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1.
Transl Cancer Res ; 8(2): 542-551, 2019 Apr.
Article in English | MEDLINE | ID: mdl-35116786

ABSTRACT

BACKGROUND: Chordoma is a low-grade aggressive bone tumor with a high local recurrence. MicroRNAs (miRNAs) have been reported to play crucial roles in the development of chordoma. Our previous study has shown miR-1290 is associated with muscle invasion and the prognosis of chordoma. However, the underlying mechanism of miR-1290 in chordoma remains unclear. In this study, we aimed to explore the function of miR-1290 in the biological behaviors of chordoma. METHODS: Sixteen sacral chordoma samples and 10 fetal nucleus pulposus specimens were collected for the detection of miR-1290 and Robo1 at the First Affiliated Hospital of Soochow University. Bioinformatic analysis and a luciferase reporter assay was used to verify the interaction between miR-1290 and the target gene robo1 in chordoma. Effects of miR-1290 expression on chordoma cell proliferation and invasion were explored by clone formation and Transwell assay in vitro. The underlying mechanisms of miR-1290 and Robo1 in chordoma cell proliferation and invasion were also explored in the U-CH1 cell line. RESULTS: In vitro functional analysis, including clone formation, and Transwell assays indicated overexpression of miR-1290 significantly suppressed chordoma cell proliferation and invasion. Bioinformatic analysis revealed Robo1 as a potential target of miR-1290, and luciferase reporter assays demonstrated the association between miR-1290 and the Robo1 gene in U-CH1 cells. Robo1 was further confirmed to be up-regulated in chordoma tissues by immunohistochemistry (IHC), which is negatively correlated with miR-1290 expression in chordoma tissue. Additionally, we found down-regulation of miR-1290 could induce the expression of Robo1 in chordoma cells, while the elevation of miR-1290 expression could inhibit Robo1 expression in chordoma cells. CONCLUSIONS: miR-1290 inhibits chordoma cell proliferation and invasion by negatively regulating the Robo1 gene.

2.
Oncotarget ; 8(68): 112623-112635, 2017 Dec 22.
Article in English | MEDLINE | ID: mdl-29348851

ABSTRACT

Chordoma is a rare bone tumor with high recurrence rate, but the mechanism of its development is unclear. Long non-coding RNAs(lncRNAs) are recently revealed to be regulators in a variety of biological processed by targeting on mRNA transcription. Their expression profile and function in chordoma have not been investigated yet. In this study, we firstly performed the comprehensive analysis of the lncRNA and coding genes expression analysis with three chordoma samples and three fetal nucleus pulposus tissues. lncRNA and gene microarrays were used to determine the differentially expressed lncRNAs and protein coding genes. 2786 lncRNAs and 3286 coding genes were significantly up-regulated in chordoma, while 2042 lncRNAs and 1006 coding genes were down-regulated. Pearson correlation analysis was conducted to correlate differentially expressed lncRNAs with protein coding genes, indicating a comprehensive lncRNA-coding gene co-expression network in chordoma. Cis-correlation analysis showed that various transcripts of MEG3 and MEG8 were paired with the most differentially expressed gene DLK1. As located in the same locus, we further analyzed the miRNA clusters in this region, and identified that 61.22% of these miRNAs were significantly down-regulated, implying the silence of the imprinted gene cluster DLK1-MEG3. Overexpression of MEG3 suppressed the proliferation of chordoma cells. Our study pointed out the potential role of lncRNAs in chordoma, presented the lncRNA-coding genes co-expression profile, and revealed that imprinted gene cluster DLK1-MEG3 contributes to the pathogenesis of chordoma development.

3.
Biomed Res Int ; 2016: 4085305, 2016.
Article in English | MEDLINE | ID: mdl-27034937

ABSTRACT

PURPOSE: To evaluate whether subacromial osteolysis, one of the major complications of the clavicle hook plate procedure, affects shoulder function. METHODS: We had performed a retrospective study of 72 patients diagnosed with a Neer II lateral clavicle fracture or Degree-III acromioclavicular joint dislocation in our hospital from July 2012 to December 2013. All these patients had undergone surgery with clavicle hook plate and were divided into two groups based on the occurrence of subacromial osteolysis. By using the Constant-Murley at the first follow-up visit after plates removal, we evaluated patients' shoulder function to judge if it has been affected by subacromial osteolysis. RESULTS: We have analyzed clinical data for these 72 patients, which shows that there is no significant difference between group A (39 patients) and group B (33 patients) in age, gender, injury types or side, and shoulder function (the Constant-Murley scores are 93.38 ± 3.56 versus 94.24 ± 3.60, P > 0.05). CONCLUSION: The occurrence of subacromial osteolysis is not rare, and also it does not significantly affect shoulder function.


