RESUMO
BACKGROUND: To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein. METHODS: We established a novel fusion gene, immunocasp-3, composed of NH2-terminal leader sequence fused with an anti-prostate-specific membrane antigen (PSMA) antibody (J591), the furin cleavage sequences of diphtheria toxin (Fdt), and the reverse coding sequences of the large and small subunits of caspase-3 (revcaspase-3). The expressing level of the immunocasp-3 gene was evaluated by using the reverse transcription-PCR (RT-PCR) and western blot analysis. Cell viability assay and cytotoxicity assay were used to evaluate its anti-tumor effects in vitro. Apoptosis was confirmed by electron microscopy and Annexin V-FITC staining. The antitumor effects of immunocasp-3 were assessed in nude mice xenograft models containing PSMA-overexpressing LNCaP cells. RESULTS: This study shows that the immunocasp-3 proteins selectively recognized and induced apoptotic death in PSMA-overexpressing LNCaP cells in vitro, where apoptotic cells were present in 15.3% of the cells transfected with the immunocasp-3 expression vector at 48 h after the transfection, in contrast to 5.5% in the control cells. Moreover, LNCaP cells were significantly killed under the condition of the co-culture of the immunocasp-3-secreting Jurkat cells and more than 50% of the LNCaP cells died when the two cell lines were co-cultured within 5 days. In addition, The expression of immunocasp-3 also significantly suppressed tumor growth and greatly prolonged the animal survival rate in vivo. CONCLUSION: A novel fusion gene, immunocasp-3, may represent a viable approach to treating PSMA-positive prostate cancer.
Assuntos
Adenocarcinoma/terapia , Antígenos de Superfície , Terapia Genética , Glutamato Carboxipeptidase II , Neoplasias da Próstata/terapia , Adenocarcinoma/patologia , Animais , Antígenos de Superfície/genética , Fusão Gênica Artificial , Caspase 3/genética , Terapia Genética/métodos , Glutamato Carboxipeptidase II/genética , Humanos , Imunotoxinas/genética , Masculino , Camundongos Nus , Neoplasias da Próstata/patologia , Células Tumorais CultivadasRESUMO
OBJECTIVE: To assess the feasibility and safety of robot-assisted laparoscopic radical prostatectomy (RLRP) in the treatment of prostate cancer. METHODS: Using the da Vinci robot surgical system, we performed RLRP for 34 patients with localized prostate cancer and analyzed the intraoperative and follow-up data. RESULTS: The procedures were performed successfully in all the patients, with the mean operation time of 198 min (range 135-340 min), average blood loss of 257 ml (range 50-700 ml), and 1 case of blood transfusion, but no postoperative complications. Three cases had positive surgical margins. Postoperative examination at 4 weeks showed PSA > 0.2 microg/L in 2 cases, suggestive of residual tumor, for which maximal androgen block therapy was administered. The other 32 patients were followed up for 3-10 (mean 7.5) months, during which the average level of serum tPSA remained < 0.2 microg/L. Urinary continence was found in 94% (32/34) and 97% (33/34) of the patients at 3 and 6 months, respectively, of whom 77% (26/34) and 88% (30/34) had no urinary leakage (0 pad per day). CONCLUSION: RLRP, with its advantages of less perioperative blood loss, low rate of positive margin, and good urinary continence, is a safe and effective surgical option for the treatment of prostate cancer.
