SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Österborg Anders) "

Sökning: WFRF:(Österborg Anders)

  • Resultat 21-30 av 43
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
21.
  • Hedenus, Michael, 1945- (författare)
  • Clinical impact of epoetins in the treatment of anemia with special emphasis on patients with lymphoid malignancies. : dosing, iron supplementation and safety
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this thesis was to determine the relevant dose of arbepoetin-alfa (DA) in patients with lymphoproliferative diseases (LPD) and chemotherapy induced anemia (CIA), to study the clinical impact of intravenous (IV) iron supplementation combined with epoetin beta treatment, to identify factors that might predict hemoglobin (Hb) response to treatment with epoetins and to investigate safety of DA.A dose-finding phase II study was able to assess a reasonable DA dose of 2.25 μg/kg once weekly for the treatment of CIA in patients with LPD. Dose-response trends were observed for the different dose cohorts although not statistically significant for any of the endpoints. However a significantly higher proportion of patients achieved Hb response (increase ≥2 g/dL) in the combined DA groups than in placebo (P<0.001).A larger pivotal phase II trial was performed in a similar setting o confirm that the dose 2.25μg/kg once weekly was appropriate and safe. The proportion of patients achieving Hb response was significantly higher in the DA group (60%) than in the placebo group (18%) (P<0,001) and resulted in higher mean changes in Hb than placebo from baseline, 2.66 g/dl versus 0.69 /dl. Also a significantly lower proportion of patients in the DA group (31%) received RBC tranfusions than in the placebo group (48%). The short-term safety of DA with the tested dose was confirmed. The efficacy of DA was consistent for all end points independent of malignancy type or baseline endogenous erythropoietin serum levels.The correction of moderate anemia in truly iron repleted patients with clinically stable LPD not receiving hemotherapy or RBC transfusions with epoetin beta treatment, with or without IV iron treatment was studied in an open label randomized trial. Also the impact on iron kinetics was assessed. The mean change in Hb concentration from baseline to end of treatment (EOT ) was 2.91 versus 1.50 g/dL respectively (P<0.0001). There was a significant (P<0.0001) difference in mean Hb at EOT between the iron and no-iron groups (13.0 g/dL versus 11.8 g/dL). Hb response was achieved by significantly more patients in the iron group (P=0.0012)than in the no-iron group (93% versus 53%) and the median time to achieve a Hb response was 6 weeks in the iron group compared with 12 weeks in the no-iron group. The mean weekly epoetin dose per patient was statistically significant lower in the iron group at week 13 (P =0.029) and at least 25% lower at EOT.To investigate the long-term safety of DA in cancer patients with CIA four previously published double blind, randomized placebo-controlled phase II -III studies were analysed (n = 1.129). Median durations of progression-free survival and overall survival was comparable between DA and placebo for lung cancer (median follow up 15.8 months), for LPD (median follow up 32.6 months) and in the pooled population (follow up 4 months).
  •  
22.
  • Hojjat-Farsangi, Mohammad, et al. (författare)
  • Spontaneous immunity against the receptor tyrosine kinase ROR1 in patients with chronic lymphocytic leukemia
  • 2015
  • Ingår i: PLOS One. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1932-6203.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: ROR1 is a receptor tyrosine kinase expressed in chronic lymphocytic leukemia (CLL) and several other malignancies but absent in most adult normal tissues. ROR1 is considered an onco-fetal antigen. In the present study we analysed spontaneous humoral and cellular immunity against ROR1 in CLL patients. Materials and Methods: Antibodies against ROR1 were analysed in 23 patients and 20 healthy donors by ELISA and Western blot. Purified serum IgG from patients was tested for cytotoxicity against CLL cells using the MTT viability assay. A cellular immune response against ROR1 derived HLA-A2 restricted 9 aa and 16 aa long peptides were analysed using peptide loaded dendritic cells co-cultured with autologous T cells from CLL patients (n = 9) and healthy donors (n = 6). IFN-γ, IL-5 and IL-17A-secreting T cells were assessed by ELISPOT and a proliferative response using a H3-thymidine incorporation assay. Results: The majority of CLL patients had antibodies against ROR1. Significantly higher titers of antiROR1 antibodies were noted in patients with non-progressive as compared to progressive disease. The extracellular membrane-close ROR1 KNG domain seemed to be an immunodominant epitope. Ten patients with high titers of anti-ROR1 binding antibodies were tested for cytotoxicity. Five of those had cytotoxic anti-ROR1 antibodies against CLL cells. ROR1-specific IFN-γ and IL-17A producing T cells could be detected in CLL patients, preferentially in non-progressive as compared to patients with progressive disease (p < 0.05). Conclusion: ROR1 seemed to spontaneously induce a humoral as well as a T cell response in CLL patients. The data support the notion that ROR1 might be a specific neo-antigen and may serve as a target for immunotherapy.
