (rs4295627, CCDC26; P = 2.34 x 10(-18)), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)), 20q13.33 (rs6010620, RTEL1; P = 2.52 x 10(-12)) and 11q23.3 (rs498872, PHLDB1; P = 1.07 x 10(-8)). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.

  • 162. Shete, Sanjay
    et al.
    Lau, Ching C
    Houlston, Richard S
    Claus, Elizabeth B
    Barnholtz-Sloan, Jill
    Lai, Rose
    Il'yasova, Dora
    Schildkraut, Joellen
    Sadetzki, Siegal
    Johansen, Christoffer
    Bernstein, Jonine L
    Olson, Sara H
    Jenkins, Robert B
    Yang, Ping
    Vick, Nicholas A
    Wrensch, Margaret
    Davis, Faith G
    McCarthy, Bridget J
    Leung, Eastwood Hon-Chiu
    Davis, Caleb
    Cheng, Rita
    Hosking, Fay J
    Armstrong, Georgina N
    Liu, Yanhong
    Yu, Robert K
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa L
    Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the gliogene consortium2011In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 71, no 24, p. 7568-7575Article in journal (Refereed)
    Abstract [en]

    Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma. Cancer Res; 71(24); 7568-75. (C) 2011 AACR.

  • 163. Shi, Hong
    et al.
    Bevier, Melanie
    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.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Foersti, Asta
    Prognostic impact of polymorphisms in the MYBL2 interacting genes in breast cancer2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 131, no 3, p. 1039-1047Article in journal (Refereed)
    Abstract [en]

    MYBL2 is a transcription factor, which regulates the expression of genes involved in cancer progression. In this study, we investigated whether putative functional variants in genes regulating MYBL2 (E2F1, E2F3 and E2F4) or in genes, which are regulated by MYBL2 (BCL2, BIRC5, COL1A1, COL1A2, COL5A2, ERBB2, CLU, LIN9 and TOP2A) affect breast cancer (BC) susceptibility and clinical outcome. Twenty-eight SNPs were genotyped in a population-based series of 782 Swedish BC cases and 1,559 matched controls. BC-specific survival analysis of BIRC5 suggested that carriers of the minor allele of rs8073069 and rs1042489 have a worse survival compared with the major homozygotes (HR 2.46, 95% CI 1.39-4.36 and HR 1.81, 95% CI 1.01-3.25, respectively). The poor survival was observed especially in women with aggressive tumours. Multivariate analysis supported the role of rs8073069 as an independent prognostic marker. For BCL2, minor allele carriers of rs1564483 were more likely to have hormone receptor-positive tumours than the major homozygotes. Another SNP in BCL2, rs4987852, was associated with tumour stages II-IV and histologic grade 3. In CLU, the minor allele carriers of rs9331888 were more likely to have tumours with regional lymph node metastasis and stages II-IV than the major homozygotes. In conclusion, our study suggests a role of genetic variation in BIRC5, BCL2 and CLU as progression and prognostic markers for BC, supporting previous studies based on the expression of the genes.

  • 164.
    Sjödin, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Guo, Dongsheng
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hofer, Per-Åke
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Mammaglobin in normal human sweat glands and human sweat gland tumors2003In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 121, no 2, p. 428-429Article in journal (Other academic)
  • 165.
    Sjödin, Anna
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Guo, Dongsheng
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Lund-Johansen, Morten
    Krossnes, Bård Kronen
    Lilleng, Peer
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Secretoglobins in the human pituitary: high expression of lipophilin B and its down-regulation in pituitary adenomas2005In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 109, no 4, p. 381-386Article in journal (Refereed)
    Abstract [en]

    Secretoglobins are small secreted proteins, the expression of which has mostly been associated with secretory mucosal epithelia. Several secretoglobins have been implicated in the development of various human cancers. Allelic deletions of chromosome 11q13 correlates with the invasiveness of pituitary tumors. Intriguingly, several secretoglobin genes are located on 11q13; however, for most of these genes the expression in the pituitary and pituitary tumors have not been investigated. Antibodies specific for the secretoglobin lipophilin B (SCGB1D2, BU101) were developed and used in an immunohistochemical analysis of a human normal tissue microarray. Prominent lipophilin B immunoreactivity was found in the secretory cells of the anterior pituitary. Eight of nine analyzed pituitary adenomas showed a reduction in lipophilin B immunoreactivity compared to normal pituitary. However, there was no apparent association between lipophilin B immunoreactivity and hormone production or tumor invasiveness. Expression of eight different secretoglobin mRNAs were analyzed in normal pituitary and the pituitary adenoma cell line HP75 by highly specific quantitative real-time reverse transcription-PCR assays. Lipophilins B and C (SCGB2A1, mammaglobin B) were the most prominently expressed secretoglobin mRNAs in the pituitary. No secretoglobin mRNA was detected in the HP75 cells. The present report demonstrates, for the first time, lipophilin B expression in the pituitary and its apparent down-regulation in pituitary adenomas.

  • 166.
    Sjödin, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Guo, Dongsheng
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sørhaug, Sveinung
    Bjermer, Leif
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Dysregulated secretoglobin expression in human lung cancers2003In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 41, no 1, p. 49-56Article in journal (Refereed)
    Abstract [en]

    Lipophilins A, B, C, mammaglobin, and uteroglobin are members of the secretoglobin family of small, secreted, proteins. The functions of these proteins are not well understood but uteroglobin has been implicated in the development of cancers. Uteroglobin is known to be highly expressed in normal lung and down-regulated in lung cancers but expression of the other secretoglobins in normal lung and lung neoplasms have not been investigated. Therefore, we developed quantitative real-time reverse transcription (RT-) PCR assays for the different secretoglobins and evaluated their expression in normal and neoplastic lung tissues. The secretoglobin transcript levels were quantitated by real-time RT-PCR in samples from three normal lungs, 24 lung tumors including six small cell lung carcinomas, seven adenocarcinomas, and five squamous cell carcinomas, and in cell lines from three small cell lung carcinomas and one mesothelioma. Uteroglobin was confirmed to be abundantly expressed in normal lung and the different lung tumors showed down-regulated uteroglobin expression. Of the other secretoglobins, only lipophilin C was detected in normal lung, albeit at low levels. The lung tumors, however, frequently showed neo- or up-regulation of lipophilins A, B, C, and mammaglobin. The results constitute the first quantitative evaluation of secretoglobin expression in normal and neoplastic human lung tissues and demonstrate dysregulation in various human lung cancers. These findings could have important biological and diagnostic implications.

  • 167.
    Sjödin, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ljuslinder, Ingrid
    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.
    Mammaglobin and lipophilin B expression in breast tumors and their lack of effect on breast cancer cell proliferation.2008In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 28, no 3A, p. 1493-1498Article in journal (Refereed)
    Abstract [en]

    Mammaglobin (SCGB2A2) and lipophilin B (SCGB1D2) are members of the secretoglobin polypeptide family. Mammaglobin has been shown to be overexpressed in breast tumor tissue, indicating that mammaglobin might confer a growth advantage to mammaglobin-expressing tumor cells. Materials and Methods: The mammaglobin and lipophilin B mRNA expression levels were investigated in seven breast tumors and matched non-neoplastic tissues from the same patients using quantitative real-time RT-PCR. The effect of mammaglobin and lipophilin B expression on breast cancer cell proliferation rates was investigated by analyzing retrovirally transduced Hs578T cell clones. Cell proliferation rates were determined during the exponential growth phase by analyzing the change in lactate dehydrogenase activity over time. Results: All analyzed breast cancer tumors had lower expression levels of mammaglobin and lipophilin B than the respective mean level of the non-neoplastic breast tissues; no prominent overexpression was evident. There was high variability in the expression of mammaglobin and lipophilin B among the non-neoplastic samples, showing that caution should be taken when evaluating their over- and underexpression in tumors. The expression levels of mammaglobin and lipophilin B correlated with each other in the analyzed samples (p=0.001). Ectopic overexpression of mammaglobin and lipophilin B did not affect the cell proliferation rate of Hs578T breast carcinoma cells in vitro. Conclusion: Our findings suggest that the overexpression of mammaglobin observed in certain breast tumors is an epiphenomenon not causally involved in breast carcinogenesis.

