uu.seUppsala universitets publikasjoner
Endre søk
Begrens søket
1234567 151 - 200 of 655
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 151.
    Eriksson, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Gustafsson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Fryknäs, Mårten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Gullbo, Joachim
    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.
    Nygren, Peter
    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 medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Repositioning Of Quinacrine For Treatment Of Acute Myeloid Leukemia - Synergies And In Vivo Effects2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, s. 367-368Artikkel i tidsskrift (Annet vitenskapelig)
  • 152.
    Eriksson, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Osterros, Albin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hassan, Sadia Bashir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Gullbo, Joachim
    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.
    Rickardson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. 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.
    Nygren, Peter
    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.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Repositioning of Quinacrine for Treatment of Acute Myeloid Leukemia2014Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 21Artikkel i tidsskrift (Annet vitenskapelig)
  • 153.
    Eriksson, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Österroos, Albin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hassan, Sadia Bashir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Gullbo, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Rickardson, Linda
    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.
    Nygren, Peter
    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.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia2015Inngår i: Blood Cancer Journal, ISSN 2044-5385, E-ISSN 2044-5385, Vol. 5, artikkel-id e307Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 mu M drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug-drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis.

  • 154.
    Eriksson, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Milenova, Ioanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Wenthe, Jessica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Moreno, Rafael
    IDIBELL Inst Catala Oncol, Barcelona, Spain..
    Ullenhag, Gustav
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Dimberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Alemany, Ramon
    IDIBELL Inst Catala Oncol, Barcelona, Spain..
    Loskog, Angelica S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Activating CD40 While Inhibiting IL6R Induces Cytokine Production without PDL1 Upregulation in DCs2017Inngår i: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 25, nr 5 S1, s. 54-54Artikkel i tidsskrift (Annet vitenskapelig)
  • 155.
    Eriksson, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Moreno, R
    Milenova, I. Yoanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Liljenfeldt, L
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Dieterich, L C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Christiansson, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Karlsson, H
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Ullenhag, Gustav
    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.
    Mangsbo, Sara M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Dimberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Alemany, R
    Loskog, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Activation of myeloid and endothelial cells by CD40L gene therapy supports T-cell expansion and migration into the tumor microenvironment2017Inngår i: Gene Therapy, ISSN 0969-7128, E-ISSN 1476-5462, Vol. 24, nr 2, s. 92-103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate T-helper 1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer. Further, the CD40L mechanisms of action were elucidated in cancer models. The results demonstrated that the virus transferring TMZ-CD40L had oncolytic capacity in pancreatic cancer cells and could control tumor progression. TMZ-CD40L was a potent stimulator of human myeloid cells and T-cell responses. Further, CD40L-mediated stimulation increased tumor-infiltrating T cells in vivo, which may be due to a direct activation of endothelial cells to upregulate receptors for lymphocyte attachment and transmigration. In conclusion, CD40L-mediated gene therapy is an interesting concept for the treatment of tumors with high levels of M2 macrophages, such as pancreatic cancer, and an oncolytic virus as carrier of CD40L may further boost tumor killing and immune activation.

  • 156.
    Eriksson, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wenthe, Jessica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Irenaeus, Sandra
    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. Univ Uppsala Hosp, Dept Oncol, Uppsala, Sweden..
    Loskog, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Lokon Pharma AB, Uppsala, Sweden..
    Ullenhag, Gustav
    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. Univ Uppsala Hosp, Dept Oncol, Uppsala, Sweden..
    Gemcitabine reduces MDSCs, tregs and TGF beta-1 while restoring the teff/treg ratio in patients with pancreatic cancer2016Inngår i: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 14, artikkel-id 282Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cancer immunotherapy can be potentiated by conditioning regimens such as cyclophosphamide, which reduces the level of regulatory T cells (tregs). However, myeloid suppressive cells are still remaining. Accordingly to previous reports, gemcitabine improves immune status of cancer patients. In this study, the role of gemcitabine was further explored to map its immunological target cells and molecules in patients with pancreatic cancer.

    Methods: Patient blood was investigated by flow cytometry and cytokine arrays at different time points during gemcitabine treatment.

    Results: The patients had elevated myeloid-derived suppressor cells (MDSCs), and Tregs at diagnosis. Myeloid cells were in general decreased by gemcitabine. The granulocytic MDSCs were significantly reduced while monocytic MDSCs were not affected. In vitro, monocytes responding to IL-6 by STAT3 phosphorylation were prevented to respond in gemcitabine medium. However, gemcitabine could not prevent STAT3 phosphorylation in IL-6-treated tumor cell lines. TGF beta-1 was significantly reduced after only one treatment and continued to decrease. At the same time, the effector T cell:Treg ratio was increased and the effector T cells had full proliferative capacity during the gemcitabine cycle. However, after a resting period, the level of suppressor cells and TGF beta-1 had been restored showing the importance of continuous conditioning.

    Conclusions: Gemcitabine regulates the immune system in patients with pancreatic cancer including MDSCs, Tregs and molecules such as TGF beta-1 but does not hamper the ability of effector lymphocytes to expand to stimuli. Hence, it may be of high interest to use gemcitabine as a conditioning strategy together with immunotherapy.

  • 157.
    Eriksson, Oskar
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Asplund, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hegde, Geeta
    Human Prot Atlas Project, Lab Surgpath, Mumbai Site, Bombay, Maharashtra, India..
    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.
    Navani, Sanjay
    Human Prot Atlas Project, Lab Surgpath, Mumbai Site, Bombay, Maharashtra, India..
    Ponten, Fredrik
    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.
    Siegbahn, A
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    A stromal cell population in the large intestine identified by tissue factor expression that is lost during colorectal cancer progression2016Inngår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 116, nr 6, s. 1050-1059Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Colorectal cancer (CRC) is a major cause of morbidity and mortality, and the composition of the tumour stroma is a strong predictor of survival in this cancer type. Tissue factor (TF) functions as the trigger of haemostasis together with its ligand coagulation factor VII/ VIIa, and TF expression has been found in tumour cells of colorectal tumours. However, TF expression in the CRC tumour stroma or its relationship to patient outcome has not yet been studied. To address this question we developed and validated a specific anti-TF antibody using standardised methods within the Human Protein Atlas project. We used this antibody to investigate TF expression in normal colorectal tissue and CRC using immunofluorescence and immunohistochemistry in two patient cohorts. TF was strongly expressed in a cell population immediately adjacent to the colorectal epithelium. These TF-positive cells were ACTA2-negative but weakly vimentin-positive, defining a specific population of pericryptal sheath cells. In colorectal tumours, TF-positive sheath cells were progressively lost after the adenoma-to-carcinoma transition, demonstrating downregulation of this source of TF in CRC. Furthermore, loss of sheath cell TF was significantly associated with poor overall and disease-specific survival in rectal but not colon cancers. In conclusion, we demonstrate that TF is a marker of a specific cell population in the large intestine, which is lost during CRC progression. Our results highlight the role of the tumour stroma in this cancer type and suggest TF to be a potential prognostic biomarker in rectal cancers through the identification of pericryptal sheath cells.

  • 158.
    Erlandsson, J.
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Colorectal Surg, Stockholm, Sweden.
    Pettersson, D.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Norrtalje Sjukhus, Dept Surg, Norrtalje, Sweden.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Holm, T.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Colorectal Surg, Stockholm, Sweden.
    Martling, A.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Colorectal Surg, Stockholm, Sweden.
    Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy2019Inngår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 106, nr 9, s. 1248-1256Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The optimal timing of surgery for rectal cancer after radiotherapy (RT) is disputed. The Stockholm III trial concluded that it was oncologically safe to delay surgery for 4-8weeks after short-course RT (SRT), with fewer postoperative complications compared with SRT with surgery within a week. Other studies have indicated that an even shorter interval between RT and surgery (0-3 days) might be beneficial. The aim of this study was to identify the optimal interval to surgery after RT.

    Methods: Patients were analysed as treated, in terms of overall treatment time (OTT), the interval from the start of RT until the day of surgery. Patients receiving SRT (5x5Gy) were categorized according to OTT: 7 days (group A), 8-13 days (group B), 5-7weeks (group C) and 8-13weeks (group D). Patients receiving long-course RT (25x2Gy) were grouped into those with an OTT of 9-11weeks (group E) or 12-14weeks (group F). Outcomes assessed were postoperative complications and early mortality.

    Results: A total of 810 patients were analysed (group A, 100; group B, 247; group C, 192; group D, 160; group E, 52; group F, 59). Baseline patient characteristics were similar. There were significantly more overall complications in group B than in groups C and D. Adjusted odds ratios, with B as the reference group, were: 0.72 (95 per cent c. i. 0.40 to 1.32; P = 0.289), 0.50 (0.30 to 0.84; P = 0.009) and 0.39 (0.23 to 0.65; P < 0.001) for groups A, C and D respectively. Early mortality was similar in all groups. There were no significant differences between long-course RT groups.