  •  
23.
  • Hojjat-Farsangi, Mohammad, et al. (författare)
  • The tyrosine kinase receptor ROR1 is constitutively phosphorylated in chronic lymphocytic leukemia (CLL) cells
  • 2013
  • Ingår i: PLOS ONE. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1932-6203.
  • Tidskriftsartikel (refereegranskat)abstract
    • Phosphorylation of receptor tyrosine kinases (RTKs) has a key role in cellular functions contributing to the malignant phenotype of tumor cells. We and others have previously demonstrated that RTK ROR1 is overexpressed in chronic lymphocytic leukemia (CLL). Silencing siRNA downregulated ROR1 and induced apoptosis of CLL cells. In the present study we analysed ROR1 isoforms and the phosphorylation pattern in CLL cells (n=38) applying western blot and flow-cytometry using anti-ROR1 antibodies and an anti-phospho-ROR1 antibody against the TK domain. Two major ROR1 bands with the size of 105 and 130 kDa respectively were identified, presumably representing unglycosylated (immature) and glycosylated (mature) ROR1 respectively as well as a 260 kDa band which may represent dimerized ROR1. A ROR1 band of 64 kDa that may correspond to a C-terminal fragment was also noted, present only in the nucleus. The 105 kDa ROR1 isoform was more frequently expressed in non-progressive as compared to progressive CLL patients (p=0.03). The 64, 105, 130 and 260 kDa bands were constitutively phosphorylated both at tyrosine and serine residues. Phosphorylation intensity of the mature (130 kDa) isoform was significantly higher in progressive than in non-progressive disease (p<0.001). Incubation of CLL cells with a mouse anti-ROR1 KNG or an anti-ROR1 CRD mAb respectively induced dephosphorylation of ROR1 before entering apoptosis. In conclusion CLL cells expressed different isoforms of ROR1 which were constitutively phosphorylated. The mature, phosphorylated ROR1 isoform was associated with a progressive disease stage. Targeting ROR1 by mAbs induced specific dephosphorylation and leukemic cell death. ROR1 might be an interesting therapeutic target.
  •  
24.
  • Kalushkova, Antonia, et al. (författare)
  • Polycomb target genes are silenced in multiple myeloma
  • 2010
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:7, s. e11483-
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpressed gene signature in MM patient cells compared to normal counterpart plasma cells. This profile was enriched for previously defined H3K27-tri-methylated genes, targets of the Polycomb group (PcG) proteins in human embryonic fibroblasts. Additionally, the silenced gene signature was more pronounced in ISS stage III MM compared to stage I and II. Using chromatin immunoprecipitation (ChIP) assay on purified CD138+ cells from four MM patients and on two MM cell lines, we found enrichment of H3K27me3 at genes selected from the profile. As the data implied that the Polycomb-targeted gene profile would be highly relevant for pharmacological treatment of MM, we used two compounds to chemically revert the H3K27-tri-methylation mediated gene silencing. The S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin (DZNep) and the histone deacetylase inhibitor LBH589 (Panobinostat), reactivated the expression of genes repressed by H3K27me3, depleted cells from the PRC2 component EZH2 and induced apoptosis in human MM cell lines. In the immunocompetent 5T33MM in vivo model for MM, treatment with LBH589 resulted in gene upregulation, reduced tumor load and increased overall survival. Taken together, our results reveal a common gene signature in MM, mediated by gene silencing via the Polycomb repressor complex. The importance of the underexpressed gene profile in MM tumor initiation and progression should be subjected to further studies.
