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  • 51. Anclair, M
    et al.
    Hovén, E
    Lannering, B
    Boman, K K
    Parental fears following their child's brain tumor diagnosis and treatment2009Ingår i: Journal of Pediatric Oncology Nursing, ISSN 1043-4542, E-ISSN 1532-8457, Vol. 26, nr 2, s. 68-74Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The objective of this study is to portray the illness-related threats experienced by parents of children after the diagnosis of central nervous system (CNS) tumor. Parents were asked to rate the extent to which they experienced a set of specific fears related to their child's brain tumor and its treatment. Outcomes for parents of CNS tumor patients (n = 82) were compared with those of reference parents of patients treated for acute lymphoblastic leukemia (n = 208). The fears about an illness recurrence and the late effects of treatment were most prominent among parents of CNS tumor patients. For 7 out of 11 kinds of fear, parents of CNS tumor patients expressed a stronger fear than the reference group. More than a quarter of the parents of children treated for CNS tumors feared a complete decline of the child. Parents of CNS tumor patients experience relatively heightened cancer related fears in several domains. The fear of devastating consequences felt by one fourth of parents signals the need of individualized psychological support and information at diagnosis and follow-up to facilitate parental coping with the posttreatment situation.

  • 52.
    Ander, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård.
    Grönqvist, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård.
    Cernvall, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård.
    Engvall, Gunn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Hedström, Mariann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Ljungman, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Lyhagen, Johan
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Mattsson, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård.
    von Essen, Louise
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård.
    Development of health-related quality of life and symptoms of anxiety and depression among persons diagnosed with cancer during adolescence: a 10-year follow-up study2016Ingår i: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 25, nr 5, s. 582-589Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The main aim was to investigate the development of health-related quality of life (HRQOL) and symptoms of anxiety and depression in a cohort diagnosed with cancer during adolescence from shortly after up to 10 years after diagnosis.

    Methods: Participants (n = 61) completed the SF-36 and the HADS shortly; six, 12, and 18 months; and two, three, four, and 10 years (n = 28) after diagnosis. Polynomial change trajectories were used to model development.

    Results: Polynomial change trajectories showed an initial increase which abated over time into a decrease which abated over time for the SF-36 subscales Mental Health and Vitality; an initial decline which abated over time into an increase for HADS anxiety; and an initial decline which abated over time into an increase which abated over time for HADS depression. The SF-36 mental component summary showed no change from two to 10 years after diagnosis whereas the SF-36 physical component summary showed an increase from two years after diagnosis which declined over time. Ten years after diagnosis 29% reported possible anxiety.

    Conclusions: Development of HRQOL and symptoms of anxiety and depression appears to be nonlinear among persons diagnosed with cancer during adolescence. Well into permanent survivorship an increase in symptoms of anxiety is shown and approximately a third of the participants report possible anxiety. The findings indicate the need for: studies designed to pinpoint the times of highest psychological risk, clinical follow-up focusing on psychological problems, and development of effective psychological interventions for survivors of adolescent cancer

  • 53.
    Ander, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård.
    Norberg, Annika Lindahl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård.
    Ljungman, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Ljotsson, Brjann
    von Essen, Louise
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård.
    Identification of Cancer-related Psychological Suffering Experienced by Young People Diagnosed with Cancer During Adolescence and Development of a Psychological Treatment to Reduce This Suffering2015Konferensbidrag (Refereegranskat)
  • 54.
    Ander, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Thorsell Cederberg, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Lindahl Norberg, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    von Essen, Louise
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk psykologi i hälso- och sjukvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Losing your context - Exploration of emotional suffering after cancer during adolescence2016Konferensbidrag (Refereegranskat)
  • 55.
    Ander, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Thorsell Cederberg, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    von Essen, Louise
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Hovén, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård. Karolinska institutet.
    Exploration of psychological distress experienced by survivors of adolescent cancer reporting a need for psychological support2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 4, artikel-id e0195899Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    In this qualitative study, we aimed to provide an in-depth exploration of cancer-related psychological distress experienced by young survivors of cancer during adolescence reporting a need for psychological support.

    Methods

    Two individual interviews were held with ten young survivors of cancer diagnosed in adolescence. The interviews were audio-recorded and transcribed verbatim. Analysis followed the guidelines for inductive qualitative manifest content analysis.

    Results

    The survivors described distress experienced during and after the end of treatment. Five categories comprising 14 subcategories were generated. The categories included: A tough treatment, Marked and hindered, Not feeling good enough, Struggling with the fragility of life, and finally, An ongoing battle with emotions.

    Conclusion

    Young survivors of adolescent cancer reporting a need for psychological support described feeling physically, socially, and mentally marked by the cancer experience. They struggled with powerlessness, insecurity, social disconnection, loneliness, and feelings of being unimportant and a failure, and had difficulties understanding and managing their experiences. These concerns should be addressed in psychological treatments for the population irrespective of which approach or model is used to understand survivors’ difficulties. A transdiagnostic approach targeting processes that underpin different manifestations of distress may be effective.

  • 56.
    Ander, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Wikman, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Ljótsson, Brjánn
    Karolinska Inst, Div Psychol, Dept Clin Neurosci, Stockholm, Sweden.
    Grönqvist, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Ljungman, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Woodford, Joanne
    Univ Exeter, Coll Life & Environm Sci, CEDAR, Psychol, Exeter, Devon, England.
    Lindahl Norberg, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    von Essen, Louise
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Guided Internet-Administered Self-Help to Reduce Symptoms Of Anxiety and Depression Among Adolescents and Young Adults Diagnosed With Cancer During Adolescence (U-CARE: YoungCan): study protocol for a feasibility trial2017Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, nr 1, artikel-id e013906Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction A subgroup of adolescents and young adults diagnosed with cancer during adolescence reports elevated levels of anxiety and depressive symptoms and unmet needs for psychological support. Evidence-based psychological treatments tailored for this population are lacking. This protocol describes a feasibility study of a guided-internet-administered self-help programme (YoungCan) primarily targeting symptoms of anxiety and depression among young persons diagnosed with cancer during adolescence and of the planned study procedures for a future controlled trial. Methods/analysis The study is an uncontrolled feasibility trial with a pre-post and 3-month follow-up design. Potential participants aged 15-25years, diagnosed with cancer during adolescence, will be identified via the Swedish Childhood Cancer Registry. 30 participants will be included. Participants will receive YoungCan, a 12-week therapist-guided, internet-administered self-help programme consisting primarily of cognitive-behavioural therapy organised into individually assigned modules targeting depressive symptoms, worry and anxiety, body dissatisfaction and post-traumatic stress. Interactive peer support and psychoeducative functions are also available. Feasibility outcomes include: recruitment and eligibility criteria; data collection; attrition; resources needed to complete the study and programme; safety procedures; participants' and therapists' adherence to the programme; and participants' acceptability of the programme and study methodology. Additionally, mechanisms of impact will be explored and data regarding symptoms of anxiety, depression, post-traumatic stress, body dissatisfaction, reactions to social interactions, quality of life, axis I diagnoses according to the Mini International Neuropsychiatric Interview and healthcare service use will be collected. Exploratory analyses of changes in targeted outcomes will be conducted. Ethics/dissemination This feasibility protocol was approved by the Regional Ethical Review Board in Uppsala, Sweden (ref: 2016/210). Findings will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals and presentations at scientific and clinical conferences.

  • 57. Andersen, Christen Lykkegaard
    et al.
    Bjorn, Mads Emil
    McMullin, Mary Frances
    Harrison, Claire
    Samuelsson, Jan
    Ejerblad, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Zweegman, Sonja
    Fernandes, Savio
    Bareford, David
    Knapper, Steven
    Lofvenberg, Eva
    Linder, Olle
    Andreasson, Bjorn
    Ahlstrand, Erik
    Jensen, Morten Krogh
    Bjerrum, Ole Weis
    Vestergaard, Hanne
    Larsen, Herdis
    Klausen, Tobias Wirenfeldt
    Mourits-Andersen, Torben
    Skov, Vibe
    Thomassen, Mads
    Kruse, Torben
    Gronbaek, Kirsten
    Hasselbalch, Hans Carl
    Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat2014Ingår i: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 38, nr 7, s. 816-821Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<0.0001) and 1.7 times higher than in ET (P = 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms. (C) 2014 Elsevier Ltd. All rights reserved.

  • 58. Andersen, Niels S.
    et al.
    Pedersen, Lone B.
    Laurell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Elonen, Erkki
    Kolstad, Arne
    Boesen, Anne Marie
    Pedersen, Lars M.
    Lauritzsen, Grete F.
    Ekanger, Roald
    Nilsson-Ehle, Herman
    Nordstrom, Marie
    Freden, Susanne
    Jerkeman, Mats
    Eriksson, Mikael
    Vaart, Jaan
    Malmer, Beatrice
    Geisler, Christian H.
    Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma2009Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 27, nr 26, s. 4365-4370Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.

  • 59.
    Andersson, Jennie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Rosestedt, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Imaging of HER2 may improve the outcome of external irradiation therapy for prostate cancer patients2015Ingår i: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 9, nr 2, s. 950-954Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prostate cancer (PCa) is the most common type of cancer among males. Human epidermal growth factor receptor type 2 (HER2) expression in PCa has been reported by several studies and its involvement in the progression towards androgen-independent PCa has been discussed. External irradiation is one of the existing therapies, which has been demonstrated to be efficient in combination with androgen deprivation therapy for the treatment of advanced PCa. However, 20-40% of patients develop recurrent and more aggressive PCa within 10 years. The current study investigates the involvement of HER2 in survival and radioresistance in PCa cells and we hypothesized that, by monitoring HER2 expression, treatment may be personalized. The PCa cell lines, LNCap, PC3 and DU-145, received a 6 Gy single dose of external irradiation. The number of PC3 cells was not affected by a single dose of radiation, whereas a 5-fold decrease in cell number was detected in LNCap (P<0.00001) and DU-145 (P<0.0001) cells. The HER2 expression in PC3 exhibited a significant increase post irradiation, however, the expression was stable in the remaining cell lines. The administration of trastuzumab post-irradiation resulted in a 2-fold decrease in the PC3 cell number, while the drug did not demonstrate additional effects in LNCap and DU-145 cells, when compared with that of irradiation treatment alone. The results of the present study demonstrated that an increase in membranous HER2 expression in response to external irradiation may indicate cell radioresistance. Furthermore, imaging of HER2 expression prior to and following external irradiation may present a step towards personalized therapy in PCa.

