دورية أكاديمية
Effects of neoadjuvant zoledronate and radiation therapy on cell survival, cell cycle distribution, and clinical status in canine osteosarcoma.
العنوان: | Effects of neoadjuvant zoledronate and radiation therapy on cell survival, cell cycle distribution, and clinical status in canine osteosarcoma. |
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المؤلفون: | Norquest CJ; Department of Veterinary Medicine & Surgery, University of Missouri College of Veterinary Medicine, Columbia, MO, United States., Rogic A; Department of Veterinary Medicine & Surgery, University of Missouri College of Veterinary Medicine, Columbia, MO, United States., Gimotty PA; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania School of Medicine, Philadelphia, PA, United States., Maitz CA; Department of Veterinary Medicine & Surgery, University of Missouri College of Veterinary Medicine, Columbia, MO, United States., Rindt H; Department of Veterinary Medicine & Surgery, University of Missouri College of Veterinary Medicine, Columbia, MO, United States., Ashworth HL; Department of Veterinary Medicine & Surgery, University of Missouri College of Veterinary Medicine, Columbia, MO, United States., Bryan JN; Department of Veterinary Medicine & Surgery, University of Missouri College of Veterinary Medicine, Columbia, MO, United States., Donnelly LL; Department of Veterinary Medicine & Surgery, University of Missouri College of Veterinary Medicine, Columbia, MO, United States., McCleary-Wheeler AL; Department of Veterinary Medicine & Surgery, University of Missouri College of Veterinary Medicine, Columbia, MO, United States., Flesner BK; Department of Veterinary Medicine & Surgery, University of Missouri College of Veterinary Medicine, Columbia, MO, United States.; Department of Clinical Sciences & Advanced Medicine, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, United States. |
المصدر: | Frontiers in veterinary science [Front Vet Sci] 2024 Jan 31; Vol. 11, pp. 1237084. Date of Electronic Publication: 2024 Jan 31 (Print Publication: 2024). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Media S.A Country of Publication: Switzerland NLM ID: 101666658 Publication Model: eCollection Cited Medium: Print ISSN: 2297-1769 (Print) Linking ISSN: 22971769 NLM ISO Abbreviation: Front Vet Sci Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Media S.A., [2014]- |
مستخلص: | Introduction: Zoledronic acid (ZOL) is a third-generation bisphosphonate with a higher affinity for bone resorption areas than earlier bisphosphonates (i.e., pamidronate, PAM). In human medicine, ZOL provides improved bone pain relief and prolonged time to skeletal-related events compared to its older generational counterparts. Preclinical studies have investigated its role as an anti-neoplastic agent, both independently and synergistically, with radiation therapy (RT). ZOL and RT act synergistically in several neoplastic human cell lines: prostate, breast, osteosarcoma, and fibrosarcoma. However, the exact mechanism of ZOL's radiosensitization has not been fully elucidated. Methods: We investigated ZOL's ability to induce apoptosis in canine osteosarcoma cell lines treated with various doses of megavoltage external beam radiotherapy. Second, we evaluated cell cycle arrest in ZOL-treated cells to assess several neo-adjuvant time points. Finally, we treated 20 dogs with naturally occurring appendicular OS with 0.1 mg/kg ZOL IV 24 h before receiving 8 Gy of RT (once weekly fraction x 4 weeks). Results: We found that apoptosis was increased in all ZOL-treated cell lines compared to controls, and the combination of ZOL and RT resulted in dissimilar apoptosis between Abrams and D-17 and HMPOS cell lines. Cell cycle arrest (G2/M phase) was minimal and variable between cell lines but perhaps greatest at 48 h post-ZOL treatment. Only 10% of dogs treated with ZOL and RT developed pathologic fractures, compared to 44% of dogs historically treated with PAM and RT ( p = 0.027). Discussion: ZOL and RT appear to be a well-tolerated combination treatment scheme for non-surgical candidates; future studies must elucidate the ideal timing of ZOL. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Norquest, Rogic, Gimotty, Maitz, Rindt, Ashworth, Bryan, Donnelly, McCleary-Wheeler and Flesner.) |
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فهرسة مساهمة: | Keywords: cancer pain; osteosarcoma; pathologic fracture; radiation therapy; zoledronate |
تواريخ الأحداث: | Date Created: 20240216 Latest Revision: 20240217 |
رمز التحديث: | 20240217 |
مُعرف محوري في PubMed: | PMC10867971 |
DOI: | 10.3389/fvets.2024.1237084 |
PMID: | 38362299 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2297-1769 |
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DOI: | 10.3389/fvets.2024.1237084 |