  •  
25.
  • Kimby, Eva, et al. (författare)
  • Long-term molecular remissions in patients with indolent lymphoma treated with rituximab as a single agent or in combination with interferon alpha-2a : a randomized phase II study from the Nordic Lymphoma Group
  • 2008
  • Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 49:1, s. 102-112
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this phase II randomized trial was to evaluate the effect and safety of interferon-alpha2a (IFN) in combination with extended dosing rituximab in patients with symptomatic, advanced indolent lymphoma responding to a standard single course of rituximab. Totally 123 patients were treated with rituximab 375 mg/m2 once weekly for 4 weeks leading to 14 complete response (CR; 11%), 56 partial response (PR; 46%), and 13 minor responses (MR; 11%). Patients achieving either PR or MR were randomized to four more infusions of rituximab alone (n = 36) or in combination with five weeks of IFN (n = 33), with an overall response rate (CR + PR) of 78% and 94%, respectively. Significantly more patients in the combination arm improved their response from PR/MR to CR (P < 0.05) and more maintained their responses for > or = 24 months (72% versus 50%), respectively. Overall, 26 out of the 52 patients who achieved CR underwent minimal residual disease (MRD) evaluation. Totally 17 of these (65%) achieved MRD negativity, 14 of whom remain in CR after 4.8 years' follow-up. The addition of IFN to rituximab was generally safe, but reversible thrombocytopenia and neutropenia were noted in one and six patients, respectively, requiring a reduction in the IFN dose. Extended rituximab is effective and well tolerated and combination with IFN seems to improve both the quality and duration of the responses, providing the opportunity to achieve long-term molecular CRs and prolonged failure-free survival without chemotherapy.
  •  
26.
  • Kokhaei, Parviz, et al. (författare)
  • Expression of erythropoietin receptor and in vitro functional effects of epoetins in B-cell malignancies
  • 2007
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:12, s. 3536-3544
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Erythropoietin (EPO) and EPO receptor (EPO-R) expression have been reported in solid tumors and are claimed to regulate tumor growth; however, no data have been published on this issue in B-cell malignancies or normal lymphoid cells. This report describes genomic/protein EPO-R expression and in vitro effects of recombinant human EPO (epoetin) in B-cell chronic lymphocytic leukemia (B-CLL), mantle-cell lymphoma (MCL), and multiple myeloma (MM). Experimental Design: Blood samples were obtained from patients with B-CLL, MCL, and healthy volunteers, and bone marrow was obtained from MM patients. EPO-R mRNA was detected by reverse transcription-PCR. EPO-R surface expression was investigated by flow cytometry using digoxigenin-labeled epoetin and polyclonal rabbit anti–EPO-R antibody for intracellular receptor. Tumor cell stimulation was determined in vitro using [3H]thymidine incorporation and CD69 expression after exposure to epoetin α or β or darbepoetin α. Results: EPO-R mRNA was detected in mononuclear cells from 32 of 41 (78%) B-CLL and 5 of 7 (71%) MCL patients, and 21 of 21 (100%) MM samples. Expression was also detected in highly purified T cells from six of eight B-CLL patients, four of four MM patients, and normal donor B and T cells. Surface EPO-R protein was not detected. Intracellular EPO-R staining with anti–EPO-R antibodies was unspecific. No tumor-stimulatory effect was observed with high epoetin concentrations. Conclusions:EPO-R gene is frequently expressed in lymphoid malignancies and normal B and T cells. However, there was no surface protein expression and no epoetin-induced in vitro stimulation of tumor B cells, indicating that epoetin therapy in vivo is likely to be safe in patients with lymphoid malignancies.
  •  
27.
