Primary mobile vertebral column sarcomas: Prognostic factors vary by histologic subtypes.

BACKGROUND: Primary sarcomas originating from the mobile spine portends a particularly sinister outcome. Rarity of the disease process has resulted in inconsistent data due to small sample size and heterogeneity in patient selection and analytics. METHODS: Surveillance, Epidemiology and End Result (SEER) database from 1975 to 2017 was queried to report incidence and survival data in 712 patients in the United States. Kaplan-Meier and Cox Regression were used to determine the prognostic factors affecting survival. RESULTS: Incidence of spinal sarcoma was 0.019 per 100,000 persons in 2017 and has not significantly changed since 2000 (p > 0.05). Disease-specific 5-year survival for the entire cohort was 57%. Osteosarcoma has the worst 5-year survival (39%) and chondrosarcoma has the best 5-year survival (69%). Independent predictors of survival for the entire cohort included age, grade, and stage. Stage was an independent predictor of survival for every histologic subtype. Additional predictors of survival for spinal osteosarcoma, Ewing sarcoma, and chondrosarcoma included age, size, and grade, respectively. CONCLUSIONS: The current study is an analysis of a population-based registry reporting incidence survival data for patients with sarcoma of mobile vertebral column. Survival and prognostic factors vary by histologic subtypes. There is lack of improvement in survival over the last three decades.

A Cisplatin-Selective Fluorescent Probe for Real-Time Monitoring of Mitochondrial Platinum Accumulation in Living Cells.

Mitochondria have emerged as important targets for cisplatin in cancer therapy. Apart from cisplatin, anticancer Pt complexes based on similar scaffolds have also been developed to target mitochondria. Yet cellular processing of cisplatin or these mitochondria-targeting Pt analogues remained unexplored, largely due to a lack of tools capable of probing these Pt drugs within an intracellular environment. We developed the first mitochondria-targeted fluorescent probe for real-time monitoring of Pt accumulation in mitochondria. We applied the probe to investigate mitochondria as cellular targets for Pt drug complexes and uncovered two distinct pathways whereby these Pt complexes could be delivered to mitochondria after cell entry.

A Ratiometric Fluorescent Probe for Cisplatin: Investigating the Intracellular Reduction of Platinum(IV) Prodrug Complexes.

The PtIV prodrug strategy has emerged as an excellent alternative to tackle the problems associated with conventional PtII drug therapy. However, there is a lack of tools to study how this new class of PtIV drugs are processed at the cellular level. Herein, we report the first ratiometric probe for cisplatin detection and use it to investigate PtIV anticancer complexes in biological systems. The probe was able to distinguish between cisplatin and its PtIV derivatives, allowing us to probe the intracellular reduction of PtIV prodrug complexes. The correlation between the amount of active PtII species available after intracellular reduction of PtIV complexes and their cytotoxicity and the role glutathione plays in the reduction of PtIV complexes were investigated.

Stable Toll-Like Receptor 10 Knockdown in THP-1 Cells Reduces TLR-Ligand-Induced Proinflammatory Cytokine Expression.

Toll-like receptor 10 (TLR10) is the only orphan receptor whose natural ligand and function are unknown among the 10 human TLRs. In this study, to test whether TLR10 recognizes some known TLR ligands, we established a stable TLR10 knockdown human monocytic cell line THP-1 using TLR10 short hairpin RNA lentiviral particle and puromycin selection. Among 60 TLR10 knockdown clones that were derived from each single transduced cell, six clones were randomly selected, and then one of those clones, named E7, was chosen for the functional study. E7 exhibited approximately 50% inhibition of TLR10 mRNA and protein expression. Of all the TLRs, only the expression of TLR10 changed significantly in this cell line. Additionally, phorbol 12-myristate 13-acetate-induced macrophage differentiation of TLR10 knockdown cells was not affected in the knockdown cells. When exposed to TLR ligands, such as synthetic diacylated lipoprotein (FSL-1), lipopolysaccharide (LPS), and flagellin, significant induction of proinflammatory cytokine gene expression including Interleukin-8 (IL-8), Interleukin-1 beta (IL-1ß), Tumor necrosis factor-alpha (TNF-α) and Chemokine (C-C Motif) Ligand 20 (CCL20) expression, was found in the control THP-1 cells, whereas the TLR10 knockdown cells exhibited a significant reduction in the expression of IL-8, IL-1ß, and CCL20. TNF-α was the only cytokine for which the expression did not decrease in the TLR10 knockdown cells from that measured in the control cells. Analysis of putative binding sites for transcription factors using a binding-site-prediction program revealed that the TNF-α promoter does not have putative binding sites for AP-1 or c-Jun, comprising a major transcription factor along with NF-κB for TLR signaling. Our results suggest that TLR10 is involved in the recognition of FSL-1, LPS, and flagellin and TLR-ligand-induced expression of TNF-α does not depend on TLR10.