  • 168.
    Sjöström, Olle
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Silander, Gustav
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Syk, Ingvar
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Numan Hellquist, Barbro
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Disparities in colorectal cancer between Northern and Southern Sweden: a report from the new RISK North database2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 12, p. 1622-1630Article in journal (Refereed)
    Abstract [en]

    Background: Geographic cancer health disparities have been reported in Sweden. The disparities are not fully understood, but may be attributed to differences in exposure to risk factors as well as differences in health care, socioeconomics and demography. The aim of this study was to describe the new nationwide population based RISK North database and its potential by analysing health disparities in colorectal cancer between Northern and Southern Sweden.

    Methods: Cancer-specific data from the National Cancer Quality Registers for colorectal, gastric and oesophageal cancer and brain tumours were linked to several nationwide registers hereby creating a new database – RISK North. To exemplify the potential of RISK North, we analyzed differences in colorectal cancer incidence, mortality and survival in relation to gender, age, cohabitation and education between Northern and Southern Sweden 2007–2013.

    Results: In colon cancer, the age-adjusted incidence per 100.000 was lower in Northern than Southern Sweden, 35.9 in the North vs. 41.1 in the South (p < .01); mortality rates were 11.0 vs. 12.2 (p < .01). For rectal cancer, incidence rates were 17.6 vs. 19.7 (p < .01) and mortality rates 5.33 vs. 5.89 (p = .07), respectively. The largest difference in incidence was demonstrated for colon cancer among individuals >79 years old (190. vs. 237, i.e., ∼20%). Survival in colon cancer was higher in Southern Sweden, HR 0.92 (0.87–0.98) adjusted for age, gender, co-habiting, education and m-stage at diagnosis. No difference in survival was seen for rectal cancer.

    Conclusions: The new RISK North database enabled analysis of cancer disparities between Northern and Southern Sweden. The incidence of colorectal cancer were lower in the North of Sweden whereas colon cancer survival was higher in the South. These differences can be further analysed utilising the RISK North database.

  • 169.
    Sjöström, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Liu, Yanhong
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Broholm, Helle
    Johansen, Christoffer
    Collatz-Laier, Helle
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Genetic variations in EGF and EGFR and glioblastoma outcome2010In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 12, no 8, p. 815-821Article in journal (Refereed)
    Abstract [en]

    Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete tagging of the epidermal growth factor (EGF) and EGF receptor (EGFR) gene polymorphisms as potential prognostic factors. Thirty tagging single-nucleotide polymorphisms (SNPs) in EGF and 89 tagging SNPs in EGFR were analyzed for association with survival in 176 glioblastoma cases. Validation analyses were performed for 4 SNPs in a set of 638 glioblastoma patients recruited at The University of Texas M. D. Anderson Cancer Center (MDACC). Three hundred and seventy-four glioblastoma patients aged 50 years or older at diagnosis were subanalyzed to enrich for de novo arising glioblastoma. We found 7 SNPs in haplotype 4 in EGF that were associated with prognosis in glioblastoma patients. In EGFR, 4 of 89 SNPs were significantly associated with prognosis but judged as false positives. Four of the significantly associated EGF polymorphisms in haplotype block 4 were validated in a set from MDACC; however, none of the associations were clearly replicated. rs379644 had a hazard ratio (HR) of 1.19 (0.94-1.51) in the whole population with 18.6 months survival in the risk genotype compared with 24.5 in the reference category. As the median age differed slightly between the 2 study sets, the MDACC cases aged 50 or older at diagnosis were analyzed separately (rs379644, HR 1.32 [0.99-1.78]), which is marginally significant and partially validates our findings. This study is, to our knowledge, the first to perform a comprehensive tagging of the EGF and EGFR genes, and the data give some support that EGF polymorphisms might be associated with poor prognosis. Further confirmation in independent data sets of prospective studies is necessary to establish EGF as prognostic risk factor.

  • 170.
    Sjöström, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ghasimi, Soma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Broholm, H.
    Brannstrom, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Johansen, C.
    Collatz-Laier, H.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    EGFR expression and glioblastoma outcome2012In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 14, no Suppl. 3, p. 19-19Article in journal (Other academic)
  • 171.
    Sjöström, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännstrom, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Broholm, H
    Department of Pathology, The Center of Diagnostic Investigations, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
    Johansen, C
    Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
    Collatz-Laier, H
    Department of ENT Head and Neck Surgery, Slagelse Hospital, Slagelse, Denmark.
    Liu, Y
    Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA.
    Bondy, M
    Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Genetic variations in VEGF and VEGFR2 and glioblastoma outcome2011In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 104, no 2, p. 523-527Article in journal (Refereed)
    Abstract [en]

    Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs significantly associated to survival, namely rs2071559 and rs12502008. However, these results are likely to be false positives due to multiple testing and could not be confirmed in a separate dataset. Overall, this study provides little evidence that VEGF and VEGFR2 polymorphisms are important for glioblastoma survival.

  • 172.
    Spetz, Agneta
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Salander, Pär
    Umeå University, Faculty of Social Sciences, Department of Social Work. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    A specialist nurse-function in neurooncology: a qualitative study of possibilities, limitations, and pitfalls2005In: Palliative & Supportive Care, ISSN 1478-9515, E-ISSN 1478-9523, Vol. 3, no 2, p. 121-130Article in journal (Refereed)
  • 173.
    Spetz, Agneta
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Salander, Pär
    Umeå University, Faculty of Social Sciences, Department of Social Work. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    A specialist nurse as a resource for family members to patients with brain tumors: an action research study2008In: Cancer Nursing, ISSN 0162-220X, E-ISSN 1538-9804, Vol. 31, no 4, p. E18-26Article in journal (Refereed)
    Abstract [en]

    There are few scientific publications available with a focus on the value of supportive care services for patients with brain tumors and their families. The present study is part of a project where a specialist nurse (SN) function was implemented for patients with malignant glioma and their next-of-kin. The purpose of the present study was to identify how next-of-kin made use of the SN function. To identify what they asked for when they contacted the nurse is a way of understanding the vulnerability of family members and thus to learn how to provide better support to the benefit of the family. In accordance to a design inspired by action research, the SN approached patients and next-of-kin during diagnosis at the Departments of Oncology/Neurosurgery and informed them that they could use her as a resource when they wanted. The SN documented all contacts with the next-of-kin of 16 consecutive patients in field notes during the course of the disease: telephone calls and personal meetings-who contacted whom, about what, and with what outcome. In addition, summarizing interviews were conducted. The study is based on the field notes and complemented with the interview data. Different needs were expressed throughout the relationship between the next-of-kin and the SN: initially, conversation about the sick family member was paramount, but as time passed, talk about oneself came to the forefront, and thereafter, they also commented on the relationship to the SN in a more personal tone. The relationship to the SN per se is important-the SN function can be far more than a provider of information. Altogether, the platform provided by the SN easily lends itself to the conceptualization of "a secure base" in attachment theory.

