Osteosarcoma is the most common primary malignancy of bones and primarily occurs in adolescents and young adults.However,a second smaller peak of osteosarcoma incidence was reported in the elderly aged more than 60.El...Osteosarcoma is the most common primary malignancy of bones and primarily occurs in adolescents and young adults.However,a second smaller peak of osteosarcoma incidence was reported in the elderly aged more than 60.Elderly patients with osteosarcoma exhibit different characteristics compared to young patients,which usually results in a poor prognosis.The mechanism underlying osteosarcoma development in elderly patients is intriguing and of significant value in clinical applications.Senescent cells can accelerate tumor progression by metabolic reprogramming.Recent research has shown that methylmalonic acid(MMA)was significantly up-regulated in the serum of older individuals and played a central role in the development of aggressive characteristics.We found that the significant accumulation of MMA in elderly patients imparted proliferative potential to osteosarcoma cells.The expression of MAFB was excessively up-regulated in osteosarcoma specimens and was further enhanced in response to MMA accumulation as the patient aged.Specifically,we first confirmed a novel molecular mechanism between cellular senescence and cancer,in which the MMA-driven transcriptional reprogramming of the MAFB-NOTCH3 axis accelerated osteosarcoma progression via the activation of PI3K-AKT pathways.Moreover,the down-regulation of the MAFB-NOTCH3 axis increased the sensitivity and effect of AKT inhibitors in osteosarcoma through significant inhibition of AKT phosphorylation.In conclusion,we confirmed that MAFB is a novel age-dependent biomarker for osteosarcoma,and targeting the MAFB-NOTCH3 axis in combination with AKT inhibition can serve as a novel therapeutic strategy for elderly patients with osteosarcoma in experimental and clinical trials.展开更多
The authors regret that some data errors were made in"Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression"at ...The authors regret that some data errors were made in"Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression"at Figure 5F for the colony formation of MNNG/HOS cells with si-NOTCH3 and 5G for the tranwell assay of U2OS cells with si-NOCTH3.Correction and supplementation to Figure 5.The author used confusing experimental data and did not notice these errors when submitting the original manuscript.Here,the authors made the latest corrections to the data of the batch of U2OS cells and MNNG/HOS cells transfected with si-NoTCH3.The authors confirm that this correction will not alter the conclusions in the original manuscript.展开更多
Reconstruction after resection has always been an urgent problem in the treatment of bone tumours.There are many methods that can be used to reconstruct bone defects;however,there are also many complications,and it is...Reconstruction after resection has always been an urgent problem in the treatment of bone tumours.There are many methods that can be used to reconstruct bone defects;however,there are also many complications,and it is difficult to develop a safe and effective reconstruction plan for the treatment of bone tumours.With the rapid development of digital orthopaedics,three-dimensional printing technology can solve this problem.The three-dimensional printing of personalised prostheses has many advantages.It can be used to print complex structures that are difficult to fabricate using traditional processes and overcome the problems of stress shielding and low biological activity of conventional prostheses.In this study,12 patients with bone tumours were selected as research subjects,and based on individualised reverse-engineering design technology,a three-dimensional model of each prosthesis was designed and installed using medical image data.Ti6Al4V was used as the raw material to prepare the prostheses,which were used to repair bone defects after surgical resection.The operation time was 266.43±21.08 minutes(range 180-390 minutes),and intraoperative blood loss was 857.26±84.28 mL(range 800-2500 mL).One patient had delayed wound healing after surgery,but all patients survived without local tumour recurrence,and no tumour metastasis was found.No aseptic loosening or structural fracture of the prosthesis,and no non-mechanical prosthesis failure caused by infection,tumour recurrence,or progression was observed.The Musculo-Skeletal Tumour Society(MSTS)score of limb function was 22.53±2.09(range 16-26),and ten of the 12 patients scored≥20 and were able to function normally.The results showed that three-dimensional printed prostheses with an individualised design can achieve satisfactory short-term clinical efficacy in the reconstruction of large bone defects after bone tumour resection.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82072979).
文摘Osteosarcoma is the most common primary malignancy of bones and primarily occurs in adolescents and young adults.However,a second smaller peak of osteosarcoma incidence was reported in the elderly aged more than 60.Elderly patients with osteosarcoma exhibit different characteristics compared to young patients,which usually results in a poor prognosis.The mechanism underlying osteosarcoma development in elderly patients is intriguing and of significant value in clinical applications.Senescent cells can accelerate tumor progression by metabolic reprogramming.Recent research has shown that methylmalonic acid(MMA)was significantly up-regulated in the serum of older individuals and played a central role in the development of aggressive characteristics.We found that the significant accumulation of MMA in elderly patients imparted proliferative potential to osteosarcoma cells.The expression of MAFB was excessively up-regulated in osteosarcoma specimens and was further enhanced in response to MMA accumulation as the patient aged.Specifically,we first confirmed a novel molecular mechanism between cellular senescence and cancer,in which the MMA-driven transcriptional reprogramming of the MAFB-NOTCH3 axis accelerated osteosarcoma progression via the activation of PI3K-AKT pathways.Moreover,the down-regulation of the MAFB-NOTCH3 axis increased the sensitivity and effect of AKT inhibitors in osteosarcoma through significant inhibition of AKT phosphorylation.In conclusion,we confirmed that MAFB is a novel age-dependent biomarker for osteosarcoma,and targeting the MAFB-NOTCH3 axis in combination with AKT inhibition can serve as a novel therapeutic strategy for elderly patients with osteosarcoma in experimental and clinical trials.
文摘The authors regret that some data errors were made in"Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression"at Figure 5F for the colony formation of MNNG/HOS cells with si-NOTCH3 and 5G for the tranwell assay of U2OS cells with si-NOCTH3.Correction and supplementation to Figure 5.The author used confusing experimental data and did not notice these errors when submitting the original manuscript.Here,the authors made the latest corrections to the data of the batch of U2OS cells and MNNG/HOS cells transfected with si-NoTCH3.The authors confirm that this correction will not alter the conclusions in the original manuscript.
基金This study was supported by the National Natural Science Foundation of China(No.81904231).
文摘Reconstruction after resection has always been an urgent problem in the treatment of bone tumours.There are many methods that can be used to reconstruct bone defects;however,there are also many complications,and it is difficult to develop a safe and effective reconstruction plan for the treatment of bone tumours.With the rapid development of digital orthopaedics,three-dimensional printing technology can solve this problem.The three-dimensional printing of personalised prostheses has many advantages.It can be used to print complex structures that are difficult to fabricate using traditional processes and overcome the problems of stress shielding and low biological activity of conventional prostheses.In this study,12 patients with bone tumours were selected as research subjects,and based on individualised reverse-engineering design technology,a three-dimensional model of each prosthesis was designed and installed using medical image data.Ti6Al4V was used as the raw material to prepare the prostheses,which were used to repair bone defects after surgical resection.The operation time was 266.43±21.08 minutes(range 180-390 minutes),and intraoperative blood loss was 857.26±84.28 mL(range 800-2500 mL).One patient had delayed wound healing after surgery,but all patients survived without local tumour recurrence,and no tumour metastasis was found.No aseptic loosening or structural fracture of the prosthesis,and no non-mechanical prosthesis failure caused by infection,tumour recurrence,or progression was observed.The Musculo-Skeletal Tumour Society(MSTS)score of limb function was 22.53±2.09(range 16-26),and ten of the 12 patients scored≥20 and were able to function normally.The results showed that three-dimensional printed prostheses with an individualised design can achieve satisfactory short-term clinical efficacy in the reconstruction of large bone defects after bone tumour resection.
