Osteosarcoma (OS) is rare cancer with bimodal age distribution with peaks observed in children and young adults. Typically, OS is treated with pre-surgery neoadjuvant therapy, surgical excision, and post-surgery chemotherapy. However, the efficacy of treatment on disease prognosis and objective response is not currently optimal, often resulting in drug resistance; in turn, highlighting the need to understand mechanisms driving resistance to therapy in OS patients. Using Doxycycline (Dox)-sensitive and resistant variants of OS cells lines KHOS and U2OS, we found that the resistant variants KHOS-DR and U2OS-DR have significantly higher in vitro proliferation. Treating the Dox-sensitive KHOS/U2OS cells with exosomes isolated from KHOS-DR/U2OS-DR made them resistant to treatment with Dox in vitro and in vivo and enhanced tumor growth and progression, while decreasing overall survival. Expression of the long non-coding RNA (lncRNA) ANCR was significantly higher in the KHOS-DR and U2OS-DR variants. SiRNA-mediated knockdown of ANCR decreased in vitro proliferation, while increasing sensitivity to Dox treatment in the KHOS-DR/U2OS-DR cells. Expression of the exosomal lncRNA ANCR was critical for drug resistance and OS tumor progression in xenografts and was correlated to resistance to Adriamycin and overall survival is patients with OS. These results establish lncRNA ANCR as a critical mediator of resistance to therapy in OS patients, highlighting it as a potential therapeutic target in OS patients.
Giant cell tumor of bone (GCTB) is a rare, benign, but locally aggressive bone tumor. It has a high tendency for local recurrence, which may increase the incidence of lung metastasis. Currently, an optimal treatment strategy has not been established because of the rarity of pulmonary metastatic GCTB. Denosumab is the preferred regimen for unresectable metastatic lesions; however, there are no alternative treatment options when patients are resistant to denosumab. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively competes for the vascular endothelial growth factor receptor 2 (VEGFR-2) ATP binding site, and several studies have analyzed the effectiveness of apatinib in advanced or metastatic tumors. However, there is no report of apatinib as an anti-angiogenesis therapy for pulmonary metastatic GCTB to date. Here, we present a case of a 26-year-old female who was diagnosed with recurrent and pulmonary metastatic GCTB. Immunohistochemical (IHC) staining indicated that the tumor cells were positive for VEGFR-2. Denosumab was administered to control the metastases; nevertheless, disease progression was confirmed after four months of treatment. Given the IHC results and rapid disease progression, apatinib was added to the treatment strategy. After 42 months of treatment, the patient showed noticeable symptomatic improvement and considerable tumor shrinkage.
Background Large malignant bone tumors and revision limb salvage procedures often result in massive bone loss, leaving a short residual bone segment that cannot accommodate a standard stem for endoprosthesis fixation. Three-dimensional-printed (3DP) short stem with porous structure seems to be an alternative for short-segment fixation. This retrospective study aims to evaluate surgical outcomes, radiographical results, limb functions, and complications of using 3DP porous short stems in massive endoprosthesis replacement. Methods Between July 2018 to February 2021, 12 patients with massive bone loss undergoing reconstruction with custom-made, short-stemmed massive endoprostheses were identified. Endoprosthesis replacement involved the proximal femur (n = 4), distal femur (n = 1), proximal humerus (n = 4), distal humerus (n = 1), and proximal radius (n = 2). Results The mean percentage of resected bone was 72.4% of the whole length of the bone, ranging from 58.4 to 88.5%. The mean length of 3DP porous short stems was 6.3 cm. The median follow-up was 38 months (range, 22–58 months). The mean MSTS score was 89%, ranging from 77% to 93%. Radiographical assessment results showed bone in-growth to the porous structure in 11 patients, and the implants were well osseointegrated. Breakage of the 3DP porous short stem occurred in one patient intraoperatively. The patient developed aseptic loosening (Type 2) four-month after surgery and underwent revision with a plate applied to assist fixation. The implant survivorship was 91.7% at 2 years. No other complications were detected, such as soft-tissue failures, structural failures, infection, or tumor progression. Conclusions 3DP custom-made short stem with porous structure is a viable method for fixation of the massive endoprosthesis in the short segment after tumor resection, with satisfactory limb function, great endoprosthetic stability, and low complication rates.
Osteosarcoma is the most common primary malignant bone tumor with a high metastatic potential. Nowadays, there is a lack of new markers to identify prognosis of osteosarcoma patients with response to medical treatment. Recent studies have shown that hematological markers can reflect to some extent the microenvironment of an individual with the potential to predict patient prognosis. However, most of the previous studies have studied the prognostic value of a single hematological index, and it is difficult to comprehensively reflect the tumor microenvironment of patients. Here, we comprehensively collected 16 hematological markers and constructed a hematological prognostic scoring system (HPSS) using LASSO cox regression analysis. HPSS contains many indicators such as immunity, inflammation, coagulation and nutrition. Our results suggest that HPSS is an independent prognostic factor for overall survival in osteosarcoma patients and is an optimal addition to clinical characteristics and well suited to further identify high-risk patients from clinically low-risk patients. HPSS-based nomograms have good predictive ability. Finally, HPSS also has some hints for immunotherapy response in osteosarcoma patients.
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