■骨肉瘤是最常见的原发性恶性骨肿瘤。尽管化疗最近取得了进展,但播散性疾病患者的预后仍然很差。此外,目前的治疗方案具有严重副作用的显著风险.因此,对于具有改善的安全性的有效疗法存在未满足的临床需求.牛磺罗定是一种抗菌剂,已显示可在不同类型的癌细胞系中诱导细胞死亡。
■在这项研究中,我们研究了牛磺罗定在骨肉瘤动物模型中的抗肿瘤和抗血管生成作用。注射K7M2鼠骨肉瘤细胞,肌内和腹膜内,在第0天进入60只BALB/c小鼠。然后将动物随机接受2%牛磺罗定(800mg/kg)治疗,牛磺罗定1%(400毫克/千克),或通过静脉内或腹膜内给药的NaCl0.9%对照7天。
■35天后,小鼠被安乐死,并收集肿瘤进行分析。18只小鼠由于并发症被排除在分析之外。从第9天至第21天,2%牛磺罗定腹膜内治疗组中的体重显著降低,与该组中的死亡率升高一致。与对照组相比,1%(p=0.003)和2%(p=0.006)腹膜内牛磺罗定治疗组中的腹膜内肿瘤重量显著更低。对肌内肿瘤或静脉内施用牛磺罗定没有观察到抗肿瘤作用。治疗组之间的微血管密度或有丝分裂率没有显着差异。2%牛磺罗定腹膜内组的体重减轻和死亡率升高表明,较低的1%剂量是优选的。
■总而言之,没有抗血管生成活性的证据,牛磺罗定对骨肉瘤的抗肿瘤作用是有限的。此外,其毒性特征给予进一步评估。鉴于这些观察,需要进一步研究完善牛磺罗定在骨肉瘤治疗中的应用。
UNASSIGNED: Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy. Moreover, current treatment regimens bear a significant risk of serious side effects. Thus, there is an unmet clinical need for effective therapies with improved safety profiles. Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.
UNASSIGNED: In this study, we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma. K7M2 murine osteosarcoma cells were injected, both intramuscular and intraperitoneal, into 60 BALB/c mice on day zero. Animals were then randomized to receive treatment with taurolidine 2% (800 mg/kg), taurolidine 1% (400 mg/kg), or NaCl 0.9% control for seven days by intravenous or intraperitoneal administration.
UNASSIGNED: After 35 days, mice were euthanized, and the tumors were harvested for analysis. Eighteen mice were excluded from the analysis due to complications. Body weight was significantly lower in the 2% taurolidine intraperitoneal treatment group from day 9 to 21, consistent with elevated mortality in this group. Intraperitoneal tumor weight was significantly lower in the 1% (p = 0.003) and 2% (p = 0.006) intraperitoneal taurolidine treatment groups compared to the control. No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine. There were no significant differences in microvessel density or mitotic rate between treatment groups. Reduced body weight and elevated mortality in the 2% taurolidine intraperitoneal group suggest that the lower 1% dose is preferable.
UNASSIGNED: In conclusion, there is no evidence of antiangiogenic activity, and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited. Moreover, its toxic profile grants further evaluation. Given these observations, further research is necessary to refine the use of taurolidine in osteosarcoma treatment.