    Conclusion: These results suggest that surgery should optimally be delayed for 4-12weeks (OTT 5-13weeks) after SRT.

  • 159.
    Erlandsson, Johan
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Holm, Torbjörn
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Pettersson, David
    Karolinska Inst, Dept Mol Med & Surg, Norrtalje, Sweden.;Norrtalje Hosp, Dept Surg, Norrtalje, Sweden..
    Berglund, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Cedermark, Björn
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Radu, Calin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Johansson, Hemming
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Machado, Mikael
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Karolinska Inst, Ersta Hosp, Stockholm, Sweden..
    Hjern, Fredrik
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Karolinska Inst, Ersta Hosp, Stockholm, Sweden..
    Hallböök, Olof
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Syk, Ingvar
    Lund Univ, Dept Surg, Malmo, Sweden..
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Martling, Anna
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial2017Inngår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 18, nr 3, s. 336-346Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery.

    Methods: In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 x 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4-8 weeks (short-course radiotherapy with delay) or 25 x 2 Gy radiation dose with surgery after 4-8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1.7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813.

    Findings: Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33.4 months (range 18.2-62.2) in the short-course radiotherapy group and 19.3 months (8.5-39.5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33.3 months (range 17.8-114.3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1.44 [95% CI 0.41-5.11]; long-course radiotherapy with delay 2.24 [0.71-7.10]; p=0.48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient (<1%) of 357 after short-course radiotherapy, 23 (7%) of 355 after short-course radiotherapy with delay, and six (5%) of 128 patients after long-course radiotherapy with delay. Frequency of postoperative complications was similar between all arms when the three-arm randomisation was analysed (65 [50%] of 129 patients in the short-course radiotherapy group; 48 [38%] of 128 patients in the short-course radiotherapy with delay group; 50 [39%] of 128 patients in the long-course radiotherapy with delay group; odds ratio [OR] vs short-course radiotherapy: short-course radiotherapy with delay 0.59 [95% CI 0.36-0.97], long-course radiotherapy with delay 0.63 [0.38-1.04], p=0.075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0.61 [95% CI 0.45-0.83] p=0.001).

    Interpretation: Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery.

  • 160.
    Erlandsson, Johan
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Karolinska Univ Hosp, Dept Colorectal Canc, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Lorinc, Ester
    Skane Univ Hosp, Dept Pathol & Cytol, Div Pathol Lund, Lund, Sweden;Dept Clin Sci, Div Oncol & Pathol, Barngatan 2B, SE-22185 Lund, Sweden.
    Ahlberga, Madelene
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Karolinska Univ Hosp, Dept Colorectal Canc, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Pettersson, David
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Norrtalje Sjukhus, Dept Surg, Norrtalje, Sweden;TioHundra AB, Kirurgmottagningen, Box 905, S-76129 Norrtalje, Sweden.
    Holm, Torbjorn
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Karolinska Univ Hosp, Dept Colorectal Canc, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Martling, Anna
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Karolinska Univ Hosp, Dept Colorectal Canc, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Tumour regression after radiotherapy for rectal cancer - Results from the randomised Stockholm III trial2019Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 135, s. 178-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and purpose: Neoadjuvant radiotherapy (RT) in rectal cancer induces tumour regression with a possible complete response (pCR). The optimal fractionation and timing to surgery is not established. The Stockholm III trial randomly assigned 840 patients to 5 x 5 Gy surgery within one week (SRT), 5 x 5 Gy with surgery after 4-8 weeks, and 2 Gy x 25 with surgery after 4-8 weeks (LRT-delay). The aim of this substudy was to assess tumour regression and correlation to survival. Material and methods: All available microscopy slides were assessed by one pathologist, blinded to treatment, regarding tumour regression, graded according to the Dworak system (TRG), TNM-stage and other standard histopathology characteristics. Patients' data were collected from the Swedish ColoRectal Cancer Registry. Outcomes were TRG, pCR-rates, overall survival (OS) and time to recurrence (TTR). Results: 318, 285 and 94 patients were included in the SRT, SRT-delay and LRT-delay groups. Median follow up was 5.7 years. There were significantly lower tumour stages after SRT-delay. pCR was seen in 1 (0.3%), 29 (10.4%) and 2 (2.2%) patients in SRT, SRT-delay and LRT-delay, respectively. The pCR and Dworak grade 4 were associated with superior survival. pCR vs no-pCR Hazard Ratio (95% Confidence Interval) OS: 0.51 (0.26-0.99) p = 0.046, TTR: 0.27 (0.09-0.86) p = 0.027. Conclusion: SRT-delay induces pCR in about 10% of the patients and is in this aspect superior to 25 x 2 Gy. A complete tumour response, TRG 4 using the Dworak system, or a pCR, is associated with superior OS and TTR.

  • 161.
    Eskelund, Christian Winther
    et al.
    Rigshosp, Dept Hematol, Copenhagen, Denmark;Biotech Res & Innovat Ctr, Copenhagen, Denmark.
    Albertsson-Lindblad, Alexandra
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Oncol & Pathol, Lund, Sweden.
    Kolstad, Arne
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
    Laurell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Raty, Riikka
    Helsinki Univ Hosp, Dept Hematol, Helsinki, Finland.
    Pedersen, Lone Bredo
    Rigshosp, Dept Hematol, Copenhagen, Denmark.
    Geisler, Christian Hartmann
    Rigshosp, Dept Hematol, Copenhagen, Denmark.
    Jerkeman, Mats
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Oncol & Pathol, Lund, Sweden.
    Gronbaek, Kirsten
    Rigshosp, Dept Hematol, Copenhagen, Denmark;Biotech Res & Innovat Ctr, Copenhagen, Denmark.
    Lenalidomide plus bendamustine-rituximab does not overcome the adverse impact of TP53 mutations in mantle cell lymphoma2018Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, nr 11, s. E541-E543Artikkel i tidsskrift (Annet vitenskapelig)
  • 162.
    Everhov, Åsa H
    et al.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.; Södersjukhuset, Dept Surg, SE-11861 Stockholm, Sweden.
    Ekberg, Sara
    Unit of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet.
    Hirschberg, Angelica Lindén
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Bergmark, Karin
    Sahlgrens Acad, Dept Oncol, Gothenburg, Sweden.
    Rådestad, Angelique Flöter
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Glimelius, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Smedby, Karin E
    Unit of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet.
    Lost workdays in uterine cervical cancer survivors compared to the general population: impact of treatment and relapse.2016Inngår i: Journal of cancer survivorship, ISSN 1932-2259, E-ISSN 1932-2267, Vol. 10, nr 3, s. 514-523Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The aim of the present study was to examine the risk of lost workdays due to sick leave and disability pension by treatment modality and relapse in a population-based cohort of cervical cancer survivors versus matched comparators.

    METHODS: We identified 1971 cervical cancer patients aged ≤60 years (median 42) at diagnosis in Sweden 2003-2009 and 9254 population comparators. Information on sociodemographic and clinical characteristics, sick leave, and disability pension was retrieved from nationwide prospective registers. Differences in the annual mean number of lost workdays were calculated by linear regression, and hazard ratios (HRs) of disability pension were calculated by Cox regression analysis, with follow-up through September 2013.

    RESULTS: Cervical cancer patients had more lost workdays annually than comparators up to 8 years following diagnosis. Relapse-free patients had more lost workdays than comparators up to 4 years. Risk of disability pension during follow-up was increased among the relapse-free patients treated with hysterectomy (HR 1.8 [95 % confidence interval (CI) 1.1-2.8]), hysterectomy plus chemotherapy and/or radiotherapy (HR 2.5 [95 % CI 1.2-5.4]), or chemotherapy and/or radiotherapy alone (HR 3.0 [95 % CI 1.3-6.8]), compared with the population. Women treated with fertility-sparing surgery did not have more lost workdays than the population beyond the first year and were not at increased risk of disability pension.

    CONCLUSION: We observed a long-standing increased risk of lost workdays among cervical cancer patients, overall, as well as among relapse-free patients.

    IMPLICATIONS FOR CANCER SURVIVORS: Extensive but not limited treatment was associated with increased risk of lost workdays, possibly reflecting an association between treatment side effects and work ability.

  • 163.
    Fahlström, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Nyholm, Tufve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Perfusion Magnetic Resonance Imaging Changes in Normal Appearing Brain Tissue after Radiotherapy in Glioblastoma Patients may Confound Longitudinal Evaluation of Treatment Response2018Inngår i: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 52, nr 2, s. 143-151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The aim of this study was assess acute and early delayed radiation-induced changes in normal-appearing brain tissue perfusion as measured with perfusion magnetic resonance imaging (MRI) and the dependence of these changes on the fractionated radiotherapy (FRT) dose level.

