Background: The goal of this study was to determine whether there are correlations between various options of surgical treatment and long-term outcome for spinal osteosarcoma.Methods: This was a retrospective review of 16 patients with spinal osteosarcoma, who underwent surgical treatment from 1999 to 2010. Seven patients were given totalen blocspondylectomy (TES), while nine received piecemeal resection (there were seven cases of total piecemeal spondylectomy, one of sagittal resection, and one of vertebrectomy). The outcome and prognosis of the patients were evaluated, grouped by surgical treatment.Results: All 16 cases were followed for an average of 42.4 months. At follow-up, all patients noted that pain had eased or had gradually disappeared. Three months after surgery, eight patients (50.0%) had improved 1 to 2 grades in their neurological status, based on Frankel scoring. Six (37.5%) patients experienced local recurrence of the tumor, nine (56.3%) had metastases, and five (31.3%) died of the disease. Of the six patients who received a wide or marginalen blocresection, none developed local recurrence or died from the disease. Conversely, of the ten patients who received intralesional or contaminated resections, six (60%) relapsed and five (50%) died from the disease.Conclusions: TES, with a wide margin, should be planned for patients with osteosarcoma of the cervical and thoracolumbar spine, whenever possible. When the patients are not candidates foren blocresection, total piecemeal spondylectomy is an appropriate choice for osteosarcoma in the mobile spine.

Background: The present study was designed to explore the underlying role of hypoxia-inducible factor 1α (HIF-1α) in reactive oxygen species (ROS) formation and apoptosis in osteosarcoma (OS) cells induced by hypoxia. Methods: In OS cells, ROS accumulated and apoptosis increased within 24 h after exposure to low HIF-1α expression levels. A co-expression analysis showed that HIF was positively correlated with Forkhead box class O1 (FoxO1) expression and negatively correlated with CYP-related genes from the National Center for Biotechnology Information’s Gene Expression Omnibus (NCBI GEO) datasets. Hypoxia also considerably increased HIF-1α and FoxO1 expression. Moreover, the promoter region of FoxO1 was directly regulated by HIF-1α. We inhibited HIF-1α via siRNA and found that the ROS accumulation and apoptosis induced by hypoxia in OS cells decreased. In this study, a murine xenograft model of BALB-c nude mice was adopted to test tumour growth and measure the efficacy of 2-ME + As₂O₃ treatment. Results: Ad interim knockdown of HIF-1α also inhibited manganese-dependent superoxide dismutase (MnSOD), catalase and sestrin 3 (Sesn3) expression in OS cells. Furthermore, hypoxia-induced ROS formation and apoptosis in OS cells were associated with CYP450 protein interference and were ablated by HIF-1α silencing via siRNA. Conclusions: Our data reveal that HIF-1α inhibits ROS accumulation by directly regulating FoxO1 in OS cells, which induces MnSOD, catalase and Sesn3 interference, thus resulting in anti-oxidation effects. The combination of an HIF-1α inhibitor (2-mercaptoethanol,2-ME) and ROS inducer (arsenous oxide, As₂O₃) can prohibit proliferation and migration and promote apoptosis in MG63 cells in vitro while inhibiting tumour growth in vivo.

Three dimensional (3D)-printing technology facilitates complex spine surgery with unique advantages in artificial vertebral body design and manufacturing. In this study, we aimed to demonstrate how a 3D-printed spinal implant is utilized in the management of multi-level spinal tumors and integrates with comprehensive oncologic treatment. Eight spinal or paraspinal tumor patients requiring spinal reconstruction after total en bloc spondylectomy were selected as candidates for 3D-printed titanium artificial vertebral body implants. All patients underwent surgery on three or more vertebral segments or complex spinal junction segments. The clinical, oncological, and surgical characteristics of patients were collected. Of the eight candidates, seven suffered from pain and/or limb disorder. Six underwent successful 3D-printed spinal implantation, while two failed due to implant mismatching and were converted to conventional reconstruction. Of the six patients undergoing 3D-printed spinal implant surgery: (i) Five had recurrent tumors; (ii) three underwent neoadjuvant therapy; (iii) the median surgery time was 414 min; (iv) the median blood loss was 2150 ml; (v) the median blood transfusion was 2000 ml; (vi) the median length of hospital stay was 9 days; (vii) four patients received adjuvant therapy after surgery; and (viii) all patients experienced no pain, moved freely, and had no local recurrence at a median of 11.5 months post-operative follow-up. Spinal reconstruction with a 3D-printed titanium artificial vertebral body allows for total en bloc resection of complex multi-level spinal tumors. Combined with neoadjuvant and adjuvant therapy, these patients had excellent postoperative outcomes, longterm normal spinal function, and associated low local recurrence probability.