  • Kokhaei, Parviz, et al. (författare)
  • Ibrutinib-A double-edge sword in cancer and autoimmune disorders
  • 2015
  • Ingår i: Journal of Drug Targeting. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1061-186X. ; 24:5, s. 373-385
  • Tidskriftsartikel (refereegranskat)abstract
    • Targeted therapies have appeared as new treatment options for several disease types, including cancer and autoimmune disorders. Of several targets, tyrosine kinases (TKs) are among the most promising. Overexpression of TKs provides a target for novel therapeutic agents, including small molecule inhibitors of tyrosine kinases (TKI). Ibrutinib (PCI-32765) is a TKI of Bruton’s tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells. In addition to inhibitory effects, recent studies have shown that ibrutinib has multiple immunomodulatory effects. It binds covalently to IL-2 inducible tyrosine kinase (Itk) in T lymphocytes and suppresses the survival of T-helper (Th) 2 cells. This changes the balance of Th1/Th2 cells toward Th1 subset, which are the main immune cells targeting tumor cells. The dual activity of ibrutinib has paid a great attention and several studies are evaluating the anti-tumor and immunomodulatory effects in cancer, autoimmune disorders and infectious diseases. In this article we review the inhibitory and immunomodulatory effects of ibrutinib in B-cell malignancies, autoimmune diseases and infections, as well as the communication between the Ror1 receptor tyrosine kinase and BCR and effects of ibrutinib on this crosstalk.
  •  
28.
  • Leeksma, Alexander C., et al. (författare)
  • Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity : A multi-center study
  • 2020
  • Ingår i: Haematologica. - 0390-6078. ; 105:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence of a CK. Current knowledge on genomic arrays in CLL is based on outcomes of single center studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2293 arrays from 13 diagnostic laboratories according to established standards. CNAs were found outside regions captured by CLL FISH probes in 34% of patients, and several of them including gains of 8q, deletions of 9p and 18p (p<0.01) were linked to poor outcome after correction for multiple testing. Patients (n=972) could be divided in three distinct prognostic subgroups based on the number of CNAs. Only high genomic complexity (high-GC), defined as 5 CNAs emerged as an independent adverse prognosticator on multivariable analysis for time to first treatment (Hazard ratio: 2.15, 95% CI: 1.36-3.41; p=0.001) and overall survival (Hazard ratio: 2.54, 95% CI: 1.54-4.17; p<0.001; n=528). Lowering the size cutoff to 1 Mb in 647 patients did not significantly improve risk assessment. Genomic arrays detected more chromosomal abnormalities and performed at least as well in terms of risk stratification compared to simultaneous chromosome banding analysis as determined in 122 patients. Our findings highlight genomic array as an accurate tool for CLL risk stratification.
  •  
29.
  • Lindemalm, Christina, et al. (författare)
  • Immune response, depression and fatigue in relation to support intervention in mammary cancer patients
  • 2008
  • Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 16:1, s. 57-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Goal of work To study the effect of support intervention on immune function in breast cancer patients. Materials and methods Breast cancer patients from an ongoing prospective randomised quality-of -life study were chosen for assaying immune functions in relation to a support-group intervention program running on a residential basis. Twenty-one women received adjuvant-combined radio-chemotherapy (CT-RT) and 20 women radiotherapy (RT). Eleven CT-RT and ten RT patients were randomised to support-group intervention, the rest served as controls. Immune tests for NK cells and NK-cell cytotoxicity, as well as lymphocyte subpopulations and response to antigen were performed before intervention, 2, 6, and 12 months later, in parallel to controls and healthy volunteers (n=11). Depression, anxiety and fatigue were evaluated by the Hospital Anxiety and Depression (HAD) and the Norwegian Fatigue questionnaire. The density of NK cell receptors and in vitro quantitation of functional NK cytotoxicity against K562 cell line were evaluated. Four-colour flow cytometry was used to detect signal transduction molecules and cytokine expression. T-cell proliferate response to purified protein derivate (PPD) antigen was evaluated. Results No significant immune effect of support intervention could be found. The immune variables were severely disarranged compared to healthy volunteers but showed a statistically significant improvement over time. The majority of patients suffered from fatigue but had low scores for depression and anxiety. Conclusion No effect on immune parameters could be detected from support intervention. The long-lasting immune suppression might override a putative effect of the intervention. Low depression scores may contribute to the absence of a detectable effect.