    Patients and methods: Seventeen patients with glioma WHO grade III-IV treated with FRT were included in this prospective study, seven were excluded because of inconsistent FRT protocol or missing examinations. Dynamic susceptibility contrast MRI and contrast-enhanced 3D-T1-weighted (3D-T1w) images were acquired prior to and in average (standard deviation): 3.1 (3.3), 34.4 (9.5) and 103.3 (12.9) days after FRT. Pre-FRT 3D-T1w images were segmented into white- and grey matter. Cerebral blood volume (CBV) and cerebral blood flow (CBF) maps were calculated and co-registered patient-wise to pre-FRT 3D-T1w images. Seven radiation dose regions were created for each tissue type: 0-5 Gy, 5-10 Gy, 10-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy and 50-60 Gy. Mean CBV and CBF were calculated in each dose region and normalised (nCBV and nCBF) to the mean CBV and CBF in 0-5 Gy white- and grey matter reference regions, respectively.

    Results: Regional and global nCBV and nCBF in white- and grey matter decreased after FRT, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in grey matter.

    Conclusions: Our data suggest that radiation-induced perfusion changes occur in normal-appearing brain tissue after FRT. This can cause an overestimation of relative tumour perfusion using dynamic susceptibility contrast MRI, and can thus confound tumour treatment evaluation.

  • 164.
    Fahlström, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Fransson, Samuel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Nyholm, Tufve
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Dynamic Contrast-Enhanced Magnetic Resonance Imaging May Act as a Biomarker for Vascular Damage in Normal Appearing Brain Tissue after Radiotherapy in Patients with Glioblastoma2018Inngår i: Acta Radiologica Open, ISSN 2058-4601, Vol. 7, nr 11Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising perfusion method and may be useful in evaluating radiation-induced changes in normal-appearing brain tissue.

    Purpose: To assess whether radiotherapy induces changes in vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) derived from DCE-MRI in normal-appearing brain tissue and possible relationships to radiation dose given.

    Material and Methods: Seventeen patients with glioblastoma treated with radiotherapy and chemotherapy were included; five were excluded because of inconsistencies in the radiotherapy protocol or early drop-out. DCE-MRI, contrast-enhanced three-dimensional (3D) T1-weighted (T1W) images and T2-weighted fluid attenuated inversion recovery (T2-FLAIR) images were acquired before and on average 3.3, 30.6, 101.6, and 185.7 days after radiotherapy. Pre-radiotherapy CE T1W and T2-FLAIR images were segmented into white and gray matter, excluding all non-healthy tissue. Ktrans and Ve were calculated using the extended Kety model with the Parker population-based arterial input function. Six radiation dose regions were created for each tissue type, based on each patient's computed tomography-based dose plan. Mean Ktrans and Ve were calculated over each dose region and tissue type.

    Results: Global Ktrans and Ve demonstrated mostly non-significant changes with mean values higher for post-radiotherapy examinations in both gray and white matter compared to pre-radiotherapy. No relationship to radiation dose was found.

    Conclusion: Additional studies are needed to validate if Ktrans and Ve derived from DCE-MRI may act as potential biomarkers for acute and early-delayed radiation-induced vascular damages. No dose-response relationship was found.

  • 165.
    Fakhoury, Isabelle
    et al.
    Amer Univ Beirut, Dept Biol, Beirut, Lebanon..
    Saad, Walid
    Amer Univ Beirut, Dept Chem & Petr Engn, Beirut, Lebanon..
    Bouhadir, Kamal
    Amer Univ Beirut, Dept Chem, Beirut, Lebanon..
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Schneider-Stock, Regine
    Univ Erlangen Nurnberg, Inst Pathol, Expt Tumor Pathol, Erlangen, Germany..
    Gali-Muhtasib, Hala
    Amer Univ Beirut, Dept Biol, Beirut, Lebanon.;Amer Univ Beirut, Dept Anat, Cell Biol, Physiol,Fac Med, Beirut, Lebanon..
    Uptake, delivery, and anticancer activity of thymoquinone nanoparticles in breast cancer cells2016Inngår i: Journal of nanoparticle research, ISSN 1388-0764, E-ISSN 1572-896X, Vol. 18, nr 7, artikkel-id 210Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thymoquinone (TQ) is a promising anticancer molecule but its development is hindered by its limited bioavailability. Drug encapsulation is commonly used to overcome low drug solubility, limited bioavailability, and nonspecific targeting. In this project, TQ nanoparticles (TQ-NP) were synthesized and characterized. The cytotoxicity of the NP was investigated in nontumorigenic MCF-10-A breast cells, while the uptake, distribution, as well as the anticancer potential were investigated in MCF-7 and MDA-MB-231 breast cancer cells. Flash Nanoprecipitation and dynamic light scattering coupled with scanning electron microscopy were used to prepare and characterize TQ-NP prior to measuring their anticancer potential by MTT assay. The uptake and subcellular intake of TQ-NP were evaluated by fluorometry and confocal microscopy. TQ-NP were stable with a hydrodynamic average diameter size around 100 nm. Entrapment efficiency and loading content of TQ-NP were high (around 80 and 50 %, respectively). In vitro, TQ-NP had equal or enhanced anticancer activity effects compared to TQ in MCF-7 and aggressive MDA-MB-231 breast cancer cells, respectively, with no significant cytotoxicity of the blank NP. In addition, TQ and TQ-NP were relatively nontoxic to MCF-10-A normal breast cells. TQ-NP uptake mechanism was both time and concentration dependent. Treatment with inhibitors of endocytosis suggested the involvement of caveolin in TQ-NP uptake. This was further confirmed by subcellular localization findings showing the colocalization of TQ-NP with caveolin and transferrin as well as with the early and late markers of endocytosis. Altogether, the results describe an approach for the enhancement of TQ anticancer activity and uncover the mechanisms behind cell-TQ-NP interaction.

  • 166.
    Fessé, Per
    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, Experimentell och klinisk onkologi.
    Qvarnström, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Nyman, Jan
    Hermansson, Ingegerd
    Ahlgren, Johan
    Turesson, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    UV-Radiation Response Proteins Reveal Undifferentiated Cutaneous Interfollicular Melanocytes with Hyperradiosensitivity to Differentiation at 0.05 Gy Radiotherapy Dose Fractions2019Inngår i: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 191, nr 1, s. 93-106Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To date, the response activated in melanocytes by repeated genotoxic insults from radiotherapy has not been explored. We hypothesized that the molecular pathways involved in the response of melanocytes to ionizing radiation and ultraviolet radiation (UVR) are similar. Skin punch biopsies, not sun-exposed, were collected from prostate cancer patients before, as well as at 1 and 6.5 weeks after daily doses of 0.05-1.1 Gy. Interfollicular melanocytes were identified by ΔNp63- and eosin-periodic acid Schiff staining. Immunohistochemistry and immunofluorescence were performed to detect molecular markers of the melanocyte lineage. Melanocytes were negative for ΔNp63, and the number remained unchanged over the treatment period. At radiation doses as low as 0.05 Gy, melanocytes express higher protein levels of microphthalmia-associated transcription factor (MITF) and Bcl-2. Subsets of MITF- and Bcl-2-negative melanocytes were identified among interfollicular melanocytes in unexposed skin; the cell number in both subsets was reduced after irradiation in a way that indicates low-dose hyperradiosensitivity. A corresponding increase in MITF- and Bcl-2-positive cells was observed. PAX3 and SOX10 co-localized to some extent with MITF in unexposed skin, more so with radiation exposure. Low doses of ionizing radiation also intensified c-KIT and DCT staining. Nuclear p53 and p21 were undetectable in melanocytes. Apoptosis and proliferation could not be observed. In conclusion, undifferentiated interfollicular melanocytes were identified, and responded with differentiation in a hypersensitive manner at 0.05 Gy doses. Radioresistance regarding cell death was maintained up to fractionated doses of 1.1 Gy, applied for 7 weeks. The results suggest that the initial steps of melanin synthesis are common to ionizing radiation and UVR, and underline the importance of keratinocyte-melanocyte interaction behind hyperpigmentation and depigmentation to radiotherapy.

