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| 3. |
- Fergedal, May, et al.
(author)
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Differences in CD14 and alpha-naphthyl acetate esterase positivity and relation to prognosis in AML
- 1998
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In: Leukemia Research. - Oxford, United Kingdom : Elsevier. - 0145-2126 .- 1873-5835. ; 22:1, s. 25-30
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Journal article (peer-reviewed)abstract
- Alpha-naphthyl acetate esterase (ANAE) and CD14 expression, used for determination of monocytic cells, were compared and related to prognosis in 65 AML patients. Bone marrow aspiration material from AML patients has been used for the cytochemistry as well as flow cytometry. All non-erythroid cells have been included in the evaluation in both methods. 17/65 cases showed at least 15% difference between the proportion CD14 and ANAE positive cells. Cases with 20% or more CD14 positivity had poorer prognosis. For FAB classes M0-M3, presence of 10% or more CD14 was negative for overall survival (P = 0.01). ANAE did not show significant prognostic influence.
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| 4. |
- Gruber, A, et al.
(author)
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A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia
- 2003
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In: Leukemia Research. - 0145-2126 .- 1873-5835. ; 27, s. 323-
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Journal article (peer-reviewed)abstract
- The cyclosporine analog Valspodar (PSC 833, Novartis Pharma) is a strong inhibitor of the mdr1 gene product p-glycoprotein (pgp). A phase I/II study was conducted in order to evaluate if addition of Valspodar to treatment with daunorubicin and cytarabine, given to patients with primary refractory or relapsed acute myeloid leukemia, could increase the complete remission rate. Fifty-three patients were treated in cohorts of three to six patients. Twelve patients reached a complete remission in bone marrow, five of whom also normalized their peripheral blood values. Three patients experienced treatment-related deaths from pneumonia, liver failure and cerebral hemorrhage, respectively. It is concluded that Valspodar 10mg/kg per 24h in combination with daunorubicin 45mg/m2 for 3 days and cytarabine 1g/m2 twice daily for 4 days is tolerable in this heavily pre-treated group of patients. Due to the moderate treatment results, the phase II part of the study was ended prematurely. The modulation of only pgp did not give an obvious improvement of the treatment results in this group of patients. ⌐ 2002 Elsevier Science Ltd. All rights reserved.
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| 5. |
- Knaust, Eva, 1944-, et al.
(author)
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Different effects of metabolic inhibitors and cyclosporin A on daunorubicin transport in leukemia cells from patients with AML
- 2003
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In: Leukemia Research. - 0145-2126 .- 1873-5835. ; 27:2, s. 183-191
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Journal article (peer-reviewed)abstract
- The objective of this study was to determine the role of transport proteins in daunorubicin (Dnr) accumulation and efflux in leukemia cells from 36 patients with acute myeloid leukemia (AML). Mononuclear cells were isolated and incubated with 1 μM Dnr with/without addition of 3 μM cyclosporin A (CyA) or metabolic inhibitors (MI). Cellular Dnr concentration in leukemia blast cells was measured with flow cytometry. After washing and reincubation of the cells in drug-free medium, Dnr efflux was followed with/without addition of CyA or MI. Levels of mRNA expression for mdr1, multidrug resistance associated protein (mrp) and lung resistance protein (lrp) were determined with reverse transcriptase-polymerase chain reaction (RT-PCR). MI enhanced cellular Dnr accumulation to a higher extent than CyA whereas CyA reduced Dnr efflux more efficiently than MI (P<0.001). There was a significant difference in Dnr accumulation between samples with low and high mdr1 mRNA levels but only in the presence of MI or CyA. Our results imply that other factors than P-glycoprotein (Pgp) are of major importance for in vitro Dnr accumulation in AML blasts and that the role of Pgp as a drug efflux pump is not conclusive.
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| 6. |
- Uggla, Bertil, 1962-, et al.
(author)
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Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh leukemic cells
- 2001
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In: Leukemia Research. - Oxford, United Kingdom : Elsevier. - 0145-2126 .- 1873-5835. ; 25:11, s. 961-966
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Journal article (peer-reviewed)abstract
- Topoisomerase IIalpha (topoII alpha) is the target enzyme for several antineoplastic drugs. Correlation between low expression of topo IIalpha and drug resistance has been shown in vitro, but there is limited evidence of a correlation to initial response to treatment or to overall prognosis. Normal cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo IIalpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of topo IIalpha in leukemic cells from 25 patients with acute leukemia by flow cytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed >50% positive cells in G0/G1, and another five samples showed >20%. This finding could possibly provide an explanation to previous difficulties in correlating topo IIalpha expression with clinical outcome. Six of eight patients, where >20% of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for clinical response to cytostatic drugs.
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| 8. |
- Andersen, Christen Lykkegaard, et al.
(author)
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Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat
- 2014
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In: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 38:7, s. 816-821
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Journal article (peer-reviewed)abstract
- YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<0.0001) and 1.7 times higher than in ET (P = 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms.
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| 10. |
- Besses, Carlos, et al.
(author)
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Cytoreductive treatment patterns for essential thrombocythemia in Europe. Analysis of 3643 patients in the EXELS study
- 2013
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In: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 37:2, s. 162-168
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Journal article (peer-reviewed)abstract
- EXELS is an ongoing phase IV non-interventional study; 3643 high-risk patients with essential thrombocythemia (ET) were recruited across 13 European countries. We report patient characteristics and cytoreductive treatment patterns of ET across Europe. Hydroxycarbamide (HC; 64.3%) and anagrelide (22.0%) were the two main cytoreductive treatments prescribed. The proportions of patients taking either HC or anagrelide varied across countries, as did the number of patients receiving anti-aggregatory therapy in addition to cytoreductive treatment. This real-world evidence demonstrates that, generally, treatment patterns of ET across Europe adhere to expert recommendations, with some notable variations between countries.
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