The phosphatase and tensin homolog (PTEN) gene, an important tumor-suppressor gene, has been demonstrated to have the potential for inhibiting proliferation, migration and invasion in various types of cancer cells. The aim of the present study was to investigate the effect of PTEN expression on osteosarcoma (OS) cells. The wild-type PTEN plasmid was transfected into OS U2-OS cells. The effects of PTEN on the adhesion, migration and invasion of U2-OS cells were evaluated by cell adhesion analysis, in vitro scratch and Transwell assays, respectively. The levels of MMP-2 and MMP-9, and focal adhesion kinase (FAK) protein regulated by PTEN were detected via western blot analysis. Meanwhile, the level of intracellular FAK phosphorylation was observed. The results from the present study showed that overexpression of PTEN transcription and protein were observed in U2-OS cells following PTEN transfection. Furthermore, the migration, invasion and adhesion capabilities of the cells with PTEN transfection were significantly decreased compared to these capacities in the cells without PTEN. Meanwhile, it was shown that there was downregulation of MMP-9, FAK and p-FAK concomitant with the elevation of the intracellular PTEN level. It is therefore evident that the upregulation of PTEN may attenuate the adhesion, migration and invasion capabilities of OS cells. The mechanisms of the effects of PTEN on OS cells may be correlated with a reduction in the related genes by PTEN regulation.
This study aimed to investigate the effect of long non‐coding RNA XLOC_003810 on the activation of CD4+ T cells and expression of PD‐1/PD‐L1 in patients with myasthenia gravis‐related thymoma (MG‐T). Thymus specimens and thymic mononuclear cells were obtained from MG and MG‐T patients or cardiac surgery patients undergoing thoracotomy who were selected as negative controls (NC). XLOC_003810 expression was examined using quantitative real‐time PCR (qRT‐PCR). Frequency of CD4+ T cells and proportion of CD4+PD‐1+ T cells and CD14+PD‐L1+ monocytes were quantified by flow cytometry. The release of inflammatory cytokines was measured by qRT‐PCR and enzyme‐linked immunosorbent assay. Compared with the NC group, expression of XLOC_003810, frequency of CD4+ T cells and the production of inflammatory cytokines were increased in patients with MG and MG‐T. XLOC_003810 overexpression significantly increased the frequency of CD4+ T cells, facilitated the production of inflammatory cytokines and decreased the proportion of CD4+PD‐1+ T cells and CD14+PD‐L1+ monocytes in the thymic mononuclear cells. In contrast, XLOC_003810 knockdown exerted the opposite effect. Together, XLOC_003810 promotes T cell activation and inhibits PD‐1/PD‐L1 pathway in patients with MG‐T.
The present study aimed to investigate the effects of cold atmospheric plasma (CAP)-activated Ringer's solution on osteosarcoma cell lines MG63 and U2OS, and to identify the molecular mechanism underlying these effects. CAP-activated Ringer's solution was used to treat osteosarcoma cell lines MG63 and U2OS for 30 min. Cell viability was measured using the MTT method. The apoptosis rate was detected using Annexin-V and propidium iodide. The expression levels of cytochrome c, caspase-3 and polyADP ribose polymerase (PARP) in MG63 cells were analyzed via western blotting. The change in mitochondrial membrane potential was detected via the JC-1 dye method and verified by the level of reactive oxygen species (ROS). CAP-activated Ringer's solution inhibited the proliferation of MG63 and U2OS cells in a dose-and time-dependent manner. Furthermore, CAP-activated Ringer's solution induced the apoptosis of MG63 cells, increased the intracellular ROS level, decreased the mitochondrial membrane potential level, and induced the release of cytochrome c. CAP-activated Ringer's solution inhibits osteosarcoma cell proliferation through intracellular ROS-mediated mitochondrial apoptosis.
