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  • 51.
    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.
    Moysiadis, Theodoros
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Hadzidimitriou, Anastasia
    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. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    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. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Jeromin, Sabine
    MLL Munich Leukemia Lab, Munich, Germany.
    Agathangelidis, Andreas
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    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.
    Sutton, Lesley Ann
    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.
    Minga, Eva
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Scarfo, Lydia
    IRCCS Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Rossi, Davide
    Oncol Inst Southern Switzerland, Bellinzona, Switzerland.
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England.
    Villamor, Neus
    Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain.
    Parker, Helen
    Univ Southampton, Canc Res UK Ctr, Acad Unit Canc Sci, Canc Genon, Southampton, Hants, England;Univ Southampton, Fac Med, Expt Canc Med Ctr, Southampton, Hants, England.
    Kotaskova, Jana
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic;Univ Hosp Brno, Brno, Czech Republic.
    Stalika, Evangelia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece;G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic;Univ Hosp Brno, Brno, Czech Republic.
    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.
    Cortese, Diego
    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.
    Navarro, Alba
    Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain.
    Delgado, Julio
    Hosp Clin Barcelona, Hematol Dept, Barcelona, Spain.
    Larrayoz, Marta
    Univ Southampton, Canc Res UK Ctr, Acad Unit Canc Sci, Canc Genon, Southampton, Hants, England;Univ Southampton, Fac Med, Expt Canc Med Ctr, Southampton, Hants, England.
    Young, Emma
    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.
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.
    Juliusson, Gunnar
    Lund Univ & Hosp, Lund Stem Cell Ctr, Dept Hematol, Lund, Sweden.
    Sheehy, Oonagh
    Belfast City Hosp, Dept Hematooncol, Belfast, Antrim, North Ireland.
    Catherwood, Mark
    Belfast City Hosp, Dept Hematooncol, Belfast, Antrim, North Ireland.
    Strefford, Jonathan C.
    Univ Southampton, Canc Res UK Ctr, Acad Unit Canc Sci, Canc Genon, Southampton, Hants, England;Univ Southampton, Fac Med, Expt Canc Med Ctr, Southampton, Hants, England.
    Stavroyianni, Niki
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
    Belessi, Chrysoula
    Nikea Gen Hosp, Hematol Dept, Piraeus, Greece.
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic;Univ Hosp Brno, Brno, Czech Republic.
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England.
    Gaidano, Gianluca
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy.
    Campo, Elias
    Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain;Univ Barcelona, Dept Pathol, Barcelona, Spain.
    Haferlach, Claudia
    MLL Munich Leukemia Lab, Munich, Germany.
    Ghia, Paolo
    IRCCS Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Rosenquist, Richard
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Stamatopoulos, Kostas
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.
    Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia2019Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 104, nr 2, s. 360-369Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to first -treatment and a treatment probability at Five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or ST3B1 mutations were associated with the shortest time-to-First treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.

  • 52.
    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.
    Puiggros, A.
    Hosp del Mar, Lab Citogenet Mol, Serv Patol, Barcelona, Spain.;Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain..
    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, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nguyen-Khac, F.
    Univ Paris 06, Hop Pitie Salpetriere, Hematol Dept, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Gardiner, A.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Plevova, K.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Ortega, M.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Hosp Univ Vall dHebron, Barcelona, Spain..
    Collado, R.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Consorcio Hosp Gen Univ Valencia, Valencia, Spain..
    Gonzalez, T.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Fdn Publ Galega Med Xen, Santiago De Compostela, Spain..
    Granada, I.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Hosp Badalona Germans Trias & Pujol, Badalona, Spain..
    Luno, E.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Hosp Univ Cent Asturias, Oviedo, Spain..
    Kotaskova, J.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Davis, Z.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Strefford, J.
    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..
    Davi, F.
    Univ Paris 06, Hop Pitie Salpetriere, Hematol Dept, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Athanasiadou, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Rosenquist, Richard Brandell
    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.
    Oscier, D.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Sola, B. Espinet
    Hosp del Mar, Lab Citogenet Mol, Serv Patol, Barcelona, Spain.;Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    ADDITIONAL TRISOMIES AMONGST PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA CARRYING TRISOMY 12: THE PARTNER CHROMOSOME MAKES A DIFFERENCE2015Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, s. 224-224Artikkel i tidsskrift (Annet vitenskapelig)
  • 53.
    Baliakas, Panagiotis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Puiggros, Anna
    Hosp Mar, Lab Citogenet Mol Servei Patol, Barcelona, Spain.;IMIM Hosp Mar, Canc Res Program, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Xochelli, Aliki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Sutton, Lesley-Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Nguyen-Khac, Florence
    Hop La Pitie Salpetriere, AP HP, Dept Hematol, Paris, France.;Univ Paris 06, UMRS 1138, Paris, France..
    Gardiner, Anne
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Plevova, Karla
    Univ Hosp Brno, Brno, Czech Republic..
    Minga, Eva
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Hadzidimitriou, Anastasia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Walewska, Renata
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    McCarthy, Helen
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Ortega, Margarita
    Hosp Univ Vall Hebron, Barcelona, Spain..
    Collado, Rosa
    Consorcio Hosp Gen Univ Valencia, Valencia, Spain..
    Gonzalez, Teresa
    Fdn Publ Galega Med Xenom, Santiago De Compostela, Spain..
    Granada, Isabel
    Univ Autonoma Barcelona, ICO Hosp Gerans Trias & Pujol, Inst Recerca Leucemia Josep Carreras IJC, Badalona, Spain..
    Luno, Elisa
    Hosp Univ Cent Asturias, Oviedo, Spain..
    Kotaskova, Jana
    Masaryk Univ, Cent European Inst Technol, CS-60177 Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Moysiadis, Theodoros
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Davis, Zadie
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Strefford, Jonathan C.
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, CS-60177 Brno, Czech Republic..
    Davi, Frederic
    Athanasiadou, Anastasia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Espinet, Blanca
    Hosp Mar, Lab Citogenet Mol Servei Patol, Barcelona, Spain.;IMIM Hosp Mar, Canc Res Program, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Additional trisomies amongst patients with chronic lymphocytic leukemia carrying trisomy 12: the accompanying chromosome makes a difference2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, nr 7, s. 299-302Artikkel i tidsskrift (Fagfellevurdert)
  • 54.
    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.
    Strefford, Jonathan C.
    Bikos, Vasilis
    Parry, Marina
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Oscier, David
    Splenic marginal-zone lymphoma: ontogeny and genetics2015Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 56, nr 2, s. 301-310Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Splenic marginal-zone lymphoma (SMZL) is a rare tumor that has recently emerged as a prototype for how the interplay between genetics and environment shapes the natural history of lymphomas. Indeed, the recent identification of molecular immunogenetic subgroups within SMZL may prove to be relevant not only for the sub-classification of the disease but also for improved understanding of the underlying biology. In contrast to other B-cell lymphomas, SMZL lacks a characteristic genetic lesion, although the majority of cases harbor genomic aberrations, as recently revealed by high-throughput studies that identified recurrent genetic aberrations, several in pathways related to marginal-zone differentiation and B-cell signaling. Here we provide an overview of recent research into the molecular and cellular biology of SMZL and related disorders, with special emphasis on immunogenetics and genomic aberrations, and discuss the value of molecular and cellular markers for the diagnosis and differential diagnosis of these entities.

  • 55.
    Baliakas, Panagiotis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Xochelli, Aliki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. ;G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Minga, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Karavalakis, G.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Athanasiadou, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Stalika, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Douka, V.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Protopappa, M.
    Gen Hosp Serres, Hematol Dept, Serres, Greece..
    Mpanti, A.
    Papageorgiou Hosp, Dept Hematol, Thessaloniki, Greece..
    Kotsianidis, I.
    Democritus Univ Thrace, Dept Hematol, Alexandroupolis, Greece..
    Papaioannou, M.
    Aristotle Univ Thessaloniki, AHEPA Hosp, Dept Hematol, Thessaloniki, Greece..
    Stavroyianni, N.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    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..
    Hadzidimitriou, A.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Hypogammaglobulinemia In Chronic Lymphocytic Leukemia: Clinicobiological Associations2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, s. 438-438Artikkel i tidsskrift (Annet vitenskapelig)
  • 56.
    Ballesteros, J.
    et al.
    Vivia Biotech, Tres Cantos, Spain..
    Scarfo, L.
    Univ Vita Salute San Raffaele, Milan, Italy.;Osped San Raffaele, Milan, Italy..
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Xochelli, A.
    Ctr Res & Technol Hellas, Thessaloniki, Greece..
    Ranghetti, P.
    Univ Vita Salute San Raffaele, Milan, Italy.;Osped San Raffaele, Milan, Italy..
    Primo, D.
    Vivia Biotech, Tres Cantos, Spain..
    Robles, A.
    Vivia Biotech, Tres Cantos, Spain..
    Gorrochategui, J.
    Vivia Biotech, Tres Cantos, Spain..
    Martinez Lopez, J.
    Hosp 12 Octubre, Madrid, Spain..
    de la Serna, J.
    Hosp 12 Octubre, Madrid, Spain..
    Gonzalez, M.
    Hosp Clin Univ Salamanca, Salamanca, Spain..
    Munugalavadla, V.
    Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA..
    Tannheimer, S.
    Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA..
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Stamatopoulos, K.
    Ctr Res & Technol Hellas, Thessaloniki, Greece..
    Ghia, P.
    Univ Vita Salute San Raffaele, Milan, Italy.;Osped San Raffaele, Milan, Italy..
    Ex Vivo Lymph Node Native Microenvironment Assay Shows Novel Antiproliferative Activity For Idelalisib And Ibrutinib On Cll Cells2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, s. 426-426Artikkel i tidsskrift (Annet vitenskapelig)
  • 57.
    Ballesteros, Joan
    et al.
    Vivia Biotech, Madrid, Spain..
    Scarfo, Lydia
    Ist Sci San Raffaele, Unit Lymphoid Malignancies, Dept Oncohematol, I-20132 Milan, Italy..
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Xochelli, Aliki
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Ranghetti, Pamela
    Univ Vita Salute San Raffaele, Milan, Italy.;Osped San Raffaele, Madrid, Spain..
    Primo, Daniel
    Vivia Biotech, Madrid, Spain..
    Robles, Alicia
    Vivia Biotech, Madrid, Spain..
    Gorrochategui, Julian
    Vivia Biotech, Madrid, Spain..
    Martinez-Lopez, Joaquin
    Hosp Univ 12 Octubre, Madrid, Spain..
    De la Serna, Javier
    Hosp Univ 12 Octubre, Madrid, Spain..
    Gonzalez, Marcos
    Hosp Clin Univ Salamanca, Salamanca, Spain..
    Munugalavadla, Veerendra
    Gilead Sci, Foster City, CA USA..
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Stamatopoulos, Kostas
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Queva, Christophe
    Gilead Sci, Foster City, CA USA..
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS Ist Sci San Raffaele, Milan, Italy..
    An Innovative High-Throughput Ex Vivo Drug Assay Incorporating the Native Microenvironment Reveals a Novel Mechanism of Action of Idelalisib in CLL2015Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, nr 23Artikkel i tidsskrift (Annet vitenskapelig)
  • 58. Barrington, Sally F
    et al.
    Kirkwood, Amy A
    Franceschetto, Antonella
    Fulham, Michael J
    Roberts, Thomas H
    Almquist, Helén
    Brun, Eva
    Hjorthaug, Karin
    Viney, Zaid N
    Pike, Lucy C
    Federico, Massimo
    Luminari, Stefano
    Radford, John
    Trotman, Judith
    Fosså, Alexander
    Berkahn, Leanne
    Molin, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    D'Amore, Francesco
    Sinclair, Donald A
    Smith, Paul
    O'Doherty, Michael J
    Stevens, Lindsey
    Johnson, Peter W
    PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.2016Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, nr 12, s. 1531-1538Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

  • 59.
    Baskaran, Sathish
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Almstedt, Elin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Hansson, Caroline
    Sahlgrenska Cancer Center, Institute of Medicine, Gothenburg, Sweden.
    Kalushkova, Antonia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Atienza Párraga, Alba
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Spyrou, Argyris
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Forsberg Nilsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Jernberg Wiklund, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Elfineh, Lioudmila
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Weishaupt, Holger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Kundu, Soumi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Krona, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Nelander, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    ZBTB16 orchestrates growth and invasion in glioblastomaManuskript (preprint) (Annet vitenskapelig)
  • 60. Baumann, Pia
    et al.
    Nyman, Jan
    Hoyer, Morten
    Wennberg, Berit
    Gagliardi, Giovanna
    Lax, Ingmar
    Drugge, Ninni
    Ekberg, Lars
    Friesland, Signe
    Johansson, Karl-Axel
    Lund, Jo-Asmund
    Morhed, Elisabeth
    Nilsson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Levin, Nina
    Paludan, Merete
    Sederholm, Christer
    Traberg, Anders
    Wittgren, Lena
    Lewensohn, Rolf
    Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy.2009Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 27, nr 20, s. 3290-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The impact of stereotactic body radiotherapy (SBRT) on 3-year progression-free survival of medically inoperable patients with stage I non-small-cell lung cancer (NSCLC) was analyzed in a prospective phase II study.