  • 167.
    Fonnes, T.
    et al.
    Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, CCBIO, Bergen, Norway;Haukeland Hosp, Dept Obstet & Gynaecol, Bergen, Norway.
    Trovik, J.
    Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, CCBIO, Bergen, Norway;Haukeland Hosp, Dept Obstet & Gynaecol, Bergen, Norway.
    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.
    Fasmer, K. E.
    Haukeland Hosp, Dept Radiol, Ctr Nucl Med PET, Bergen, Norway;Haukeland Hosp, Dept Radiol, Bergen, Norway.
    Marcickiewicz, J.
    Univ Gothenburg, Dept Gynaecol, Sahlgrenska Acad, Gothenburg, Sweden;Hallands Hosp Varberg, Dept Obstet & Gynaecol, Varberg, Sweden.
    Tingulstad, S.
    St Olavs Hosp, Dept Gynaecol, Trondheim, Norway.
    Staff, A. C.
    Oslo Univ Hosp, Dept Gynaecol, Oslo, Norway;Univ Oslo, Oslo, Norway.
    Bjorge, L.
    Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, CCBIO, Bergen, Norway;Haukeland Hosp, Dept Obstet & Gynaecol, Bergen, Norway.
    Amant, F.
    Katholieke Univ Leuven, Dept Gynaecol Oncol, UZGasthuisberg, Leuven, Belgium;Netherlands Canc Inst, Ctr Gynaecol Oncol, Amsterdam, Netherlands;Acad Med Ctr, Amsterdam, Netherlands.
    Haldorsen, I. S.
    Haukeland Hosp, Dept Radiol, Bergen, Norway;Univ Bergen, Sect Radiol, Dept Clin Med, Bergen, Norway.
    Werner, H. M. J.
    Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, CCBIO, Bergen, Norway;Haukeland Hosp, Dept Obstet & Gynaecol, Bergen, Norway.
    Akslen, L. A.
    Univ Bergen, Sect Pathol, Dept Clin Med, Ctr Canc Biomarkers CCBIO, Bergen, Norway;Haukeland Hosp, Dept Pathol, Bergen, Norway.
    Tangen, I. L.
    Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, CCBIO, Bergen, Norway;Haukeland Hosp, Dept Obstet & Gynaecol, Bergen, Norway.
    Krakstad, C.
    Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, CCBIO, Bergen, Norway;Haukeland Hosp, Dept Obstet & Gynaecol, Bergen, Norway.
    Asparaginase-like protein 1 expression in curettage independently predicts lymph node metastasis in endometrial carcinoma: a multicentre study2018Inngår i: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 125, nr 13, s. 1695-1703Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective Design Correct preoperative identification of high-risk patients is important to optimise surgical treatment and improve survival. We wanted to explore if asparaginase-like protein 1 (ASRGL1) expression in curettage could predict lymph node metastases and poor outcome, potentially improving preoperative risk stratification. Multicentre study. Setting Population Ten hospitals in Norway, Sweden and Belgium. Women diagnosed with endometrial carcinoma. Methods Main outcome measures ASRGL1 expression in curettage specimens from 1144 women was determined by immunohistochemistry. ASRGL1 status related to disease-specific survival, lymph node status, preoperative imaging parameters and clinicopathological data. Results Conclusions ASRGL1 expression had independent prognostic value in multivariate survival analyses, both in the whole patient population (hazard ratio (HR) 1.63, 95% CI 1.11-2.37, P = 0.012) and in the low-risk curettage histology subgroup (HR 2.54, 95% CI 1.44-4.47, P = 0.001). Lymph node metastases were more frequent in women with low expression of ASRGL1 compared with women with high ASRGL1 levels (23% versus 10%, P < 0.001), and low ASRGL1 level was found to independently predict lymph node metastases (odds ratio 2.07, 95% CI 1.27-3.38, P = 0.003). Low expression of ASRGL1 in curettage independently predicts lymph node metastases and poor disease-specific survival.

  • 168.
    Fonnes, Tina
    et al.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Berg, Hege F.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Bredholt, Therese
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    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.
    Sortland, Kristina
    Univ Bergen, Dept Biomed, Bergen.
    Berg, Anna
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Salvesen, Helga B.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Akslen, Lars A.
    Haukeland Hosp, Dept Pathol, Bergen; Univ Bergen, Ctr Canc Biomarkers, Dept Clin Med, Sect Pathol, Bergen.
    Werner, Henrica M. J.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Trovik, Jone
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Tangen, Ingvild L.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Krakstad, Camilla
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer, and is frequently lost in metastatic lesions2018Inngår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 148, nr 1, s. 197-203Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective

    Loss of Asparaginase-like protein 1 (ASRGL1) has been suggested as a prognostic biomarker in endometrial carcinoma. Our objective was to validate this in a prospectively collected, independent patient cohort, and evaluate ASRGL1 expression in endometrial carcinoma precursor lesion and metastases.

    Methods

    782 primary endometrial carcinomas, 90 precursor lesions (complex atypical hyperplasia), and 179 metastases (from 87 patients) were evaluated for ASRGL1 expression by immunohistochemistry in relation to clinical and histopathological data. ASRGL1 mRNA level was investigated in 237 primary tumors and related to survival and ASRGL1 protein expression.

    Results

    Low expression of ASRGL1 protein and ASRGL1 mRNA predicted poor disease specific survival (P < 0.001). In multivariate survival analyses ASRGL1 had independent prognostic value both in the whole patient cohort (Hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.04–2.26, P = 0.031) and within the endometrioid subgroup (HR: 2.64, CI: 1.47–4.74, P = 0.001). Low ASRGL1 expression was less frequent in patients with low grade endometrioid primary tumors compared to high grade endometrioid and non-endometrioid primary tumors, and ASRGL1 was lost in the majority of metastatic lesions.

    Conclusions

    In a prospective setting ASRGL1 validates as a strong prognostic biomarker in endometrial carcinoma. Loss of ASRGL1 is associated with aggressive disease and poor survival, and is demonstrated for the first time to have independent prognostic value in the entire endometrial carcinoma patient population.

  • 169. Fredholm, H.
    et al.
    Magnusson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lindstrom, L. S.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Eaker, Sonja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lindman, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Bergh, J.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Pontén, Fredrik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Frisell, J.
    Fredriksson, I.
    Breast cancer in young women - age a risk factor only in those not given chemotherapy2014Inngår i: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 23, nr S1, s. S12-S12, artikkel-id HM31Artikkel i tidsskrift (Annet vitenskapelig)
  • 170.
    Fredholm, Hanna
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, P9 03, SE-17176 Stockholm, Sweden..
    Magnusson, Kristina
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Lindstrom, Linda S.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden..
    Tobin, Nicholas P.
    Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, Stockholm, Sweden..
    Lindman, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Bergh, Jonas
    Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, Stockholm, Sweden.;Karolinska Oncol, Radiumhemmet, Karolinska Univ Hosp, Stockholm, Sweden..
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Regional Cancer Center, Uppsala University Hospital, Uppsala, 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.
    Frisell, Jan
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, P9 03, SE-17176 Stockholm, Sweden..
    Fredriksson, Irma
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, P9 03, SE-17176 Stockholm, Sweden..
    Breast cancer in young women and prognosis: How important are proliferation markers?2017Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 84, s. 278-289Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim:

    Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.

    Methods:

    Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged >= 40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins.

    Results:

    Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age < 40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A ( HR 6.21 [2.17-17.6]).

    Conclusions:

    The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.

  • 171.
    Frenzel, K.
    et al.
    BioNTech Grp Mainz, Mainz, Germany..
    Heesen, L.
    BioNTech Grp Mainz, Mainz, Germany..
    Bolte, S.
    BioNTech Grp Mainz, Mainz, Germany..
    Bukur, V.
    BioNTech Grp Mainz, Mainz, Germany..
    Diken, M.
    TRON gGmbH, TRON, Mainz, Germany..
    Derhovanessian, E.
    BioNTech Grp Mainz, Mainz, Germany..
    Kreiter, S.
    BioNTech Grp Mainz, Mainz, Germany..
    Kuhn, A.
    BioNTech Grp Mainz, Mainz, Germany..
    Kuehlcke, K.
    EUFETS GmbH, Idar Oberstein, Germany..
    Löwer, M.
    TRON gGmbH, TRON, Mainz, Germany..
    De Greve, J.
    UZ Brussels, Dept Med & Mol Oncol, Brussels, Belgium..
    Lindman, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Pascolo, S.
    Univ Zurich, URPP Translat Canc Res, Zurich, Switzerland..
    Schmidt, M.
    Univ Med Mainz, Klin & Poliklin Geburtshilfe & Frauengesundheit, Mainz, Germany..
    Schneeweiss, A.
    NCT Heidelberg, Sekt Gynakol Onkol, Heidelberg, Germany..
    Sjöblom, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Thielemans, K.
    Univ Hosp Brussels, Dept Immunol Physiol, Brussels, Belgium..
    Zitvogel, L.
    Gustave Roussy Inst Cancerol, Tumour Immunol & Immunotherapy, Villejuif, France..
    Tuereci, Ö.
    CI3 Cluster Individualized Immunointervent, Mainz, Germany..
    Sahin, U.
    BioNTech Grp Mainz, Mainz, Germany..
    Mutanome engineered RNA immuno-therapy (MERIT) for patients with triple negative breast cancer2017Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, nr suppl 11Artikkel i tidsskrift (Annet vitenskapelig)
  • 172.
    Fristedt Duvefelt, Charlotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Lub, Susanne
    Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, (VUB) Belgium..
    Prasoon, Agarwal
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Arngården, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Hammarberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Maes, Ken
    Van Valckenborgh, Els
    Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, (VUB) Belgium..
    Vanderkerekn, Karin
    Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, (VUB) Belgium..
    Jernberg-Wiklund, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Increased resistance to proteaome inhibitors in multiple myeloma mediated by cIAP2: implications for a combinatorial treatment2015Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, nr 24, s. 20621-20635Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite the introduction of new treatment options for multiple myeloma (MM), a majority of patients relapse due to the development of resistance. Unraveling new mechanisms underlying resistance could lead to identification of possible targets for combinatorial treatment. Using TRAF3 deleted/mutated MM cell lines, we evaluated the role of the cellular inhibitor of apoptosis 2 (cIAP2) in drug resistance and uncovered the plausible mechanisms underlying this resistance and possible strategies to overcome this by combinatorial treatment. In MM, cIAP2 is part of the gene signature of aberrant NF-kappa B signaling and is heterogeneously expressed amongst MM patients. In cIAP2 overexpressing cells a decreased sensitivity to the proteasome inhibitors bortezomib, MG132 and carfilzomib was observed. Gene expression analysis revealed that 440 genes were differentially expressed due to cIAP2 overexpression. Importantly, the data imply that cIAPs are rational targets for combinatorial treatment in the population of MM with deleted/mutated TRAF3. Indeed, we found that treatment with the IAP inhibitor AT-406 enhanced the anti-MM effect of bortezomib in the investigated cell lines. Taken together, our results show that cIAP2 is an important factor mediating bortezomib resistance in MM cells harboring TRAF3 deletion/mutation and therefore should be considered as a target for combinatorial treatment.