  • 174. Stacey, Simon N
    et al.
    Sulem, Patrick
    Zanon, Carlo
    Gudjonsson, Sigurjon A
    Thorleifsson, Gudmar
    Helgason, Agnar
    Jonasdottir, Aslaug
    Besenbacher, Soren
    Kostic, Jelena P
    Fackenthal, James D
    Huo, Dezheng
    Adebamowo, Clement
    Ogundiran, Temidayo
    Olson, Janet E
    Fredericksen, Zachary S
    Wang, Xianshu
    Look, Maxime P
    Sieuwerts, Anieta M
    Martens, John W M
    Pajares, Isabel
    Garcia-Prats, Maria D
    Ramon-Cajal, Jose M
    de Juan, Ana
    Panadero, Angeles
    Ortega, Eugenia
    Aben, Katja K H
    Vermeulen, Sita H
    Asadzadeh, Fatemeh
    van Engelenburg, K C Anton
    Margolin, Sara
    Shen, Chen-Yang
    Wu, Pei-Ei
    Försti, Asta
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jonsson, Thorvaldur
    Sigurdsson, Helgi
    Alexiusdottir, Kristin
    Gudmundsson, Julius
    Sigurdsson, Asgeir
    Frigge, Michael L
    Gudmundsson, Larus
    Kristjansson, Kristleifur
    Halldorsson, Bjarni V
    Styrkarsdottir, Unnur
    Gulcher, Jeffrey R
    Hemminki, Kari
    Lindblom, Annika
    Kiemeney, Lambertus A
    Mayordomo, Jose I
    Foekens, John A
    Couch, Fergus J
    Olopade, Olufunmilayo I
    Gudbjartsson, Daniel F
    Thorsteinsdottir, Unnur
    Rafnar, Thorunn
    Johannsson, Oskar T
    Stefansson, Kari
    Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.2010In: PLoS genetics, ISSN 1553-7404, Vol. 6, no 7, p. e1001029-Article in journal (Refereed)
    Abstract [en]

    We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.

  • 175.
    Svenson, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nordfjäll, Katarina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Manjer, Jonas
    Nilsson, Peter
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Breast cancer survival is associated with telomere length in peripheral blood cells2008In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 68, no 10, p. 3618-3623Article in journal (Refereed)
    Abstract [en]

    Telomeres are essential for maintaining chromosomal stability. Previous studies have indicated that individuals with shorter blood telomeres may be at higher risk of developing various types of cancer, such as in lung, bladder, and kidney. We have analyzed relative telomere length (RTL) of peripheral blood cells in relation to breast cancer incidence and prognosis. The study included 265 newly diagnosed breast cancer patients and 446 female controls. RTL was measured by real-time PCR, and our results show that the patient group displayed significantly longer telomeres compared with controls (P < 0.001). Age-adjusted odds ratios (OR) for breast cancer risk increased with increasing telomere length, with a maximal OR of 5.17 [95% confidence interval (95% CI), 3.09-8.64] for the quartile with the longest telomeres. Furthermore, RTL carried prognostic information for patients with advanced disease. Node positive (N+) patients with short telomeres (</=median) showed an increased survival compared with N+ patients with long telomeres (P = 0.001). For patients with ages <50 years with tumors >16 mm (median tumor diameter), short telomeres were associated with a significantly better outcome than longer telomeres (P = 0.006). Cox regression analysis showed that long RTL was a significant independent negative prognostic factor (hazards ratio, 2.92; 95% CI, 1.33-6.39; P = 0.007). Our results indicate that blood RTL may serve as a prognostic indicator in breast cancer patients with advanced disease.

  • 176.
    Tabatabaei, Pedram
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Glucose metabolites, glutamate and glycerol in malignant glioma tumours during radiotherapy.2008In: J Neurooncol, ISSN 0167-594X, Vol. 90, no 1, p. 35-39Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The metabolism of malignant glioma was studied in 13 patients. The main objective was to perform a study of the metabolic pattern of glucose, lactate, pyruvate, glutamate and glycerol in tumour tissue during base-line conditions and to detect any changes in the metabolism during radiotherapy.

    METHOD:

    During a stereotactic biopsy, two microdialysis catheters were implanted: one in tumour and one in peri-tumoural tissue. Fasting samples were analysed daily, before and during 5 days of radiotherapy given with 2 Gy fractions.

    RESULTS:

    Base-line levels of glucose and pyruvate were significantly lower in tumour compared to peri-tumoural tissue (P = 0.04 and 0.023, respectively). The lactate/pyruvate ratio was significantly higher in tumour tissue (P = 0.022). In general, the levels of lactate, glutamate and glycerol were higher in tumour tissue, although not statistically significant. Further, we could not detect any significant changes during the 5 days of radiotherapy in any of the metabolites analysed.

    CONCLUSION:

    Radiotherapy up to 10 Gy given in five fractions does not influence the glucose metabolism nor does it induce any acute cytotoxic effect detected with glutamate or glycerol in malignant glioma, as assessed by microdialysis. The study confirms the glycolytic properties of glucose metabolism in malignant glioma.

  • 177. Taphoorn, Martin J. B.
    et al.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bottomley, Andrew
    Cloughesy, Timothy
    Wick, Wolfgang
    Mason, Warren P.
    Saran, Frank
    Nishikawa, Ryo
    Hilton, Magalie
    Theodore-Oklota, Christina
    Ravelo, Arliene
    Chinot, Olivier L.
    Health-Related Quality of Life in a Randomized Phase III Study of Bevacizumab, Temozolomide, and Radiotherapy in Newly Diagnosed Glioblastoma2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 19, p. 2166-U205Article in journal (Refereed)
    Abstract [en]

    Purpose As glioblastoma progresses, patients experience a decline in health-related quality of life (HRQoL). Delaying this decline is an important treatment goal. In newly diagnosed glioblastoma, progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide (RT/TMZ) versus placebo plus RT/TMZ (phase III AVAglio study; hazard ratio, 0.64; 95% CI, 0.55 to 0.74; P < .001). To ensure that addition of bevacizumab to standard-of-care therapy was not associated with HRQoL detriment, HRQoL assessment was a secondary objective. Patients and Methods Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BN20 at each tumor assessment (Appendix Table A1, online only). Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated (stable: < 10-point change; clinically relevant deterioration/improvement: 10-point change). Deterioration-free survival was the time to deterioration/progression/death; time to deterioration was the time to deterioration/death. Results Most evaluable patients who had not progressed (> 74%) completed all HRQoL assessments for at least 1 year of treatment, and almost all completed at least one HRQoL assessment at baseline (98.3% and 97.6%, bevacizumab and placebo arms, respectively). Mean changes from baseline did not reach a clinically relevant difference between arms for most items. HRQoL declined at progression in both arms. The addition of bevacizumab to RT/TMZ resulted in statistically longer (P < .001) deterioration-free survival across all items. Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm (v bevacizumab) for any HRQoL item. Conclusion The addition of bevacizumab to standard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period.

  • 178. Taphoorn, Martin J. B.
    et al.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Reg Canc Ctr Stockholm.
    Bottomley, Andrew
    Cloughesy, Timothy
    Wick, Wolfgang
    Mason, Warren
    Saran, Frank
    Nishikawa, Ryo
    Ravelo, Arliene
    Hilton, Magalie
    Chinot, Olivier L.
    HEALTH-RELATED QUALITY OF LIFE (HRQOL) ANALYSES IN THE AVAGLIO STUDY, A RANDOMIZED, PLACEBO-CONTROLLED PHASE III TRIAL OF BEVACIZUMAB, TEMOZOLOMIDE AND RADIOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA2013In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 15, no Supplement: 3, p. 232-232Article in journal (Other academic)
  • 179.
    Thomasson, Marcus
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Guo, D
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    LRIG1 and epidermal growth factor receptor in renal cell carcinoma: a quantitative RT-PCR and immunohistochemical analysis2003In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 89, no 7, p. 1285-1289Article in journal (Refereed)
    Abstract [en]

    In all, 31 renal cell carcinomas (RCCs) were examined for expression of the potential tumour suppressor LRIG1 (formerly Lig-1) and the epidermal growth factor receptor (EGFR). Eight matched samples of uninvolved kidney cortex were also evaluated. Gene expression was examined by quantitative real-time RT-PCR. In the eight matched sample pairs (uninvolved kidney cortex and tumour), protein expression was examined by immunohistochemistry. Conventional (clear cell) tumours showed an expected upregulation of EGFR. LRIG1 expression was generally downregulated in conventional and papillary RCC but not in chromophobic RCC. The ratio between EGFR and LRIG1 was more than 2.5-fold higher in the eight tumours compared with matched uninvolved kidney cortex and was at least two-fold higher than the mean normal ratio in 21 of 31 samples analysed. The observed downregulation of LRIG1 and increased EGFR/LRIG1 ratios are consistent with LRIG1 being a suppressor of oncogenesis in RCC by counteracting the tumour-promoting properties of EGFR. Further studies are justified to elucidate the explicit role of LRIG1 in the oncogenesis of RCC.