Subject(s)
Clavicle/surgery , Fractures, Bone/surgery , Osteolysis/physiopathology , Postoperative Complications/physiopathology , Shoulder/surgery , Adolescent , Adult , Aged , Bone Plates , Clavicle/physiopathology , Female , Fracture Fixation, Internal/methods , Fractures, Bone/complications , Fractures, Bone/physiopathology , Humans , Male , Middle Aged , Shoulder/physiopathology , Shoulder Dislocation/physiopathology , Shoulder Dislocation/surgery
4.
Int J Clin Exp Pathol ; 8(11): 14741-8, 2015.
Article in English | MEDLINE | ID: mdl-26823799

ABSTRACT

Sacral chordoma is a rare spine tumor with a high recurrence rate even after optimal therapy. Previous studies have demonstrated that the PI3K/AKT pathway plays a pivotal role in chordoma, and high expression of pAKT is associated with poor prognosis. Recently, PHLPP was recognized to be a tumor suppressor that targets AKT. We analyzed the expression of PHLPP1 and AKT2 in 37 chordoma samples and 11 fetal nucleus pulposus samples by immunohistochemical staining. Of the chordoma cases, 40.5% (15/37) showed strong cytoplasmic staining (score ≥3) for PHLPP1, which was significantly lower than the 90.9% (10/11) of fetal nucleus pulposus samples (P = 0.004). Conversely, strong immunohistochemical staining for AKT2 was observed in 75.7% (28/37) of chordoma samples, which was significantly higher than 36.4% (4/11) of fetal nucleus pulposus (P = 0.021). Kaplan-Meier survival curves and log-rank test showed that patients with high expression of PHLPP1 experienced longer progression free survival time than those with low PHLPP1 expression (P = 0.011). Further multivariate Cox regression analysis indicated that PHLPP1 expression level and surgical approaches were independent risk factors for chordoma recurrence (P = 0.023 and P = 0.022). However, PHLPP1 expression was not statistically related to patients' total survival time. Conclusively, our results suggest that PHLPP1 plays a crucial role in sacral chordoma, and may be a promising biomarker for prognosis. Meanwhile, manipulation of PHLPP1 expression is also a potential therapeutic approach for the treatment of sacral chordoma.


Subject(s)
Biomarkers, Tumor/analysis , Chordoma/pathology , Nuclear Proteins/biosynthesis , Phosphoprotein Phosphatases/biosynthesis , Spinal Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Chordoma/mortality , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Nuclear Proteins/analysis , Phosphoprotein Phosphatases/analysis , Polymerase Chain Reaction , Prognosis , Proportional Hazards Models , Sacrum/pathology
5.
Med Oncol ; 31(11): 247, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25260803

ABSTRACT

Sacral chordoma is an aggressive bone tumor with a high local recurrence rate. Surgery remains the standard treatment because of its resistance to chemotherapy and radiotherapy. However, recurrence occurs frequently even after complete surgical resection. Great effort has been invested in discovering novel biomarkers and therapeutic targets. To date, the molecular mechanism is still unclear. In this study, we evaluated the expression of sphingosine kinase 1 (SPHK1) in 42 sacral chordoma samples and 16 distant normal tissue specimens by immunohistochemical staining. In addition, we analyzed its association with the clinical factors and patients' prognosis. Of all the chordoma samples, 69 % (29/42) showed high expression of SPHK1, whereas, only 19 % (3/16) of distant normal tissues expressed a high level of SPHK1 (p = 0.001). Chi-square analysis revealed that high expression of SPHK1 was significantly correlated with tumor recurrence (p = 0.019) and invasion into surrounding muscle (p = 0.005), while the data did not indicate any association with patients' gender, age, tumor location and size (p > 0.05). Kaplan-Meier survival curve and log-rank test showed that patients with high expression of SPHK1 possessed shorter continuous disease-free survival time. Conclusively, SPHK1 may become a potential biomarker for sacral chordoma in predicting its recurrence and patients' prognosis.


