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1.  Palliative transpedicular partial corpectomy without anterior vertebral reconstruction in lower thoracic and thoracolumbar junction spinal metastases 
The thoracolumbar junction is the transition from a stiff (thoracic spine) to a mobile zone (lumbar spine) and is relatively unstable compared with the thoracic and lumbar portions of the spine. The need for anterior reconstruction after a corpectomy has been emphasized by several authors. However, for patients with a relatively short life expectancy, anterior reconstruction may be unnecessary. Posterior instrumentation alone may be sufficient to provide pain relief and stability for such patients. The goal of this study was to assess the postoperative outcomes and survival rates of patients with tumor metastases of the lower thoracic spine and thoracolumbar junction (T10–L1) who underwent transpedicular partial corpectomy without anterior vertebral reconstruction.
From November 2001 to February 2015, 29 patients diagnosed with symptomatic spinal cord compression caused by tumor metastasis involving T10 to L1 underwent palliative surgery that involved a posterolateral transpedicular partial corpectomy without anterior reconstruction. The surgical indication was neurologic progression. A follow-up was conducted for all of the patients, including reviewing medical records and performing an examination in the outpatient department.
The patients ranged in age from 33 to 83 years (mean, 61.6 years). Neurologic improvement by at least one Frankel grade was noted in 75.9 % of the patients (N = 22). Neither intraoperative mortality nor implant failure was reported. The median survival rate was 7.43 months (range, 0.47–28 months).
The results of this study suggest that the stability of implants can be maintained up to 28 months with satisfying functional outcome after a palliative posterolateral transpedicular partial corpectomy without anterior reconstruction.
PMCID: PMC4504462  PMID: 26183322
Anterior vertebral reconstruction; Cancer; Implant failure; Partial corpectomy; Posterior instrumentation; Posterolateral transpedicular approach; Spinal metastasis; Stability; Survival rate; Thoracolumbar junction tumor
2.  Tamoxifen use reduces the risk of osteoporotic fractures in women with breast cancer in Asia: a nationwide population-based cohort study 
Bone mineral density changes with tamoxifen treatment have been reported in pre- and post-menopausal women with breast cancer. However, there remains controversy as to whether tamoxifen significantly reduces fracture rates in different age groups. Breast cancer occurs at 10-20 years younger in Asian women compared with Western women. Therefore we conducted this population-based case-control study to determine whether or not tamoxifen use is associated with osteoporotic fractures.
Patients and methods
We selected 75488 women with breast cancer with no prior history of fractures from the Longitudinal Health Insurance Database for Catastrophic Illness Patients in 2000-2011. They were followed from the date of the diagnosis of breast cancer to the date a hip, vertebral or wrist fracture occurred. Because the use of tamoxifen was a time-dependent variable, we used a Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of a fracture.
There were 50257 and 25231 women with breast cancer who did and did not receive tamoxifen treatment, respectively. The tamoxifen users had lower risks for overall fractures with hazard ratios (HRs) of 0.52 and 0.59 in the crude and adjusted models (95 % CI = 0.45-0.61 and 0.51-0.69), respectively. They also had lower risks for hip (HR = 0.55, 95 % CI = 0.45-0.67) and vertebral (HR = 0.64, 95 % CI = 0.50-0.82) fractures in the adjusted model. The risk of fractures decreased with an increasing dosage of tamoxifen. Regardless of the age group, the tamoxifen users had a lower risk of fractures than the non-users.
In this Asian population-based case-control study, tamoxifen use was associated with a reduction in osteoporotic fractures, especially in hip fractures.
PMCID: PMC4438570  PMID: 25989902
Breast cancer; Fracture; Risk; Tamoxifen; Population-based cohort study
3.  CCL5 promotes VEGF-dependent angiogenesis by down-regulating miR-200b through PI3K/Akt signaling pathway in human chondrosarcoma cells 
Oncotarget  2014;5(21):10718-10731.
