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  • 101.
    Green, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Mirghani, Rajaa A.
    Rymark, Per
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Pharmacogenetics of Paclitaxel in the Treatment of Ovarian Cancer – a Pilot Study in Preparation of Individualized Chemotherapy2007Inngår i: Clinical Cancer Research, ISSN 1078-0432Artikkel i tidsskrift (Fagfellevurdert)
  • 102.
    Green Landell, Malin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Tillfors, Maria
    Dept. of Behavioural, Social and Legal Sciences Örebro University.
    Furmark, Tomas
    Dept. of Psychology Uppsala University.
    Bohlin, Gunilla
    Dept. of Psychology Uppsala University.
    Andersson, Gerhard
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Avdelningen för klinisk och socialpsykologi (CS). Linköpings universitet, Filosofiska fakulteten.
    Göran Svedin, Carl
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barn- och ungdomspsykiatri. Linköpings universitet, Hälsouniversitetet.
    Social phobia in Swedish adolescents: Prevalence and gender differences2009Inngår i: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 44, nr 1, s. 1-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The aim of this study was to investigate the prevalence of self-reported social phobia in a community sample of Swedish adolescents in junior high school, at the risk-period for developing social phobia. Of particular interest was to investigate gender differences in prevalence across ages. Prevalence of sub-threshold social phobia was also studied. Methods Students in grades 6-8 (aged 12-14) from seventeen schools in five Swedish municipalities were screened by means of a self-report questionnaire, the social phobia screening questionnaire-for children (SPSQ-C). Results Data from a sample of 2,128 students were analysed and showed a point-prevalence rate of 4.4% (95% CI 3.5-5.2) and a significant gender difference (6.6% girls vs. 1.8% boys, P < 0.001). No significant differences in prevalence of probable cases emerged across the ages. At sub-threshold level, marked social fear of at least one social situation was reported by 13.8% of the total group. "Speaking in front of class and "calling someone unfamiliar on the phone were the most feared social situations. In the social phobia group, 91.4% reported impairment in the school-domain due to their social fear. Conclusion Social phobia is a common psychiatric condition in Swedish adolescents, especially in girls. As impairment in the school-domain is reported to a high degree, professionals and teachers need to recognize social phobia in adolescents so that help in overcoming the difficulties can be offered.

  • 103.
    Gunnarsson, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Jerevall, Piiha-Lotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Hammar, Karl
    Linköpings universitet, Institutionen för datavetenskap. Linköpings universitet, Tekniska högskolan.
    Olsson, Birgit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Nordenskjöld, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Jansson, Agneta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi.
    Stål, Olle
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Amplification of HSD17B1 has prognostic significance in postmenopausal breast cancer2008Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 108, nr 1, s. 35-41Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In situ synthesis of estrogens is believed to be of great importance for the progression of breast cancer. In postmenopausal women most estrogens are synthesized in peripheral hormone-target tissues from circulating precursor steroids, by the enzymes involved in formation of active estrogens. One of the enzymes involved in this process is 17β-hydroxysteroid dehydrogenase (17β-HSD) type 1. This enzyme catalyzes the interconversion of estrone (E1) to the biologically more potent estradiol (E2). The gene coding for 17β-HSD type 1 (HSD17B1) is located at 17q12-21. The aim of this study was to investigate altered gene copy number of HSD17B1 in breast cancer. We used real-time PCR and examined 387 postmenopausal breast tumors for amplification of HSD17B1, and if an increased mRNA level of this enzyme is associated with amplification of the gene. We also investigated whether amplification of HSD17B1 has a prognostic value. There was a significant correlation between gene copy number of HSD17B1 and mRNA expression level (P = 0.00002). ER-positive patients with amplification of HSD17B1 showed lower breast cancer survival than patients without amplification (P = 0.025). Among ER-negative patients there was no significant correlation between increased gene copy number of HSD17B1 and prognosis. Furthermore, we found that amplification of the gene had prognostic significance in multivariate analysis adjusting for other clinicopathological variables. © 2007 Springer Science+Business Media, LLC.

  • 104.
    Hackshaw, Allan
    et al.
    University College London.
    Baum, Michael
    University College London.
    Fornander, Tommy
    Stockholm Breast Cancer Study Group.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Nicolucci, Antonio
    Group Interdisciplinare Valutaz Interventi Oncology.
    Monson, Kathryn
    University College London.
    Forsyth, Sharon
    University College London.
    Reczko, Krystyna
    University College London.
    Johansson, Ulla
    Stockholm Breast Cancer Study Group.
    Fohlin, Helena
    Stockholm Breast Cancer Study Group.
    Valentini, Miriam
    Group Interdisciplinare Valutaz Interventi Oncology.
    Sainsbury, Richard
    University College London.
    Long-term Effectiveness of Adjuvant Goserelin in Premenopausal Women With Early Breast Cancer2009Inngår i: JOURNAL OF THE NATIONAL CANCER INSTITUTE, ISSN 0027-8874, Vol. 101, nr 5, s. 341-349Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Systematic reviews have found that luteinizing hormone-releasing hormone (LHRH) agonists are effective in treating premenopausal women with early breast cancer.

    We conducted long-term follow-up (median 12 years) of 2706 women in the Zoladex In Premenopausal Patients (ZIPP), which evaluated the LHRH agonist goserelin (3.6 mg injection every 4 weeks) and tamoxifen (20 or 40 mg daily), given for 2 years. Women were randomly assigned to receive each therapy alone, both, or neither, after primary therapy (surgery with or without radiotherapy/chemotherapy). Hazard ratios and absolute risk differences were used to assess the effect of goserelin treatment on event-free survival (breast cancer recurrence, new tumor or death), overall survival, risk of recurrence of breast cancer, and risk of dying from breast cancer, in the presence or absence of tamoxifen.

    Fifteen years after the initiation of treatment, for every 100 women not given tamoxifen, there were 13.9 (95% confidence interval [CI] = 17.5 to 19.4) fewer events among those who were treated with goserelin compared with those who were not treated with goserelin. However, among women who did take tamoxifen, there were 2.8 fewer events (95% CI = 7.7 fewer to 2.0 more) per 100 women treated with goserelin compared with those not treated with goserelin. The risk of dying from breast cancer was also reduced at 15 years: For every 100 women given goserelin, the number of breast cancer deaths was lower by 2.6 (95% CI = 6.6 fewer to 2.1 more) and 8.5 (95% CI = 2.2 to 13.7) in those who did and did not take tamoxifen, respectively, although in the former group the difference was not statistically significant.

    Two years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy. In women who did not take tamoxifen, there was a large benefit of goserelin treatment on survival and recurrence, and in women who did take tamoxifen, there was a marginal potential benefit on these outcomes when goserelin was added.

  • 105.
    Hagglund, H
    et al.
    Hematol Centre, Stockholm, Sweden .
    Machaczka, M
    Hematol Centre, Stockholm, Sweden .
    Remberger, M
    Hematol Centre, Stockholm, Sweden .
    Hallbook, H
    Department Hematol, Uppsala, Sweden .
    Lazarevic, V
    Department Hematol, Lund, Sweden .
    Wahlin, A
    Department Hematol, Umea, Sweden .
    Malm, C
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Kimby, E
    Hematol Centre, Stockholm, Sweden .
    Johansson, J-E
    Department Hematol, Gothenburg, Sweden .
    Allo HSCT with RIC for poor-risk CLL in Sweden: donor T-cell engraftment 3 months after transplantation predicts long-term survival in BONE MARROW TRANSPLANTATION, vol 46, issue , pp S365-S3652011Inngår i: BONE MARROW TRANSPLANTATION, Nature Publishing Group , 2011, Vol. 46, s. S365-S365Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 106.
    Hallbeck, Anna-Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Walz, Thomas M.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Briheim, Kristina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Wasteson, Åke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    TGF-alpha and ErbB2 production in synovial joint tissue: increased expression in arthritic joints2005Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 34, nr 3, s. 204-211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Cell types present in synovial joint tissues and during synovitis are known to produce epidermal growth factor receptor (EGFR)/ErbB-1/HER-1 and the potent EGFR-ligand transforming growth factor-alpha (TGF-) in vitro. Concomitant expression of TGF-, EGFR, and ErbB2 gives a strong proliferative drive in vitro and in vivo. However, the presence of TGF- and members of the EGFR/EGFR-ligand family has not been thoroughly investigated in joint tissue in vivo. We aimed to determine whether TGF-, EGFR, and ErbB2 are present in human synovial joints, especially during rheumatoid arthritis (RA).

    Methods: TGF- protein was immunodetected in knee synovial fluid (SF) collected from 23 RA patients, eight patients with other arthritic conditions, two osteoarthritis (OA) patients, and six post-traumatic patients (control). TGF- mRNA and TGF-, ErbB2, EGFR, and CD68 immunoreactivity were detected in knee synovial biopsies (6 RA/2 OA/6 control) using in situ hybridization and immunohistochemistry. TGF- mRNA was determined in SF cells by reverse transcription polymerase chain reaction (RT-PCR) and/or the Northern blot technique.

    Results: TGF- protein was found in the synovial membrane (SM) and in the majority of SF samples. TGF- levels were significantly higher (p<0.001) in SF of RA patients than controls, TGF- protein and mRNA were increased and more widespread in SM of RA patients. In addition, white blood cells collected from RA SF expressed TGF- mRNA. Immunoreactivity for ErbB2 was found in SM and was more widespread in RA patients than in controls.

    Conclusion: The presence of TGF- in normal SF and SM may indicate a physiological maintenance function. The increased expression of TGF- and ErbB2 in RA SF and SM may give rise to an abnormal growth pattern, contributing to inflammatory synovial hyperplasia.

  • 107.
    Hallbeck, Anna-Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Walz, Thomas M.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Wasteson, Åke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Interleukin-6 enhances transforming growth factor-alpha mRNA expression in macrophage-like human monocytoid (U-937-1) cells2001Inngår i: Bioscience Reports, ISSN 0144-8463, Vol. 21, nr 3, s. 325-339Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have previously reported that the human monocytoid cell line U-937-1 constitutively expresses transforming growth factor-alpha (TGF-α) and that the steady-state levels of TGF-α mRNA as well as TGF-α protein release increase when U-937-1 cells are differentiated towards monocytes/macrophages. Interleukin-6 (IL-6), which has been shown to have growth-stimulatory effects on a number of cell types, has recently been shown to enhance TGF-α expression in keratinocytes. In the present study we investigated whether TGF-α expression in macrophage-like cells could be regulated by IL-6 using U-937-1 cells as a model system of monocyte/macrophage differentiation.

    U-937-1 cells were differentiated with retinoic acid (RA), vitamin D3 (Vit-D3) or phorbol-12-myristate-13-acetate (PMA) for 4 days and were then treated with human recombinant IL-6 (1000 IU/ml) for up to 24 hr. Northern blot analysis revealed that cells differentiated with PMA, inducing the phenotype of a secretory macrophage, markedly increased their TGF-α mRNA levels (2.7-fold) when treated with IL-6; the response was maximal at 6 hr and remained high at 12 hr. The expression of the TGF-α gene was accompanied by release of TGF-α protein into the cell culture medium, irrespective of differentiating agent, as demonstrated by enzyme-linked immunosorbent assay (ELISA), as well as by surface expression of pro-TGF-α as determined by indirect immunofluorescent cytometry. However, the superinduction of the TGF-α gene by IL-6 in cells differentiated with PMA was not accompanied by any increase in TGF-α protein release or pro-TGF-α surface expression.

    We conclude that since IL-6 causes increased steady-state levels of TGF-α mRNA in macrophage-like cells, it may prime these cells for production of this growth factor. Furthermore, we have shown that the IL-6 receptor complex is functional in U-937-1 cells induced to differentiate towards a secretory macrophage by treatment with PMA.

