Publications (16) View all
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Article: Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase III trial.
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ABSTRACT: The Nordic Myeloma Study Group (NMSG) conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to no consolidation in bortezomib naïve patients with newly diagnosed multiple myeloma. Overall, 370 patients were centrally randomly assigned three months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomisation was 27 months for the bortezomib group compared to 20 months for the control group (p=0.05). Fifty-one out of 90 patients in the treatment group compared to 32 out of 90 controls improved their response after randomisation (p=0.007). No difference in overall survival was seen. Fatigue was reported more commonly by the bortezomib treated patients in self-reported quality of life (QoL) questionnaires, whereas no other major differences QoL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in ≥ VGPR at randomisation. Consolidation with bortezomib after ASCT in bortezomib naïve patients improves PFS without interfering with QoL. (This study was registered at www.clinicaltrials.gov as #NCT00417911.).Blood 04/2013; · 9.90 Impact Factor -
Article: Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma.
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ABSTRACT: In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P < .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was registered at www.clinicaltrials.gov as #NCT00218855.Blood 05/2010; 116(9):1405-12. · 9.90 Impact Factor -
Article: Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest.
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ABSTRACT: The platelet inhibitor clopidogrel is administered to patients treated with therapeutic hypothermia following cardiac arrest due to acute coronary syndromes. Interactions with proton pump inhibitors and genetics are factors with a known potential to attenuate the platelet inhibition of clopidogrel. In patients treated with therapeutic hypothermia, reduced gastrointestinal function and hypothermia may also reduce the effect of clopidogrel. To investigate the net platelet inhibition of clopidogrel, we have measured the platelet reactivity index in patients treated with therapeutic hypothermia. Twenty-five Caucasian patients treated with clopidogrel and therapeutic hypothermia were prospectively included. Therapeutic hypothermia was defined as 33-34°C and delivered for 24h. Clopidogrel loading doses (300-600 mg) were administered enterally the day of admission and followed by 75 mg daily. Blood samples were collected on day 1 (n=25) and day 3 (n=16). The samples were analysed for inhibition by clopidogrel with a vasodilator stimulated phosphoprotein phosphorylation kit. On day 1 and day 3, platelet reactivity index was 0.77±0.09 and 0.57±0.16, respectively. The number of patients with a satisfactory antiplatelet effect (defined as platelet reactivity index <0.5) were 0 (0%) and 5 (31%), respectively. In patients treated with therapeutic hypothermia after cardiac arrest, the effect of clopidogrel on platelets was virtually nonexistent on day 1 after administration, with some improvement on day 3.Resuscitation 12/2010; 81(12):1627-31. · 3.60 Impact Factor -
Article: Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization.
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ABSTRACT: The adipose hormone leptin and its receptor are important for regulation of food intake and energy metabolism. Leptin also is involved in the growth of different tissues. In this study, we show the expression of leptin in primary cultures of normal human osteoblasts (hOBs) as evidenced by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry. Release of leptin into the medium also was found. Leptin was not detected in commercially available hOBs (NHOst) or in three different human monoclonal osteosarcoma cell lines. Leptin expression was observed in OBs in the mineralization and/or the osteocyte transition period but not during the matrix maturation period. Furthermore, hOBs and osteosarcoma cell lines expressed the long signal-transducing form of the leptin receptor (OB-Rb) as shown by RT-PCR. We observed no significant changes in leptin or OB-Rb genes in hOBs after incubation with recombinant leptin, indicating no autoregulation of the leptin expression. Incubation of both hOBs entering the mineralization phase and osteosarcoma cell lines with recombinant leptin markedly increased the number of mineralized nodules as shown by alizarin S staining. These findings indicate that leptin may be of importance for osteoblastic cell growth and bone mineralization.Journal of Bone and Mineral Research 09/2001; 16(8):1426-33. · 6.37 Impact Factor -
Article: Bone morphogenetic protein-4 inhibits proliferation and induces apoptosis of multiple myeloma cells.
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ABSTRACT: Bone morphogenetic proteins (BMPs) can be isolated from organic bone matrix and are able to initiate de novo cartilage and bone formation. Here it is shown that BMP-4 inhibited DNA synthesis in a dose-dependent manner in 3 IL-6-dependent multiple myeloma (MM) cell lines (OH-2, IH-1, and ANBL-6). In contrast, no effect on DNA synthesis was observed in 3 IL-6-independent MM cell lines (JJN-3, U266, and RPMI 8226). BMP-4 induced cell cycle growth arrest in the G(0)/G(1) phase in OH-2 and ANBL-6 cells but not in IH-1 cells. BMP-4 induced apoptosis in OH-2 and IH-1 cells, but not significantly in ANBL-6 cells. Furthermore, BMP-4 induced apoptosis in freshly isolated MM cells from 4 of 13 patients. In the OH-2 and ANBL-6 cell lines and in a patient sample, immunoblotting showed that BMP-4 down-regulated IL-6-induced tyrosine phosphorylation of Stat3, suggesting a mechanism for the apparent antagonism between IL-6 and BMP-4. BMP-4 or analogues may be attractive therapeutic agents in MM because of possible beneficial effects on both tumor burden and bone disease.Blood 02/2001; 97(2):516-22. · 9.90 Impact Factor
