Incidences and reasons of postoperative surgical site infection after lumbar spinal surgery: a large population study.

PURPOSE: The purpose of this study was to determine the incidences of postoperative acute surgical site infection (SSI) after lumbar spinal surgery and its possible reasons in our hospital during the past 9 years. METHODS: This is a retrospective study with a large sample size. The medical records of all included patients were reviewed, and patients with acute SSI were identified. The incidence and possible reasons of SSI were determined. RESULTS: A total of 7240 patients who underwent posterior lumbar spinal surgery were included in this study, and the total incidence of postoperative SSI was 1.53% (111/7240). Gram-negative bacteria were found to be dominant in postoperative wound infections after lumbar spinal surgery. And Escherichia coli were the most common pathogen in patients with SSI. The rate of postoperative SSI following lumbar spinal surgery was increased at first and then decreased during the past 9 years. Additionally, from 2011 to 2014, it was mainly deep infection in these patients, and then was mainly superficial infection from 2015 to 2019. Patients with lumbar spinal stenosis had the highest incidence of postoperative SSI (2.39%, P < 0.001). There was also a significant difference for the number of SSI cases among different surgeons. CONCLUSION: Based on a large population analysis, Gram-negative bacteria were the most common pathogen in postoperative SSI after lumbar spinal surgery. And patients with lumbar spinal stenosis had the highest incidence of SSI. Increasing the intervention of Gram-negative may be an important step to reduce the postoperative SSI after lumbar spinal surgery.

Neuron-specific enolase, histopathological types, and age as risk factors for bone metastases in lung cancer.

Lung cancer is a malignant tumor with high metastatic ability and bone is the most common site of distant metastasis of it. However, the independent risk factors for bone metastases of lung cancer remain largely to be elucidated. Here, we conducted a retrospective study to evaluate the correlation between clinical-pathological parameters, serum levels of neuron-specific enolase and CYFRA21-1, and bone metastases in lung cancer patients. The results revealed that patients with bone metastases were younger than those without metastases. Adenocarcinoma was the most frequent type of histopathology in patients with bone metastases. And the incidence of bone metastasis in patients with adenocarcinoma was significantly higher than those with other histopathological subtypes ( p < 0.001). Furthermore, the serum concentration of neuron-specific enolase was significantly higher in patients with bone lesions than those without bone metastases. Multivariate logistic regression analysis showed that patients' age (odds ratio = 1.024, p < 0.001), concentrations of neuron-specific enolase (odds ratio = 1.212, p = 0.004), and histopathological types (odds ratio = 0.995, p = 0.001) were the independent risk factors for bone metastases in patients with lung cancer. Thus, physicians should pay attention to these factors in order to identify bone metastasis earlier while patient was primarily diagnosed as having lung cancer.

Demethylation-mediated miR-129-5p up-regulation inhibits malignant phenotype of osteogenic osteosarcoma by targeting Homo sapiens valosin-containing protein (VCP).

Previous studies demonstrated that increased Homo sapiens valosin-containing protein (VCP) may be involved in osteosarcoma (OS) metastasis. However, the underlying mechanism of VCP over-expression in OS remains unknown. In the present study, we found a significantly negative correlation between miR-129-5p and VCP protein expression in OS tissues with pulmonary metastasis (Spearman's rho, rs = -0.948). Bioinformatical prediction, Luciferase reporter assay, Western blot, and RT-PCR assays performed on OS cells indicated that VCP is a target of miR-129-5p. In addition, three CPG islands in the region of miR-129-5p promoter were detected by bioinformatical prediction, and significantly higher expression of miR-129-5p and lower methylation level of miR-129-2 gene in OS cells treated with 5-Aza-2'-deoxycytidine (a potent DNA demethylating agent) than in those untreated cells were observed. Furthermore, lower migratory and invasive ability was found in cells with elevated miR-129-5p than in those with decreased miR-129-5p. These findings indicated that increased miR-129-5p may be mediated by demethylation and inhibit OS cell migration and invasion by targeting VCP in OS, and targeting miR-129-5p/VCP signaling pathway may serve as a therapeutic strategy for OS management, although further studies will be necessary.

Inhibition of fatty acid synthase suppresses U-2 OS cell invasion and migration via downregulating the activity of HER2/PI3K/AKT signaling pathway in vitro.

