Self-amplifying RNA (saRNA) is an extremely promising platform because it can produce more protein for less RNA. We used a sort and sequence approach to identify host cell factors associated with transgene expression from saRNA; the hypothesis was that cells with different expression levels would have different transcriptomes. We tested this in CDK4/hTERT immortalized human muscle cells transfected with Venezuelan equine encephalitis virus (VEEV)-derived saRNA encoding GFP.
View Article and Find Full Text PDFAnthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models, and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were (1) to evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; (2) to assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma.
View Article and Find Full Text PDFBackground: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity.
View Article and Find Full Text PDFThis good practice paper (GPP) is intended to support clinicians in assessing patient fitness for bleomycin and in management of bleomycin pulmonary toxicity (BPT) where it occurs. Bleomycin, originally developed as an antibiotic in the 1960s, has been a cornerstone of therapy for classical Hodgkin lymphoma (CHL) since results of its use in combination with doxorubicin, vincristine and dacarbazine (ABVD) were first published by Bonadonna et al in 1975 1. The same author recognised high rates of respiratory morbidity in these patients 2, and bleomycin-;related pulmonary toxicity (BPT) is now a well-;recognised and feared complication with its use.
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