Chondrosarcoma is the second most common primary malignant bone cancer, with potential for local invasion and distant metastasis. Chemokine CCL5 (formerly RANTES) of the CC-chemokine family plays a crucial role in metastasis. Angiogenesis is essential for the cancer metastasis. However, correlation of CCL5 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma is still unknown. CCL5-mediated VEGF expression was assessed by qPCR, ELISA, and Western blotting. CCL5-induced angiogenesis was examined by migration and tube formation in endothelial progenitor cells in vitro. CCL5 increased VEGF expression and also promoted chondrosarcoma conditional medium-mediated angiogenesis in vitro and in vivo. Stimulation of chondrosarcoma with CCL5 augmented PI3K and Akt phosphorylation, while PI3K and Akt inhibitor or siRNA abolished CCL5-induced VEGF expression and angiogenesis. We also demonstrated CCL5 inhibiting miR-200b expression and miR-200b mimic reversing the CCL5-enhanced VEGF expression and angiogenesis. Moreover, in chondrosarcoma patients showed the positive correlation between CCL5 and VEGF; negative correlation between CCL5 and miR-200b. Taken together, results demonstrate CCL5 promoting VEGF-dependent angiogenesis in human chondrosarcoma cells by down-regulating miR-200b through PI3K/Akt signaling pathway.
PMCID: PMC4279405  PMID: 25301739
Angiogenesis; CCL5; Chondrosarcoma; miR-200b; VEGF
4.  Risk factors for subsidence in anterior cervical fusion with stand-alone polyetheretherketone (PEEK) cages: a review of 82 cases and 182 levels 
To determine risk factors for subsidence in patients treated with anterior cervical discectomy and fusion (ACDF) and stand-alone polyetheretherketone (PEEK) cages.
Materials and methods
Records of patients with degenerative spondylosis or traumatic disc herniation resulting in radiculopathy or myelopathy between C2 and C7 who underwent ACDF with stand-alone PEEK cages were retrospectively reviewed. Cages were filled with autogenous cancellous bone harvested from iliac crest or hydroxyapatite. Subsidence was defined as a decrease of 3 mm or more of anterior or posterior disc height from that measured on the postoperative radiograph. Eighty-two patients (32 males, 50 females; 182 treatment levels) were included in the analysis.
Most patients had 1–2 treatment levels (62.2 %), and 37.8 % had 3–4 treatment levels. Treatment levels were from C2–7. Of the 82 patients, cage subsidence occurred in 31 patients, and at 39 treatment levels. Multivariable analysis showed that subsidence was more likely to occur in patients with more than two treatment levels, and more likely to occur at treatment levels C5–7 than at levels C2–5. Subsidence was not associated with postoperative alignment change but associated with more disc height change (relatively oversized cage).
Subsidence is associated with a greater number of treatment levels, treatment at C5–7 and relatively oversized cage use.
PMCID: PMC4168225  PMID: 25099076
Anterior cervical discectomy; Fusion; Stand-alone; PEEK cage; Subsidence
5.  Adiponectin Enhances Intercellular Adhesion Molecule-1 Expression and Promotes Monocyte Adhesion in Human Synovial Fibroblasts 
PLoS ONE  2014;9(3):e92741.
Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and is involved in energy homeostasis. Adiponectin expression is significantly high in the synovial fluid of patients with osteoarthritis (OA). Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that mediates monocyte adhesion and infiltration during OA pathogenesis. Adiponectin-induced expression of ICAM-1 in human OA synovial fibroblasts (OASFs) was examined by using qPCR, flow cytometry and western blotting. The intracellular signaling pathways were investigated by pretreated with inhibitors or transfection with siRNA. The monocyte THP-1 cell line was used for an adhesion assay with OASFs. Stimulation of OASFs with adiponectin induced ICAM-1 expression. Pretreatment with AMP-activated protein kinase (AMPK) inhibitors (AraA and compound C) or transfection with siRNA against AMPKα1 and two AMPK upstream activator- liver kinase B1 (LKB1) and calmodulin-dependent protein kinase II (CaMKII) diminished the adiponectin-induced ICAM-1 expression. Stimulation of OASFs with adiponectin increased phosphorylation of LKB1, CaMKII, AMPK, and c-Jun, resulting in c-Jun binding to AP-1 element of ICAM-1 promoter. In addition, adiponectin-induced activation of the LKB1/CaMKII, AMPK, and AP-1 pathway increased the adhesion of monocytes to the OASF monolayer. Our results suggest that adiponectin increases ICAM-1 expression in human OASFs via the LKB1/CaMKII, AMPK, c-Jun, and AP-1 signaling pathway. Adiponectin-induced ICAM-1 expression promoted the adhesion of monocytes to human OASFs. These findings may provide a better understanding of the pathogenesis of OA and can utilize this knowledge to design a new therapeutic strategy.
PMCID: PMC3965461  PMID: 24667577
6.  HGF and c-Met Interaction Promotes Migration in Human Chondrosarcoma Cells 
PLoS ONE  2013;8(1):e53974.