  • 60. Andersson, Ken G.
    et al.
    Rosestedt, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Varasteh, Zohreh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Malm, Magdalena
    Sandström, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Lofblom, John
    Stahl, Stefan
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Comparative evaluation of 111In-labeled NOTA‑conjugated affibody molecules for visualization of HER3 expression in malignant tumors2015Ingår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 34, nr 2, s. 1042-1048Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Expression of human epidermal growth factor receptor type 3 (HER3) in malignant tumors has been associated with resistance to a variety of anticancer therapies. Several anti-HER3 monoclonal antibodies are currently under pre-clinical and clinical development aiming to overcome HER3-mediated resistance. Radionuclide molecular imaging of HER3 expression may improve treatment by allowing the selection of suitable patients for HER3-targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. In a recent study, we selected affibody molecules with affinity to HER3 at a low picomolar range. The aim of the present study was to develop an anti-HER3 affibody molecule suitable for labeling with radiometals. The HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA HER3-specific affibody molecules were labeled with indium-111 (In-111) and assessed in vitro and in vivo for imaging properties using single photon emission computed tomography (SPECT). Labeling of HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA with In-111 provided stable conjugates. In vitro cell tests demonstrated specific binding of the two conjugates to HER3-expressing BT-474 breast carcinoma cells. In mice bearing BT-474 xenografts, the tumor uptake of the two conjugates was receptor-specific. Direct in vivo comparison of In-111-HEHEHE-Z08698-NOTA and In-111-HEHEHE-Z08699-NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for In-111-HEHEHE-Z08698-NOTA [12 +/- 3 vs. 8 +/- 1,4 h post injection (p.i)] due to more efficient blood clearance. In-111-HEHEHE-Z08698-NOTA is a promising candidate for imaging of HER3-expression in malignant tumors using SPECT. Results of the present study indicate that this conjugate could be used for patient stratification for anti-HER3 therapy.

  • 61.
    Andersson, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Bergström, Evelina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    "Rehabilitering med samtalsterapi och yoga": En utvärdering av Akademiska sjukhusets projekt för cancerpatienter2010Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    SAMMANFATTNING

    Syfte: Syftet med undersökningen var att utvärdera effekterna av behandlingen i projektet ”Rehabilitering med samtalsterapi och yoga” med avseende på upplevt fysiskt, socialt, känslomässigt och funktionellt välbefinnande, samt undersöka deltagarnas tillfredsställelse med rehabiliteringen. Metod: Utvärderingen gjordes våren 2010 med kvantitativ metod och deskriptiv, longitudinell design. Alla som skulle börja i nybörjarkursen ombads att delta. Enkäter delades ut före och efter deltagande i max tre rehabiliteringskurser. Deltagarantalet i utvärderingen var 22. Svaren analyserades med hjälp av beskrivande statistik och beroende T-test. Resultat: Det kunde inte påvisas några signifikanta skillnader över tid mellan skalorna Fysiskt välbefinnande (p=,507), Socialt välbefinnande (p=,936), Känslomässigt välbefinnande (p=,493) och Funktionellt välbefinnande (p=,388). Vid analys av de enskilda frågorna i skalorna fanns heller inga signifikanta skillnader. Enligt patientutvärderingen ansåg alla deltagare att yoga- och samtalsterapin, i olika grad, har hjälpt dem att hantera sin situation och 95,5% (n=21) säger att de skulle kunna rekommendera denna kurs till en vän i liknande situation. Slutsats: Rehabiliteringsprojektet skulle kunna utvecklas ytterligare, men bör fortsätta ges som ett komplement till traditionell onkologisk behandling då den anses vara betydelsefull för deltagarna. P.g.a. brister skulle en ny utvärdering behöva göras.

  • 62. Andersson, Sonia
    et al.
    Mints, Miriam
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Lindell, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Gustavsson, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Lambe, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Wilander, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females: A retrospective database study2014Ingår i: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, nr 4, s. 1528-1532Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18145 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.

  • 63.
    Andersson, Therese M. -L.
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    Johansson, Anna L. V.
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    Fredriksson, Irma
    Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden..
    Lambe, Mats
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.;Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Cancer during pregnancy and the postpartum period: A population-based study2015Ingår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 121, nr 12, s. 2072-2077Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUNDThe purpose of this study was to assess patterns of cancer occurrence during pregnancy and the postpartum period. METHODSThis was a register-based study using data from the Swedish Multi-Generation Register and the National Cancer Register from 1963 to 2007. Pregnancy-associated cancer (PAC) was defined as a malignancy detected during pregnancy or within 2 years of delivery and was assessed in 7 time windows: pregnancy, trimesters 1-3, 0-6 months, 7-12 months, and second year postpartum. Population incidence rates by 5-year age groups and periods were used to estimate the expected number of PACs for each site. The observed versus the expected (O/E) number of cases was estimated with 95% confidence intervals (CI). RESULTSThe 3 most common malignancies during pregnancy were melanoma (n=232), breast (n=139) and cervical cancer (n=139). With a slightly different rank order, these cancers are also the most common in women of childbearing age. The number of observed cases during pregnancy was lower than expected for all cancers, with a combined O/E ratio for all sites of 0.46 (95% CI, 0.43-0.49). The O/E ratio was close to 1 during all postpartum intervals, including 0-6 months (0.93; 95% CI, 0.88-0.98), 7-12 months (0.96; 95% CI, 0.91-1.01), and during the second year after delivery (0.95; 95% CI, 0.92-0.99). CONCLUSIONSThe rate of cancer during pregnancy was lower than expected for all sites, a finding that could not be explained entirely by delayed diagnosis. A rebound in the number of observed cases after delivery was restricted to melanoma, nervous system malignancies, and breast and thyroid cancer. Cancer 2015;121:2072-2077. (c) 2015 American Cancer Society. Fewer cancers than expected are found during pregnancy, a finding that cannot be explained entirely by delayed diagnosis.

  • 64. Andersson, Therese M-L
    et al.
    Dickman, Paul W.
    Eloranta, Sandra
    Sjovall, Annika
    Lambe, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lambert, Paul C.
    The loss in expectation of life after colon cancer: a population-based study2015Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, artikel-id 412Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To demonstrate how assessment of life expectancy and loss in expectation of life can be used to address a wide range of research questions of public health interest pertaining to the prognosis of cancer patients. Methods: We identified 135,092 cases of colon adenocarcinoma diagnosed during 1961-2011 from the population-based Swedish Cancer Register. Flexible parametric survival models for relative survival were used to estimate the life expectancy and the loss in expectation of life. Results: The loss in expectation of life for males aged 55 at diagnosis was 13.5 years (95 % CI 13.2-13.8) in 1965 and 12.8 (12.4-13.3) in 2005. For males aged 85 the corresponding figures were 3.21 (3.15-3.28) and 2.10 (2.04-2.17). The pattern was similar for females, but slightly greater loss in expectation of life. The loss in expectation of life is reduced given survival up to a certain time point post diagnosis. Among patients diagnosed in 2011, 945 life years could potentially be saved if the colon cancer survival among males could be brought to the same level as for females. Conclusion: Assessment of loss in expectation of life facilitates the understanding of the impact of cancer, both on individual and population level. Clear improvements in survival among colon cancer patients have led to a gain in life expectancy, partly due to a general increase in survival from all causes.

  • 65.
    Andersson, Yvette
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Vastmanland Cty Hosp, Dept Surg, SE-72189 Vasteras, Sweden.
    Bergkvist, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Vastmanland Cty Hosp, Dept Surg, SE-72189 Vasteras, Sweden.
    Frisell, J.
    Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    de Boniface, J.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Capio St Gorans Hosp, Dept Surg, Stockholm, Sweden.
    Do clinical trials truly mirror their target population?: An external validity analysis of national register versus trial data from the Swedish prospective SENOMIC trial on sentinel node micrometastases in breast cancer2019Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 177, nr 2, s. 469-475Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Increasing evidence suggests that completion axillary lymph node dissection (ALND) may be omitted in breast cancer patients with limited axillary nodal metastases. However, the representativeness of trial participants for the original clinical practice population, and thus, the generalizability of published trials have been questioned. We propose the use of background data from national registers as a means to assess whether trial participants mirror their target population and to strengthen the generalizability and implementation of trial outcomes.

    Methods: The Swedish prospective SENOMIC trial, omitting a completion ALND in breast cancer patients with sentinel lymph node micrometastases, reached full target accrual in 2017. To assess the generalizability of trial results for the target population, a comparative analysis of trial participants versus cases reported to the Swedish National Breast Cancer Register (NKBC) was performed.

    Results: Comparing 548 trial participants and 1070 NKBC cases, there were no significant differences in age, tumor characteristics, breast surgery, or adjuvant treatment. Only the mean number of sentinel lymph nodes with micrometastasis per individual was lower in trial participants than in register cases (1.06 vs. 1.09, p=0.037).

    Conclusions: Patients included in the SENOMIC trial are acceptably representative of the Swedish breast cancer target population. There were some minor divergences between trial participants and the NKBC population, but taking these into consideration, upcoming trial outcomes should be generalizable to breast cancer patients with micrometastases in their sentinel lymph node biopsy.