  • 173.
    Fristedt, Richard
    et al.
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci, SE-22185 Lund, Sweden..
    Borg, David
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci, SE-22185 Lund, Sweden..
    Hedner, Charlotta
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci, SE-22185 Lund, Sweden..
    Berntsson, Jonna
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci, SE-22185 Lund, Sweden..
    Nodin, Bjorn
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci, SE-22185 Lund, Sweden..
    Eberhard, Jakob
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci, SE-22185 Lund, Sweden..
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Jirström, Karin
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci, SE-22185 Lund, Sweden..
    Prognostic impact of tumour-associated B cells and plasma cells in oesophageal and gastric adenocarcinoma2016Inngår i: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 7, nr 6, s. 848-859Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: While it is well established that the cell-mediated immune response plays an important role in cancer progression and spread, the role of the humoral immune response in this regard has been less studied. According to the existing literature, dense infiltration of B cells or plasma cells appears to correlate mainly with an improved prognosis in several types of cancer, but their prognostic impact in oesophageal and gastric cancer has not yet been described. Methods: Immunohistochemistry was applied on tissue microarrays (TMA) to assess the stromal density of B cells (CD20+) and plasma cells [CD138+ or immunoglobulin kappa C (IGKC+)] in chemo-/radiotherapy-naive tumours from a consecutive cohort of 174 patients with resected oesophageal or gastric adenocarcinoma. Cox proportional hazard's modelling was applied to examine the impact of the investigated markers on overall survival (OS) and time to recurrence (TTR). Results: In curatively treated patients with oesophageal adenocarcinoma, high expression of IGKC was an independent predictor of a prolonged OS [hazard ratio (HR) 0.10; 95% confidence interval (CI), 0.02-0.57], and TTR (HR 0.15; 95% CI, 0.03-0.71). In curatively treated patients with gastric adenocarcinoma, high expression of IGKC independently predicted a prolonged OS (HR 0.46; 95 % CI, 0.24-0.87) and TTR (HR 0.46; 95% CI, 0.21-0.98). Expression of CD20 was not prognostic, and CD138 expression was only prognostic in unadjusted analysis of TTR in gastric cancer. Conclusions: These results demonstrate, for the first time, that abundant infiltration of IGKC+ plasma cells independently predicts a prolonged survival in both oesophageal and gastric cancer.

  • 174.
    Fryknäs, Mårten
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Zhang, Xiaonan
    Linkping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.;Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, SE-17176 Stockholm, Sweden..
    Bremberg, Ulf
    Beactica, SE-75450 Uppsala, Sweden..
    Senkowski, Wojciech
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Olofsson, Maria Hägg
    Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, SE-17176 Stockholm, Sweden..
    Brandt, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Persson, Ingmar
    Swedish Univ Agr Sci, Dept Chem & Biotechnol, POB 7015, SE-75651 Uppsala, Sweden..
    D'Arcy, Padraig
    Linkping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden..
    Gullbo, Joachim
    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.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Schughart, Leoni Kunz
    Tech Univ Dresden, OncoRay Natl Ctr Radiat Res Oncol, D-01307 Dresden, Germany..
    Linder, Stig
    Linkping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.;Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, SE-17176 Stockholm, Sweden..
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Iron chelators target both proliferating and quiescent cancer cells2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 38343Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation. Compounds that chelate iron possess anti-cancer activity, an effect largely attributed to inhibition of ribonucleotide reductase in proliferating cells. Here we show that iron chelators decrease mitochondrial energy production, an effect poorly tolerated by metabolically stressed tumor cells. These pleiotropic features make iron chelators an attractive option for the treatment of solid tumors containing heterogeneous populations of proliferating and quiescent cells.

  • 175.
    Fukuhara, Mari
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Agnarsdottir, Margret
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Edqvist, Per-Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Coter, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    SATB2 is expressed in Merkel cell carcinoma2016Inngår i: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 308, nr 6, s. 449-454Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Merkel cell carcinoma (MCC) is a rare aggressive skin cancer with neuroendocrine differentiation. With immunohistochemistry, the tumor cells stain for both neuroendocrine (i.e., synaptophysin and chromogranin A) and epithelial markers. The epithelial marker cytokeratin 20 (CK20) stains positive with immunohistochemistry in a vast majority of MCCs. The expression of the special AT-rich sequence-binding protein (SATB2) was analyzed in MCC (n = 20) together with other forms of skin cancer and neuroendocrine tumors (n = 51) using immunohistochemistry. The results were compared to the expression of CK20, synaptophysin, and chromogranin A. The majority of the MCCs stained positive for synaptophysin and chromogranin A (95 vs 80 % respectively), and 75 % of the MCCs showed cytoplasmic positivity for CK20 and nuclear positivity for SATB2, with two discordant cases lacking expression of one of these markers. We conclude that immunohistochemistry for SATB2 can be used as an additional marker with similar sensitivity and specificity as CK20 for the diagnosis of Merkel cell carcinoma, suggesting a clinical utility in difficult cases where MCC is suspected.

  • 176.
    Gargiulo, Piera
    et al.
    Swiss Grp Clin Canc Res SAKK Coordinating Ctr, Effingerstr 33, CH-3008 Bern, Switzerland.
    Dietrich, Daniel
    Swiss Grp Clin Canc Res SAKK Coordinating Ctr, Effingerstr 33, CH-3008 Bern, Switzerland.
    Herrmann, Richard
    Univ Hosp, Basel, Switzerland.
    Bodoky, Gyorgy
    Szt Laszlo Teaching Hosp, Budapest, Hungary.
    Ruhstaller, Thomas
    Kantonsspital, St Gallen, Switzerland.
    Scheithauer, Werner
    Univ Vienna, Med Sch, Vienna, Austria.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Berardi, Simona
    Swiss Grp Clin Canc Res SAKK Coordinating Ctr, Effingerstr 33, CH-3008 Bern, Switzerland.
    Pignata, Sandro
    Fdn G Pascale, Ist Nazl Tumori, Dept Urol & Gynecol, Naples, Italy.
    Brauchli, Peter
    Swiss Grp Clin Canc Res SAKK Coordinating Ctr, Effingerstr 33, CH-3008 Bern, Switzerland.
    Predicting mortality and adverse events in patients with advanced pancreatic cancer treated with palliative gemcitabine-based chemotherapy in a multicentre phase III randomized clinical trial: the APC-SAKK risk scores2019Inngår i: THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, ISSN 1758-8340, Vol. 11, artikkel-id UNSP 1758835918818351Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The prognosis of advanced pancreatic cancer (APC) is poor and differs considerably among patients. Therefore, it is clinically relevant to identify patients with APC who are more likely to benefit from palliative chemotherapy with reduced risk of toxicity. To date, there is no prognostic score universally recommended to help clinicians in planning the therapeutic management. Methods: Using individual patient data from 319 cases of APC treated with gemcitabine-based chemotherapy and enrolled in the SAKK 44/00-CECOG/PAN.1.3.001 randomized trial, several baseline variables, including inflammatory markers, were analysed post hoc as predictors of mortality and/or grade 3 or 4 chemotherapy-related toxicity and separate risk scores were developed. Results: Median survival of the study patients was 7.9 months (interquartile range 3.7-13.3 months). Independent predictors of mortality included increased Aspartate transaminase (ASAT), low performance status, increased derived neutrophil to lymphocyte ratio, increased Carbohydrate Antigen 19-9 (CA 19-9), low haemoglobin, presence of pain, presence of metastasis and increased alkaline phosphatase (ALP). During the study, 117 patients experienced at least one grade 3 or 4 adverse event. Independent predictors of toxicity included white blood cells, ALP, renal function and bilirubin levels at baseline. Both models displayed moderate levels of discrimination (C-statistic 0.68 and 0.64 for mortality and toxicity, respectively) and adequate calibration. Conclusions: We developed simple-to-use prognostic scores for mortality and severe toxicity for patients with APC. These scores can be useful in daily practice to identify patients with increased risk of death or toxicity and to plan the most appropriate therapeutic strategy to improve survival and quality of life. Further prospective studies to validate such scores are needed.

