Fei Sheng

CEP55 promotes the proliferation and invasion of tumour cells via the AKT signalling pathway in osteosarcoma

The molecular mechanisms underlying the development of osteosarcoma (OS) are not fully understood. In this study, we investigated for the first time the clinical significance and biological activity of centrosomal protein 55 (CEP55) in OS. We found that CEP55 was overexpressed in OS, and the CEP55 expression level in OS was correlated with metastasis and poor prognosis. Through in vitro experiments, we confirmed that CEP55 knockdown significantly induced cell cycle arrest at G1 phase and suppressed OS cell proliferation, migration and invasion. In addition, CEP55 knockdown suppressed OS tumour growth in nude mice. Global gene expression profiling of CEP55-silenced MNNG/HOS cells showed that the AKT pathway might be involved in the regulation of OS cell activity. Two downstream factors of AKT signalling, CCND1 and FN1, were found to have significantly higher expression in tumour tissues, and their mRNA expression levels were strongly correlated with CEP55 expression. To conclude, our data suggest that CEP55 can be used as a prognostic marker for OS, highlighting the significance of CEP55 signalling as a putative therapeutic target.

Grayscale Inversion View Can Improve the Reliability for Measuring Proximal Junctional Kyphosis in Adolescent Idiopathic Scoliosis

BACKGROUNDnProximal junctional kyphosis (PJK) is a common phenomenon after long segmental fusion surgery of adolescent idiopathic scoliosis. However, the inability to reliably identify vertebral endplates on lateral upright radiographs has made an accurate measurement of proximal junctional angle (PJA) technically impossible in many patients. The aim of this study was to determine whether a grayscale inversion view is more reliable to measure PJA and to assess PJK accurately.nnnMETHODSnA total of 162 patients with adolescent idiopathic scoliosis who underwent posterior spinal fusion surgeries were included in this study. PJA was measured on preoperative lateral standing films using 3 methods (upper-instrumented vertebrae [UIV]xa0+ 1, UIVxa0+ 2, and UIV to T2) on both standard view and grayscale inversion view. Two physicians independently measured the PJA twice at a 1-month interval. Intra- and interobserver reliabilities were compared between the 2 radiographic views. Forty patients with preoperative magnetic resonance imaging (MRI) scans were randomly selected. PJA was measured for these patients on both views of lateral standing films and MRI images. The correlation coefficients between PJA obtained on MRI and PJA obtained on radiographs with different views were calculated respectively.nnnRESULTSnThe intraclass correlation coefficients were greater in a grayscale inversion view than in a standard view in all 3 methods for both observers, and the intraclass correlation coefficients of interobserver reliabilities also were greater in a grayscale inversion view. The correlation coefficient between PJA obtained on grayscale inversion view and preoperative MRI was greater in all methods compared with standard view.nnnCONCLUSIONSnGrayscale inversion view can be a more reliable tool for the evaluation of PJK as compared with the conventional measurement. We recommend the application of a grayscale inversion view to measure PJA and assess PJK in clinical practice, particularly for patients instrumented to the upper thoracic spine.

Variants of FasL and ABCC5 are predictive of outcome after chemotherapy-based treatment in osteosarcoma

Objectives Previous pharmacogenetics studies showed that genetic variants could be indicative of the response to chemotherapy. We aimed to investigate whether variants of FasL, MSH2, ABCC5, CASP3 and CYP3A4 are associated with the outcome after chemotherapy-based treatment in osteosarcoma. Methods 132 osteosarcoma patients who had completed the neoadjuvant chemotherapy in our center were included. 5-year progression-free survival (PFS) was assessed from the initial treatment to the earliest sign of disease progression or death from any cause. 5 SNPs were genotyped using TaqMan SNP Genotyping Assay, including rs763110 of FasL, rs4638843 of MSH2, rs939338 of ABCC5, rs2720376 of CASP3 and rs4646437 of CYP3A4. Patients were classified into two groups according to the 5-year PFS (event/no event). The chi-square test was used to analyze difference of genotype frequency. Logistic regression analysis was used to determine the independent predictors of the PFS rate. Results The overall 5-year PFS was 61.4% (81/132). Genotype TT/CT of rs763110 and genotype GG/AG of rs939338 were significantly associated with the event of 5-year PFS (pu202f=u202f0.028 for rs763110; pu202f=u202f0.039 for rs939338). Patients with no risk allele showed a 5-year PFS of 73.7% (42/57), which was significantly higher than a PFS of 54.2% (26/48) for patients with one risk allele and 48.1% (13/27) for patients with two different risk alleles (p = 0.03). Logistic regression analysis showed that allele T of FasL rs763110 and allele G of ABCC5 rs939338 were independent risk factors of the 5-year PFS. The ORs were 2.14 (95%CIu202f=u202f1.13–3.35, pu202f=u202f0.01) for rs763110 and 1.73 (95%CIu202f=u202f1.05–2.52, pu202f=u202f0.03) for rs939338, respectively. Conclusions The association of variants of FASL and ABCC5 with survival outcome after chemotherapy was validated in patients with osteosarcoma. Our findings may provide a new insight into a more personalized treatment for patients with osteosarcoma.