  • 180.
    Thomasson, Marcus
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Junttila, Teemu T
    Elenius, Klaus
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    ErbB4 is downregulated in renal cell carcinoma: a quantitative RT-PCR and immunohistochemical analysis of the epidermal growth factor receptor family2004In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 43, no 5, p. 453-459Article in journal (Refereed)
  • 181.
    Thomasson, Marcus
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gene expression pattern of the epidermal growth factor receptor family and LRIG1 in renal cell carcinoma2012In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 5, no 216, p. 1-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies have revealed altered expression of epidermal growth factor receptor (EGFR)-family members and their endogenous inhibitor leucine-rich and immunoglobulin-like domains 1 (LRIG1) in renal cell carcinoma (RCC). In this study, we analyzed the gene expression levels of EGFR-family members and LRIG1, and their possible associations with clinical parameters in various types of RCC, individually.

    METHODS: Gene expression levels of EGFR-family members and LRIG1 were analyzed in 104 RCC samples, including 81 clear cell RCC (ccRCC), 15 papillary RCC (pRCC), and 7 chromophobe RCC (chRCC) by quantitative real-time RT-PCR. Associations between gene expression levels and clinical data, including tumor grade, stage, and patient survival were statistically assessed.

    RESULTS: Compared to kidney cortex, EGFR was up-regulated in ccRCC and pRCC, LRIG1 and ERBB2 were down-regulated in ccRCC, and ERBB4 was strongly down-regulated in all RCC types. ERBB3 expression did not differ between RCC types or between RCC and the kidney cortex. The expression of the analyzed genes did not correlate with patient outcome.

    CONCLUSIONS: This study revealed that the previously described up-regulation of EGFR and down-regulation of ERBB4 occurred in all analyzed RCC types, whereas down-regulation of ERBB2 and LRIG1 was only present in ccRCC. These observations illustrate the need to evaluate the different RCC types individually when analyzing molecules of interest and potential biological markers.

  • 182.
    Thomasson, Marcus
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wang, Baofeng
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahlman, Anna
    Persson, Jenny Liao
    Josefsson, Andreas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Granfors, Torvald
    Egevad, Lars
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    LRIG1 and the liar paradox in prostate cancer: A study of the expression and clinical significance of LRIG1 in prostate cancer.2011In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, no 12, p. 2843-2852Article in journal (Refereed)
    Abstract [en]

    The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signalling and a proposed tumour suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In the present study, the expression of LRIG1 protein in prostate cancer was evaluated for the first time. Immunohistochemistry was performed on tissue microarrays from two different patient series: 355 Swedish patients diagnosed by transurethral resection and 293 American patients who underwent radical prostatectomy. In the Swedish series, high expression of LRIG1 correlated with Gleason score, T-stage, tumour cell proliferation, vascular density, and epidermal growth factor receptor (EGFR) phosphorylation. Among the 256 Swedish patients, followed by watchful waiting, high LRIG1 expression was significantly associated with short overall and prostate cancer-specific survival. In contrast, in the U.S. series, high LRIG1 expression was significantly associated with longer overall survival. In vitro cell experiments showed that LRIG1 was induced by androgen stimulation, and its expression inhibited prostate cancer cell proliferation. Thus, LRIG1 expression was an independent marker for poor survival in the untreated patient series, perhaps as a secondary marker of androgen receptor and/or EGFR activation. On the contrary, LRIG1 was a marker for good prognosis after prostatectomy, which might be due to its growth inhibiting properties. We propose that LRIG1 is an important determinant of prostate cancer growth, and the implications of its expression on patient outcome depend upon the clinical and biological circumstances.

  • 183. Thompson, Patricia A.
    et al.
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tsavachidis, Spyros
    Brewster, Abenaa
    Sahin, Aysegul
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa L.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Loss of LRIG1 Locus Increases Risk of Early and Late Relapse of Stage I/II Breast Cancer2014In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 11, p. 2928-2935Article in journal (Refereed)
    Abstract [en]

    Gains and losses at chromosome 3p12-21 are common in breast tumors and associated with patient outcomes. We hypothesized that the LRIG1 gene at 3p14.1, whose product functions in ErbB-family member degradation, is a critical tumor modifier at this locus. We analyzed 971 stage I/II breast tumors using Affymetrix Oncoscan molecular inversion probe arrays that include 12 probes located within LRIG1. Copy number results were validated against gene expression data available in the public database. By partitioning the LRIG1 probes nearest exon 12/13, we confirm a breakpoint in the gene and show that gains and losses in the subregions differ by tumor and patient characteristics including race/ethnicity. In analyses adjusted for known prognostic factors, loss of LRIG1 was independently associated with risk of any relapse (HR, 1.90; 95% CI, 1.32-2.73), relapse >= 5 years (HR, 2.39; 95% CI, 1.31-4.36), and death (HR, 1.55; 95% CI, 1.11-2.16). Analyses of copy number across chromosome 3, as well as expression data from pooled, publicly available datasets, corroborated the hypothesis of an elevated and persistent risk among cases with loss of or low LRIG1. We concluded that loss/low expression of LRIG1 is an independent risk factor for breast cancer metastasis and death in stage I/II patients. Increased hazard in patients with loss/low LRIG1 persists years after diagnosis, suggesting that LRIG1 is acting as a critical suppressor of tumor metastasis and is an early clinical indicator of risk for late recurrences in otherwise low-risk patients.

  • 184. Thomsen, Hauke
    et al.
    da Silva Filho, Miguel Inacio
    Woltmann, Andrea
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Eyfjord, Jorunn E.
    Hamann, Ute
    Manjer, Jonas
    Enquist-Olsson, Kerstin
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Cancer Center Stockholm Gotland, Stockholm, Sweden.
    Herms, Stefan
    Hoffmann, Per
    Chen, Bowang
    Huhn, Stefanie
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Foersti, Asta
    Inbreeding and homozygosity in breast cancer survival2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 16467Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWASs) help to understand the effects of single nucleotide polymorphisms (SNPs) on breast cancer (BC) progression and survival. We performed multiple analyses on data from a previously conducted GWAS for the influence of individual SNPs, runs of homozygosity (ROHs) and inbreeding on BC survival. (I.) The association of individual SNPs indicated no differences in the proportions of homozygous individuals among short-time survivors (STSs) and long-time survivors (LTSs). (II.) The analysis revealed differences among the populations for the number of ROHs per person and the total and average length of ROHs per person and among LTSs and STSs for the number of ROHs per person. (III.) Common ROHs at particular genomic positions were nominally more frequent among LTSs than in STSs. Common ROHs showed significant evidence for natural selection (iHS, Tajima's D, Fay-Wu's H). Most regions could be linked to genes related to BC progression or treatment. (IV.) Results were supported by a higher level of inbreeding among LTSs. Our results showed that an increased level of homozygosity may result in a preference of individuals during BC treatment. Although common ROHs were short, variants within ROHs might favor survival of BC and may function in a recessive manner.