Subject(s)
Adaptor Proteins, Signal Transducing/biosynthesis , Biomarkers, Tumor/biosynthesis , Chordoma/metabolism , Gene Expression Regulation, Neoplastic , Sacrum/metabolism , Spinal Neoplasms/metabolism , Adolescent , Adult , Aged , Chordoma/diagnosis , Disease-Free Survival , Follow-Up Studies , Humans , Middle Aged , Prognosis , Sacrum/pathology , Young Adult
6.
Med Oncol ; 31(4): 886, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24535608

ABSTRACT

Sacral chordoma is an aggressive, locally invasive neoplasm, and has a poor prognosis. However, the molecular basis for the clinical behavior remains unknown. The purpose of this study was to investigate the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and mammalian target of rapamycin (mTOR) in sacral chordoma, and explore their roles in the prognosis. PTEN and mTOR were detected immunohistochemically in 40 sacral chordoma tissues and 10 adjacent normal tissues. Correlations between PTEN and mTOR expression and clinicopathological factors were analyzed. Kaplan-Meier survival curves and log-rank test were used to analyze the continuous disease-free survival time (CDFS). The expression of PTEN in sacral chordoma was significantly lower than that in adjacent normal tissues, while the levels of mTOR expression in sacral chordoma were significantly higher than that in adjacent normal tissues (P = 0.000, P = 0.030). The positive expression of mTOR appears to correlate with the negative expression of PTEN in sacral chordoma (P = 0.021). PTEN-negative expression and mTOR-positive expression were associated with tumor invasion into the surrounding muscles (P = 0.038, P = 0.014). Log-rank test showed that PTEN-negative and mTOR-positive expressions had an important impact on the patients' CDFS (P = 0.011, P = 0.015). Our results suggest that PTEN and mTOR might play an important role in the local invasiveness of sacral chordoma. PTEN and mTOR might be recognized as important prognostic predictors of recurrence and could be used as potential therapeutic targets for the treatment for sacral chordoma.


Subject(s)
Chordoma/metabolism , Gene Expression Regulation, Neoplastic , PTEN Phosphohydrolase/metabolism , Sacrum/pathology , Spinal Neoplasms/metabolism , TOR Serine-Threonine Kinases/metabolism , Adolescent , Adult , Aged , Biomarkers, Tumor/metabolism , Chordoma/diagnosis , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Spinal Neoplasms/diagnosis , Young Adult
7.
Oncol Lett ; 6(1): 251-255, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23946813

ABSTRACT

The present study aimed to assess a posterior approach for the surgical resection of giant sacral neurogenic tumors, and to evaluate the oncological and functional outcomes. A total of 16 patients with giant sacral neurogenic tumors underwent pre-operative embolization and subsequent posterior sacral resection between January 2000 and June 2010. Benign tumors were identified in 12 cases, while four cases exhibited malignant peripheral nerve sheath tumors (MPNSTs). An evaluation of the operative techniques used, the level of blood loss, any complications and the functional and oncological outcomes was performed. All tumor masses were removed completely without intra-operative shock or fatalities. The mean tumor size was 17.5 cm (range, 11.5-28 cm) at the greatest diameter. The average level of intra-operative blood loss was 1,293 ml (range, 400-4,500 ml). Wound complications occurred in four patients (25%), including three cases of cutaneous necrosis and one wound infection. The mean follow-up time was 59 months (range, 24-110 months). Tumor recurrence or patient mortality as a result of the disease did not occur in any of the patients with benign sacral neurogenic tumors. The survival rate of the patients with malignant lesions was 75% (3/4 patients) since 25 % (1/4 patients) had multiple local recurrences and succumbed to the disease. The patients with benign tumors scored an average of 92.8% on the Musculoskeletal Tumor Society (MSTS) score functional evaluation, while the patients with malignant tumors scored an average of 60.3%. A posterior approach for the surgical resection of giant sacral neurogenic tumors, combined with pre-operative embolization may be safely conducted with satisfactory oncological and functional outcomes.