Chondrosarcoma is a type of highly malignant tumor with a potent capacity for local invasion and causing distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Hepatocyte growth factor (HGF) has been demonstrated to stimulate cancer proliferation, migration, and metastasis. However, the effect of HGF on migration activity of human chondrosarcoma cells is not well known. Here, we found that human chondrosarcoma tissues demonstrated significant expression of HGF, which was higher than that in normal cartilage. We also found that HGF increased the migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. c-Met inhibitor and siRNA reduced HGF-increased cell migration and MMP-2 expression. HGF treatment resulted in activation of the phosphatidylinositol 3′-kinase (PI3K)/Akt/PKCδ/NF-κB pathway, and HGF-induced expression of MMP-2 and cell migration was inhibited by specific inhibitors or siRNA-knockdown of PI3K, Akt, PKCδ, and NF-κB cascades. Taken together, our results indicated that HGF enhances migration of chondrosarcoma cells by increasing MMP-2 expression through the c-Met receptor/PI3K/Akt/PKCδ/NF-κB signal transduction pathway.
PMCID: PMC3540013  PMID: 23320110
7.  CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling Pathway 
PLoS ONE  2012;7(12):e51097.
Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. CTGF is abundantly expressed in osteoarthritis (OA). However, the relationship between CTGF and IL-6 in OA synovial fibroblasts (OASFs) is mostly unknown.
Methodology/Principal Findings
OASFs showed significant expression of CTGF, and expression was higher than in normal SFs. OASFs stimulation with CTGF induced concentration-dependent increases in IL-6 expression. CTGF mediated IL-6 production was attenuated by αvβ5 integrin neutralized antibody and apoptosis signal-regulating kinase 1 (ASK1) shRNA. Pretreatment with p38 inhibitor (SB203580), JNK inhibitor (SP600125), AP-1 inhibitors (Curcumin and Tanshinone IIA), and NF-κB inhibitors (PDTC and TPCK) also inhibited the potentiating action of CTGF. CTGF-mediated increase of NF-κB and AP-1 luciferase activity was inhibited by SB203580 and SP600125 or ASK1 shRNA or p38 and JNK mutant.
Our results suggest that CTGF increased IL-6 production in OASFs via the αvβ5 integrin, ASK1, p38/JNK, and AP-1/NF-κB signaling pathways.
PMCID: PMC3515445  PMID: 23227240
8.  Hepatocyte Growth Factor Increases Osteopontin Expression in Human Osteoblasts through PI3K, Akt, c-Src, and AP-1 Signaling Pathway 
PLoS ONE  2012;7(6):e38378.
Hepatocyte growth factor (HGF) has been demonstrated to stimulate osteoblast proliferation and participated bone remodeling. Osteopontin (OPN) is a secreted phosphoglycoprotein that belongs to the SIBLING family and is present during bone mineralization. However, the effects of HGF on OPN expression in human osteoblasts are large unknown.
Methodology/Principal Findings
Here we found that HGF induced OPN expression in human osteoblasts dose-dependently. HGF-mediated OPN production was attenuated by c-Met inhibitor and siRNA. Pretreatment of osteoblasts with PI3K inhibitor (Ly294002), Akt inhibitor, c-Src inhibitor (PP2), or AP-1 inhibitor (curcumin) blocked the potentiating action of HGF. Stimulation of osteoblasts with HGF enhanced PI3K, Akt, and c-Src activation. In addition, incubation of cells with HGF also increased c-Jun phosphorylation, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the OPN promoter. HGF-mediated AP-1-luciferase activity and c-Jun binding to the AP-1 element was reduced by c-Met inhibitor, Ly294002, Akt inhibitor, and PP2.
Our results suggest that the interaction between HGF and c-Met increases OPN expression in human osteoblasts via the PI3K, Akt, c-Src, c-Jun, and AP-1 signaling pathway.
PMCID: PMC3366938  PMID: 22675553
9.  Endoscopic discectomy of L5-S1 disc herniation via an interlaminar approach: Prospective controlled study under local and general anesthesia 
Open discectomy remains the standard method for treatment of lumbar disc herniation, but can traumatize spinal structure and leaves symptomatic epidural scarring in more than 10% of cases. The usual transforaminal approach may be associated with difficulty reaching the epidural space due to anatomical peculiarities at the L5–S1 level. The endoscopic interlaminar approach can provide a direct pathway for decompression of disc herniation at the L5–S1 level. This study aimed to evaluate the clinical results of endoscopic interlaminar lumbar discectomy at the L5–S1 level and compare the technique feasibility, safety, and efficacy under local and general anesthesia (LA and GA, respectively).