  • 177.
    Garske, Ulrike
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sandström, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Fröss-Baron, Katarzyna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Lundin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Johansson, Silvia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Khan, Tanweera Shaheena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Lundqvist, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity2018Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, nr 6, s. 970-988Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Peptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome.

    METHODS: Lu-DOTA-octreotate with co-infusion of a mixed amino acid solution, and cycles were repeated until the absorbed dose to the kidneys reached 23 Gy or there were other reasons for stopping therapy. The Ki-67 index was ≤2% in 47 patients (23.5%), 3-20% in 121 (60.5%) and >20% in 16 (8%).

    RESULTS: In 123 patients (61.5%) the absorbed dose to the kidneys reached 23 Gy with three to nine cycles during first-line therapy; in no patient was a dose to the bone marrow of 2 Gy reached. The best responses (according to RECIST 1.1) were a complete response (CR) in 1 patient (0.5%), a partial response (PR) in 47 (23.5%), stable disease (SD) in 135 (67.5%) and progressive disease (PD) in 7 (3.5%). Median progression-free survival was 27 months (95% CI 22-30 months) in all patients, 33 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 15 months in those in whom it did not. Median overall survival (OS) was 43 months (95% CI 39-53 months) in all patients, 54 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 25 months in those in whom it did not. Median OS was 60 months in patients with a best response of PR or CR, 42 months in those with SD and 16 months in those with PD. Three patients (1.5%) developed acute leukaemia, 1 patient (0.5%) chronic leukaemia (unconfirmed) and 30 patients (15%) grade 3 or 4 bone marrow toxicity. Eight patients (4%) developed grade 2 kidney toxicity and one patient (0.5%) grade 4 kidney toxicity.

    CONCLUSIONS: Lu-DOTA-octreotate is feasible. Patients in whom the absorbed dose to the kidneys reached 23 Gy had a longer OS than those in whom it did not. Patients with CR/PR had a longer OS than those with SD. Bone marrow dosimetry did not predict toxicity.

  • 178.
    Gemenetzi, K.
    et al.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.
    Stalika, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.
    Vardi, A.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.
    Psomopoulos, F. E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.
    Minga, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
    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.
    Hadzidimitriou, A.
    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. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    HIGH THROUGHPUT IMMUNOPROFILING OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS ASSIGNED TO STEREOTYPED SUBSET #4: NOVEL INSIGHTS INTO THE DEPTH, DIVERSITY AND TEMPORAL DYNAMICS OF CLONAL EVOLUTION2017Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, nr Suppl. 2, s. 67-67, artikkel-id P242Artikkel i tidsskrift (Annet vitenskapelig)
  • 179.
    Gemenetzi, Katerina
    et al.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Galigalidou, Chrysi
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Vlachonikola, Elisavet
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece..
    Stalika, Evangelia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.; G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.; G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Xochelli, Aliki
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki , Greece.; G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    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.
    Karypidou, Maria
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Touloumenidou, Tasoula
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Minga, Evangelia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece..
    Douka, Vasiliki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Iskas, Michalis
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Athanasiadou, Anastasia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Makris, Antonios
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki , Greece..
    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..
    Hadzidimitriou, Anastasia
    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. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece..
    Stamatopoulos, Kostas
    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..
    Tp53 gene p72R polymorphism in chronic lymphocytic leukemia: incidence and clinical significance amongst cases with unmutated immunoglobulin receptors2017Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 58, nr 3, s. 726-728Artikkel i tidsskrift (Fagfellevurdert)
  • 180.
    Georgantzi, Kleopatra
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnneurologi/Barnonkologi.
    Tsolakis, Apostolos V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi. Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden;Karolinska Univ Hosp Solna, CCK, Stockholm, Sweden.
    Jakobson, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnneurologi/Barnonkologi.
    Christofferson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Grimelius, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Synaptic Vesicle Protein 2 and Vesicular Monoamine Transporter 1 and 2 Are Expressed in Neuroblastoma2019Inngår i: Endocrine pathology, ISSN 1046-3976, E-ISSN 1559-0097, Vol. 30, nr 3, s. 173-179Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuroblastoma (NB), the most common extracranial cancer in childhood, exhibits neuroendocrine (NE) differentiation. Two well-established NE markers, chromogranin A (CgA) and synaptophysin (syn), are used in the histopathological diagnostics. Our aims were to explore if the NE markers synaptic vesicle protein 2 (SV2) and vesicular monoamine transporter 1 (VMAT1) and 2 (VMAT2) also are expressed in human NB and if so, evaluate their usefulness in NB histopathological diagnostics. Tumor specimens from 21 NB patients, before and/or after chemotherapy, were immunostained for CgA, syn, SV2, VMAT1, and VMAT2. Clinical data was extracted from patients' records. SV2 was highly expressed in NB, as was CgA while syn was less frequently expressed compared to the other two. Both VMATs were expressed in several NB, VMAT2 in more cases than VMAT1 and its expression was similar to syn. Chemotherapy did not affect the immunoreactivity in an obvious way. SV2 was highly expressed in NB and can thus be useful marker in NB diagnostics. VMAT1 and VMAT2 were also expressed in NB but similar to syn less reliable as tumor markers.

  • 181.
    Georgiou, Konstantinos
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden..
    Chen, Longyun
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden.;BGI Shenzhen, Shenzhen, Peoples R China..
    Berglund, Mattias
    Karolinska Inst, Dept Biosci & Nutr, Solna, Sweden..
    Ren, Weicheng
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden..
    de Miranda, Noel F. C. C.
    Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands..
    Lisboa, Susana
    Univ Porto, Portuguese Oncol Inst, Dept Genet, Rua Campo Alegre 823, P-4100 Oporto, Portugal.;Univ Porto, Abel Salazar Biomed Sci Inst, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Fangazio, Marco
    Columbia Univ, Inst Canc Genet, New York, NY USA..
    Zhu, Shida
    BGI Shenzhen, Shenzhen, Peoples R China..
    Hou, Yong
    BGI Shenzhen, Shenzhen, Peoples R China..
    Wu, Kui
    BGI Shenzhen, Shenzhen, Peoples R China..
    Fang, Wenfeng
    Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.;Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China..
    Wang, Xianhuo
    Tianjin Med Univ Canc Inst & Hosp, Dept Lymphoma, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China..
    Meng, Bin
    Tianjin Med Univ Canc Inst & Hosp, Dept Lymphoma, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China..
    Zhang, Li
    Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.;Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China..
    Zeng, Yixin
    Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.;Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China..
    Bhagat, Govind
    Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA..
    Nordenskjold, Magnus
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.;Karolinska Univ Hosp, Solna, Sweden..
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Dalla-Favera, Riccardo
    Columbia Univ, Inst Canc Genet, New York, NY USA..
    Zhang, Huilai
    Tianjin Med Univ Canc Inst & Hosp, Dept Lymphoma, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China..
    Teixeira, Manuel R.
    Univ Porto, Portuguese Oncol Inst, Dept Genet, Rua Campo Alegre 823, P-4100 Oporto, Portugal.;Univ Porto, Abel Salazar Biomed Sci Inst, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Pasqualucci, Laura
    Columbia Univ, Inst Canc Genet, New York, NY USA..
    Peng, Roujun
    Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.;Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China..
    Pan-Hammarstrom, Qiang
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden..
    Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas2016Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, nr 24, s. 3026-3034Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive types of B-cell lymphoma. Deregulation of proto-oncogene expression after a translocation, most notably to the immunoglobulin heavy-chain locus (IGH), is one of the hallmarks of DLBCL. Using whole-genome sequencing analysis, we have identified the PD-L1/PD-L2 locus as a recurrent translocation partner for IGH in DLBCL. PIM1 and TP63 were also identified as novel translocation partners for PD-L1/PD-L2. Fluorescence in situ hybridization was furthermore used to rapidly screen an expanded DLBCL cohort. Collectively, a subset of samples was found to be affected by gains (12%), amplifications (3%), and translocations (4%) of the PD-L1/PD-L2 locus. RNA sequencing data coupled with immunohistochemistry revealed that these cytogenetic alterations correlated with increased expression of PD-L1 but not of PD-L2. Moreover, cytogenetic alterations affecting the PD-L1/PD-L2 locus were more frequently observed in the non-germinal center B cell-like (non-GCB) subtype of DLBCL. These findings demonstrate the genetic basis of PD-L1 overexpression in DLBCL and suggest that treatments targeting the PD-1-PD-L1/PD-L2 axis might benefit DLBCL patients, especially those belonging to the more aggressive non-GCB subtype.