8.
Int J Pharm ; 441(1-2): 285-90, 2013 Jan 30.
Article in English | MEDLINE | ID: mdl-23194887

ABSTRACT

Oral administration of celecoxib (Clx), which is the traditional treatment for osteoarthritis (OA), is accompanied by a high risk for cardiovascular events, while intra-articular injection of hyaluronate (HA) is a well-documented treatment for knee OA. To improve OA therapy while reducing the adverse effects, we formulate Clx-loaded liposomes embedded in HA gel, then administer the liposomal Clx-HA combination via intra-articular injection. Clx-loaded liposomes showed high efficiency encapsulation (>99%). In vitro release studies demonstrated that the release of Clx from lipsosomes was delayed by the combination of HA with liposomes. We examined the effect of intra-articular injection of liposomal Clx-HA combination on cartilage degeneration in rabbit knee OA model. The rabbits were treated with a single intra-articular injection of a single drug, either Clx liposome or HA, or liposomal Clx-HA combination. Using an incapacitance tester and the histopathological study, it was verified that the liposomal Clx-HA combination was more effective than a single drug in pain control and cartilage protection.


Subject(s)
Arthritis, Experimental/drug therapy , Hyaluronic Acid/pharmacology , Osteoarthritis, Knee/drug therapy , Pyrazoles/pharmacology , Sulfonamides/pharmacology , Animals , Arthritis, Experimental/physiopathology , Cartilage, Articular/drug effects , Cartilage, Articular/pathology , Celecoxib , Cyclooxygenase 2 Inhibitors/administration & dosage , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/toxicity , Gels , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/toxicity , Injections, Intra-Articular , Liposomes , Osteoarthritis, Knee/physiopathology , Pain/drug therapy , Pain/etiology , Pyrazoles/administration & dosage , Pyrazoles/toxicity , Rabbits , Sulfonamides/administration & dosage , Sulfonamides/toxicity , Viscosupplements/administration & dosage , Viscosupplements/pharmacology , Viscosupplements/toxicity
10.
J Clin Neurosci ; 18(6): 763-7, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21507652

ABSTRACT

Despite the literature supporting the efficacy of kyphoplasty for treatment of osteoporotic vertebral compression fractures in multiple myeloma, few reports exist documenting its use in the treatment of malignant vertebral compression fractures (MVCF) caused by metastases. Accordingly, we sought to evaluate the feasibility, efficacy and safety of kyphoplasty in the treatment of MVCF without epidural involvement. We performed a retrospective review of clinical outcome data for 48 patients with multiple spinal metastases treated with kyphoplasty. Outcome data (vertebral body height variation, degree of kyphosis, visual analog scale score for pain, Oswestry Disability Index score, the Short Form-36 [SF-36] questionnaire score for function) were collected preoperatively, postoperatively, and at 1 month, 6 months, 1 year, and 2 years after treatment. Significant improvements in all of the outcome measures were observed postoperatively and throughout the duration of follow-up. The mean anterior vertebral body height variation improved from 52.7 ± 16.8% preoperatively to 85.3% ± 13.2% postoperatively (p < 0.001). Kyphotic angle improved from 16.4° ± 4.7° preoperatively to 8.4° ± 2.5° postoperatively (p < 0.001). The mean visual analog scale score decreased significantly from presurgery to postsurgery (7.4 ± 2.1 to 3.8 ± 1.6; p<0.001), as did the Oswestry Disability Index score (71.5 ± 16.7 to 32.4 ± 9.6; p<0.001). The SF-36 scores for bodily pain, physical function, vitality, and social functioning all also showed significant improvement (p<0.05). Kyphoplasty is an effective, minimally invasive procedure for the stabilization of pathological vertebral fractures caused by metastatic disease, even in levels with vertebral wall deficiency, leading to a statistically significant reduction in pain, improvement in function and prevention of further kyphotic deformity of the spine.


Subject(s)
Fractures, Compression/etiology , Fractures, Compression/surgery , Kyphoplasty/methods , Neoplasm Metastasis/physiopathology , Spinal Neoplasms/complications , Aged , Aged, 80 and over , Cohort Studies , Female , Fracture Fixation, Internal/methods , Fractures, Compression/diagnostic imaging , Humans , Male , Middle Aged , Pain Measurement , Retrospective Studies , Spinal Fractures/surgery , Spinal Neoplasms/secondary , Thoracic Vertebrae/surgery , Time Factors , Tomography, X-Ray Computed/methods , Treatment Outcome
12.
J Neurooncol ; 101(3): 357-63, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20549300

