ORCID Profile
0000-0001-8955-2909
Current Organisation
University of North Carolina at Chapel Hill
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Massachusetts Medical Society
Date: 22-12-2011
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-11-2015
DOI: 10.1126/SCITRANSLMED.AAB1803
Abstract: Histone chaperone FACT acts in a positive feedback loop with MYCN and is a therapeutic target in neuroblastoma.
Publisher: American Society of Hematology
Date: 26-06-2014
DOI: 10.1182/BLOOD-2013-07-517086
Abstract: The high-resolution structure of the complex disulfide-bonded TIL′E′ (D′) region of VWF is presented. The major factor VIII binding site is localized around a flexible region on the TIL′ domain.
Publisher: American Association for Cancer Research (AACR)
Date: 16-05-2021
DOI: 10.1158/1078-0432.CCR-20-2357
Abstract: We investigated whether targeting chromatin stability through a combination of the curaxin CBL0137 with the histone deacetylase (HDAC) inhibitor, panobinostat, constitutes an effective multimodal treatment for high-risk neuroblastoma. The effects of the drug combination on cancer growth were examined in vitro and in animal models of MYCN- lified neuroblastoma. The molecular mechanisms of action were analyzed by multiple techniques including whole transcriptome profiling, immune deconvolution analysis, immunofluorescence, flow cytometry, pulsed-field gel electrophoresis, assays to assess cell growth and apoptosis, and a range of cell-based reporter systems to examine histone eviction, heterochromatin transcription, and chromatin compaction. The combination of CBL0137 and panobinostat enhanced nucleosome destabilization, induced an IFN response, inhibited DNA damage repair, and synergistically suppressed cancer cell growth. Similar synergistic effects were observed when combining CBL0137 with other HDAC inhibitors. The CBL0137 anobinostat combination significantly delayed cancer progression in xenograft models of poor outcome high-risk neuroblastoma. Complete tumor regression was achieved in the transgenic Th-MYCN neuroblastoma model which was accompanied by induction of a type I IFN and immune response. Tumor transplantation experiments further confirmed that the presence of a competent adaptive immune system component allowed the exploitation of the full potential of the drug combination. The combination of CBL0137 and panobinostat is effective and well-tolerated in preclinical models of aggressive high-risk neuroblastoma, warranting further preclinical and clinical investigation in other pediatric cancers. On the basis of its potential to boost IFN and immune responses in cancer models, the drug combination holds promising potential for addition to immunotherapies.
Publisher: Georg Thieme Verlag KG
Date: 2005
DOI: 10.1160/TH05-03-0165
Abstract: Bernard-Soulier syndrome (BSS) is an extremely rare hereditary bleeding disorder, caused by mutations occurring in the Glycoprotein (GP) Ibα, GPIbβ and GP9 genes that encode for the corresponding subunits of platelet GPIb-V-IX adhesion receptor complex. BSS has been reported in many populations, mostly behaving in an autosomal-recessive manner. While the great majority of BSS mutations are unique to a single in idual or family, the GP9 1828A G Asn45Ser mutation, which we have identified in an undocumented Australian Caucasian, has already been reported in multiple unrelated Caucasian families from various Northern and Central European countries. Haplotype analysis of 19 BSS patients from 15 unrelated Northern European families (including 2 compound heterozygote siblings from a British family previously published, and 17 1828A G Asn45Ser homozygotes), showed that 14 of these BSS patients from 11 of the 1828A G Asn45Ser homozygote families share a common haplotype at the chromosomal region 3’ to the GP9 gene. Hence, the results suggest that the GP9 1828A GAsn45Ser mutation in these families is ancient, and its frequent emergence in the European population is the result of a founder effect rather than recurrent mutational events. Association of the 1828A G Asn45Ser mutation with variant haplotypes in 4 other Northern European BSS families raised the possibility of a second founder event, or rare recombinations in these families. Additional members from these ‘atypical’ lineages would need to be screened to resolve this question.
Location: United States of America
No related grants have been discovered for Edward Tuddenham.