RESUMO
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.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Basocelular/tratamento farmacológico , DNA Catalítico/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , DNA Catalítico/efeitos adversos , DNA Catalítico/farmacocinética , Feminino , Humanos , Injeções Intralesionais , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
Tentamos aqui estabelecer um parâmetro objetivo para diferenciar crescimento piloso normal de hirsutismo em mulheres jovens brancas brasileiras e, baseado neste trabalho, passamos a definir como hirsutas as mulheres que apresentaram ++ ou mais cruzes de pêlos em três ou mais das regiöes analisadas. Discutimos também dados interessantes de uso em prática ambulatorial diária