  • 66.
    Andersson, Yvette
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Vastmanland Cty Hosp, Dept Surg, S-72189 Vasteras, Sweden.
    Bergkvist, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Vastmanland Cty Hosp, Dept Surg, S-72189 Vasteras, Sweden.
    Frisell, J.
    Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    de Boniface, J.
    Capio St Gorans Hosp, Dept Surg, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes2018Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 171, nr 2, s. 359-369Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The clinical significance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a worse cancer-specific and event-free survival for patients with micrometastases than node-negative individuals, but could not demonstrate a significant difference in overall survival (OS). Due to the tendency of breast cancer to relapse after more than 5-10 years, we now report the long-term survival of the cohort.

    Methods: Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort. Sentinel lymph node biopsy was always performed. Patients were classified in four groups according to their overall nodal stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan-Meier survival estimates and Cox proportional hazard regression models were applied.

    Results: Median follow-up was 156 months. Ten-year cancer-specific survival and OS were significantly lower in case of micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrometastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-specific survival and OS were significantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy than those with macrometastases (24.4 vs. 53.9%).

    Conclusions: Lymph node micrometastases in breast cancer have a prognostic significance. This study demonstrates a similar survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.

  • 67.
    Angenendt, Linus
    et al.
    Univ Hosp Munster, Munster, Germany.
    Röllig, Christoph
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Montesinos, Pau
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Martinez-Cuadron, David
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Barragan, Eva
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Garcia, Raimundo
    Gen Hosp Castellon, Castellon de La Plana, Spain.
    Botella, Carmen
    Hosp Gen Alicante, Alicante, Spain.
    Martinez, Pilar
    Hosp 12 Octubre, Madrid, Spain.
    Ravandi, Farhad
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kadia, Tapan
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kantarjian, Hagop M.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Cortes, Jorge
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Juliusson, Gunnar
    Lund Univ, Lund, Sweden.
    Lazarevic, Vladimir
    Lund Univ, Lund, Sweden.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lehmann, Sören
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Recher, Christian
    CHU Toulouse, Toulouse, France.
    Pigneux, Arnaud
    CHU Bordeaux, Hop Haut Leveque, Bordeaux, France.
    Bertoli, Sarah
    CHU Toulouse, Toulouse, France.
    Dumas, Pierre-Yves
    CHU Bordeaux, Hop Haut Leveque, Bordeaux, France.
    Dombret, Herve
    Paris Diderot Univ, Paris, France.
    Preudhomme, Claude
    Inst Natl Sante & Rech Med Lille, Lille, France.
    Micol, Jean-Baptiste
    Paris Saclay Univ, Gustave Roussy, Villejuif, France.
    Terre, Christine
    Ctr Transfus Sanguine, Le Chesnay, France.
    Racil, Zdenek
    Masaryk Univ, Univ Hosp Brno, Brno, Czech Republic.
    Novak, Jan
    Charles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Prague, Czech Republic.
    Zak, Pavel
    Charles Univ Prague, Univ Hosp Hradec Kralove, Hradec Kralove, Czech Republic.
    Wei, Andrew H.
    Monash Univ, Alfred Hosp, Melbourne, Vic, Australia.
    Tiong, Ing S.
    Monash Univ, Alfred Hosp, Melbourne, Vic, Australia.
    Wall, Meaghan
    St Vincents Hosp, Melbourne, Vic, Australia.
    Estey, Elihu
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Shaw, Carole
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Exeler, Rita
    Univ Munster, Munster, Germany.
    Wagenführ, Lisa
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Stölzel, Friedrich
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Thiede, Christian
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Stelljes, Matthias
    Univ Hosp Munster, Munster, Germany.
    Lenz, Georg
    Univ Hosp Munster, Munster, Germany.
    Mikesch, Jan-Henrik
    Univ Hosp Munster, Munster, Germany.
    Serve, Hubert
    Univ Hosp Frankfurt, Frankfurt, Germany.
    Ehninger, Gerhard
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Berdel, Wolfgang E.
    Univ Hosp Munster, Munster, Germany.
    Kramer, Michael
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Krug, Utz
    Klinikum Leverkusen, Leverkusen, Germany.
    Schliemann, Christoph
    Univ Hosp Munster, Munster, Germany.
    Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts2019Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, nr 29, s. 2632-2642Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.

    METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.

    RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.

    CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.

  • 68.
    Anthony, L.
    et al.
    Univ Kentucky, Lexington, KY USA..
    Kulke, M. H.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Hoersch, D.
    Zent Klin Bad Berka, Bad Berka, Germany..
    Bergsland, E.
    UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Lombard-Bohas, C.
    Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France..
    Kunz, P.
    Stanford Univ, Palo Alto, CA 94304 USA..
    Valle, J. W.
    Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England..
    Kassler-Taub, K.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Fleming, R.
    Charite, Berlin, Germany..
    Pavel, M.
    Charite, Berlin, Germany..
    Impact of Concomitant Medication on Efficacy of Telotristat Ethyl - A Post Hoc Subgroup Analysis of the Phase 3 TELESTAR Study in Carcinoid Syndrome2017Ingår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, s. 212-212Artikel i tidskrift (Övrigt vetenskapligt)
  • 69.
    Anthony, Lowell B.
    et al.
    Univ Kentucky, Markey Canc Ctr, Lexington, KY USA.
    Kulke, Matthew H.
    Boston Univ, Med Ctr, Boston, MA USA.
    Caplin, Martyn E.
    Royal Free Hosp, ENETS Ctr Excellence, Neuroendocrine Tumor Unit, London, England.
    Bergsland, Emily
    Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Pavel, Marianne
    Charite, Dept Hepatol & Gastroenterol, Berlin, Germany.
    Hoersch, Dieter
    Zentralklin Bad Berka, Ctr Neuroendocrine Tumors, Dept Gastroenterol Endocrinol, Bad Berka, Germany.
    Warner, Richard R. P.
    Icahn Sch Med Mt Sinai, Div Gastroenterol, New York, NY 10029 USA.
    O'Dorisio, Thomas M.
    Univ Iowa, Dept Internal Med Endocrinol & Metab, Iowa City, IA USA.
    Dillon, Joseph S.
    Univ Iowa, Dept Internal Med Endocrinol & Metab, Iowa City, IA USA.
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Kassler-Taub, Kenneth
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Liang, Wenjun
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome2019Ingår i: The Oncologist, ISSN 1083-7159, E-ISSN 1549-490X, Vol. 24, nr 8, s. E662-E670Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter survival. Carcinoid syndrome is linked to tumoral secretion of serotonin and other bioactive substances. The subsequent debilitating diarrhea and urgency to defecate pose significant health risks. In previous studies, telotristat ethyl, a tryptophan hydroxylase inhibitor, was effective and well tolerated in treating carcinoid syndrome diarrhea. We present pooled safety data from five clinical trials with telotristat ethyl in patients with carcinoid syndrome. Subjects, Materials, and Methods Adverse events reported during telotristat ethyl treatment were pooled from two phase II and three phase III clinical trials in 239 patients with carcinoid syndrome. Long-term safety of telotristat ethyl and causes of hospitalization and death were reviewed; overall survival was estimated. Results Mean (median; range) duration of exposure and follow-up was 1.3 years (1.1 years; 1 week to 5.7 years), with 309 total patient-years of exposure. Leading causes of hospitalization were gastrointestinal disorders or were related to the underlying tumor and related treatment. Survival estimates at 1, 2, and 3 years were 93%, 88%, and 77%. Nearly all deaths were due to progression or complication of the underlying disease; none were attributable to telotristat ethyl. There was one death in year 4. Conclusion Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome. Implications for Practice Carcinoid syndrome can cause persistent diarrhea, even in patients treated with somatostatin analogs. Across five clinical trials in patients with carcinoid syndrome, telotristat ethyl has been well tolerated and efficacious, providing clinicians with a new approach to help control carcinoid syndrome diarrhea, in addition to somatostatin analog therapy. By reducing the stool frequency in patients with carcinoid syndrome whose diarrhea is refractory to anticholinergics, such as loperamide and atropine/diphenoxylate, and somatostatin analog dose escalation, improvement in quality of life becomes an achievable goal.

  • 70.
    Antonodimitrakis, Pantelis Clewemar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Olofsson, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Grimelius, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wassberg, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion: a retrospective study2017Ingår i: International Journal of Endocrine Oncology, Vol. 4, nr 1, s. 9-22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: Vasoactive intestinal polypeptide producing neuroendocrine tumors are rare and cause severe hormonal symptoms. Patients/methods: Eighteen patients with vasoactive intestinal polypeptide producing neuroendocrine tumors were analyzed with reviews of medical records, radiology and tumor tissue specimens. Results: Twelve patients (67%) had liver metastases at diagnosis. Chemotherapy, somatostatin analogs and interferon were given as medical therapies. Streptozocin/5-fluorouracil produced an objective response in 40% of the evaluable patients. Somatostatin analogs gave a clinical/biochemical response in eight out of nine patients. Transarterial embolization of the liver and peptide receptor radionuclide therapy was given to refractory cases. Sixteen patients died during the observation period. The median overall survival from diagnosis was 102 months. Conclusion: Systemic chemotherapy and somatostatin analogs should be given in cases of advanced disease or for hormonal symptoms.

  • 71. Arase, Mayu
    et al.
    Horiguchi, Kana
    Ehata, Shogo
    Morikawa, Masato
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tsutsumi, Shuichi
    Aburatani, Hiroyuki
    Miyazono, Kohei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Koinuma, Daizo
    Transforming growth factor-beta-induced lncRNA-Smad7 inhibits apoptosis of mouse breast cancer JygMC(A) cells2014Ingår i: Cancer Science, ISSN 1347-9032, E-ISSN 1349-7006, Vol. 105, nr 8, s. 974-982Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transforming growth factor (TGF)-beta exhibits both pro-apoptotic and anti-apoptotic effects on epithelial cells in a context-dependent manner. The anti-apoptotic function of TGF-beta is mediated by several downstream regulatory mechanisms, and has been implicated in the tumor-progressive phenotype of breast cancer cells. We conducted RNA sequencing of mouse mammary gland epithelial (NMuMG) cells and identified a long non-coding RNA, termed lncRNA-Smad7, which has anti-apoptotic functions, as a target of TGF-beta lncRNA-Smad7 was located adjacent to the mouse Smad7 gene, and its expression was induced by TGF-beta in all of the mouse mammary gland epithelial cell lines and breast cancer cell lines that we evaluated. Suppression of lncRNA-Smad7 expression cancelled the anti-apoptotic function of TGF-beta In contrast, forced expression of lncRNA-Smad7 rescued apoptosis induced by a TGF-beta type I receptor kinase inhibitor in the mouse breast cancer cell line JygMC(A). The anti-apoptotic effect of lncRNA-Smad7 appeared to occur independently of the transcriptional regulation by TGF-beta of anti-apoptotic DEC1 and pro-apoptotic Bim proteins. Small interfering RNA for lncRNA-Smad7 did not alter the process of TGF-beta-induced epithelial-mesenchymal transition, phosphorylation of Smad2 or expression of the Smad7 gene, suggesting that the contribution of this lncRNA to TGF-beta functions may be restricted to apoptosis. Our findings suggest a complex mechanism for regulating the anti-apoptotic and tumor-progressive aspects of TGF-beta signaling.

  • 72.
    Arce, Maximiliano
    et al.
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Adv Ctr Chron Dis ACCDiS, Santiago, Chile.
    Pinto, Mauricio P.
    Pontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile.
    Galleguillos, Macarena
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile.
    Munoz, Catalina
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile.
    Lange, Soledad
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile.
    Ramirez, Carolina
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile.
    Erices, Rafaela
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Univ Mayor, Vicerrectoria Invest, Santiago 7510041, Chile.
    Gonzalez, Pamela
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile.
    Velasquez, Ethel
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Comis Chilena Energia Nucl CCHEN, Santiago, Chile.
    Tempio, Fabian
    Univ Chile, Fac Med, Inst Biomed Sci, Santiago 8380453, Chile.
    Lopez, Mercedes N.
    Univ Chile, Fac Med, Inst Biomed Sci, Santiago 8380453, Chile;Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile.
    Salazar-Onfray, Flavio
    Univ Chile, Fac Med, Inst Biomed Sci, Santiago 8380453, Chile;Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile.
    Cautivo, Kelly
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile.
    Kalergis, Alexis M.
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile;Biomed Res Consortium Chile, Santiago 8331010, Chile.
    Cruz, Sebastian
    Fdn Ciencia & Vida, Lab Immunoncol, Santiago, Chile.
    Lladser, Alvaro
    Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile;Fdn Ciencia & Vida, Lab Immunoncol, Santiago, Chile.
    Lobos-Gonzalez, Lorena
    Adv Ctr Chron Dis ACCDiS, Santiago, Chile;Fdn Ciencia & Vida, Lab Immunoncol, Santiago, Chile;Univ Desarrollo, Fac Med, Regenerat Med Ctr, Clin Alemana, Santiago 7650568, Chile.
    Valenzuela, Guillermo
    Pontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile.
    Olivares, Nixa
    Pontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile.
    Saez, Claudia
    Pontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile.
    Koning, Tania
    Univ Austral Chile, Fac Med, Immunol Inst, Valdivia 5110566, Chile.
    Sanchez, Fabiola A.
    Univ Austral Chile, Fac Med, Immunol Inst, Valdivia 5110566, Chile.
    Fuenzalida, Patricia
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile.
    Godoy, Alejandro
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Roswell Pk Comprehens Canc Ctr, Dept Urol, Buffalo, NY 14203 USA.
    Contreras Orellana, Pamela
    Adv Ctr Chron Dis ACCDiS, Santiago, Chile;Univ Chile, Fac Med, Lab Cellular Commun, ICBM, Santiago 8380453, Chile.
    Leyton, Lisette
    Adv Ctr Chron Dis ACCDiS, Santiago, Chile;Univ Chile, Fac Med, Lab Cellular Commun, ICBM, Santiago 8380453, Chile.
    Lugano, Roberta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Dimberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Quest, Andrew F. G.
    Adv Ctr Chron Dis ACCDiS, Santiago, Chile;Univ Chile, Fac Med, Lab Cellular Commun, ICBM, Santiago 8380453, Chile.
    Owen, Gareth, I
    Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Adv Ctr Chron Dis ACCDiS, Santiago, Chile;Pontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile;Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile.
    Coagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation2019Ingår i: Cancers, ISSN 2072-6694, Vol. 11, nr 8, artikel-id 1103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hypercoagulable state is linked to cancer progression; however, the precise role of the coagulation cascade is poorly described. Herein, we examined the contribution of a hypercoagulative state through the administration of intravenous Coagulation Factor Xa (FXa), on the growth of solid human tumors and the experimental metastasis of the B16F10 melanoma in mouse models. FXa increased solid tumor volume and lung, liver, kidney and lymph node metastasis of tail-vein injected B16F10 cells. Concentrating on the metastasis model, upon coadministration of the anticoagulant Dalteparin, lung metastasis was significantly reduced, and no metastasis was observed in other organs. FXa did not directly alter proliferation, migration or invasion of cancer cells in vitro. Alternatively, FXa upon endothelial cells promoted cytoskeleton contraction, disrupted membrane VE-Cadherin pattern, heightened endothelial-hyperpermeability, increased inflammatory adhesion molecules and enhanced B16F10 adhesion under flow conditions. Microarray analysis of endothelial cells treated with FXa demonstrated elevated expression of inflammatory transcripts. Accordingly, FXa treatment increased immune cell infiltration in mouse lungs, an effect reduced by dalteparin. Taken together, our results suggest that FXa increases B16F10 metastasis via endothelial cell activation and enhanced cancer cell-endothelium adhesion advocating that the coagulation system is not merely a bystander in the process of cancer metastasis.

  • 73. Ardenfors, Oscar
    et al.
    Dasu, Alexandru
    Kopeć, Mariusz
    Gudowska, Irena
    Modelling of a proton spot scanning system using MCNP62017Ingår i: Journal of Physics: Conference Series, ISSN 1742-6588, Vol. 860, s. 012025-Artikel i tidskrift (Refereegranskat)
  • 74. Ardenfors, Oscar
    et al.
    Dasu, Alexandru
    Lillhök, Jan
    Persson, Linda
    Gudowska, Irena
    Out-of-field doses from secondary radiation produced in proton therapy and the associated risk of radiation-induced cancer from a brain tumor treatment.2018Ingår i: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 53, s. 129-136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To determine out-of-field doses produced in proton pencil beam scanning (PBS) therapy using Monte Carlo simulations and to estimate the associated risk of radiation-induced second cancer from a brain tumor treatment.

    METHODS: Simulations of out-of-field absorbed doses were performed with MCNP6 and benchmarked against measurements with tissue-equivalent proportional counters (TEPC) for three irradiation setups: two irradiations of a water phantom using proton energies of 78-147 MeV and 177-223 MeV, and one brain tumor irradiation of a whole-body phantom. Out-of-field absorbed and equivalent doses to organs in a whole-body phantom following a brain tumor treatment were subsequently simulated and used to estimate the risk of radiation-induced cancer. Additionally, the contribution of absorbed dose originating from radiation produced in the nozzle was calculated from simulations.

    RESULTS: Out-of-field absorbed doses to the TEPC ranged from 0.4 to 135 µGy/Gy. The average deviation between simulations and measurements of the water phantom irradiations was about 17%. The absorbed dose contribution from radiation produced in the nozzle ranged between 0 and 70% of the total dose; the contribution was however small in absolute terms. The absorbed and equivalent doses to the organs ranged between 0.2 and 60 µGy/Gy and 0.5-151 µSv/Gy. The estimated lifetime risk of radiation-induced second cancer was approximately 0.01%.

    CONCLUSIONS: The agreement of out-of-field absorbed doses between measurements and simulations was good given the sources of uncertainties. Calculations of out-of-field organ doses following a brain tumor treatment indicated that proton PBS therapy of brain tumors is associated with a low risk of radiation-induced cancer.

  • 75. Ardenfors, Oscar
    et al.
    Gudowska, Irena
    Flejmer, Anna Maria
    Dasu, Alexandru
    Impact of irradiation setup in proton spot scanning brain therapy on organ doses from secondary radiation2018Ingår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 180, nr 1-4, s. 261-266Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A Monte Carlo model of a proton spot scanning pencil beam was used to simulate organ doses from secondary radiation produced from brain tumour treatments delivered with either a lateral field or a vertex field to one adult and one paediatric patient. Absorbed doses from secondary neutrons, photons and protons and neutron equivalent doses were higher for the vertex field in both patients, but the differences were low in absolute terms. Absorbed doses ranged between 0.1 and 43 μGy.Gy-1 in both patients with the paediatric patient receiving higher doses. The neutron equivalent doses to the organs ranged between 0.5 and 141 μSv.Gy-1 for the paediatric patient and between 0.2 and 134 μSv.Gy-1 for the adult. The highest neutron equivalent dose from the entire treatment was 7 mSv regardless of field setup and patient size. The results indicate that different field setups do not introduce large absolute variations in out-of-field doses produced in patients undergoing proton pencil beam scanning of centrally located brain tumours.

  • 76. Ardenfors, Oscar
    et al.
    Henry, Thomas
    Gudowska, Irena
    Poludniowski, Gavin
    Dasu, Alexandru
    Organ doses from a proton gantry-mounted cone-beam computed tomography system characterized with MCNP6 and GATE2018Ingår i: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 53, s. 56-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To determine organ doses from a proton gantry-mounted cone-beam computed tomography (CBCT) system using two Monte Carlo codes and to study the influence on organ doses from different acquisition modes and repeated imaging.

