TY  - JOUR
A1  - Carmela Vegliante, Maria
A1  - Royo, Cristina
A1  - Palomero, Jara
A1  - Salaverria, Itziar
A1  - Balint, Balazs
A1  - Martin-Guerrero, Idoia
A1  - Agirre, Xabier
A1  - Lujambio, Amaia
A1  - Richter, Julia
A1  - Xargay-Torrent, Silvia
A1  - Bea, Silvia
A1  - Hernandez, Luis
A1  - Enjuanes, Anna
A1  - Jose Calasanz, Maria
A1  - Rosenwald, Andreas
A1  - Ott, German
A1  - Roman-Gomez, Jose
A1  - Prosper, Felipe
A1  - Esteller, Manel
A1  - Jares, Pedro
A1  - Siebert, Reiner
A1  - Campo, Elias
A1  - Martin-Subero, Jose I.
A1  - Amador, Virginia
T1  - Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications
JF  - PLoS ONE
N2  - Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with unmethylated DNA and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and other lymphoid neoplasms do not express SOX11. Such repression was associated with silencing histone marks H3K9me2 and H3K27me3. The SOX11 promoter of non-malignant cells was consistently unmethylated whereas lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation. SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms, it seems to be functionally inert, as SOX11 is already silenced in the hematopoietic system. In contrast, the pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications.
KW  - Mantle cell lymphoma
KW  - Defined burkitts lymphoma
KW  - Transcription-factor
KW  - Gene-expression
KW  - High-resolution
KW  - DNA methylation
KW  - Nuclear expression
KW  - Cancer
KW  - Microarray
KW  - Survival
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135325
VL  - 6
IS  - 6
ER  - 
TY  - JOUR
A1  - Stuckensen, Kai
A1  - Lamo-Espinosa, José M.
A1  - Muiños-López, Emma
A1  - Ripalda-Cemboráin, Purificación
A1  - López-Martínez, Tania
A1  - Iglesias, Elena
A1  - Abizanda, Gloria
A1  - Andreu, Ion
A1  - Flandes-Iparraguirre, María
A1  - Pons-Villanueva, Juan
A1  - Elizalde, Reyes
A1  - Nickel, Joachim
A1  - Ewald, Andrea
A1  - Gbureck, Uwe
A1  - Prósper, Felipe
A1  - Groll, Jürgen
A1  - Granero-Moltó, Froilán
T1  - Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP−2 and enhanced bone regeneration
JF  - Materials
N2  - In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing.
KW  - rhBMP–2
KW  - collagen sponge
KW  - cryostructured scaffolds
KW  - bone critical size defect
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195966
SN  - 1996-1944
VL  - 12
IS  - 19
ER  -