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An amendment to this paper has been published and can be accessed via the original article.
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Developing novel therapeutic agents against chondrosarcoma is important. SF2523 is a PI3K-Akt-mTOR and bromodomain-containing protein 4 (BRD4) dual inhibitor. Its activity in human chondrosarcoma cells is tested. Our results show that SF2523 potently inhibited survival, proliferation and migration, and induced apoptosis activation in SW1353â¯cells and primary human chondrosarcoma cells. The dual inhibitor was yet non-cytotoxic to the primary human osteoblasts and OB-6 osteoblastic cells. SF2523 blocked Akt-mTOR activation and downregulated BRD4-regulated genes (Bcl-2 and c-Myc) in chondrosarcoma cells. It was more efficient in killing chondrosarcoma cells than other established PI3K-Akt-mTOR and BRD4 inhibitors, including JQ1, perifosine and OSI-027. In vivo, intraperitoneal injection of SF2523 (30â¯mg/kg) potently inhibited subcutaneous SW1353 xenograft tumor growth in severe combined immunodeficient mice. Akt-mTOR inhibition as well as Bcl-2 and c-Myc downregulation were detected in SF2523-treated SW1353 tumor tissues. In conclusion, targeting PI3K-Akt-mTOR and BRD4 by SF2523 potently inhibited chondrosarcoma cell growth in vitro and in vivo.
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Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Condrossarcoma/tratamento farmacológico , Morfolinas/farmacologia , Piranos/farmacologia , Adulto , Animais , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Linhagem Celular Tumoral , Condrossarcoma/metabolismo , Condrossarcoma/patologia , Humanos , Masculino , Camundongos SCID , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Piranos/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidoresRESUMO
BACKGROUND: Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer. METHODS: In situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on bone metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis. RESULTS: Herein, we found that miR-124 was significantly reduced in metastatic bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter bone metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the bone metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in bone metastases was associated with a poor prognosis. CONCLUSIONS: Thus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent bone metastases of breast cancer.
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Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Interleucina-11/genética , MicroRNAs/genética , Interferência de RNA , Animais , Neoplasias Ósseas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Diferenciação Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Modelos Animais de Doenças , Feminino , Humanos , Hibridização In Situ , Estimativa de Kaplan-Meier , Camundongos , Modelos Biológicos , Metástase Neoplásica , Osteoclastos/citologia , Osteoclastos/metabolismo , Prognóstico , Microambiente TumoralRESUMO
Four new alkaloids, (-)-8'-oxo-agelasine D (2), ageloxime B (3), (+)-2-oxo-agelasidine C (4), and 4-bromo-N-(butoxymethyl)-1H-pyrrole-2-carboxamide (5), and the known compound (-)-ageloxime D (1) were isolated from the marine sponge Agelas mauritiana. Their chemical structures were established on the basis of spectroscopic analysis. Compounds 1 and 3 both showed antifungal activity against Cryptococcus neoformans and antileishmanial activity against Leishmania donovani in vitro. Compound 3 also exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureusin vitro.
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Agelas/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Infecções Estafilocócicas/microbiologia , Alcaloides/química , Animais , Antibacterianos/química , Anti-Infecciosos/química , Cryptococcus neoformans/efeitos dos fármacos , Leishmania donovani/efeitos dos fármacos , Biologia Marinha , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacosRESUMO
PURPOSE: To investigate risk factors for instrumentation failure (IF) in titanium (Ti) mesh reconstruction for thoracic and lumbar tumors. PATIENTS AND METHODS: The clinical data of patients with thoracic or lumbar tumors who received Ti mesh reconstruction via the posterior approach in our hospital from 2013 to 2018 were analyzed retrospectively. The observation indexes included sex, age, BMI, the vertebra resection mode, the number of resected vertebral segments, application of bone cement, radiotherapy, chemotherapy, revision or primary surgery, and primary tumor metastasis. Correlations between these factors and IF were analyzed by Kaplan-Meier survival and logistics regression analyses. RESULTS: The 178 patients included 108 males and 70 females with a mean age of 48.09±16.21 (6-78) years and a mean follow-up period of 51.18 (24-90) months. The data showed that 17 patients (9.55%) were inflicted with IF, involving the thoracic vertebra in 11 cases, thoracolumbar vertebrae (T12-L1) in 2 cases, and lumbar vertebrae in 4 cases. The mean interval between surgery to IF was 35.18±14.17 (14-59) months. Univariate analysis showed that total vertebral body resection, the number of resected vertebral segments, radiotherapy and multiple tumor resection were potential factors for IF, while multivariate analysis showed that only total vertebral body resection, the number of resected vertebral segments and radiotherapy were independent factors. CONCLUSION: Total vertebra resection, the number of resected vertebral segments (≥2) and radiotherapy before and after operation were significant risk factors related to IF.