    PATIENTS AND METHODS: Fifty-seven patients with T1NOMO (70%) and T2N0M0 (30%) were included between August 2003 and September 2005 at seven different centers in Sweden, Norway, and Denmark and observed up to 36 months. SBRT was delivered with 15 Gy times three at the 67% isodose of the planning target volume.

    RESULTS: Progression-free survival at 3 years was 52%. Overall- and cancer-specific survival at 1, 2, and 3 years was 86%, 65%, 60%, and 93%, 88%, 88%, respectively. There was no statistically significant difference in survival between patients with T1 or T2 tumors. At a median follow-up of 35 months (range, 4 to 47 months), 27 patients (47%) were deceased, seven as a result of lung cancer and 20 as a result of concurrent disease. Kaplan-Meier estimated local control at 3 years was 92%. Local relapse was observed in four patients (7%). Regional relapse was observed in three patients (5%). Nine patients (16%) developed distant metastases. The estimated risk of all failure (local, regional, or distant metastases) was increased in patients with T2 (41%) compared with those with T1 (18%) tumors (P = .027).

    CONCLUSION: With a 3-year local tumor control rate higher than 90% with limited toxicity, SBRT emerges as state-of-the-art treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances.

  • 61.
    Berglund, Åke
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Ullen, Anders
    Karolinska Univ Hosp, Dept Oncol, Solna, Sweden..
    Lisyanskaya, Alla
    City Clin Oncol Ctr, St Petersburg State Healthcare Inst, St Petersburg, Russia..
    Orlov, Sergey
    St Petersburg State Med Univ, State Educ Inst Higher Profess Educ, St Petersburg, Russia..
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Tholander, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Lewensohn, Rolf
    Karolinska Univ Hosp, Dept Oncol, Solna, Sweden..
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Spira, Jack
    Oncopeptides AB, Stockholm, Sweden..
    Harmenberg, Johan
    Oncopeptides AB, Stockholm, Sweden..
    Jerling, Markus
    Oncopeptides AB, Stockholm, Sweden..
    Alvfors, Carina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ringbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Nordstrom, Eva
    Oncopeptides AB, Stockholm, Sweden..
    Soderlind, Karin
    Oncopeptides AB, Stockholm, Sweden..
    Gullbo, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies2015Inngår i: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 33, nr 6, s. 1232-1241Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose Melflufen (melphalan flufenamide, previously designated J1) is an optimized and targeted derivative of melphalan, hydrolyzed by aminopeptidases overexpressed in tumor cells resulting in selective release and trapping of melphalan, and enhanced activity in preclinical models. Methods This was a prospective, single-armed, open-label, first-in-human, dose-finding phase I/IIa study in 45 adult patients with advanced and progressive solid tumors without standard treatment options. Most common tumor types were ovarian carcinoma (n = 20) and non-small-cell lung cancer (NSCLC, n = 11). Results In the dose-escalating phase I part of the study, seven patients were treated with increasing fixed doses of melflufen (25-130 mg) Q3W. In the subsequent phase IIa part, 38 patients received in total 115 cycles of therapy at doses of 30-75 mg. No dose-limiting toxicities (DLTs) were observed at 25 and 50 mg; at higher doses DLTs were reversible neutropenias and thrombocytopenias, particularly evident in heavily pretreated patients, and the recommended phase II dose (RPTD) was set to 50 mg. Response Evaluation Criteria In Solid Tumors (RECIST) evaluation after 3 cycles of therapy (27 patients) showed partial response in one (ovarian cancer), and stable disease in 18 patients. One NSCLC patient received nine cycles of melflufen and progressed after 7 months of therapy. Conclusions In conclusion, melflufen can safely be given to cancer patients, and the toxicity profile was as expected for alkylating agents; RPTD is 50 mg Q3W. Reversible and manageable bone marrow suppression was identified as a DLT. Clinical activity is suggested in ovarian cancer, but modest activity in treatment of refractory NSCLC.

  • 62.
    Bergqvist, Michael
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Umea Univ, Dept Radiat Sci, Umea, Sweden.
    Holgersson, Georg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Bondarenko, Igor
    Grechanaya, Elena
    Maximovich, Alexey
    Andor, György
    Klockare, Maria
    Thureson, Marcus
    Jerling, Markus
    Harmenberg, Johan
    Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer2017Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, nr 3, s. 441-447Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT).

    MATERIAL AND METHODS: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m(2) in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles.

    RESULTS: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL.

    CONCLUSION: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.

  • 63.
    Bernatsky, Sasha
    et al.
    McGill Univ, Ctr Hlth, Res Inst, Div Clin Epidemiol, Montreal, PQ, Canada.
    Garcia, Hector A. Velasquez
    Univ British Columbia, BC Canc Res Ctr, Vancouver, BC, Canada;Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada.
    Spinelli, John J.
    Univ British Columbia, BC Canc Res Ctr, Vancouver, BC, Canada;Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada.
    Gaffney, Patrick
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Smedby, Karin E.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden;Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden.
    Ramsey-Goldman, Rosalind
    Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
    Wang, Sophia S.
    Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA USA.
    Adami, Hans-Olov
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
    Albanes, Demetrius
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
    Angelucci, Emanuele
    Osped Oncol Riferimento Reg A Businco, Hematol Unit, Cagliari, Italy.
    Ansell, Stephen M.
    Mayo Clin, Dept Med, Rochester, MN USA.
    Asmann, Yan W.
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA.
    Becker, Nikolaus
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
    Benavente, Yolanda
    Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Programme, Barcelona, Spain.
    Berndt, Sonja I.
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
    Bertrand, Kimberly A.
    Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
    Birmann, Brenda M.
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Boeing, Heiner
    German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany.
    Boffetta, Paolo
    Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
    Bracci, Paige M.
    Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
    Brennan, Paul
    Int Agcy Res Canc, Lyon, France.
    Brooks-Wilson, Angela R.
    BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada.
    Cerhan, James R.
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
    Chanock, Stephen J.
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
    Clavel, Jacqueline
    Ctr Res Epidemiol & Stat Sorbonne Paris Cite CRES, INSERM, Epidemiol Childhood & Adolescent Canc Grp, Paris, France.
    Conde, Lucia
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA;Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
    Cotenbader, Karen H.
    Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA.
    Cox, David G.
    Ctr Leon Berard, INSERM, Canc Res Ctr Lyon, U1052, Lyon, France.
    Cozen, Wendy
    Univ Southern Calif, USC Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
    Crouch, Simon
    Univ York, Dept Hlth Sci, York, N Yorkshire, England.
    De Roos, Anneclaire J.
    Drexel Univ, Dornsife Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA.
    de Sanjose, Silvia
    Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Programme, Barcelona, Spain;CIBERESP, Barcelona, Spain.
    Di Lollo, Simonetta
    Univ Florence, Dept Surg & Translat Med, Sect Anatomopathol, Florence, Italy.
    Diver, W. Ryan
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
    Dogan, Ahmet
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA;Mem Sloan Kettering Canc Ctr, Dept Lab Med, 1275 York Ave, New York, NY 10021 USA;Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
    Foretova, Lenka
    Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic;MF MU, Brno, Czech Republic.
    Ghesquieres, Herve
    Ctr Leon Berard, Dept Hematol, Lyon, France.
    Giles, Graham G.
    Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Habermann, Thomas M.
    Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA.
    Haioun, Corinne
    Henri Mondor Hosp, Lymphoid Malignancies Unit, Creteil, France;Univ Paris Est, Creteil, France.
    Hartge, Patricia
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
    Hjalgrim, Henrik
    Statens Serum Inst, Dept Epidemiol Res, Div Hlth Surveillance & Res, Copenhagen, Denmark.
    Holford, Theodore R.
    Yale Sch Publ Hlth, Dept Biostat, New Haven, CT USA.
    Holly, Elizabeth A.
    Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
    Jackson, Rebecca D.
    Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
    Kaaks, Rudolph
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
    Kane, Eleanor
    Univ York, Dept Hlth Sci, York, N Yorkshire, England.
    Kelly, Rachel S.
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Klein, Robert J.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.
    Kraft, Peter
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
    Kricker, Anne
    Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW, Australia.
    Lan, Qing
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
    Lawrence, Charles
    Westat Corp, Rockville, MD USA.
    Liebow, Mark
    Mayo Clin, Dept Med, Rochester, MN USA.
    Lightfoot, Tracy
    Univ York, Dept Hlth Sci, York, N Yorkshire, England.
    Link, Brian K.
    Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA.
    Maynadie, Marc
    Univ Bourgogne Franche Comte, Registre Hemopathies Malignes Cote Or, EA 4184, Dijon, France;Dijon Univ Hosp, Dijon, France.
    Mckay, James
    Int Agcy Res Canc, Lyon, France.
    Melbye, Mads
    Statens Serum Inst, Dept Epidemiol Res, Div Hlth Surveillance & Res, Copenhagen, Denmark.
    Molina, Thierry J.
    Univ Paris 05, Sorbonne Paris Cite, Necker Enfants Malad, AP HP,Dept Pathol, Paris, France.
    Monnereau, Alain
    Ctr Res Epidemiol & Stat Sorbonne Paris Cite CRES, INSERM, Epidemiol Childhood & Adolescent Canc Grp, Paris, France.
    Morton, Lindsay M.
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
    Nieters, Alexandra
    Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany.
    North, Kari E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
    Novak, Anne J.
    Mayo Clin, Dept Med, Rochester, MN USA.
    Offit, Kenneth
    Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
    Purdue, Mark P.
    Ontario Hlth Study, Toronto, ON, Canada.
    Rais, Marco
    Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Monserrato, Italy.
    Riby, Jacques
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA;Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
    Roman, Eve
    Univ York, Dept Hlth Sci, York, N Yorkshire, England.
    Rothman, Nathaniel
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
    Salles, Gilles
    Hosp Civils Lyon, Dept Hematol, Pierre Benite, France.
    Severi, Gianluca
    Human Genet Fdn, Turin, Italy.
    Severson, Richard K.
    Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
    Skibola, Christine F.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA;Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
    Slager, Susan L.
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
    Smith, Alex
    Univ York, Dept Hlth Sci, York, N Yorkshire, England.
    Smith, Martyn T.
    Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
    Southey, Melissa C.
    Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
    Staines, Anthony
    Dublin City Univ, Sch Nursing & Human Sci, Dublin, Ireland.
    Teras, Lauren R.
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
    Thompson, Carrie A.
    Mayo Clin, Dept Med, Rochester, MN USA.
    Tilly, Herve
    Univ Rouen, Ctr Heni Becquerel, Rouen, France.
    Tinker, Lesley F.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
    Tjonneland, Anne
    Danish Canc Soc, Res Ctr, Copenhagen, Denmark.
    Turner, Jenny
    Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW, Australia.
    Vajdic, Claire M.
    Univ New South Wales, Ctr Big Data Res Hlth, Sydney, NSW, Australia.
    Vermeulen, Roel C. H.
    Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
    Vijai, Joseph
    Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
    Vineis, Paolo
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England.
    Virtamo, Jarmo
    Natl Inst Hlth & Welf, Chron Dis Prevent Unit, Helsinki, Finland.
    Wang, Zhaoming
    St Jude Childrens Res Hosp, Dept Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA.
    Weinstein, Stephanie
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
    Witzig, Thomas E.
    Mayo Clin, Dept Med, Rochester, MN USA.
    Zelenetz, Andrew
    Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
    Zeleniuch-Jacquotte, Anne
    NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
    Zhang, Yawei
    Yale Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA.
    Zheng, Tongzhang
    Brown Sch Publ Hlth, Dept Epidemiol, Providence, RI USA.
    Zucca, Mariagrazia
    Univ Cagliari, Dept Biomed Sci, Monserrato, Italy.
    Clarke, Ann E.
    Univ Calgary, Div Rheumatol, Calgary, AB, Canada.
    Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma2017Inngår i: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 4, nr 1, artikkel-id UNSP e000187Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.