  • 185. Varadi, Verena
    et al.
    Bevier, Melanie
    Grzybowska, Ewa
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Enquist, 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.
    Butkiewicz, Dorota
    Pamula-Pilat, Jolanta
    Tecza, Karolina
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Foersti, Asta
    Genetic variation in genes encoding for polymerase zeta subunits associates with breast cancer risk, tumour characteristics and survival2011In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 129, no 1, p. 235-245Article in journal (Refereed)
    Abstract [en]

    Chromosomal instability is a known hallmark of many cancers. DNA polymerases represent a group of enzymes that are involved in the mechanism of chromosomal instability as they have a central function in DNA metabolism. We hypothesized that genetic variation in the polymerase genes may affect gene expression or protein configuration and by that cancer risk and clinical outcome. We selected four genes encoding for the catalytic subunits of the polymerases beta, delta, theta and zeta (POLB, POLD1, POLQ and REV3L, respectively) and two associated proteins (MAD2L2 and REV1) because of their previously reported association with chromosomal instability and/or tumorigenesis. We selected potentially functional and most informative tagging single nucleotide polymorphisms (SNPs) for genotyping in a population-based series of 783 Swedish breast cancer (BC) cases and 1562 controls. SNPs that showed a significant association in the Swedish population were additionally genotyped in a Polish population consisting of 506 familial/early onset BC cases and 568 controls. SNPs in all three polymerase zeta subunit genes associated either with BC risk or prognosis. Two SNPs in REV3L and one SNP in MAD2L2 associated with BC risk: rs462779 (multiplicative model: OR 0.79, 95% CI 0.68-0.92), rs3204953 (dominant model: OR 1.28, 95% CI 1.05-1.56) and rs2233004 (recessive model: OR 0.49, 95% CI 0.28-0.86). Homozygous carriers of the minor allele C of the third SNP in REV3L, rs11153292, had significantly worse survival compared to the TT genotype carriers (HR 2.93, 95% CI 1.34-6.44). Minor allele carriers of two REV1 SNPs (rs6761391 and rs3792142) had significantly more often large tumours and tumours with high histological grade and stage. No association was observed for SNPs in POLB, POLQ and POLD1. Altogether, our data suggest a significant role of genetic variation in the polymerase zeta subunit genes regarding the development and progression of BC.

  • 186. Varadi, Verena
    et al.
    Bevier, Melanie
    Grzybowska, Ewa
    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.
    Butkiewicz, Dorota
    Pamula-Pilat, Jolanta
    Tecza, Karolina
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Genetic variation in ALCAM and other chromosomal instability genes in breast cancer survival2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 131, no 1, p. 311-319Article in journal (Refereed)
    Abstract [en]

    Chromosomal instability is a hallmark of many cancers and it has a potential to predict clinical outcome of a cancer patient. We hypothesized that genes whose expression status differs between chromosomal stable and unstable breast tumors represent target genes for the identification of genetic variants predicting breast cancer (BC) risk, disease progression, and survival. We used a published list of 38 genes associated with chromosomal instability as a basis for searching potentially functional and informative tagging single nucleotide polymorphisms (SNPs). As a result, 33 SNPs in 16 genes were genotyped in a population-based series of 783 Swedish BC cases. Two SNPs in the ALCAM gene associated with BC-specific survival. For rs1044243, the HR was 4.35 (95% CI 1.34-14.18), and for rs1157, the HR was 3.42 (95% CI 1.32-8.83) for the homozygous carriers of the minor alleles. For the minor allele carriers of CCL18 SNP rs14304, we observed a significant association with aggressive tumor characteristics: large tumor size (OR 1.53, 95% CI 1.10-2.14), positive lymph node metastasis (OR 1.75, 95% CI 1.02-3.00), and high stage (OR 1.37, 95% CI 1.02-1.85). In a Polish population consisting of 506 familial/early onset BC cases, no association with event-free survival for the ALCAM SNPs nor any association with tumor characteristics for the CCL18 SNP were observed, suggesting either a chance finding in the Swedish population or population-based or etiological differences between sporadic and familial/early onset BC.

  • 187. Varadi, Verena
    et al.
    Brendle, Annika
    Brandt, Andreas
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Svenson, Ulrika
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Polymorphisms in telomere-associated genes, breast cancer susceptibility and prognosis2009In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 45, no 17, p. 3008-3016Article in journal (Refereed)
    Abstract [en]

    Telomeres are essential structures for maintaining chromosomal stability and their length has been reported to correlate with cancer risk and clinical outcome. Single nucleotide polymorphisms (SNPs) in genes encoding telomere-associated proteins could affect telomere length and chromosomal stability by influencing gene expression or protein configuration in the telomeres. Here, we report the results of the first association study on genetic variation in telomere-associated genes and their effect on telomere length, breast cancer (BC) susceptibility and prognosis. We genotyped 14 potentially functional and most informative SNPs in nine telomere-associated genes (TERT, TEP1, TERF1, TERF2, TERF2IP, ACD, POT1, TNKS and TNKS2) in 782 incident BC cases and 1559 matched controls. Relative telomere length (RTL) varied statistically significantly between the genotypes of the SNPs rs446977 (TEP1, p=0.04), rs938886 (TEP1, p=0.04) and rs6990097 (TNKS, p=0.04). However, none of them was associated with BC susceptibility and only rs6990097 correlated with regional lymph node metastasis (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.08-1.77). The strongest association with BC susceptibility was observed for rs3785074 (TERF2, OR 0.51, 95% CI 0.31-0.83) and rs10509637 (TNKS2, OR 1.33, 95% CI 1.08-1.62). Haplotype and diplotype analysis confirmed the association of the TNKS2 gene with BC susceptibility. rs3785074 (TERF2) was additionally associated with histologic grade (OR 1.44, 95% CI 1.08-1.92) and negative oestrogen receptor status (OR 2.93, 95% CI 1.13-7.58). None of the SNPs showed a significant correlation with survival of the breast cancer patients. With these results, none of the SNPs represents any valuable prognostic marker for BC.

  • 188. Wang, Zhaoming
    et al.
    Rajaraman, Preetha
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Chung, Charles C.
    Zhang, Weijia
    McKean-Cowdin, Roberta
    Michaud, Dominique
    Yeager, Meredith
    Ahlbom, Anders
    Albanes, Demetrius
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Freeman, Laura E. Beane
    Buring, Julie E.
    Butler, Mary Ann
    Carreon, Tania
    Feychting, Maria
    Gapstur, Susan M.
    Gaziano, J. Michael
    Giles, Graham G.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. 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.
    Hoffman-Bolton, Judith
    Inskip, Peter D.
    Kitahara, Cari M.
    Marchand, Loic Le
    Linet, Martha S.
    Li, Shengchao
    Peters, Ulrike
    Purdue, Mark P.
    Rothman, Nathaniel
    Ruder, Avima M.
    Sesso, Howard D.
    Severi, Gianluca
    Stampfer, Meir
    Stevens, Victoria L.
    Visvanathan, Kala
    Wang, Sophia S.
    White, Emily
    Zeleniuch-Jacquotte, Anne
    Hoover, Robert
    Fraumeni, Joseph F.
    Chatterjee, Nilanjan
    Hartge, Patricia
    Chanock, Stephen J.
    Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data2015In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 36, no 7, p. 684-688Article in journal (Refereed)
    Abstract [en]

    We confirmed strong association of rs78378222:A>C (per allele odds ratio [OR] = 3.14; P = 6.48 x 10(-11)), a germline rare single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma (1,856 cases and 4,955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma multiforme) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with approximate to 3 kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma.