  •  
30.
  • Mattsson, Agnes, et al. (författare)
  • Idelalisib (PI3Kδ inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia : A Swedish nation-wide real-world report on consecutively identified patients
  • 2023
  • Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 111:5, s. 715-721
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesWe examined the efficacy and toxicity of the PI3Kδ inhibitor idelalisib in combination with rituximab salvage therapy in consecutively identified Swedish patients with chronic lymphocytic leukemia (CLL).Methods and ResultsThirty-seven patients with relapsed/refractory disease were included. The median number of prior lines of therapy was 3 (range 1–11); the median age was 69 years (range 50–89); 22% had Cumulative Illness Rating Scale (CIRS) >6 and 51% had del(17p)/TP53 mutation. The overall response rate was 65% (all but one was partial response [PR]). The median duration of therapy was 9.8 months (range 0.9–44.8). The median progression-free survival was 16.4 months (95% CI: 10.4–26.3) and median overall survival had not been reached (75% remained alive at 24 months of follow-up). The most common reason for cessation of therapy was colitis (n = 8, of which seven patients experienced grade ≥3 colitis). The most common serious adverse event was grade ≥3 infection, which occurred in 24 patients (65%).ConclusionsOur real-world results suggest that idelalisib is an effective and relatively safe treatment for patients with advanced-stage CLL when no other therapies exist. Alternative dosing regimens and new PI3K inhibitors should be explored, particularly in patients who are double-refractory to inhibitors of BTK and Bcl-2.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 21-30 av 43
Typ av publikation
tidskriftsartikel (37)
annan publikation (4)
doktorsavhandling (1)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (37)
övrigt vetenskapligt/konstnärligt (6)
Författare/redaktör
Österborg, Anders (43)
Hansson, Lotta (14)
Jernberg-Wiklund, He ... (12)
Nilsson, Kenneth (11)
Nowak, Piotr (7)
Ljungman, Per (7)
visa fler...
Strömberg, Thomas (7)
Bergman, Peter (7)
Aleman, Soo (7)
Chen, Puran (7)
Ljunggren, Hans-Gust ... (7)
Buggert, Marcus (7)
Blennow, Ola (7)
Mielke, Stephan (7)
Söderdahl, Gunnar (7)
Smith, C. I. Edvard (7)
Akber, Mira (7)
Carlson, Kristina (5)
Öberg, Fredrik (5)
Bogdanovic, Gordana (5)
Vesterbacka, Jan (5)
Muschiol, Sandra (5)
Agarwal, Prasoon (4)
Kalushkova, Antonia (4)
Wullimann, David (4)
Gao, Yu (4)
Hammarberg, Anna (4)
Hojjat-Farsangi, Moh ... (4)
Rosenquist, Richard (3)
Okrój, Marcin (3)
Healy, Katie (3)
Dimberg, Anna (3)
Birgegård, Gunnar, 1 ... (2)
Gascon, Pere (2)
Hedenus, Michael (2)
Nilsson, Peter (2)
Kokhaei, Parviz (2)
Hagberg, Hans (2)
Hober, Sophia, Profe ... (2)
Enroth, Stefan (2)
Alzrigat, Mohammad (2)
Párraga, Alba Atienz ... (2)
Ma, Anqi (2)
Jin, Jian (2)
Stamatopoulos, Kosta ... (2)
Ghia, Paolo (2)
Johansson, Hemming (2)
Blom, Anna M. (2)
Axelsson, Per (2)
Palma, Marzia (2)
visa färre...
Lärosäte
Karolinska Institutet (29)
Uppsala universitet (24)
Umeå universitet (9)
Lunds universitet (7)
Kungliga Tekniska Högskolan (3)
Örebro universitet (2)
Språk
Engelska (39)
Odefinierat språk (4)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (25)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy