RESUMO
The hydrolysis of endocannabinoids has profound effects on the function of the endocannabinoid signaling system in the regulation of prostate carcinoma cells. Prostate carcinoma cells exhibit a wide range of hydrolysis activity for 2-arachidonoylglycerol (2-AG), the major endocannabinoid. However, enzyme(s) responsible for 2-AG hydrolysis and their functions in prostate cancer have not been characterized. In this study, we demonstrated that fatty acid amide hydrolase (FAAH) was differentially expressed in normal and prostate carcinoma cells. In PC-3 cells, overexpression of FAAH resulted in increased FAAH protein, 2-AG hydrolysis, cell invasion and cell migration. Conversely, small-interfering RNA (siRNA) knockdown of FAAH in LNCaP cells decreased FAAH protein, 2-AG hydrolysis and cell invasion. Furthermore, CAY10401, a FAAH inhibitor, decreased cell invasion and it enhanced the reduction of invasion in FAAH siRNA-transfected LNCaP cells. Immunohistochemistry staining of commercial tissue microarrays (TMAs) demonstrated FAAH staining in 109 of 157 cores of prostate adenocarcinomas but weak staining in 1 of 8 cores of normal prostate tissues. These results suggest that FAAH regulates 2-AG hydrolysis and invasion of prostate carcinoma cells and is potentially involved in prostate tumorigenesis.
Assuntos
Adenocarcinoma/enzimologia , Amidoidrolases/biossíntese , Neoplasias da Próstata/enzimologia , Amidoidrolases/efeitos dos fármacos , Ácidos Araquidônicos/metabolismo , Western Blotting , Movimento Celular/fisiologia , Cromatografia Líquida , Endocanabinoides , Inibidores Enzimáticos/farmacologia , Expressão Gênica , Glicerídeos/metabolismo , Humanos , Imuno-Histoquímica , Masculino , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrometria de Massas por Ionização por Electrospray , Análise Serial de Tecidos , TransfecçãoRESUMO
INTRODUCTION: Locally advanced tumors in the olfactory area commonly have central nervous system (CNS) involvement and are often incurable. CASE REPORT: We report the treatment of a 25-year-old male patient who presented with a large, neuroendocrine tumor arising from the ethmoid complex. This locally invasive lesion extended beyond the orbits and into the anterior cranial fossa with associated intracranial involvement. An endoscopic nasal biopsy demonstrated a poorly differentiated neuroendocrine tumor. The patient was treated with 4 cycles of combination induction chemotherapy with irinotecan and cisplatin followed by radiation therapy with concurrent weekly cisplatin. He had a complete response to this therapy confirmed with biopsies that demonstrated no residual disease at 8 weeks after chemoradiotherapy. He remained disease free one and a half years following surgery. CONCLUSION: To our knowledge, this combination treatment approach has not been reported in the literature.