  • 189. Wang, Zhaoming
    et al.
    Zhu, Bin
    Zhang, Mingfeng
    Parikh, Hemang
    Jia, Jinping
    Chung, Charles C
    Sampson, Joshua N
    Hoskins, Jason W
    Hutchinson, Amy
    Burdette, Laurie
    Ibrahim, Abdisamad
    Hautman, Christopher
    Raj, Preethi S
    Abnet, Christian C
    Adjei, Andrew A
    Ahlbom, Anders
    Albanes, Demetrius
    Allen, Naomi E
    Ambrosone, Christine B
    Aldrich, Melinda
    Amiano, Pilar
    Amos, Christopher
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andriole, Gerald
    Andrulis, Irene L
    Arici, Cecilia
    Arslan, Alan A
    Austin, Melissa A
    Baris, Dalsu
    Barkauskas, Donald A
    Bassig, Bryan A
    Beane Freeman, Laura E
    Berg, Christine D
    Berndt, Sonja I
    Bertazzi, Pier Alberto
    Biritwum, Richard B
    Black, Amanda
    Blot, William
    Boeing, Heiner
    Boffetta, Paolo
    Bolton, Kelly
    Boutron-Ruault, Marie-Christine
    Bracci, Paige M
    Brennan, Paul
    Brinton, Louise A
    Brotzman, Michelle
    Bueno-de-Mesquita, H Bas
    Buring, Julie E
    Butler, Mary Ann
    Cai, Qiuyin
    Cancel-Tassin, Geraldine
    Canzian, Federico
    Cao, Guangwen
    Caporaso, Neil E
    Carrato, Alfredo
    Carreon, Tania
    Carta, Angela
    Chang, Gee-Chen
    Chang, I-Shou
    Chang-Claude, Jenny
    Che, Xu
    Chen, Chien-Jen
    Chen, Chih-Yi
    Chen, Chung-Hsing
    Chen, Constance
    Chen, Kuan-Yu
    Chen, Yuh-Min
    Chokkalingam, Anand P
    Chu, Lisa W
    Clavel-Chapelon, Francoise
    Colditz, Graham A
    Colt, Joanne S
    Conti, David
    Cook, Michael B
    Cortessis, Victoria K
    Crawford, E David
    Cussenot, Olivier
    Davis, Faith G
    De Vivo, Immaculata
    Deng, Xiang
    Ding, Ti
    Dinney, Colin P
    Di Stefano, Anna Luisa
    Diver, W Ryan
    Duell, Eric J
    Elena, Joanne W
    Fan, Jin-Hu
    Feigelson, Heather Spencer
    Feychting, Maria
    Figueroa, Jonine D
    Flanagan, Adrienne M
    Fraumeni, Joseph F
    Freedman, Neal D
    Fridley, Brooke L
    Fuchs, Charles S
    Gago-Dominguez, Manuela
    Gallinger, Steven
    Gao, Yu-Tang
    Gapstur, Susan M
    Garcia-Closas, Montserrat
    Garcia-Closas, Reina
    Gastier-Foster, Julie M
    Gaziano, J Michael
    Gerhard, Daniela S
    Giffen, Carol A
    Giles, Graham G
    Gillanders, Elizabeth M
    Giovannucci, Edward L
    Goggins, Michael
    Gokgoz, Nalan
    Goldstein, Alisa M
    Gonzalez, Carlos
    Gorlick, Richard
    Greene, Mark H
    Gross, Myron
    Grossman, H Barton
    Grubb, Robert
    Gu, Jian
    Guan, Peng
    Haiman, Christopher A
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hankinson, Susan E
    Harris, Curtis C
    Hartge, Patricia
    Hattinger, Claudia
    Hayes, Richard B
    He, Qincheng
    Helman, Lee
    Henderson, Brian E
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hoffman-Bolton, Judith
    Hohensee, Chancellor
    Holly, Elizabeth A
    Hong, Yun-Chul
    Hoover, Robert N
    Hosgood, H Dean
    Hsiao, Chin-Fu
    Hsing, Ann W
    Hsiung, Chao Agnes
    Hu, Nan
    Hu, Wei
    Hu, Zhibin
    Huang, Ming-Shyan
    Hunter, David J
    Inskip, Peter D
    Ito, Hidemi
    Jacobs, Eric J
    Jacobs, Kevin B
    Jenab, Mazda
    Ji, Bu-Tian
    Johansen, Christoffer
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Johnson, Alison
    Kaaks, Rudolf
    Kamat, Ashish M
    Kamineni, Aruna
    Karagas, Margaret
    Khanna, Chand
    Khaw, Kay-Tee
    Kim, Christopher
    Kim, In-Sam
    Kim, Jin Hee
    Kim, Yeul Hong
    Kim, Young-Chul
    Kim, Young Tae
    Kang, Chang Hyun
    Jung, Yoo Jin
    Kitahara, Cari M
    Klein, Alison P
    Klein, Robert
    Kogevinas, Manolis
    Koh, Woon-Puay
    Kohno, Takashi
    Kolonel, Laurence N
    Kooperberg, Charles
    Kratz, Christian P
    Krogh, Vittorio
    Kunitoh, Hideo
    Kurtz, Robert C
    Kurucu, Nilgun
    Lan, Qing
    Lathrop, Mark
    Lau, Ching C
    Lecanda, Fernando
    Lee, Kyoung-Mu
    Lee, Maxwell P
    Le Marchand, Loic
    Lerner, Seth P
    Li, Donghui
    Liao, Linda M
    Lim, Wei-Yen
    Lin, Dongxin
    Lin, Jie
    Lindstrom, Sara
    Linet, Martha S
    Lissowska, Jolanta
    Liu, Jianjun
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lloreta, Josep
    Lu, Daru
    Ma, Jing
    Malats, Nuria
    Mannisto, Satu
    Marina, Neyssa
    Mastrangelo, Giuseppe
    Matsuo, Keitaro
    McGlynn, Katherine A
    McKean-Cowdin, Roberta
    McNeill, Lorna H
    McWilliams, Robert R
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Meltzer, Paul S
    Mensah, James E
    Miao, Xiaoping
    Michaud, Dominique S
    Mondul, Alison M
    Moore, Lee E
    Muir, Kenneth
    Niwa, Shelley
    Olson, Sara H
    Orr, Nick
    Panico, Salvatore
    Park, Jae Yong
    Patel, Alpa V
    Patino-Garcia, Ana
    Pavanello, Sofia
    Peeters, Petra H M
    Peplonska, Beata
    Peters, Ulrike
    Petersen, Gloria M
    Picci, Piero
    Pike, Malcolm C
    Porru, Stefano
    Prescott, Jennifer
    Pu, Xia
    Purdue, Mark P
    Qiao, You-Lin
    Rajaraman, Preetha
    Riboli, Elio
    Risch, Harvey A
    Rodabough, Rebecca J
    Rothman, Nathaniel
    Ruder, Avima M
    Ryu, Jeong-Seon
    Sanson, Marc
    Schned, Alan
    Schumacher, Fredrick R
    Schwartz, Ann G
    Schwartz, Kendra L
    Schwenn, Molly
    Scotlandi, Katia
    Seow, Adeline
    Serra, Consol
    Serra, Massimo
    Sesso, Howard D
    Severi, Gianluca
    Shen, Hongbing
    Shen, Min
    Shete, Sanjay
    Shiraishi, Kouya
    Shu, Xiao-Ou
    Siddiq, Afshan
    Sierrasesumaga, Luis
    Sierri, Sabina
    Loon Sihoe, Alan Dart
    Silverman, Debra T
    Simon, Matthias
    Southey, Melissa C
    Spector, Logan
    Spitz, Margaret
    Stampfer, Meir
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stern, Mariana C
    Stevens, Victoria L
    Stolzenberg-Solomon, Rachael Z
    Stram, Daniel O
    Strom, Sara S
    Su, Wu-Chou
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sung, Sook Whan
    Swerdlow, Anthony
    Tan, Wen
    Tanaka, Hideo
    Tang, Wei
    Tang, Ze-Zhang
    Tardon, Adonina
    Tay, Evelyn
    Taylor, Philip R
    Tettey, Yao
    Thomas, David M
    Tirabosco, Roberto
    Tjonneland, Anne
    Tobias, Geoffrey S
    Toro, Jorge R
    Travis, Ruth C
    Trichopoulos, Dimitrios
    Troisi, Rebecca
    Truelove, Ann
    Tsai, Ying-Huang
    Tucker, Margaret A
    Tumino, Rosario
    Van Den Berg, David
    Van Den Eeden, Stephen K
    Vermeulen, Roel
    Vineis, Paolo
    Visvanathan, Kala
    Vogel, Ulla
    Wang, Chaoyu
    Wang, Chengfeng
    Wang, Junwen
    Wang, Sophia S
    Weiderpass, Elisabete
    Weinstein, Stephanie J
    Wentzensen, Nicolas
    Wheeler, William
    White, Emily
    Wiencke, John K
    Wolk, Alicja
    Wolpin, Brian M
    Wong, Maria Pik
    Wrensch, Margaret
    Wu, Chen
    Wu, Tangchun
    Wu, Xifeng
    Wu, Yi-Long
    Wunder, Jay S
    Xiang, Yong-Bing
    Xu, Jun
    Yang, Hannah P
    Yang, Pan-Chyr
    Yatabe, Yasushi
    Ye, Yuanqing
    Yeboah, Edward D
    Yin, Zhihua
    Ying, Chen
    Yu, Chong-Jen
    Yu, Kai
    Yuan, Jian-Min
    Zanetti, Krista A
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Zhou, Baosen
    Mirabello, Lisa
    Savage, Sharon A
    Kraft, Peter
    Chanock, Stephen J
    Yeager, Meredith
    Landi, Maria Terese
    Shi, Jianxin
    Chatterjee, Nilanjan
    Amundadottir, Laufey T
    Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.332014In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, no 24, p. 6616-6633Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

