한빛사논문
- 조회2,534
Abstract
Eun-Ae Cho MBBSa †, Fergal J Moloney MD a b †, Hong Cai MD c, Annie Au-Yeung BSc c, Carlos China MD d, Prof Richard A Scolyer MD e f, Benafsha Yosufi BSc f, Mark J Raftery PhD g, Jason Z Deng PhD h, Stephen W Morton PhD h, Prof Paula T Hammond PhD h, Hendrik-Tobias Arkenau MD i, Prof Diona L Damian MBBS a f, Douglas J Francis PhD j, Prof Colin N Chesterman MBBS c, Prof Ross St C Barnetson MD a, Prof Gary M Halliday DSc a † *, Prof Levon M Khachigian DSc c † *
a Dermatology, Sydney Medical School, Bosch Institute, Royal Prince Alfred Hospital at University of Sydney, Sydney, NSW, Australia
b Department of Dermatology, Mater Misericordiae University Hospital, Dublin, Ireland
c Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia
d Woolcock Institute of Medical Research, Sydney, NSW, Australia
e Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
f Melanoma Institute Australia, Sydney, NSW, Australia
g Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, Australia
h Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge MA, USA
i Sarah Cannon Research UK, London, UK
j DF Preclinical Services Pty Ltd, Canberra, ACT, Australia
*Correspondence to: Prof Levon M Khachigian, Centre for Vascular Research, University of New South Wales, Sydney, Gate 9 C25, High Street, Randwick, NSW 2052, Australia
Prof Gary M Halliday, Dermatology, Blackburn Building D06, University of Sydney, Sydney, NSW 2006, Australia
† E-AC, FJM, GMH, and LMK contributed equally to the writing of the paper
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.
논문정보
- Research article
- 2013년 05월 (BRIC 등록일 2013-05-20)
- 국외 연구진
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