  • 64.
    Berndt, Sonja I.
    et al.
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Camp, Nicola J.
    Huntsman Canc Inst, Dept Internal Med, Div Hematol & Hematol Malignancies, Salt Lake City, UT 84112 USA.;Univ Utah, Sch Med, Salt Lake City, UT 84112 USA..
    Skibola, Christine F.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.;Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35233 USA.;Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA..
    Vijai, Joseph
    Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA..
    Wang, Zhaoming
    NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Gaithersburg, MD 20877 USA..
    Gu, Jian
    Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA..
    Nieters, Alexandra
    Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79108 Freiburg, Baden Wurttembe, Germany..
    Kelly, Rachel S.
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London W2 1PG, England..
    Smedby, Karin E.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, S-17176 Stockholm, Sweden..
    Monnereau, Alain
    Sorbonne Paris Cite CRESS, INSERM, Ctr Res Epidemiol & Stat, Epidemiol Childhood & Adolescent Canc Grp, F-94807 Paris, France.;Univ Paris 05, F-75270 Paris, France.;Inst Bergonie, Registre Hemopathies Malignes Gironde, F-33076 Bordeaux, France..
    Cozen, Wendy
    Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.;Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA..
    Cox, Angela
    Univ Sheffield, Dept Oncol, Sheffield S10 1NS, S Yorkshire, England..
    Wang, Sophia S.
    City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Duarte, CA 91030 USA..
    Lan, Qing
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Teras, Lauren R.
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA..
    Machado, Moara
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.;Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, BR-31270901 Belo Horizonte, MG, Brazil..
    Yeager, Meredith
    NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Gaithersburg, MD 20877 USA..
    Brooks-Wilson, Angela R.
    BC Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.;Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada..
    Hartge, Patricia
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Purdue, Mark P.
    Ontario Hlth Study, Toronto, ON M5G 0A3, Canada..
    Birmann, Brenda M.
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA 02115 USA..
    Vajdic, Claire M.
    Univ New S Wales, Ctr Big Data Res Hlth, Sydney, NSW 2052, Australia..
    Cocco, Pierluigi
    Univ Cagliari, Dept Publ Hlth Clin & Mol Med, I-09042 Cagliari, Italy..
    Zhang, Yawei
    Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA..
    Giles, Graham G.
    Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia.;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia..
    Zeleniuch-Jacquotte, Anne
    NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA.;NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA.;NYU, Langone Med Ctr, Perlmutter Canc Ctr, New York, NY 10016 USA..
    Lawrence, Charles
    WESTAT Corp, Rockville, MD 20850 USA..
    Montalvan, Rebecca
    WESTAT Corp, Rockville, MD 20850 USA..
    Burdett, Laurie
    NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Gaithersburg, MD 20877 USA..
    Hutchinson, Amy
    NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Gaithersburg, MD 20877 USA..
    Ye, Yuanqing
    Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA..
    Call, Timothy G.
    Mayo Clin, Div Hematol, Rochester, MN 55905 USA..
    Shanafelt, Tait D.
    Mayo Clin, Dept Med, Rochester, MN 55905 USA..
    Novak, Anne J.
    Mayo Clin, Dept Med, Rochester, MN 55905 USA..
    Kay, Neil E.
    Mayo Clin, Div Hematol, Rochester, MN 55905 USA..
    Liebow, Mark
    Mayo Clin, Dept Med, Rochester, MN 55905 USA..
    Cunningham, Julie M.
    Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA..
    Allmer, Cristine
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA..
    Hjalgrim, Henrik
    Statens Serum Inst, Div Hlth Surveillance & Res, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark..
    Adami, Hans-Olov
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Melbye, Mads
    Statens Serum Inst, Div Hlth Surveillance & Res, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.;Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA..
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Chang, Ellen T.
    Exponent Inc, Ctr Epidemiol & Computat Biol, Hlth Sci, Menlo Pk, CA 94025 USA.;Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA..
    Glenn, Martha
    Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT 84112 USA..
    Curtin, Karen
    Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84108 USA..
    Cannon-Albright, Lisa A.
    Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84108 USA.;Vet Affairs Med Ctr, George E Wahlen Dept, Salt Lake City, UT 84148 USA..
    Diver, W. Ryan
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA..
    Link, Brian K.
    Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA..
    Weiner, George J.
    Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA..
    Conde, Lucia
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.;Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35233 USA.;Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA..
    Bracci, Paige M.
    Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA..
    Riby, Jacques
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.;Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35233 USA.;Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA..
    Arnett, Donna K.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.;Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35233 USA..
    Zhi, Degui
    Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35233 USA..
    Leach, Justin M.
    Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35233 USA..
    Holly, Elizabeth A.
    Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA..
    Jackson, Rebecca D.
    Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA..
    Tinker, Lesley F.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98117 USA..
    Benavente, Yolanda
    Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Programme, Barcelona 08908, Spain.;CIBER Epidemiol & Salud Publ CIBERESP, Barcelona 08036, Spain..
    Sala, Nuria
    Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona 08908, Spain.;Catalan Inst Oncol IDIBELL, Translat Res Lab, Barcelona 08908, Spain..
    Casabonne, Delphine
    Inst Catala Oncol, IDIBELL, Canc Epidemiol Res Programme, Unit Infect & Canc UNIC, Barcelona 08908, Spain.;CIBER Epidemiol & Salud Publ CIBERESP, Madrid 28029, Spain..
    Becker, Nikolaus
    German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Baden Wurttembe, Germany..
    Boffetta, Paolo
    Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA..
    Brennan, Paul
    Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France..
    Foretova, Lenka
    Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic.;MF MU, Brno 65653, Czech Republic..
    Maynadie, Marc
    Univ Burgundy, Registre Hemopathies Malignes Cote dOr, EA 4184, F-21070 Dijon, France.;Dijon Univ Hosp, F-21070 Dijon, France..
    McKay, James
    Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France..
    Staines, Anthony
    Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland..
    Chaffee, Kari G.
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA..
    Achenbach, Sara J.
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA..
    Vachon, Celine M.
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA..
    Goldin, Lynn R.
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Strom, Sara S.
    Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA..
    Leis, Jose F.
    Mayo Clin, Div Hematol Oncol, Phoenix, AZ 85054 USA..
    Weinberg, J. Brice
    Duke Univ, Dept Med, Durham, NC 27710 USA.;VA Med Ctr, Durham, NC 27710 USA..
    Caporaso, Neil E.
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Norman, Aaron D.
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA..
    De Roos, Anneclaire J.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98117 USA.;Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA..
    Morton, Lindsay M.
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Severson, Richard K.
    Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA..
    Riboli, Elio
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London W2 1PG, England..
    Vineis, Paolo
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Human Genet Fdn, I-10126 Turin, Italy..
    Kaaks, Rudolph
    German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Baden Wurttembe, Germany..
    Masala, Giovanna
    Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, I-50139 Florence, Italy..
    Weiderpass, Elisabete
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.;Arctic Univ Norway, Univ Tromso, Dept Community Med, Fac Hlth Sci, N-9037 Tromso, Norway.;Canc Registry Norway, Inst Populat Based Canc Res, Dept Res, N-0304 Oslo, Norway.;Folkhalsan Res Ctr, Genet Epidemiol Grp, FI-00250 Helsinki, Finland..
    Chirlaque, Maria-Dolores
    CIBER Epidemiol & Salud Publ CIBERESP, Barcelona 08036, Spain.;Murcia Reg Hlth Author, Dept Epidemiol, E-30008 Murcia, Spain..
    Vermeulen, Roel C. H.
    Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands.;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3584 CX Utrecht, Netherlands..
    Travis, Ruth C.
    Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7LF, England..
    Southey, Melissa C.
    Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia..
    Milne, Roger L.
    Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia.;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia..
    Albanese, Demetrius
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Virtamo, Jarmo
    Natl Inst Hlth & Welf, Chron Dis Prevent Unit, FI-00271 Helsinki, Finland..
    Weinstein, Stephanie
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Clavel, Jacqueline
    Sorbonne Paris Cite CRESS, INSERM, Ctr Res Epidemiol & Stat, Epidemiol Childhood & Adolescent Canc Grp, F-94807 Paris, France.;Univ Paris 05, F-75270 Paris, France..
    Zheng, Tongzhang
    Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA..
    Holford, Theodore R.
    Yale Univ, Sch Publ Hlth, Dept Stat, New Haven, CT 06520 USA..
    Villano, Danylo J.
    Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA..
    Maria, Ann
    Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA..
    Spinelli, John J.
    BC Canc Agcy, Canc Control Res, Vancouver, BC V5Z 1L3, Canada.;Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V6T 1Z3, Canada..
    Gascoyne, Randy D.
    BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada.;Univ British Columbia, Dept Pathol, Vancouver, BC V6T 1Z3, Canada..
    Connors, Joseph M.
    BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada.;Univ British Columbia, Dept Med, Vancouver, BC V6T 1Z3, Canada..
    Bertrand, Kimberly A.
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA 02115 USA..
    Giovannucci, Edward
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Kraft, Peter
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA..
    Kricker, Anne
    Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia..
    Turner, Jenny
    Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW 2109, Australia.;Douglass Hanly Moir Pathol, Dept Histopathol, N Ryde, NSW 2113, Australia..
    Ennas, Maria Grazia
    Univ Cagliari, Dept Biomed Sci, I-09042 Cagliari, Italy..
    Ferri, Giovanni M.
    Univ Bari, Interdisciplinary Dept Med, I-70124 Bari, Italy..
    Miligi, Lucia
    Canc Prevent & Res Inst ISPO, Environm & Occupat Epidemiol Unit, I-50139 Florence, Italy..
    Liang, Liming
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA..
    Ma, Baoshan
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Dalian Maritime Univ, Coll Informat Sci & Technol, Dalian 116026, Liaoning Provin, Peoples R China..
    Huang, Jinyan
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Crouch, Simon
    Univ York, Dept Hlth Sci, York Y010 5DD, N Yorkshire, England..
    Park, Ju-Hyun
    Dongguk Univ, Dept Stat, Seoul 100715, South Korea..
    Chatterjee, Nilanjan
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    North, Kari E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.;Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA..
    Snowden, John A.
    Univ Sheffield, Dept Oncol, Sheffield S10 1NS, S Yorkshire, England.;Sheffield Teaching Hosp NHS Fdn Trust, Royal Hallamshire Hosp, Dept Haematol, Sheffield S10 2TN, S Yorkshire, England..
    Wright, Josh
    Univ Sheffield, Dept Oncol, Sheffield S10 1NS, S Yorkshire, England.;Sheffield Teaching Hosp NHS Fdn Trust, Royal Hallamshire Hosp, Dept Haematol, Sheffield S10 2TN, S Yorkshire, England..
    Fraumeni, Joseph F.
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Offit, Kenneth
    Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA..
    Wu, Xifeng
    Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA..
    de Sanjose, Silvia
    Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Programme, Barcelona 08908, Spain.;CIBER Epidemiol & Salud Publ CIBERESP, Barcelona 08036, Spain..
    Cerhan, James R.
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA..
    Chanock, Stephen J.
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Rothman, Nathaniel
    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
    Slager, Susan L.
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA..
    Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia2016Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, artikkel-id 10933Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

  • 65.
    Berntsen, Sveinung
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Aaronson, Neil K
    Buffart, Laurien
    Börjeson, Sussanne
    Demmelmaier, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Hellbom, Maria
    Hojman, Pernille
    Igelström, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Johansson, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Pingel, Ronnie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Raastad, Truls
    Velikova, Galina
    Åsenlöf, P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Nordin, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Design of a randomized controlled trial of physical training and cancer (Phys-Can) - the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome2017Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, nr 1, artikkel-id 218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Cancer-related fatigue is a common problem in persons with cancer, influencing health-related quality of life and causing a considerable challenge to society. Current evidence supports the beneficial effects of physical exercise in reducing fatigue, but the results across studies are not consistent, especially in terms of exercise intensity. It is also unclear whether use of behaviour change techniques can further increase exercise adherence and maintain physical activity behaviour. This study will investigate whether exercise intensity affects fatigue and health related quality of life in persons undergoing adjuvant cancer treatment. In addition, to examine effects of exercise intensity on mood disturbance, adherence to oncological treatment, adverse effects from treatment, activities of daily living after treatment completion and return to work, and behaviour change techniques effect on exercise adherence. We will also investigate whether exercise intensity influences inflammatory markers and cytokines, and whether gene expressions following training serve as mediators for the effects of exercise on fatigue and health related quality of life.

    METHODS/DESIGN: Six hundred newly diagnosed persons with breast, colorectal or prostate cancer undergoing adjuvant therapy will be randomized in a 2 × 2 factorial design to following conditions; A) individually tailored low-to-moderate intensity exercise with or without behaviour change techniques or B) individually tailored high intensity exercise with or without behaviour change techniques. The training consists of both resistance and endurance exercise sessions under the guidance of trained coaches. The primary outcomes, fatigue and health related quality of life, are measured by self-reports. Secondary outcomes include fitness, mood disturbance, adherence to the cancer treatment, adverse effects, return to activities of daily living after completed treatment, return to work as well as inflammatory markers, cytokines and gene expression.

    DISCUSSION: The study will contribute to our understanding of the value of exercise and exercise intensity in reducing fatigue and improving health related quality of life and, potentially, clinical outcomes. The value of behaviour change techniques in terms of adherence to and maintenance of physical exercise behaviour in persons with cancer will be evaluated.

    TRIAL REGISTRATION: NCT02473003 , October, 2014.