Lung cancer (LC), prostate cancer (PC), and breast cancer (BC) are the three most prevalent cancers that lead to bone metastasis (BoM). In this study, we conducted an integrated analysis of single-cell transcriptomic data from the primary tumors and BoM across PC, LC, and BC. We discover a novel subtype of tumor-associated macrophages (TAMs) that are positive both for matrix metalloproteinase 19 (MMP19) and receptor activator of nuclear factor-κB (RANK) expression (MMP19⁺ RANK⁺ TAMs). MMP19⁺ RANK⁺ TAMs demonstrate an increased level of M2 polarization and act as a critical driving factor for LC-BoM. MMP19⁺ RANK⁺ TAMs are organized in a ring-like arrangement surrounding the tumor nests, constructing a barrier structure that impedes the infiltration of CD8⁺ T cells into the tumor core in LC-BoM. RANKL inhibitor Denosumab has been shown to effectively reduce the level of M2 polarization, decrease the population of MMP19⁺ RANK⁺ TAMs, and disrupt their barrier structure. Denosumab facilitates the infiltration of CD8⁺ T cells into the interior of LC-BoM tissues. Based on this mechanism, we observed in both clinical cohorts and preclinical models that RANKL inhibitor can enhance the efficacy of immunotherapy in treating LC-BoM.

3D-printed hemipelvic endoprosthesis is an emerging solution for personalized limb-salvage reconstruction after periacetabular tumor resection. Further clinical studies are still required to report its surgical characteristics, outcomes, benefits and drawbacks. Sixteen consecutive patients underwent periacetabular tumor wide resection and pelvic reconstruction with a 3D-printed hemipelvic endoprosthesis from 2018 to 2021. The surgical characteristics and outcomes are described. The mean follow-up duration was 17.75 months (range, 6 to 46 months). Five patients underwent surgery for type I + II resection and reconstruction, seven for type II + III resection and reconstruction, three for type II resection and reconstruction, and one for type I + II + IV resection and reconstruction. The incidence of postoperative complication was 12.5% (2/16) for deep venous thrombosis (DVT), 12.5% (2/16) for pneumonia, and 12.5% (2/16) for would deep or superficial infection. During follow-up, two patients (12.5%) suffered hip dislocation and underwent revision surgery. CT demonstrated an obvious prosthetic porous structure–bone fusion after follow-up of at least 6 months. At the final follow-up, 12 lived with no evidence of disease while four lived with disease; no patients experienced pain; and 15 had independent ambulation, with a mean Musculoskeletal Tumor Society (MSTS) score of 85.8% (range, 26.7% to 100%). 3D-printed hemipelvic endoprosthesis facilitates wide resection of periacetabular tumor and limb-salvage reconstruction, thus resulting in good oncological and functional outcomes. The custom-made nature is able to well mimic the skeletal anatomy and microstructure and promote osseointegration. Perioperative complications and rehabilitation exercise still need to be stressed for this engineering technology-assisted major orthopedic surgery.

Melanoma is one of the most aggressive and heterogeneous life-threatening cancers. However, the heterogeneity of melanoma and its impact on clinical outcomes are largely unknown. In the present study, intra-tumoral heterogeneity of melanoma cell subpopulations was explored using public single-cell RNA sequencing data. Marker genes, transcription factor regulatory networks, and gene set enrichment analysis were further analyzed. Marker genes of each malignant cluster were screened to create a prognostic risk score, and a nomogram tool was further generated to predict the prognosis of melanoma patients. It was found that malignant cells were divided into six clusters by different marker genes and biological characteristics in which the cell cycling subset was significantly correlated with unfavorable clinical outcomes, and the Wnt signaling pathway-enriched subset may be correlated with the resistance to immunotherapy. Based on the malignant marker genes, melanoma patients in TCGA datasets were divided into three groups which had different survival rates and immune infiltration states. Five malignant cell markers (PSME2, ARID5A, SERPINE2, GPC3, and S100A11) were selected to generate a prognostic risk score. The risk score was associated with overall survival independent of routine clinicopathologic characteristics. The nomogram tool showed good performance with an area under the curve value of 0.802.