  • 108.
    Hallbeck, Anna-Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Walz, Thomas M.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Wasteson, Åke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Lindström, Annelie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Cooperation of endogenous HER-family members in synovial sarcoma cells: stimulation of HER-2/ErbB2 is dependent on EGFR activation2007Artikkel i tidsskrift (Fagfellevurdert)
  • 109. Hardell, L
    et al.
    van Bavel, B
    Lindstrom, G
    Carlberg, M
    Dreifaldt, AC
    Wijkstrom, H
    Starkhammar, Hans
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Eriksson, M
    Hallquist, A
    Kolmert, T
    Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular cancer2003Inngår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 111, nr 7, s. 930-934Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An increasing incidence of testicular cancer has been reported from several countries in the Western world during the last decades. According to current hypothesis, testicular cancer is initiated during the fetal period, and exposure to endocrine disruptors, i.e., xenoestrogens, has been of concern. In this investigation we studied the concentrations of the sum of 38 polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene, hexachlorobenzene (HCB), and chlordanes, in 61 cases with testicular cancer and 58 age-matched controls. Furthermore, case and control mothers were also asked to participate, and 44 case mothers and 45 control mothers agreed. They were of similar age. In cases only the concentration on lipid basis of cis-nonachlordane was significantly increased, whereas case mothers showed significantly increased concentrations of the sum of PCBs, HCB, trans- and cis-nonachlordane, and the sum of chlordanes. Among case mothers the sum of PCBs yielded an odds ratio (OR) of 3.8, 95% confidence interval (CI), 1.4-10 was calculated using the median concentration for the control mothers as cutoff value. For HCB, OR = 4.4 (95% CI, 1.7-12), for trans-nonachlordane, OR = 4.1 (95% CI, 1.5-11), for cis-nonachlordane, OR = 3.1 (95% CI, 1.2-7.8), and for sum of chlordanes, OR = 1.9 (95% CI, 0.7-5.0). No consistent different risk pattern was found for seminoma. or nonseminoma testicular cancer.

  • 110.
    Hatschek, T
    et al.
    Karolinska Institute.
    Carlsson, L
    Sundsvall General Hospital.
    Einbeigi, Z
    Sahlgrens University Hospital.
    Lidbrink, E
    Karolinska Institute.
    Linderholm, B
    Sahlgrens University Hospital.
    Lindh, B
    Umeå University Hospital.
    Loman, N
    Skåne University Hospital Lund.
    Malmberg, M
    Helsingborg General Hospital.
    Rotstein, S
    Karolinska Institute.
    Soderberg, M
    Skåne University Hospital.
    Sundquist, M
    Kalmar General Hospital.
    Walz, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Hellstrom, M
    Karolinska University Hospital.
    Svensson, H
    Sahlgrens University Hospital.
    Astrom, G
    Karolinska Institute.
    Brandberg, Y
    Karolinska Institute.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Filosofiska fakulteten.
    Ferno, M
    Lund University.
    Bergh, J
    Karolinska Institute.
    Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial2012Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 131, nr 3, s. 939-947Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(A (R))) and paclitaxel (Taxol(A (R))) alone (ET) or in combination with capecitabine (Xeloda(A (R)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.

  • 111.
    Hatschek, T
    et al.
    Karolinska University Hospital.
    Einbeigi, Z
    Sahlgrens University Hospital.
    Walz, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Malmberg, M
    Helsingborg Hospital.
    Loman, N
    Lund University Hospital.
    Carlsson, L
    Sundsvall Hospital.
    Soderberg, M
    Malmo University Hospital.
    Linderholm, B
    Sahlgrens University Hospital.
    Lindh, B
    Norrland University Hospital.
    Sundqvist, M
    Kalmar Hospital.
    Individually dose-adjusted treatment with epirubicin and paclitaxel with or without capecitabine as 1st line treatment in metastatic breast cancer. A randomized multicenter trial in EJC SUPPLEMENTS, vol 8, issue 3, pp 195-1962010Inngår i: EJC SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2010, Vol. 8, nr 3, s. 195-196Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 112.
    Hayat Roshanai, Afsaneh
    et al.
    BMC, Sweden Uppsala University, Sweden .
    Lampic, Claudia
    Karolinska Institute, Sweden Uppsala University, Sweden .
    Ingvoldstad, Charlotta
    Uppsala University, Sweden .
    Stenmark-Askmalm, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Bjorvatn, Chathrine
    University of Bergen, Norway .
    Rosenquist, Richard
    Uppsala University, Sweden .
    Nordin, Karin
    University of Bergen, Norway Uppsala University, Sweden .
    What Information Do Cancer Genetic Counselees Prioritize?2012Inngår i: Journal of Genetic Counseling, ISSN 1059-7700, E-ISSN 1573-3599, Vol. 21, nr 4, s. 510-526Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study explored the informational needs of individuals attending genetic counseling for hereditary cancer, using a free-choice and a forced choice method. Prior to the consultation the informational needs of 334 counselees from Sweden and Norway were assessed by the QUOTE-gene (ca) questionnaire and by a study specific forced choice method, using Q-methodology. Questionnaire responses indicated that counselees major concerns pertained to the need to be taken seriously, to be provided with sufficient risk estimation and medical/genetic information and to be involved in the decision making process. Furthermore, prior to counseling, counselees noted that the counselors consideration and skillfulness were also extremely important. Analysis of the Q-sorting results revealed that counselees needs could be assigned to one of five groups: the "need for facts; caring communication and medical information; information and support in communicating the genetic information to others; practical care and practical/medical information". Particularly noteworthy, counselees with varying backgrounds characteristics prioritized different needs. Cancer genetic counselees probably have different needs due to their medical and demographic background when attending genetic counseling. Addressing counselees specific concerns more sufficiently and thereby increasing the overall effectiveness of the counseling session requires increased insight into individual needs, by for instance, utilizing screening methods such as QUOTE-gene (ca) prior to the counseling session.

  • 113.
    Hedayati, Elham
    et al.
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Schedin, Anna
    Karolinska Institute, Stockholm.
    Nyman, Hakan
    Karolinska Institute, Stockholm.
    Alinaghizadeh, Hassan
    Karolinska Institute, Stockholm.
    Albertsson, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    The effects of breast cancer diagnosis and surgery on cognitive functions2011Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, nr 7, s. 1027-1036Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Women with breast cancer (BC) report cognitive impairment. Receiving a BC diagnosis may have a negative psychological impact. We sought to determine whether a diagnosis of BC and subsequent surgical treatment reduced cognitive function. Material and methods. We recruited women, who had a positive radiographic finding, consecutively from the mammography screening program at Stockholm South General Hospital. All subjects completed the Headminder Web-based neuropsychological battery Cognitive Stability Index (CSI) for response speed, processing speed, memory, and attention at enrolment (T1, Baseline). CSI was administered again, after BC was ruled out, or after sector resection or mastectomy, if BC was confirmed by cytology or biopsy (T2, Retest). Results and conclusion. Of the 148 women approached, 146 were enrolled; 69 were healthy and 77 had BC. Comparison between groups at baseline, according to independent t-test, showed significant differences in response speed and processing speed. Cognitive abilities did not decline in either group on any of the measured domains. Our results suggest that a diagnosis of BC and subsequent surgery is not associated with substantial cognitive decline at retest. However, the lack of improvement in attention at retest among BC patients may be suggestive of a decline.

  • 114.
    Hellstrom-Lindberg, E.
    et al.
    Hellström-Lindberg, E., Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden, Department of Medicine, Karolinska Institute, Huddinge University Hospital, 141 86 Stockholm, Sweden.
    Gulbrandsen, N.
    Department of Haematology, Ullevål Hospital, Oslo, Norway.
    Lindberg, G.
    Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
    Ahlgren, T.
    Depts. Med./Haematol. the Hospitals, Malmö, Sweden.
    Dahl, I.M.S.
    Depts. Med./Haematol. the Hospitals, Tromsö, Norway.
    Dybedal, I.
    Depts. Med./Haematol. the Hospitals, Trondheim, Norway.
    Grimfors, G.
    Karolinska Hospital, Stockholm, Sweden.
    Hesse-Sundin, E.
    Karolinska Hospital, Eskilstuna, Sweden.
    Hjorth, M.
    Karolinska Hospital, Lidköping, Sweden.
    Kanter-Lewensohn, L.
    Department of Pathology, Karolinska Hospital, Stockholm, Sweden.
    Linder, O.
    Karolinska Hospital, Örebro, Sweden.
    Luthman, M.
    St. Göran Hospital, Stockholm, Sweden.
    Lofvenberg, E.
    Löfvenberg, E., St. Göran Hospital, Umeå, Sweden.
    Oberg, G.
    Öberg, G., St. Göran Hospital, Uppsala, Sweden.
    Porwit-MacDonald, A.
    Department of Pathology, Karolinska Hospital, Stockholm, Sweden.
    Rådlund, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Samuelsson, J.
    Southern Hospital, Stockholm, Sweden.
    Tangen, J.M.
    Department of Haematology, Ullevål Hospital, Oslo, Norway.
    Winquist, I.
    Southern Hospital, Lund, Sweden.
    Wisloff, F.
    Department of Haematology, Ullevål Hospital, Oslo, Norway.
    A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: Significant effects on quality of life2003Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 120, nr 6, s. 1037-1046Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have published previously a prototype of a decision model for anaemic patients with myelodysplastic syndromes (MDS), in which transfusion need and serum erythropoietin (S-Epo) were used to define three groups with different probabilities of erythroid response to treatment with granulocyte colony-stimulating factor (G-CSF) + Epo. S-Epo = 500 U/l and a transfusion need of < 2 units/month predicted a high probability of response to treatment, S-Epo > 500 U/l and =2 units/month for a poor response, whereas the presence of only one negative prognostic marker predicted an intermediate response. A total of 53 patients from a prospective study were included in our evaluation sample. Patients with good or intermediate probability of response were treated with G-CSF + Epo. The overall response rate was 42% with 28.3% achieving a complete and 13.2% a partial response to treatment. The response rates were 61% and 14% in the good and intermediate predictive groups respectively. The model retained a significant predictive value in the evaluation sample (P < 0.001). Median duration of response was 23 months. Scores for global health and quality of life (QOL) were significantly lower in MDS patients than in a reference population, and fatigue and dyspnoea was significantly more prominent. Global QOL improved in patients responding to treatment (P = 0.01). The validated decision model defined a subgroup of patients with a response rate of 61% (95% confidence interval 48-74%) to treatment with G-CSF + Epo. The majority of these patients have shown complete and durable responses.

  • 115.
    Hoglund, Martin
    et al.
    University of Uppsala Hospital, Sweden .
    Sandin, Fredrik
    Regional Cancer Centre, Sweden .
    Hellstrom, Karin
    Regional Cancer Centre, Sweden .
    Bjoreman, Mats
    University Hospital, Sweden .
    Bjorkholm, Magnus
    Karolinska University Hospital, Sweden .
    Brune, Mats
    Sahlgrens University Hospital, Sweden .
    Dreimane, Arta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ekblom, Marja
    Skåne University Hospital, Sweden .
    Lehmann, Soren
    Karolinska University Hospital, Sweden .
    Ljungman, Per
    Karolinska University Hospital, Sweden .
    Malm, Claes
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Markevarn, Berit
    Umeå University Hospital, Sweden .
    Myhr-Eriksson, Kristina
    Sunderby Luleå Hospital, Sweden .
    Ohm, Lotta
    Karolinska University Hospital, Sweden .
    Olsson-Stromberg, Ulla
    University of Uppsala Hospital, Sweden .
    Sjalander, Anders
    Umeå University, Sweden .
    Wadenvik, Hans
    Sahlgrens University Hospital, Sweden .
    Simonsson, Bengt
    University of Uppsala Hospital, Sweden .
    Stenke, Leif
    Karolinska University Hospital, Sweden .
    Richter, Johan
    Skåne University Hospital, Sweden .
    Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry2013Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, nr 7, s. 1284-1292Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Clinical management guidelines on malignant disorders are generally based on data from clinical trials with selected patient cohorts. In Sweden, more than 95% of all patients diagnosed with chronic myeloid leukemia (CML) are reported to the national CML registry, providing unique possibilities to compile population-based information. This report is based on registry data from 2002 to 2010, when a total of 779 patients (425 men, 354 women; median age, 60 years) were diagnosed with CML (93% chronic, 5% accelerated, and 2% blastic phase) corresponding to an annual incidence of 0.9/100 000. In 2002, approximately half of the patients received a tyrosine kinase inhibitor as initial therapy, a proportion that increased to 94% for younger (andlt;70 years) and 79% for older (andgt;80 years) patients during 2007-2009. With a median follow-up of 61 months, the relative survival at 5 years was close to 1.0 for patients younger than 60 years and 0.9 for those aged 60 to 80 years, but only 0.6 for those older than 80 years. At 12 months, 3% had progressed to accelerated or blastic phase. Sokal, but not European Treatment and Outcome Study, high-risk scores were significantly linked to inferior overall and relative survival. Patients living in university vs nonuniversity catchment areas more often received tyrosine kinase inhibitors up front but showed comparable survival.

  • 116.
    Holm, C
    et al.
    Lund University.
    Kok, M
    Netherlands Cancer Institute.
    Michalides, R
    Netherlands Cancer Institute.
    Fles, R
    Netherlands Cancer Institute.
    Koornstra, R H T
    Netherlands Cancer Institute.
    Wesseling, J
    Netherlands Cancer Institute.
    Hauptmann, M
    Netherlands Cancer Institute.
    Neefjes, J
    Netherlands Cancer Institute.
    Peterse, J L
    Netherlands Cancer Institute.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Landberg, G
    Lund University.
    Linn, S C
    Netherlands Cancer Institute.
    Phosphorylation of the oestrogen receptor alpha at serine 305 and prediction of tamoxifen resistance in breast cancer2009Inngår i: JOURNAL OF PATHOLOGY, ISSN 0022-3417, Vol. 217, nr 3, s. 372-379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phosphorylation of oestrogen receptor a at serine 305 (ER alpha S305-P) induces tamoxifen resistance in experimental studies, but does not influence response to other endocrine agents, such as fulvestrant. We evaluated ER alpha S305-P using immunohistochemistry in 377 breast carcinomas from premenopausal participants of a randomized trial (n = 248) and patients with advanced disease (n = 129). Among the premenopausal patients, adjuvant tamoxifen improved recurrence-free survival (RFS) for ER alpha S305-P-negative tumours (multivariate HR = 0.53, 95% CI 0.32-0.86, p = 0.010), but not for ER alpha S305-P-positive tumours (multivariate HR = 1.01, 95% CI 0.33-3.05, p = 0.99) (interaction p = 0.131). Notably, ER alpha S305-P was not significantly associated with RFS in patients not treated with tamoxifen (multivariate HR = 0.64, 95% CI 0.30-1.37, p = 0.248), indicating that ER alpha S305-P is a marker for treatment outcome rather than tumour progression. Given the direct experimental link between ER alpha S305-P and tamoxifen resistance and these first clinical data suggesting that premenopausal patients with ER alpha S305-P-positive breast cancer are resistant to adjuvant tamoxifen, further research is encouraged to study whether alternative endocrine treatment should be considered for this subgroup.

  • 117.
    Holm, Karolina
    et al.
    Lund University, Sweden .
    Grabau, Dorthe
    Skåne University Hospital, Sweden .
    Lovgren, Kristina
    Lund University, Sweden .
    Aradottir, Steina
    Lund University, Sweden .
    Gruvberger-Saal, Sofia
    Lund University, Sweden .
    Howlin, Jillian
    Lund University, Sweden .
    Saal, Lao H
    Lund University, Sweden .
    Ethier, Stephen P
    Medical University of S Carolina, SC 29425 USA .
    Bendahl, Par-Ola
    Lund University, Sweden .
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Malmstrom, Per
    Lund University, Sweden .
    Ferno, Marten
    Lund University, Sweden .
    Ryden, Lisa
    Lund University, Sweden .
    Hegardt, Cecilia
    Lund University, Sweden .
    Borg, Ake
    Lund University, Sweden .
    Ringner, Markus
    Lund University, Sweden Lund University, Sweden .
    Global H3K27 trimethylation and EZH2 abundance in breast tumor subtypes2012Inngår i: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261, Vol. 6, nr 5, s. 494-506Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polycomb repressive complex 2 (PRC2) and its core member enhancer of zeste homolog 2 (EZH2) mediate the epigenetic gene silencing mark: trimethylation of lysine 27 on histone 3 (H3K27me3). H3K27me3 is characteristic of the chromatin at genes involved in developmental regulation in undifferentiated cells. Overexpression of EZH2 has been found in several cancer types such as breast, prostate, melanoma and bladder cancer. Moreover, overexpression is associated with highly proliferative and aggressive types of breast and prostate tumors. We have analyzed the abundance of EZH2 and H3K27me3 using immunohistochemistry in two large and Well-characterized breast tumor data sets encompassing more than 400 tumors. The results have been analyzed in relation to the molecular subtypes of breast tumors (basal-like, luminal A, luminal B, HER2-enriched and normal-like), as well as in subtypes defined by clinical markers (triple negative, ER+/HER2-/Ki67low, ER+/HER2-/Ki67high and HER2+), and were validated in representative breast cancer cell lines by western blot. We found significantly different expression of both EZH2 and H3K27me3 across all subtypes with high abundance of EZH2 in basal-like, triple negative and HER2-enriched tumors, and high H3K27me3 in luminal A, HER2-enriched and normal-like tumors. Intriguingly, the two markers show an inverse correlation, particularly for the basal-like and triple negative tumors. Consequently, high expression of EZH2 was associated with poor distant disease-free survival whereas high expression of H3K27me3 was associated with better survival. Additionally, none of 182 breast tumors was found to carry a previously described EZH2 mutation affecting Tyr641. Our observation that increased expression of EZH2 does not necessarily correlate with increased abundance of H3K27me3 supports the idea that EZH2 can have effects beyond epigenetic silencing of target genes in breast cancer.

  • 118.
    Holmqvist, A
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Gao, Jingfang
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Adell, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    The location of lymphangiogenesis is an independent prognostic factor in rectal cancers with or without preoperative radiotherapy2010Inngår i: ANNALS OF ONCOLOGY, ISSN 0923-7534, Vol. 21, nr 3, s. 512-517Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Lymphangiogenesis and angiogenesis are essential for tumour development and progression. The lymphatic vessel density (LVD) and blood vessel density (BVD) and their relationship to outcome have been studied extensively, however the clinical significance of the location of LVD/BVD in tumour is not known. In the present study, the location and degree of LVD/BVD and their relationship to preoperative radiotherapy (RT), clinicopathological, histopathological and biological factors were studied in rectal cancer patients participating in a Swedish clinical trial of preoperative RT. Patients and methods: The location and degree of LVD/BVD were analysed in primary tumours (n = 138/140) and in their subgroups of non-RT (n = 74) and RT (n = 64/66). Further, the degree of LVD/BVD was examined in the corresponding distant normal mucosa (n = 35/31) and adjacent normal mucosa (n = 72/91). All sections were immunohistochemically examined by using D2-40 and CD34 antibodies. Results: In the whole series of the patients, a higher LVD at the periphery was related to negative p53 expression (P = 0.03) and favourable survival independent of tumour-node-metastasis stage, differentiation and p53 expression (P = 0.03). LVD was increased in p53-negative tumours after RT (P = 0.01). Conclusion: LVD at the periphery of the tumour was an independent prognostic factor in rectal cancer patients.

  • 119.
    Holmqvist, Annica E
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    THE LOCATION OF LYMPHANGIOGENESIS IS AN INDEPENDENT PROGNOSTIC FACTOR IN RECTAL CANCERS WITH OR WITHOUT PREOPERATIVE RADIOTHERAPY in ANNALS OF ONCOLOGY, vol 21, issue , pp 212-2122010Inngår i: ANNALS OF ONCOLOGY, Oxford University Press , 2010, Vol. 21, s. 212-212Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 120.
    Holmqvist Knutsen, Annica
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Gao, Jing-Fang
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Holmlund, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Adell, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Filosofiska fakulteten.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy: A study in a Swedish rectal cancer trial of preoperative radiotherapy2012Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, nr 65Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Purpose: The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients.

    Material and Methods: PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by Western blot.

    Results: In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (p = 0.03). No survival relationship in patients with RT was observed (p = 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (p = 0.68)/inner tumour area (p = 0.49).

    Conclusions: PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.

     

  • 121.
    Holmqvist (Knutsen), Annica
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Holmlund, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Ardsby, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Pathak, Surajit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    PINCH expression in relation to radiation response in co-cultured colon cancer cells and in rectal cancer patients2013Inngår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 30, nr 5, s. 2097-2104Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Particularly interesting new cysteine-histidine rich protein (PINCH), involved in cell spreading, motility and proliferation, has been shown to enhance radioresistance in colon cancer cell lines. The expression of PINCH in relation to radiation was studied in co-cultured colon cancer cells. Furthermore, the clinical significance between PINCH and radiotherapy (RT) was analyzed in rectal cancer patients with or without RT. The relative PINCH expression in colon cancer (KM12C) cells cultured separately and in co-culture was examined by western blotting and real-time PCR, and was analyzed over a period of 8 and 24 h after radiation. PINCH expression was immunohistochemically examined in 137 primary rectal tumors for which 65 cases did not receive RT and 72 cases received RT. PINCH expression tended to decrease from that in the separately cultured KM12C cells without radiation to that in cells with radiation at 8 h (P=0.060); while in the co-cultured cells, no significant difference was found (P=0.446). In patients with RT, strong PINCH expression was related to worse survival, when compared to patients with weak expression, independent of TNM stage, degree of differentiation, age and p53 status (P=0.029, RR 4.03, 95% CI 1.34-12.1). No survival relationship for the patients without RT was observed (P=0.287). A statistical interaction analysis between PINCH, RT and survival showed a trend towards significance (P=0.057). In conclusion, PINCH predicts survival in rectal cancer patients with RT, but not in patients without RT. The expression of PINCH may be regulated by radiation and by environmental factors surrounding the cells.

  • 122.
    Höglund, M
    et al.
    Uppsala University Hospital.
    Bjoreman, M
    Örebro University Hospital.
    Björkholm, M
    Karolinska Institutet.
    Brune, M
    Sahlgrenska University Hospital.
    Ekblom, M
    Lund University Hospital.
    Hellström, K
    Regional Oncology Centre Uppsala.
    Lehmann, S
    Karolinska Institutet .
    Ljungman, P
    Karolinska Institutet.
    Malm, Claes
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Markevarn, B
    Umeå University Hospital.
    Sandin, F
    Regional Oncology Centre Uppsala.
    Stenke, L
    Karolinska Institutet.
    Wadenvik, H
    Sahlgrenska University Hospital.
    Wahlin, A
    Umeå University Hospital.
    Richter, J
    Lund University Hospital.
    Simonsson, B
    REAL WORLD DATA ON CHRONIC MYELOID LEUKEMIA - A REPORT FROM THE SWEDISH POPULATION BASED CML-REGISTRY in HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, vol 95, issue , pp 337-3382010Inngår i: HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, Pensiero Scientifico / Ferrata Storti Foundation , 2010, Vol. 95, s. 337-338Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 123. Iacopetta, B
    et al.
    Russo, A
    Bazan, V
    Dardanoni, G
    Gebbia, N
    Soussi, T
    Kerr, D
    Elsaleh, H
    Soong, R
    Kandioler, D
    Janschek, E
    Kappel, S
    Lung, M
    Leung, C-S S
    Ko, J M
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Jansson, Agneta
    Shorthouse, AJ
    Silverman, ML
    Kato, S
    Ishioka, C
    Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study2006Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 17, s. 842-847Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

         

  • 124.
    Jahnson, Staffan
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Damm, Ole
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Urologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Hellsten, Sverker
    Malmö University Hospital.
    Holmang, Sten
    Gothenburg University Hospital.
    Liedberg, Fredrik
    Vaxjö County Hospital.
    Ljungberg, Borje
    Umeå University Hospital.
    Malmstrom, Per-Uno
    Uppsala University Hospital.
    Mansson, Wiking
    Lund University Hospital.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Wijkstom, Hans
    Karolinska University Hospital.
    Urinary diversion after cystectomy for bladder cancer: A population-based study in Sweden2010Inngår i: SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY, ISSN 0036-5599, Vol. 44, nr 2, s. 69-75Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. To investigate the type of urinary diversion performed after cystectomy in patients with muscle-invasive bladder cancer in Sweden, using data from a population-based national register. Material and methods. Since 1997, the Swedish Bladder Cancer Register has included more than 90% of all patients with newly diagnosed bladder cancer. The different types of urinary diversion performed in 1997-2003 were analysed, comparing non-continent diversion (ileal conduit) with continent reconstruction (bladder substitution or continent cutaneous diversion). Results. During the study period, 3463 patients were registered with clinical T2-T4 non-metastatic bladder cancer. Cystectomy was performed in 1141 patients with ileal conduit in 732 (64%) and continent reconstruction in 409 (36%). Ileal conduit was used more frequently in females than males (p = 0.019), in patients older than 75 years (p andlt; 0.00001), and in those with less favourable TNM classification. Continent reconstruction was done more often at university hospitals than at county hospitals (p andlt; 0.00001), but rarely in the northern and western healthcare regions compared with other regions (p andlt; 0.00001). Nationwide, the proportion of registered continent reconstructions decreased, although the absolute number was relatively stable (50-60 per year). Conclusions. Continent reconstruction after cystectomy for muscle-invasive bladder cancer is performed more often in some healthcare regions and in patients at university hospitals than in county hospitals, indicating a substantial provider influence on the choice of urinary diversion. Over time, the proportion of these procedures has decreased, while the absolute number has remained low and stable; therefore, concentration in high-volume hospitals specialized in bladder cancer and continent reconstruction seems appropriate.