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OBJECTIVE: To study the clinical features, treatment methods and outcome of solitary plasmacytoma of cervical spine. METHODS: From January 1995 to December 2007, the data of 23 cases with solitary plasmacytoma of cervical spine was analyzed. There were 16 males and 7 females (mean age 56 years, range: 32 - 76 years). Two cases underwent radiotherapy alone and 21 patients received surgery. According to WBB staging system, surgical procedures were defined as total or subtotal resection (6 cases), appendix resection (4 cases), sagittal resection (3 cases) and total spondylectomy (8 cases). All surgical cases were managed using an anterior approach, posterior approach or combined anterior and posterior approach. The cervical spinal reconstruction was achieved through anterior cervical titanium plate and titanium mesh cage filled with auto iliac graft or bone cement, or anterior and posterior combined instrumented fusion. All patients received radiotherapy as adjunctive therapy. RESULTS: Follow-up of the 23 cases lasted 24.0 - 143.0 months (mean: 64.7 months). Neck pains obviously improved, and nerve compression symptoms disappeared or improved after surgery. Neurological function improved by 1 - 2 grades based on Frankel grading system. All the internal fixations were fused well and stability of the cervical spine was fine and no spine instability could be seen in our series. The bone graft fusion rate was 100%. During the follow-up period, 6 surgical cases had local recurrence and finally progressed to multiple myeloma (MM) and 3 died. Two cases without surgical treatment progressed to MM in 1 year and 1.5 years after confirmed diagnosis. They were given systemic chemotherapy. The other 15 patients had disease-free survival and after surgery and adjunctive radiotherapy. Obvious abnormity were not found in such examinations as M protein, bone marrow aspiration and emission computed tomography or PET-CT examinations. CONCLUSIONS: Solitary plasmacytoma of cervical spine is rarely seen clinically. Surgery is recommended as the primary management for patients with overt bone destruction and spinal instability or neurological dysfunction. Tumor excision with adjunctive radiotherapy can obviously reduce local recurrences and lower the possibility of progression to MM. The patients with progression to MM should receive chemotherapy according to chemotherapy protocol while the prognosis is comparatively worse.
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Vértebras Cervicais , Plasmocitoma/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Ossifying fibroma (OF) is a benign tumor commonly occurring in the mandible and maxilla. Spinal involvement of OFs is of great rarity. To the best of our knowledge, only 3 cases in the thoracic and lumbar spine have been reported. CASE DESCRIPTION: We present the case of a 22-year-old woman with an OF of the atlas, which, to the best of our knowledge, is the first described OF in the cervical spine. The related data were also reviewed. Only 3 spinal OFs involving the thoracic spine to the sacrum have been reported. CONCLUSIONS: Spinal involvement of OFs seldom occurs. To the best of our knowledge, we have reported the first OF involving the cervical spine. Differentiating OFs from primary spinal tumors is necessary. OFs have locally aggressive behavior and a high risk of recurrence. Complete resection, followed by regular examinations, should be the ideal choice for treatment.
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Vértebras Cervicais/cirurgia , Fibroma Ossificante/diagnóstico , Procedimentos Ortopédicos , Neoplasias da Coluna Vertebral/diagnóstico , Vértebras Cervicais/diagnóstico por imagem , Feminino , Fibroma Ossificante/diagnóstico por imagem , Fibroma Ossificante/cirurgia , Humanos , Fusão Vertebral , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Adulto JovemRESUMO
BACKGROUND: With the occurrence and improvement of immunohistochemistry and other pathological diagnostic techniques, gastrointestinal stromal tumor (GIST) has been gradually recognized. With the prolonged survival of patients with GISTs, reports about the bone metastasis of GIST increased. However, the knowledge of GISTs is rather limited due to its very low incidence. METHODS: Cochrane and Medline database (via PubMed) were searched in July 2019 with related keywords to acquire the literature related to the bone metastasis of GIST. Then, the literature was reviewed and references were also scanned to identify the possible related reports. Study data comprising age, sex, primary location, metastasis interval time, immunohistochemistry index, management and prognosis were recorded and analyzed. RESULTS: Forty-five patients with bone metastases of GIST, with a mean age of 61.09 years, were included. The small intestine and stomach were the most common primary sites, followed by the rectum. Patients with small intestine primary sites had bone metastases that occurred earlier than the bone metastases stomach and rectum primary sites. The spine was the most common site of bony metastases. The mean survival time after GIST diagnosis was more than 64.02 months. Patients younger than 60 years old had a worse prognosis than those older than 60 years old. Furthermore, patients with spinal involvement had a worse prognosis than those without spinal involvement. Surgical interventions combined with targeted therapies guaranteed a better prognosis. CONCLUSION: Bone metastasis of GIST, which mainly occurs in the spine, is rather rare. Patients with GISTs of the small intestine and stomach suffered from bone metastasis more frequently and earlier than patients with GISTs in other primary sites. Age, sex, primary tumor location, treatment mode for the primary lesions and metastases, and spine involvement may be potential factors that affect the prognosis of GIST patients with bone metastases.
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STUDY DESIGN: This was a retrospective study. OBJECTIVE: To describe a novel reconstruction strategy using a T-shaped titanium mesh cage with posterior cervical screw-rod fixation after total spondylectomy of axis tumors. SUMMARY OF BACKGROUND DATA: Instability of the upper cervical spine because of tumors in axis (C2) often results in devastating complications. Surgical resection and reconstruction after spondylectomy of C2 remain a technical challenge because of the intricate anatomies, vital adjacent tissues, and the unique spinal biomechanics in this special region. MATERIALS AND METHODS: The novel reconstruction mode included the construction of the anterior aspect conducted with a specially made titanium mesh cage and the posterior cervical fixation only. Patients who received total C2 tumors spondylectomy and reconstruction with this novel mode in our center between January 2009 and December 2017 were retrospectively analyzed to evaluate the efficacy of this novel reconstruction method. RESULTS: A total of 24 patients with C2 tumor received total spondylectomy and the new mode of local reconstruction. The neurological deficits recovered well and local pain relieved significantly (P<0.001) during the mean follow-up time of 22 months. Perioperative complications were rare and controllable. No internal fixation failure occurred. The mobility of the occipital-cervical junction was largely preserved in all patients. CONCLUSIONS: This novel reconstruction mode using an anterior "T-shaped" mesh cage with posterior screw-rod fixation provides satisfactory stability and motion of occipital-cervical junction with limited complications, and therefore may prove to be an ideal option for management of C2 tumors. LEVEL OF EVIDENCE: Level IV.