  • 182. Gerdtsson, Axel
    et al.
    Håkansson, Ulf
    Törnblom, Magnus
    Jancke, George
    Negaard, Helene F S
    Glimelius, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Halvorsen, Dag
    Karlsdóttir, Ása
    Haugnes, Hege Sagstuen
    Andreassen, Kristine Engen
    Larsen, Signe Melsen
    Holmberg, Göran
    Wahlqvist, Rolf
    Tandstad, Torgrim
    Cohn-Cedermark, Gabriella
    Ståhl, Olof
    Kjellman, Anders
    Surgical Complications in Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumour: A Population-based Study from the Swedish Norwegian Testicular Cancer Group.2019Inngår i: European urology oncology, ISSN 2588-9311, artikkel-id S2588-9311(19)30128-2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Reports on perioperative complications after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for nonseminoma germ cell tumour (NSGCT) are from experienced single centres, with a lack of population-based studies.

    OBJECTIVE: To assess the complications of bilateral and unilateral PC-RPLND.

    DESIGN, SETTING, AND PARTICIPANTS: A prospective, population-based, observational multicentre study included all patients with NSGCT who underwent PC-RPLND in Norway and Sweden during 2007-2014. Of a total of 318 patients, 87 underwent bilateral PC-RPLND and 231 underwent unilateral PC-RPLND. The median follow-up was 6 yr.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bilateral and unilateral PC-RPLND were compared for the outcomes of intra- and postoperative complications (graded by Clavien-Dindo) and retrograde ejaculation (with or without nerve-sparing surgery). Complications were reported as absolute counts and percentages. The χ2 test was used for comparisons.

    RESULTS AND LIMITATIONS: The incidence of intraoperative complications was higher for bilateral PC-RPLND than for unilateral PC-RPLND (14% vs 4.3%, p = 0.003), with ureteral injury as the most frequent reported complication (2% of the patients). Postoperative complications were more common after bilateral than after unilateral PC-RPLND (45% vs 25%, p = 0.001) with Clavien ≥3b reported in 8.3% and 2.2%, respectively (p = 0.009). Lymphatic leakage was the most common complication occurring in 11% of the patients. Retrograde ejaculation occurred more frequently after bilateral than after unilateral surgery (59% vs 32%, p < 0.001). Limitations of the study include reporting of retrograde ejaculation, which was based on a chart review.

    CONCLUSIONS: Intra- and postoperative complications including retrograde ejaculation are more frequent after bilateral PC-RPLND than after unilateral PC-RPLND.

    PATIENT SUMMARY: Lymph node dissection in patients with testicular cancer puts them at risk of complications. In this study, we present the complications after lymph node dissection.

  • 183.
    Ghaneh, Paula
    et al.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England;Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Kleeff, Jorg
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England;Martin Luther Univ Halle Wittenberg, Univ Hosp Halle, Dept Surg, Halle, Germany.
    Halloran, Christopher M.
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Raraty, Michael
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Jackson, Richard
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    Melling, James
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Jones, Owain
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England.
    Palmer, Daniel H.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    Cox, Trevor F.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    Smith, Chloe J.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    O'Reilly, Derek A.
    Manchester Royal Infirm, Dept Surg, Manchester, Lancs, England.
    Izbicki, Jakob R.
    Univ Hamburg, Dept Surg, Med Inst UKE, Hamburg, Germany.
    Scarfe, Andrew G.
    Univ Alberta, Dept Oncol, Div Med Oncol, Cross Canc Inst 2228, Edmonton, AB, Canada.
    Valle, Juan W.
    The Christie, Dept Med Oncol, Manchester, Lancs, England.
    McDonald, Alexander C.
    Beatson West Scotland Canc Ctr, Dept Med Oncol, Glasgow, Lanark, Scotland.
    Carter, Ross
    Glasgow Royal Infirm, Dept Surg, Glasgow, Lanark, Scotland.
    Tebbutt, Niall C.
    Austin Hlth, Dept Med Oncol, Melbourne, Vic, Australia.
    Goldstein, David
    Univ New South Wales, Prince Wales Hosp, Dept Med Oncol, Sydney, NSW, Australia;Univ New South Wales, Sch Clin, Sydney, NSW, Australia.
    Padbury, Robert
    Flinders Med Ctr, Dept Surg, Adelaide, SA, Australia.
    Shannon, Jennifer
    Nepean Canc Ctr, Dept Med Oncol, Nepean, ON, Australia;Univ Sydney, Sydney, NSW, Australia.
    Dervenis, Christos
    Agia Olga Hosp, Dept Surg, Athens, Greece.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Deakin, Mark
    Univ Hosp North Staffordshire, Dept Surg, Stoke On Trent, Staffs, England.
    Anthoney, Alan
    Univ Leeds, St Jamess Univ Hosp, Div Oncol, Leeds, W Yorkshire, England.
    Lerch, Markus M.
    Univ Med Greifswald, Dept Med A, Greifswald, Germany.
    Mayerle, Julia
    Univ Med Greifswald, Dept Med A, Greifswald, Germany.
    Olah, Attila
    Petz Aladar Hosp, Dept Surg, Gyor, Hungary.
    Rawcliffe, Charlotte L.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England.
    Campbell, Fiona
    Heidelberg Univ, Dept Surg, Heidelberg, Germany.
    Strobel, Oliver
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Pathol, Liverpool, Merseyside, England.
    Buechler, Markus W.
    Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Pathol, Liverpool, Merseyside, England.
    Neoptolemos, John P.
    Univ Liverpool, Liverpool Canc Res, UK Canc Trials Unit, Liverpool, Merseyside, England;Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Surg, Liverpool, Merseyside, England;Heidelberg Univ, Dept Surg, Heidelberg, Germany.
    The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma2019Inngår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 269, nr 3, s. 520-529Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective and Background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies

    Methods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial.

    Results: There were 1151 patients, of whom 505 (43.9%) had an RI resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative R0 >1 mm) tumors, 25.4 (21.6 30.4) months for 146 (12.7%) patients with RI <1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R 1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥ 1, maximum tumor size, and RI-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status. WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence.

    Conclusions: RI-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

  • 184.
    Ghia, P.
    et al.
    Univ Vita Salute San Raffaele, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst Milan, Milan, Italy..
    Nadel, B.
    Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France..
    Sander, B.
    Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, SE-14186 Stockholm, Sweden..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Stevenson, F. K.
    Univ Southampton, Canc Res UK Ctr, Canc Sci Unit, Fac Med,Southampton Gen Hosp, Southampton, Hants, England..
    Early stages in the ontogeny of small B-cell lymphomas: genetics and microenvironment2017Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, nr 5, s. 395-414Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this review, we focus on the mechanisms underlying lymphomagenesis in chronic lymphocytic leukaemia, follicular lymphoma, mantle cell lymphoma and splenic marginal zone lymphoma. The cells of origin of these small B-cell lymphomas are distinct, as are the characteristic chromosomal lesions and clinical courses. One shared feature is retention of expression of surface immunoglobulin. Analysis of this critical receptor reveals the point of differentiation reached by the cell of origin. Additionally, the sequence patterns of the immunoglobulin-variable domains can indicate a role for stimulants of the B-cell receptor before, during and after malignant transformation. The pathways driven via the B-cell receptor are now being targeted by specific kinase inhibitors with exciting clinical effects. To consider routes to pathogenesis, potentially offering earlier intervention, or to identify causative factors, genetic tools are being used to track pretransformation events and the early phases in lymphomagenesis. These methods are revealing that chromosomal changes are only one of the many steps involved, and that the influence of surrounding cells, probably multiple and variable according to tissue location, is required, both to establish tumours and to maintain growth and survival. Similarly, the influence of the tumour microenvironment may protect malignant cells from eradication by treatment, and the resulting minimal residual disease will eventually give rise to relapse. The common and different features of the four lymphomas will be summarized to show how normal B lymphocytes can be subverted to generate tumours, how these tumours evolve and how their weaknesses can be attacked by targeted therapies.