  • 66.
    Berntsson, Jonna
    et al.
    Lund Univ, Dept Clin Sci Lund, Oncol & Pathol..
    Svensson, Maria C.
    Lund Univ, Dept Clin Sci Lund, Oncol & Pathol..
    Leandersson, Karin
    Lund Univ, Dept Translat Med, Canc Immunol..
    Nodin, Bjorn
    Lund Univ, Dept Clin Sci Lund, Oncol & Pathol..
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Larsson, Anna H.
    Lund Univ, Dept Clin Sci Lund, Oncol & Pathol..
    Eberhard, Jakob
    Lund Univ, Dept Clin Sci Lund, Oncol & Pathol..
    Jirstrom, Karin
    Lund Univ, Dept Clin Sci Lund, Oncol & Pathol..
    The clinical impact of tumour-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite: A cohort study2017Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, nr 8, s. 1654-1666Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Accumulating evidence demonstrates an association between dense infiltration of lymphocytes and prognosis in colorectal cancer (CRC), but whether this prognostic impact differs by tumour location remains unknown. This study investigated the prognostic impact of cytotoxic and regulatory T cells in CRC, with particular referennfiltrating T cce to the anatomical subsite of the primary tumour. The density of CD3(+), CD8(+) and FoxP3(+) tumour-iells was calculated in tissue microarrays with tumours from 557 incident CRC cases from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of high and low lymphocyte density on 5-year overall survival, in subgroup analysis of right colon, left colon and rectum. High CD8(+) cell density was a favourable prognostic factor for patients with right-sided colon tumours (hazard ratio [HR]=0.53, 95% confidence interval [CI] 0.29-0.95), independent of age, sex, TNM stage, differentiation grade and vascular invasion, with a significant prognostic interaction between CD8(+) cells and right-sidedness (p=0.031). High FoxP3(+) cell density was an independent favourable prognostic factor only in patients with rectal tumours (HR=0.54, 95% CI 0.30-0.99), and CD3(+) cell density was an independent favourable prognostic factor for tumours in the right colon and rectum, but there was no significant prognostic interaction between CD3(+) or FoxP3(+) cells and sidedness. These results demonstrate that the prognostic impact of tumour-infiltrating lymphocytes in CRC differs by primary tumour site, further indicating that tumour location may be an important factor to take into consideration in therapeutic decisions, including eligibility for immunotherapy.

  • 67.
    Bhoday, J.
    et al.
    Croydon Univ Hosp, Royal Marsden NHS Fdn Trust, Croydon, England.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Tait, D.
    Royal Marsden NHS Fdn Trust, London, England.
    Glynne-Jones, R.
    Mt Vernon Ctr Canc Treatment, Mt Vernon, Middx, England.
    Adams, R.
    Cardiff Univ, Cardiff, S Glam, Wales;Velindre Canc Ctr, Cardiff, S Glam, Wales.
    Brown, G.
    Imperial Coll London, London, England.
    Session 4: What should we do for poor responders after chemoradiotherapy: bad biology or should the fight go on?2018Inngår i: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 20, nr Suppl. 1, s. 97-99Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Just over 50% of patients with advanced rectal cancer have a poor response to chemoradiotherapy with resultant poor outcomes. Professor Glimelius reviews the evidence base for defining such patients and the potential role, if any, of further treatment.

  • 68.
    Bhoi, Sujata
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala University.
    Prognostic markers and DNA methylation profiling in lymphoid malignancies2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In recent years, great progress has been achieved towards identifying novel biomarkers in lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), at the genomic, transcriptomic and epigenomic level for accurate risk-stratification and prediction of treatment response. In paper I, we validated the prognostic relevance of a recently proposed RNA-based marker in CLL, UGT2B17, and analyzed its expression levels in 253 early-stage patients. Besides confirming its prognostic impact in multivariate analysis, we could identify 30% of IGHV-mutated CLL (M-CLL) cases with high expression and poor outcome, which otherwise lacked any other poor-prognostic marker. In paper II, we investigated the prognostic impact of a previously reported 5 CpG signature that divides CLL patients into three clinico-biological subgroups, namely naive B-cell-like CLL (n-CLL), memory B-cell-like CLL (m-CLL) and intermediate CLL (i-CLL), in 135 CLL patients using pyrosequencing. We validated the signature as an independent marker in multivariate analysis and further reported that subset #2 cases were predominantly classified as i-CLL, although displaying a similar outcome as n-CLL. In paper III, we investigated the methylation status and expression level of miR26A1 in both CLL (n=70) and MCL (n=65) cohorts. High miR26A1 methylation was associated with IGHV-unmutated (U-CLL) and shorter overall survival (OS) in CLL, while it was uniformly hypermethylated in MCL. Furthermore, overexpression of miR26A1 resulted in significant downregulation of EZH2 that in turn led to increased apoptosis. In paper IV, we performed DNA methylation profiling in 176 CLL cases assigned to one of 8 major stereotyped subsets (#1-8) in relation to non-subset CLL (n=325) and different normal B-cell subpopulations. Principal component analysis of subset vs. non-subset CLL revealed that U-CLL and M-CLL subsets generally clustered with n-CLL and m-CLL, respectively, indicating common cellular origins. In contrast, subset #2 emerged as the first defined member of the i-CLL subgroup, which in turn alludes to a distinct cellular origin for subset #2 and i-CLL patients. Altogether, this thesis confirms the prognostic significance of RNA and epigenetic-based markers in CLL, provides insight into the mechanism of miRNA deregulation in lymphoid malignancies and further unravels the DNA methylation landscape in stereotyped subsets of CLL.

     

    Delarbeid
    1. UGT2B17 expression: a novel prognostic marker within IGHV-mutated chronic lymphocytic leukemia?
    Åpne denne publikasjonen i ny fane eller vindu >>UGT2B17 expression: a novel prognostic marker within IGHV-mutated chronic lymphocytic leukemia?
    Vise andre…
    2016 (engelsk)Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, nr 2, s. E63-E65Artikkel i tidsskrift, Letter (Fagfellevurdert) Published
    Emneord
    CLL; UGT2B17; prognostic markers
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-271300 (URN)10.3324/haematol.2015.136440 (DOI)000379156300007 ()26589911 (PubMedID)
    Tilgjengelig fra: 2016-01-07 Laget: 2016-01-07 Sist oppdatert: 2019-04-01
    2. Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #2
    Åpne denne publikasjonen i ny fane eller vindu >>Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #2
    Vise andre…
    2016 (engelsk)Inngår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 11, nr 6, s. 449-455Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Based on the methylation status of 5 single CpG sites, a novel epigenetic classification of chronic lymphocytic leukemia (CLL) was recently proposed, classifying CLL patients into 3 clinico-biological subgroups with different outcome, termed memory like CLL (m-CLL), naive like CLL (n-CLL), and a third intermediate CLL subgroup (i-CLL). While m-CLL and n-CLL patients at large corresponded to patients carrying mutated and unmutated IGHV genes, respectively, limited information exists regarding the less defined i-CLL group. Using pyrosequencing, we investigated the prognostic impact of the proposed 5 CpG signature in a well-characterized CLL cohort (135 cases), including IGHV-mutated and unmutated patients as well as clinically aggressive stereotyped subset #2 patients. Overall, we confirmed the signature's association with established prognostic markers. Moreover, in the presence of the IGHV mutational status, the epigenetic signature remained independently associated with both time-to-first-treatment and overall survival in multivariate analyses. As a prime finding, we observed that subset #2 patients were predominantly classified as i-CLL, probably reflecting their borderline IGHV mutational status (97-99% germline identity), though having a similarly poor prognosis as n-CLL patients. In summary, we validated the epigenetic classifier as an independent factor in CLL prognostication and provide further evidence that subset #2 is a member of the i-CLL group, hence supporting the existence of a third, intermediate epigenetic subgroup.

    Emneord
    CLL, epigenetic classification, methylation, prognosis
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-303408 (URN)10.1080/15592294.2016.1178432 (DOI)000380902700006 ()27128508 (PubMedID)
    Forskningsfinansiär
    Swedish Cancer SocietySwedish Research Council
    Tilgjengelig fra: 2016-09-19 Laget: 2016-09-19 Sist oppdatert: 2018-01-10bibliografisk kontrollert
    3. Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression
    Åpne denne publikasjonen i ny fane eller vindu >>Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression
    Vise andre…
    2016 (engelsk)Inngår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 11, nr 5, s. 335-343Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Downregulation of miR26A1 has been reported in various B-cell malignancies; however, the mechanism behind its deregulation remains largely unknown. We investigated miR26A1 methylation and expression levels in a well-characterized series of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). From 450K methylation arrays, we first observed miR26A1 (cg26054057) as uniformly hypermethylated in MCL (n = 24) (all >75%), while CLL (n = 18) showed differential methylation between prognostic subgroups. Extended analysis using pyrosequencing confirmed our findings and real-time quantitative PCR verified low miR26A1 expression in both CLL (n = 70) and MCL (n = 38) compared to normal B-cells. Notably, the level of miR26A1 methylation predicted outcome in CLL, with higher levels seen in poor-prognostic, IGHV-unmutated CLL. Since EZH2 was recently reported as a target for miR26A1, we analyzed the expression levels of both miR26A1 and EZH2 in primary CLL samples and observed an inverse correlation. By overexpression of miR26A1 in CLL and MCL cell lines, reduced EZH2 protein levels were observed using both Western blot and flow cytometry. In contrast, methyl-inhibitor treatment led to upregulated miR26A1 expression with a parallel decrease of EZH2 expression. Finally, increased levels of apoptosis were observed in miR26A1-overexpressing cell lines, further underscoring the functional relevance of miR26A1. In summary, we propose that epigenetic silencing of miR26A1 is required for the maintenance of increased levels of EZH2, which in turn translate into a worse outcome, as shown in CLL, highlighting miR26A1 as a tumor suppressor miRNA.

    Emneord
    Chronic lymphocytic leukemia, DNA methylation, mantle cell lymphoma, microRNA, tumor suppressor
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-298924 (URN)10.1080/15592294.2016.1164375 (DOI)000377274700002 ()27052808 (PubMedID)
    Forskningsfinansiär
    Swedish Research CouncilSwedish Cancer Society
    Tilgjengelig fra: 2016-07-12 Laget: 2016-07-12 Sist oppdatert: 2017-11-28bibliografisk kontrollert
    4. Genome-wide DNA methylation profiling in chronic lymphocytic leukemia patients carrying stereotyped B-cell receptors
    Åpne denne publikasjonen i ny fane eller vindu >>Genome-wide DNA methylation profiling in chronic lymphocytic leukemia patients carrying stereotyped B-cell receptors
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-328613 (URN)
    Tilgjengelig fra: 2017-08-28 Laget: 2017-08-28 Sist oppdatert: 2017-09-06
  • 69.
    Bhoi, Sujata
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Baliakas, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Cortese, Diego
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Sevov, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Smedby, Karin E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Juliusson, Gunnar
    Sutton, Lesley-Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mansouri, Larry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    UGT2B17 expression: a novel prognostic marker within IGHV-mutated chronic lymphocytic leukemia?2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, nr 2, s. E63-E65Artikkel i tidsskrift (Fagfellevurdert)
  • 70.
    Bhoi, Sujata
    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.
    Ljungström, Viktor
    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.
    Baliakas, Panagiotis
    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.
    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. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Juliusson, Gunnar
    Lund Univ, Dept Lab Med, Stem Cell Ctr, Hematol & Transplantat, Lund, Sweden..
    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.
    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.
    Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #22016Inngår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 11, nr 6, s. 449-455Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Based on the methylation status of 5 single CpG sites, a novel epigenetic classification of chronic lymphocytic leukemia (CLL) was recently proposed, classifying CLL patients into 3 clinico-biological subgroups with different outcome, termed memory like CLL (m-CLL), naive like CLL (n-CLL), and a third intermediate CLL subgroup (i-CLL). While m-CLL and n-CLL patients at large corresponded to patients carrying mutated and unmutated IGHV genes, respectively, limited information exists regarding the less defined i-CLL group. Using pyrosequencing, we investigated the prognostic impact of the proposed 5 CpG signature in a well-characterized CLL cohort (135 cases), including IGHV-mutated and unmutated patients as well as clinically aggressive stereotyped subset #2 patients. Overall, we confirmed the signature's association with established prognostic markers. Moreover, in the presence of the IGHV mutational status, the epigenetic signature remained independently associated with both time-to-first-treatment and overall survival in multivariate analyses. As a prime finding, we observed that subset #2 patients were predominantly classified as i-CLL, probably reflecting their borderline IGHV mutational status (97-99% germline identity), though having a similarly poor prognosis as n-CLL patients. In summary, we validated the epigenetic classifier as an independent factor in CLL prognostication and provide further evidence that subset #2 is a member of the i-CLL group, hence supporting the existence of a third, intermediate epigenetic subgroup.