One hundred twenty-three patients with L5–S1 disc herniation underwent endoscopic interlaminar lumbar discectomy from October 2006 to June 2009 by two spine surgeons using different anesthesia preferences in two medical centers. Visual analog scale (VAS) scores for back pain and leg pain and Oswestry Disability Index (ODI) sores were recorded preoperatively, and at 3, 6, and 12 months postoperatively. Results were compared to evaluate the technique feasibility, safety, and efficacy under LA and GA.
VAS scores for back pain and leg pain and ODI revealed statistically significant improvement when they were compared with preoperative values. Mean hospital stay was statistically shorter in the LA group. Complications included one case of dural tear with rootlet injury and three cases of recurrence within 1 month who subsequently required open surgery or endoscopic interlaminar lumbar discectomy. There were no medical or infectious complications in either group.
Disc herniation at the L5–S1 level can be adequately treated endoscopically with an interlaminar approach. GA and LA are both effective for this procedure. However, LA is better than GA in our opinion.
PMCID: PMC3130490  PMID: 21748045
General anesthesia; interlaminar approach; local anesthesia; lumbar disc herniation; percutaneous endoscopic discectomy
10.  Intradiscal electrothermal therapy in the treatment of chronic low back pain: Experience with 93 patients 
Low back pain (LBP) has become a main cause of absenteeism and disability in industrialized societies. Chronic LBP is an important health issue in modern countries. Discogenic LBP is one of the causes of chronic low back pain. The management of chronic discogenic LBP has been limited to either conservative treatment or operative treatment. Intradiscal electrothermal therapy (IDET) is now being performed as an alternative treatment.
Ninety-three consecutive patients undergoing IDET at 134 disc levels from October 2004 to January 2007 were prospectively evaluated. All patients had discogenic disease with chronic LBP, as determined by clinical features, physical examination and image studies, and had failed to improve with conservative treatment for at least 6 months. Follow-up period was from 1 week to 3 or more years postoperatively.
There were 50 male and 43 female patients, with a mean age of 46.07 years (range, 21-65 years). The results were classified as symptom free (100% improvement), better (≥50% improvement), slightly better (<50% improvement), unchanged and aggravated. Eighty-nine patients were followed up in the first week; of them, 77 (86.52%) patients had improvement (4, symptom free; 45, better; and 28, slightly better). The improvement rate gradually decreased to 80.90% in 1 year; and 73.91%, in 3 years.
In conclusion, IDET offers a safe, minimally invasive therapy option for carefully selected patients with chronic discogenic LBP who have not responded to conservative treatment. Although IDET appears to provide intermediate-term relief of pain, further studies with long-term follow-up are necessary.
PMCID: PMC2940097  PMID: 20847918
Chronic low back pain; intradiscal electrothermal therapy; discogenic pain
11.  Cyclooxygenase-2 enhances α2β1 integrin expression and cell migration via EP1 dependent signaling pathway in human chondrosarcoma cells 
Molecular Cancer  2010;9:43.
Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. Interaction of COX-2 with its specific EP receptors on the surface of cancer cells has been reported to induce cancer invasion. However, the effects of COX-2 on migration activity in human chondrosarcoma cells are mostly unknown. In this study, we examined whether COX-2 and EP interaction are involved in metastasis of human chondrosarcoma.
We found that over-expression of COX-2 or exogenous PGE2 increased the migration of human chondrosarcoma cells. We also found that human chondrosarcoma tissues and chondrosarcoma cell lines had significant expression of the COX-2 which was higher than that in normal cartilage. By using pharmacological inhibitors or activators or genetic inhibition by the EP receptors, we discovered that the EP1 receptor but not other PGE receptors is involved in PGE2-mediated cell migration and α2β1 integrin expression. Furthermore, we found that human chondrosarcoma tissues expressed a higher level of EP1 receptor than normal cartilage. PGE2-mediated migration and integrin up-regulation were attenuated by phospholipase C (PLC), protein kinase C (PKC) and c-Src inhibitor. Activation of the PLCβ, PKCα, c-Src and NF-κB signaling pathway after PGE2 treatment was demonstrated, and PGE2-induced expression of integrin and migration activity were inhibited by the specific inhibitor, siRNA and mutants of PLC, PKC, c-Src and NF-κB cascades.
Our results indicated that PGE2 enhances the migration of chondrosarcoma cells by increasing α2β1 integrin expression through the EP1/PLC/PKCα/c-Src/NF-κB signal transduction pathway.
PMCID: PMC2837621  PMID: 20178602

Results 1-11 (11)