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Vértebras Cervicais/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Parafusos Ósseos , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Próteses e Implantes , Amplitude de Movimento Articular , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos , Titânio , Resultado do Tratamento , Adulto JovemRESUMO
STUDY DESIGN: Experimental study. OBJECTIVE: To examine the role of endothelin-1 (ET-1) and the Notch signaling pathway in giant cell tumor (GCT) of the spine. SUMMARY OF BACKGROUND DATA: Previously published studies have shown that the Notch signaling pathway has a role in tumor invasion and that ET-1 is involved in tumor invasion and angiogenesis. However, the roles of both Notch signaling and ET-1 in GCT of the spine remain unknown. METHODS: Expression of ET-1 in tissue samples from patients with spinal GCT, and adjacent normal tissue, were analyzed by immunohistochemistry and western blot. GCT stromal cells (GCTSCs) were isolated and ET-1 expression was demonstrated by immunofluorescence. Cell viability and cell migration of GCTSCs and human vascular endothelial cells following ET-1 treatment were assessed using the cell counting kit-8 assay and a transwell assay. Receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) mRNA expression was determined following ET-1 treatment of GCTSCs using quantitative real-time polymerase chain reaction. In GCTSCs treated with ET-1 and the ET-1 signaling antagonist, BQ-123, levels of cyclin D1, vascular endothelial growth factor, matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), Jagged1, Hes1, Hey2, and Notch intracellular domain were examined by western blot. RESULTS: Compared with normal adjacent tissue, ET-1 was highly expressed in GCT tissue. In GCTSCs studied in vitro, treatment with ET-1 significantly increased GCTSC and human vascular endothelial cells growth and migration and increased the expression of RANKL and OPG, meanwhile the ratio of RANKL/OPG was increased, in GCTSCs, it upregulated the production of cyclin D1, vascular endothelial growth factor, MMP-2, MMP-9, Jagged1, Hes1, Hey2, and Notch intracellular domain expression in a dose-dependent manner. Treatment with BQ-123 reversed these effects. CONCLUSION: In GCT of the spine, ET-1 showed increased expression. In cultured GCTSCs, ET-1 treatment activated the Notch signaling pathway. LEVEL OF EVIDENCE: 2.
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Carcinogênese/metabolismo , Endotelina-1/metabolismo , Tumores de Células Gigantes/metabolismo , Receptores Notch/metabolismo , Neoplasias da Coluna Vertebral/metabolismo , Humanos , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: To determine the outcome of combined anterior C2,3 reduction and fusion with posterior compressive C2 pedicle screw fixation for the management of unstable Hangman's fractures. METHODS: Sixteen cases of unstable Hangman's fractures were retrospectively reviewed through X-ray, MRI and three dimensional CT scans. Pre- and postoperative radiographs were measured for translation and angulation of C2,3. Skull traction under extension poison was conducted in all the patients right after their admission. Then anterior C2,3 discectomy followed by interbody fusion, either with iliac autograft or with box cage, and locking plate fixation were performed in each case. Because dissatisfied reduction, mainly residual large fracture gap or kyphosis, was found by the C-arm fluoroscopy during operations, posterior compressive C2 pedicle screw fixation was performed in one stage. According to the Levine-Edwards classification, there were 12 cases of type II, 2 of type I a and 2 of type III in this group. RESULTS: Follow-up ranged 6-38 months, averaged 26 months. Fracture union and bone graft fusion were completed in an average of 4 months after operation. Complaints of neck pain and numbness of limbs disappeared in all patients after surgery, but range of neck motion decreased compared with normal people. Translation of C2 decreased from (4.2 +/- 1.4) mm preoperatively to (2.3 +/- 1.1) mm postoperatively, while angulation of C2,3 decreased from 8.6 degrees +/- 2.1 degrees preoperatively to 2.6 degrees +/- 1.0 degrees postoperatively. Both have statistical significance (P < 0.05). No implant failure or infection was observed. CONCLUSIONS: The classification of Hangman's fracture should be modified in combination with MRI and CT scans to determine the stability of the fracture. Combined anterior C2,3 reduction and fusion with posterior compressive C2 pedicle screw fixation is the treatment of choice for patients with unstable Hangman's fractures.
