Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.Wh...Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.While KIF18B overexpression in osteosarcoma tissue is clearly detected,its specific function in the disease process remains to be established.Methods:K IF18B expression was assessed in osteosarcoma tissues and cells.We additionally evaluated the effects of KIF18B on proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.Results:Our results showed overexpression of KIF18B in osteosarcoma tissues and cells.Knockdown of K IF18B induced G1/S phase arrest and significantly inhibited proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.K IF18B regulated P-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli(APC)tumor suppressor gene in osteosarcoma cells.Conclusions:KIF18B plays a carcinogenic role in osteosarcoma by regulating expression ofβ-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC.Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.展开更多
Objective： To assess the efficacy of conservative chemotherapy for inoperable desmoid tumor（DT） and analyze the prognostic factors.Methods：From November 2008 to April 2016,71 patients of inoperable DT were treated...Objective： To assess the efficacy of conservative chemotherapy for inoperable desmoid tumor（DT） and analyze the prognostic factors.Methods：From November 2008 to April 2016,71 patients of inoperable DT were treated with vinorelbine and low-dose methotrexate in the Department of Bone and Soft Tissue Tumors,Peking University Cancer Hospital＆Institute,and enrolled in this retrospective study.The chemotherapy duration is one year.The efficacy of chemotherapy and the prognosis were observed.Results：Of the 71 patients,55% were female.Age of onset varied from 1 to 47 years,and the median age was 14years.Only 11（15.5%）cases suffered primary tumor.The distribution of the site of tumors was：31（43.7%）in the trunk,36（50.7%）in the limbs,and 4（5.6%）in the peritoneal and pelvic cavity.The size of tumor（the maximum diameter）differed from 2 to 37 cm with a mean of 9.3 cm.The median follow-up duration was 28（range,6–87）months.Common side effects included：nausea and vomiting,liver injury,bone marrow suppression and oral ulcers.When the chemotherapy finished,1（1.4%）case achieved complete response,24（33.8%）achieved partial response,37（52.1%）achieved stable disease and 9（12.7%）had progressive disease.The overall response rate was 87.3%.The progression-free survival（PFS）of the participants were from 6 to 87 months,and the 2-,3-and 5-year PFS was 79.9%,68.4% and 36.3%,respectively.No significant difference was identified in PFS in subgroups of gender,age of onset,age of chemotherapy,tumor site and tumor size.Conclusions：For recurrent,inoperable and progressive DT,enough course of chemotherapy with vinorelbine combined with low-dose methotrexate was an optional choice for local control.展开更多
There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,i...There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration.We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate(CMCS/SA)gel network.This had the advantages of:improved compressive strength,ease of handling,and an optimized interface for bioactive bone in-growth.The new composites with 2%CMCS/SA showed the most favorable physicochemical properties,including mechanical strength,wash-out resistance,setting time,injectable time and heat release.Biologically,the composite promoted the attachment and proliferation of osteoblast cells.It was also found to induce osteogenic differentiation in vitro,as verified by expression of osteogenic markers.In terms of molecular mechanisms,data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation ofβ-catenin,which is dependent on focal adhesion kinase.Through micro-computed tomography and histological analysis,we found that the MPC-CMCS/SA scaffolds,compared with MPC alone,showed increased bone regeneration in a rat calvarial defect model.Overall,our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.展开更多
Magnesium phosphate bone cements(MPC)have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability.However,their poor porosity and permeability limit os...Magnesium phosphate bone cements(MPC)have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability.However,their poor porosity and permeability limit osteogenic cell ingrowth and vascularization,which is critical for bone regeneration.In the current study,we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix(ECM)-mimicking electrospun silk fibroin(SF)nanofibers.The SF-embedded MPC(SM)exhibited a heterogeneous and hierarchical structure,which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth.Besides,the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide.Bone marrow stem cells(BMSCs)adhered excellently on SM,as illustrated by formation of more pseudopodia.CCK8 assay showed that SM promoted early proliferation of BMSCs.Our study also verified that SM increased the expression of OPN,RUNX2 and BMP2,suggesting enhanced osteogenic differentiation of BMSCs.We screened for osteogenesis-related pathways,including FAK signaing,Wnt signaling and Notch signaling,and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway,proved by the downregulation of NICD1,Hes1 and Hey2.In addition,using a bone defect model of rat calvaria,the study revealed that SM exhibited enhanced osteogenesis,bone ingrowth and vascularization compared with MPC alone.No adverse effect was found after implantation of SM in vivo.Overall,our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.展开更多
基金grants from the National Natural Science Foundation of China(Grant No.81802689)China International Medical Foundation(Grant No.Z-2014-06-15331)Conflict of interest。
文摘Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.While KIF18B overexpression in osteosarcoma tissue is clearly detected,its specific function in the disease process remains to be established.Methods:K IF18B expression was assessed in osteosarcoma tissues and cells.We additionally evaluated the effects of KIF18B on proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.Results:Our results showed overexpression of KIF18B in osteosarcoma tissues and cells.Knockdown of K IF18B induced G1/S phase arrest and significantly inhibited proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.K IF18B regulated P-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli(APC)tumor suppressor gene in osteosarcoma cells.Conclusions:KIF18B plays a carcinogenic role in osteosarcoma by regulating expression ofβ-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC.Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.
