| 11. |
- Jadersten, M., et al.
(författare)
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Targeting SAMHD1 with hydroxyurea in first-line cytarabine-based therapy of newly diagnosed acute myeloid leukaemia: Results from the HEAT-AML trial
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 292:6, s. 925-940
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Tidskriftsartikel (refereegranskat)abstract
- Background Treatment of newly diagnosed acute myeloid leukaemia (AML) is based on combination chemotherapy with cytarabine (ara-C) and anthracyclines. Five-year overall survival is below 30%, which has partly been attributed to cytarabine resistance. Preclinical data suggest that the addition of hydroxyurea potentiates cytarabine efficacy by increasing ara-C triphosphate (ara-CTP) levels through targeted inhibition of SAMHD1. Objectives In this phase 1 trial, we evaluated the feasibility, safety and efficacy of the addition of hydroxyurea to standard chemotherapy with cytarabine/daunorubicin in newly diagnosed AML patients. Methods Nine patients were enrolled and received at least two courses of ara-C (1 g/m(2)/2 h b.i.d. d1-5, i.e., a total of 10 g/m(2) per course), hydroxyurea (1-2 g d1-5) and daunorubicin (60 mg/m(2) d1-3). The primary endpoint was safety; secondary endpoints were complete remission rate and measurable residual disease (MRD). Additionally, pharmacokinetic studies of ara-CTP and ex vivo drug sensitivity assays were performed. Results The most common grade 3-4 toxicity was febrile neutropenia (100%). No unexpected toxicities were observed. Pharmacokinetic analyses showed a significant increase in median ara-CTP levels (1.5-fold; p = 0.04) in patients receiving doses of 1 g hydroxyurea. Ex vivo, diagnostic leukaemic bone marrow blasts from study patients were significantly sensitised to ara-C by a median factor of 2.1 (p = 0.0047). All nine patients (100%) achieved complete remission, and all eight (100%) with validated MRD measurements (flow cytometry or real-time quantitative polymerase chain reaction [RT-qPCR]) had an MRD level <0.1% after two cycles of chemotherapy. Treatment was well-tolerated, and median time to neutrophil recovery >1.0 x 10(9)/L and to platelet recovery >50 x 10(9)/L after the start of cycle 1 was 19 days and 22 days, respectively. Six of nine patients underwent allogeneic haematopoietic stem-cell transplantation (allo-HSCT). With a median follow-up of 18.0 (range 14.9-20.5) months, one patient with adverse risk not fit for HSCT experienced a relapse after 11.9 months but is now in second complete remission. Conclusion Targeted inhibition of SAMHD1 by the addition of hydroxyurea to conventional AML therapy is safe and appears efficacious within the limitations of the small phase 1 patient cohort. These results need to be corroborated in a larger study.
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| 12. |
- Brahme, A., et al.
(författare)
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Evaluation of a GEM and CAT-based detector for radiation therapy beam monitoring
- 2000
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 454, s. 136-141
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Tidskriftsartikel (refereegranskat)abstract
- We are developing a radiation therapy beam monitor for the Karolinska Institute. This monitor will consist of two consecutive detectors confined in one gas chamber: a keV-photon detector, which will allow diagnostic quality visualization of the patient, and a MeV-photon detector, that will measure the absolute intensity of the therapy beam and its position with respect to the patient. Both detectors are based on highly radiation resistant gas and solid photon to electron converters, combined with GEMs and a CAT as amplification structures. We have performed systematic studies of the high-rate characteristics of the GEM and the CAT, as well as tested the electron transfer through these electron multipliers and various types of converters. The tests show that the GEM and the CAT satisfy all requirements for the beam monitoring system. As a result of these studies we successfully developed and tested a full section of the beam monitor equipped with a MeV-photon converter placed between the GEM and the CAT.
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| 17. |
- HUDNER, J, et al.
(författare)
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PREPARATION OF YBA2CU3O7-X FILMS AND YBA2CU3O7-X/Y2O3 MULTILAYERS USING COEVAPORATION AND ATOMIC OXYGEN
- 1993
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 73, s. 3096-3098
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Tidskriftsartikel (refereegranskat)abstract
- Thin layers of YBa2Cu3O7-x (YBCO) deposited on LaAlO3 substrates have been prepared in situ by coevaporation of Y, Ba, and Cu. Incorporation of oxygen was accomplished by an atomic oxygen beam source with high cracking efficiency. The total oxygen flow at the substrate could be kept low enough to permit the use of a quadrupole mass spectrometer for evaporation rate monitoring. Films were strongly c-axis oriented with rocking curve full width at half-maximum values of 0.6-degrees. Transport measurements on patterned films yielded critical current densities of 6 x 10(6) A/cm2 at 77 K. The deposition method was demonstrated to be feasible for preparation of Y2O3/YBCO heterostructures.
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| 18. |
- Iacobaeus, C., et al.
(författare)
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A high position resolution X-ray detector : An Edge on illuminated capillary plate combined with a gas amplification structure
- 2006
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Ingår i: IEEE Transactions on Nuclear Science. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9499 .- 1558-1578. ; 53:2, s. 554-561
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Tidskriftsartikel (refereegranskat)abstract
- We have developed and successfully tested a prototype of a new high position resolution hybrid X-ray detector. It contains a thin-wall lead glass capillary plate converter of X-rays combined with a microgap parallel-plate avalanche chamber operating in various gas mixtures at 1 atm. The operation of these converters was studied in a wide range of X-ray energies (from 6 to 60 keV) at incident angles varying from 0-90 degrees. The detection efficiency, depending on the geometry, photon's energy, incident angle and the mode of operation was between 5-30% in single step mode and up to 50% in a multi-layered combination. Depending on the capillary's geometry, the position resolution achieved was between 50-250 mu m in digital form and was practically independent of the photon's energy or gas mixture. The usual lead glass capillary plates operated without noticeable charging up effects at counting rates of 50 Hz/mm(2) and hydrogen treated capillaries-up to 10(5) Hz/mm(2). The developed detector has several important potential advantages over the exciting X-ray detectors and may open new possibilities for medical imaging, for example in mammography, portal imaging, radiography (including security devices), as well as many other applications.
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| 19. |
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| 20. |
- Iacobaeus, C., et al.
(författare)
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Advances in capillary-based gaseous UV imaging detectors
- 2004
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 525:02-jan, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- We studied gain and position resolution of gaseous UV-photon detectors combining single- and cascaded-glass capillary-plate multipliers and CsI photocathodes. Two modes of operation were investigated: a conventional one, where the main amplification occurs within capillary holes and a parallel-plate amplification mode, where the main amplification occurs between the capillary plate and the readout anode. Results of these studies demonstrate that in the parallel-plate amplification mode one can reach both high gains (> 10(5)) and good position resolutions (similar to 100 mum) even with a single-element multiplier. This offers a compact amplification structure, which can be used in many applications.
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