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| 2. |
- Feldman, E. J., et al.
(författare)
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On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia
- 2008
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 22:9, s. 1707-1711
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Tidskriftsartikel (refereegranskat)abstract
- Lonafarnib is an orally bio-available farnesyltransferase inhibitor that prevents farnesylation of specific target proteins including Ras. In a multicenter study, 67 patients with advanced myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) were treated with a continuous oral dose of 200-300 mg of lonafarnib and were evaluated for hematologic, pathologic and pharmacodynamic response. The median age of patients was 70 years (range 44-86). There were 32 patients with MDS (RAEB-20 and RAEB-t-12) and 35 with CMML. Overall 16 (24%) of the patients responded with two patients achieving a complete remission and one a partial response. Responses were seen in 6/32 and 10/35 patients with MDS and CMML, respectively. Of the 19 patients who were platelet transfusion-dependent prior to treatment, 5 (26%) became transfusion-free for a median duration of 185 days. A decrease in the farnesylation of the HDJ-2 protein measured in patient-derived cells was observed in the majority of patients during treatment with lonafarnib, but no clear correlation between changes in farnesylation and clinical effect could be made. Gastrointestinal toxicity was significant with 19% of patients discontinuing therapy due to diarrhea, nausea and/or anorexia. Lonafarnib has demonstrable activity in patients with advanced MDS and CMML.
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| 3. |
- Misra, Deepankar, et al.
(författare)
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Two-Center Double-Capture Interference in Fast He2++H2 Collisions
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:15, s. 153201-
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Tidskriftsartikel (refereegranskat)abstract
- We report the first observation of Young-type interference effects in a two-electron transfer process. These effects change strongly as the projectile velocity changes in fast (1.2 and 2.0 MeV) He^{2+}-H_2 collisions as manifested in strong variations of the double-electron capture rates with the H_2 orientation. This is consistent with fully quantum mechanical calculations, which ignore sequential electron transfer, and a simple projectile de Broglie wave picture assuming that two-electron transfer probabilities are higher in collisions where the projectile passes close to either one of the H_2 nuclei.
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| 5. |
- Saussele, S., et al.
(författare)
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Klinische Forschung im „European LeukemiaNet”
- 2006
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Ingår i: Deutsche Medizinische Wochenschrift. - : Georg Thieme Verlag KG. - 0012-0472 .- 1439-4413. ; 131:43, s. 2423-2426
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Tidskriftsartikel (refereegranskat)abstract
- Because of their mortality, morbidity and incidence in all age groups, leukemias represent a challenge and a cost factor for society. In research, they serve as models for a variety of diseases and have a pivotal function in basic research and for patient care. The European LeukemiaNet (ELN) is a EU funded Network of excellence. Its major goal is the construction of an exemplary cooperative leukemia network for the improvement of medical care and of health related research in acute and chronic leukemias. This is achieved by improved mechanisms of cooperation among 78 national leukemia study groups and their 83 interdisciplinary partner groups that deal with the leukemias in research and in patient care in 22 countries. The network integrates about 1000 researchers in 125 participating institutions. In practice, cooperation between clinical and research groups is mediated by various instruments that improve communication, flow of information and interdisciplinary cooperation, and also increase information transfer from top research institutions to clinical translation. The improved cooperation and the accelerated information transfer from the „bench to the bedside” results in a better patient care that ultimately results in improved survival of patients and in superior competitiveness of involved research workers and clinicians. The major goals are: Establishing common information and communication structures, Creation of European networks for each leukemia Establishing European platforms for each inter-disciplinary speciality Performing clinical trials on an European level Establishing European leukemia registries Developing common definitions and standards Developing guidelines and meta-analyses Spread of excellence To reach these goals the network is organized in 17 Workpackages (WPs) each of which is subdivided into several components and deliverables. The WPs represent central services, set up European networks for each major leukemia or related syndrome and interdisciplinary European platforms for diagnostic specialities, and support treatment research, registries, meta-analyses and guidelines. After the second year of networking, the main structures concerning management, communication and information of the ELN have been established and consolidated. Web-based information is available on the central website (www.leukemia-net.org). Communication is accomplished through annual symposia, regular network and WP-meetings (nearly 60 in 2005), website, and the biannual newsletters. A central randomization service and registries are available for distinct leukemia entities, and a prototype of the electronic data capture facility service has been implemented. Several studies were initiated and are ongoing on a European level. Nearly all WPs have prepared or are preparing guidelines or consensus papers, e. g. guidelines on CML therapy, definitions for transplantation associated microangiopathy (TAM), therapy of infections in leukemias, harmonization of molecular monitoring in CML and a consensus on microarray-technology based diagnostics in leukemias. The main goals of the second funding period have been achieved, and thus the ELN is well prepared for further progress in its goals to improve diagnosis and treatment of the leukemias.
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| 6. |
- Schef, P, et al.
(författare)
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Disentanglement of magnetic field mixing reveals the spontaneous M2 decay rate for a metastable level in Xe
- 2005
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 72:2, s. 020501-
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the radiative decay of the metastable level 5d(4)D(7/2) in Xe+. Theoretically we find the decay to be heavily dominated by an M2 transition and not by M1/E2 transitions. Lifetime measurements of 5d(4)D(7/2) in a storage ring are difficult since magnetic mixing of the metastable with a short-lived level quenches its population. Decay rates were determined at different magnetic field strengths (B) in order to allow a nonlinear extrapolation to B=0. The experimental lifetime of 2.4 +/- 0.8 s was in agreement with the calculated value, but much smaller than previously estimated.
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| 10. |
- Brune, Mats, 1950, et al.
(författare)
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Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 108:1, s. 88-96
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.
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