    METHODS: The CBCT system was characterized with MCNP6 and GATE using measurements of depth doses in water and spatial profiles in air. The beam models were validated against absolute dose measurements and used to simulate organ doses from CBCT imaging with head, thorax and pelvis protocols. Anterior and posterior 190° scans were simulated and the resulting organ doses per mAs were compared to those from 360° scans. The influence on organ doses from repeated imaging with different imaging schedules was also investigated.

    RESULTS: The agreement between MCNP6, GATE and measurements with regard to depth doses and beam profiles was within 4% for all protocols and the corresponding average agreement in absolute dose validation was 4%. Absorbed doses for in-field organs from 360° scans ranged between 6 and 8 mGy, 15-17 mGy and 24-54 mGy for the head, thorax and pelvis protocols, respectively. Cumulative organ doses from repeated CBCT imaging ranged between 0.04 and 0.32 Gy for weekly imaging and 0.2-1.6 Gy for daily imaging. The anterior scans resulted in an average increase in dose per mAs of 24% to the organs of interest relative to the 360° scan, while the posterior scan showed a 37% decrease.

    CONCLUSIONS: A proton gantry-mounted CBCT system was accurately characterized with MCNP6 and GATE. Organ doses varied greatly depending on acquisition mode, favoring posterior scans.

  • 77.
    Armuand, G. M.
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Nilsson, J.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Rodriguez-Wallberg, K. A.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Reprod Med, Stockholm, Sweden..
    Malmros, J.
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Paediat Oncol Unit, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Arvidson, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnneurologi/Barnonkologi.
    Lampic, C.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Wettergren, L.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Physicians' self-reported practice behaviour regarding fertility-related discussions in paediatric oncology in Sweden2017Ingår i: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 26, nr 10, s. 1684-1690Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of this study was to investigate practice behaviours of Swedish physicians with regard to discussing the impact of cancer treatment on fertility with paediatric oncology patients and their parents, and to identify factors associated with such discussions.

    Methods: A cross-sectional survey study was conducted targeting all physicians in Sweden working in paediatric oncology care settings. Participants responded to a questionnaire measuring practice behaviour, attitudes, barriers, and confidence in knowledge. Multivariable logistic regression was used to determine factors associated with seldom discussing fertility.

    Results: More than half of the physicians routinely talked with their patients/parents about the treatment's potential impact on fertility (male patients: 62%; female patients: 57%; P = 0.570). Factors associated with less frequently discussing fertility with patients/parents were working at a non-university hospital (male patients: OR 11.49, CI 1.98-66.67; female patients: OR 33.18, CI 4.06-271.07), concerns that the topic would cause worry (male patients: OR 8.23, CI 1.48-45.89; female patients: OR 12.38, CI 1.90-80.70), and perceiving the parents as anxious (male patients: OR 7.18, CI 1.20-42.85; female patients: OR 11.65, CI 1.32-103.17).

    Conclusions: Based on our findings, we recommend structured training in how to communicate about fertility issues in stressful situations, which in turn might increase fertility-related discussions in paediatric oncology.

  • 78.
    Arthur, R.
    et al.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
    Williams, R.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Malmstrom, H.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;Swedish Orphan Biovitrum, Stockholm, Sweden.
    Lambe, M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Hammar, N.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;AstraZeneca, Global Med Dev Med Evidence & Observat Res, Stockholm, Sweden.
    Walldius, G.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Robinsson, D.
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Jungner, I.
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden;CALAB Res, Stockholm, Sweden.
    Van Hemelrijck, M.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study2018Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, nr 11, s. 2254-2262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.

  • 79.
    Arthur, Rhonda
    et al.
    Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England..
    Møller, Henrik
    Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England..
    Garmo, Hans
    Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England.;Reg Canc Ctr, Uppsala, Sweden..
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England.;Reg Canc Ctr, Uppsala, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Departments of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University.
    Malmstrom, Hakan
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden..
    Lambe, Mats
    Univ Uppsala Hosp, Dept Surg Sci, Uppsala, Sweden.;Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden.;Karolinska Inst, Dept Biostat, Stockholm, Sweden..
    Hammar, Niklas
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.;AstraZeneca Sverige, Sodertalje, Sweden..
    Walldius, Goran
    Karolinska Inst, Inst Environm Med, Dept Cardiovasc Epidemiol, Stockholm, Sweden..
    Robinson, David
    Departments of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University.
    Jungner, Ingmar
    Karolinska Inst, Dept Clin Epidemiol Unit, Stockholm, Sweden.;CALAB Res, Stockholm, Sweden..
    Van Hemelrijck, Mieke
    Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England.;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden..
    Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories2016Ingår i: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 5, nr 6, s. 1307-1318Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 mu g/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 mu g/L compared to PSA 4.0-9.9 mu g/L. Hypertriglyceridemia was also positively associated with PSA>20 mu g/L. Hyperglycemic men had a greater odds of intermediate-and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention.

  • 80.
    Arthur, Rhonda
    et al.
    Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY 10461 USA;Kings Coll London, Translat Oncol & Urol Res, London, England;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk, Bronx, NY 10461 USA.
    Møller, Henrik
    Kings Coll London, Translat Oncol & Urol Res, London, England.
    Garmo, Hans
    Kings Coll London, Translat Oncol & Urol Res, London, England;Uppsala Univ Hosp, Dept Surg Sci, Uppsala, Sweden.
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Holmberg, Lars
    Kings Coll London, Translat Oncol & Urol Res, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malmström, Håkan
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;Swedish Orphan Biovitrum Sobi, Biostat Data Management & Med Writing, Res & Dev, Stockholm, Sweden.
    Lambe, Mats
    Uppsala Univ Hosp, Reg Canc Ctr, Uppsala, Sweden.
    Hammar, Niklas
    AstraZeneca, Med Evidence & Observat Res, Global Med Dev, Molndal, Sweden.
    Walldius, Göran
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Jungner, Ingmar
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden;CALAB Res, Stockholm, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Translat Oncol & Urol Res, London, England.
    Serum glucose, triglycerides, and cholesterol in relation to prostate cancer death in the Swedish AMORIS study2019Ingår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 30, nr 2, s. 195-206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Lifestyle-related conditions such as obesity are associated with prostate cancer progression, but the associations with hyperglycemia and dyslipidemia are unclear. This study, therefore, aims to examine the association of glucose, triglycerides, and total cholesterol with prostate cancer death

    Methods: From the Swedish AMORIS cohort, we selected 14,150 men diagnosed with prostate cancer between 1996 and 2011 who had prediagnostic measurements of serum glucose, triglycerides, and total cholesterol. Multivariable Cox proportional hazards regressionmodels were used to determine the hazard ratios for death in relation to the aforementioned metabolic markers.

    Results: Using clinical cut-off points, a non-significant positive association was observed between glucose and prostate cancer death. When compared to those with glucose in the lowest quartile, those in the highest quartile had greater risk of prostate cancer death (HR 1.19; 95% CI 1.02-1.39). However, neither total cholesterol nor triglycerides were associated with prostate cancer death. Glucose and triglycerides were positively associated with overall, cardiovascular, and other deaths. Hypercholesterolemia was only associated with risk of CVD death.

    Conclusion: Our results suggest that glucose levels may influence prostate cancer survival, but further studies using repeated measurements are needed to further elucidate how glucose levels may influence prostate cancer progression.

  • 81.
    Arving, Cecilia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Rissanen, Ritva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Ahlgren, Johan
    Nordin, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Effects of a Stepped Care Stress Management Intervention on Cancer-Related Traumatic Stress Symptoms Among Breast Cancer Patients: A Randomized Study of Group Versus Individual Setting2014Ingår i: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 23, nr Suppl. 3, s. 171-171, artikel-id P1-0300Artikel i tidskrift (Övrigt vetenskapligt)
  • 82.
    Arving, Cecilia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Thormodsen, Inger
    Berntsen, Sveinung
    Nordin, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Identifying Variables Associated With the Course of Fatigue Among Cancer Patients During Adjuvant and Curative Treatment2014Ingår i: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 23, s. 176-176Artikel i tidskrift (Övrigt vetenskapligt)
  • 83.
    Arving, Cecilia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Wadensten, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Johansson, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Registered Nurses' Thoughts on Blended Learning in a Postgraduate Course in Cancer care: Content Analyses of Web Surveys and a Focus Group Interview2014Ingår i: Journal of Cancer Education, ISSN 0885-8195, E-ISSN 1543-0154, Vol. 29, nr 2, s. 278-283Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose of the research was to describe registered nurses' (RNs) (n = 53) thoughts on the blended learning format in a 'specialist nursing programme in cancer care'. The study was conducted in autumn 2007 and 2008. A content analysis of answers to open-ended questions in a web-based questionnaire and a focus group interview were carried out. The analysis revealed that the RNs appreciated blended learning. The web lectures facilitated learning and gave RNs access to the education at any time. However, according to the RNs, knowledge is gained through interaction between RNs and teachers, and this aspect needed to be improved. The RNs also thought that the content of the seminars on campus should focus on evidence-based nursing knowledge and practical skills, not just taught as stable facts and procedures. The result from the present study could help to improve the design and content of advanced nursing courses using a blended learning format.

  • 84. Ask, Anders
    et al.
    Björk-Eriksson, Thomas
    Zackrisson, Björn
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    The potential of proton beam radiation therapy in head and neck cancer2005Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, nr 8, s. 876-80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In head and neck cancer, including thyroid cancer, it is assessed that at least 300 patients annually will gain sufficiently from proton beam therapy, both to improve tumour control and to decrease toxicity to compensate for the increased treatment costs using protons.

  • 85. Ask, Anders
    et al.
    Johansson, Bengt
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    The potential of proton beam radiation therapy in gastrointestinal cancer2005Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, nr 8, s. 896-903Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In gastrointestinal cancers, it is assessed that at least 345 patients, mainly non-resectable rectal cancers, oesophageal and liver cancers, are eligible. Great uncertainties do however exist both in the number of patients with gastrointestinal cancers suitable for radiation therapy, and in the proportion of those where proton beams may give sufficiently better results.

  • 86. Asklund, Thomas
    et al.
    Malmstrom, Annika
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Bjor, Ove
    Henriksson, Roger
    Brain tumors in Sweden: Data from a population-based registry 1999-20122015Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, nr 3, s. 377-384Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. The Swedish brain tumor registry has, since it was launched in 1999, provided significant amounts of data on histopathological diagnoses and on important aspects of surgical and medical management of these patients. The purpose is mainly quality control, but also as a resource for research. Methods. Three Swedish healthcare regions, constituting 40% of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to SNOMED/WHO classification, symptoms, performance status, pre- and postoperative radiology, tumor size and localization, extent of surgery and occurrence of postoperative complications, postoperative treatment, such as radiotherapy and/or chemotherapy, other treatments, complications and toxicity, occurrence of reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse. Results. Surgical radicality has been essentially constant, whereas the use of early (within 72 hours) postoperative CT and MRI has increased, especially for high-grade glioma, which is a reflection of quality of surgery. Survival of patients with high-grade glioma has increased, especially in the age group 60-69. Patients aged 18-39 years had a five-year survival of 40%. Waiting times for the pathological report has been slightly prolonged. Geographical differences do exist for some of the variables. Conclusion. Population-based registration is valuable for assessment of clinical management, which could have impact on patient care. As a result of short survival and/or the propensity to affect cognitive functions this patient group has considerable difficulties to make their voices heard in society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.

  • 87.
    Aspenström, Pontus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Activated Rho GTPases in Cancer-The Beginning of a New Paradigm2018Ingår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, nr 12, artikel-id 3949Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Involvement of Rho GTPases in cancer has been a matter of debate since the identification of the first members of this branch of the Ras superfamily of small GTPases. The Rho GTPases were ascribed important roles in the cell, although these were restricted to regulation of cytoskeletal dynamics, cell morphogenesis, and cell locomotion, with initially no clear indications of direct involvement in cancer progression. This paradigm has been challenged by numerous observations that Rho-regulated pathways are often dysregulated in cancers. More recently, identification of point mutants in the Rho GTPases Rac1, RhoA, and Cdc42 in human tumors has finally given rise to a new paradigm, and we can now state with confidence that Rho GTPases serve as oncogenes in several human cancers. This article provides an expose of current knowledge of the roles of activated Rho GTPases in cancers.

  • 88.
    Assadian, Farzaneh
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Sandström, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Bondeson, Kåre
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Lidian, Adnan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Svensson, Catharina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Akusjärvi, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Bergqvist, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Punga, Tanel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Distribution and Molecular Characterization of Human Adenovirus and Epstein-Barr Virus Infections in Tonsillar Lymphocytes Isolated from Patients Diagnosed with Tonsillar Diseases2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 5, artikel-id e0154814Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Surgically removed palatine tonsils provide a conveniently accessible source of T and B lymphocytes to study the interplay between foreign pathogens and the host immune system. In this study we have characterised the distribution of human adenovirus (HAdV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in purified tonsillar T and B cell-enriched fractions isolated from three patient age groups diagnosed with tonsillar hypertrophy and chronic/recurrent tonsillitis. HAdV DNA was detected in 93 out of 111 patients (84%), while EBV DNA was detected in 58 patients (52%). The most abundant adenovirus type was HAdV-5 (68%). None of the patients were positive for HCMV. Furthermore, 43 patients (39%) showed a co-infection of HAdV and EBV. The majority of young patients diagnosed with tonsillar hypertrophy were positive for HAdV, whereas all adult patients diagnosed with chronic/recurrent tonsillitis were positive for either HAdV or EBV. Most of the tonsils from patients diagnosed with either tonsillar hypertrophy or chronic/recurrent tonsillitis showed a higher HAdV DNA copy number in T compared to B cell-enriched fraction. Interestingly, in the majority of the tonsils from patients with chronic/recurrent tonsillitis HAdV DNA was detected in T cells only, whereas hypertrophic tonsils demonstrated HAdV DNA in both T and B cell-enriched fractions. In contrast, the majority of EBV positive tonsils revealed a preference for EBV DNA accumulation in the B cell-enriched fraction compared to T cell fraction irrespective of the patients' age.

  • 89. Atienza-Párraga, Alba
    et al.
    Diamanti, Klev
    Nylund, Patrick
    Skaftason, Aron
    Ma, Anqi
    Jin, Jian
    Martín-Subero, José Ignacio
    Öberg, Fredrik
    Komorowski, Jan
    Jernberg-Wiklund, Helena
    Kalushkova, Antonia
    Epigenomic re-configuration of primary multiple myeloma underlies the synergistic effect of combined DNMT and EZH2 inhibition.Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Multiple myeloma (MM) is characterized by an overexpression of EZH2 and a subsequent increase in H3K27me3-mediated silencing. However, the genome-wide redistribution of this mark in context with other epigenetic tags remains largely unexplored. Here, we show that EZH2 physically interacts with DNMT1 and that combined inhibition leads to a reduced G2/M arrest and increased apoptosis in MM. In addition, we present a catalogue of the genomic regulatory regions in normal plasma cells (NPC) as defined by their individual combination of histone marks. We used ChIP-seq and ATAC-seq data to generate whole-genome NPC chromatin annotations which we further analysed using DNA methylation arrays and RNA-seq. Comparison between NPC and MM demonstrated that, despite the global hypomethylation, enhancers show a tendency towards a higher DNA methylation levels in MM, whereas Polycomb and heterochromatic sites, highly methylated in NPC, show intermediate levels of the mark. Across all examined regulatory regions, 5-azacytidine treatment strongly reduced DNA methylation in MM. Furthermore, we find an extensive re-structuration of the global histone patterns in MM. We noticed a widespread increase in H3K27me3 except at active TSSs/promoters and enhancers, where we found a selective gain of the mark, suggestive of a directed silencing. In contrast, poised TSSs lose H3K27me3 and gain the activation mark H3K27ac, reflecting potential activation. Taken together, we present a comprehensive map of the epigenomic changes in MM as compared to NPC and provide insights into the interplay between EZH2 and DNMT1 in MM.

  • 90.
    Aulin, Julia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Hijazi, Ziad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ezekowitz, Michael D.
    Lankenau Inst Med Res, Wynnewood, PA USA.;Ctr Heart, Wynnewood, PA USA..
    Andersson, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Connolly, Stuart J.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Huber, Kurt
    Dept Internal Med Cardiol & Emergency Med 3, Vienna, Austria..
    Reilly, Paul A.
    Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA..
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Oldgren, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation2015Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 170, nr 6, s. 1151-1160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Inflammation has been associated with cardiovascular disease and the burden of atrial fibrillation (AF). In this study we evaluate inflammatory biomarkers and future cardiovascular events in AF patients in the RE-LY study. Methods Interleukin-6 (IL-6), C-reactive protein (CRP) (n = 6,187), and fibrinogen (n = 4,893) were analyzed at randomization; outcomes were evaluated by Cox models and C-statistics. Results Adjusted for clinical risk factors IL-6 was independently associated with stroke or systemic embolism (P =.0041), major bleedings (P =.0001), vascular death (P<.0001), and a composite thromboembolic outcome (ischemic stroke, systemic embolism, myocardial infarction, pulmonary embolism and vascular death) (P<.0001). CRP was independently related to myocardial infarction (P =.0047), vascular death (P =.0004), and the composite thromboembolic outcome (P =.0001). When further adjusted for cardiac (troponin andN-terminal fragment B-type natriuretic peptide [NT-proBNP]) and renal (cystatin-C) biomarkers on top of clinical risk factors IL-6 remained significantly related to vascular death (P<.0001), major bleeding (P<.0170) and the composite thromboembolic outcome (P<.0001), and CRP to myocardial infarction (.0104). Fibrinogen was not associated with any outcome. C-index for stroke or systemic embolism increased from 0.615 to 0.642 (P =.0017) when adding IL-6 to the clinically used CHA(2)DS(2)-VASc risk score with net reclassification improvement of 28%. Conclusion In patients with AF, IL-6 is related to higher risk of stroke and major bleeding, and both markers are related to higher risk of vascular death and the composite of thromboembolic events independent of clinical risk factors. Adjustment for cardiovascular biomarkers attenuated the prognostic value, although IL-6 remained related to mortality, the composite of thromboembolic events, and major bleeding, and CRP to myocardial infarction.