The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based DOX-loaded implant and to evaluate the efficacy and drug metabolism distribution of the implant in intratumoral chemotherapy for osteosarcoma (OS). In this study, implants containing DOX, poly( d , l -lactide-co-glycolide), and polyethylene glycol 4000 were prepared by melt-molding method. Then, the antitumor activity and systemic drug distribution of the implants were tested in a K7M2 OS bearing mouse model. The scanning electron microscope images showed that DOX was uniformly dispersed in the polymer matrix. Both the in vitro and in vivo release profiles of implants are characterized by three-phase release. Implantation of DOX-loaded implants into tumors can inhibit tumor growth in a dose-dependent manner. The pharmacokinetic behavior shows that intratumor chemotherapy through implants has a much higher drug concentration in tumors than in normal tissues, which may be the reason for improving antitumor activity and reducing systemic side effects. In summary, the drug release of the implants prepared in this study is sustained and stable, which promotes long-term local accumulation of drugs in tumors, improves the efficacy of chemotherapy and has low toxicity to normal tissues.
BackgroundReconstruction of pelvis girdle stability after tumor-induced hemipelvectomy remains challenging. We surgically treated 13 patients with custom-made, three-dimensional printed hemipelvic prostheses. We aim to identify the preliminary outcomes for patients who have been managed with more mixed regions of prosthetic pelvic reconstruction and the feasibility of two reconstructive systems.MethodsSeven male patients and 6 female patients treated at our center between January 2019 and May 2021 were included. There were 11 primary sarcomas and 2 solitary bone metastases. After en bloc tumor resection, two types of personalized, three-dimensional printed prostheses were fixed to restore the stability and rebuild the load transfer. The position of the reconstructed hemipelvis was evaluated on an anteroposterior plain radiograph. The complications and outcomes were traced. One amputation specimen was discovered through histological analysis of the porous structure.ResultsThe operative duration was 467 ± 144 min, and the blood loss was 3,119 ± 662 ml. During a follow-up of 22.4 ± 8.5 months, two patients had delayed wound healing and one had a second-stage flap transfer. One patient with osteosarcoma died of pulmonary metastasis 27 months after surgery. Two patients with marginal resection suffered from local recurrence and had extra surgeries. One patient had traumatic hip dislocation 2 months after surgery and manipulative reduction was performed. The acetabular inclination of the affected side was 42.2 ± 4.3°, compared with 42.1 ± 3.9° on the contralateral side. The horizontal distance between the center of the femoral head and the middle vertical line was 10.4 ± 0.6 cm, while the reconstructed side was 9.8 ± 0.8 cm. No significant difference in acetabular position after surgery was found (p > 0.05). The amputation specimen harvested from one patient with local recurrence demonstrated bone and soft tissue ingrowth within the three-dimensional printed trabecular structure. Walking ability was preserved in all patients who are still alive and no prosthesis-related complications occurred. The MSTS score was 22.0 ± 3.7.ConclusionsBoth types of custom-made, three-dimensional printed prostheses manifested excellent precision, mechanical stability, and promising functional rehabilitation. The porous structure exhibited favorable histocompatibility to facilitate the ingrowth of bone and soft tissue.
Ferroptosis, a form of regulated cell death induced by excessive accumulation of reactive oxygen species and lipid peroxidation, has recently attracted extensive attention due to its ability to effectively suppress tumors and overcome drug resistance. Unlike previously reported metal nanomaterials that induce ferroptosis via the Fenton reaction, arsenene nanosheets can effectively deplete intracellular glutathione and then induce ferroptosis by inhibiting glutathione peroxidase 4. In this study, we designed target-modified arsenene nanosheets loaded with cisplatin (Her2-ANs@CDDP), which are capable of selective uptake by tumor cells. Her2-ANs@CDDP promotes both apoptosis and ferroptosis through a reciprocal cascade reaction between cisplatin and the carrier, respectively, and we demonstrate that it can significantly inhibit the activity of drug-resistant cells. Arsenene nanosheets kill drug-resistant tumor cells by inducing ferroptosis and restoring the sensitivity of drug-resistant cells to cisplatin. Cisplatin-loaded arsenene nanosheets can be prepared simply, and exert synergistic effects that overcome drug resistance. They show great potential for applications in the clinical treatment of chemotherapy-insensitive osteosarcoma, expanding the uses of arsenic in the treatment of solid tumors. Graphical abstract
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