ABSTRACT

Sacral chordoma is a vessel-rich and infiltrative tumor, but the fundamental knowledge of its biological behavior remains unknown. This study was designed to investigate the expression levels and contributions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the angiogenesis and recurrence of sacral chordoma and their correlations. An immunohistochemical method was used to investigate the expression of VEGF, MMP-9, and microvascular density (MVD) in 36 patients with sacral chordoma. Their differences in expressions were statistically analyzed and their correlations with angiogenesis and recurrence were evaluated. The mean MVD of sacral chordomas was significantly higher than that of the adjacent normal tissues (P = 0.033). Immunoreactivity for VEGF and MMP-9 was significantly higher in sacral chordoma tissues than in adjacent normal tissues (P = 0.008, P = 0.005). The mean MVD of VEGF and MMP-9 were statistically higher in positive group than in negative group (P = 0.015, P = 0.004), respectively . Moreover, a significant correlation was found between the VEGF and MMP-9 (P = 0.002). The log-rank test revealed that continuous disease-free survival time (CDFS) was significantly shorter in the MMP-9-positive group than in the MMP-9-negative group (P = 0.019), but the difference in the VEGF-positive group and the VEGF-negative group was not statistically significant (P = 0.938). Our data suggest that VEGF and MMP-9 might act with a synergistic effect and can positively regulate the angiogenesis in sacral chordoma. Positive expression of MMP-9 might indicate the local recurrence of sacral chordoma. The result suggests that some specific drugs which inhibit VEGF, MMP-9, or their receptors may have a good therapeutic effect for sacral chordoma.


Subject(s)
Biomarkers, Tumor/metabolism , Chordoma/metabolism , Matrix Metalloproteinase 9/metabolism , Neovascularization, Pathologic/metabolism , Sacrum/metabolism , Spinal Neoplasms/metabolism , Vascular Endothelial Growth Factor A/metabolism , Adolescent , Adult , Aged , Chordoma/blood supply , Chordoma/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neovascularization, Pathologic/pathology , Prognosis , Sacrum/blood supply , Sacrum/pathology , Spinal Neoplasms/blood supply , Spinal Neoplasms/pathology , Young Adult
13.
J Spinal Disord Tech ; 24(4): 230-4, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20634724

ABSTRACT

STUDY DESIGN: A retrospective study, analyzing the risk factors for postoperative wound infections of the sacral chordoma after surgical excision. OBJECTIVE: To determine the preoperative, intraoperative, and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing sacral chordoma resection. SUMMARY OF BACKGROUND DATA: Postoperative wound infection after spinal operations is a dreaded complication. The risk factors have been investigated earlier, but the patients with sacral chordoma may be distinct. METHODS: Between January 1992 and December 2007, 45 patients with sacral chordomas were treated with surgical resection. Data regarding preoperative and intraoperative risk factors for postoperative wound infection were evaluated using univariate analysis and multivariable conditional logistic regression. Odds ratios with 95% confidence intervals and P values were calculated. RESULTS: Of the 45 patients with sacral chordoma, 16 (35.6%) acquired postoperative wound infection. Significant risk factors associated with postoperative wound infection in the univariate analysis included the following: albumin <3.0, previous surgery, operating time, instrumentation, and surgical team. Albumin<3.0, operating time >6 hours, and previous surgery were statistically significant in the multivariable model. CONCLUSIONS: Patients undergoing sacral tumor surgery may be at greater risk for developing wound complications. In this study, it seems that albumin<3.0, operating time >6 hours, and previous surgery may predict those patients that were more prone to developing postoperative wound infection. Using a single surgical team and no instrumentation seems to provide protection against postoperative wound infection in this patient population.


Subject(s)
Chordoma/surgery , Sacrum/surgery , Spinal Neoplasms/surgery , Surgical Wound Infection , Adolescent , Adult , Aged , Chordoma/blood , Chordoma/diagnostic imaging , Cohort Studies , Female , Humans , Male , Middle Aged , Radiography , Retrospective Studies , Risk Factors , Sacrum/diagnostic imaging , Serum Albumin/metabolism , Spinal Neoplasms/blood , Spinal Neoplasms/diagnostic imaging , Surgical Wound Infection/blood , Surgical Wound Infection/etiology , Time Factors , Young Adult
14.
J Clin Neurosci ; 17(10): 1280-5, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20627583