  • 91. Avall-Lundqvist, Elisabeth
    et al.
    Staf, Christian
    Bjurberg, Maria
    Borgfeldt, Christer
    Dahm-Kahler, Pernilla
    Falconer, Henrik
    Holmberg, Erik
    Kjolhede, Preben
    Stålberg, Karin Glimskär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Rosenberg, Per
    Hogberg, Thomas
    A population-based study of pelvic serous carcinoma in Sweden: Primary site, FIGO stage and survival.2015Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, nr 15Artikel i tidskrift (Övrigt vetenskapligt)
  • 92.
    Babaei, Masoud
    et al.
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.;German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis NCT, Heidelberg, Germany..
    Balavarca, Yesilda
    German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis NCT, Heidelberg, Germany..
    Jansen, Lina
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany..
    Lemmens, Valery
    Netherlands Comprehens Canc Org IKNL, Utrecht, Netherlands.;Erasmus MC Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands..
    van Erning, Felice N.
    Netherlands Comprehens Canc Org IKNL, Utrecht, Netherlands.;Erasmus MC Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands..
    van Eycken, Liesbet
    Belgian Canc Registry, Brussels, Belgium..
    Vaes, Evelien
    Belgian Canc Registry, Brussels, Belgium..
    Sjövall, Annika
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Ulrich, Cornelia M.
    German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis NCT, Heidelberg, Germany.;Huntsman Canc Inst, Salt Lake City, UT USA.;Univ Utah, Salt Lake City, UT USA..
    Schrotz-King, Petra
    German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis NCT, Heidelberg, Germany..
    Brenner, Hermann
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.;German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis NCT, Heidelberg, Germany.;German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany..
    Administration of adjuvant chemotherapy for stage II-III colon cancer patients: An European population-based study2018Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, nr 7, s. 1480-1489Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The advantage of adjuvant chemotherapy (ACT) for treating Stage III colon cancer patients is well established and widely accepted. However, many patients with Stage III colon cancer do not receive ACT. Moreover, there are controversies around the effectiveness of ACT for Stage II patients. We investigated the administration of ACT and its association with overall survival in resected Stage II (overall and stratified by low-/high-risk) and Stage III colon cancer patients in three European countries including The Netherlands (2009-2014), Belgium (2009-2013) and Sweden (2009-2014). Hazard ratios (HR) for death were obtained by Cox regression models adjusted for potential confounders. A total of 60244 resected colon cancer patients with pathological Stages II and III were analyzed. A small proportion (range 9-24%) of Stage II and over half (range 55-68%) of Stage III patients received ACT. Administration of ACT in Stages II and III tumors decreased with higher age of patients. Administration of ACT was significantly associated with higher overall survival in high-risk Stage II patients (in The Netherlands (HR; 95%CI = 0.82 (0.67-0.99), Belgium (0.73; 0.59-0.90) and Sweden (0.58; 0.44-0.75)), and in Stage III patients (in The Netherlands (0.47; 0.43-0.50), Belgium (0.46; 0.41-0.50) and Sweden (0.48; 0.43-0.54)). In Stage III, results were consistent across subgroups including elderly patients. Our results show an association of ACT with higher survival among Stage III and high-risk Stage II colon cancer patients. Further investigations are needed on the selection criteria of Stages II and III colon cancer patients for ACT.

  • 93.
    Babaei, Masoud
    et al.
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, INF 581, Heidelberg, Germany..
    Jansen, Lina
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, INF 581, Heidelberg, Germany..
    Balavarca, Yesilda
    German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis, Heidelberg, Germany..
    Sjovall, Annika
    Karolinska Inst, Ctr Digest Dis, Stockholm, Sweden..
    Bos, Amanda
    Comprehens Canc Org Netherlands, Utrecht, Netherlands.;Erasmus MC Univ Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands..
    van de Velde, Tony
    Netherlands Canc Inst, Biometr Dept, Amsterdam, Netherlands..
    Moreau, Michel
    Inst Jules Bordet, Datactr, Brussels, Belgium..
    Liberale, Gabriel
    Inst Jules Bordet, Datactr, Brussels, Belgium..
    Goncalves, Ana Filipa
    Portuguese Oncol Inst Porto, Porto, Portugal..
    Bento, Maria Jose
    Portuguese Oncol Inst Porto, Porto, Portugal..
    Ulrich, Cornelia M.
    German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis, Heidelberg, Germany.;German Canc Res Ctr, German Canc Consortium, Heidelberg, Germany..
    Schrotz-King, Petra
    German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis, Heidelberg, Germany..
    Lemmens, Valery
    Comprehens Canc Org Netherlands, Utrecht, Netherlands.;Erasmus MC Univ Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands..
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Brenner, Hermann
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, INF 581, Heidelberg, Germany.;German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis, Heidelberg, Germany.;German Canc Res Ctr, German Canc Consortium, Heidelberg, Germany..
    Neoadjuvant Therapy in Rectal Cancer Patients With Clinical Stage II to III Across European Countries: Variations and Outcomes2018Ingår i: Clinical colorectal cancer, ISSN 1533-0028, Vol. 17, nr 1, s. E129-E142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study is the largest observational study on neoadjuvant therapy in patients with stage II & III rectal cancer by including high-quality data from large population-based and clinical cancer registries. We observed large variations in administration of neoadjuvant chemo(radio) therapy across European countries. Our results support major survival advantages of patients treated with neoadjuvant radiotherapy. Background: Neoadjuvant therapy improves survival of patients with clinical stage II and III rectal cancer in clinical trials. In this study, we investigated the administration of neoadjuvant radiotherapy (neo-RT) and neoadjuvant chemoradiotherapy (neo-CRT) and its association with survival in resected patients in 2 European countries (The Netherlands and Sweden) and at 3 specialist centers. Materials and Methods: Administration of neoadjuvant treatment (all registries) and overall survival after surgery in The Netherlands and Sweden were assessed. Hazard ratios (HRs) were obtained using Cox regression adjusted for potential confounders. Results: A total of 16,095 rectal cancer patients with clinical stage II and III were eligible for analyses. Large variations in administration of neo-RT and neo-CRT were observed. Elderly patients less often received neo-RT and neo-CRT. Patients with stage III disease received neo-CRT more frequently than neo-RT. Administration of neo-RT versus surgery without neoadjuvant treatment was significantly associated with improved survival in The Netherlands (HR, 0.62; 95% confidence interval [CI], 0.53-0.73) as well as in Sweden (HR, 0.79; 95% CI, 0.69-0.90). Administration of neo-CRT was associated with enhanced survival in The Netherlands (HR, 0.62; 95% CI, 0.50-0.78) but not in Sweden (HR, 0.97; 95% CI, 0.80-1.18). The mortality of patients treated with neo-CRT compared with neo-RT showed inconsistent results in population-based centers. Conclusions: Our results support an association of neo-RT with enhanced survival among stage II and III rectal cancer patients. Comparing neo-CRT with neo-RT, larger variations and inconsistent results with respect to survival were observed across centers.

  • 94.
    Backman, Samuel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Maharjan, Rajani
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Falk Delgado, Alberto
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Crona, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Cupisti, Kenko
    Marien Hosp, Dept Surg, Euskirchen, Germany..
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Björklund, Peyman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Global DNA Methylation Analysis Identifies Two Discrete clusters of Pheochromocytoma with Distinct Genomic and Genetic Alterations2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 44943Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pheochromocytomas and paragangliomas (PPGLs) are rare and frequently heritable neural-crest derived tumours arising from the adrenal medulla or extra-adrenal chromaffin cells respectively. The majority of PPGL tumours are benign and do not recur with distant metastases. However, a sizeable fraction of these tumours secrete vasoactive catecholamines into the circulation causing a variety of symptoms including hypertension, palpitations and diaphoresis. The genetic landscape of PPGL has been well characterized and more than a dozen genes have been described as recurrently mutated. Recent studies of DNA-methylation have revealed distinct clusters of PPGL that share DNA methylation patterns and driver mutations, as well as identified potential biomarkers for malignancy. However, these findings have not been adequately validated in independent cohorts. In this study we use an array-based genome-wide approach to study the methylome of 39 PPGL and 4 normal adrenal medullae. We identified two distinct clusters of tumours characterized by different methylation patterns and different driver mutations. Moreover, we identify genes that are differentially methylated between tumour subcategories, and between tumours and normal tissue.

  • 95.
    Backman, Samuel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Norlén, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Crona, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing2017Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, nr 2, s. 705-712Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.

    PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.

    RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.

    CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.

  • 96. Baecklund, Fredrik
    et al.
    Foo, Jia-Nee
    Bracci, Paige
    Darabi, Hatef
    Karlsson, Robert
    Hjalgrim, Henrik
    Rosenquist Brandell, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Hematologi och immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Adami, Hans-Olov
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Melbye, Mads
    Conde, Lucia
    Liu, Jianjun
    Humphreys, Keith
    Skibola, Christine F.
    Smedby, Karin E.
    A comprehensive evaluation of the role of genetic variation in follicular lymphoma survival2014Ingår i: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 15, s. 113-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Survival in follicular lymphoma (FL) is highly variable, even within prognostic groups defined by tumor grade and the Follicular Lymphoma International Prognostic Index. Studies suggest that germline single nucleotide polymorphisms (SNPs) may hold prognostic information but further investigation is needed. Methods: We explored the association between SNPs and FL outcome using two approaches: 1) Two independent genome-wide association studies (GWAS) of similar to 300.000 SNPs followed by a meta-analysis encompassing 586 FL patients diagnosed in Denmark/Sweden 1999-2002 and in the United States 2001-2006; and 2) Investigation of 22 candidate-gene variants previously associated with FL outcome in the Danish/Swedish cohort (N = 373). We estimated time to lymphoma-specific death (approach 1 and 2) and lymphoma progression (approach 2) with hazard ratios (HR) and 95% confidence intervals (CI) in a multivariable Cox regression model. Results: In the GWAS meta-analysis, using a random effects model, no variants were associated with lymphoma-specific death at a genome-wide significant level (p < 5.0x10(-8)). The strongest association was observed for tightly linked SNPs on 17q24 near the ABCA10 and ABCA6 genes (rs10491178 HRrandom = 3.17, 95% CI 2.09-4.79, prandom = 5.24x10(-8)). The ABCA10 and ABCA6 genes belong to a family of genes encoding for ABC transporter proteins, implicated in multidrug resistance. In line with a previous study, rs2466571 in CD46 (HR = 0.73, 95% CI 0.58-0.91, p = 0.006) showed nominal association with lymphoma progression, as did two highly linked SNPs in IL8 (rs4073 HR = 0.78, 95% CI 0.62-0.97, p = 0.02; rs2227307 HR = 0.75, 95% CI 0.60-0.94, p = 0.01) previously associated with overall survival. Conclusions: The results suggest a possible role for multidrug resistance in FL survival and add to the evidence that genetic variation in CD46 and IL8 may have prognostic implications in FL. Our findings need further confirmation in other independent populations or in a larger multicenter GWAS.

