6 research outputs found

    A Dedicated breast positron emission tomography scanner : proof of concept

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    Purpose: This study developed and tested a novel scanner constructed for dedicated positron emission tomography (PET) of the breast. The breast PET (B-PET) scanner is designed with two opposing detectors using curve plate NaI(Tl) detectors to achieve a combination of high spatial resolution and energy resolution. Methods: Phantom and clinical studies (n = 20) with ¹⁸F-fluorodeoxyglucose were carried out on the whole-body Philips Allegro scanner and the B-PET scanner. Images were subjectively assessed by an expert panel. Results: Phantom studies indicated improved contrast for B-PET over conventional PET. Of the 20 clinical studies with breast cancer demonstrated on whole-body fluorodeoxyglucose PET, 10 B-PET scans showed agreement. Of the remaining 10 studies, three had breasts that were too small to be imaged, four had lesions that were too deep to be captured in the field of view, and three were excluded due to technical errors. Conclusions: Compared with conventional PET, B-PET images provided greater detail in breast lesions suggesting that the low-cost and relatively simple design of B-PET may potentially be an important adjunct to traditional mammography in helping determine the nature of a lesion.5 page(s

    Pharmacological EZH2 inhibition combined with retinoic acid treatment promotes differentiation and apoptosis in rhabdomyosarcoma cells

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    BACKGROUND: rhabdomyosarcomas (RMS) are predominantly paediatric sarcomas thought to originate from muscle precursor cells due to impaired myogenic differentiation. Despite intensive treatment, 5-year survival for patients with advanced disease remains low (&lt; 30%), highlighting a need for novel therapies to improve outcomes. Differentiation therapeutics are agents that induce differentiation of cancer cells from malignant to benign. The histone methyltransferase, Enhancer of Zeste Homolog 2 (EZH2) suppresses normal skeletal muscle differentiation and is highly expressed in RMS tumours.RESULTS: we demonstrate combining inhibition of the epigenetic modulator EZH2 with the differentiating agent retinoic acid (RA) is more effective at reducing cell proliferation in RMS cell lines than single agents alone. In PAX3-FOXO1 positive RMS cells this is due to an RA-driven induction of the interferon pathway resulting in apoptosis. In fusion negative RMS, combination therapy led to an EZH2i-driven upregulation of myogenic signalling resulting in differentiation. In both subtypes, EZH2 is significantly associated with enrichment of trimethylated lysine 27 on histone 3 (H3K27me3) in genes that are downregulated in untreated RMS cells and upregulated with EZH2 inhibitor treatment. These results provide insight into the mechanism that drives the anti-cancer effect of the EZH2/RA single agent and combination treatment and indicate that the reduction of EZH2 activity combined with the induction of RA signalling represents a potential novel therapeutic strategy to treat both subtypes of RMS.CONCLUSIONS: the results of this study demonstrate the potential utility of combining EZH2 inhibitors with differentiation agents for the treatment of paediatric rhabdomyosarcomas. As EZH2 inhibitors are currently undergoing clinical trials for adult and paediatric solid tumours and retinoic acid differentiation agents are already in clinical use this presents a readily translatable potential therapeutic strategy. Moreover, as inhibition of EZH2 in the poor prognosis FPRMS subtype results in an inflammatory response, it is conceivable that this strategy may also synergise with immunotherapies for a more effective treatment in these patients.</p
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