Summary Background The nuclear transcription factor c-Jun is preferentially expressed in basal-cell carcinoma. Dz13 is a deoxyribozyme that targets JUN messenger RNA and has inhibited the growth of a ...range of tumours in mice. We did a phase 1 study to assess safety and tolerability in human beings. Methods Adults with nodular basal-cell carcinoma were recruited from Royal Prince Alfred Hospital, Sydney, Australia, between September, 2010, and October, 2011. Patients were assigned to receive one intratumoral injected dose of 10, 30, or 100 μg Dz13, in a 50 μL volume of lipid carrier, and were assessed for adverse effects in the first 24 h then at 7, 14, and 28 days after injection. Treated tumours were surgically excised 14 days after injection and compared with the baseline biopsy samples for expression of c-Jun and tumorigenesis markers. Findings Nine patients were recruited, of whom three received each dose of Dz13. All patients completed the study with no drug-related serious adverse events. No systemic Dz13 exposure was detected. c-Jun expression was reduced in the excised tumours of all nine (100%) patients, compared with baseline, and histological tumour depth had decreased in five (56%) of nine. Proportions of cells positive for caspases 3, 8, and 9 and P53 were increased, but those of cells positive for Bcl-2 and MMP-9 were decreased. Infiltration by inflammatory and immune cells was stimulated. Interpretation Dz13 was safe and well tolerated after single intratumoral injections at all doses. Funding Cancer Institute NSW, Cancer Council Australia, and National Health and Medical Research Council.
Patients given implantable cardioverter defibrillators (ICDs) after arrhythmic events or sudden cardiac arrest (SCA) experience psychosocial distress. ICDs now are inserted for the primary prevention ...of SCA in patients with heart failure; the psychosocial impact of ICDs on patients with heart failure is unknown. Changes in psychosocial status in these ICD recipients were examined. ICD recipients (n = 57) completed depression, anxiety, and social support inventories every 6 months for up to 2 years. Initially, 35% of recipients were depressed and 45% of recipients were anxious. In linear mixed models, depression decreased over time overall but increased in those who experienced ICD shocks. Anxiety decreased in New York Heart Association class III ICD recipients but not in class II ICD recipients. Decreases in social support were related to age: the younger the patient the greater the decrease. A significant proportion of ICD recipients were depressed or anxious, or had diminished social support even after 2 years. Investigation of strategies to improve ICD recipients' psychosocial status is warranted.
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