FASN plays an important role in the malignant phenotype of various tumors. Our previous studies show that inhibition FASN could induce apoptosis and inhibit proliferation in human osteosarcoma (OS) cell in vivo and vitro. The aim in this study was to investigate the effect of inhibition FASN on the activity of HER2/PI3K/AKT axis and invasion and migration of OS cell. The expression of FASN, HER2 and p-HER2(Y1248) proteins was detected by immunohistochemistry in OS tissues from 24 patients with pulmonary metastatic disease, and the relationship between FASN and p-HER2 as well as HER2 was investigated. The results showed that there was a positive correlation between FASN and HER2 as well as p-HER2 protein expression. The U-2 OS cells were transfected with either the FASN specific RNAi plasmid or the negative control RNAi plasmid. FASN mRNA was measured by RT-PCR. Western blot assays was performed to examine the protein expression of FASN, HER2, p-HER2(Y1248), PI3K, Akt and p-Akt (Ser473). Migration and invasion of cells were investigated by wound healing and transwell invasion assays. The results showed that the activity of HER2/PI3K/AKT signaling pathway was suppressed by inhibiting FASN. Meanwhile, the U-2OS cells migration and invasion were also impaired by inhibiting the activity of FASN/HER2/PI3K/AKT. Our results indicated that inhibition of FASN suppresses OS cell invasion and migration via down-regulation of the "HER2/PI3K/AKT" axis in vitro. FASN blocker may be a new therapeutic strategy in OS management.

The risk factors for postoperative ileus following posterior thoraco-lumbar spinal fusion surgery.

OBJECTIVE: Postoperative ileus (PI) is a common complication following posterior thoraco-lumbar spinal fusion surgery. It usually slows patient's recovery and increases postoperative morbidity. However, the risk factors associated with PI in patients undergoing posterior thoraco-lumbar spinal fusion surgery are still unclear. The purpose of this study is to investigate the potential risk factors for PI in those patients. PATIENTS AND METHODS: A prospective study was conducted and 426 patients received posterior thoraco-lumbar spinal fusion surgery between March 2017 and February 2018 were included in this study. The associations between different clinical factors and PI were analyzed. A logistic regression analysis was performed to detect independent risk factors for PI. The cut-off value, sensitivity and specificity of these independent factors were calculated by receiver operating characteristic (ROC) curve. RESULTS: In this study, 8.2% (35/426) of these patients were identified with PI. The average length of postoperative hospital stay was 12.54 ±â€¯6.06 days in patients with PI compared with 8.91 ±â€¯3.81 days in patients without PI (P =  0.001). These results indicated that surgical duration, PLIF approach, blood loss and length of postoperative diet restriction were potential risk factors for PI in patients with thoraco-lumbar spinal fusion surgery. The cut-off values of surgical duration, blood loss and length of postoperative diet restriction were 4.375 h, 750 ml and 9.5 h, respectively. Combination of surgical duration, PLIF approach, blood loss and length of postoperative diet restriction has the highest predictive value for PI (AUC = 0.910, P <  0.001). CONCLUSION: Based on the study, surgical duration, PLIF approach, blood loss and length of postoperative diet restriction were the independent risk factors for PI in patients with posterior thoraco-lumbar spinal fusion surgery. Combined those factors has the highest risk for developing PI.

Are Routine Postoperative Laboratory Tests Really Necessary After Lumbar Spinal Surgery?

BACKGROUND: For patients undergoing lumbar spinal surgery, many surgeons routinely perform laboratory tests within 3 days after surgery. However, few studies have reported the necessity for routine laboratory tests for patients with uncomplicated cases within 3 days after surgery. METHODS: We performed a retrospective study of patients with lumbar degenerative disease who had undergone lumbar spinal surgery from May 2014 to May 2017. The perioperative patient information was recorded. The abnormal postoperative laboratory tests were recorded. Finally, the incidence and risk factors for patients requiring postoperative clinical treatment were analyzed. RESULTS: A total of 1915 patients were included in the present study. Postoperative laboratory tests had been ordered for 870 patients (45.43%). Of these patients, only a small proportion had required postoperative clinical intervention to treat abnormal serum hemoglobin (2.53%), albumin (1.95%), serum potassium (0.92%), or serum calcium (6.55%) levels. Multivariate logistic regression analysis showed that female gender and operative time were risk factors for the need for blood transfusion after lumbar spinal surgery. Age and operative time were risk factors for patients requiring albumin supplementation after lumbar spinal surgery. Finally, intraoperative blood loss and operative time were independent risk factors for patients requiring calcium supplementation after surgery. CONCLUSIONS: Owing to the small number of postoperative clinical interventions for abnormal laboratory test results, we believe that the use of routine laboratory tests within 3 days after lumbar spinal surgery for patients with uncomplicated cases are unnecessary. Our results showed that operative time is a potential risk factor for the necessity for clinical treatment after lumbar spinal surgery.