  • 71.
    Bhoi, Sujata
    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.
    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.
    Castellano, G.
    IDIBAPS, Barcelona, Spain.
    Sutton, Lesley Ann
    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.
    Papakonstantinou, N.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Queiros, A.
    Univ Barcelona, Dept Fundamentos Clin, Barcelona, Spain.
    Ek, S.
    Lund Univ, Dept Immunotechnol, Lund, Sweden.
    Emruli, V. K.
    Lund Univ, Dept Immunotechnol, Lund, Sweden.
    Plevova, K.
    Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic;Masaryk Univ, Fac Med, Brno, Czech Republic;Masaryk Univ, CEITEC Cent European Inst Technol, Ctr Mol Med, Brno, Czech Republic.
    Ntoufa, S.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Davis, Z.
    Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England.
    Young, Emma
    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.
    Göransson, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Isaksson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Smedby, K. E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.
    Gaidano, G.
    Univ Piemonte Orientale, Dept Translat Med, Div Hematol, Novara, Italy.
    Langerak, A. W.
    Univ Med Ctr, Erasmus MC, Dept Immunol, Rotterdam, Netherlands.
    Davi, F.
    Pitie Salpetriere, Paris, France;Univ Paris 06, Paris, France.
    Rossi, D.
    Oncol Inst Southern Switzerland, Hematol Dept, Bellinzona, Switzerland.
    Oscier, D.
    Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England.
    Pospisilova, S.
    Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic;Masaryk Univ, Fac Med, Brno, Czech Republic;Masaryk Univ, CEITEC Cent European Inst Technol, Ctr Mol Med, Brno, Czech Republic.
    Ghia, P.
    Univ Vita Salute San Raffaele, Div Expt Oncol, Milan, Italy;IRCCS San Raffaele Sci Inst, Milan, Italy.
    Campo, E.
    IDIBAPS, Barcelona, Spain;Univ Barcelona, Dept Fundamentos Clin, Barcelona, Spain.
    Stamatopoulos, K.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Martin-Subero, J. -I
    Rosenquist, Richard
    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. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    DNA METHYLATION PROFILING IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS CARRYING STEREOTYPED B-CELL RECEPTORS: A DIFFERENT CELLULAR ORIGIN FOR SUBSET #2?2017Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, nr Suppl. 2, s. 68-68, artikkel-id P244Artikkel i tidsskrift (Annet vitenskapelig)
  • 72.
    Biccler, Jorne Lionel
    et al.
    Aalborg Univ Hosp, Aalborg, Denmark;Aalborg Univ, Aalborg, Denmark.
    Glimelius, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Karolinska Inst, Solna, Sweden.
    Eloranta, Sandra
    Karolinska Inst, Solna, Sweden.
    Smeland, Knut B.
    Oslo Univ Hosp, Oslo, Norway.
    Brown, Peter de Nully
    Copenhagen Univ Hosp, Copenhagen, Denmark.
    Jakobsen, Lasse Hjort
    Aalborg Univ Hosp, Aalborg, Denmark;Aalborg Univ, Aalborg, Denmark.
    Frederiksen, Henrik
    Odense Univ Hosp, Odense, Denmark.
    Jerkeman, Mats
    Lund Univ, Lund, Sweden.
    Fosså, Alexander
    Oslo Univ Hosp, Oslo, Norway;KG Jebsen Ctr B Cell Malignancies, Oslo, Norway.
    Andersson, Therese M. L.
    Karolinska Inst, Solna, Sweden.
    Holte, Harald
    Oslo Univ Hosp, Oslo, Norway;KG Jebsen Ctr B Cell Malignancies, Oslo, Norway.
    Bögsted, Martin
    Aalborg Univ Hosp, Aalborg, Denmark;Aalborg Univ, Aalborg, Denmark.
    El-Galaly, Tarec Christoffer
    Aalborg Univ Hosp, Aalborg, Denmark;Aalborg Univ, Aalborg, Denmark.
    Smedby, Karin E.
    Karolinska Inst, Solna, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Relapse Risk and Loss of Lifetime After Modern Combined Modality Treatment of Young Patients With Hodgkin Lymphoma: A Nordic Lymphoma Epidemiology Group Study2019Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, nr 9, s. 703-713Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Estimates of short- and long-term survival for young patients with classic Hodgkin lymphoma (cHL) are of considerable interest. We investigated cHL prognosis in the era of contemporary treatment at different milestones during the follow-up.

    PATIENTS AND METHODS: On the basis of a Nordic cohort of 2,582 patients diagnosed at ages 18 to 49 years between 2000 and 2013, 5-year relapse risks and 5-year restricted losses in expectation of lifetime were estimated for all patients and for patients who achieved event-free survival (EFS) for 12 (EFS12), 24 (EFS24), 36 (EFS36) or 60 (EFS60) months. The median follow-up time was 9 years (range, 2.9 to 16.8 years).

    RESULTS: The 5-year overall survival was 95% (95% CI, 94% to 96%). The 5-year risk of relapse was 13.4% (95% CI, 12.1% to 14.8%) overall but decreased to 4.2% (95% CI, 3.8% to 4.6%) given that patients reached EFS24. Relapse risk for patients treated with six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) was comparable to that of patients treated with six to eight courses of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) despite more adverse risk criteria among patients treated with BEACOPP. Both from diagnosis and if EFS24 was reached, the losses in expectation of lifetime during the following 5 years were small (from diagnosis, 45 days [95% CI, 35 to 54 days] and for patients who reached EFS24, 13 days [95% CI, 7 to 20 days]). In stage-stratified analyses of 5-year restricted loss in expectation of lifetime, patients with stages I to IIA disease had no noteworthy excess risk of death after they reached EFS24, whereas risk remained measurable for patients with stages IIB to IV cHL.

    CONCLUSION: Real-world data on young patients with cHL from the Nordic countries show excellent outcomes. The outlook is particularly favorable for patients who reach EFS24, which supports limited relapse-oriented clinical follow-up.

  • 73. Bieghs, Liesbeth
    et al.
    Lub, Susanne
    Fostier, Karel
    Maes, Ken
    Van Valckenborgh, Els
    Menu, Eline
    Johnsen, Hans E
    Overgaard, Michael T
    Larsson, Olle
    Axelson, Magnus
    Nyegaard, Mette
    Schots, Rik
    Jernberg-Wiklund, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Vanderkerken, Karin
    De Bruyne, Elke
    The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic2014Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 5, nr 22, s. 11193-11208Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The ABT-analogous 737, 263 and 199 are BH3 mimetics showing potent anti-myeloma (MM) activity, but only on defined molecular subgroups of MM patients presenting a Bcl-2high/Mcl-1low profile. IGF-1 is a major survival factor in MM regulating the expression of Bcl-2 proteins and might therefore be a resistance factor to these ABT-analogous. We first show that IGF-1 protected human MM cell lines (HMCLs) against ABT-737. Concurrently, the IGF-1 receptor inhibitor picropodophyllin (PPP) synergistically sensitized HMCL, primary human MM and murine 5T33MM cells to ABT-737 and ABT-199 by further decreasing cell viability and enhancing apoptosis. Knockdown of Bcl-2 by shRNA protected MM cells to ABT-737, while Mcl-1 shRNA sensitized the cells. PPP overcame the Bcl-2 dependency of ABT-737, but failed to completely overcome the protective effect of Mcl-1. In vivo, co-treatment of 5T33MM bearing mice significantly decreased tumor burden and prolonged overall survival both in a prophylactic and therapeutic setting. Interestingly, proteasome inhibitor resistant CD138- 5T33MM cells were more sensitive to ABT-737, whereas PPP alone targeted the CD138+ cells more effectively. After co-treatment, both subpopulations were targeted equally. Together, the combination of an IGF-1R inhibitor and an ABT-analogue displays synergistic anti-myeloma activity providing the rational for further (pre)clinical testing.

  • 74.
    Bikos, Vasilis
    et al.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Karypidou, Maria
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Stalika, Evangelia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Xochelli, Aliki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Sutton, Lesley-Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Papadopoulos, George
    CERTH, Informat Technol Inst, Thessaloniki, Greece..
    Agathangelidis, Andreas
    Univ Vita Salute San Raffaele, Div Expt Oncol, Milan, Italy.;Univ Vita Salute San Raffaele, Dept Oncohematol, Milan, Italy.;Ist Sci San Raffaele, Milan, Italy..
    Papadopoulou, Evdoxia
    CERTH, Informat Technol Inst, Thessaloniki, Greece..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Algara, Patricia
    Hosp Virgen Salud, Dept Pathol, Toledo, OH, Spain..
    Kanellis, George
    Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece..
    Traverse-Glehen, Alexandra
    Univ Lyon, Hosp Civils Lyon, Dept Pathol & Hematol, Lyon, France..
    Mollejo, Manuela
    Hosp Virgen Salud, Dept Pathol, Toledo, OH, Spain..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Ponzoni, Maurilio
    Ist Sci San Raffaele, Pathol Unit, I-20132 Milan, Italy..
    Gonzalez, David
    Inst Canc Res, Sect Haematooncol, London SW3 6JB, England..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Matutes, Estella
    Inst Canc Res, Sect Haematooncol, London SW3 6JB, England..
    Angel Piris, Miguel
    Hosp Univ Marques de Valdecilla, Santander, Spain..
    Papadaki, Theodora
    Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece..
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Div Expt Oncol, Milan, Italy.;Univ Vita Salute San Raffaele, Dept Oncohematol, Milan, Italy.;Ist Sci San Raffaele, Milan, Italy..
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Darzentas, Nikos
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Tzovaras, Dimitrios
    CERTH, Informat Technol Inst, Thessaloniki, Greece..
    Belessi, Chrysoula
    Nikea Gen Hosp, Hematol Dept, Piraeus, Greece..
    Hadzidimitriou, Anastasia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors2016Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, nr 8, s. 2032-2040Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation. Experimental Design: We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM). Results: ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV) 1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P = 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene). Conclusions: These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease.

  • 75.
    Birgisson, Helgi
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Edlund, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Wallin, Ulrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Kultima, Hanna Göransson
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mayrhofer, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Isaksson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sundström, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer2015Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, artikkel-id 125Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer. Methods: Disease stage II-IV colon cancer patients (n = 121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis. Results: Patients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination. Conclusions: The present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.

  • 76.
    Bjorke, Ann Christin Helgesen
    et al.
    Univ Agder, Dept Publ Hlth Sport & Nutr, Kristiansand, Norway.
    Sweegers, Maike G.
    Vrije Univ, Amsterdam Univ, Amsterdam Publ Hlth Inst, Dept Epidemiol & Biostat,Med Ctr, Amsterdam, Netherlands;Vrije Univ, Amsterdam Univ, Canc Ctr Amsterdam, Med Ctr, Amsterdam, Netherlands.
    Buffart, Laurien M.
    Vrije Univ, Amsterdam Univ, Amsterdam Publ Hlth Inst, Dept Epidemiol & Biostat,Med Ctr, Amsterdam, Netherlands;Vrije Univ, Amsterdam Univ, Canc Ctr Amsterdam, Med Ctr, Amsterdam, Netherlands;Vrije Univ, Amsterdam Univ, Dept Med Oncol, Med Ctr, Amsterdam, Netherlands.
    Raastad, Truls
    Norwegian Sch Sport Sci, Oslo, Norway.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Berntsen, Sveinung
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom. Univ Agder, Dept Publ Hlth Sport & Nutr, Kristiansand, Norway.
    Which exercise prescriptions optimize V̇O2max during cancer treatment?: a systematic review and meta-analysis2019Inngår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 29, nr 9, s. 1274-1287Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The aims of the present systematic review and meta-analysis were to investigate the effect of exercise on maximal oxygen uptake ((V) over dot O(2)max) and to investigate whether exercise frequency, intensity, duration, and volume are associated with changes in (V) over dotO(2)max among adult patients with cancer undergoing treatment. Medline and Embase through OvidSP were searched to identify randomized controlled trials. Two reviewers extracted data and assessed the risk of bias. The overall effect size and differences in effects for different intensities and frequencies were calculated on change scores and post-intervention (V) over dot O(2)max data, and the meta-regression of exercise duration and volumes was analyzed using the Comprehensive Meta-Analysis software. Fourteen randomized controlled trials were included in the systematic review, comprising 1332 patients with various cancer types receiving (neo-) adjuvant chemo-, radio-, and/or hormone therapy. Exercise induced beneficial changes in (V) over dotO(2)max compared to usual care (effect size = 0.46, 95% Confidence Interval = 0.23-0.69). Longer session duration (P = 0.020), and weekly duration (P = 0.010), larger weekly volume (P < 0.001), and shorter intervention duration (P = 0.005) were significantly associated with more beneficial changes in (V) over dot O(2)max. No differences in effects between subgroups with respect to frequency and intensity were found. In conclusion, exercise has beneficial effects on (V) over dotO(2)max in patients with cancer undergoing (neo-) adjuvant treatment. As interventions with larger exercise volumes and longer session durations resulted in larger beneficial changes in (V) over dot O(2)max, exercise frequency, intensity, and duration should be considered carefully for sufficient exercise volume to induce changes in (V) over dot O(2)max for this patient group.

  • 77.
    Bjurberg, Maria
    et al.
    Lund Univ, Skane Univ Hosp, Dept Haematol Oncol & Radiat Phys, Lasarettsgatan 23, SE-22185 Lund, Sweden;Lund Univ, Dept Clin Sci, Lasarettsgatan 23, SE-22185 Lund, Sweden.
    Holmberg, Erik
    Reg Canc Ctr West, Reg Vastra Gotaland, SE-41345 Gothenburg, Sweden;Sahlgrens Acad, Inst Clin Sci, Dept Oncol, SE-41345 Gothenburg, Sweden.
    Borgfeldt, Christer
    Skane Univ Hosp, Dept Obstet & Gynaecol, SE-22185 Lund, Sweden;Lund Univ, SE-22185 Lund, Sweden.
    Flöter-Rådestad, Angelique
    Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Div Obstet & Gynaecol, SE-17176 Stockholm, Sweden.
    Dahm-Kähler, Pernilla
    Sahlgrens Univ Hosp, Dept Obstet & Gynaecol, SE-41345 Gothenburg, Sweden.
    Hjerpe, Elisabet
    Visby Hosp, Dept Gynaecol & Obstet, SE-62155 Visby, Sweden.
    Högberg, Thomas
    Lund Univ, Dept Canc Epidemiol, SE-22100 Lund, Sweden.
    Kjolhede, Preben
    Linkoping Univ Hosp, Dept Obstet & Gynaecol, SE-58185 Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden.
    Marcickiewicz, Janusz
    Reg Canc Ctr West, Reg Vastra Gotaland, SE-41345 Gothenburg, Sweden;Halland Hosp, Dept Obstet & Gynaecol, SE-43281 Varberg, Sweden.
    Rosenberg, Per
    Linkoping Univ, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden;Linkoping Univ, Dept Oncol, SE-58185 Linkoping, Sweden.
    Stålberg, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Tholander, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hellman, Kristina
    Karolinska Univ Hosp, Dept Gynaecol Canc, Theme Canc, SE-17176 Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linkoping Univ, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden;Linkoping Univ, Dept Oncol, SE-58185 Linkoping, Sweden.
    Primary treatment patterns and survival of cervical cancer in Sweden: A population-based Swedish Gynecologic Cancer Group Study2019Inngår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 155, nr 2, s. 229-236Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival. Methods: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma. Results: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p < 0.001). In stage IIA1 74% had CTRL, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p < 0.001). Stages III-IVA; <40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p < 0.001). RS stage IVB 7%. Conclusion: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy. (C) 2019 Elsevier Inc. All rights reserved.

