RESUMO
Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Preparações de Ação Retardada/farmacologia , Doxorrubicina/farmacologia , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Compostos Férricos/química , Campos Magnéticos , Camundongos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Nanopartículas/química , Nanopartículas/ultraestrutura , Propriedades de Superfície , Carga Tumoral/efeitos dos fármacosRESUMO
PURPOSE: Adjuvant chemotherapy use in stage II colorectal cancer (CRC) is debated. We evaluated the prognostic significance of clinicopathological features recommended by most guidelines for identifying high-risk stage II CRC and adjuvant chemotherapeutic response. METHODS: We enrolled 1,039 stage II CRC patients who underwent curative surgery at Taipei Veterans General Hospital from January 2005 to December 2010. Seventy-seven patients who received radiotherapy were excluded. The endpoint was disease-free survival. RESULTS: Of 962 patients, 37 had stage T4 tumors; 50, lymphovascular invasion; 39, poor differentiation; 249, preoperative carcinoembryonic antigen (CEA) levels >5 ng/mL; and 53 underwent emergent operations. One hundred ninety-four patients received 5-fluorouracil-based adjuvant chemotherapy. During a median follow-up period of 60.2 months, recurrence developed in 110 patients (11.4 %). The 5-year disease-free survival (DFS) was 87.6 %. In multivariate analysis, preoperative CEA >5 ng/ml (p = 0.001), emergent operation for obstruction/perforation (p = 0.008), lymphovascular invasion (p = 0.014), and T4 disease (p = 0.030) were significantly associated with poor DFS. High-risk stage II patients (n = 484) benefited from adjuvant chemotherapy (5-year DFS with and without adjuvant chemotherapy, 87.3 vs. 78.9 %; p = 0.028). CONCLUSIONS: Adjuvant chemotherapy improved DFS in high-risk stage II CRC patients, but not in low-risk patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. This study aimed to investigate the role of CEA reduction ratio after preoperative chemoradiotherapy (CRT). METHODS: We enrolled 284 patients who underwent preoperative CRT followed by radical surgical resection. Patients were divided into 3 groups: serum CEA levels before CRT (pre-CRT CEA) less than 5 ng/mL (group 1); pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio of 50% or more (group 2); and pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio less than 50% (group 3). RESULTS: The 5-year disease-free survival (DFS) rate was not different between groups 1 (71.8%) and 2 (69.4%) but was signiï¬cantly lower in group 3 (49.5%). CEA group, lymph node status after CRT (ypN) stage, and histologic type were independent prognostic factors for DFS on multivariate analysis. CONCLUSIONS: CEA reduction ratio might be an independent prognostic factor for DFS in rectal cancer patients treated with preoperative CRT and radical surgery.
Assuntos
Adenocarcinoma/terapia , Antígeno Carcinoembrionário/sangue , Quimiorradioterapia Adjuvante , Neoplasias Retais/terapia , Adenocarcinoma/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Neoplasias Retais/sangue , Reto/cirurgia , Estudos Retrospectivos , Tegafur/administração & dosagem , Resultado do Tratamento , Uracila/administração & dosagemRESUMO
BACKGROUND: To investigate the impact of concurrent chemoradiotherapy (CCRT) on stage IV rectum cancer. METHODS: Between 2000 and 2011, 297 consecutive patients diagnosed with stage IV rectum cancer (synchronous metastasis) were enrolled. Cox proportional hazard analyses were used for prognostic factors determination, and the Kaplan-Meier method was used for survival analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matched patients for validation studies. RESULTS: In total, 63 patients received CCRT and 234 did not. The patients in the CCRT group were younger, had more low-lying lesions, and had more T4 lesions, lung metastases, metastasectomies, and oxaliplatin-based upfront chemotherapy. Before propensity-score matching, a younger age (HR = 0.662, P = 0.016), lower carcinoembryonic antigen (CEA) level (≤20 ng/ml) (HR = 0.531, P = 0.001), no metastasectomy (HR = 3.214, P < 0.001), and no CCRT (HR = 1.844, P = 0.019) were independent prognostic factors after controlling for other confounding factors. After matching, only CEA and metastasectomy, but not CCRT, were independent prognostic factors. The survival benefit of CCRT was restricted to patients who undergo subsequent metastasectomy. CONCLUSIONS: Upfront CCRT only provided a survival benefit in patients with stage IV rectum cancer who undergo subsequent metastasectomy.