Potential Molecular Mechanisms of AURKB in the Oncogenesis and Progression of Osteosarcoma Cells: A Label-Free Quantitative Proteomics Analysis.

Our previous study indicated that knockdown of Aurora-B inhibit the proliferation of osteosarcoma cells. But the function and molecular mechanisms of Aurora-B in osteosarcoma cells growth and metastasis remains unclear. The aim of this study was to investigate the molecular mechanisms of Aurora-B in the progression of osteosarcoma. Osteosarcoma cells (U2-OS and 143B) were treated with specific Lentivirus-Vectors (up or downregulation Aurora-B). The ability of cells proliferation, migration, and invasion was measured using Cell-Counting Kit-8, wound healing and transwell invasion assays. Furthermore, based on label-free quantitative proteomic analysis of potential molecular mechanisms of Aurora-B in human 143B cells. A total of 25 downregulated and 76 upregulated differentially expressed proteins were screened in terms of the change in their expression abundance. We performed functional annotation and functional enrichment analyses. Gene ontology enrichment, KEGG analysis, and protein-protein interaction networks were constructed and analyzed. We found that the PTK2 may play an important role in the progression of osteosarcoma cells. Finally, Western blot revealed that expression of PTK2, AKT, PI3K, and nuclear factor-kappaB increased after over expression of Aurora-B. Overall, these data highlight that Aurora-B may promote the malignant phenotype of osteosarcoma cells by activating the PTK2/PI3K/AKt/nuclear factor-KappaB pathway.

Let-7a inhibits osteosarcoma cell growth and lung metastasis by targeting Aurora-B.

PURPOSE: Accumulating studies showed that the expression of microRNAs (miRNAs) was dysregulated in osteosarcoma (OS). In this study, we sought to investigate the effect of let-7a on OS progression and its potential molecular mechanism. PATIENTS AND METHODS: Quantitative real-time PCR (qRT-PCR) was performed to evaluate the expression level of let-7a and Aurora-B (AURKB) in OS tissues and cells. The OS cells were treated with let-7a mimic, let7a inhibitor, negative mimic and Lv-AURKB combined with let-7a. The ability of cell proliferation, migration and invasion was measured using Cell Counting Kit-8 (CCK-8) and wound-healing and transwell invasion assays. The protein of AURKB, NF-κßp65, MMP2 and MMP9 was measured by Western blot analysis. Xenograft model was performed to investigate the effects of let-7a on tumor growth and metastasis. The lung metastasis was measured by counting the metastatic node using H&E staining. RESULTS: Let-7a expression was significantly underexpressed in OS cell lines and tissues compared with human osteoblast cell lines, hFOB1.19, and adjacent normal bone tissues. Exogenous let-7a inhibited the viability, migratory and invasive ability of OS cells in vitro. In addition, the overexpression of AURKB in OS cells could partly rescue let-7a-mediated tumor inhibition. Also, the overexpression of let-7a inhibited OS cell growth and lung metastasis in vivo. Furthermore, the results showed that let-7a could decrease the expression of NF-κßp65, MMP2 and MMP9 proteins by targeting AURKB in OS cells. CONCLUSION: Let-7a inhibits the malignant phenotype of OS cells by targeting AURKB at least partially. Targeting let-7a and AURKB/NF-κß may be a novel therapeutic strategy for the treatment of OS.

The risk factors of bone metastases in patients with lung cancer.

The risk factors of bone metastasis in patients with lung cancer are still unclear. Here, a retrospective study including a series of consecutive patients who were diagnosed with lung cancer between January 2005 and November 2016 was carried out. A total of 2021 patients with lung cancer were included in this study and 23.9% of them were found to be bone metastases. For patients with bone metastases, adenocarcinoma (62.1%) was the most common pathological subtype, and rib (62.3%) was the most frequent distant metastatic site, followed by thoracic (53.8%) and lumbar spine (40.4%). The histopathologic type, CA-125 level and the concentration of alkaline phosphatase (ALP) were identified as the independent risk factors for bone metastases in lung cancer (P = 0.002, P = 0.001 and P < 0.001). The sensitivities and specificities of diagnosing bone metastasis by CA-125 were 32.1% and 80.8%, and by ALP were 41.3% and 77.1%, respectively. Thus, the incidence of bone metastases in lung cancer patients was relative high, and physicians should pay attention to the histopathologic type, the serum CA-125 and ALP concentrations when patients were firstly diagnosed with lung cancer for early detecting bone metastases.

Blocking fatty acid synthase inhibits tumor progression of human osteosarcoma by regulating the human epidermal growth factor receptor 2/phosphoinositide 3-kinase/protein kinase B signaling pathway in xenograft models.

Previous studies have demonstrated that fatty acid synthase (FASN) is overexpressed in osteosarcoma (OS) cells and tissues and, therefore, knockdown of FASN may inhibit OS cell proliferation, migration and invasion via regulation of the human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase (PI3K)/protein kinase B(Akt) signaling pathway in vitro. However, the tumor microenvironment has a crucial role in the determination of tumor malignant phenotype. The aim of the present study was to investigate the effect of knockdown of FASN on OS progression and the potential molecular mechanism in nude mice with orthotopic tumor implants in vivo. Results demonstrated that the knockdown of FASN markedly suppressed the growth and metastasis of OS, at least partially, by blocking the HER2/PI3K/Akt signal pathway in mice with intratibial 143B OS xenografts. These results suggest that the FASN/HER2/PI3K/Akt signaling pathway may be a potential therapeutic target for OS management.

HELQ reverses the malignant phenotype of osteosarcoma cells via CHK1-RAD51 signaling pathway.

HELQ is a DNA helicase important for repair of DNA lesions and has been linked to several types of cancer. However, little is known about its relationship with osteosarcoma (OS) and its mechanism. In the present study, the expression of HELQ and its downstream mediators in OS cells was assayed by quantitative PCR and western blot analysis. The function of HELQ in OS cells was investigated by Transwell invasion, wound healing, CCK8 assays and Comet assay. The results demonstrated that HELQ gene and protein were expressed in OS cells. OS cell invasion, migration, proliferation and DNA damage repair were enhanced by HELQ knock-down with shRNA-lentivirus and inhibited by HELQ overexpression with lentivirus transfection. Furthermore, the antitumor activities of HELQ may be associated with upregulated expression of the DNA damage-related proteins CHK1 and RAD51. Our findings indicated that HELQ confers an anti-invasive phenotype on OS cells by activating the CHK1-RAD51 signaling pathway and suggested that HELQ could be recognized as a promising therapeutic target for OS and other types of malignant tumors.

One-stage posterior surgical management of lumbosacral spinal tuberculosis with nonstructural autograft.