  • 125.
    Jakubowska, A
    et al.
    Pomeranian Medical University, Poland .
    Rozkrut, D
    University of Szczecin, Poland .
    Antoniou, A
    University of Cambridge, England .
    Hamann, U
    Deutsch Krebsforschungszentrum DKFZ, Germany .
    Scott, R J
    University of Newcastle, Australia Hunter Medical Research Institute, Australia .
    McGuffog, L
    University of Cambridge, England .
    Healy, S
    Queensland Institute Medical Research, Australia .
    Sinilnikova, O M
    Centre Hospital University of Lyon, France University of Lyon 1, France .
    Rennert, G
    Technion Israel Institute Technology, Israel Technion Israel Institute Technology, Israel Technion Israel Institute Technology, Israel .
    Lejbkowicz, F
    Technion Israel Institute Technology, Israel Technion Israel Institute Technology, Israel Technion Israel Institute Technology, Israel .
    Flugelman, A
    Technion Israel Institute Technology, Israel Technion Israel Institute Technology, Israel Technion Israel Institute Technology, Israel .
    Andrulis, I L
    Cancer Care Ontario, Canada Mt Sinai Hospital, Canada .
    Glendon, G
    Cancer Care Ontario, Canada Mt Sinai Hospital, Canada .
    Ozcelik, H
    Mt Sinai Hospital, Canada .
    Thomassen, M
    Odense University Hospital, Denmark .
    Paligo, M
    University Hospital Pisa, Italy .
    Aretini, P
    University Hospital Pisa, Italy .
    Kantala, J
    Karolinska University Hospital, Sweden .
    Aroer, B
    Karolinska University Hospital, Sweden .
    Von Wachenfeldt, A
    Karolinska University Hospital, Sweden .
    Liljegren, A
    Karolinska University Hospital, Sweden .
    Loman, N
    University of Lund Hospital, Sweden .
    Herbst, K
    University of Lund Hospital, Sweden .
    Kristoffersson, U
    University of Lund Hospital, Sweden .
    Rosenquist, R
    Uppsala University, Sweden .
    Karlsson, P
    Sahlgrens University Hospital, Sweden .
    Stenmark-Askmalm, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Melin, B
    Umeå University, Sweden .
    Nathanson, K L
    University of Penn, PA 19104 USA University of Penn, PA 19104 USA .
    Domchek, S M
    University of Penn, PA 19104 USA University of Penn, PA 19104 USA .
    Byrski, T
    Pomeranian Medical University, Poland .
    Huzarski, T
    Pomeranian Medical University, Poland .
    Gronwald, J
    Pomeranian Medical University, Poland .
    Menkiszak, J
    Pomeranian Medical University, Poland .
    Cybulski, C
    Pomeranian Medical University, Poland .
    Serrano, P
    Pomeranian Medical University, Poland .
    Osorio, A
    Spanish National Cancer Research Centre, Spain Spanish National Cancer Research Centre, Spain .
    Cajal, T R
    Hospital Santa Creu and Sant Pau, Spain .
    Tsitlaidou, M
    National Centre Science Research Demokritos, Greece .
    Benitez, J
    Spanish National Cancer Research Centre, Spain Spanish National Cancer Research Centre, Spain .
    Gilbert, M
    Deutsch Krebsforschungszentrum DKFZ, Germany .
    Rookus, M
    Netherlands Cancer Institute, Netherlands .
    Aalfs, C M
    University of Amsterdam, Netherlands .
    Kluijt, I
    Netherlands Cancer Institute, Netherlands .
    Boessenkool-Pape, J L
    Netherlands Cancer Institute, Netherlands .
    Meijers-Heijboer, H E J
    Vrije University of Amsterdam Medical Centre, Netherlands .
    C Oosterwijk, J
    University of Groningen, Netherlands .
    J van Asperen, C
    Leiden University of Medical Centre, Netherlands .
    J Blok, M
    University Hospital Maastricht, Netherlands .
    R Nelen, M
    Radboud University of Nijmegen Medical Centre, Netherlands .
    M W van den Ouweland, A
    Erasmus MC, Netherlands .
    Seynaeve, C
    Erasmus MC, Netherlands .
    B van der Luijt, R
    University of Medical Centre Utrecht, Netherlands .
    Devilee, P
    Leiden University of Medical Centre, Netherlands Leiden University of Medical Centre, Netherlands .
    F Easton, D
    University of Cambridge, England .
    Peock, S
    University of Cambridge, England .
    Frost, D
    University of Cambridge, England .
    Platte, R
    University of Cambridge, England .
    D Ellis, S
    University of Cambridge, England .
    Fineberg, E
    University of Cambridge, England .
    G Evans, D
    NHS Fdn Trust, England .
    Lalloo, F
    NHS Fdn Trust, England .
    Eeles, R
    Royal Marsden NHS Fdn Trust, England .
    Jacobs, C
    Guys and St Thomas NHS Fdn Trust, England .
    Adlard, J
    Yorkshire Regional Genet Serv, England .
    Davidson, R
    Yorkhill Hospital, Scotland .
    Eccles, D
    University of Southampton, England .
    Cole, T
    Birmingham Womens Hospital Healthcare NHS Trust, England .
    Cook, J
    Sheffield Childrens Hospital, England .
    Godwin, A
    University of Kansas Medical Centre, KS USA .
    Bove, B
    Fox Chase Cancer Centre, PA 19111 USA .
    Stoppa-Lyonnet, D
    Institute Curie, France Institute Curie, France University of Paris 05, France .
    Caux-Moncoutier, V
    Institute Curie, France .
    Belotti, M
    Institute Curie, France .
    Tirapo, C
    Institute Curie, France .
    Mazoyer, S
    University of Lyon 1, France .
    Barjhoux, L
    University of Lyon 1, France .
    Boutry-Kryza, N
    Centre Hospital University of Lyon, France .
    Pujol, P
    CHU Arnaud de Villeneuve, France CRCM dAurelle, France .
    Coupier, I
    CHU Arnaud de Villeneuve, France CRLCC Val dAurelle, France .
    Peyrat, J-P
    Centre Oscar Lambret, France .
    Vennin, P
    Centre Oscar Lambret, France .
    Muller, D
    CLCC Paul Strauss, France .
    Fricker, J-P
    CLCC Paul Strauss, France .
    Venat-Bouvet, L
    Centre Hospital University of Dupuytren, France .
    Johannsson, OTh
    Landspitali University Hospital, Iceland University of Iceland, Iceland .
    Isaacs, C
    Georgetown University, DC USA .
    Schmutzler, R
    University Hospital Cologne, Germany University Hospital Cologne, Germany .
    Wappenschmidt, B
    University Hospital Cologne, Germany University Hospital Cologne, Germany .
    Meindl, A
    University of Munich, Germany .
    Arnold, N
    University of Kiel, Germany .
    Varon-Mateeva, R
    Institute Human Genet, Germany .
    Niederacher, D
    University of Dusseldorf, Germany .
    Sutter, C
    University of Heidelberg Hospital, Germany .
    Deissler, H
    University Hospital Ulm, Germany .
    Preisler-Adams, S
    University of Munster, Germany .
    Simard, J
    University of Laval, Canada Centre Hospital University of Quebec, Canada .
    Soucy, P
    University of Laval, Canada Centre Hospital University of Quebec, Canada .
    Durocher, F
    University of Laval, Canada Centre Hospital University of Quebec, Canada .
    Chenevix-Trench, G
    Queensland Institute Medical Research, Australia .
    Beesley, J
    Queensland Institute Medical Research, Australia .
    Chen, X
    Queensland Institute Medical Research, Australia .
    Rebbeck, T
    University of Penn, PA 19104 USA University of Penn, PA 19104 USA .
    Couch, F
    Mayo Clin, MN USA Mayo Clin, MN USA .
    Wang, X
    Mayo Clin, MN USA .
    Lindor, N
    Mayo Clin, MN USA .
    Fredericksen, Z
    Mayo Clin, MN USA .
    S Pankratz, V
    Mayo Clin, MN USA .
    Peterlongo, P
    Fdn IRCCS Ist Nazl Tumori INT, Italy Fdn Ist FIRC Oncology Mol, Italy .
    Bonanni, B
    Ist Europeo Oncol, Italy .
    Fortuzzi, S
    Fdn Ist FIRC Oncology Mol, Italy 84 Cogentech Cancer Genet Test Lab, Italy .
    Peissel, B
    Fdn IRCCS Ist Nazl Tumori INT, Italy .
    Szabo, C
    Mayo Clin, MN USA .
    L Mai, P
    Department Health and Human Serv, MD 20852 USA .
    T Loud, J
    Department Health and Human Serv, MD 20852 USA .
    Lubinski, J
    Pomeranian Medical University, Poland .
    Association of PHB 1630 C andgt; T and MTHFR 677 C andgt; T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study2012Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, nr 12, s. 2016-2024Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. less thanbrgreater than less thanbrgreater thanMETHODS: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 Candgt;T (rs6917) polymorphism and the MTHFR 677 Candgt;T (rs1801133) polymorphism, respectively. less thanbrgreater than less thanbrgreater thanRESULTS: There was no evidence of association between the PHB 1630 Candgt;T and MTHFR 677 Candgt;T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 Candgt;T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95% CI 1.10-2.04 and HR 2.16, 95% CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. less thanbrgreater than less thanbrgreater thanCONCLUSION: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers.

  • 126.
    Jancke, Georg
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Damm, Ole
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Rosell, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Jahnson, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Risk factors for local recurrence in patients with pTa/pT1 urinary bladder cancer2008Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 42, nr 5, s. 417-421Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. This study evaluated risk factors for local tumour recurrence, defined as recurrence at the same location in the bladder within 18 months after primary resection in patients with newly diagnosed pTa or pT1 bladder cancer. Patients and methods. The study included 472 patients with newly diagnosed pTa/T1 bladder cancer between 1992 and 2001. The patients were followed prospectively in accordance with a control programme and possible risk factors for tumour recurrence were registered. Results. Local tumour recurrence was observed in 164 (35%) patients, another 117 (25%) patients had recurrence at other locations in the bladder (non-local recurrence) and 191 (40%) had no recurrence at all. Tumour size and multiple tumours were significantly associated with a higher risk for developing local recurrence as opposed to non-local recurrence. Tumour category was of borderline statistical significance. Gender and tumour grade were not found to be risk factors for developing local recurrence. Conclusion. Tumour size and multiplicity are risk factors for development of recurrence at the same location in the bladder as the primary tumour. Local tumour recurrence may be a result of non-radical primary transurethral resection. One may consider recommending standard re-resection within 6-8 weeks in patients with tumours >3 cm or those with multiple primary tumours. © 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS).