  • 78.
    Björkholm, Magnus
    et al.
    Karolinska Univ Hosp Solna, Dept Med, Div Hematol, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Weibull, Caroline E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Eloranta, Sandra
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden;Karolinska Univ Hosp Solna, Stockholm, Sweden.
    Smedby, Karin E.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden;Karolinska Univ Hosp Solna, Stockholm, Sweden.
    Glimelius, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden;Karolinska Univ Hosp Solna, Stockholm, Sweden.
    Dickman, Paul W.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Greater attention should be paid to developing therapies for elderly patients with Hodgkin lymphoma: A population-based study from Sweden2018Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 101, nr 1, s. 106-114Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Forty percent of Hodgkin lymphoma (HL) patients are older than 50years at diagnosis, a fact which is not commonly recognized. Older patients do significantly worse than younger patients and are rarely included in clinical trials.

    Methods: Using data from Swedish Cancer and Lymphoma Registries, we estimated relative survival ratios (RSRs) for 7997 HL patients (diagnosed 1973-2013; 45% 50years).

    Results: The 1-year RSRs (95% confidence interval; CI) for males aged 45-59, 60-69, 70-80, and 81years and over, diagnosed in 2013, were 0.95 (0.91-0.97), 0.88 (0.81-0.92), 0.74 (0.63-0.81), and 0.52 (0.35-0.67), respectively. The corresponding 1-year RSRs for females were 0.97 (0.94-0.98), 0.91 (0.85-0.95), 0.82 (0.73-0.88), and 0.66 (0.50-0.77). No improvements in 1-year of 5-year relative survival from 2000 to 2013 were observed for patients aged 45-59 or 60-69 but there were modest improvements for patients aged 70years and older. Importantly, we saw no changes in the distribution of disease or patient characteristics between 2000 and 2013.

    Conclusions: Elderly patients constitute a large group with clearly unmet medical needs. Our findings motivate a more active approach to including elderly patients in clinical trials. Our study provides a baseline for outcome comparison after the broader introduction of targeted drugs.

  • 79.
    Bjørge, Tone
    et al.
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.;Canc Registry Norway, Oslo, Norway..
    Gissler, Mika
    Natl Inst Hlth & Welf THL, Helsinki, Finland..
    Ording, Anne Gulbech
    Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark..
    Engeland, Anders
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.;Norwegian Inst Publ Hlth, Dept Pharmacoepidemiol, Div Mental & Phys Hlth, Bergen, Norway..
    Glimelius, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Leinonen, Maarit
    Finnish Canc Registry, Canc Soc Finland, Helsinki, Finland..
    Sørensen, Henrik Toft
    Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark..
    Tretli, Steinar
    Canc Registry Norway, Oslo, Norway..
    Ekbom, Anders
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Troisi, Rebecca
    NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD USA..
    Grotmol, Tom
    Canc Registry Norway, Oslo, Norway..
    Reproductive history and risk of colorectal adenocarcinoma in parous women: a Nordic population-based case-control study2016Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 115, nr 11, s. 1416-1420Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history. Methods: We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders. Results: We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found. Conclusions: In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women.

  • 80.
    Blanco, G.
    et al.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Puiggros, A.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Baliakas, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Athanasiadou, A.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Garcia-Malo, M. D.
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Collado, R.
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain..
    Xochelli, A.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rodriguez-Rivera, M.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Ortega, M.
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Calasanz, M. J.
    Univ Navarra, Dept Genet, Serv Citogenet, Pamplona, Spain..
    Luno, E.
    Hosp Univ Cent Asturias, Serv Hematol, Oviedo, Spain..
    Vargas, M. T.
    Hosp Univ Virgen de la Macarena, Seville, Spain..
    Grau, J.
    Univ Autonoma Barcelona, Inst Recerca Leucemia Josep Carreras IJC, ICO Hosp Germans Trias & Pujol, Serv Lab Hematol, Badalona, Spain..
    Martinez-Laperche, C.
    Hosp GU Gregorio Maranon, Serv Hematol, Lab Genet Hematol, Madrid, Spain.;Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain..
    Valiente, A.
    Complejo Hospitalario Navarra, Serv Genet, Pamplona, Spain.;Complejo Hospitalario Navarra, Serv Hematol, Pamplona, Spain..
    Papaioannou, G.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Cervera, J.
    Hosp Univ La Fe, Unidad Genet, Valencia, Spain..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Pinan, M. A.
    Hosp Cruces, Serv Hematol, Bilbao, Spain..
    Stalika, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Hernandez-Rivas, J. M.
    Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, IBSAL,IBMCC,CSIC,Serv Hematol, Salamanca, Spain..
    Batlle, A.
    Hosp Univ Marques de Valdecilla, Serv Hematol, Santander, Spain..
    Salido, M.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Ortuno, F.
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Melero, C.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Robles, D.
    Hosp Txagorritxu, Serv Hematol, Vitoria, Spain..
    Ferrer, A.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Ivars, D.
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain..
    Rodriguez, A.
    Hosp Univ Virgen de la Macarena, Seville, Spain..
    Gonzalez, M.
    Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, IBSAL,IBMCC,CSIC,Serv Hematol, Salamanca, Spain..
    Bosch, F.
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Abrisqueta, P.
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Stamatopoulos, K.
    G Papanicolaou Hosp, Inst Appl Biosci, CERTH, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, Inst Appl Biosci, CERTH, HCT Unit, Thessaloniki, Greece..
    Espinet, B.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Chromosome 8 Abnormalities Are Associated With An Even Worse Outcome And Karyotype Complexity In Patients With Chronic Lymphocytic Leukemia And Tp53 Aberrations2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, s. 229-230Artikkel i tidsskrift (Annet vitenskapelig)
  • 81.
    Blanco, Gonzalo
    et al.
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain.;Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain..
    Puiggros, Anna
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Baliakas, Panagiotis
    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.
    Athanasiadou, Anastasia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Garcia-Malo, MaDolores
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Collado, Rosa
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain..
    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.
    Rodriguez-Rivera, Maria
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Ortega, Margarita
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Jose Calasanz, Ma
    Univ Navarra, Dept Genet, Serv Citogenet, Pamplona, Spain..
    Luno, Elisa
    Hosp Univ Cent Asturias, Serv Hematol, Oviedo, Spain..
    Vargas, MaTeresa
    Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBIS, UGC Hematol, Seville, Spain..
    Grau, Javier
    Univ Autonoma Barcelona, Inst Recerca Leucemia Josep Carreras IJC, ICO Hosp Germans Trias & Pujol, Serv Hematol, Badalona, Spain..
    Martinez-Laperche, Carolina
    Hosp GU Gregorio Maranon, Inst Invest Sanitaria Gregorio Maranon, Serv Hematol, Lab Genet Hematol, Madrid, Spain..
    Valiente, Alberto
    Complejo Hospitalario Navarra, Serv Genet & Hematol, Pamplona, Spain..
    Cervera, Jose
    Hosp Univ La Fe, Unidad Genet, Valencia, Spain..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Gimeno, Eva
    Hosp del Mar, Serv Hematol, Barcelona, Spain..
    Abella, Eugenia
    Hosp del Mar, Serv Hematol, Barcelona, Spain..
    Stalika, Evangelia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Ma Hernandez-Rivas, Jesus
    Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, CSIC,Serv Hematol,IBSAL,IBMCC, Salamanca, Spain..
    Jose Ortuno, Francisco
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Robles, Diego
    Hosp Txagorritxu, Serv Hematol, Vitoria, Spain..
    Ferrer, Ana
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Ivars, David
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain..
    Gonzalez, Marcos
    Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, CSIC,Serv Hematol,IBSAL,IBMCC, Salamanca, Spain..
    Bosch, Francesc
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Abrisqueta, Pau
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Espinet, Blanca
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Karyotypic complexity rather than chromosome 8 abnormalities aggravates the outcome of chronic lymphocytic leukemia patients with TP53 aberrations2016Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, nr 49, s. 80916-80924Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (TP53abs; chromosome 17p deletion and/or TP53 mutation) exhibit an unfavorable clinical outcome. Chromosome 8 abnormalities, namely losses of 8p (8p-) and gains of 8q (8q+) have been suggested to aggravate the outcome of patients with TP53abs. However, the reported series were small, thus hindering definitive conclusions. To gain insight into this issue, we assessed a series of 101 CLL patients harboring TP53 disruption. The frequency of 8p- and 8q+ was 14.7% and 17.8% respectively. Both were associated with a significantly (P < 0.05) higher incidence of a complex karyotype (CK, >= 3 abnormalities) detected by chromosome banding analysis (CBA) compared to cases with normal 8p (N-8p) and 8q (N-8q), respectively. In univariate analysis for 10- year overall survival (OS), 8p- (P = 0.002), 8q+ (P = 0.012) and CK (P = 0.009) were associated with shorter OS. However, in multivariate analysis only CK (HR = 2.47, P = 0.027) maintained independent significance, being associated with a dismal outcome regardless of chromosome 8 abnormalities. In conclusion, our results highlight the association of chromosome 8 abnormalities with CK amongst CLL patients with TP53abs, while also revealing that CK can further aggravate the prognosis of this aggressive subgroup.