  • 190. Weller, Michael
    et al.
    van den Bent, Martin
    Hopkins, Kirsten
    Tonn, Jörg C.
    Stupp, Roger
    Falini, Andrea
    Cohen-Jonathan-Moyal, Elizabeth
    Frappaz, Didier
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Balana, Carmen
    Chinot, Olivier
    Ram, Zvi
    Reifenberger, Guido
    Soffietti, Riccardo
    Wick, Wolfgang
    EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma2014In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 15, no 9, p. E395-E403Article, review/survey (Refereed)
    Abstract [en]

    This guideline provides recommendations for diagnostic and therapeutic procedures for patients with malignant gliomas. We differentiate evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein should provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline contributes to a critical appreciation of concurrent drugs with a focus on the controlled use of anticonvulsants and steroids. It should serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarised here will need interdisciplinary structures of care for patients with brain tumours and structured processes of diagnostic and therapeutic procedures.

  • 191. Westman, Bodil
    et al.
    Kirkpatrick, Lily
    Ebrahim, Fereshte
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sharp, Lena
    Patient-reported experiences on supportive care strategies following the introduction of the first Swedish national cancer strategy and in accordance with the new patient act2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 3, p. 382-392Article in journal (Refereed)
    Abstract [en]

    Introduction: Several supportive care strategies are described in Swedish legislation and policy documents, such as the National Cancer Strategy and the Patient act. No previous systematic evaluation from a patient perspective has been performed. The aim of this study was to evaluate how these supportive care strategies are experienced by patients treated for cancer in the Stockholm-Gotland region.

    Material and methods: In this cross-sectional study, we identified patients (diagnosed with gynaecological, haematological, upper gastrointestinal and head and neck cancer during 2014) from the Swedish Cancer Register. The European Organization of Research and Treatment of Cancer, EORTC, Quality of Life Questionnaires, QLQ-C30, Information QLQ-INFO25 and a study-specific questionnaire was used to collect data during follow-up after cancer treatment. We collected data on 869 cancer patients' perception of availability and access to supportive care strategies and how they were experienced.

    Results: Among the supportive care strategies suggested in the legislation and policy documents, just over half of the patients (n=393, 53%) reported that they had access to a contact nurse, while 43% (n=312) had received an individual written care plan and 16% (n=137) had been referred to palliative care. Only 29% (n=218) of the patients reported that they had received information about patient advocacy groups and 8% (n=62) on medical second opinions from their cancer care team.

    Discussion: The supportive care strategies suggested in Swedish legislation and policy documents may be useful but are only available for some patients. The implementation goals for the National Cancer Strategy and the Swedish Patient act have not been reached.

  • 192.
    Wibom, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ghasimi, Soma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Van Loo, P.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ryden, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    EGFR gene variants are associated with specific somatic aberrations in glioma2012In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 14, no Suppl. 3, p. 46-46Article in journal (Other academic)
  • 193.
    Wibom, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ghasimi, Soma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Van Loo, Peter
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lau, Ching
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    EGFR gene variants are associated with specific somatic aberrations in glioma2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e47929-Article in journal (Refereed)
    Abstract [en]

    A number of gene variants have been associated with an increased risk of developing glioma. We hypothesized that the reported risk variants may be associated with tumor genomic instability. To explore potential correlations between germline risk variants and somatic genetic events, we analyzed matched tumor and blood samples from 95 glioma patients by means of SNP genotyping. The generated genotype data was used to calculate genome-wide allele-specific copy number profiles of the tumor samples. We compared the copy number profiles across samples and found two EGFR gene variants (rs17172430 and rs11979158) that were associated with homozygous deletion at the CDKN2A/B locus. One of the EGFR variants (rs17172430) was also associated with loss of heterozygosity at the EGFR locus. Our findings were confirmed in a separate dataset consisting of matched blood and tumor samples from 300 glioblastoma patients, compiled from publically available TCGA data. These results imply there is a functional effect of germline EGFR variants on tumor progression.

  • 194.
    Wibom, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Pettersson, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment2006In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 94, no 12, p. 1853-1863Article in journal (Refereed)
    Abstract [en]

    Radiotherapy is one of the mainstays of glioblastoma (GBM) treatment. This study aims to investigate and characterise differences in protein expression patterns in brain tumour tissue following radiotherapy, in order to gain a more detailed understanding of the biological effects. Rat BT4C glioma cells were implanted into the brain of two groups of 12 BDIX-rats. One group received radiotherapy (12 Gy single fraction). Protein expression in normal and tumour brain tissue, collected at four different time points after irradiation, were analysed using surface enhanced laser desorption/ionisation - time of flight - mass spectrometry (SELDI-TOF-MS). Mass spectrometric data were analysed by principal component analysis (PCA) and partial least squares (PLS). Using these multivariate projection methods we detected differences between tumours and normal tissue, radiation treatment-induced changes and temporal effects. 77 peaks whose intensity significantly changed after radiotherapy were discovered. The prompt changes in the protein expression following irradiation might help elucidate biological events induced by radiation. The combination of SELDI-TOF-MS with PCA and PLS seems to be well suited for studying these changes. In a further perspective these findings may prove to be useful in the development of new GBM treatment approaches.

  • 195.
    Wibom, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Vandetanib alters the protein pattern in malignant glioma and normal brain in the BT4C rat glioma model2010In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 37, no 4, p. 879-890Article in journal (Refereed)
    Abstract [en]

    The treatment of glioblastoma is unsatisfactory. Improved understanding of the biological effects of treatment, together with development of new tools to predict outcome of the initiated treatment are therefore of great need. Vandetanib (ZD6474) is mainly a vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) receptor tyrosine kinase inhibitor. This study investigated the pattern of protein expression in brain tumor and normal brain tissue, following treatment with vandetanib in a rat glioma model. BT4C-cells were stereotactically implanted into the brain of BD IX rats. The rats were divided into three different experiments. The treatment schedule for experiments one and two consisted of daily, oral doses of vandetanib from day 6 until day 12 or 20 after implantation, respectively. In the third experiment, each animal received a single dose of vandetanib on day 19 after implantation and was then sacrificed 2, 8 or 24 h thereafter. The protein expression profiles were analyzed by SELDI-TOF-MS and evaluated with multivariate statistical methods. Following treatment with vandetanib, we found significantly altered protein expression pattern in malignant glioma and normal brain. Analyzing protein spectra is an interesting option to assess biological effects induced in brain tissue by signal transduction inhibitors such as vandetanib.

  • 196.
    Wibom, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sjöström, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Broholm, Helle
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Johansen, Christoffer
    Collatz-Laier, Helle
    Hepworth, Sara
    McKinney, Patricia A
    Bethke, Lara
    Houlston, Richard S
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    DNA-repair gene variants are associated with glioblastoma survival2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 3, p. 325-332Article in journal (Refereed)
    Abstract [en]

    Patient outcome from glioma may be influenced by germline variation. Considering the importance of DNA repair in cancer biology as well as in response to treatment, we studied the relationship between 1458 SNPs, which captured the majority of the common genetic variation in 136 DNA repair genes, in 138 glioblastoma samples from Sweden and Denmark. We confirmed our findings in an independent cohort of 121 glioblastoma patients from the UK. Our analysis revealed nine SNPs annotating MSH2, RAD51L1 and RECQL4 that were significantly (p < 0.05) associated with glioblastoma survival.

