RESUMEN
BACKGROUND: Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the patients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients with metastatic colorectal cancer is approximately 22-24 months. Some immunotherapeutic approaches had been attempted in colon cancer patients to significantly increase overall survival. A vaccine based approach has shown a novel direction for colon cancer prevention and therapy. METHODS: In this study, the experiments were designed including prevention and therapeutic stages in order to attain effect against tumor recurrence in clinical settings. The anti-tumor efficacy of a novel cytokine adjuvant vaccine that contained cytokines GM-CSF and IL-2 and inactivated colon CT26.WT whole cell antigen was evaluated in BALB/c mouse tumor models by measuring tumor growth post vaccination and the survival time of tumor-bearing mice, analyzing the expression and distribution of CD4, CD8, CD11c, CD80, CD86 and CD83 positive cells in control and treated mice by flow cytometry and immunochemistry. The tumor-specific cytotoxic T cells (CTL) were analyzed by tumor proliferation and the lactic dehydrogenates (LDH) release assays. IFN-γ, IL-2 and GM-CSF secretion in serum was assayed by ELISA. RESULTS: Our results suggested that cytokine adjuvant vaccine significantly inhibited tumor growth and extended the survival period at least 160d. It was found that the levels of CD8 + T and the tumor-specific cytotoxicity were significantly higher in prevention and treatment group vaccinated by cytokine adjuvant vaccine. CD8 + T cells play a key role in anti-tumor response. CONCLUSIONS: The novel GM-CSF and IL-2 based adjuvant vaccine effectively activated autologous T-cell response and represented a promising immunotherapeutic approach for patients with colon cancer.
RESUMEN
Interleukin-6 (IL-6), a central proinflammatory cytokine, may be involved in both development and progression of many human malignancies. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms with susceptibility and overall survival of osteosarcoma in a Chinese population. A total of 412 subjects, including 206 patients with osteosarcoma and 206 healthy controls, were recruited and were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in this study. Significant differences of genotype distribution were observed between osteosarcoma cases and controls at the IL-6 -174 G/C genotypes. Compared with the homozygote GG, the heterozygous GC genotype was associated with significantly increased risk for osteosarcoma (odds ratio [OR] = 1.58, 95 % confidence interval [CI] = 1.13-3.05, p = 0.028); the CC genotype was associated with increased risk for osteosarcoma (OR = 1.57, 95 % CI = 1.21-3.26, p = 0.022). Moreover, the genotype CC of IL-6 -174 G/C carried a higher risk of osteosarcoma metastasis and later Enneking stages, compared with the GG genotype. The IL-6 -174 G/C genotype was associated with risk for development and metastasis of osteosarcoma in Chinese Han population.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Óseas/mortalidad , Interleucina-6/genética , Osteosarcoma/mortalidad , Polimorfismo de Nucleótido Simple/genética , Adulto , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Metástasis de la Neoplasia , Estadificación de Neoplasias , Osteosarcoma/genética , Osteosarcoma/secundario , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Accumulating studies suggest that multidrug resistance is related to expression of p53, P-glycoprotein (Pgp) and Glutathione S-Transferase-pi (GST-pi). This study was to estimate mutant p53 expression and its correlation with drug resistance related proteins Pgp and GST-pi expression in colorectal adenocarcinoma patients. MATERIAL AND METHODS: Immunohistochemical ABC technique was used to detect the expression of mutant p53 protein, Pgp and GST-pi in 404 cases with colorectal adenocarcinoma. RESULTS: A low frequency of mutant p53 accumulation was observed, consistent with findings in colorectal cancers (CRCs) from other Asian populations. Accumulation of mutant p53 was related to AJCC staging (p < 0.05). Pgp expression was significantly correlated with tumor location (p = 0.039) and gender (p = 0.043). The positive percentage of Pgp and GST-pi expression was all significantly higher in mutant p53 protein positive group than mutant p53 protein negative cases (r = 0.634, p < 0.001 and r = 0.680, p < 0.001, respectively). CONCLUSIONS: These findings demonstrate association of three biomarkers with clinicopathologic parameters of colorectal carcinoma, and overexpression of Pgp and GST-pi was closely correlated with mutant p53.