Search

Kehan Xu,1,* Jialin Li,1,* Mengzi Hu,2,* Hao Zhang,1 Jian Yang,1 Haiyi Gong,1 Bo Li,1 Wei Wan,1 Jianru Xiao1 1Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 2Department of Orthopedics, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianru Xiao; Wei Wan Email jianruxiao83@smmu.edu.cn; ggflyfish@126.comPurpose: The purpose of this retrospective study was to identify preoperative inflammatory biomarkers and clinical parameters and evaluate their prognostic significance in patients with spinal metastasis from clear cell renal cell carcinoma (CCRCC).Patients and methods: Correlations of overall survival (OS) with traditional clinical parameters and inflammatory indicators including the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), albumin–globulin ratio (AGR), and C-reactive protein to albumin ratio (CRP/Alb ratio) were analyzed in 95 patients with spinal metastasis from CCRCA using the Kaplan–Meier method to identify potential prognostic factors. Factors with P values ≤ 0.1 were subjected to multivariate analysis by Cox regression analysis. P values ≤ 0.05 were considered statistically significant.Results: The 95 patients included in this study were followed up by a mean of 48.8 months (median 51 months; range 6–132 months), during which 21 patients died, with a death rate of 22.1%. The statistical results indicated that patients with total piecemeal spondylectomy (TPS), targeted therapy, NLR < 3.8 and PLR < 206.9 had a significantly longer OS rate.Conclusion: TPS and targeted therapy could significantly prolong the OS of patients with spinal metastasis from CCRCC. In addition, NLR and PLR are robust and convenient prognostic indicators that have a discriminatory ability superior to other inflammatory biomarkers.Keywords: clear cell renal cell carcinoma, spinal metastasis, overall survival, prognosis, inflammatory biomarkers

Metformin, an ancient drug commonly used for treating type II diabetes, has been associated to anti-cancer capacity in a variety of developing cancers, though the mechanism remains elusive. Here, we aimed to examine the inhibitory effect of metformin in osteosarcoma. Herein, we demonstrated that metformin treatment blocked proliferation progression by causing accumulation of G2/M phase in U2OS and 143B cells. Furthermore, metformin treatment triggered programmed cell death process in osteosarcoma cell lines. Further research indicated the induction of apoptosis and autophagy triggered by metformin could remarkably attenuate after the treatment of ROS scavenger NAC and JNK inhibitor SP600125. Additionally, our results showed that NAC-suppressed JNK/c-Jun signaling pathway could have been activated through metformin treatment. Lastly, metformin could inhibit osteosarcoma growth under safe dose in vivo. Thus, we propose that metformin could induce cell cycle arrest as well as programmed cell death, including apoptosis and autophagy, through ROS-dependent JNK/c-Jun cascade in human osteosarcoma. This metformin-induced pathway provides further insights into its antitumor potential molecular mechanism and illuminates potential cancer targets for osteosarcoma.

Introduction Amphiphysin 1 (AMPH-1) is involved in endocytosis, and its expression is upregulated in osteosarcoma compared with osteofibrous dysplasia. Methods We investigated the role of AMPH-1 in osteosarcoma cells via both gain-of-function and loss-of-function experiments. Results Knockdown of AMPH-1 in osteosarcoma cells promoted cell cycle progression and cell proliferation and attenuated apoptosis. Notably, silencing AMPH-1 increased osteosarcoma progression in a mouse tumor model. The results obtained upon AMPH-1 knockdown and AMPH-1 overexpression indicates that AMPH-1 is involved in regulating MEK/ERK signaling. Conclusion These data suggest that AMPH-1 plays an important role in osteosarcoma and may represent a novel therapeutic target for osteosarcoma treatment.