  • 82. Blein, Sophie
    et al.
    Bardel, Claire
    Danjean, Vincent
    McGuffog, Lesley
    Healey, Sue
    Barrowdale, Daniel
    Lee, Andrew
    Dennis, Joe
    Kuchenbaecker, Karoline B.
    Soucy, Penny
    Terry, Mary Beth
    Chung, Wendy K.
    Goldgar, David E.
    Buys, Saundra S.
    Janavicius, Ramunas
    Tihomirova, Laima
    Tung, Nadine
    Dorfling, Cecilia M.
    van Rensburg, Elizabeth J.
    Neuhausen, Susan L.
    Ding, Yuan Chun
    Gerdes, Anne-Marie
    Ejlertsen, Bent
    Nielsen, Finn C.
    Hansen, Thomas V. O.
    Osorio, Ana
    Benitez, Javier
    Andres Conejero, Raquel
    Segota, Ena
    Weitzel, Jeffrey N.
    Thelander, Margo
    Peterlongo, Paolo
    Radice, Paolo
    Pensotti, Valeria
    Dolcetti, Riccardo
    Bonanni, Bernardo
    Peissel, Bernard
    Zaffaroni, Daniela
    Scuvera, Giulietta
    Manoukian, Siranoush
    Varesco, Liliana
    Capone, Gabriele L.
    Papi, Laura
    Ottini, Laura
    Yannoukakos, Drakoulis
    Konstantopoulou, Irene
    Garber, Judy
    Hamann, Ute
    Donaldson, Alan
    Brady, Angela
    Brewer, Carole
    Foo, Claire
    Evans, D. Gareth
    Frost, Debra
    Eccles, Diana
    Douglas, Fiona
    Cook, Jackie
    Adlard, Julian
    Barwell, Julian
    Walker, Lisa
    Izatt, Louise
    Side, Lucy E.
    Kennedy, M. John
    Tischkowitz, Marc
    Rogers, Mark T.
    Porteous, Mary E.
    Morrison, Patrick J.
    Platte, Radka
    Eeles, Ros
    Davidson, Rosemarie
    Hodgson, Shirley
    Cole, Trevor
    Godwin, Andrew K.
    Isaacs, Claudine
    Claes, Kathleen
    De Leeneer, Kim
    Meindl, Alfons
    Gehrig, Andrea
    Wappenschmidt, Barbara
    Sutter, Christian
    Engel, Christoph
    Niederacher, Dieter
    Steinemann, Doris
    Plendl, Hansjoerg
    Kast, Karin
    Rhiem, Kerstin
    Ditsch, Nina
    Arnold, Norbert
    Varon-Mateeva, Raymonda
    Schmutzler, Rita K.
    Preisler-Adams, Sabine
    Markov, Nadja Bogdanova
    Wang-Gohrke, Shan
    de Pauw, Antoine
    Lefol, Cedrick
    Lasset, Christine
    Leroux, Dominique
    Rouleau, Etienne
    Damiola, Francesca
    Dreyfus, Helene
    Barjhoux, Laure
    Golmard, Lisa
    Uhrhammer, Nancy
    Bonadona, Valerie
    Sornin, Valerie
    Bignon, Yves-Jean
    Carter, Jonathan
    Van Le, Linda
    Piedmonte, Marion
    DiSilvestro, Paul A.
    de la Hoya, Miguel
    Caldes, Trinidad
    Nevanlinna, Heli
    Aittomaki, Kristiina
    Jager, Agnes
    van den Ouweland, Ans M. W.
    Kets, Carolien M.
    Aalfs, Cora M.
    van Leeuwen, Flora E.
    Hogervorst, Frans B. L.
    Meijers-Heijboer, Hanne E. J.
    Oosterwijk, Jan C.
    van Roozendaal, Kees E. P.
    Rookus, Matti A.
    Devilee, Peter
    van der Luijt, Rob B.
    Olah, Edith
    Diez, Orland
    Teule, Alex
    Lazaro, Conxi
    Blanco, Ignacio
    Del Valle, Jesus
    Jakubowska, Anna
    Sukiennicki, Grzegorz
    Gronwald, Jacek
    Lubinski, Jan
    Durda, Katarzyna
    Jaworska-Bieniek, Katarzyna
    Agnarsson, Bjarni A.
    Maugard, Christine
    Amadori, Alberto
    Montagna, Marco
    Teixeira, Manuel R.
    Spurdle, Amanda B.
    Foulkes, William
    Olswold, Curtis
    Lindor, Noralane M.
    Pankratz, Vernon S.
    Szabo, Csilla I.
    Lincoln, Anne
    Jacobs, Lauren
    Corines, Marina
    Robson, Mark
    Vijai, Joseph
    Berger, Andreas
    Fink-Retter, Anneliese
    Singer, Christian F.
    Rappaport, Christine
    Kaulich, Daphne Geschwantler
    Pfeiler, Georg
    Tea, Muy-Kheng
    Greene, Mark H.
    Mai, Phuong L.
    Rennert, Gad
    Imyanitov, Evgeny N.
    Mulligan, Anna Marie
    Glendon, Gord
    Andrulis, Irene L.
    Tchatchou, Sandrine
    Toland, Amanda Ewart
    Pedersen, Inge Sokilde
    Thomassen, Mads
    Kruse, Torben A.
    Jensen, Uffe Birk
    Caligo, Maria A.
    Friedman, Eitan
    Zidan, Jamal
    Laitman, Yael
    Lindblom, Annika
    Melin, Beatrice
    Arver, Brita
    Loman, Niklas
    Rosenquist, Richard Brandell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Olopade, Olufunmilayo I.
    Nussbaum, Robert L.
    Ramus, Susan J.
    Nathanson, Katherine L.
    Domchek, Susan M.
    Rebbeck, Timothy R.
    Arun, Banu K.
    Mitchell, Gillian
    Karlan, Beth Y.
    Lester, Jenny
    Orsulic, Sandra
    Stoppa-Lyonnet, Dominique
    Thomas, Gilles
    Simard, Jacques
    Couch, Fergus J.
    Offit, Kenneth
    Easton, Douglas F.
    Chenevix-Trench, Georgia
    Antoniou, Antonis C.
    Mazoyer, Sylvie
    Phelan, Catherine M.
    Sinilnikova, Olga M.
    Cox, David G.
    An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers2015Inngår i: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 17, artikkel-id 61Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

  • 83.
    Blom, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Alvarsson, Jonathan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Andersson, Claes R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Ex Vivo Assessment of Drug Activity in Patient Tumor Cells as a Basis for Tailored Cancer Therapy2016Inngår i: JALA, ISSN 2211-0682, Vol. 21, nr 1, s. 178-187Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although medical cancer treatment has improved during the past decades, it is difficult to choose between several first-line treatments supposed to be equally active in the diagnostic group. It is even more difficult to select a treatment after the standard protocols have failed. Any guidance for selection of the most effective treatment is valuable at these critical stages. We describe the principles and procedures for ex vivo assessment of drug activity in tumor cells from patients as a basis for tailored cancer treatment. Patient tumor cells are assayed for cytotoxicity with a panel of drugs. Acoustic drug dispensing provides great flexibility in the selection of drugs for testing; currently, up to 80 compounds and/or combinations thereof may be tested for each patient. Drug response predictions are obtained by classification using an empirical model based on historical responses for the diagnosis. The laboratory workflow is supported by an integrated system that enables rapid analysis and automatic generation of the clinical referral response.

  • 84.
    Blom, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Andersson, Claes R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Predictive Value of Ex Vivo Chemosensitivity Assays for Individualized Cancer Chemotherapy: A Meta-Analysis2017Inngår i: SLAS TECHNOLOGY, ISSN 2472-6303, Vol. 22, nr 3, s. 306-314Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Current treatment strategies for chemotherapy of cancer patients were developed to benefit groups of patients with similar clinical characteristics. In practice, response is very heterogeneous between individual patients within these groups. Precision medicine can be viewed as the development toward a more fine-grained treatment stratification than what is currently in use. Cell-based drug sensitivity testing is one of several options for individualized cancer treatment available today, although it has not yet reached widespread clinical use. We present an up-to-date literature meta-analysis on the predictive value of ex vivo chemosensitivity assays for individualized cancer chemotherapy and discuss their current clinical value and possible future developments.

  • 85.
    Blom, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Senkowski, Wojciech
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Jarvius, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Berglund, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Rubin, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Lenhammar, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Parrow, Vendela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Andersson, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Loskog, Angelica
    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.
    Fryknäs, Mårten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Nygren, Peter
    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.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    The anticancer effect of mebendazole may be due to M1 monocyte/macrophage activation via ERK1/2 and TLR8-dependent inflammasome activation2017Inngår i: Immunopharmacology and immunotoxicology, ISSN 0892-3973, E-ISSN 1532-2513, Vol. 39, nr 4, s. 199-210Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation. The MBZ-induced gene expression signature in the promyeloblastic HL-60 cell line was strongly enriched in genes involved in monocyte/macrophage pro-inflammatory (M1) activation. This was subsequently validated using MBZ-treated THP-1 monocytoid cells that demonstrated gene expression, surface markers and cytokine release characteristic of the M1 phenotype. At high concentrations MBZ substantially induced the release of IL-1 beta and this was further potentiated by lipopolysaccharide (LPS). At low MBZ concentrations, cotreatment with LPS was required for MBZ-stimulated IL-1 beta secretion to occur. Furthermore, we show that the activation of protein kinase C, ERK1/2 and NF-kappaB were required for MBZ-induced IL-1 release. MBZ-induced IL-1 release was found to be dependent on NLRP3 inflammasome activation and to involve TLR8 stimulation. Finally, MBZ induced tumor-suppressive effects in a coculture model with differentiated THP-1 macrophages and HT29 colon cancer cells. In summary, we report that MBZ induced a pro-inflammatory (M1) phenotype of monocytoid cells, which may, at least partly, explain MBZ's anticancer activity observed in animal tumor models and in the clinic.

  • 86.
    Blomberg, Carl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Nilsson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Holgersson, Georg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Edlund, Per
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Adwall, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ekman, Simon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Brattström, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Bergström, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Randomized Trials of Systemic Medically-treated Malignant Mesothelioma: A Systematic Review2015Inngår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, nr 5, s. 2493-2501Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category.

  • 87.
    Blomquist, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Ronne Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Borota, Ljubisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Gál, Gyula
    Nilsson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Montelius, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Grusell, Erik
    Isacsson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Positive correlation between occlusion rate and nidus size of proton beam treated brain arteriovenous malformations (AVMs)2016Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, nr 1, s. 105-112Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Proton beam radiotherapy of arteriovenous malformations (AVM) in the brain has been performed in Uppsala since 1991. An earlier study based on the first 26 patients concluded that proton beam can be used for treating large and medium sized AVMs that were considered difficult to treat with photons due to the risk of side effects. In the present study we analyzed the result from treating the subsequent 65 patients.

    MATERIAL AND METHODS: A retrospective review of the patients' medical records, treatment protocols and radiological results was done. Information about gender, age, presenting symptoms, clinical course, the size of AVM nidus and rate of occlusion was collected. Outcome parameters were the occlusion of the AVM, clinical outcome and side effects.

    RESULTS: The rate of total occlusion was overall 68%. For target volume 0-2cm(3) it was 77%, for 3-10 cm(3) 80%, for 11-15 cm(3) 50% and for 16-51 cm(3) 20%. Those with total regress of the AVM had significantly smaller target volumes (p < 0.009) higher fraction dose (p < 0.001) as well as total dose (p < 0.004) compared to the rest. The target volume was an independent predictor of total occlusion (p = 0.03). There was no difference between those with and without total occlusion regarding mean age, gender distribution or symptoms at diagnosis. Forty-one patients developed a mild radiation-induced brain edema and this was more common in those that had total occlusion of the AVM. Two patients had brain hemorrhages after treatment. One of these had no effect and the other only partial occlusion from proton beams. Two thirds of those presenting with seizures reported an improved seizure situation after treatment.

    CONCLUSION: Our observations agree with earlier results and show that proton beam irradiation is a treatment alternative for brain AVMs since it has a high occlusion rate even in larger AVMs.

  • 88.
    Blomstrand, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Käkkirurgi.
    Thor, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Käkkirurgi.
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Erdheim-Chester disease presenting as periodontal disease: Experience of treatment with cladribine, interferon-a, local radiotherapy and anakinra2016Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, nr 2, s. 248-250Artikkel i tidsskrift (Fagfellevurdert)
  • 89.
    Boeckelman, Camilla
    et al.
    Helsinki Univ Hosp, Dept Surg;Univ Helsinki, Res Programs Unit.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Need for adjuvant chemotherapy after colon cancer surgery - has it decreased?2017Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 5, s. 629-633Artikkel i tidsskrift (Annet vitenskapelig)
  • 90.
    Botling, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Biobanking of fresh frozen tissue from clinical surgical specimens: transport logistics, sample selection, and histologic characterization.2011Inngår i: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 675, s. 299-306Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Access to high-quality fresh frozen tissue is critical for translational cancer research and molecular -diagnostics. Here we describe a workflow for the collection of frozen solid tissue samples derived from fresh human patient specimens after surgery. The routines have been in operation at Uppsala University Hospital since 2001. We have integrated cryosection and histopathologic examination of each biobank sample into the biobank manual. In this way, even small, macroscopically ill-defined lesions can be -procured without a diagnostic hazard due to the removal of uncharacterized tissue from a clinical -specimen. Also, knowledge of the histomorphology of the frozen tissue sample - tumor cell content, stromal components, and presence of necrosis - is pivotal before entering a biobank case into costly molecular profiling studies.

  • 91.
    Botling, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Sandelin, Martin
    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.
    Immune Biomarkers on the Radar-Comprehensive "Immunograms" for Multimodal Treatment Prediction2017Inngår i: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, nr 5, s. 770-772Artikkel i tidsskrift (Annet vitenskapelig)
  • 92.
    Braendengen, Morten
    et al.
    Oslo Univ Hosp, Dept Oncol, Sect Gastrointestinal Oncol, Oslo, Norway.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Preoperative radiotherapy or chemoradiotherapy in rectal cancer - Is survival improved?: An update of the "Nordic" LARC study in non-resectable cancers2018Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, nr 3, s. 392-395Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The randomized "Nordic" LARC study compared preoperative long-course radiotherapy alone (RT) or with chemotherapy (CRT) in the most locally advanced/ugly rectal cancers. Despite significantly better local control in the CRT group, no overall survival benefit was seen after 10 years follow-up. The relations between local control and survival are discussed.

  • 93. Bujko, K.
    et al.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Valentini, V.
    Michalski, W.
    Spalek, M.
    Postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy: A meta-analysis of randomized trials comparing surgery +/- a fluoropyrimidine and surgery plus a fluoropyrimidine +/- oxaliplatin2015Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 41, nr 6, s. 713-723Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is no consensus on the role of postoperative chemotherapy in patients with rectal cancer who have received preoperative radio(chemo)therapy. Materials and methods: A systematic review and meta-analysis were performed of trials that used preoperative radio(chemo)therapy and randomized patients either between postoperative chemotherapy and observation or between a fluoropyrimidine only (FU-only) and a fluoropyrimidine with oxaliplatin (FU-OXA) as postoperative chemotherapy. Results: Five randomized studies compared postoperative chemotherapy with observation in a total of 2398 patients. None of these trials demonstrated a statistically significant benefit of chemotherapy for OS and DFS. The pooled differences in OS and DFS did not differ statistically significantly between the chemotherapy group and the observation group. The hazard ratios (HRs) and 95% confidence intervals (CIs) were 0.95 (CI: 0.82-1.10), P = 0.49 and 0.92 (CI: 0.80-1.04), P = 0.19, respectively. In the subgroup of trials in which randomization was performed after surgery (n = 753), a statistically significant positive pooled chemotherapy effect was observed for DFS (HR = 0.79, 95% CI: 0.62-1.00, P = 0.047), but not for OS (P = 0.39). Four randomized trials compared adjuvant FU OXA with adjuvant FU-only in 2710 patients. In two trials, the difference in DFS between groups was statistically significant in favour of FU OXA, and in the other two trials, the difference was not significant. The pooled difference in DFS between the FU OXA group and the FU-only group was not statistically significant: HR = 0.84 (CI: 0.66-1.06), P = 0.15. Conclusion: The use of postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy is not based on strong scientific evidence. (C) 2015 Elsevier Ltd. All rights reserved.

