| 1. |
- Bergh Thorén, Fredrik, 1976, et al.
(författare)
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Antitumor properties of histamine in vivo.
- 2011
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 17:5, s. 537; author reply 537-8
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Blennow, Kaj, 1958
(författare)
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Biomarkers in Alzheimer's disease drug development.
- 2010
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 16:11, s. 1218-22
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Forskningsöversikt (refereegranskat)abstract
- Biomarkers may be of great value in Alzheimer's disease drug development to select the most optimal drug candidates for large and expensive phase 3 clinical trials. Biomarkers will also be important to provide evidence that a drug affects the underlying pathophysiology of the disease, which, together with a beneficial effect on the clinical course, will be essential for labeling the drug as having a disease-modifying effect.
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| 3. |
- Blennow, Kaj, 1958, et al.
(författare)
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Semagacestat's fall: where next for AD therapies?
- 2013
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 19:10, s. 1214-5
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Milk modulates the microbiota
- 2012
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 18:8
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
- Coulon, Severine, et al.
(författare)
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Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia
- 2011
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 17:11, s. 163-1456
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Tidskriftsartikel (refereegranskat)abstract
- Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (TfR1)-bound polymeric IgA1 (pIgA1). Under homeostatic conditions, erythroblast numbers were increased in mice expressing human IgA1 compared to control mice. Hypoxic stress of these mice led to increased amounts of pIgA1 and erythroblast expansion. Expression of human IgA1 or treatment of wild-type mice with the TfR1 ligands pIgA1 or iron-loaded transferrin (Fe-Tf) accelerated recovery from acute anemia. TfR1 engagement by either pIgA1 or Fe-Tf increased cell sensitivity to Epo by inducing activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. These cellular responses were mediated through the TfR1-internalization motif, YXX Phi. Our results show that pIgA1 and TfR1 are positive regulators of erythropoiesis in both physiological and pathological situations. Targeting this pathway may provide alternate approaches to the treatment of ineffective erythropoiesis and anemia.
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| 8. |
- D'Arcy, Pádraig, et al.
(författare)
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Inhibition of proteasome deubiquitinating activity as a novel cancer therapy
- 2011
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Ingår i: Nature Medicine. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1546-170X .- 1078-8956.
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitin-tagged substrates are degraded by the 26S proteasome, which is a multisubunit complex comprising a proteolytic 20S core particle capped by 19S regulatory particles. The approval of bortezomib for the treatment of multiple myeloma validated the 20S core particle as an anticancer drug target. Here we describe the small molecule b-AP15 as a previously unidentified class of proteasome inhibitor that abrogates the deubiquitinating activity of the 19S regulatory particle. b-AP15 inhibited the activity of two 19S regulatory-particle-associated deubiquitinases, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b-AP15 induced tumor cell apoptosis that was insensitive to TP53 status and overexpression of the apoptosis inhibitor BCL2. We show that treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model. Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target.
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| 9. |
- Delorme, Richard, et al.
(författare)
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Progress toward treatments for synaptic defects in autism.
- 2013
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 19:6, s. 685-694
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. For the majority of affected individuals, the cause of ASD remains unknown, but in at least 20% of the cases, a genetic cause can be identified. There is currently no cure for ASD; however, results from mouse models indicate that some forms of the disorder could be alleviated even at the adult stage. Genes involved in ASD seem to converge on common pathways altering synaptic homeostasis. We propose, given the clinical heterogeneity of ASD, that specific 'synaptic clinical trials' should be designed and launched with the aim of establishing whether phenotype 'reversals' could also occur in humans.
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