Retrospective survival analysis of 44 undifferentiated high grade pleomorphic sarcoma (UPS) of the spine.To identify factors related to overall survival (OS) and help decision making in the treatment of undifferentiated high grade pleomorphic sarcoma of the spine.UPS is an aggressive malignant tumor rarely originating from the spine. Due to its scarcity, only a few studies had been reported to describe the clinical features, treatments, and outcomes of sporadic cases, devoid of evaluation on prognostic factors.Enrolled in this survival analysis were 44 patients who underwent surgery and adjuvant therapies from January 1999 to December 2015. Kaplan-Meier methods were applied to estimate the overall survival. A multivariate Cox algorithm was applied to recognize factors independently associated with overall survival.Multivariate analysis suggested that age greater than or equal to 55 years (hazard ratio [HR], 3.923, P 0.001), Eastern Cooperative Oncology Group (ECOG) score four (HR, 4.656, P 0.001), and subtotal resection or piecemeal total resection (HR, 4.375, P 0.001) were independently associated with poor overall survival.We identified independent prognostic factors of UPS of the spine. Subtotal resection or piecemeal total resection, age more than or equal to 55 years and ECOG score four are factors adversely affecting overall survival of patients with UPS of the spine.4.

A retrospective study of 46 patients with malignant epithelioid vascular tumors (MEVT) in the spine was performed.The purpose of this study was to illustrate the clinic characteristics of MEVT in the spine and to discuss prognostic factors by survival analysis.MEVT in the spine is relatively uncommon, and there is little published information regarding this subject. Therefore, prognostic factors of this disease are still controversial.The univariate and multivariate analysis of various clinic characteristics were performed to identify the independent factor that affects prognosis for patients with MEVT in the spine who underwent surgical treatment in Changzheng Hospital Orthopedics Oncological Center (CHOOC) between 2005 and 2015. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method to identify potential prognostic factors. Factors with P values of 0.1 or less were subjected to multivariate analysis by Cox regression analysis. P values of 0.05 or less was considered statistically significant.A total of 46 patients with MEVT in the spine were included in the study. The mean follow-up period was 42.6 months (range, 5-143 mo). Recurrence was detected in 22 patients after initial surgery in our center, whereas death in 18 patients. The univariate analysis suggested that age (30 yr/≥30 yr), metastasis, preoperative Frankel score, postoperative Frankel score, malignant grade and resection mode were potential prognostic factors for DFS and OS. However, as they were submitted to multivariate analyses, only malignant grade and resection mode were independent prognostic factors.Total en bloc spondylectomy can significantly improve DFS for MEVT in the spine and low-grade malignancy was favorable factor for DFS. Total spondylectomy and low-grade malignancy considerably improve OS for patients with MEVT in the spine.4.

Background: A retrospective study of patients with repeatedly recurrent spinal chordoma (RRSC) was performed. The objective of this study was to evaluate the independent prognostic factors for RRSC improving life expectancy and discuss the most appropriate treatment modality. Methods: Medical data and follow-up record of patients who were diagnosed as RRSC and were surgically treated in Changzheng hospital between July 2010 and September 2017 were reviewed systematically. Univariate and multivariate analysis were performed to identify possible independent prognostic factors for patients with RRSC. Recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier method. Factors with P < 0.1 were subjected to multivariate analysis by Cox regression analysis. P < 0.05 was considered statistically significant. Results: Sixty-five consecutive patients with RRSC were included in this study. Local recurrence was detected in thirty-three patients, while death was occurred in twenty-one patients. The mean follow-up period was 34.3 months. The statistical results revealed that number of recurrence (NOR), surgical method, and surgical margin were independent prognostic factors for RFS and preoperative Frankel score (PFS) was favorable prognostic factor for OS. Moreover, subtype analysis suggested that treatment method could make significant difference for prognosis of patients with RRSC. Conclusion: Less NOR, total resection, and wide surgical margin could significantly reduce the risk of local recurrence of RRSC. PFS of A-C was adverse prognostic factor for OS. Total en bloc resection or total piecemeal resection with postoperative radiotherapy is recommended as ideal treatment method for prolonging life expectancy.