  • 127.
    Jancke, Georg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Chebil, Gunilla
    County Hospital, Helsingborg, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Bladder Wash Cytology at Diagnosis of Ta-T1 Bladder Cancer Is Predictive for Recurrence and Progression2012Inngår i: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 80, nr 3, s. 625-631Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE To evaluate the effect of the bladder wash cytology finding at the primary diagnosis of Stage Ta-T1 urinary bladder cancer on recurrence and progression. less thanbrgreater than less thanbrgreater thanMETHODS The clinical and pathologic characteristics of all patients with primary Stage Ta-T1 urinary bladder cancer were prospectively registered. The data were divided according to the bladder wash cytology results at diagnosis. Multivariate analyses were performed to determine the influence of bladder wash cytology on recurrence and progression. less thanbrgreater than less thanbrgreater thanRESULTS The analysis included 768 evaluable patients with a mean follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). High-grade malignant bladder wash cytology was predictive for recurrence and progression (P andlt; .001 and P = .036, respectively). Other factors affecting recurrence were missing bladder wash cytology data, tumors size 16-30 mm and andgt;30 mm, Stage T1 tumor category, and multiplicity (P = .008, P = .006, P andlt; .001, P = .002, and P andlt; .001, respectively). Progression was also associated with T1 tumor category, local recurrence, and primary concomitant carcinoma in situ (P andlt; .001, P andlt; .001, and P = .024, respectively). less thanbrgreater than less thanbrgreater thanCONCLUSION High-grade malignant bladder wash cytology at the primary diagnosis was predictive for recurrence and progression. This could be taken into account in designing future follow-up schedules.

  • 128.
    Jancke, Georg
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Impact of tumour size on recurrence and progression in Ta/T1 carcinoma of the urinary bladder2011Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 45, nr 6, s. 388-392Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. This study aimed to evaluate the impact of tumour size on recurrence and progression in a population-based series of non-muscle-invasive bladder cancers. Material and methods. Clinical and pathological characteristics of patients with primary Ta/bladder cancer were registered. The patients tumours were categorized by size into five size groups (1-10, 11-20, 21-30, 31-40 and andgt;40 mm) or three size groups (1-15, 16-30 and andgt;30 mm). Results. The analysis included 768 evaluable patients with a mean follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). Tumour size was associated with recurrence for tumours sized 21-30, 31-40 and andgt;40 mm (p = 0.03, p andlt; 0.001, p andlt; 0.001, respectively) in the five size group and for tumours sized 16-30 and andgt;30 mm (p = 0.003 and p andlt; 0.001) in the three size group. Other factors affecting recurrence were T1 tumour category, multiplicity and surgery performed by residents (p andlt; 0.001, p andlt; 0.001, p = 0.002, respectively). Considering progression, there was no significant association with tumour size, and T1 category and local recurrence were the only significant risk factors (both p andlt; 0.001). Conclusion. Tumour size andlt;= 15 mm is associated with a lower risk of recurrence but not progression. Dividing tumour size into three size groups gives additional information compared with two size groups with cut-off at 30 mm.

  • 129.
    Jancke, Georg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Residual tumour in the marginal resection after a complete transurethral resection is associated with local recurrence in Ta/T1 urinary bladder cancer2012Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, nr 5, s. 343-347Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. This study investigated the presence of residual tumour in the marginal resection (MR) after a complete transurethral resection (TURB) of Ta/T1 transitional urinary bladder cancer. The association between positive MR and recurrence was analysed. Material and methods. After macroscopically complete TURB, a marginal resection of 7 mm (corresponding to the diameter of the resection loop) was removed around the entire resection area. Univariate and multivariate Cox regression analyses were performed to assess the influence of residual disease on recurrence. Results. In all, 94 patients with a median follow-up time of 36 months were included, and residual tumour in the MR was present in 24 (26%). The recurrence rates for all cases, for those with a tumour-positive and a tumour-free MR were 60 (64%), 20 (83%) and 40 (57%), respectively. Local recurrence was found in 14 (58%) of the patients with tumour presence in the MR compared to 13 (19%) of those with a tumour-free margin. A positive MR was significantly associated with overall recurrence (p andlt; 0.001) and local recurrence (p = 0.001). Conclusion. Incomplete transurethral resection of bladder cancer is common, as demonstrated in 26% patients with positive MR. The presence of tumour in the MR may be a risk factor for recurrence, and particularly local recurrence.

  • 130.
    Jansson , Agneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    17Beta-hydroxysteroid dehydrogenase enzymes and breast cancer2009Inngår i: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, ISSN 0960-0760 , Vol. 114, nr 1-2, s. 64-67Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sex steroids play an important role in the development and differentiation in several tissues. Biologically active hormones that are locally converted in endocrine organs in the tissue where they exert their effects without release into extracellular space is a field of endocrinology that has been called intracrinology. In pre-menopausal women the ovary is the main source of estrogens, but in post-menopausal women the estrogen production as main site of synthesis moves to peripheral tissues and almost all of the sex steroids are synthesised from precursors of adrenal origin. In breast cancer 60-80% of the tumors express high levels of oestrogen receptor (ER) alpha which gives estrogen a proliferative effect. Breast tumors tend to have a higher intratumoral estrogen concentration than normal breast tissue and plasma, and in situ synthesis and the metabolism of estrogens is believed to be of great importance for the development and progression of the disease. The activity of estrogen metabolizing enzymes in breast are mainly aromatase, estrone sulfatases and 17HSD enzymes. 17HSD1 and 17HSD2 are the family members known to be of main importance in breast cancer. High expression of 17HSD1 has been associated to poor prognosis in breast cancer and late relapse among patients with ER-positive tumors. One of the mechanisms behind high 17HSD1 expression is gene amplification. Low or absent expression of 17HSD2 is associated to decreased survival in ER-positive breast cancer. 17HSD14 is one of the latest discovered 17HSD enzymes, transfection of 17HSD14 in human breast cancer cells significantly decreased the levels of estradiol in the culture medium. Low expression of 17HSD14 mRNA expression in breast cancer was correlated to decreased survival.

    The understanding of intratumoral synthesis of sex steroids in breast cancer is crucial to understand the disease both in pre- and post-menopausal women. Further studies are desirable to state the direct role of these enzymes in breast cancer and which patients that may benefit from new therapeutic strategies targeting 17HSD enzymes. The new inhibitors targeting 17HSD1 have shown promising results in preclinical studies to have clinical potential in the future.

  • 131.
    Jansson, Agneta
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Carlsson, Jonas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska högskolan.
    Olsson, Anette
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Storm, Petter
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Margolin, Sara
    Department of Oncology, Karolinska University Hospital/ Södersjukhuset, Stockholm, Sweden.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk genetik. Linköpings universitet, Hälsouniversitetet.
    Stenmark Askmalm, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Lindblom, Annika
    Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Persson, Bengt
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska högskolan.
    Stål, Olle
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet.
    A new polymorphism in the coding region of exon four in HSD17B2 in relation to risk of sporadic and hereditary breast cancer2007Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 106, nr 1, s. 57-64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In situ synthesis of oestrogens is of great importance in the development and progression of breast cancer. 17β-hydroxysteroid dehydrogenase (17HSD) type 2 catalyses oxidation from oestradiol to oestrone, and thereby protects the breast epithelial cells from oestradiol. Low expression of 17HSD type 2 has been associated with decreased survival in breast cancer, but no studies have investigated the mechanism behind the low expression. The 17HSD type 2 gene (HSD17B2) was screened for mutations with Single Stranded Conformation Polymorphism (SSCP)-DNA sequencing in 59 sporadic breast cancer cases, 19 hereditary breast cancer cases and seven breast cancer cell lines. DNA samples from 226 healthy individuals were used to identify if changes were previously unknown polymorphisms. No mutation was detected and therefore mutations in HSD17B2 do not explain why some breast tumours exhibit low 17HSD type 2 expression. However, a previously unknown polymorphism was found in exon four (Met226Val). Using molecular modelling, we found that the substituted residue is located at the outer part of the steroid binding site, probably causing minor alterations in the substrate binding. We further studied if the polymorphism contributes to breast cancer susceptibility in a larger material, but did not find an increased risk in the group of 317 sporadic breast cancer patients, 188 breast cancer patients with two close relatives with breast cancer or 122 hereditary breast cancer patients, compared to the healthy control group. We suggest that the detected polymorphism does not contribute to a higher risk of developing breast cancer.

  • 132.
    Jansson, Agneta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Delander, Lovisa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Fornander, Tommy
    Karolinska University Hospital.
    Skoog, Lambert
    Karolinska University Hospital.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Ratio of 17HSD1 to 17HSD2 protein expression predicts the outcome of tamoxifen treatment in postmenopausal breast cancer patients.2009Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 15, nr 10, s. 3610-3616Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Estrogens have great significance in the development of breast cancer. After menopause, most estrogen biosynthesis is done in peripheral tissue, and the main enzymes involved in balancing the amount of estrone against estradiol are 17beta-hydroxysteroid dehydrogenases (17HSD). The aim of this study was to investigate the prognostic and tamoxifen predictive values of 17HSD1 and 17HSD2 expression. EXPERIMENTAL DESIGN: Tumors from low-risk breast cancer patients randomized to adjuvant tamoxifen therapy or no adjuvant treatment were analyzed with immunohistochemistry to investigate protein expression of 17HSD1 and 17HSD2 in 912 cases. All patients had lymph node-negative breast cancer and were postmenopausal at the time of diagnosis. RESULTS: Low 17HSD1 expression was associated with significant benefit from tamoxifen treatment among patients with estrogen receptor (ER)-positive tumors (P < 0.001). For patients with a 17HSD1 score not exceeding that of 17HSD2, tamoxifen increased the rate of distant recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.23-0.60) and breast cancer-specific survival (hazard ratio, 0.30; 95% confidence interval, 0.16-0.54), whereas no apparent effect was observed when the 17HSD1 score was higher than that of 17HSD2. The interaction was significant for both distant recurrence-free survival (P = 0.036) and breast cancer-specific survival (P = 0.014). In the cohort of systemically untreated patients, no prognostic importance was observed. CONCLUSIONS: This is the first report that clearly distinguishes between the prognostic and predictive importance of 17HSD1 and 17HSD2 in ER-positive breast cancer treated with or without tamoxifen. Our data suggest that the 17HSD1/17HSD2 ratio might be useful as a predictive factor for tamoxifen treatment in ER-positive breast cancer patients.

  • 133.
    Jansson, Agneta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Ki-67 expression in relation to clinicopathological variables and prognosis in colorectal adenocarcinomas1997Inngår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 105, nr 9, s. 730-734Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ki-67 is a protein associated with cell proliferation which is expressed in all phases of the cell cycle except Go. In the present study, Ki-67 expression in 255 human colorectal adenocarcinomas was examined using immunohistochemistry with the monoclonal antibody MIB-1. One hundred and fifty-seven (62%) cases had more than 50% positive tumour cells and 98 (38%) cases less than 50%. The tumours showed a wide range of Ki-67 expression, from 13% to 90%, which indicated a variation in proliferative activity. There was no significant relationship between Ki-67 expression and sex, age, tumour location, Dukes' stage, growth pattern, differentiation, DNA content, S-phase fraction or survival (p > 0.05). In conclusion, the proliferative activity as measured by Ki-67 antibody was not related to clinicopathology and prognosis in colorectal cancer.

  • 134.
    Jerevall, Piiha-Lotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Homeobox B13 in breast cancer: Prediction of tamoxifen benefit2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    A major issue in the management of breast cancer is to identify patients who are less likely to be cured after primary treatment and would benefit from adjuvant chemotherapy. Of great importance is also identification of patients with only local disease who traditionally would be given chemotherapy but would survive without. In this thesis we have validated the utility of the two-gene ratio HOXB13:IL17BR, which previously has been demonstrated to predict disease-free survival in tamoxifen-treated breast cancer patients. We have also studied the prognostic and predictive utility of a single gene as a biomarker in breast cancer medicine.

    We could confirm that HOXB13:IL17BR may classify patients with different treatment benefit; only patients with a low value showed benefit from prolonged duration of tamoxifen therapy, whereas for the group with high ratios, the long-term recurrence rate did not improve with longer treatment duration.