ABSTRACT

Pre-operative embolization of hypervascular spinal tumors can be helpful in tumour resection; however, few studies have been reported on its effectiveness in sacral tumors. We aimed to investigate the value of surgical excision with pre-operative transarterial embolization for primary sacral tumors and evaluate the long-term follow-up outcomes. Data were obtained from a consecutive series of 60 patients (33 female, 27 male) who had sacral tumors and who, between 1992 and 2007, underwent surgical excision in conjunction with arterial embolization. The evaluation parameters included intraoperative blood loss, transfusion, treatment, local recurrence and complications associated with surgery. All tumor masses were resected without intraoperative shock or death. The mean intraoperative blood loss was 1168.3mL (range: 200-5700mL) and the mean transfusion amount was 5.2 units (range: 0-35 units). Radical wide excision was performed on eight patients, marginal excision was conducted for 34 patients and intralesional excision was undertaken for the remaining 18 patients. The mean follow-up period was 75.2months (range: 15-180months). Nineteen (31.7%) patients developed local recurrences. Of the patients who had at least the second sacral roots and the unilateral S3 preserved, 33 (84.6%) had normal bladder function and 34 (87.2%) had normal bowel control. Pre-operative arterial embolization may significantly reduce the likelihood of intraoperative hemorrhage, and has the potential to assist surgeons in completing tumor resection and improving the outcomes for these patients.


Subject(s)
Chordoma/therapy , Embolization, Therapeutic/methods , Sacrum/pathology , Spinal Cord Neoplasms/therapy , Adolescent , Adult , Aged , Angiography, Digital Subtraction/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Sacrum/surgery , Young Adult
15.
J Orthop Res ; 28(2): 258-64, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19639633

ABSTRACT

BMP-binding peptide (BBP) enhances the osteogenic activity of recombinant human bone morphogenetic protein-2 (rhBMP-2), but the mechanism underlying the enhancement remains unclear. We aimed to elucidate the potential enhanced efficacy of BBP using critical-sized segmental femoral bone defects in rats. Seventy defects in seven groups of rats were filled with various amounts (0, 2, 5, and 10 microg) of rhBMP-2 with or without 1000 microg BBP. Radiographs were obtained after 4 and 8 weeks. The animals were euthanized at 8 weeks, and femoral specimens were assessed manually, evaluated for bone volume using microcomputed tomography, and subjected to histological or biomechanical analysis. Although 10 microg rhBMP-2 yielded consistent results in terms of bone healing and quality of bone repair across the segmental defect, lower doses of rhBMP-2 failed to induce satisfactory bone healing. However, the combined administration of lower doses of rhBMP-2 and BBP induced the formation of significantly large amounts of bone. Our results suggest that the combined administration of rhBMP-2 and BBP facilitates bone healing and has potential clinical applications.


Subject(s)
Bone Morphogenetic Proteins/administration & dosage , Femur/injuries , Fractures, Bone/drug therapy , Recombinant Proteins/administration & dosage , Transforming Growth Factor beta/administration & dosage , Animals , Bone Morphogenetic Protein 2 , Bone Regeneration/drug effects , Dose-Response Relationship, Drug , Drug Therapy, Combination/methods , Femur/diagnostic imaging , Femur/drug effects , Fracture Healing/drug effects , Fractures, Bone/diagnostic imaging , Male , Models, Animal , Rats , Rats, Inbred Lew , Treatment Outcome , X-Ray Microtomography
16.
Spine (Phila Pa 1976) ; 34(23): 2537-44, 2009 Nov 01.
Article in English | MEDLINE | ID: mdl-19841613