OBJECTIVE: Lumbosacral spinal tuberculosis is rare in current population. Previous studies have reported effective outcomes about anterior, antero-posterior and posterior surgery for treating tuberculosis of lumbosacral region. However, the bone grafts used in these studies are mainly structural bone and mesh cage. The purpose of this study is to evaluate the efficacy and safety of nonstructural autograft in the surgical treatment of lumbosacral tuberculosis by one-stage posterior procedure. PATIENTS AND METHODS: A total of 21 patients with lumbosacral tuberculosis were retrospectively reviewed between January 2012 and December 2014. All the patients underwent one-stage posterior debridement, interbody fusion with nonstructural autograft and posterior instrumentation. The preoperative and postoperative erythrocyte sedimentation rates (ESR), C-reactive protein (CRP) and visual analogue scale (VAS) were recorded. Preoperative and postoperative lumbosacral angle and intervertebral space height were measured on the plain films. American Spinal Injury Association (ASIA) Impairment Scale was used to evaluate the neurological outcomes of the patients. RESULTS: The average follow up period was 22.9±6.7months (range 12-36 months). The preoperative ESR and CRP were 33.4±10.5mm/h and 30.3±20.3mg/l, respectively, which decreased to 15.2±7.1mm/h and 10.6±5.8mg/l postoperatively with significant differences (P<0.05). The lumbosacral angles and intervertebral space height were increased from preoperative 20.4°±4.5° and 9.7±1.9mm to postoperative 25.6°±4.6° and 12.3±2.1mm, respectively (P<0.001 and P<0.001). At the final follow up, a loss of 2.1°of lumbosacral angles and 1.6mm of intervertebral space height was observed. The VAS scores were decreased from 4.73 to 2.71. Bony fusion was achieved in all patients at 6 months after surgery. Neurological outcomes were improved with 1-2 grades in most of the patients. One patient got wound infection and was cured by daily dressing. Complications related to instrumentation or neurological deficit weren't observed. CONCLUSION: Combined with one-stage posterior debridement and instrumentation, interbody fusion with nonstructural autograft is an effective option for lumbosacral tuberculosis.

A comparison of local bone graft with PEEK cage versus iliac bone graft used in anterior cervical discectomy and fusion.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is a popular procedure for patients with cervical spondylotic myelopathy, but few studies reported the clinical outcomes of cervical local bone graft with a PEEK cage used in it. This retrospective study was performed to compare the clinical and radiological outcomes of using local bone graft with a PEEK cage versus iliac bone graft in ACDF. PATIENTS AND METHODS: A total of 60 consecutive patients who underwent ACDF were evaluated from January 2010 to January 2013. Twenty-nine patients received ACDF with a PEEK cage combined with cervical local bone graft (local bone group) and 31 patients received ACDF with autologous tricortical iliac bone graft (iliac bone group). The intraoperative and perioperative complications of both groups were recorded. Preoperative and postoperative radiographs were taken to calculate the ratio of interbody height to the disc height and the interbody bony fusion rate. The Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) were used to estimate postoperative clinical outcomes. RESULTS: The mean follow-up duration was 25.0±3.8months in the local bone group and 24.4±3.4months in the iliac bone group (P=0.56). Although there was no significant difference between the two groups in terms of blood loss (P=0.17), the length of surgery was significantly less in the local bone group comparing with that of iliac bone group (P=0.01). Postoperatively, VAS scores were significantly decreased, and JOA scores were improved in both groups. However, no statistically significant differences were found between the two groups at final follow up (P=0.45 and P=0.93). The disc space height and segmental interbody angle at the surgical segment were greater in local bone group than those in the iliac bone group (P<0.001 and P<0.001). The fusion rates were 93.1% in local bone group and 90.3% in the iliac bone group at last follow up (P=0.70). Perioperative complication rates in local bone group and iliac bone groups were 6.8% and 29%, respectively (P=0.04). CONCLUSIONS: Based on this study, patients receiving ACDF with local bone graft combined with a PEEK cage had significant shorter operation time, lower perioperative complications rate, and better radiological results comparing with those with an iliac bone graft alone. It seems that the local bone graft with a PEEK cage appears to be a safe alternative to the iliac bone graft for ACDF.

Serum calcium, alkaline phosphotase and hemoglobin as risk factors for bone metastases in bladder cancer.

Early detection of bone metastases is helpful for the treatment of bladder cancer (BC). In this study, we investigated the potential risk factors for bone metastasis in newly diagnosed patients with BC. A total of 902 patients diagnosed with BC between January 2000 and August 2016 were retrospectively reviewed. Of these patient, 50 (5.5%) were identified with bone metastasis. The serum levels of alkaline phosphatase (ALP) and calcium were significantly higher in patients with bone metastases than those without bone metastases (P = 0.015 and P<0.001). And the concentration of hemoglobin (HB) was significant lower in bone metastatic patients compared with non bone metastatic patients (P = 0.009). Multivariate logistic regression analysis indicated that ALP, HB and calcium were independent risk factors for bone metastases in patients with BC. The cut off values of ALP, HB and calcium were 116 U/L, 37.5g/L and 2.54 mmol/L according to the receiver operating characteristic (ROC) curves analysis. And combined ALP, HB with calcium had the highest diagnostic accuracy for predicting bone metastases in BC patients (AUC = 0.760, P<0.001). Therefore, for newly diagnosed patients with BC, the concentrations of ALP >116 U/L, HB <37.5 g/Land calcium >2.54 mmol/L were the risk factors for developing bone metastases. Combined ALP, HB with calcium was more useful to diagnose the bone metastases.