文摘Objective： To assess the efficacy of conservative chemotherapy for inoperable desmoid tumor（DT） and analyze the prognostic factors.Methods：From November 2008 to April 2016,71 patients of inoperable DT were treated with vinorelbine and low-dose methotrexate in the Department of Bone and Soft Tissue Tumors,Peking University Cancer Hospital＆Institute,and enrolled in this retrospective study.The chemotherapy duration is one year.The efficacy of chemotherapy and the prognosis were observed.Results：Of the 71 patients,55% were female.Age of onset varied from 1 to 47 years,and the median age was 14years.Only 11（15.5%）cases suffered primary tumor.The distribution of the site of tumors was：31（43.7%）in the trunk,36（50.7%）in the limbs,and 4（5.6%）in the peritoneal and pelvic cavity.The size of tumor（the maximum diameter）differed from 2 to 37 cm with a mean of 9.3 cm.The median follow-up duration was 28（range,6–87）months.Common side effects included：nausea and vomiting,liver injury,bone marrow suppression and oral ulcers.When the chemotherapy finished,1（1.4%）case achieved complete response,24（33.8%）achieved partial response,37（52.1%）achieved stable disease and 9（12.7%）had progressive disease.The overall response rate was 87.3%.The progression-free survival（PFS）of the participants were from 6 to 87 months,and the 2-,3-and 5-year PFS was 79.9%,68.4% and 36.3%,respectively.No significant difference was identified in PFS in subgroups of gender,age of onset,age of chemotherapy,tumor site and tumor size.Conclusions：For recurrent,inoperable and progressive DT,enough course of chemotherapy with vinorelbine combined with low-dose methotrexate was an optional choice for local control.
基金support of the National Natural Science Foundation of China(No.81802689,51772233)the Provincial Key Research and Development Program of Hubei,China(No.2020BCB058)+2 种基金State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(Wuhan University of Technology)(2021-KF-22)the Major Special Projects of Technological Innovation of Hubei Province(No.2019ACA130)the Application Foundation and Front Research Program of Wuhan(No.2018010401011273).
文摘There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration.We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate(CMCS/SA)gel network.This had the advantages of:improved compressive strength,ease of handling,and an optimized interface for bioactive bone in-growth.The new composites with 2%CMCS/SA showed the most favorable physicochemical properties,including mechanical strength,wash-out resistance,setting time,injectable time and heat release.Biologically,the composite promoted the attachment and proliferation of osteoblast cells.It was also found to induce osteogenic differentiation in vitro,as verified by expression of osteogenic markers.In terms of molecular mechanisms,data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation ofβ-catenin,which is dependent on focal adhesion kinase.Through micro-computed tomography and histological analysis,we found that the MPC-CMCS/SA scaffolds,compared with MPC alone,showed increased bone regeneration in a rat calvarial defect model.Overall,our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.
基金support of the Provincial Key Resaearch and Development Program of Hubei,China (No.2020BCB058)Youth Science and Technology Talent Project of Hubei Province (2023DJC163).
文摘Magnesium phosphate bone cements(MPC)have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability.However,their poor porosity and permeability limit osteogenic cell ingrowth and vascularization,which is critical for bone regeneration.In the current study,we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix(ECM)-mimicking electrospun silk fibroin(SF)nanofibers.The SF-embedded MPC(SM)exhibited a heterogeneous and hierarchical structure,which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth.Besides,the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide.Bone marrow stem cells(BMSCs)adhered excellently on SM,as illustrated by formation of more pseudopodia.CCK8 assay showed that SM promoted early proliferation of BMSCs.Our study also verified that SM increased the expression of OPN,RUNX2 and BMP2,suggesting enhanced osteogenic differentiation of BMSCs.We screened for osteogenesis-related pathways,including FAK signaing,Wnt signaling and Notch signaling,and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway,proved by the downregulation of NICD1,Hes1 and Hey2.In addition,using a bone defect model of rat calvaria,the study revealed that SM exhibited enhanced osteogenesis,bone ingrowth and vascularization compared with MPC alone.No adverse effect was found after implantation of SM in vivo.Overall,our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.