ABSTRACT

STUDY DESIGN: The kinematic study of human lumbar spinal movements. OBJECTIVE: To investigate how disc degeneration and the degeneration of facet joint, ligaments, and paraspinal muscles are associated with lumbar segmental mobility. SUMMARY OF BACKGROUND DATA: Previous studies revealed relationship between spinal motion and osteoarthritic changes of facet joint as well as disc degeneration; however, little is known about the association of disc, facet joint, ligament, and muscle degeneration with lumbar segmental motion characteristics. METHODS: The 1580 lumbar motion segments from 316 patients (200 male, 116 female) underwent Kinetic magnetic resonance imaging, which were used to assess disc degeneration (grade I-V) and facet joint degeneration (grade 1-4), interspinous ligament (ISL) degeneration (grade 1-4), ligamentum flavum hypertrophy (LFH), and fatty degeneration of muscles. Segmental translational and angular motion in the flexion, extension, and neutral postures were digitally automatically measured by MR analyzer. RESULTS: Grade II (46.77%) disc, grade 1 (48.35%) facet joint degeneration, and grade 1 (64.1%) ISL were most common. LFH was most common in L4-L5 (49/330, 14.8%). In younger age (<35), grade I disc and grade 1 facet joint were predominant compared with the older age (35< or = and <45) in which grade III, IV, and V disc and grade 2 facet joint were predominant (P < 0.05). Translational motion increased significantly in high grade of disc and facet joint (except grade V disc and grade 4 facet joint) and with LFH in L1-L5 (P < 0.05). Angular motion significantly decreased in grade V disc, grade 4 ISL, and without LFH in L1-L5 (P < 0.05). According to muscle fatty degeneration, translational and angular motions were not significantly changed. CONCLUSION: Our results support that facet joint degeneration is followed by disc degeneration according to age. Increased translational movements of the lumbar segments occurred in severe disc degeneration accompanied by facet joint degeneration or the presence of LFH even if the movements were stabilized in the advanced status. Therefore, the current status of the intervertebral discs, facet joints, and ligamentum flavum should be taken into consideration when evaluating stability within the lumbar spine.


Subject(s)
Intervertebral Disc Degeneration/physiopathology , Ligamentum Flavum/pathology , Longitudinal Ligaments/pathology , Lumbar Vertebrae/pathology , Range of Motion, Articular/physiology , Spine/pathology , Zygapophyseal Joint/pathology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Analysis of Variance , Chi-Square Distribution , Female , Humans , Intervertebral Disc/pathology , Intervertebral Disc/physiopathology , Intervertebral Disc Degeneration/pathology , Ligamentum Flavum/physiopathology , Longitudinal Ligaments/physiopathology , Lumbar Vertebrae/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Movement/physiology , Spine/physiopathology , Zygapophyseal Joint/physiopathology
17.
J Clin Neurosci ; 16(11): 1443-8, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19683929

ABSTRACT

The aim of this study is to evaluate an integrated cage and plate device (the plate cage Benezech, PCB) filled with autogenous bone in anterior cervical discectomy and fusion. The fused segment height, lordosis, and fusion were assessed by postoperative radiographic examination at different intervals. Patients were evaluated using Odom's criteria and the Short Form (SF)-36 Health Survey questionnaire. The mean follow-up duration was 4.1 years. Fusion was achieved in 90.0%, 96.0% and 100% of patients at 3 months, 6 months and at final visit, respectively. The fused segment height and lordosis were restored and maintained. Cage subsidence (3mm) occurred at one level and settling was observed at three levels. An excellent-to-good result was achieved in 81.8% of patients. The data from the SF-36 questionnaire revealed significant postoperative improvement (p<0.01) except for social function and mental health. This study suggests that patients instrumented with PCB can obtain good radiographic and clinical results and that PCB is a safe and effective device in cervical anterior fusion.


Subject(s)
Bone Plates , Diskectomy , Spinal Cord Injuries/surgery , Spinal Fusion/instrumentation , Spinal Fusion/methods , Adult , Aged , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/pathology , Diskectomy/methods , Female , Health Surveys , Humans , Male , Middle Aged , Retrospective Studies , Spinal Cord Injuries/diagnostic imaging , Spinal Cord Injuries/pathology , Surveys and Questionnaires , Tomography, X-Ray Computed/methods , Treatment Outcome
18.
Eur Spine J ; 18(6): 877-83, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19357877