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Vértebra Cervical Áxis/lesões , Fixação Interna de Fraturas/métodos , Fraturas da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Adulto , Idoso , Vértebra Cervical Áxis/cirurgia , Pinos Ortopédicos , Vértebras Cervicais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the effects of surgical treatment and prognosis of aneurysmal bone cyst (ABC) in mobile spine. METHODS: A total of 12 patients with ABC were operated on from 1996 to 2006, and the clinical data were retrospectively reviewed. The patients included 7 male and 5 female, aged from 16 to 52 years (mean, 29 years). Surgical interventions were selected according to WBB criteria. Seven patients underwent total spondylectomy, four underwent resection of posterior arch, one patient received sagittal resection only. Anti-poster or post-lateral approach reconstruction with bone-graft or bone cement and transpedicular screws fixation were performed in the cases. Eight cases received radiotherapy after the operation. RESULTS: The mean operation blood lose was 3210 ml. The patients were followed-up for 10 to 116 months (mean, 41.8 months). Seven patients got complete recover of spinal cord function, 4 patients experienced local recurrence in 1-2 years post operation. One patient died of multiple metastasis of chondrosarcoma after radiotherapy. CONCLUSIONS: ABC in spine is an aggressive disease with high local recurrence rate. Enbloc if possible provides the best result, with excellent prognosis. Radiotherapy should be selected carefully.
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Cistos Ósseos Aneurismáticos/cirurgia , Doenças da Coluna Vertebral/cirurgia , Adolescente , Adulto , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiografia , Estudos Retrospectivos , Doenças da Coluna Vertebral/diagnóstico por imagem , Resultado do TratamentoRESUMO
BACKGROUND CONTEXT: Endothelin-1 (ET-1) is an inflammatory mediator associated with cartilage end plate (CEP) degeneration in the intervertebral disc (IVD). SOX9 is downregulated during CEP degeneration, along with its targets, collagen II and aggrecan. Wnt/ß-catenin signaling is associated with CEP degeneration and a downstream target of SOX9; however, the precise mechanism of CEP degeneration and the role of ET-1 are largely unknown. PURPOSE: The purpose of the study was to evaluate the influence of the endothelin-A receptor antagonist, BQ-123, on ET-1-induced effects on cartilaginous end plate cells (CECs) associated with CEP degeneration via the Wnt/ß-catenin signaling pathway. STUDY DESIGN/SETTING: The influence of ET-1 on the expression levels of collagen II, aggrecan, and SOX9 in CECs and the effect of BQ-123 in this context were investigated. METHODS: To establish a model for CEP degeneration, three lumbar discs (L3-L4, L4-L5, and L5-L6 levels) in New Zealand white rabbits were punctured close to the vertebral end plate using a 14G needle. Intervertebral disc degeneration was evaluated by magnetic resonance imaging 4 weeks after vertebral end plate injury. CECs were then isolated from the degenerated CEPs to allow evaluation of the role of ET-1 and BQ-123 and to investigate their effects on the Wnt/ß-catenin signaling pathway. The expression of ET-1 in CECs from degenerated CEPs was analyzed by immunofluorescent staining. Changes in the levels of collagen II, aggrecan, and SOX9 were evaluated in CECs by real-time polymerase chain reaction and by Western blotting. The Wnt/ß-catenin signaling pathway was also investigated by Western blotting. RESULTS: After 4 weeks, IVDs with vertebral end plate injury exhibited clear signs of disc degeneration. Immunofluorescent staining showed that ET-1 was expressed in the cytoplasm of CECs. Endothelin-1 stimulation significantly inhibited the expression of collagen II, aggrecan, and SOX9 in CECs, whereas BQ-123 increased the levels of these three molecules. In addition, ET-1 stimulation increased the expression of ß-catenin, cyclin D1, and Dvl1 in the Wnt/ß-catenin signaling pathway of CECs from degenerated discs and reduced the expression of GSK-3ß, whereas BQ-123 had the opposite effect. CONCLUSIONS: Endothelin-1 can reduce levels of collagen II, aggrecan, and SOX9 in CECs through activation of the Wnt/ß-catenin signaling pathway, whereas BQ-123 attenuates these negative effects, highlighting a new molecular mechanism with potential for exploitation for treatment of CEP degeneration.