    The combination of HOXB13:IL17BR and the molecular grade index (MGI), another prognostic marker, has been shown to outperform either alone in predicting risk of breast cancer recurrence. We validated the prognostic utility of HOXB13:IL17BR+MGI in a large randomized patient cohort and found that this risk classification identified more than 50% of the tamoxifen-treated lymph node-negative patients as having a less than 3% risk of distant recurrence and breast cancer death. Furthermore, we developed and tested a continuous risk model of HOXB13:IL17BR+MGI called Breast Cancer Index (BCI), for estimation of recurrence risk at the individual level. Our study shows that BCI has the ability to identify more than 50% of patients with a low risk of recurrence more accurately than using traditional risk assessment. These results suggest that BCI may help clinicians to make better informed treatment decisions and spare toxic chemotherapy for a large group of breast cancer patients.

    The protein expression of HOXB13 was also shown to be a valuable predictor in postmenopausal patients. High expression was associated with worse outcome after tamoxifen therapy. In a premenopausal cohort, patients with hormone receptor-positive tumors showed benefit from tamoxifen regardless of HOXB13 expression. Further analysis indicated that estrogen receptor β (ERβ) modified the performance of HOXB13 as a predictor of treatment effect and should be taken into account when identifying patients less likely to respond to the therapy given.

    In conclusion, BCI identifies patients with a very low risk of distant recurrence. It may be utilized in the management of breast cancer patients to optimize the use of chemotherapy. HOXB13 protein expression may be used as a marker for tamoxifen benefit, but its performance in premenopausal patients might be modified by ERβ.

    Delarbeid
    1. Exploring the two-gene ratio in breast cancer – independent roles for HOXB13 and IL17BR in prediction of clinical outcome
    Åpne denne publikasjonen i ny fane eller vindu >>Exploring the two-gene ratio in breast cancer – independent roles for HOXB13 and IL17BR in prediction of clinical outcome
    Vise andre…
    2008 (engelsk)Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 107, nr 2, s. 225-234Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients. We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients. A further objective was to investigate any prognostic effects of the ratio in systemically untreated premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we hypothesized that these genes may have individual prognostic or predictive power.

    Patients and methods: Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 randomized postmenopausal patients and 93 systemically untreated premenopausal patients.

    Results: A high HOXB13:IL17BR ratio was associated with aggressive tumor characteristics, as were low levels of IL17BR alone. The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment, with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio (recurrence rate ratio: RR=0.39; p=0.030), or low expression of HOXB13 (RR=0.37; p=0.015). No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups. The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate analysis. In the systemically untreated cohort, only IL17BR showed independent prognostic significance.

    Conclusion: We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy, with a high ratio or a high expression rendering patients less likely to respond. We have also shown that IL17BR might be an independent prognostic factor in breast cancer.

    sted, utgiver, år, opplag, sider
    Institutionen för klinisk och experimentell medicin, 2008
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-11861 (URN)10.1007/s10549-007-9541-8 (DOI)
    Merknad
    The original publication is available at www.springerlink.com: Piiha-Lotta Jerevall, Sara Brommesson, Carina Strand, Sofia Gruvberger-Saal, Per Malmström, Bo Nordenskjöld, Sten Wingren, Peter Söderkvist, Mårten Fernö and Olle Stål, Exploring the two-gene ratio in breast cancer – independent roles for HOXB13 and IL17BR in prediction of clinical outcome, 2008, Breast Cancer Research and Treatment, (107), 2, 225-234. http://dx.doi.org/10.1007/s10549-007-9541-8. Copyright: Springer, www.springerlink.comTilgjengelig fra: 2008-05-21 Laget: 2008-05-21 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial
    Åpne denne publikasjonen i ny fane eller vindu >>Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial
    Vise andre…
    2011 (engelsk)Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, nr 11, s. 1762-1769Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer.

    Methods: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomized prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modeling.

    Results: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorized as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorized as low-risk with an 8.3% 10-year distant recurrence risk.

    Conclusion: Retrospective analysis of this randomized, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.

    sted, utgiver, år, opplag, sider
    Nature Publishing Group, 2011
    Emneord
    Breast Cancer Index, recurrence, risk assessment, gene expression profiling, prognosis
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-68122 (URN)10.1038/bjc.2011.145 (DOI)000290953200016 ()
    Konferanse
    32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium. December 10, San Diego
    Merknad
    Original Publication: Piiha-Lotta Jerevall, Xiai-Jun Ma, Hongying Li, Ranelle Salunga, Nicole C. Kesty, Mark G. Erlander, Dennis Sgroi, Birgitta Holmlund, Lambert Skoog, Tommy Fornander, Bo Nordenskjöld and Olle Stål, Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial, 2011, British Journal of Cancer, (104), 11, 1762-1769. http://dx.doi.org/10.1038/bjc.2011.145 Copyright: Nature Publishing Group http://npg.nature.com/ Tilgjengelig fra: 2011-05-11 Laget: 2011-05-11 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    3. Predictive relevance of HOXB13 protein expression for tamoxifen benefit in breast cancer
    Åpne denne publikasjonen i ny fane eller vindu >>Predictive relevance of HOXB13 protein expression for tamoxifen benefit in breast cancer
    Vise andre…
    2010 (engelsk)Inngår i: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 12, nr 4Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    ABSTRACT: INTRODUCTION: The HOXB13:IL17BR index has been identified to predict clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer. Further studies have shown that HOXB13 in particular can indicate benefit of prolonged tamoxifen treatment. Patients with high-expressing tumors did not benefit from prolonged treatment, suggesting that HOXB13 might be involved in tamoxifen resistance. No studies have been made regarding the HOXB13 protein levels in breast cancer. The aim of our study was to investigate whether tamoxifen benefit can be correlated to different levels of HOXB13 protein expression. METHODS: We used immunohistochemistry to analyze protein levels of HOXB13 in tumor samples from 912 postmenopausal node-negative breast cancer patients randomized to adjuvant tamoxifen therapy or no endocrine treatment. RESULTS: Tamoxifen-treated patients with estrogen receptor-positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival (DRFS) (hazard ratio = 0.38, 95% confidence interval = 0.23 to 0.60, P = 0.000048). However, for patients with a high or intermediate HOXB13 tumor expression, tamoxifen did not prolong the DRFS compared with the untreated patients (hazard ratio = 0.88, 95% confidence interval = 0.47 to 1.65, P = 0.69). Interaction between HOXB13 expression and benefit from tamoxifen was statistically significant for DRFS (P = 0.035). No prognostic value could be ascribed to HOXB13 among systemically untreated patients. CONCLUSIONS: A high HOXB13 expression was associated with decreased benefit from tamoxifen, which indicates that HOXB13 protein level may be used as a predictive marker for tamoxifen treatment.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-58819 (URN)10.1186/bcr2612 (DOI)
    Tilgjengelig fra: 2010-08-27 Laget: 2010-08-27 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    4. Homeobox B13 protein expression in a randomized tamoxifen trial of premenopausal breast cancer
    Åpne denne publikasjonen i ny fane eller vindu >>Homeobox B13 protein expression in a randomized tamoxifen trial of premenopausal breast cancer
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Homeobox B13 (HOXB13), part of the two-gene expression index HOXB13:IL17BR, has proven its capacity as a predictive factor of tamoxifen benefit in breast cancer. HOXB13 mRNA expression, as well as protein levels, have shown predictive value in postmenopausal patients. High levels were associated with decreased tamoxifen benefit and may indicate endocrine resistance. Here, we have analyzed HOXB13 protein expression in premenopausal breast cancer. We quantified the levels of HOXB13 with immunohistochemistry in tumor samples from 487 patients on tissue microarrays. Patients were diagnosed with stage II invasive breast cancer and randomized to tamoxifen or no endocrine treatment. HOXB13 protein analysis was successful for 367 patients. Data were correlated with clinicopathological variables. Investigation of tamoxifen benefit in patients with tumors expressing estrogen receptor (ER) α, progesterone receptor, or both, showed that patients with high HOXB13 levels had benefit from tamoxifen (hazard ratio for recurrences 0.43, 95% CI: 0.28-1.01, p=0.053). Corresponding numbers for the low HOXB13 group were 0.69 (95% CI: 0.44-1.07, p=0.10). For further analysis, we stratified the patients based on tumor ERβ status, which may function as a modifier of the performance of HOXB13 as a treatment predictive factor. For the ERβ positive subset of patients, there was a tendency towards a low HOXB13 expression associated with a better tamoxifen response. However, an increased benefit from tamoxifen, in terms of a longer recurrence-free survival (RFS), was associated with high HOXB13 expression in the ERβ negative group. The interaction between HOXB13 and treatment effect for RFS in the ERβ-negative group was significant in a multivariate model (p=0.04). In conclusion, in our study cohort, ERβ seems to be an additional determinant to HOXB13 protein expression for endocrine treatment prediction in premenopausal breast cancer. To identify patients less likely to respond to tamoxifen therapy, both HOXB13 and ERβ status should be taken into account.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-68120 (URN)
    Tilgjengelig fra: 2011-05-11 Laget: 2011-05-11 Sist oppdatert: 2011-05-12bibliografisk kontrollert
  • 135.
    Jerevall, Piiha-Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Brommesson, Sara
    Lund University Hospital.
    Strand, Carina
    Lund University Hospital.
    Gruvberger-Saal, Sofia
    Lund University Hospital.
    Malmström, Per
    Lund University Hospital.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Wingren, Sten
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Fernö, Mårten
    Lund University Hospital.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Exploring the two-gene ratio in breast cancer – independent roles for HOXB13 and IL17BR in prediction of clinical outcome2008Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 107, nr 2, s. 225-234Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients. We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients. A further objective was to investigate any prognostic effects of the ratio in systemically untreated premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we hypothesized that these genes may have individual prognostic or predictive power.

    Patients and methods: Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 randomized postmenopausal patients and 93 systemically untreated premenopausal patients.

    Results: A high HOXB13:IL17BR ratio was associated with aggressive tumor characteristics, as were low levels of IL17BR alone. The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment, with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio (recurrence rate ratio: RR=0.39; p=0.030), or low expression of HOXB13 (RR=0.37; p=0.015). No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups. The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate analysis. In the systemically untreated cohort, only IL17BR showed independent prognostic significance.

    Conclusion: We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy, with a high ratio or a high expression rendering patients less likely to respond. We have also shown that IL17BR might be an independent prognostic factor in breast cancer.

  • 136.
    Jerevall, Piiha-Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Jansson, A.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Fornander, T.
    Karolinska University Hospital.
    Skoog, L.
    Karolinska University Hospital.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    HOXB13 protein expression predicts the benefit of tamoxifen treatment in breast cancer patients: in CANCER RESEARCH, vol 69, issue 2, Supplement 1, pp 358S-358S2009Inngår i: CANCER RESEARCH, 2009, Vol. 69, nr 2, s. 358S-358SKonferansepaper (Fagfellevurdert)
    Abstract [en]

    Background: The two-gene expression ratio HOXB13:IL17BR, originally from a microarray analysis, has been shown to be indicative of clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer, with a high ratio associated with decreased disease-free survival. Analysis of a cohort of breast cancer patients randomized to 2 or 5 years of adjuvant tamoxifen therapy showed that the two-gene ratio and expression of the HOXB13 gene alone were predictive of the benefit of prolonged tamoxifen treatment. Patients with tumors expressing HOXB13 at high levels were unresponsive to prolonged adjuvant treatment, suggesting that this gene is involved in tamoxifen resistance. It is suggested that a high two-gene ratio may indicate impaired ER signaling, which is known to predict resistance to tamoxifen. To our knowledge, there are no studies investigating the HOXB13 protein levels in breast cancer.

    Methods: We have analyzed the protein expression of HOXB13 with immunohistochemistry in tumor samples from 912 postmenopausal node negative breast cancer patients randomized to 2 years of tamoxifen or no endocrine treatment. After 2 years, recurrence-free patients were randomized to 3 more years of tamoxifen, or no further therapy. This selection enabled us to investigate the treatment predictive value of HOXB13.

