A5049608650- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- TGF-β signaling in diseases
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Protein Tyrosine Phosphatases
- PI3K/AKT/mTOR signaling in cancer
- Bone health and treatments
- Protein Kinase Regulation and GTPase Signaling
- Glycosylation and Glycoproteins Research
- Cell death mechanisms and regulation
- Bone Metabolism and Diseases
- Cytokine Signaling Pathways and Interactions
- Photodynamic Therapy Research Studies
- Heterotopic Ossification and Related Conditions
- Signaling Pathways in Disease
- GDF15 and Related Biomarkers
- Histone Deacetylase Inhibitors Research
- Biochemical and Molecular Research
- Melanoma and MAPK Pathways
- Chemokine receptors and signaling
- Cancer Mechanisms and Therapy
- Cutaneous lymphoproliferative disorders research
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
Norwegian University of Science and Technology
2015-2024
St Olav's University Hospital
2017-2024
University Hospital Heidelberg
2023
Heidelberg University
2023
Oslo University Hospital
2020-2021
Norwegian Cancer Society
2000
Activins are members of the TGF-β family ligands that have multiple biological functions in embryonic stem cells as well differentiated tissue. Serum levels activin A were found to be elevated pathological conditions such cachexia, osteoporosis and cancer. Signaling by through canonical ALK4-ACVR2 receptor complexes activates transcription factors SMAD2 SMAD3. Activin has a strong affinity type 2 receptors, feature they share with some bone morphogenetic proteins (BMPs). is also myeloma...
Multiple myeloma is a hematological cancer that considered incurable despite advances in treatment strategy during the last decade. Therapies targeting single pathways are unlikely to succeed due heterogeneous nature of malignancy. Proliferating cell nuclear antigen (PCNA) multifunctional protein essential for DNA replication and repair often overexpressed cells. Many proteins involved cellular stress response interact with PCNA through five amino acid sequence AlkB homologue 2...
The rational design of inhibitors the bHLH-ZIP oncoprotein c-Myc is hampered by a lack structure in its monomeric state. We describe herein novel, low-molecular-weight, synthetic α-helix mimetics that recognize helical transcriptionally active coiled-coil association with obligate partner Max. These compounds perturb heterodimer's binding to canonical E-box DNA sequence without causing protein–protein dissociation, heralding new mechanistic class "direct" inhibitors. In addition...
Although chemo-immunotherapy has led to an improved overall survival for most B-cell lymphoma types, relapsed and refractory disease remains a challenge. The malaria drug artesunate previously been identified as growth suppressor in some cancer types was tested new treatment option lymphoma.We included sensitivity screen B cell lines. preclinical properties of single agent vitro 18 lines representing different histologies vivo aggressive xenograft model, using NSG mice. Artesunate-treated...
Purified recombinant proteins for use in biomedical research are invaluable to investigate protein function. However, purity varies batches made mammalian expression systems, such as CHO-cells or HEK293-cells. This study points caution while investigating effects of related the transforming growth factor (TGF)-β superfamily. TGF-β itself is a very potent cytokine and has on cells femtomolar range. Thus, even small amounts contaminating purified may influence experimental results given that...
Circulating tumor DNA is a promising biomarker to monitor load and genome alterations. We explored the presence of circulating in multiple myeloma patients its relation disease activity during long-term follow-up. used digital droplet polymerase chain reaction analysis recurrent mutations, mainly mitogen activated protein kinase pathway genes NRAS, KRAS BRAF. Mutations were identified by next-generation sequencing or bone marrow plasma cells, their analyzed 251 archived serum samples...
Abstract Multiple myeloma (myeloma in short) is an incurable cancer of antibody-producing plasma cells that comprise 13% all hematological malignancies. The proteasome inhibitor bortezomib has improved treatment significantly, but inherent and acquired resistance to the drug remains a problem. We here show bortezomib-induced cytotoxicity was completely dampened when were supplemented with cysteine or its derivative, glutathione (GSH) ANBL-6 INA-6 cell lines. GSH major component antioxidative...
ABSTRACT TGF-β/BMP superfamily ligands require heteromeric complexes of type 1 and 2 receptors for ligand-dependent downstream signaling. Activin A, a TGF-β member, inhibits growth multiple myeloma cells, but the mechanism this is unknown. We therefore aimed to clarify how activins affect cell survival. A activates transcription factors SMAD2/3 through ALK4 receptor, may also activate SMAD1/5/8 mutated variants receptor ALK2 (also known as ACVR1). demonstrate that activin B in cells...