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Antagonistas dos Receptores de Endotelina/farmacologia , Endotelina-1/farmacologia , Degeneração do Disco Intervertebral/metabolismo , Disco Intervertebral/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Via de Sinalização Wnt , Agrecanas/metabolismo , Animais , Colágeno/metabolismo , Disco Intervertebral/metabolismo , Coelhos , beta Catenina/metabolismoRESUMO
Giant cell tumor of the bone (GCTB) is a locally aggressive tumor with a certain distant metastatic rate. For sacral GCT (SGCT) and pelvic GCT (PGCT), surgery has its limitations, especially for unresectable or recurrent tumors. Selective arterial embolization (SAE) is reported to be an option for treatment in several cases, but there are few systematic reviews on the effects of SAE on SGCT and/or PGCT. Medline and Embase databases were searched for eligible English articles. Inclusion and exclusion criteria were conducted before searching. All the clinical factors were measured by SPSS software, with P-values ≤0.05 considered statistically significant. A total of 9 articles were retrieved, including 44 patients receiving SAE ranging from 1 to 10 times. During the mean follow-up period of 85.8 months, the radiographic response rate was 81.8%, with a local control and overall survival rate of 75% and 81.8%, respectively. No bowel, bladder, or sexual dysfunction was observed. Three patients developed distant metastases and finally died. Patients with primary tumors tended to have better prognosis than those with recurrence (P = 0.039). The favorable outcomes of SAE suggest that it may be an alternative treatment for SGCT and PGCT patients for whom surgery is not appropriate.
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Neoplasias Ósseas/terapia , Embolização Terapêutica/métodos , Tumor de Células Gigantes do Osso/terapia , Neoplasias Pélvicas/terapia , Neoplasias da Coluna Vertebral/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos , Sacro , Resultado do Tratamento , Adulto JovemRESUMO
B-cell CLL/lymphoma 9 protein (BCL-9), a multi-functional co-factor in Wnt signaling, induced carcinogenesis as well as promoting tumor progression, metastasis and chemo-resistance in colorectal cancer (CRC). However, the mechanisms for increased BCL-9 expression in CRC were not well understood. Here, we report that hypoxia, a hallmark of solid tumors, induced BCL-9 mRNA expression in human CRC cells. Analysis of BCL-9 promoter revealed two functional hypoxia-responsive elements (HRE-B and HRE-C) that can be specifically bound with and be transactivated by hypoxia inducible factors (HIF) -1α but not HIF-2α. Consistently, ectopic expression of HIF-1α but not HIF-2α transcriptionally induced BCL-9 expression levels in cells. Knockdown of endogenous HIF-1α but not HIF-2α by siRNA largely abolished the induction of HIF by hypoxia. Furthermore, there was a strong association of HIF-1α expression with BCL-9 expression in human CRC specimens. In summary, results from this study demonstrated that hypoxia induced BCL-9 expression in human CRC cells mainly through HIF-1α, which could be an important underlying mechanism for increased BCL-9 expression in CRC.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Proteínas de Neoplasias/genética , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , Elementos de Resposta , Fatores de Transcrição , Ativação TranscricionalRESUMO
OBJECTIVE: To investigate the feasibility and safety of en bloc resection of cervical primary malignant bone tumors by a combined anterior and posterior approach based on a three-dimensional (3-D) printing model. METHODS: Five patients with primary malignant bone tumors of the cervical spine underwent en bloc resection via a one-stage combined anteroposterior approach in our hospital from March 2013 to June 2014. They comprised three men and two women of mean age 47.2 years (range, 26-67 years). Three of the tumors were chondrosarcomas and two chordomas. Preoperative 3-D printing models were created by 3-D printing technology. Sagittal en bloc resections were planned based on these models and successfully performed. A 360° reconstruction was performed by spinal instrumentation in all cases. Surgical margins, perioperative complications, local control rate and survival rate were assessed. RESULTS: All patients underwent en bloc excision via a combined posterior and anterior approach in one stage. Mean operative time and estimated blood loss were 465 minutes and 1290 mL, respectively. Mean follow-up was 21 months. Wide surgical margins were achieved in two patients and marginal resection in three; these three patients underwent postoperative adjuvant radiation therapy. One vertebral artery was ligated and sacrificed in each of three patients. Nerve root involved by tumor was sacrificed in three patients with preoperative upper extremity weakness. One patient (Case 3) had significant transient radiculopathy with paresis postoperatively. Another (Case 4) with C 4 and C 5 chordoma had respiratory difficulties and pneumonia after surgery postoperatively. He recovered completely after 2 weeks' management with a tracheotomy tube and antibiotics in the intensive care unit. No cerebrovascular complications and wound infection were observed. No local recurrence or instrumentation failure were detected during follow-up. CONCLUSION: Though technically challenging, it is feasible and safe to perform en bloc resection of cervical primary bone tumors. This is the most effective means of managing cervical spine tumors. Preoperative 3-D printing modelling enables better anatomical understanding of the relationship between the tumor and cervical spine and can assist in planning the surgical procedure.