    Results: Data on HOXB13 protein expression were obtained from 866 patients (see table). Tamoxifen treated patients with estrogen receptor (ER) positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival (hazard ratio (HR) 0.37, 95% CI 0.23-0.60, p=0.000048). However, for patients with a high or intermediate HOXB13 tumor expression, tamoxifen did not prolong the distant recurrence-free survival compared to the untreated patients (HR=0.83, 95% CI 0.45-1.54, p=0.55). The interaction between HOXB13 expression and benefit from tamoxifen was statistically significant (p=0.046). HOXB13 did not have any prognostic value among systemically untreated patients.

  • 137.
    Jerevall, Piiha-Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Jansson, Agneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Fornander, Tommy
    Department of Oncology, Karolinska University Hospital.
    Skoog, Lambert
    Department of Clinical Pathology and Cytology, Karolinska University Hospital.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Predictive relevance of HOXB13 protein expression for tamoxifen benefit in breast cancer2010Inngår i: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 12, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ABSTRACT: INTRODUCTION: The HOXB13:IL17BR index has been identified to predict clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer. Further studies have shown that HOXB13 in particular can indicate benefit of prolonged tamoxifen treatment. Patients with high-expressing tumors did not benefit from prolonged treatment, suggesting that HOXB13 might be involved in tamoxifen resistance. No studies have been made regarding the HOXB13 protein levels in breast cancer. The aim of our study was to investigate whether tamoxifen benefit can be correlated to different levels of HOXB13 protein expression. METHODS: We used immunohistochemistry to analyze protein levels of HOXB13 in tumor samples from 912 postmenopausal node-negative breast cancer patients randomized to adjuvant tamoxifen therapy or no endocrine treatment. RESULTS: Tamoxifen-treated patients with estrogen receptor-positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival (DRFS) (hazard ratio = 0.38, 95% confidence interval = 0.23 to 0.60, P = 0.000048). However, for patients with a high or intermediate HOXB13 tumor expression, tamoxifen did not prolong the DRFS compared with the untreated patients (hazard ratio = 0.88, 95% confidence interval = 0.47 to 1.65, P = 0.69). Interaction between HOXB13 expression and benefit from tamoxifen was statistically significant for DRFS (P = 0.035). No prognostic value could be ascribed to HOXB13 among systemically untreated patients. CONCLUSIONS: A high HOXB13 expression was associated with decreased benefit from tamoxifen, which indicates that HOXB13 protein level may be used as a predictive marker for tamoxifen treatment.

  • 138.
    Jerevall, Piiha-Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Jansson, Agneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Källström, Ann-Christine
    Department of Surgery, Helsingborg hospital, Helsingborg, Sweden.
    Landberg, Göran
    Center for Molecular Pathology, Lund University, Malmö University hospital, Malmö, Sweden.
    Fernö, Mårten
    Divison of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Homeobox B13 protein expression in a randomized tamoxifen trial of premenopausal breast cancerManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Homeobox B13 (HOXB13), part of the two-gene expression index HOXB13:IL17BR, has proven its capacity as a predictive factor of tamoxifen benefit in breast cancer. HOXB13 mRNA expression, as well as protein levels, have shown predictive value in postmenopausal patients. High levels were associated with decreased tamoxifen benefit and may indicate endocrine resistance. Here, we have analyzed HOXB13 protein expression in premenopausal breast cancer. We quantified the levels of HOXB13 with immunohistochemistry in tumor samples from 487 patients on tissue microarrays. Patients were diagnosed with stage II invasive breast cancer and randomized to tamoxifen or no endocrine treatment. HOXB13 protein analysis was successful for 367 patients. Data were correlated with clinicopathological variables. Investigation of tamoxifen benefit in patients with tumors expressing estrogen receptor (ER) α, progesterone receptor, or both, showed that patients with high HOXB13 levels had benefit from tamoxifen (hazard ratio for recurrences 0.43, 95% CI: 0.28-1.01, p=0.053). Corresponding numbers for the low HOXB13 group were 0.69 (95% CI: 0.44-1.07, p=0.10). For further analysis, we stratified the patients based on tumor ERβ status, which may function as a modifier of the performance of HOXB13 as a treatment predictive factor. For the ERβ positive subset of patients, there was a tendency towards a low HOXB13 expression associated with a better tamoxifen response. However, an increased benefit from tamoxifen, in terms of a longer recurrence-free survival (RFS), was associated with high HOXB13 expression in the ERβ negative group. The interaction between HOXB13 and treatment effect for RFS in the ERβ-negative group was significant in a multivariate model (p=0.04). In conclusion, in our study cohort, ERβ seems to be an additional determinant to HOXB13 protein expression for endocrine treatment prediction in premenopausal breast cancer. To identify patients less likely to respond to tamoxifen therapy, both HOXB13 and ERβ status should be taken into account.

  • 139.
    Jerevall, Piiha-Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Ma, Xiai-Jun
    bioTheranostics, San Diego, CA, USA.
    Li, Hongying
    bioTheranostics, San Diego, CA, USA.
    Salunga, Ranelle
    Massachusetts General Hospital, USA.
    Kesty, Nicole C.
    bioTheranostics, 9640 Towne Centre Dr Suite 200, San Diego, CA 92121, USA.
    Erlander, Mark G.
    Karolinska Institute, Stockholm, Sweden.
    Sgroi, Dennis
    Harvard Medical School, Boston, MA, USA.
    Holmlund, Birgitta
    Karolinska Institute, Stockholm, Sweden.
    Skoog, Lambert
    Karolinska Institute, Stockholm, Sweden.
    Fornander, Tommy
    Karolinska Institute, Stockholm, Sweden.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial2011Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, nr 11, s. 1762-1769Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer.

    Methods: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomized prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modeling.

    Results: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorized as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorized as low-risk with an 8.3% 10-year distant recurrence risk.

    Conclusion: Retrospective analysis of this randomized, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.

  • 140.
    Jerhammar, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Ceder, Rebecca
    Karolinska Institute, Stockholm.
    Garvin, Stina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Grenman, Reidar
    Turku University Hospital, Finland.
    C Grafstrom, Roland
    Karolinska Institute, Stockholm.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma2010Inngår i: CANCER BIOLOGY and THERAPY, ISSN 1538-4047, Vol. 10, nr 12, s. 1244-1251Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Radiotherapy remains the backbone of head and neck cancer therapy but response is sometimes impeded by tumor radioresistance. Identifying predictive biomarkers of radiotherapy response is a crucial step towards personalized therapy. The aim of this study was to explore gene expression data in search of biomarkers predictive of the response to radiotherapy in head and neck squamous cell carcinoma (HNSCC). Microarray analysis was performed on five cell lines with various intrinsic radiosensitivity, selected from a panel of 29 HNSCC cell lines. The bioinformatics approach included Gene Ontology (GO) enrichment profiling and Ingenuity Pathway Analysis (IPA). The GO-analysis detected 16 deregulated categories from which development, receptor activity and extracellular region represented the largest groups. Fourteen hub genes (CEBPA, CEBPB, CTNNB1, FN1, MYC, MYCN, PLAU, SDC4, SERPINE1, SP1, TAF4B, THBS1, TP53 and VLDLR) were identified from the IPA network analysis. The hub genes in the highest ranked network, (FN1, SERPINE1, THBS1 and VLDLR) were further subjected to qPCR analysis in the complete panel of 29 cell lines. Of these genes, high FN1 expression associated to high intrinsic radiosensitivity (p = 0.047). In conclusion, gene ontologies and hub genes of importance for intrinsic radiosensitivity were defined. The overall results suggest that FN1 should be explored as a potential novel biomarker for radioresistance.

  • 141.
    Jerhammar, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Johansson, Ann-Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Jansson, Agneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Welander, Jenny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    YAP1 Gene Amplification is a Marker for Cetuximab Resistance in Head and Neck CancerManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The epidermal growth factor receptor (EGFR) is commonly overexpressed in head and neck squamous cell carcinomas (HNSCC). The monoclonal antibody cetuximab (Erbitux®) inhibits its signaling and has been approved for treatment of HNSCC. However, since many patients do not benefit from cetuximab treatment, predictive biomarkers of cetuximab response are required. The present study aims at finding novel markers of cetuximab resistance.

    The intrinsic cetuximab sensitivity of 35 HNSCC cell lines was determined, and revealed a great variation in the response between cell lines. Five cell lines (14%) were cetuximab sensitive, and 12 (34%) were resistant. Interestingly, two cell lines proliferated after cetuximab treatment.

    10 cell lines (five cetuximab sensitive and five cetuximab resistant) were selected for gene copy number array analysis on the Affymetrix SNP 6.0 platform. 39 protein coding genes were amplified in cetuximab resistant cells and normal in sensitive cells, all present on genomic regions 11q22.1 or 5p13-15. Five genes were selected for quantitative PCR  verification, namely, YAP1 and TRPC6 (11q22.1) and PDCD6, TPPP, and PTGER4 (5p13-15). An extended panel of totally 10 cetuximab resistant and 10 sensitive cell lines verified that YAP1 amplified cells are cetuximab resistant.

    YAP1 gene amplification was highly correlated to the YAP1 mRNA expression, which was significantly higher in cetuximab resistant cells than in sensitive. YAP1 downregulation resulted in increased cetuximab sensitivity in one of two cetuximab resistant cell lines investigated and growth inhibition in another. We conclude that YAP1 is a marker for cetuximab resistance in head and neck cancer.

  • 142.
    Jogi, Annika
    et al.
    Lund University, Malmo University Hospital, Department Lab Med, Centre Mol Pathol, SE-20502 Malmo, Sweden Lund University, CREATE Hlth Centre Translat Canc Research, SE-20502 Malmo, Sweden .
    Brennan, Donal J
    University Coll Dublin, Sch Biomol and Biomed Science, Conway Institute, Dublin 2, Ireland .
    Ryden, Lisa
    Lund University, Div Surg, Department Clin Science, SE-20502 Malmo, Sweden .
    Magnusson, Kristina
    Uppsala University, Department Genet and Pathol, Rudbeck Lab, Uppsala, Sweden .
    Ferno, Marten
    University Lund Hospital, Div Oncol, Department Clin Science, S-22185 Lund, Sweden .
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Borgquist, Signe
    University Lund Hospital, Div Oncol, Department Clin Science, S-22185 Lund, Sweden .
    Uhlen, Mathias
    AlbaNova University Centre, Royal Institute Technology, Department Biotechnol, Stockholm, Sweden .
    Landberg, Goran
    Lund University, Malmo University Hospital, Department Lab Med, Centre Mol Pathol, SE-20502 Malmo, Sweden .
    Pahlman, Sven
    Lund University, Malmo University Hospital, Department Lab Med, Centre Mol Pathol, SE-20502 Malmo, Sweden Lund University, CREATE Hlth Centre Translat Canc Research, SE-20502 Malmo, Sweden .
    Ponten, Fredrik
    Lund University, Div Surg, Department Clin Science, SE-20502 Malmo, Sweden .
    Jirstrom, Karin
    Lund University, Malmo University Hospital, Department Lab Med, Centre Mol Pathol, SE-20502 Malmo, Sweden Lund University, CREATE Hlth Centre Translat Canc Research, SE-20502 Malmo, Sweden .
    Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer2009Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 22, nr 12, s. 1564-1574Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Single-strand RNA-binding proteins (RBPs) are involved in many aspects of RNA metabolism and in the regulation of gene transcription. The RBP RBM3 was recently suggested to be a proto-oncogene in colorectal cancer; however, such a role has not been corroborated by previous studies in the colon or other tumor types, and the prognostic implications of tumor-specific RBM3 expression remain unclear. Mono-specific antibodies against RBM3 were generated. Antibody specificity was confirmed using siRNA gene silencing, western blotting and immunohistochemistry on a panel of breast cancer cell lines. Using tissue microarrays and IHC, RBM3 protein expression was examined in 48 normal tissues and in 20 common cancers. Additional analysis in two independent breast cancer cohorts (n = 1016) with long-term follow-up was also carried out. RBM3 was upregulated in cancer compared to normal tissues. The nuclear expression of RBM3 in breast cancer was associated with low grade (Pandlt;0.001), small tumors (Pandlt;0.001), estrogen receptor (ER) positivity (Pandlt;0.001) and Ki-67 negativity (Pandlt;0.001) in both the breast cancer cohorts. An increased nuclear expression of RBM3 was associated with a prolonged overall and recurrence-free survival. The prognostic value was particularly pronounced in hormone receptor-positive tumors and remained significant in multivariate interaction analysis after controlling for tamoxifen treatment (HR: 0.49, 95% CI: 0.30-0.79, P = 0.004). These data strongly indicate that nuclear RBM3 is an independent favorable prognostic factor in breast cancer, and seems to have a specific role in ER-positive tumors.

