在骨肉瘤小鼠模型中探索陶乐定对肿瘤重量和微血管密度的影响。

IF 2 4区 医学 Q3 ONCOLOGY Oncology Research Pub Date : 2024-06-20 eCollection Date: 2024-01-01 DOI:10.32604/or.2024.050907
Lisanne K A Neijenhuis, Leuta L Naumann, Sonia A M Ferkel, Samuel J S Rubin, Stephan Rogalla
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引用次数: 0

摘要

背景:骨肉瘤是最常见的恶性原发性骨肿瘤:骨肉瘤是最常见的恶性原发性骨肿瘤。尽管近年来化疗技术不断进步,但扩散性骨肉瘤患者的预后仍然很差。此外,目前的治疗方案存在严重副作用的风险。因此,临床上对安全性更高的有效疗法的需求尚未得到满足。陶乐定是一种抗菌剂,已被证明能诱导不同类型癌细胞株的细胞死亡:在这项研究中,我们考察了滔罗立定在骨肉瘤动物模型中的抗肿瘤和抗血管生成作用。第零天,向 60 只 BALB/c 小鼠肌肉注射和腹腔注射 K7M2 小鼠骨肉瘤细胞。然后,小鼠随机接受 2% taurolidine(800 毫克/千克)、1% taurolidine(400 毫克/千克)或 0.9% NaCl 对照组的静脉或腹腔给药治疗,为期 7 天:35 天后,小鼠被安乐死,并收获肿瘤进行分析。由于并发症,18 只小鼠未纳入分析。从第9天到第21天,2%妥洛尼定腹腔给药组的体重明显降低,这与该组死亡率升高相一致。与对照组相比,1%(p = 0.003)和 2%(p = 0.006)腹腔注射滔罗立定治疗组的腹腔内肿瘤重量明显较低。肌肉注射或静脉注射滔罗立定均未观察到抗肿瘤作用。治疗组之间的微血管密度和有丝分裂率没有明显差异。2%滔罗立定腹腔注射组的体重降低,死亡率升高,这表明1%的较低剂量更可取:总之,没有证据表明滔罗立定具有抗血管生成活性,本研究中观察到的滔罗立定对骨肉瘤的抗肿瘤作用有限。此外,其毒性也需要进一步评估。鉴于这些观察结果,有必要开展进一步研究,以完善陶罗林在骨肉瘤治疗中的应用。
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Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma.

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% (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.

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.

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来源期刊
Oncology Research
Oncology Research 医学-肿瘤学
CiteScore
4.40
自引率
0.00%
发文量
56
审稿时长
3 months
期刊介绍: Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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