  • 197. Wick, Wolfgang
    et al.
    Chinot, Olivier L.
    Bendszus, Martin
    Mason, Warren
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Reg Canc Ctr Stockholm Gotland, Stockholm, Sweden.
    Saran, Frank
    Nishikawa, Ryo
    Revil, Cedric
    Kerloeguen, Yannick
    Cloughesy, Timothy
    Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma2016In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 18, no 10, p. 1434-1441Article in journal (Refereed)
    Abstract [en]

    Evaluation of glioblastoma disease status may be complicated by treatment-induced changes and discordance between enhancing and nonenhancing MRI. Exploratory analyses are presented (prospectively assessed pseudoprogression and therapy-related tumor pattern changes) from the AVAglio trial (bevacizumab or placebo plus radiotherapy/temozolomide for newly diagnosed glioblastoma). MRI was done every 8 weeks (beginning 4 wk after chemoradiotherapy) using prespecified and standardized T1 and T2 protocols. Progressive disease (PD) at 10 weeks was reconfirmed at 18 weeks to distinguish pseudoprogression. Progression-free survival (PFS), excluding cases of confirmed pseudoprogression, was assessed (post-hoc/exploratory). Tumor progression patterns were determined at each disease assessment/PD (prespecified/exploratory). Of patients with PD in the bevacizumab and placebo arms, 143/354 (40.4%) and 155/387 (40.1%), respectively, had PD due to contrast-enhancing lesions, and 51/354 (14.4%) and 53/387 (13.7%) had PD due to nonenhancing lesions. Of all patients in the bevacizumab arm (n = 458), 2.2% had confirmed pseudoprogression versus 9.3% in the placebo arm (n = 463). Baseline characteristics did not differ between patients with/without pseudoprogression (including for MGMT status). Excluding confirmed pseudoprogression, PFS (hazard ratio: 0.65, 95% CI: 0.56-0.75; P < .0001, bevacizumab vs placebo) was comparable to the intent-to-treat population. At PD, most patients had the same tumor focus (local/multifocal, > 84%) and infiltrative profile (> 88%) as at baseline; no shift to a diffuse or multifocal phenotype was observed. Pseudoprogression complicated progression assessment in a small but relevant number of patients but had negligible impact on PFS. Bevacizumab did not appear to adversely impact tumor progression patterns.

  • 198.
    Wode, Kathrin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Nursing. Regional Cancer Center Stockholm Gotland, Stockholm, Sweden; Department for Upper Gastrointestinal Cancer, K42, Karolinska University Hospital, Stockholm, Sweden.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Regional Cancer Center Stockholm Gotland, Stockholm, Sweden.
    Sharp, Lena
    Stoltenberg, Anna
    Nordberg, Johanna Hök
    Cancer patients' use of complementary and alternative medicine in Sweden: a cross-sectional study2019In: BMC Complementary and Alternative Medicine, ISSN 1472-6882, E-ISSN 1472-6882, Vol. 19, article id 62Article in journal (Refereed)
    Abstract [en]

    Background: Access to and advice on Complementary and Alternative Medicine (CAM) are uncommon within Swedish conventional cancer care and little is known about cancer patients' own use of CAM. The aim of this cross-sectional study was to explore Swedish cancer patients patterns of CAM use, their experiences and preferences.

    Methods. Questionnaires were distributed consecutively to 1297 cancer patients at a university hospital's out-patient oncology units. The response rate was 58% (n=755). Descriptive statistics were used to analyze the survey data. A logistic regression model was used to investigate the association between CAM use and gender, age and level of education. Open-ended responses were analyzed, using qualitative content analysis.

    Results: Lifetime CAM use was reported by 34% (n=256), and 26% (n=198) used CAM after cancer diagnosis. Being female, younger and having higher education predicted CAM use. Most commonly used methods were natural products including vitamins and mineralsand relaxation. Main reasons for CAM use were improvement of physical, general and emotional wellbeing and increasing the body's ability to fight cancer. Satisfaction with CAM usage was generally high. Reported adverse effects were few and mild; 54% of users spent <50 Euro a month on CAM. One third had discussed their CAM use with cancer care providers. More than half of all participants thought that cancer care providers should be able to discuss (58%) and to consider (54%) use of CAM modalities in cancer care.

    Conclusions: Despite limited access and advice within conventional cancer care, one fourth of Swedish cancer patients use CAM. The insufficient patient-provider dialogue diverges with most patients' wish for professional guidance in their decisions and integration of CAM modalities in conventional cancer care. Concurrent and multimodal CAM use implies challenges and possibilities for cancer care that need to be considered.

  • 199. Woltmann, Andrea
    et al.
    Chen, Bowang
    Lascorz, Jesus
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Eyfjord, Jorunn E.
    Hamann, Ute
    Manjer, Jonas
    Enquist-Olsson, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herms, Stefan
    Hoffmann, Per
    Hemminki, Kari
    Lenner, Per
    Forsti, Asta
    Systematic Pathway Enrichment Analysis of a Genome-Wide Association Study on Breast Cancer Survival Reveals an Influence of Genes Involved in Cell Adhesion and Calcium Signaling on the Patients' Clinical Outcome2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, p. e98229-Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWASs) may help to understand the effects of genetic polymorphisms on breast cancer (BC) progression and survival. However, they give only a focused view, which cannot capture the tremendous complexity of this disease. Therefore, we investigated data from a previously conducted GWAS on BC survival for enriched pathways by different enrichment analysis tools using the two main annotation databases Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The goal was to identify the functional categories (GO terms and KEGG pathways) that are consistently overrepresented in a statistically significant way in the list of genes generated from the single nucleotide polymorphism (SNP) data. The SNPs with allelic p-value cut-offs 0.005 and 0.01 were annotated to the genes by excluding or including a 20 kb up-and down-stream sequence of the genes and analyzed by six different tools. We identified eleven consistently enriched categories, the most significant ones relating to cell adhesion and calcium ion binding. Moreover, we investigated the similarity between our GWAS and the enrichment analyses of twelve published gene expression signatures for breast cancer prognosis. Five of them were commonly used and commercially available, five were based on different aspects of metastasis formation and two were developed from meta-analyses of published prognostic signatures. This comparison revealed similarities between our GWAS data and the general and the specific brain metastasis gene signatures as well as the Oncotype DX signature. As metastasis formation is a strong indicator of a patient's prognosis, this result reflects the survival aspect of the conducted GWAS and supports cell adhesion and calcium signaling as important pathways in cancer progression.

  • 200. Wu, Xuping
    et al.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergqvist, Michael
    Bergström, Stefan
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gullbo, Joachim
    Lennartsson, Johan
    Hesselius, Patrik
    Ekman, Simon
    Expression of EGFR and LRIG proteins in oesophageal carcinoma with emphasis on patient survival and cellular chemosensitivity.2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 1, p. 69-76Article in journal (Refereed)
    Abstract [en]

    Abstract Background. Leucine-rich and immunoglobulin-like domains 1-3 (LRIG1-3) proteins have been implicated in the regulation of EGFR signalling. In the present study, we investigated the clinical implications of the expression of EGFR and LRIG1-3 in oesophageal carcinoma, as well as the correlation between their expression levels and the chemosensitivity of oesophageal carcinoma cell lines. Patients and methods. Tumours from 80 patients with oesophageal carcinoma were investigated for the expression of EGFR and LRIG proteins by immunohistochemistry. Oesophageal carcinoma cell lines were investigated for their expression of EGFR and LRIG1, 2, and 3 by quantitative real time RT-PCR and for their sensitivity to commonly used chemotherapeutics by a cytotoxicity assay. Results and discussion: Based on a total score of intensity and expression rates, a trend towards survival difference was found for EGFR (p = 0.09) and LRIG2 (p = 0.18) whereas for LRIG1 and -3 there was no trend towards any association with survival. Correlation analysis revealed a correlation with the clinical expression of EGFR and LRIG3 (p = 0.0007). Significant correlations were found between LRIG1 expression levels and sensitivity to cisplatin (r = -0.74), docetaxel (r = -0.69), and vinorelbine (r = -0.82) in oesophageal carcinoma cell lines. EGFR and the LRIG proteins may be functionally involved in oesophageal carcinoma, but larger materials are needed to fully elucidate the clinical implication.

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