  • 143.
    Johanson, V
    et al.
    Sahlgrens University Hospital.
    Wilson, B.
    Odense University Hospital.
    Abrahamsson, A.
    Karolinska University Hospital.
    Jianu, C.
    St Olav Hospital.
    Calissendorff, J.
    Karolinska University Hospital.
    Wall, Najme
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Gronbaek, H.
    Aarhus University Hospital.
    Florholmen, J.
    Department Gastroenterol and Nutr, Tromso.
    Granberg, D.
    University Hospital, Uppsala.
    Ohberg, A.
    Ipsen AB.
    A Randomized, Cross-Over Study in Patients with Neuroendocrine Tumors (NETs) to Assess Patient Preference of Lanreotide Autogel Given by either Self/Partner or Healthcare Professional in NEUROENDOCRINOLOGY, vol 94, issue , pp 29-292011Inngår i: NEUROENDOCRINOLOGY, Karger , 2011, Vol. 94, s. 703-710Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Background: Lanreotide Autogel® is supplied in prefilled syringes. Therefore, it is possible for patients with neuroendocrine tumors to use self-/partner-administered injections. The primary objective of this study was to assess the proportion of patients preferring self/partner injections over injections administered by health care professionals, and to describe the impact of self/partner administration on efficacy, safety, and costs. Methods: Of 62 eligible patients, 26 (42%) patients with neuroendocrine tumors treated with a stable dose of lanreotide Autogel 90 mg or 120 mg every 4 weeks agreed to participate in this Phase IV, international, open-label, crossover study, conducted at hospitals in Sweden, Norway, and Denmark. Patients were randomized to two blocks, starting with administration of lanreotide Autogel by either self/partner or a health care professional. Preference for injections administered by self/partner or health care professionals was measured, as well as efficacy, safety, and health care resource utilization (both direct and indirect costs). Results: Of 25 evaluable patients, 22 (88%) preferred self/partner injections, mainly because they experienced increased independence. Based on all patients asked to participate (n = 62), 35% preferred self/partner injections on a regular basis. There was no difference in efficacy or safety between the two administration blocks. Conclusion: Many patients with neuroendocrine tumors prefer self/partner injection of lanreotide Autogel, and are able to self/partner inject without any impact on efficacy or safety. This administration method seems to provide a good alternative for suitable patients to increase patient independence and reduce the number of clinic visits.

  • 144.
    Johansson, Patrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Fohlin, Helena
    Arnesson, Lars-Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Dufmats, Monika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Nordenskjoeld, Kerstin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Improved survival for women with stage I breast cancer in south-east Sweden: A comparison between two time periods before and after increased use of adjuvant systemic therapy2009Inngår i: ACTA ONCOLOGICA, ISSN 0284-186X, Vol. 48, nr 4, s. 504-513Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose. Continuous minor steps of improvement in the management of breast cancer have resulted in decreased mortality rates during the last decades. The aim of this study was to compare the clinical outcome of patients with stage I breast cancer diagnosed during two time periods that differed with respect to adjuvant systemic therapy. Material and methods. The studied population consisted of all women 60 years of age, who were diagnosed breast cancer stage I between 1986 and 1999 in south-east Sweden, a total of 1 407 cases. The cohort was divided into two groups based on the management programmes of 1986 and 1992, hereafter referred to as Period 1 and Period 2. Before 1992 the only adjuvant systemic therapy recommended was tamoxifen for hormone receptor positive patients aged 50 years or older. During Period 2 the use of adjuvant treatment was extended to younger patients at high risk, identified by a high tumour S-phase fraction, with either hormonal or cytotoxic treatment. Results. The estimated distant recurrence-free survival rate was significantly higher during Period 2 than during Period 1 (p = 0.008). Subgroup analysis showed that the most evident reduction of distant recurrence risk was among hormone receptor-negative patients (HR = 0.58, 95% CI 0.31-1.09, p = 0.09) and among patients with a high tumour S-phase fraction (HR = 0.53, 0.30-0.93, p = 0.028). The risk reduction between the periods was still statistically significant in multivariate analysis when adjusting for different tumour characteristics and treatment modalities, indicating an influence of other factors not controlled for. One such factor may be the duration of tamoxifen treatment, which likely was more frequently five years during Period 2 than during Period 1. Conclusions. We conclude that the causes of the increase in distant recurrence free survival for women with breast cancer stage I are complex. The results support though that high-risk subgroups of stage I breast cancer patients did benefit from increased use of systemic therapy as a consequence of an updated management programme.

  • 145.
    Juliusson, Gunnar
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Celsing, F
    Linkoping Univ Hosp, S-58185 Linkoping, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden Univ Hosp MAS, Malmo, Sweden Cty Hosp, Kalmar, Sweden.
    Turesson, I
    Linkoping Univ Hosp, S-58185 Linkoping, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden Univ Hosp MAS, Malmo, Sweden Cty Hosp, Kalmar, Sweden.
    Adriansson, M
    Linkoping Univ Hosp, S-58185 Linkoping, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden Univ Hosp MAS, Malmo, Sweden Cty Hosp, Kalmar, Sweden.
    Malm, C
    Thalidomide frequently induces good partial remission and best response ever in patients with advanced myeloma and prior high dose melphalan and autotransplant.1999Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 94, nr 10, s. 546-Konferansepaper (Annet vitenskapelig)
  • 146.
    Juliusson, Gunnar
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Karlsson, K
    Frodin, U
    Backstrom, G
    Malm, Claes
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Subcutaneous Campath1H instead of thymoglobulin in nonmyeloablative allogeneic transplantation: Reduced acute toxicity, but delayed lymphocyte recovery leading to more mixed chimerism, more fatal infections and impaired long-term survival2002Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, nr 11, s. 1665-Konferansepaper (Annet vitenskapelig)
  • 147.
    Juliusson, Gunnar
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Lofgren, CR
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    Mollgard, L
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    Paul, C
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    Hoglund, M
    Tidefelt, U
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    Bjorkholm, M
    Univ Hosp, Linkoping, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Acad Hosp, Uppsala, Sweden Med Ctr Hosp, Orebro, Sweden Karolinska Hosp, S-10401 Stockholm, Sweden.
    No additional toxicity from cladribine (CdA) when given with cytosin arabinoside and idarubicin (CCI) as primary treatment of acute myeloid leukemia in elderly patients: Results from a randomized phase II-study from the leukemia group of middle Sweden (LGMS).2001Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 98, nr 11, s. 518-Konferansepaper (Annet vitenskapelig)
  • 148.
    Kallstrom, Ann-Christine
    et al.
    Helsingborg Hospital.
    Salme, Rebecka
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ryden, Lisa
    Lund University.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Jonsson, Per-Ebbe
    Helsingborg Hospital.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    17 beta-Hydroxysteroid dehydrogenase type 1 as predictor of tamoxifen response in premenopausal breast cancer2010Inngår i: EUROPEAN JOURNAL OF CANCER, ISSN 0959-8049, Vol. 46, nr 5, s. 892-900Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    17 beta-Hydroxysteroid dehydrogenases (17HSDs) are involved in the local regulation of sex steroids. 17HSD1 converts oestrone (El) to the more potent oestradiol (E2) and 17HSD2 catalyses the reverse reaction. The aim of this study was to investigate the expression of these enzymes in premenopausal breast cancers and to analyse if they have any prognostic or tamoxifen predictive value. Premenopausal patients with invasive breast cancer, stage II (UICC), were randomised to either 2 years of adjuvant tamoxifen (n = 276) or no tamoxifen (n = 288). The median follow-up was 13.9 years (range 10.5-17.5). The expression of 17HSD1 and 17HSD2 was analysed with immunohistochemistry using tissue microarrays. The enzyme expression level (-/+/++/+++) was successfully determined in 396 and 373 tumours, respectively. Women with hormone-receptor positive tumours, with low levels (-/+/++) of 17HSD1, had a 43% reduced risk of recurrence, when treated with tamoxifen (Hazard Ratio (HR) = 0.57; 95% confidence interval (CI), 0.37-0.86; p = 0.0086). On the other hand high expression (+++) of 17HSD1 was associated with no significant difference between the two treatment arms (HR = 0.91; 95% CI, 0.43-1.95; p = 0.82). The interaction between 17HSD1 and tamoxifen was significant during the first 5 years of follow-up (p = 0.023). In the cohort of systemically untreated patients no prognostic importance was observed for 17HSD1. We found no predictive or prognostic value for 17HSD2. This is the first report of 17HSD1 in a cohort of premenopausal women with breast cancer randomised to tamoxifen. Our data suggest that 17HSD1 might be a predictive factor in this group of patients.

  • 149.
    Kargi, Aysegul
    et al.
    Antalya Training and Research Hospital, Turkey Medstar Hospital, Turkey Medical Pk Hospital, Turkey .
    Bisgin, Atil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Cukurova Univ, Turkey.
    Didem Yalcin, Arzu
    Antalya Training and Research Hospital, Turkey Academic Sinica, Taiwan .
    Bulent Kargi, Ahmet
    Antalya Training and Research Hospital, Turkey Medstar Hospital, Turkey Medical Pk Hospital, Turkey .
    Sahin, Emel
    Akdeniz University, Turkey .
    Gumuslu, Saadet
    Akdeniz University, Turkey .
    Increased Serum S-TRAIL Level in Newly Diagnosed Stage-IV Lung Adenocarcinoma but not Squamous Cell Carcinoma is Correlated with Age and Smoking2013Inngår i: Asian Pacific Journal of Cancer Prevention, ISSN 1513-7368, Vol. 14, nr 8, s. 4819-4822Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Lung cancer is the leading cause of cancer mortality in the world. Many factors can protect against or facilitate its development. A TNF family member TRAIL, has a complex physiological role beyond that of merely activating the apoptotic pathway in cancer cells. Vitamin D is converted to its active form locally in the lung, and is also thought to play an important role in lung health. Our goal was to investigate the possible clinical significance of serum sTRAIL and 1,25-dihydroxyvitamin D(3) levels in patients with non-small cell lung cancer (NSCLC). Materials and Methods: Totals of 18 consecutive adenocarcinoma and 22 squamous cell carcinoma patients with stage-IV non-small cell lung cancer referred to our institute were included in this study. There were 12 men and 6 women, with ages ranging from 38 to 97 (mean 60.5) years with adenocarcinoma, and 20 men and 2 women, with ages ranging from 46 to 80 (mean 65) years with squamous cell carcinoma. Serum levels of sTRAIL and 1,25-dihydroxyvitamin D(3) were measured in all samples at the time of diagnosis. Results: sTRAIL levels in NSCLC patients were higher than in the control group. Although there was no correlation between patient survival and sTRAIL levels, the highest sTRAIL levels were correlated with age and cigarette smoking in the adenocarcinoma patients. sTRAIL level in healthy individuals were correlated with serum 1,25-dihydroxyvitamin D(3). Conclusions: Serum sTRAIL concentrations were increased in NSCLC patients, and correlated with age and smoking history, but not with overall survival.

  • 150.
    Karlsson, E
    et al.
    Karolinska University Hospital.
    Waltersson, M A
    Karolinska University Hospital.
    Bostner, Josefine
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Perez-Tenorio, Gizeh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Olsson, Birgit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Fornander, T
    Karolinska University Hospital.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Comprehensive Genomic and Transcriptomic Analysis of the 11q13 Amplicon in Breast Cancer in CANCER RESEARCH, vol 69, issue 24, pp 820S-821S2009Inngår i: CANCER RESEARCH, 2009, Vol. 69, nr 24, s. 820S-821SKonferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

1234567 101 - 150 of 359
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