  • 97.
    Bager, Ninna
    et al.
    Aarhus Univ Hosp, Dept Paediat & Adolescent Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark.
    Juul-Dam, Kristian L.
    Aarhus Univ Hosp, Dept Paediat & Adolescent Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark.
    Sandahl, Julie D.
    Aarhus Univ Hosp, Dept Paediat & Adolescent Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark.
    Abrahamsson, Jonas
    Queen Silvia Childrens Hosp, Inst Clin Sci, Dept Paediat, Gothenburg, Sweden.
    Beverloo, Berna
    Erasmus MC Sophia Childrens Hosp, Dept Cytogenet, Rotterdam, Netherlands.
    de Bont, Eveline S. J. M.
    Univ Med Ctr Groningen, Dept Paediat, Groningen, Netherlands.
    Ha, Shau-Yin
    Queen Mary Hosp, Hong Kong Paediat Haematol & Oncol Study Grp, Dept Paediat, Hong Kong, Hong Kong, Peoples R China.
    Jahnukainen, Kirsi
    Univ Helsinki, Childrens Hosp, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Jonsson, Olafur G.
    Landspital Inn, Dept Paediat, Reykjavik, Iceland.
    Kaspers, Gertjan L.
    Vrije Univ Amsterdam Med Ctr, Paediat Oncol Haematol, Amsterdam, Netherlands;Acad Princess Maxima Ctr Paediat Oncol, Utrecht, Netherlands.
    Kovalova, Zhanna
    Childrens Clin Univ Hosp, Dept Paediat, Riga, Latvia.
    Lausen, Birgitte
    Univ Copenhagen, Rigshosp, Dept Paediat & Adolescent Med, Copenhagen, Denmark.
    De Moerloose, Barbara
    Ghent Univ Hosp, Dept Paediat, Ghent, Belgium.
    Noren-Nystroem, Ulrika
    Umea Univ Hosp, Dept Med Biosci, Genet, Umea, Sweden.
    Palle, Josefine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnneurologi/Barnonkologi.
    Saks, Kadri
    SA Tallinna Lastehaigla, Dept Paediat, Tallinn, Estonia.
    Zeller, Bernward
    Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway.
    Kjeldsen, Eigil
    Aarhus Univ Hosp, Dept Cytogenet, Aarhus, Denmark.
    Hasle, Henrik
    Aarhus Univ Hosp, Dept Paediat & Adolescent Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark.
    Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia: A NOPHO-DBH-AML study2018Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 183, nr 4, s. 618-628Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993-2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2.1 and 3.3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non-CK/non-MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event-free survival (EFS; hazard ratio [HR] 1.43, P = 0.03) and overall survival (OS; HR 1.48, P = 0.01). MK was associated with a poor EFS (HR 1.57, P = 0.03) but did not show an inferior OS compared to non-MK patients (HR 1.14, P = 0.62). In a large paediatric cohort, we characterized AML with non-recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.

  • 98.
    Baliakas, Panagiotis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hadzidimitriou, A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Xochelli, Aliki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sutton, L. A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Minga, E.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Scarfo, L.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Fdn Ctr San Raffaele, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Rossi, D.
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy..
    Davis, Z.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Agathangelidis, A.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Fdn Ctr San Raffaele, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Villamor, N.
    Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain..
    Parker, H.
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Kotaskova, J.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Stalika, E.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Plevova, K.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Mansouri, Larry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Cortese, Diego
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Navarro Lopez, A.
    Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain..
    Delgado, J.
    Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain..
    Larrayoz, M.
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Belessi, C.
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Smedby, K. E.
    Dept Med, Solna, Sweden.;Karolinska Inst, Clin Epidemiol Unit, Stockholm, Sweden..
    Juliusson, G.
    Lund Univ, Lund, Sweden.;Lund Stem Cell Ctr, Hosp Dept Hematol, Lund, Sweden..
    Strefford, J. C.
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Pospisilova, S.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Oscier, D.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Gaidano, G.
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy..
    Campo, E.
    Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain.;Univ Barcelona, Dept Pathol, Barcelona, Spain..
    Ghia, P.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Fdn Ctr San Raffaele, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    REFINING PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA WITH SOMATICALLY HYPERMUTATED B-CELL RECEPTORS: A NOVEL PROGNOSTIC INDEX ON BEHALF OF THE EUROPEAN RESEARCH INITIATIVE ON CLL (ERIC)2015Ingår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, s. 52-52Artikel i tidskrift (Övrigt vetenskapligt)
  • 99.
    Baliakas, Panagiotis
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hadzidimitriou, A
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sutton, Lesley Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rossi, D
    Minga, E
    Villamor, N
    Larrayoz, M
    Kminkova, J
    Agathangelidis, A
    Davis, Z
    Tausch, E
    Stalika, E
    Kantorova, B
    Mansouri, Larry
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Scarfò, L
    Cortese, Diego
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Navrkalova, V
    Rose-Zerilli, M J J
    Smedby, K E
    Juliusson, G
    Anagnostopoulos, A
    Makris, A M
    Navarro, A
    Delgado, J
    Oscier, D
    Belessi, C
    Stilgenbauer, S
    Ghia, P
    Pospisilova, S
    Gaidano, G
    Campo, E
    Strefford, J C
    Stamatopoulos, Kostas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Recurrent mutations refine prognosis in chronic lymphocytic leukemia2015Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 29, s. 329-336Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods.

  • 100.
    Baliakas, Panagiotis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Hadzidimitriou, Anastasia
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Sutton, Lesley-Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Minga, Eva
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Agathangelidis, Andreas
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Div Mol Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, I-20132 Milan, Italy..
    Nichelatti, Michele
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Tsanousa, Athina
    Aristotle Univ Thessaloniki, Dept Informat, GR-54006 Thessaloniki, Greece..
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Div Mol Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, I-20132 Milan, Italy..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, Xiao-Jie
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Shanafelt, Tait
    Mayo Clin, Div Hematol, Dept Med, Rochester, MN USA..
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Sandberg, Yorick
    Erasmus MC, Univ Med Ctr, Dept Immunol, Rotterdam, Netherlands..
    Vojdeman, Fie Juhl
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Boudjogra, Myriam
    Hop La Pitie Salpetriere, Serv Hematol Biol, Paris, France..
    Tzenou, Tatiana
    Univ Athens, Dept Propaedeut Med, Athens, Greece..
    Chatzouli, Maria
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Chu, Charles C.
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Gardiner, Anne
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Mansouri, Larry
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Pedersen, Lone Bredo
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    van Lom, Kirsten
    Erasmus MC, Univ Med Ctr, Dept Hematol, Rotterdam, Netherlands..
    Giudicelli, Veronique
    Univ Montpellier, IMGT Int ImMunoGeneT Informat Syst, LIGM, Inst Genet Humaine, F-34059 Montpellier, France..
    Francova, Hana Skuhrova
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Nguyen-Khac, Florence
    Hop La Pitie Salpetriere, Serv Hematol Biol, Paris, France..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med, Athens, Greece..
    Juliusson, Gunnar
    Lund Univ & Hosp, Dept Hematol, Lund Stem Cell Ctr, Lund, Sweden..
    Angelis, Lefteris
    Aristotle Univ Thessaloniki, Dept Informat, GR-54006 Thessaloniki, Greece..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Lefranc, Marie-Paule
    Univ Montpellier, IMGT Int ImMunoGeneT Informat Syst, LIGM, Inst Genet Humaine, F-34059 Montpellier, France..
    Facco, Monica
    Univ Padua, Sch Med, Dept Med, Hematol & Clin Immunol Branch, I-35100 Padua, Italy.;Venetian Inst Mol Med, Padua, Italy..
    Trentin, Livio
    Univ Padua, Sch Med, Dept Med, Hematol & Clin Immunol Branch, I-35100 Padua, Italy.;Venetian Inst Mol Med, Padua, Italy..
    Catherwood, Mark
    Belfast City Hosp, Dept Haematooncol, Belfast BT9 7AD, Antrim, North Ireland..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Geisler, Christian H.
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Langerak, Anton W.
    Erasmus MC, Univ Med Ctr, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Chiorazzi, Nicholas
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Jelinek, Diane F.
    Mayo Clin, Dept Immunol, Dept Med, Rochester, MN USA..
    Darzentas, Nikos
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Belessi, Chrysoula
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, Frederic
    Hop La Pitie Salpetriere, Serv Hematol Biol, Paris, France..
    Rosenquist Barndell, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Div Mol Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, I-20132 Milan, Italy..
    Stamatopoulos, Kostas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study2014Ingår i: LANCET HAEMATOLOGY, ISSN 2352-3026, Vol. 1, nr 2, s. E74-E84Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn. Methods For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data were available. These patients were followed up in 15 academic institutions throughout Europe (in Czech Republic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collected between June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptor immunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressing unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome of our analysis was time to first treatment, defined as the time between diagnosis and date of first treatment. Findings 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 major subsets. Stereotyped subsets showed significant differences in terms of age, sex, disease burden at diagnosis, CD38 expression, and cytogenetic aberrations of prognostic significance. Patients within a specific subset generally followed the same clinical course, whereas patients in different stereotyped subsets-despite having the same immunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status-showed substantially different times to first treatment. By integrating B-cell receptor immunoglobulin stereotypy (for subsets 1, 2, and 4) into the well established Dohner cytogenetic prognostic model, we showed these, which collectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separate clinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2). Interpretation The molecular classification of chronic lymphocytic leukaemia based on B-cell receptor immunoglobulin stereotypy improves the Dohner hierarchical model and refines prognostication beyond immunoglobulin mutational status, with potential implications for clinical decision making, especially within prospective clinical trials.

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