Background Antiangiogenesis tyrosine kinase inhibitors (TKIs) have been shown to prolong progression‐free survival (PFS) in advanced osteosarcoma. Methylsulfonic apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor‐2. We aim to assess apatinib in patients with advanced high‐grade osteosarcoma progressing upon chemotherapy. Materials and Methods This phase II trial was conducted at Peking University People's Hospital. We enrolled participants (≥16 years of age) with progressive relapsed or unresectable osteosarcoma. Participants received 750 mg or 500 mg of apatinib according to body surface area once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and PFS at 4 months. Results A total of 37 participants were finally included into the analysis. Until final follow‐up, the objective response rate (complete response + partial response) was 43.24% (16/37). The 4‐month PFS rate was 56.76% (95% confidence interval [CI], 39.43%–70.84%). Median PFS and overall survival were 4.50 (95% CI, 3.47–6.27) and 9.87 (95% CI 7.97–18.93) months, respectively. Toxic effects led to dose reductions or interruptions in a total of 25 of 37 (67.57%) patients. The most common grade 3–4 adverse events were pneumothorax in six (16.22%) patients, wound dehiscence in four (10.81%), proteinuria in three (8.11%), diarrhea in three (8.11%), and palmar‐plantar erythrodysesthesia syndrome in three (8.11%). No other serious adverse events were reported during the trial. There were no treatment‐related deaths. Conclusion Apatinib is a sensitive drug for advanced osteosarcoma with a high response rate after failure of chemotherapy, with similar duration of response compared to other TKIs. Implications for Practice For advanced osteosarcoma progressing upon chemotherapy, antiangiogenesis tyrosine kinase inhibitors (TKIs) have been proved to be effective in prolonging the progression‐free survival in previous multicenter trials and have been included into new National Comprehensive Cancer Network guidelines as second‐line therapy. Apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor‐2, which is domestically made in China. This phase II trial supports the use of apatinib in patients with advanced osteosarcoma progressing after chemotherapy.

BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.

Aberrantly expressed miRNAs play a crucial role in the development of multiple cancer types, including chordoma. However, the detailed molecular mechanisms are unclear and need to be elucidated. In this study, miRNAs were screened by miRNA array analysis and then confirmed by real-time PCR analysis. We found that miR-16-5p was significantly downregulated in chordoma, and overexpression of miR-16-5p suppressed chordoma cell proliferation, invasion and migration in vitro and in vivo and correlated with the upregulated expression of E-cadherin and downregulated expression of N-cadherin and vimentin. Furthermore, Smad3 was identified as a target of miR-16-5p, and Smad3 was highly expressed in chordoma tissues. Further research showed that knockdown of Smad3 had an effect similar to that of overexpression of miR-16-5p in chordoma cells. Our findings demonstrate that miR-16-5p plays a tumor suppressor role in chordoma progression by targeting Smad3, which could provide a promising prognostic and therapeutic strategy for chordoma treatment.

Elevated levels of fibronectin (Fn) in articular cartilage have been linked to the progression of both rheumatoid and osteoarthritis. In this study, we examined intracellular events which follow ligation of Fn to its receptor, the integrin ␣ 5 ␤ 1. In addition, we examined the regulatory influence of nitric oxide on these events, since this free radical has been implicated in cartilage degradation. Exposure of chondrocytes to Fn-coated beads resulted in the circumferential clustering of the ␣ 5 ␤ 1 integrin receptor, which was accompanied by the subplasmalemmal assembly of a focal activation complex comprised of F-actin, the tyrosine kinase, focal adhesion kinase (FAK), the ras related G protein rho A, as well as tyrosine-phosphorylated proteins. Treatment with exogenous nitric oxide (NO) or catabolic cytokines which induce nitric oxide synthase blocked the assembly of F-actin, FAK, rho A and tyrosine-phosphorylated proteins while not affecting the total number of beads bound per cell nor the clustering of ␣ 5 ␤ 1 integrin. Use of a cGMP antagonist (Rp-8-Br cGMPS) or cGMP agonist (SpcGMPS) either abolished or mimicked the NO effect, respectively. Adherence of chondrocytes to fibronectin enhanced proteoglycan synthesis by twofold (vs. albumin). In addition, basic fibroblast growth factor (FGF) and insulin growth factor (IGF-1) induced proteoglycan synthesis in chondrocytes adherent to Fn but not albumin suggesting a costimulatory signal transduced by ␣ 5 ␤ l and the FGF receptor. Both constitutive and FGF stimulated proteoglycan synthesis were completely inhibited by nitric oxide. These data indicate that the ligation of ␣ 5 ␤ 1 in the chondrocyte induced the intracellular assembly of an activation complex comprised of the cytoplasmic tail of ␣ 5 ␤ 1 integrin, actin, and the signaling molecules rho A and FAK. We show that NO inhibits the assembly of the intracellular activation complex and the synthesis of proteoglycans, but has no effect on the extracellular aggregation of ␣ 5 ␤ 1 integrin. These observations provide a basis by which nitric oxide can interfere with chondrocyte functions by affecting chondrocyte-matrix interactions. (

Considering the acceptable local recurrence rate, conservative surgery aided by effective control of intraoperative hemorrhage should be considered as an alternative procedure for patients with giant cell tumors of the sacrum. The advantages include lower morbidity, reduced neurologic deficits, speed and ease of the surgical procedure, reduced blood loss, preservation of spinal and pelvic continuity, and a low recurrence rate.

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Patients with intraarticular resection and endoprosthetic replacement of the proximal humerus with reconstruction that included synthetic mesh had better shoulder function and ROM, and more stable joints than patients who had reconstruction without synthetic mesh. This result supports prior observations by others and it remains to be shown whether use of the ligament advanced reconstruction system is superior to other types of mesh or other types of reconstructions. Further investigation is needed but our results indicate that using mesh should be considered for patients with tumor resection and endoprosthetic replacement of the proximal humerus.

Background No available meta-analysis was printed to systematically introduce the MPNST clinic outcome and risk factors based on largely pooled data. This systematic review and meta-analysis aimed to investigate 5-year OS rate, 5-year EFS rate, and LR rate for MPNST, and to assess potential risk factors for prognosis. Methods Electronic articles published between January 1, 1966 and February 29, 2020 were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data for 5-year OS rate, 5-year EFS rate, LR rate, and potential risk factors for prognosis. Results Twenty-eight literatures were finally included for meta-analysis. The pooled 5-year OS rate, 5-year EFS rate, and LR rate were 49%, 37%, and 38%, respectively. The significant prognostic factors for survival were NF1 status, tumor size, depth, location, malignant grade, margin status, chemotherapy, and radiotherapy. Age and sex were not associated with survival. Conclusion Survival and local recurrence of MPNST are poor. Worse prognosis is mainly associated with NF 1, large size, deep to fascia, high grade, metastases, and location (trunk and head and neck). Complete resection with adequate surgical margins is the mainstay protective factor of MPNST patients, following necessary adjuvant therapies.