RESUMO
In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma.
Assuntos
Alendronato , Neoplasias Ósseas/tratamento farmacológico , Cisplatino , Dextranos , Portadores de Fármacos , Ácido Láctico , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Ácido Poliglicólico , Alendronato/química , Alendronato/farmacocinética , Alendronato/farmacologia , Animais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Cisplatino/química , Cisplatino/farmacocinética , Cisplatino/farmacologia , Dextranos/química , Dextranos/farmacocinética , Dextranos/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To evaluate the proximal tibiofibular joint resection on the limb salvage for osteosarcoma of the proximal tibia. METHODS: Between August 1995 and January 2004, 11 patients with osteosarcoma of proximal tibia and tibiofibular joint involved underwent resection and endoprosthetic proximal tibial replacement. Seven patients were male and 4 were female. The patients ranged in age from 14 to 23 years (mean 18 years). The surgical stage were IIB. RESULTS: The follow-up period varied from 2 to 9 years (mean 59 months). Three patients died of pulmonary metastases, 1 patient was still alive with pulmonary metastasis, 1 patient underwent amputation for local recurrence. There was 1 early skin necrosis, 2 transient palsy of the common peroneal nerve, and 2 thrombus of lower limb vein. The mean postoperative Musculoskeletal Tumor Society score of the knee joint was 70% (range 55% - 86%), the mean postoperative range of motion was 85 degrees (range 0 degrees - 120 degrees ), and the extensor lag varied from 0 degrees to 20 degrees . CONCLUSIONS: Limb salvage for osteosarcoma of the proximal tibia with proximal tibiofibular joint resection and custom-made prosthesis reconstruction has had excellent results, however, the prevention and treatment of relevant complications should be given more attention.