Transcription factor NF­YA promotes a malignant phenotype by upregulating fatty acid synthase expression.

Recent studies have revealed that increased expression of the alpha subunit of nuclear transcription factor Y (NF­YA) is associated with the malignant phenotype of various tumors. However, whether elevated expression of NF­YA promotes a malignant phenotype in osteosarcoma (OS), and the molecular mechanisms underlying this predicted effect is currently unknown. In the present study, small hairpin RNA (shRNA)­mediated knockdown of endogenous NF­YA significantly inhibited the migration and invasion capabilities of OS cells in vitro, whereas ectopic expression of NF­YA increased the migration and invasion capabilities of these cells. In addition, the induction of upregulated NF­YA expression on the malignant phenotype of OS cells was attenuated by silencing fatty acid synthase (FASN) expression. Furthermore, the expression level of FASN was increased by upregulating NF­YA, while decreased FASN expression was observed following NF­YA silencing in OS cells. The results of the present study suggest that NF­YA may promote a malignant phenotype in OS cells, in part, by activating the FASN signaling pathway, which may represent a promising target for the management of OS.

Unplanned Reoperation of Lumbar Spinal Surgery During the Primary Admission: A Multicenter Study Based on a Large Patient Population.

STUDY DESIGN: A retrospective study. OBJECTIVE: The purpose of this study was to identify the rates and reasons, and the risk factors for unplanned reoperation of lumbar spinal surgery during the primary admission in terms of a multicenter and a large patient population study. SUMMARY OF BACKGROUND DATA: Unplanned reoperation is suggested to be a useful quality indicator for spinal surgery. However, the rates of unplanned reoperation in patients underwent lumbar spinal surgery during the primary admission are not well established. METHODS: This study was performed to review all the patients who underwent lumbar spinal surgery at three institutions from January 2010 to April 2015. Patients with unplanned reoperations after primary surgery during the same admission were included in this study. The demographics, diagnosis, surgical procedure, and complications of patients were reviewed and statistical analysis was performed to investigate the incidences and risk factors of unplanned revision. RESULTS: A total of 3936 patients who underwent lumbar spinal surgery from three institutions were reviewed, and 82 (2.08%) required unplanned reoperation during the primary admission because of wound infection (0.94%), screw misplacement (0.53%), cerebrospinal fluid leakage (0.27%), wound hematoma (0.18%), and neurologic deficit (0.15%). For the diagnosis, patients with lumbar spinal spondylolisthesis had a much higher rate of reoperation (4.3%) than those of lumbar stenosis (2.3%), vertebral tumor (2.2%), vertebral fracture (1.2%), and disc herniation (1.1%) with a significant difference (P < 0.001). The revision rate was significantly higher in patients underwent posterior lumbar interbody fusion than those received transforaminal lumbar interbody fusion (P = 0.007). CONCLUSION: Unplanned reoperation rate of lumbar spinal surgery was 2.08% and the most common reasons for it were wound infection and screw misplacement. Patients with a diagnosis of lumbar spinal spondylolisthesis or who underwent posterior lumbar interbody fusion were more likely to required unplanned reoperation during the primary admission. LEVEL OF EVIDENCE: 4.

LY294002 inhibits the malignant phenotype of osteosarcoma cells by modulating the phosphatidylinositol 3­kinase/Akt/fatty acid synthase signaling pathway in vitro.

