umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Forsberg, Karin
Publications (2 of 2) Show all publications
Hjorth, M., Hjertner, O., Meldgaard Knudsen, L., Gulbrandsen, N., Holmberg, E., Trøllund Pedersen, P., . . . Swedin, A. (2012). Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.. European Journal of Haematology, 88(6), 485-496
Open this publication in new window or tab >>Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.
Show others...
2012 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 88, no 6, p. 485-496Article in journal (Refereed) Published
Abstract [en]

Objectives:  Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives. Methods:  Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms. Results:  After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group. Conclusions:  Thalidomide (50-100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.

Place, publisher, year, edition, pages
John Wiley & Sons, 2012
Keywords
multiple myeloma, thalidomide, bortezomib, randomized trial, quality of life
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-55752 (URN)10.1111/j.1600-0609.2012.01775.x (DOI)22404182 (PubMedID)
Available from: 2012-05-30 Created: 2012-05-30 Last updated: 2018-06-08Bibliographically approved
Bergemalm, D., Forsberg, K., Jonsson, P. A., Graffmo, K. S., Brännström, T., Andersen, P. M., . . . Marklund, S. L. (2009). Changes in the spinal cord proteome of an amyotrophic lateral sclerosis murine model determined by differential in-gel electrophoresis. Molecular and cellular proteomics, 8(6), 1306-1317
Open this publication in new window or tab >>Changes in the spinal cord proteome of an amyotrophic lateral sclerosis murine model determined by differential in-gel electrophoresis
Show others...
2009 (English)In: Molecular and cellular proteomics, ISSN 1535-9484, Vol. 8, no 6, p. 1306-1317Article in journal (Refereed) Published
Abstract [en]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons resulting in progressive paralysis. To date, more than 140 different mutations in the gene encoding CuZn-superoxide dismutase (SOD1) have been associated with ALS. Several transgenic murine models exist in which various mutant SOD1s are expressed. We have used differential in-gel electrophoresis (DIGE) to analyze the changes in the spinal cord proteome induced by expression of the unstable SOD1 truncation mutant G127insTGGG (G127X) in mice. Unlike mutants used in most other models, G127X lacks SOD activity and is present at low levels, thus reducing the risk of overexpression artifacts. The mice were analyzed at their peak body weights, just before onset of symptoms. Variable importance plot (VIP) analysis showed that 420 of 1,800 detected protein spots contributed significantly to the differences between the groups. By MALDI-TOF MS analysis, 54 proteins were identified. One spot was found to be a covalently linked mutant SOD1 dimer, apparently analogous to SOD1 immunoreactive bands migrating at double the molecular weight of SOD1 monomers previously detected in humans and mice carrying mutant SOD1s and in sporadic ALS cases. Analyses of affected functional pathways, and the subcellular representation of alterations suggest that the toxicity exerted by mutant SODs induces oxidative stress and affects mitochondria, cellular assembly/organization, and protein degradation.

Place, publisher, year, edition, pages
The American Society for Biochemistry and Molecular Biology,Inc, 2009
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-22132 (URN)10.1074/mcp.M900046-MCP200 (DOI)19357085 (PubMedID)
Available from: 2009-04-24 Created: 2009-04-24 Last updated: 2018-06-08Bibliographically approved
Organisations

Search in DiVA

Show all publications