// Huabo Wang 1 , Peter Teriete 2 Angela Hu Dhanya Raveendra-Panickar Kelsey Pendelton John S. Lazo 3 Julie Eiseman 4,5 Toril Holien 6 Kristine Misund Ganna Oliynyk 7 Marie Arsenian-Henriksson Nicholas D. P. Cosford Anders Sundan and Edward V. Prochownik 1,5,8 Section of Hematology/Oncology, Children’s Hospital Pittsburgh UPMC, The University Medical Center, Pittsburgh, PA, USA Cell Death Survival Networks Research Program, Sanford Burnham Prebys Discovery Institute, La Jolla, CA,...
In breast cancer, activation of bone morphogenetic protein (BMP) signaling and elevated levels BMP-antagonists have been linked to tumor progression metastasis. However, the simultaneous upregulation BMPs their antagonist, fact that both promote aggressiveness seems contradictory is not fully understood.We analyzed transcriptomes metastatic 66cl4 non-metastatic 67NR cell lines 4T1 mouse mammary model search for factors CRISPR/Cas9 gene editing was used mechanistic studies in same lines....
Activins belong to the transforming growth factor (TGF)-β family of multifunctional cytokines and signal via activin receptors ALK4 or ALK7 activate SMAD2/3 pathway. In some cases, activins also bone morphogenetic protein (BMP) receptor ALK2, causing activation SMAD1/5/8 this study, we aimed dissect how A B homodimers, AB AC heterodimers two main SMAD branches. We compared activin-induced signaling dynamics ALK4/7-SMAD2/3 ALK2-SMAD1/5 in a multiple myeloma cell line. Signaling pathway...
Multiple myeloma is a malignancy of plasma cells predominantly located in the bone marrow. A number morphogenetic proteins (BMPs) induce apoptosis vitro, and with this study we add BMP-9 to list. has been found human serum at concentrations that inhibit cancer cell growth vitro. We here show level was elevated patients (median 176 pg/ml, range 8-809) compared healthy controls 110 8-359). also present marrow able 4 out 11 primary samples by signaling through ALK2. BMP-9-induced associated...
Methyl groups can have profound effects in drug discovery but the underlying mechanisms are diverse and incompletely understood. Here we report stereospecific effect of a single, solvent-exposed methyl group bicyclic [4.3.1] aza-amides, robustly leading to 2 10-fold increase binding affinity for FK506-binding proteins (FKBPs). This resulted most potent efficient FKBP ligands known date. By combination co-crystal structures, isothermal titration calorimetry (ITC), density-functional theory...
Abstract Objectives: Hepatocyte growth factor (HGF) is a constituent of the myeloma microenvironment and elevated in sera from patients compared to healthy individuals. Increased levels serum HGF predict poor prognosis. It has previously been shown by us others can act as cells vitro although these effects have moderate. We therefore wanted investigate if could influence interleukin (IL)‐6. Methods: Myeloma cell lines primary samples were tested for combined IL‐6 inducing DNA synthesis...
Abstract Objectives The use of new drugs has improved the treatment multiple myeloma and diffuse large B‐cell lymphoma ( DLBCL ). Nevertheless, over time many patients relapse develop resistance to treatment, efforts are needed overcome drug resistance. widely used malaria artesunate been reported have antitumor activity, we aimed test effects on a panel cells. Methods Myeloma cell lines were treated with in vitro . evaluated using ATP content measurements for proliferation annexin...
Cells degrade proteins either by proteasomes that clinically are targeted for example bortezomib or carfilzomib, formation of autophagosomes and lysosomal degradation can be inhibited hydroxychloroquine (HCQ). Multiple myeloma is unique among cancers because proteasomal inhibition has good clinical effects. However, some multiple patients display intrinsic resistance to the treatment most acquire over time. We hypothesized simultaneous targeting both arms protein could a way improve myeloma....
// Toril Holien 1 , Kristine Misund Oddrun Elise Olsen Katarzyna Anna Baranowska Glenn Buene Magne Børset 1, 2 Anders Waage 3 Sundan 4 K.G. Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University Science Technology, Trondheim, Norway Immunology Transfusion St. Olav's Hospital, Hematology, CEMIR (Centre Inflammation Research), Correspondence to: Holien, e-mail: toril.holien@ntnu.no Keywords: oncology, carcinogenesis, molecular cellular...
No ligand has hitherto been designated for the Eph receptor tyrosine kinase family member, EphB6. Here, expression of an EphB6 in pro‐B leukemic cell line, Reh, is demonstrated by binding soluble EphB6‐Fc fusion protein to Reh cells. The belongs subgroup membrane spanning ligands, as suggested fact that phosphatidylinositol‐specific phospholipase C treatment did not abrogate EphB6‐Fc. Two transmembrane ephrin‐B1 and ephrin‐B2, were identified Analysis or ephrin‐B2 transfected COS cells...