In vitrocellular biocompatibility andin vivodegradation behavior of calcium phosphate-coated ZK60 magnesium alloy.

Calcium phosphate (Ca-P) surface coating is a simple but effective way to enhance both corrosion resistance and biocompatibility of ZK60 magnesium alloy. However, cell compatibility on different Ca-P layers coated on ZK60 alloy has seldom been investigated. In this study, the effects of type, morphology and corrosion protection of several Ca-P coatings formed at pH 6.5, 7.8 and 10.2 on cell behavior were examined by using an osteoblastic cell line MC3T3-E1. Furthermore,in vivobehavior in rabbits of the alloy coated with the optimum Ca-P layer was also studied. It was found that the surface factors governed the cell morphology and density. The coating morphology plays a dominant role in these surface factors. The sample coated at pH 7.8 showed the best cellular biocompatibility, suggesting that the hydroxyapatite (HAp) layer formed at pH 7.8 was the optimum coating. In rabbits, this optimum coating enhanced remarkably the corrosion resistance of the alloy. During implantation, the outermost crystals of the HAp coating were shortened and thinned due to the dissolution of HAp caused by the body fluid of the rabbits. It is indicated that ZK60 alloy coated at pH 7.8 can be applied as a biodegradable implant.

Comparing Fusion Rates Between Fresh-Frozen and Freeze-Dried Allografts in Anterior Cervical Discectomy and Fusion.

Objective: The objective of this retrospective study is to compare the fusion rates in anterior cervical discectomy and fusion surgery using freeze-dried versus fresh-frozen allografts. Methods: The study comprised 79 patients. Fifty-one patients received freeze-dried allograft (106 total spinal levels) and 28 patients received fresh-frozen allograft (50 total spinal levels). Fusion was assessed through trabecular bridging on follow-up anterior-posterior/lateral radiographs. Trabecular bridging was assessed on the superior and inferior borders of each spinal level and given a fusion grade. Complete fusion is defined as >50% bridging between superior and inferior borders of the bone graft; union is complete fusion in <26 weeks; delayed union is complete fusion after 26 weeks; and fibrous union is <50% bridging at ≥1 borders over 52 weeks. Results: All spinal levels reached complete fusion for both graft types. Of the freeze-dried treated cervical spinal levels, 77.35% (82/106) reached union (adequate trabecular bridging within 6 months) without delay compared with 80% (35/50) for the fresh-frozen bone graft group (P = 0.85). There was no significant difference in time-to-fusion analysis and no significant association between delayed union and any patient factors. In assessing Neck Disability Index (NDI), freeze-dried allografts did show a significantly greater decrease in NDI scores at 6 months (P = 0.03). At the 1 year follow-up, improvements in NDI were consistent in both allografts (P = 0.9647). Conclusions: From this study, freeze-dried and fresh-frozen allografts showed comparable rates of union, and both allografts can be used interchangeably for anterior cervical discectomy and fusion.

Highly cytotoxic gold(i)-phosphane dithiocarbamate complexes trigger an ER stress-dependent immune response in ovarian cancer cells.

Ovarian cancer is a highly aggressive disease which is treated by surgery and platinum chemotherapy. However, a significant proportion of treated patients develop resistance to platinum treatment resulting in tumor relapse. Acquired platinum resistance has been recently correlated with activation of pro-survival endoplasmic reticulum (ER) stress responses. We hypothesized that Au complexes that induce severe ER stress might counteract pro-survival cellular attempts leading to the ER stress-mediated apoptosis and reduced platinum resistance. In this work, we prepared a series of highly cytotoxic AuI-dialkyldithiocarbamate complexes and investigated their anticancer potential in ovarian cancer cells. Complexes demonstrated surprisingly low stability in chloroform, resulting in the formation of an Au chain polymer, which also displayed excellent cytotoxicity. Lead complex 2 induced oxidative stress and ER stress-mediated p53-independent apoptosis associated with PARP cleavage and cell cycle arrest at G2/M phase. Importantly, 2 caused the surface exposure of calreticulin (CRT), which is the first step in the activation of cellular immunogenic response.