  • 185.
    Gholiha, Alex R.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hollander, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Hedström, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Molin, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Smedby, Karin E
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Hjalgrim, Henrik
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Glimelius, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B-symptoms2019Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 184, nr 2, s. 192-201Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plasma cells are important prognostic actors in different malignancies. The tumour microenvironmental composition in classic Hodgkin lymphoma (cHL) is a major prognostic key element; however, clinicopathological studies regarding plasma cells in cHL are lacking. The aim of this study was to investigate CD138+ (also termed SDC1+) plasma cell and IgG4 producing (IgG4+) plasma cells infiltration in the microenvironment of cHL. Immunohistochemistry with anti-CD138 and IgG4 antibodies was performed on diagnostic tumour biopsies from 124 patients with cHL, on tissue micro array (TMA). In 120 cases, CD138+ plasma cell-infiltration was associated with the presence of B-symptoms (P = 0·028) and advanced stage, IIB-IVB (P = 0·009). In multivariate analysis, CD138+ plasma cells correlated with eosinophil infiltration (P = 0·013). The subgroup of IgG4+ plasma cells was analysed in 122 cases and only correlated to CD138+ plasma cells (P = 0·004). Patients with high proportion of tumour infiltrating CD138+ plasma cells (defined as ≥10%), had a more inferior event-free survival (P = 0·007) and overall survival (P = 0·004) than patients with a low proportion of infiltrating CD138+ plasma cells (<10%), although significance was not maintained in multivariate analysis. In summary, a high proportion of tumour-associated plasma cells in cHL reflect an important component in the microenvironment of cHL.

  • 186.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Adjuvant chemotherapy for patients with rectal cancer - will the controversy be resolved?2015Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, nr 4, s. 433-436Artikkel i tidsskrift (Annet vitenskapelig)
  • 187.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Any progress in pancreatic cancer?2016Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, nr 3, s. 255-258Artikkel i tidsskrift (Annet vitenskapelig)
  • 188.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Forty-five years in oncology, 25 years with Acta Oncologica2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 12, s. 1593-1598Artikkel i tidsskrift (Annet vitenskapelig)
  • 189.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Is the benefit of oxaliplatin in rectal cancer clinically relevant?2015Inngår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 16, nr 8, s. 883-885Artikkel i tidsskrift (Annet vitenskapelig)
  • 190.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    More than 1000 new manuscripts in 20172018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 2, s. 174-175Artikkel i tidsskrift (Annet vitenskapelig)
  • 191.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    On a prolonged interval between rectal cancer (chemo) radiotherapy and surgery2017Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, nr 1, s. 1-10Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Preoperative radiotherapy (RT) or chemoradiotherapy (CRT) is often required before rectal cancer surgery to obtain low local recurrence rates or, in locally advanced tumours, to radically remove the tumour. RT/CRT in tumours responding completely can allow an organ-preserving strategy. The time from the end of the RT/CRT to surgery or to the decision not to operate has been prolonged during recent years. After a brief review of the literature, the relevance of the time interval to surgery is discussed depending upon the indication for RT/CRT. In intermediate rectal cancers, where the aim is to decrease local recurrence rates without any need for down-sizing/-staging, short-course RT with immediate surgery is appropriate. In elderly patients at risk for surgical complications, surgery could be delayed 5-8 weeks. If CRT is used, surgery should be performed when the acute radiation reaction has subsided or after 5-6 weeks. In locally advanced tumours, where CRT is indicated, the optimal delay is 6-8 weeks. In patients not tolerating CRT, short-course RT with a 6-8-week delay is an alternative. If organ preservation is a goal, a first evaluation should preferably be carried out after about 6 weeks, with planned surgery for week 8 if the response is inadequate. In case the response is good, a new evaluation should be carried out after about 12 weeks, with a decision to start a 'watch-and-wait' programme or operate. Chemotherapy in the waiting period is an interesting option, and has been the subject of recent trials with promising results.

  • 192.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Potential value of immunoscoring in rectal cancer patients2016Inngår i: TRANSLATIONAL CANCER RESEARCH, ISSN 2218-676X, Vol. 5, nr 2, s. 94-97Artikkel i tidsskrift (Annet vitenskapelig)
  • 193.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Tell all the good news as soon as possible2016Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, nr 9-10, s. 1067-1068Artikkel i tidsskrift (Annet vitenskapelig)
  • 194.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    What is most relevant in preoperative rectal cancer chemoradiotherapy - the chemotherapy, the radiation dose or the timing to surgery?2016Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, nr 12, s. 1381-1385Artikkel i tidsskrift (Fagfellevurdert)
  • 195.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    What treatments should be skipped or intensified in localized rectal cancer?2018Inngår i: Future Oncology, ISSN 1479-6694, E-ISSN 1744-8301, Vol. 14, nr 4, s. 313-318Artikkel i tidsskrift (Annet vitenskapelig)
  • 196.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    What's new about Acta Oncologica for 2016?2015Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, nr 10, s. 1703-1705Artikkel i tidsskrift (Annet vitenskapelig)
  • 197.
    Glimelius, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Cavalli-Björkman, Nina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Does shared decision making exist in oncologic practice?2016Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, nr 2, s. 125-128Artikkel i tidsskrift (Annet vitenskapelig)
  • 198.
    Glimelius, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hohenberger, Werner Max
    Univ Klinikums Erlangen, Chirurg Klin, Erlangen, Germany..
    Matzel, Klaus E.
    Univ Klinikums Erlangen, Chirurg Klin, Erlangen, Germany..
    Sugihara, Kenichi
    Tokyo Med & Dent Univ, Tokyo, Japan..
    Quirke, Philip
    St James Univ Hosp, Leeds, W Yorkshire, England..
    Further Evaluating the Benefit of Adjuvant Chemotherapy for Colon Cancer Reply2016Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, nr 30, s. 3713-+Artikkel i tidsskrift (Fagfellevurdert)
  • 199.
    Glimelius, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Kowalski, Jan
    JK Biostat, Stockholm, Sweden.
    Nasstrom, Jacques
    PledPharma AB, Stockholm, Sweden.
    The PLIANT trial gives trustworthy data2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 6, s. 864-866Artikkel i tidsskrift (Annet vitenskapelig)
  • 200.
    Glimelius, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Manojlovic, Nebojsa
    Mil Med Acad Serbia, Clin Gastroenterol & Hepatol, Belgrade.
    Pfeiffer, Per
    Odense Univ Hosp, Dept Oncol, Odense.
    Mosidze, Baadur
    Univ Clin, LTD High Technol Med Ctr, Tbilisi.
    Kurteva, Galina
    SHATO EAD, Clin Chemotherapy, Sofia.
    Karlberg, Mia
    Karolinska Inst, Dept Pathol & Oncol, Stockholm.
    Mahalingam, Devalingam
    Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio.
    Buhl Jensen, Peter
    Buhl Oncol, Copenhagen.; PledPharma AB, Stockholm.
    Kowalski, Jan
    JK Biostat, Stockholm.
    Bengtson, Marie
    PledPharma AB, Stockholm.
    Nittve, Malin
    PledPharma AB, Stockholm.
    Nässtrom, Jacques
    PledPharma AB, Stockholm.
    Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx®): a placebo-controlled randomised phase II study (PLIANT)2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 3, s. 393-402Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC).

    Patient and methods: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2, oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible. Calmangafodipir was given in a phase I dose-finding and in a phase II placebo-controlled study, as a 5-min infusion 10 min prior to oxaliplatin. Neurotoxicity was evaluated by the physician using the Oxaliplatin Sanofi Specific Scale and by the patient using the cold allodynia test and the Leonard scale.

    Results: Eleven patients were included in phase I without any detectable toxicity to calmangafodipir. In the phase II study, 173 patients were randomised to placebo (n = 60), calmangafodipir 2 µmol/kg (n = 57) and calmangafodipir 5 µmol/kg (n = 45, initially 10 µmol/kg, n = 11). Calmangafodipir-treated patients (all three doses pooled) had less physician graded neurotoxicity (odds ratio (90% confidence interval one-sided upper level) 0.62(1.15), p = .16), significantly less problems with cold allodynia (mean 1.6 versus 2.3, p < .05) and significantly fewer sensory symptoms in the Leonard scale (cycle 1–8 mean 1.9 versus 3.0, p < .05 and during follow-up after 3 and 6 months, mean 3.5 versus 7.3, p < .01). Response rate, progression-free and overall survival did not differ among groups.

    Conclusions: Calmangafodipir at a dose of 5 µmol/kg appears to prevent the development of oxaliplatin-induced acute and delayed CIPN without apparent influence on tumour outcomes.

1234567 151 - 200 of 655
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf