Chondrosarcoma of the hands and feet.

Journal and index pages often block iframe embedding. This reader keeps the evidence details in Orthonotes and leaves the source page one click away.

Abstract

[Indexed for MEDLINE] 12. Mol Cancer Ther. 2019 Nov;18(11):2021-2029. doi: 10.1158/1535-7163.MCT-18-1020. Epub 2019 Jul 24. Anti-miRNA Oligonucleotide Therapy for Chondrosarcoma. Sun X(1), Chen Y(1)(2), Yu H(1), Machan JT(1)(3)(4), Alladin A(1), Ramirez J(1), Taliano R(5), Hart J(5), Chen Q(1), Terek RM(6)(7). Author information: (1)Department of Orthopaedics, Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, Rhode Island. (2)Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut. (3)Lifespan Biostatistics Core, Lifespan Hospital System, Providence, Rhode Island. (4)Department of Surgery, Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, Rhode Island. (5)Department of Pathology, Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, Rhode Island. (6)Department of Orthopaedics, Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, Rhode Island. Richard_Terek@Brown.edu. (7)Providence Veterans Administration Medical Center, Providence, Rhode Island. Chondrosarcoma is a highly aggressive primary malignant bone tumor mostly occurring in adults. There are no effective systemic treatments, and patients with this disease have poor survival. miR-181a is an oncomiR that is overexpressed in high-grade chondrosarcoma and promotes tumor progression. Regulator of G-protein signaling 16 (RGS16) is a target of miR-181a. Inhibition of RGS16 expression by miR-181a enhances CXC chemokine receptor 4 signaling, which in turn increases MMP1 and VEGF expression, angiogenesis, and metastasis. Here, we report the results of systemic treatment with anti-miRNA oligonucleotides (AMO) directed against miR-181a utilizing a nanopiece delivery platform (NPs). NPs were combined with a molecular beacon or anti-miR-181a oligonucleotides and are shown to transfect chondrosarcoma cells in vitro and in vivo Intratumoral injection and systemic delivery had similar effects on miR-181a expression in nude mice bearing chondrosarcoma xenografts. Systemic delivery of NPs carrying anti-miR-181a also restored RGS16 expression, decreased expression of VEGF and MMP1, MMP activity, and tumor volume by 32% at day 38, and prolonged survival from 23% to 45%. In conclusion, these data support that systemic delivery of AMO shows promise for chondrosarcoma treatment. ©2019 American Association for Cancer Research. DOI: 10.1158/1535-7163.MCT-18-1020 PMCID: PMC6825546