ABSTRACT

A congenitally narrow cervical spinal canal has been established as an important risk factor for the development of cervical spondylotic myelopathy. However, few reports have described the mechanism underlying this risk. In this study, we investigate the relationship between cervical spinal canal narrowing and pathological changes in the cervical spine using positional magnetic resonance imaging (MRI). Two hundred and ninety-five symptomatic patients underwent cervical MRI in the weight-bearing position with dynamic motion (flexion, neutral, and extension) of the cervical spine. The sagittal cervical spinal canal diameter and cervical segmental angular motion were measured and calculated. Each segment was assessed for the extent of intervertebral disc degeneration and cervical cord compression. Based on the sagittal canal diameter, the subjects were classified into three groups: A, subjects with a congenitally narrow canal, diameter of less than 13 mm; B, subjects with a normal canal, diameter of 13-15 mm; C, subjects with a wide canal, diameter of more than 15 mm. When compared with Groups A and B, the disc degeneration grades at the C3-4, C5-6, and C6-7 segments and the cervical cord compression scores at the C3-4 and C5-6 segments showed significant differences. Additionally, when compare with Groups A and C, the disc degeneration grades at all segments, except C2-3, and the cervical cord compression scores at all segments, except C2-3, showed significant differences. With respect to the cervical kinematics, few differences in the kinematics were observed between Groups B and C, however, the kinematics in Group A was different with other two groups. In Group A, the segmental mobility at the C4-5 and C6-7 segments were significantly higher than those observed in Group B, and the segmental mobility at the C3-4 segment was significantly lower than that observed in Groups B or C. We demonstrated the unique pathological and kinematic traits of cervical spine that exist in a congenitally narrow canal. We hypothesize that kinematic trait associated with a congenitally narrow canal may greatly contribute to pathological changes in the cervical spine. Our results suggest that cervical spinal canal diameter of less than 13 mm may be associated with an increased risk for development of pathological changes in cervical intervertebral discs. Subsequently, the presence of a congenitally narrow canal can expose individuals to a greater risk of developing cervical spinal stenosis.


Subject(s)
Cervical Vertebrae/abnormalities , Cervical Vertebrae/pathology , Spinal Canal/abnormalities , Spinal Canal/pathology , Spondylosis/etiology , Spondylosis/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Biomechanical Phenomena , Causality , Cervical Vertebrae/physiopathology , Disease Progression , Female , Head Movements/physiology , Humans , Intervertebral Disc Displacement/etiology , Intervertebral Disc Displacement/pathology , Intervertebral Disc Displacement/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of Tests , Radiculopathy/etiology , Radiculopathy/pathology , Radiculopathy/physiopathology , Range of Motion, Articular/physiology , Risk Factors , Spinal Canal/physiopathology , Spinal Cord Compression/etiology , Spinal Cord Compression/pathology , Spinal Cord Compression/physiopathology , Spondylosis/physiopathology , Young Adult
19.
Spine (Phila Pa 1976) ; 33(23): E870-6, 2008 Nov 01.
Article in English | MEDLINE | ID: mdl-18978580

ABSTRACT

STUDY DESIGN: Retrospective analysis using kinetic magnetic resonance images (MRIs). OBJECTIVE: To investigate the relationship of changes in the sagittal alignment of the cervical spine on the kinematics of the functional motion unit and disc degeneration. SUMMARY OF BACKGROUND DATA: Normal lordotic alignment is one of the most important factors contributing to effective motion and function of the cervical spine. Loss of normal lordotic alignment may induce pathologic changes in the kinematics and accelerate degeneration of the functional motion unit. However, the relationship of altered alignment on kinematics and degeneration has not been evaluated. METHODS: Kinetic MRIs in flexion, neutral, and extension were performed. Study participants were classified into 5 groups based on the C1-C7 Cobb angle of sagittal alignment--Group A: Kyphosis (n = 19), Group B: Straight (n = 29), Group C: Hypolordosis (n = 38), Group D: Normal (n = 63), and Group E: Hyperlordosis (n = 52).Intervertebral disc degeneration was graded (Grades 1-5), and the kinematics of the functional spinal unit were obtained. RESULTS: When the alignment shifted from normal to less lordotic, the translational motion and angular variation tended to decrease at all levels. The contribution of the C1-C2, C2-C3, and C3-C4 levels to total angular mobility tended to be higher in Group C than Group D. However, the contribution of the C4-C5, C5-C6, and C6-C7 levels tended to be lower in Group C than in Group D. The grade of disc degeneration associated with loss of lordosis tended to be higher than that associated with normal alignment at the C2-C3 and C3-C4 levels. CONCLUSION: The present study demonstrated that the changes in sagittal alignment of the cervical spine affect the kinematics. Consequently, it may cause changes in the segment subjected to maximum load for overall motion and accelerate its degeneration.


Subject(s)
Biomechanical Phenomena , Cervical Vertebrae/physiopathology , Intervertebral Disc Displacement/physiopathology , Lordosis/physiopathology , Adult , Aged , Aged, 80 and over , Cervical Vertebrae/pathology , Female , Humans , Image Processing, Computer-Assisted , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/pathology , Lordosis/complications , Lordosis/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Young Adult
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