A promoter variant of lncRNA GAS5 is functionally associated with the development of osteosarcoma

Highlights • The genetic variant rs145204276 is associated with the susceptibility of OS.• Patients with genotype del/del of rs145204276 had significantly higher expression of GAS5 in the OS tissues.• SNP rs145204276 could play a functional role in the development and progression of OS by altering the methylation status of GAS5 promoter.

An effective delivery vehicle of demineralized bone matrix incorporated with engineered collagen-binding human bone morphogenetic protein-2 to accelerate spinal fusion at low dose

AbstractThe aim of this study was to investigate the feasibility and efficacy of a new delivery matrix using demineralized bone matrix (DBM) incorporated with collagen-binding bone morphogenetic protein-2 (CBD-BMP-2) in the rat inter-transverse spinal fusion model. Sixty rats undergoing posterolateral (inter-transverse) spinal fusion were divided into 3 groups according to the fusion materials containing different components (nu2009=u200920 per group). Group A were implanted with DBM, Group B with combination of DBM and BMP-2 and Group C with combination of DBM and CBD-BMP-2. After surgery, the spinal fusion of all the rats was assessed by plain radiography, CT + 3D reconstruction, manual palpation and histological evaluation. Significant difference was found in terms of solid fusion rate among the three groups, with 95% in Group C, 65% in Group B and 0% in Group A (Pu2009<u20090.001). Compared with Groups B and A, new bone formation was observed earlier and was obvious larger, trabecular bone microarchitecture assessment was better and bone mineral density was statistically larger in Group C. In addition, more newly woven bone and osteocytes were shown by histological evaluation in Group C at 4 weeks post-operation. The present study showed CBD domain could help BMP-2 to improve the efficiency of posterolateral spinal fusion. DBM scaffold activated by collagen-binding BMP-2 was a feasible and promising bone repair vehicle.Graphical abstractThe present study showed better results in terms of plain radiography, CT + 3D reconstruction, manual palpation and histological evaluation in the rat inter-transverse spinal fusion model using DBM+CBD-BMP-2, compared with DBM+BMP-2 and DBM alone, indicating DBM scaffold activated by collagen-binding BMP-2 was a feasible and promising bone repair vehicle.n

Natural History of Postoperative Adding-On in Adolescent Idiopathic Scoliosis: What Are the Risk Factors for Progressive Adding-On?

Purpose To investigate the natural history of distal adding-on in adolescent idiopathic scoliosis (AIS) and to identify risk factors for its progression. Methods Sixty-one AIS patients with distal adding-on occurrence were included. We further classify distal adding-on into progressive and nonprogressive group according to its natural evolution. The first radiograph indicating initiation of adding-on (primary adding-on) and the last follow-up radiograph were compared in terms of the deviation of the first vertebra below instrumentation from the CSVL and the angulation of the first disc below instrumentation. Compared to primary adding-on, progressive adding-on was defined as a further increase of deviation > 5u2009mm or a further increase of angulation > 5°. Risk factors associated with the progression of adding-on were analyzed. Results Among 61 patients diagnosed with distal adding-on, 24 (39.3%) were progressive and 37 (60.7%) were nonprogressive. Lower Risser grade, open triradiate cartilage, and lowest instrumented vertebra (LIV) proximal to Substantially Stable Vertebra (SSV) were found to be significantly associated with the progressive adding-on. Besides, the distal adding-on was more likely to progress for patients with higher left shoulders than right ones after surgery. Conclusions The risk factors for the progression of adding-on included skeletal immaturity, LIV proximal to SSV, and higher left shoulders after surgery.