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Safety and tolerability of an intratumorally injected DNAzyme, Dz13, in patients with nodular basal-cell carcinoma: a phase 1 first-in-human trial (DISCOVER).

ABSTRACT: 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.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 ?g Dz13, in a 50 ?L 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.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.Dz13 was safe and well tolerated after single intratumoral injections at all doses.Cancer Institute NSW, Cancer Council Australia, and National Health and Medical Research Council.

SUBMITTER: Cho EA

PROVIDER: S-EPMC3951714 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Safety and tolerability of an intratumorally injected DNAzyme, Dz13, in patients with nodular basal-cell carcinoma: a phase 1 first-in-human trial (DISCOVER).

Cho Eun-Ae EA Moloney Fergal J FJ Cai Hong H Au-Yeung Annie A China Carlos C Scolyer Richard A RA Yosufi Benafsha B Raftery Mark J MJ Deng Jason Z JZ Morton Stephen W SW Hammond Paula T PT Arkenau Hendrik-Tobias HT Damian Diona L DL Francis Douglas J DJ Chesterman Colin N CN Barnetson Ross St C RS Halliday Gary M GM Khachigian Levon M LM

Lancet (London, England) 20130507 9880

<h4>Background</h4>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.<h4>Methods</h4>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 recei ...[more]

PMID: 23660123

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Dataset Information

Safety and tolerability of an intratumorally injected DNAzyme, Dz13, in patients with nodular basal-cell carcinoma: a phase 1 first-in-human trial (DISCOVER).

Publications

Safety and tolerability of an intratumorally injected DNAzyme, Dz13, in patients with nodular basal-cell carcinoma: a phase 1 first-in-human trial (DISCOVER).

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