Zoledronic acid enhances tumor growth and metastatic spread in a mouse model of jaw osteosarcoma.

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Oral diseases Pub Date : 2024-10-01 Epub Date: 2024-02-20 DOI:10.1111/odi.14897

Than-Thuy Nham, Romain Guiho, Régis Brion, Jérôme Amiaud, Bénédicte Brounais Le Royer, Anne Gomez-Brouchet, Françoise Rédini, Hélios Bertin

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Abstract

Objectives: Investigation of the therapeutic effect of zoledronic acid (ZA) in a preclinical model of jaw osteosarcoma (JO).

Materials and methods: The effect of 100 μg/kg ZA administered twice a week was assessed in a xenogenic mouse model of JO. The clinical (tumor growth, development of lung metastasis), radiological (bone microarchitecture by micro-CT analysis), and molecular and immunohistochemical (TRAP, RANK/RANKL, VEGF, and CD146) parameters were investigated.

Results: Animals receiving ZA exhibited an increased tumor volume compared with nontreated animals (71.3 ± 14.3 mm³ vs. 51.9 ± 19.9 mm³ at D14, respectively; p = 0.06) as well as increased numbers of lung metastases (mean 4.88 ± 4.45 vs. 0.50 ± 1.07 metastases, respectively; p = 0.02). ZA protected mandibular bone against tumor osteolysis (mean bone volume of 12.81 ± 0.53 mm³ in the ZA group vs. 11.55 ± 1.18 mm³ in the control group; p = 0.01). ZA induced a nonsignificant decrease in mRNA expression of the osteoclastic marker TRAP and an increase in RANK/RANKL bone remodeling markers.

Conclusion: The use of bisphosphonates in the therapeutic strategy for JO should be further explored, as should the role of bone resorption in the pathophysiology of the disease.

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唑来膦酸可促进颌骨肉瘤小鼠模型中肿瘤的生长和转移扩散。

目的研究唑来膦酸（ZA）在颌骨肉瘤（JO）临床前模型中的治疗效果：在异种小鼠JO模型中评估每周两次给药100 μg/kg ZA的效果。研究了临床（肿瘤生长、肺转移的发生）、放射学（通过显微 CT 分析骨的微结构）、分子和免疫组化（TRAP、RANK/RANKL、VEGF 和 CD146）参数：结果：与未接受ZA治疗的动物相比，接受ZA治疗的动物的肿瘤体积增大（D14时分别为71.3 ± 14.3 mm3 vs. 51.9 ± 19.9 mm3；p = 0.06），肺转移灶数量增加（平均分别为4.88 ± 4.45 vs. 0.50 ± 1.07个转移灶；p = 0.02）。ZA可保护下颌骨免受肿瘤溶骨的影响（ZA组的平均骨量为12.81 ± 0.53 mm3，对照组为11.55 ± 1.18 mm3；p = 0.01）。ZA诱导破骨细胞标志物TRAP的mRNA表达出现非显著性下降，而RANK/RANKL骨重塑标志物的表达出现上升：结论：应进一步探讨双膦酸盐在 JO 治疗策略中的应用，以及骨吸收在该疾病病理生理学中的作用。

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来源期刊

Oral diseases 医学-牙科与口腔外科

CiteScore

7.60

自引率

5.30%

发文量

325

审稿时长

4-8 weeks

期刊介绍： Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.