The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study.
Prostate
; 71(13): 1455-65, 2011 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-21321981
ABSTRACT
BACKGROUND:
Interleukin-6 (IL-6) is associated with prostate cancer morbidity. In several experimental models, IL-6 has been reported to have anti-apoptotic and pro-angiogenic effects. Siltuximab (CNTO 328) is a monoclonal anti-IL-6 antibody which has been successfully applied in several models representing prostate cancer. This study was designed to assess preliminary safety of siltuximab in patients with early prostate cancer. PATIENTS ANDMETHODS:
Twenty patients scheduled to undergo radical prostatectomy received either no drug or siltuximab (6 mg/kg, five patients per group with administration once, two times, and three times prior to surgery). Blood samples were collected for pharmacokinetic and pharmacodynamic analyses. Expression of elements of IL-6 signaling pathways was analyzed in tumor tissue by immunohistochemistry. Gene analysis in tumor specimens was performed with the DASL array.RESULTS:
No adverse events related to siltuximab were observed. Patients treated with siltuximab presented with higher levels of proliferation and apoptosis markers. Following a single dose, serum concentrations of siltuximab declined in a biexponential manner. This study revealed a decrease in phosphorylation of Stat3 and p44/p42 mitogen-activated protein kinases. In addition, gene expression analyses indicate down-regulation of genes immediately downstream of the IL-6 signaling pathway and key enzymes of the androgen signaling pathway.CONCLUSIONS:
Preliminary safety of siltuximab is favorable. Future studies in which siltuximab could be combined with androgen-deprivation therapy and experimental therapies in advanced prostate cancer are justified.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Regulação Neoplásica da Expressão Gênica
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Transformação Celular Neoplásica
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Interleucina-6
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Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article