Publications by authors named "B R Blyth"
Understanding the molecular pathogenesis of MLL fusion oncoprotein (MLL-FP) leukaemia has spawned epigenetic therapies that have improved clinical outcomes in this often-incurable disease. Using genetic and pharmacological approaches, we define the individual and combined contribution of KAT6A, KAT6B and KAT7, in MLL-FP leukaemia. Whilst inhibition of KAT6A/B is efficacious in some pre-clinical models, simultaneous targeting of KAT7, with the novel inhibitor PF-9363, increases the therapeutic efficacy.
View Article and Find Full Text PDF[Lu]Lu-PSMA is an effective class of therapy for patients with metastatic castration-resistant prostate cancer (mCRPC); however, progression is inevitable. The limited durability of response may be partially explained by the presence of micrometastatic deposits, which are energy-sheltered and receive low absorbed radiation with Lu due to the approximately 0.7-mm mean pathlength.
View Article and Find Full Text PDFPeptides are ideal for theranostic development as they afford rapid target accumulation, fast clearance from background tissue, and exhibit good tissue penetration. Previously, we developed a novel series of peptides that presented discreet folding propensity leading to an optimal candidate [Ga]Ga-DOTA- ([D-Glu]-Ala-Tyr-MeGly-Trp-MeNle-Asp-Nal-NH) with 50 pM binding affinity against cholecystokinin-2 receptors (CCKR). However, we were confronted with challenges of unfavorably high renal uptake.
View Article and Find Full Text PDFArticle Synopsis
- Immune checkpoint inhibitor therapy (ICI) can worsen autoimmune diseases, but a new lipidic peptide, IK14004, shows promise in promoting immunosuppressive T regulatory cells while activating CD8+ T cells.
- IK14004 effectively inhibits Lewis lung cancer growth and revitalizes exhausted CD4+ T cells, along with modulating immune responses in human cells.
- This peptide could help balance the benefits of ICI immunotherapy by minimizing autoimmune reactions without allowing tumors to escape immune detection.
Background: The kinetics of circulating tumor DNA (ctDNA) release following commencement of radiotherapy or chemoradiotherapy may reflect early tumour cell killing. We hypothesised that an increase in ctDNA may be observed after the first fraction of radiotherapy and that this could have clinical significance.
Materials And Methods: ctDNA analysis was performed as part of a prospective, observational clinical biomarker study of non-small cell lung cancer (NSCLC) patients, treated with curative-intent radiotherapy or chemoradiotherapy.