The anti-oncogenic effect of 17-DMAG via the inactivation of HSP90 and MET pathway in osteosarcoma cells

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.

Patellar dislocation following distal femoral replacement after extraarticular knee resection for bone sarcoma:A case report

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.