  • 94.
    Bystry, Vojtech
    et al.
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Agathangelidis, Andreas
    IRCCS San Raffaele Sci Inst, Div Mol Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Bikos, Vasilis
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Sutton, Lesley Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Baliakas, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hadzidimitriou, Anastasia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Darzentas, Nikos
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    ARResT/AssignSubsets: a novel application for robust subclassification of chronic lymphocytic leukemia based on B cell receptor IG stereotypy2015Inngår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 31, nr 23, s. 3844-3846Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Motivation: An ever-increasing body of evidence supports the importance of B cell receptor immunoglobulin (BcR IG) sequence restriction, alias stereotypy, in chronic lymphocytic leukemia (CLL). This phenomenon accounts for similar to 30% of studied cases, one in eight of which belong to major subsets, and extends beyond restricted sequence patterns to shared biologic and clinical characteristics and, generally, outcome. Thus, the robust assignment of new cases to major CLL subsets is a critical, and yet unmet, requirement. Results: We introduce a novel application, ARResT/AssignSubsets, which enables the robust assignment of BcR IG sequences from CLL patients to major stereotyped subsets. ARResT/AssignSubsets uniquely combines expert immunogenetic sequence annotation from IMGT/V-QUEST with curation to safeguard quality, statistical modeling of sequence features from more than 7500 CLL patients, and results from multiple perspectives to allow for both objective and subjective assessment. We validated our approach on the learning set, and evaluated its real-world applicability on a new representative dataset comprising 459 sequences from a single institution.

  • 95.
    Byström, Sanna
    et al.
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Fredolini, Claudia
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Edqvist, Per-Henrik D
    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.
    Nyaiesh, Etienne-Nicholas
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Drobin, Kimi
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Uhlen, Mathias
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Gavle Sjukhus, S-80188 Gavle, Sweden.;Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Ponten, Fredrik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Schwenk, Jochen M.
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Affinity Proteomics Exploration of Melanoma Identifies Proteins in Serum with Associations to T-Stage and Recurrence2017Inngår i: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 10, nr 3, s. 385-395Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Blood-based proteomic profiling may aid and expand our understanding of diseases and their different phenotypes. The aim of the presented study was to profile serum samples from patients with malignant melanoma using affinity proteomic assays to describe proteins in the blood stream that are associated to stage or recurrence of melanoma. MATERIAL AND METHODS: Multiplexed protein analysis was conducted using antibody suspension bead arrays. A total of 232 antibodies against 132 proteins were selected from (i) a screening with 4595 antibodies and 32 serum samples from melanoma patients and controls, (ii) antibodies used for immunohistochemistry, (iii) protein targets previously related with melanoma. The analysis was performed with 149 serum samples from patients with malignant melanoma. Antibody selectivity was then assessed by Western blot, immunocapture mass spectrometry, and epitope mapping. Lastly, indicative antibodies were applied for IHC analysis of melanoma tissues. RESULTS: Serum levels of regucalcin (RGN) and syntaxin 7 (STX7) were found to be lower in patients with both recurring tumors and a high Breslow's thickness (T-stage 3/4) compared to low thickness (T-stage 1/2) without disease recurrence. Serum levels of methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) were instead elevated in sera of T3/4 patients with recurrence. The analysis of tissue sections with S100A6 and MTHFD1L showed positive staining in a majority of patients with melanoma, and S100A6 was significantly associated to T-stage. CONCLUSIONS: Our findings provide a starting point to further study RGN, STX7, MTHFD1L and S100A6 in serum to elucidate their involvement in melanoma progression and to assess a possible contribution to support clinical indications.

  • 96.
    Carde, Patrice
    et al.
    Gustave Roussy Canc Campus, F-94805 Villejuif, France..
    Karrasch, Matthias
    European Org Res & Treatment, Canc Headquarters, Brussels, Belgium..
    Fortpied, Catherine
    European Org Res & Treatment, Canc Headquarters, Brussels, Belgium..
    Brice, Pauline
    Hop St Louis, Paris, France..
    Khaled, Hussein
    Natl Canc Inst, Cairo, Egypt..
    Casasnovas, Olivier
    Ctr Hosp Univ CHU Dijon, Dijon, France..
    Caillot, Denis
    Ctr Hosp Univ CHU Dijon, Dijon, France..
    Gaillard, Isabelle
    CHU Henri Mondor, F-94010 Creteil, France..
    Bologna, Serge
    Ctr Hosp Reg Univ CHR Nancy, Nancy, France..
    Ferme, Christophe
    Gustave Roussy Canc Campus, F-94805 Villejuif, France..
    Lugtenburg, Pieternella Johanna
    Erasmus MC, Inst Canc, Rotterdam, Netherlands..
    Morschhauser, Frank
    CHR Lille, Lille, France..
    Aurer, Igor
    Univ Hosp Ctr Zagreb, Zagreb, Croatia..
    Coiffier, Bertrand
    CHU Lyon, Lyon, France..
    Meyer, Ralph
    Juravinski Canc Ctr, Hamilton, ON, Canada..
    Seftel, Matthew
    Canc Care Manitoba, Winnipeg, MB, Canada..
    Wolf, Max
    Peter MacCallum Canc Inst, East Melbourne, Vic, Australia..
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sureda, Anna
    Hosp Santa Creu & Sant Pau, Barcelona, Spain..
    Mounier, Nicolas
    Hop Archet, Nice, France..
    Eight Cycles of ABVD Versus Four Cycles of BEACOPP(escalated) Plus Four Cycles of BEACOPP(baseline) in Stage III to IV, International Prognostic Score >= 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial2016Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, nr 17, s. 2028-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose To compare patients with high-risk stage III to IV Hodgkin lymphoma (HL) in the phase III European Organisation for Research and Treatment of Cancer 20012 Intergroup trial (Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma) who were randomly assigned to either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). Patients and Methods Patients with clinical stage III or IV HL, International Prognostic Score of 3 or higher, and age 60 years or younger received ABVD for eight cycles (ABVD(8)) or escalated-dose BEACOPP (BEACOPP(escalated)) for four cycles followed by baseline BEACOPP (BEACOPP(baseline)) for four cycles (BEACOPP(4+4)) without radiotherapy. Primary end points were event-free survival (EFS), treatment discontinuation, no complete response (CR) or unconfirmed complete response (CRu) after eight cycles, progression, relapse, or death. Secondary end points were CR rate, overall survival (OS), quality of life, secondary malignancies, and disease-free survival in CR/CRu patients. Results Between 2002 and 2010, 549 patients were randomly assigned to ABVD(8) (n = 275) or BEACOPP(4+4) (n = 274). Other characteristics included median age, 35 years; male, 75%; stage IV, 74%; "B" symptoms, 81%; and International Prognostic Score >= 4, 59%. WHO performance status was 0 (34%), 1 (48%), or 2 (17%). Median follow-upwas 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD(8) versus 69.3% for BEACOPP(4+4) (hazard ratio [HR], 0.86; 95% CI, 0.64 to 1.15; P = .312); disease-free survival was 85.8% versus 91.0% (HR, 0.59; 95% CI, 0.33 to 1.06; P = .076), and OS was 86.7% versus 90.3% (HR, 0.71; 95% CI, 0.42 to 1.21; P = .208). Death as a result of toxicity occurred in six and five patients, early discontinuation (before cycle 5) in 12 and 26 patients, treatment crossovers in five and 10 patients, and secondary malignancies in eight and 10 patients in the ABVD(8) and BEACOPP(4+4) arms, respectively. Conclusion ABVD(8) and BEACOPP(4+4) resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP(4+4) did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD(8), treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.

  • 97.
    Carreras-Puigvert, Jordi
    et al.
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Mol Biochem & Biophys, Sci Life Lab, S-17165 Stockholm, Sweden.
    Zitnik, Marinka
    Univ Ljubljana, Fac Comp & Informat Sci, SI-1000 Ljubljana, Slovenia.; Stanford Univ, Dept Comp Sci, Palo Alto, CA 94305 USA.
    Jemth, Ann-Sofie
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Mol Biochem & Biophys, Sci Life Lab, S-17165 Stockholm, Sweden.
    Carter, Megan
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.
    Unterlass, Judith E
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Mol Biochem & Biophys, Sci Life Lab, S-17165 Stockholm, Sweden.
    Hallström, Björn
    KTH Royal Inst Technol, Sci Life Lab, Cell Profiling Affin Prote, S-17165 Stockholm, Sweden.
    Loseva, Olga
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Mol Biochem & Biophys, Sci Life Lab, S-17165 Stockholm, Sweden.
    Karem, Zhir
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Mol Biochem & Biophys, Sci Life Lab, S-17165 Stockholm, Sweden.
    Calderón-Montaño, José Manuel
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Mol Biochem & Biophys, Sci Life Lab, S-17165 Stockholm, Sweden.
    Lindskog, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Edqvist, Per-Henrik D
    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.
    Matuszewski, Damian J.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ait Blal, Hammou
    KTH Royal Inst Technol, Sci Life Lab, Cell Profiling Affin Prote, S-17165 Stockholm, Sweden.
    Berntsson, Ronnie P A
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.
    Häggblad, Maria
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Biochem & Cellular Screening Facil, S-17165 Stockholm, Sweden.
    Martens, Ulf
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Biochem & Cellular Screening Facil, S-17165 Stockholm, Sweden.
    Studham, Matthew
    Stockholm Univ, Dept Biochem & Biophys, Stockholm Bioinformat Ctr, Sci Life Lab, Box 1031, S-17121 Solna, Sweden.
    Lundgren, Bo
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Biochem & Cellular Screening Facil, S-17165 Stockholm, Sweden.
    Wählby, Carolina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Sonnhammer, Erik L L
    Stockholm Univ, Dept Biochem & Biophys, Stockholm Bioinformat Ctr, Sci Life Lab, Box 1031, S-17121 Solna, Sweden.
    Lundberg, Emma
    KTH Royal Inst Technol, Sci Life Lab, Cell Profiling Affin Prote, S-17165 Stockholm, Sweden.
    Stenmark, Pål
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.
    Zupan, Blaz
    Univ Ljubljana, Fac Comp & Informat Sci, SI-1000 Ljubljana, Slovenia.; Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
    Helleday, Thomas
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Mol Biochem & Biophys, Sci Life Lab, S-17165 Stockholm, Sweden.
    A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family2017Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, nr 1, artikkel-id 1541Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.

  • 98.
    Cashin, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Considerations on the Selection Process for Cytoreductive Surgery and Hyperthermic IntraPeritoneal Chemotherapy for Colorectal Carcinomatosis Reply2015Inngår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 262, nr 2, s. e48-e49Artikkel i tidsskrift (Fagfellevurdert)
  • 99.
    Cashin, Peter H.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala Canc Clin, Uppsala, Sweden..
    Spang, N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Syk, I.
    Skane Univ Hosp, Dept Surg, S-21428 Malmo, Sweden..
    Frodin, J. E.
    Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden..
    Torkzad, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden..
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: A randomised trial2016Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 53, s. 155-162Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: First-line treatment of isolated resectable colorectal peritoneal metastases remains unclear. This study (the Swedish peritoneal study) compares cytoreductive surgery and intraperitoneal chemotherapy (surgery arm) with systemic chemotherapy (chemotherapy arm). Methods: Patients deemed resectable preoperatively were randomised to surgery and intraperitoneal 5-fluorouracil 550 mg/m(2) /d for 6 d with repeated courses every month or to systemic oxaliplatin and 5-fluorouracil regimen every second week. Both treatments continued for 6 months. Primary end-point was overall survival (OS) and secondary end-points were progression-free survival (PFS), and morbidity. Results: The study terminated prematurely when 48 eligible patients (24/arm) were included due to recruitment difficulties. Two-year OS was 54% in the surgery arm and 38% in the chemotherapy arm (p = 0.04). After 5 years, 8 versus 1 patient were alive, respectively (p = 0.02). Median OS was 25 months versus 18 months, respectively, hazard ratio 0.51 (95% confidence interval: 0.27-0.96, p = 0.04). PFS in the surgery arm was 12 months versus 11 months in the chemotherapy arm (p = 0.16) with 17% versus 0% 5-year PFS. Grade III-IV morbidity was seen in 42% and 50% of the patients, respectively. No mortalities. Conclusions: Cytoreductive surgery with intraperitoneal chemotherapy may be superior to systemic oxaliplatin-based treatment of colorectal cancer with resectable isolated peritoneal metastases.(ClinicalTrials. gov nr: NCT01524094).

  • 100.
    Cashin, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala Canc Clin, Uppsala, Sweden.
    Syk, I.
    Lund Univ, Sect Surg, Dept Clin Sci, Malmo, Sweden.
    Frodin, J. E.
    Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases2018Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, nr 7, s. 983-990Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.

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