Papers by Henrik Hjorth-hansen
Blood, 2000
Syndecan-1 is a heparan sulfate proteoglycan expressed on the surface of, and actively shed by, m... more Syndecan-1 is a heparan sulfate proteoglycan expressed on the surface of, and actively shed by, myeloma cells. Hepatocyte growth factor (HGF) is a cytokine produced by myeloma cells. Previous studies have demonstrated elevated levels of syndecan-1 and HGF in the serum of patients with myeloma, both of negative prognostic value for the disease. Here we show that the median concentrations of syndecan-1 (900 ng/mL) and HGF (6 ng/mL) in the marrow compartment of patients with myeloma are highly elevated compared with healthy controls and controls with other diseases. We show that syndecan-1 isolated from the marrow of patients with myeloma seems to exist in an intact form, with glucosaminoglycan chains. Because HGF is a heparan-sulfate binding cytokine, we examined whether it interacted with soluble syndecan-1. In supernatants from myeloma cells in culture as well as in pleural effusions from patients with myeloma, HGF existed in a complex with soluble syndecan-1. Washing myeloma cells ...
Bookmarks Related papers MentionsView impact
Haematologica, 2004
Osteopontin (OPN) is a non-collagenous matrix protein produced by various cells including osteobl... more Osteopontin (OPN) is a non-collagenous matrix protein produced by various cells including osteoblasts, osteoclasts and several types of tumor cells. It is involved in a number of physiologic and pathologic events including adhesion, angiogenesis, apoptosis, inflammation, wound healing and tumor metastasis. We wanted to investigate the potential role of OPN in multiple myeloma. Myeloma cells and stromal cells from myeloma patients were investigated as potential OPN-producers. Furthermore, OPN was tested in proliferation, migration and adhesion assays with myeloma cells. Serum and plasma OPN in myeloma patients were measured by enzyme-linked immunosorbent assay (ELISA). OPN levels were correlated to disease variables at diagnosis and to disease outcome. Myeloma cells produce OPN, and stromal cells from myeloma patients express higher levels of OPN than stromal cells from healthy controls. The myeloma cell lines ANBL-6 and INA-6 adhered to OPN. NOD/SCID mice inoculated with OPN-produci...
Bookmarks Related papers MentionsView impact
European Journal of Haematology, 2014
Bookmarks Related papers MentionsView impact
Placenta, 1996
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Leukemia, 2009
Bookmarks Related papers MentionsView impact
The Lancet Oncology, 2010
Bookmarks Related papers MentionsView impact
Experimental Hematology, 2012
Bookmarks Related papers MentionsView impact
European Journal of Haematology, 2009
Studies have revealed an association between overweight/obesity and multiple myeloma. However, th... more Studies have revealed an association between overweight/obesity and multiple myeloma. However, the factors linking a dysregulated energy metabolism to this disease have not been identified. Adipose tissue produces and secretes the adipokines leptin, adiponectin and resistin, involved in metabolism and cell growth. We measured the plasma concentrations of these three adipokines in newly diagnosed multiple myeloma as well as in patients with relapse. We further explored the importance of leptin in multiple myeloma by performing gene expression profiling in two myeloma cell lines. At diagnosis, leptin was increased (P < 0.05) in both female and male patients compared with controls. Adiponectin was reduced (P < 0.05) among male patients, whereas no significant changes in resistin were noted among any patients. In patients with relapse and treated with thalidomide, no particular adipokine pattern was revealed. Leptin induced the expression of several genes important for cell signaling, growth and viability. The plasma concentrations of leptin and adiponectin, but not resistin, were abnormal in newly diagnosed multiple myeloma. Adipose tissue may modify the growth and metabolism of myeloma cells through adipokine-mediated effects.
Bookmarks Related papers MentionsView impact
European Journal of Haematology, 2009
Page 1. Eur J Haematoll999: 63: 345-353 Printed in UK. AN rights reserved Key words: multiple mye... more Page 1. Eur J Haematoll999: 63: 345-353 Printed in UK. AN rights reserved Key words: multiple myeloma; tumor necrosis factor; 1 Fas; NF-KB; OH-2 Correspondence: Magne Bsrset. MD. Ph D., Norwegian University of Science and Technology. ...
