Heat shock protein(HSP)90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins,assisting them in folding into proper conformations.HSP90 is critical in maintaining the normal functi...Heat shock protein(HSP)90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins,assisting them in folding into proper conformations.HSP90 is critical in maintaining the normal functions of various proteins within cells,as essential factors for cellular homeostasis.Contrastingly,HSP90 simultaneously supports the maturation of cancer-related proteins,including mesenchymal epithelial transition factor(MET)within tumor cells.All osteosarcoma cell lines had elevated MET expression in the cDNA array in our possession.MET,a tyrosine kinase receptor,promotes proliferation and an anti-apoptotic state through the activation of the MET pathway constructed by HSP90.In this study,we treated osteosarcoma cells with an HSP90 inhibitor,17-demethoxygeldanamycin hydrochloride(17-DMAG),and assessed the changes in the MET signaling pathway and also the antitumor effect of the drug.The cell cycle in osteosarcoma cells administered 17-DMAG was found to be halted at the G2/M phase.Additionally,treatment with 17-DMAG inhibited cell proliferation and induced apoptosis.Inhibition of tumor cell proliferation was also observed in an in vivo model system,mice that were treated with 17-DMAG.Based on the results of this study,we were able to confirm that 17-DMAG promotes inhibition of osteosarcoma cell proliferation and induction of apoptosis by inhibition of MET,a protein highly expressed in osteosarcoma cells.This approach may be useful for the establishment of a new treatment strategy for patients resistant to the standard treatment for osteosarcoma.展开更多
BACKGROUND For the treatment of bone sarcoma in the distal femur,wide-margin resection and knee reconstruction with tumor endoprosthesis are standard therapies.Extraarticular knee resection is required in cases of tum...BACKGROUND For the treatment of bone sarcoma in the distal femur,wide-margin resection and knee reconstruction with tumor endoprosthesis are standard therapies.Extraarticular knee resection is required in cases of tumor invasion of the knee joint;however,the incidence of complications,such as aseptic loosening,prosthesis infection,and implant failure,is higher than that following intra-articular knee resection.To the best of our knowledge,there are three reports of patellar dislocations after replacement of a tumor endoprosthesis.CASE SUMMARY A 36-year-old man with no significant past medical history was admitted to our institution with continuous pain in his left knee for 4 mo.An open biopsy was performed,and the patient was diagnosed with a left distal femoral malignant bone tumor.Extra-articular knee resection and knee reconstruction with a tumor endoprosthesis were performed.Although the alignment of the tumor prosthesis was acceptable,knee instability was noticed postoperatively.The axial radiographic view of the patellar and computed tomography showed lateral patellar dislocation at 4 wk postoperatively.The patient had to undergo a lateral release and proximal realignment.He could perform his daily activities at 9 mo postoperatively.Radiography revealed no patellar re-dislocation.CONCLUSION Proximal realignment may be considered during primary surgery if there is an imbalance in the forces controlling the patellar tracking.展开更多
The phospholipase A2 （PLA2） family members arc critical regulators of membrane structure and lipid composition and have been implicated in neuroinflammation, oxidative stress and neurodegeneration. Here, we review t...The phospholipase A2 （PLA2） family members arc critical regulators of membrane structure and lipid composition and have been implicated in neuroinflammation, oxidative stress and neurodegeneration. Here, we review the published data describing regulation of cPLA2 and iPLA2 gene expression. Based on promoter sequence, cPLA2 expression can be regulated by glucocorticoid and pro-inflammatory cytokines, whereas transcription of iPLA2 can be controlled in response to sterol level. RNA degradation in 3＇ UTR and epigenetic mechanisms may be involved in the regulation of cPLA2 and iPLA2 expression, respectively. MicroRNA target sequences lie within cPLA2 and iPLA2 mRNAs. Together, these findings indicate differential regulation of cPLA2 and iPLA2 expression. It is hoped that determination of diverse regulatory mechanisms of the PLA2 family may open new doors for development of novel therapeutic compounds that modulate PLA2 expression and function in the treatment of brain diseases.展开更多
基金supported in part by the fund of National Cancer Center Research and Development(26-A-4)the Grants-in-Aid for Scientific Research(Nos.15K10451,16K10866 and 16K20063)from Japan Society for the Promotion of Science.
