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探讨牛磺罗定对骨肉瘤小鼠模型肿瘤重量和微血管密度的影响。

Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma.

机构信息

Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, Stanford University, Stanford, 94305, USA.

Department of Surgery, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.

出版信息

Oncol Res. 2024 Jun 20;32(7):1163-1172. doi: 10.32604/or.2024.050907. eCollection 2024.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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% ( = 0.003) and 2% ( = 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.

CONCLUSIONS

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.

摘要

背景

骨肉瘤是最常见的原发性恶性骨肿瘤。尽管化疗方面取得了最近的进展,但患有弥散性疾病的患者的预后仍然非常差。此外,目前的治疗方案存在严重副作用的重大风险。因此,对于具有改善安全性特征的有效疗法存在未满足的临床需求。牛磺脱氧胆酸是一种已被证明可诱导不同类型癌细胞系细胞死亡的抗菌剂。

方法

在这项研究中,我们在骨肉瘤动物模型中检查了牛磺脱氧胆酸的抗肿瘤和抗血管生成作用。在第 0 天,将 K7M2 鼠骨肉瘤细胞肌肉内和腹腔内注射到 60 只 BALB/c 小鼠中。然后,动物被随机分为静脉或腹腔内给予 2%牛磺脱氧胆酸(800mg/kg)、1%牛磺脱氧胆酸(400mg/kg)或 0.9%生理盐水对照组,共 7 天。

结果

35 天后,处死小鼠并采集肿瘤进行分析。由于并发症,18 只小鼠被排除在分析之外。从第 9 天到第 21 天,2%牛磺脱氧胆酸腹腔内治疗组的体重明显较低,这与该组死亡率升高一致。与对照组相比,1%(=0.003)和 2%(=0.006)牛磺脱氧胆酸腹腔内治疗组的腹腔内肿瘤重量明显降低。未观察到肌肉内肿瘤或牛磺脱氧胆酸静脉给药的抗肿瘤作用。各组之间微血管密度或有丝分裂率无显著差异。2%牛磺脱氧胆酸腹腔内组体重减轻和死亡率升高表明,较低的 1%剂量更为理想。

结论

总之,本研究未发现牛磺脱氧胆酸具有抗血管生成活性,并且观察到的对骨肉瘤的抗肿瘤作用有限。此外,其毒性特征需要进一步评估。鉴于这些观察结果,需要进一步研究以细化牛磺脱氧胆酸在骨肉瘤治疗中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a8/11209741/549ca23f2e48/OncolRes-32-50907-f001.jpg

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