Increasing evidence suggests that fatty acid synthase (FASN) is crucial in the carcinogenesis of various types of tumor. In addition, the phosphatidylinositol 3­kinase (PI3K)/Akt signaling pathway, which is closely associated with cellular metabolism, affects cancer biology. However, whether the malignant phenotype of osteosarcoma (OS) cells is regulated by the PI3K/Akt/FASN signaling pathway and how the PI3K family specific inhibitor, 2­(4­morpholinyl)­8­phenyl­chromone (LY294002) affects the malignant phenotype of OS cells remains to be elucidated. In the present study, U2­OS and MG­63 cells were treated with LY294002 and subsequently western blot analysis was used to examine Akt, p­Akt and FASN protein expression. Additionally, FASN mRNA was detected by reverse transcription quantitative polymerase chain reaction. MTT and fluorescence­activated cell sorting assays were used to assess proliferation and apoptosis. Migration and invasion were investigated using wound healing and transwell invasion assays. The results demonstrated that LY294002 suppressed the PI3K/Akt/FASN signaling pathway. However, the malignant phenotypes of OS cells mentioned above were significantly inhibited. The present results indicated that LY294002 inhibits the malignant phenotype of OS cells via modulation of the PI3K/Akt/FASN signaling pathway in vitro and may be a new therapeutic strategy for the management of OS.

Inhibition of Aurora-B suppresses HepG2 cell invasion and migration via the PI3K/Akt/NF-κB signaling pathway in vitro.

In the present study, the effect of Aurora-B inhibition on HepG2 cell invasion and migration in vitro was investigated. A recombinant plasmid targeting the Aurora-B gene (MiR-Aurora-B) was used to inhibit Aurora-B expression in HepG2 cells. Cell migration and invasion were investigated using Transwell migration and invasion assays. The results demonstrated that cell invasion and migration were suppressed by inhibiting Aurora-B. In addition, the effect of Aurora-B inhibition on the activity of the phosphoinositide 3-kinase (PI3K)/Akt/nuclear factor (NF)-κB signaling pathway was investigated by analyzing the protein expression levels of phosphorylated (p)-Akt, Akt, NF-κB p65, matrix metalloproteinase (MMP)-2 and MMP-9 using western blot analysis. The results demonstrated that the protein expression levels of p-Akt, NF-κB p65, MMP-2 and MMP-9 were reduced significantly by inhibiting Aurora-B. Therefore, inhibition of Aurora-B was shown to suppress hepatocellular carcinoma cell migration and invasion by decreasing the activity of the PI3K/Akt/NF-κB signaling pathway in vitro.

LY294002 suppresses the malignant phenotype and sensitizes osteosarcoma cells to pirarubicin chemotherapy.

Pirarubicin is frequently used in chemotherapy against tumors. However, clinical use is severely limited by the development of progressive dose-dependent cardiomyopathy and acquired drug resistance. LY294002 is a commonly used pharmacologic inhibitor, which selectively inhibits the phosphoinositide 3-kinase-AKT nexus. The aim of this study was to investigate the combined inhibitory effect of LY294002 and pirarubicin on human osteosarcoma (OS) cells in vitro. The inhibitory effect of LY294002 plus pirarubicin on U2-OS and MG-63 OS cell proliferation, apoptosis, migration and invasion was investigated by cell proliferation, wound healing and Transwell invasion assays. The results revealed that LY294002 and pirarubicin synergistically induced apoptosis, and inhibited the growth, migration and invasion of OS cells. This indicates that LY294002 enhanced the effects of pirarubicin on OS in vitro. LY294002 combined with pirarubicin may thus be a future therapeutic strategy in OS.

Inhibition of Aurora-B suppresses osteosarcoma cell migration and invasion.

Previous studies have suggested that Aurora-B may be involved in cancer metastasis. However, its role has been poorly evaluated in osteosarcoma (OS). The aim of this study was to investigate the correlation between Aurora-B expression and metastasis in human OS. The human OS cell line, U2-OS, and OS biopsy specimens were used in the study. The expression of Aurora-B protein was examined using immunohistochemistry and western blotting in OS tissues and U2-OS cells, respectively. AZD1152-hydroxyquinazoline-pyrazol-anilide, an inhibitor of Aurora-B, was used to inhibit Aurora-B expression in U2-OS cells. The effect of Aurora-B inhibition on U2-OS cell proliferation, invasion and migration was assessed using MTT, colony formation, wound healing and Transwell assays. The results showed that positive expression of the Aurora-B protein was observed in the nucleus, and that Aurora-B expression levels in the cases with pulmonary metastases were significantly higher than in those without metastasis. In vitro, the proliferation, invasion and migration of U2-OS cells were suppressed by the inhibition of Aurora-B. These results suggest that Aurora-B may be involved in OS metastasis, and may be a promising target in the treatment of OS metastasis.