文摘Heat shock protein(HSP)90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins,assisting them in folding into proper conformations.HSP90 is critical in maintaining the normal functions of various proteins within cells,as essential factors for cellular homeostasis.Contrastingly,HSP90 simultaneously supports the maturation of cancer-related proteins,including mesenchymal epithelial transition factor(MET)within tumor cells.All osteosarcoma cell lines had elevated MET expression in the cDNA array in our possession.MET,a tyrosine kinase receptor,promotes proliferation and an anti-apoptotic state through the activation of the MET pathway constructed by HSP90.In this study,we treated osteosarcoma cells with an HSP90 inhibitor,17-demethoxygeldanamycin hydrochloride(17-DMAG),and assessed the changes in the MET signaling pathway and also the antitumor effect of the drug.The cell cycle in osteosarcoma cells administered 17-DMAG was found to be halted at the G2/M phase.Additionally,treatment with 17-DMAG inhibited cell proliferation and induced apoptosis.Inhibition of tumor cell proliferation was also observed in an in vivo model system,mice that were treated with 17-DMAG.Based on the results of this study,we were able to confirm that 17-DMAG promotes inhibition of osteosarcoma cell proliferation and induction of apoptosis by inhibition of MET,a protein highly expressed in osteosarcoma cells.This approach may be useful for the establishment of a new treatment strategy for patients resistant to the standard treatment for osteosarcoma.
文摘BACKGROUND For the treatment of bone sarcoma in the distal femur,wide-margin resection and knee reconstruction with tumor endoprosthesis are standard therapies.Extraarticular knee resection is required in cases of tumor invasion of the knee joint;however,the incidence of complications,such as aseptic loosening,prosthesis infection,and implant failure,is higher than that following intra-articular knee resection.To the best of our knowledge,there are three reports of patellar dislocations after replacement of a tumor endoprosthesis.CASE SUMMARY A 36-year-old man with no significant past medical history was admitted to our institution with continuous pain in his left knee for 4 mo.An open biopsy was performed,and the patient was diagnosed with a left distal femoral malignant bone tumor.Extra-articular knee resection and knee reconstruction with a tumor endoprosthesis were performed.Although the alignment of the tumor prosthesis was acceptable,knee instability was noticed postoperatively.The axial radiographic view of the patellar and computed tomography showed lateral patellar dislocation at 4 wk postoperatively.The patient had to undergo a lateral release and proximal realignment.He could perform his daily activities at 9 mo postoperatively.Radiography revealed no patellar re-dislocation.CONCLUSION Proximal realignment may be considered during primary surgery if there is an imbalance in the forces controlling the patellar tracking.
文摘The phospholipase A2 （PLA2） family members arc critical regulators of membrane structure and lipid composition and have been implicated in neuroinflammation, oxidative stress and neurodegeneration. Here, we review the published data describing regulation of cPLA2 and iPLA2 gene expression. Based on promoter sequence, cPLA2 expression can be regulated by glucocorticoid and pro-inflammatory cytokines, whereas transcription of iPLA2 can be controlled in response to sterol level. RNA degradation in 3＇ UTR and epigenetic mechanisms may be involved in the regulation of cPLA2 and iPLA2 expression, respectively. MicroRNA target sequences lie within cPLA2 and iPLA2 mRNAs. Together, these findings indicate differential regulation of cPLA2 and iPLA2 expression. It is hoped that determination of diverse regulatory mechanisms of the PLA2 family may open new doors for development of novel therapeutic compounds that modulate PLA2 expression and function in the treatment of brain diseases.
