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特立帕肽不会加剧乳腺癌骨转移模型中的骨转移。

Teriparatide Does Not Exacerbate Bone Metastases in Breast Cancer Bone Metastasis Model.

作者信息

Kawaragi Takashi, Tsuchie Hiroyuki, Nagasawa Hiroyuki, Hongo Michio, Kasukawa Yuji, Nozaka Koji, Kasama Fumihito, Oya Keita, Watanabe Manabu, Tominaga Kenta, Miyakoshi Naohisa

机构信息

Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan;

Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan.

出版信息

In Vivo. 2025 Jul-Aug;39(4):1932-1940. doi: 10.21873/invivo.13992.

Abstract

BACKGROUND/AIM: Breast cancer frequently metastasizes to bone, and chemotherapy and hormone therapy can increase osteoporosis risk. Teriparatide (TPTD), an osteoporosis treatment that promotes bone formation, is contraindicated in patients with bone metastases due to concerns about osteosarcoma in animal studies. However, its effects on metastatic bone tumors remain unclear. This study aimed to evaluate TPTD's effects on breast cancer bone metastases using a mouse model.

MATERIALS AND METHODS

C57BL/6 mice were injected with E0771 breast cancer cells to establish bone metastasis and breast cancer models. Mice were assigned to the vehicle-treated group (control) or to the TPTD-treated group (80 μg/kg, subcutaneously three times weekly). Tumor weight, volume, bone destruction, pathological fractures, distant metastasis, tumor proliferation (Ki-67, BrdU), and bone microstructure were assessed at 4 and 6 weeks.

RESULTS

In both models, no significant differences in tumor weight or volume were observed between the TPTD and control groups. In the bone metastasis model, bone destruction and pathological fractures were not significantly different. No distant metastasis was observed and there were no significant differences in the percentages of Ki-67-positive and BrdU-positive cells in both models. In the bone microstructure analysis at 6 weeks post-injection, bone volume/tissue volume and trabecular thickness increased in the bone metastasis model in the TPTD group (=0.02 and <0.01, respectively), and trabecular separation decreased in the TPTD group (=0.01).

CONCLUSION

TPTD did not cause tumor growth, pathological fractures, or bone destruction in our models, indicating that it may be safe for use in breast cancer.

摘要

背景/目的:乳腺癌常转移至骨骼,化疗和激素治疗会增加骨质疏松风险。特立帕肽(TPTD)是一种促进骨形成的骨质疏松治疗药物,由于动物研究中担心骨肉瘤,骨转移患者禁用。然而,其对转移性骨肿瘤的影响尚不清楚。本研究旨在使用小鼠模型评估TPTD对乳腺癌骨转移的影响。

材料与方法

将E0771乳腺癌细胞注射到C57BL/6小鼠体内,建立骨转移和乳腺癌模型。将小鼠分为溶剂处理组(对照组)或TPTD处理组(80μg/kg,每周皮下注射三次)。在第4周和第6周评估肿瘤重量、体积、骨破坏、病理性骨折、远处转移、肿瘤增殖(Ki-67、BrdU)和骨微结构。

结果

在两个模型中,TPTD组和对照组之间在肿瘤重量或体积上均未观察到显著差异。在骨转移模型中,骨破坏和病理性骨折无显著差异。未观察到远处转移,两个模型中Ki-67阳性和BrdU阳性细胞的百分比也无显著差异。在注射后6周的骨微结构分析中,TPTD组骨转移模型中的骨体积/组织体积和小梁厚度增加(分别为=0.02和<0.01),TPTD组小梁间距减小(=0.01)。

结论

在我们的模型中,TPTD未导致肿瘤生长、病理性骨折或骨破坏,表明其用于乳腺癌可能是安全的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb50/12223623/76f04c574b52/in_vivo-39-1934-g0001.jpg

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