RESUMO
Undifferentiated pleomorphic sarcoma (UPS), once termed as malignant fibrous histiocytoma, has always been diagnosed exclusively in clinical practice because it lacks any defined resemblance to normal mesenchymal tissue. Although myxofibrosarcoma (MFS) has been separated from UPS due to its fibroblastic differentiation with myxoid stroma, UPS and MFS are still identified as a sarcoma group in terms of molecular landscapes. In this review article, we will describe the associated genes and signaling pathways involved in the process of sarcoma genesis and make a summary of conventional management, targeted therapy, immunotherapy, and some novel potential treatments of UPS/MFS. With the progressive advancements in medical technology and a better understanding about the pathogenic mechanism of UPS/MFS in the coming decades, new lights will be shed on the successful management of UPS/MFS.
RESUMO
BACKGROUND: Hip tumors often require tumor-type artificial joint replacement. The selection of the prosthesis stem (hip tumor prosthesis stem) implantation angle during the operation is important to prevent the complication of postoperative prosthesis dislocation. The aim of this study was to evaluate the role of a nickel-titanium (Ni-Ti) shape memory alloy embracing fixator in determination of the implantation angle of a hip tumor prosthesis stem and analyze its efficacy. METHODS: 36 patients with proximal femur tumor were treated with extended tumor resection and prosthetic replacement. 14 patients received prosthetic replacements with the embracing fixators fixing between the junction of the prosthesis stem and the femur temporarily, while the other 22 patients received the same replacements but without the fixators. The two groups were compared regarding occurrence of complications, limb function, and active hip range of motion (ROM). RESULTS: There was no case of hip dislocation in the group that received prosthetic replacements with the use of embracing fixators. Occurrence of deep infection had no difference between the two groups. However, better limb function and higher active (ROM) on abduction or flexion were observed in the group using embracing fixators. CONCLUSION: Ni-Ti shape memory alloy embracing fixator plays a key role in assisting the accurate implantation angle of the prosthesis stem in prosthetic replacement. The prosthesis stem can be adjusted to the optimal angle with the help of the embracing fixator. Patients have a lower risk of dislocation, better limb function, and higher active hip ROM.
RESUMO
Connexin 43- (Cx43-) mediated nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling has been found involved in the ossification of the posterior longitudinal ligament (OPLL). However, the underlying mechanism how OPLL is regulated has not been elucidated. In the present study, primary ligament fibroblast were isolated; immunoprecipitation (IP) and liquid chromatography-mass spectrometry (LC-MS) assays were applied to identify potential binding proteins of Cx43. Protein interaction was then confirmed by co-IP assay. Alkaline phosphatase (ALP) activity and alizarin red staining were used to evaluate ossification. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to assess the binding between NF-κB p65 and target gene. Lipoxygenase inhibitor (5,8,11-eicosatriynoic acid, EPA) was applied to induce endoplasmic reticulum (ER) stress, and 4-phenylbutyrate (4-PBA) was used as an ER-stress inhibitor. Expression of USP9X, Cx43, and nuclei p65 in ligaments from patients and controls was detected by Western blotting. The results showed that ubiquitin-specific protease 9 X-chromosome (USP9X), a deubiquitylating enzyme, was a candidate of Cx43 binding proteins, and USP9X inhibited Cx43 ubiquitination. In vitro experiments showed that USP9X promoted ossification of primary ligament fibroblasts and nuclear translocation of NF-κB p65 by regulating Cx43 expression. Moreover, NF-κB can bind to the USP9X promoter to promote its transcription. When ER stress was inhibited by 4-PBA, USP9X levels, NF-κB nuclei translocation, and ALP activity were decreased. Reverse results were obtained when ER stress was induced by EPA. PDTC, an NF-κB inhibitor, could abolish the effects of EPA. Furthermore, USP9X, Cx43, and nuclei p65 were significantly upregulated in ligaments from OPLL patients than non-OPLL controls. USP9X was positively correlated with CX43 and nuclei p65 in OPLL samples. Overall, the findings suggest that the ER stress-NFκB-USP9X-Cx43 signaling pathway plays an important role in OPLL progression.