Osteosarcoma is a genetically unstable malignancy that most frequently occurs in children and young adults.The lack of progress in managing this devastating disease in the clinic has prompted international researchers...Osteosarcoma is a genetically unstable malignancy that most frequently occurs in children and young adults.The lack of progress in managing this devastating disease in the clinic has prompted international researchers to collaborate to profile key genomic alterations that define osteosarcoma.A team of researchers and clinicians from China,Finland,and the United States investigated human osteosarcoma by integrating transcriptome sequencing(RNA-seq),high-density genome-wide array comparative genomic hybridization(a CGH),fluorescence in situ hybridization(FISH),reverse transcription-polymerase chain reaction(RT-PCR),Sanger sequencing,cell culture,and molecular biological approaches.Systematic analysis of genetic/genomic alterations and further functional studies have led to several important findings,including novel rearrangement hotspots,osteosarcoma-specific LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes,VEGF and Wnt signaling pathway alterations,deletion of the WWOX gene,and amplification of the APEX1 and RUNX2 genes.Importantly,these genetic events associate significantly with pathogenesis,prognosis,progression,and therapeutic activity in osteosarcoma,suggesting their potential impact on improved managements of human osteosarcoma.This international initiative provides opportunities for developing new treatment modalities to conquer osteosarcoma.展开更多
目的:应用Micro-CT评价Runx2基因修饰的骨髓间充质干细胞(MSC)静脉移植促进兔坏死股骨头修复效果。方法:24只大耳白兔经缺血性股骨头坏死造模4周后随机分为4组,A组静脉移植1×107个Runx2基因修饰的MSC,B组静脉移植1×107个Runx2...目的:应用Micro-CT评价Runx2基因修饰的骨髓间充质干细胞(MSC)静脉移植促进兔坏死股骨头修复效果。方法:24只大耳白兔经缺血性股骨头坏死造模4周后随机分为4组,A组静脉移植1×107个Runx2基因修饰的MSC,B组静脉移植1×107个Runx2 si RNA修饰的MSC,C组单纯植入1×107个MSC,D组静脉植入等量生理盐水,细胞移植后2、4、6、8周取出股骨头标本行Micro-CT检测,评价股骨头坏死修复情况。结果:2周后各组动物股骨头关节面模糊,骨密度降低,骨小梁数量及厚度均下降,骨小梁结构紊乱,但组间差异不明显;4、6周后,A、B、C组动物股骨头内骨密度和骨小梁结构未明显变化,但可见修复反应,而D组动物股骨头内骨小梁结构破坏进一步加剧;8周后,D组动物股骨头关节面塌陷,骨小梁严重缺失形成较大空洞,A、B、C组股骨头可见明显修复反应,关节面完整度、关节面下骨密度、骨小梁体积及数量、骨小梁连续性表现为A>C>B>D组。结论:MSC静脉移植可有效治疗股骨头坏死,且过表达Runx2基因修饰后能有效提升MSC移植后的治疗效果。展开更多
基金partly supported by grants from the National Natural Science Foundation of China(81372872 to JY,81402215 to XD,and 81320108022 to KC)the University Cancer Foundation via the Sister Institution Network Fund(SINF)(to JY and WZ)+2 种基金the Program for Changjiang Scholars and Innovative Research Teamin University(PCSIRT)in China(IRT1076 to JY and KC)the Liddy Shriver Sarcoma Initiative(to JY and WZ),and the National Key Scientific and Technological Project(2011ZX09307-001-04 to KC)The Tissue Bank of Tianjin Medical University Cancer Institute&Hospital is partially supported by the National Foundation for Cancer Research(US)
文摘Osteosarcoma is a genetically unstable malignancy that most frequently occurs in children and young adults.The lack of progress in managing this devastating disease in the clinic has prompted international researchers to collaborate to profile key genomic alterations that define osteosarcoma.A team of researchers and clinicians from China,Finland,and the United States investigated human osteosarcoma by integrating transcriptome sequencing(RNA-seq),high-density genome-wide array comparative genomic hybridization(a CGH),fluorescence in situ hybridization(FISH),reverse transcription-polymerase chain reaction(RT-PCR),Sanger sequencing,cell culture,and molecular biological approaches.Systematic analysis of genetic/genomic alterations and further functional studies have led to several important findings,including novel rearrangement hotspots,osteosarcoma-specific LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes,VEGF and Wnt signaling pathway alterations,deletion of the WWOX gene,and amplification of the APEX1 and RUNX2 genes.Importantly,these genetic events associate significantly with pathogenesis,prognosis,progression,and therapeutic activity in osteosarcoma,suggesting their potential impact on improved managements of human osteosarcoma.This international initiative provides opportunities for developing new treatment modalities to conquer osteosarcoma.
文摘目的:应用Micro-CT评价Runx2基因修饰的骨髓间充质干细胞(MSC)静脉移植促进兔坏死股骨头修复效果。方法:24只大耳白兔经缺血性股骨头坏死造模4周后随机分为4组,A组静脉移植1×107个Runx2基因修饰的MSC,B组静脉移植1×107个Runx2 si RNA修饰的MSC,C组单纯植入1×107个MSC,D组静脉植入等量生理盐水,细胞移植后2、4、6、8周取出股骨头标本行Micro-CT检测,评价股骨头坏死修复情况。结果:2周后各组动物股骨头关节面模糊,骨密度降低,骨小梁数量及厚度均下降,骨小梁结构紊乱,但组间差异不明显;4、6周后,A、B、C组动物股骨头内骨密度和骨小梁结构未明显变化,但可见修复反应,而D组动物股骨头内骨小梁结构破坏进一步加剧;8周后,D组动物股骨头关节面塌陷,骨小梁严重缺失形成较大空洞,A、B、C组股骨头可见明显修复反应,关节面完整度、关节面下骨密度、骨小梁体积及数量、骨小梁连续性表现为A>C>B>D组。结论:MSC静脉移植可有效治疗股骨头坏死,且过表达Runx2基因修饰后能有效提升MSC移植后的治疗效果。