Bookmarks Related papers MentionsView impact
European Journal of Haematology, 2009
Serum from 398 myeloma patients at diagnosis and serial samples from 29 patients were analysed fo... more Serum from 398 myeloma patients at diagnosis and serial samples from 29 patients were analysed for hepatocyte growth factor (HGF). HGF was elevated at diagnosis in 43% of myeloma patients compared with healthy controls (median 1.00 ng/mL and 0.44 ng/mL, respectively; P < .00001). In the group with elevated HGF levels 46% of the patients reached plateau phase, as compared with 60% of the patients with low HGF levels (P = .005), and the median survival time was 21 and 32 months, respectively (P = .002). In a univariate Cox regression analysis, HGF was a significant predictor of mortality (P = .02). In the subgroup of patients with beta 2-microglobulin levels less than or equal to 6 mg/L, high versus low HGF was a prognostic factor when a multivariate Cox regression analysis was performed. In serial samples HGF was higher at the time of diagnosis and relapse (median 0.57 ng/mL and 0.52 ng/mL, respectively; P = .0018) than at response (median 0.24 ng/mL, P = .008). We conclude that HGF may be a useful follow-up parameter in myeloma patients. Measurement of HGF may identify a group of patients with poor response to melphalan-prednisone treatment and short survival. HGF was a prognostic factor in patients with high levels of beta 2-microglobulin.
Bookmarks Related papers MentionsView impact
British Journal of Haematology, 2000
Bookmarks Related papers MentionsView impact
British Journal of Haematology, 1999
The growth factor-dependent myeloma cell line OH-2, which has previously been shown to be respons... more The growth factor-dependent myeloma cell line OH-2, which has previously been shown to be responsive to interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and lymphotoxin, was examined for response to other growth factors. Enhanced proliferation was found in the presence of IL-10, IL-15, IL-2 and insulin growth factor (IGF)-1. Proliferation was strongest in response to IL-6, intermediate and roughly equipotent in response to IL-15, IL-10 and TNF-alpha, and modest in response to IL-2 and IGF-1. IL-15 was synergistic with TNF-alpha, whereas combinations of IL-15 and the other cytokines were merely additive. IL-15-induced proliferation could not be blocked by neutralizing antibody against gp 130, the common transducer chain of IL-6 and related cytokines. IL-15 and IL-6 prevented apoptosis equally well, both better than TNF-alpha, IL-10, and IGF-1. In four out of six samples of purified primary cells, IL-15 and IL-6 induced proliferation. Furthermore, IL-15 mRNA was detected by RT-PCR in most myeloma cell lines and freshly isolated purified patient samples. IL-15 protein was detectable only in one out of about 20 tested cell supernatants from patients and myeloma cell lines. The OH-2 cell line is multi-responsive to cytokines and is a good system for the study of integration of cytokine signal transduction and growth control in myeloma. IL-15 represents a novel modality of growth regulation in myeloma.
Bookmarks Related papers MentionsView impact
Blood, 2013
Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors... more Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward define optimal response, whereas…
Bookmarks Related papers MentionsView impact
Blood, 2010
Bookmarks Related papers MentionsView impact
Blood, 2002
Bookmarks Related papers MentionsView impact
Bone morphogenetic proteins (BMPs) can be isolated from organic bone matrix and are able to initi... more 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.
Bookmarks Related papers MentionsView impact
Blood, 2009
Bookmarks Related papers MentionsView impact
Although imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chrom... more Although imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chromosome-positive (Ph(+)) leukemia, it does not prevent central nervous system (CNS) relapses resulting from poor drug penetration through the blood-brain barrier. Imatinib and dasa-tinib (a dual-specific SRC/BCR-ABL kinase inhibitor) were compared in a preclinical mouse model of intracranial Ph(+) leukemia. Clinical dasatinib treatment in patients with CNS Ph(+) leukemia was assessed. In preclinical studies, dasatinib increased survival, whereas imatinib failed to inhibit intracranial tumor growth. Stabilization and regression of CNS disease were achieved with continued dasa-tinib administration. The drug also demonstrated substantial activity in 11 adult and pediatric patients with CNS Ph(+) leukemia. Eleven evaluable patients had clinically significant, long-lasting responses, which were complete in 7 patients. In 3 additional patients, isolated CNS relapse occurred during dasatinib therapy; and in 2 of them, it was caused by expansion of a BCR-ABL-mutated dasatinib-resistant clone, implying selection pressure exerted by the compound in the CNS. Dasatinib has promising therapeutic potential in managing intracranial leukemic disease and substantial clinical activity in patients who experience CNS relapse while on imatinib therapy. This study is registered at ClinicalTrials.gov as CA180006 (#NCT00108719) and CA180015 (#NCT00110097).
Bookmarks Related papers MentionsView impact
Uploads
Papers by Henrik Hjorth-hansen