Sharma Sanjay, Karakousis Constantine P, Takita Hiroshi, Shin Kyu, Brooks Stephen P
Department of Surgery, SUNY Buffalo and Kaleida Health, Buffalo General Hospital, Buffalo, NY 14203, USA.
Neoplasia. 2004 Sep-Oct;6(5):523-8. doi: 10.1593/neo.04166.
Direct tumor injections of (CpG ODN) into murine colon tumor 26 (CT-26) tumors can induce a potent antitumor response. Tumor size at the beginning of treatment determines the final therapeutic outcome, with smaller tumors responding favorably to CpG ODN therapy whereas large tumors do not. CpG ODN injections in small tumors resulted in tumor necrosis and extensive inflammatory cell infiltration, with average survival that is significantly higher (48.1 +/- 34 days) when compared to control ODN-treated mice (16.1 +/- 3.5 days). Cytokines and chemokines are expressed at different levels in small and large CT-26 tumors following intratumoral injections of CpG ODN. We observed that granulocyte-macrophage colony-stimulating factor and interleukin (IL) 6 are the major cytokines that were overexpressed in CpG ODN-treated small tumors but not in large tumors. Similarly, several chemokines (CXCL1, CCL2, and CCL3) were also significantly higher in CpG ODN-treated small tumors compared to control ODN-treated tumors.
将(CpG寡脱氧核苷酸)直接注射到小鼠结肠肿瘤26(CT - 26)肿瘤中可诱导强大的抗肿瘤反应。治疗开始时的肿瘤大小决定最终治疗结果,较小的肿瘤对CpG寡脱氧核苷酸治疗反应良好,而大肿瘤则不然。在小肿瘤中注射CpG寡脱氧核苷酸导致肿瘤坏死和广泛的炎性细胞浸润,与对照寡脱氧核苷酸处理的小鼠(16.1±3.5天)相比,平均生存期显著更长(48.1±34天)。在肿瘤内注射CpG寡脱氧核苷酸后,细胞因子和趋化因子在大小不同的CT - 26肿瘤中表达水平不同。我们观察到,粒细胞巨噬细胞集落刺激因子和白细胞介素(IL)6是在CpG寡脱氧核苷酸处理的小肿瘤中过度表达但在大肿瘤中未过度表达的主要细胞因子。同样,与对照寡脱氧核苷酸处理的肿瘤相比,几种趋化因子(CXCL1、CCL2和CCL3)在CpG寡脱氧核苷酸处理的小肿瘤中也显著更高。