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Vértebras Cervicais/diagnóstico por imagem , Condrossarcoma/cirurgia , Procedimentos Ortopédicos/métodos , Impressão Tridimensional , Neoplasias da Coluna Vertebral/cirurgia , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Vértebras Cervicais/cirurgia , China/epidemiologia , Condrossarcoma/diagnóstico , Condrossarcoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/mortalidade , Taxa de Sobrevida/tendências , Resultado do TratamentoRESUMO
The cell division cycle 6 (CDc6) protein has been primarily investigated as a component of the pre-replicative complex for the initiation of DNA replication. Some studies have shown that CDc6 played a critical role in the development of human carcinoma. However, the expression and roles of CDc6 in the central nervous system remain unknown. We have performed an acute spinal cord injury (SCI) model in adult rats and investigated the dynamic changes of CDc6 expression in spinal cord. Western blot have found that CDc6 protein levels first significantly increase, reach a peak at day 3, and then gradually return to normal level at day 14 after SCI. Double immunofluorescence staining showed that CDc6 immunoreactivity was found in neurons, astrocytes, and microglia. Additionally, colocalization of CDc6/active caspase-3 has been detected in neurons and colocalization of CDc6/proliferating cell nuclear antigen has been detected in astrocytes and microglial. In vitro, CDc6 depletion by short interfering RNA inhibits astrocyte proliferation and reduces cyclin A and cyclin D1 protein levels. CDc6 knockdown also decreases neuronal apoptosis. We speculate that CDc6 might play crucial roles in CNS pathophysiology after SCI.
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Apoptose , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Animais , Astrócitos/metabolismo , Caspase 3/metabolismo , Ciclina A/metabolismo , Ciclina D1/metabolismo , Masculino , Microglia/metabolismo , Neurônios/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To observe the results and its related factors of surgical treatment of cervical spondylotic myelopathy (CSM). METHODS: Totally 365 CSM patients were reviewed. All patients were treated with anterior cervical decompression and fusion with autogenous iliac bone or titanium mesh cages with local bone graft. Anterior locking plates were used for fixation. Five patients received revision surgery 3 to 6 months after the initial operation. RESULTS: Clinical function was excellent in 175 patients (47.94%), good in 129 patients (35.34%), fair in 44 patients (12.05%), and poor in 17 patients (4.66%). CONCLUSION: Anterior cervical decompresion of CSM has good clinical efficacy. The timing of operation, disease severity, and surgical technique are the important factors affecting the outcome of treatment.
Assuntos
Vértebras Cervicais , Descompressão Cirúrgica , Fusão Vertebral , Osteofitose Vertebral/cirurgia , Adulto , Idoso , Placas Ósseas , Vértebras Cervicais/cirurgia , Feminino , Seguimentos , Humanos , Ílio/transplante , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Osteofitose Vertebral/complicações , Transplante Autólogo , Resultado do TratamentoRESUMO
OBJECTIVE: To study the surgical indications, approaches and the clinical results of the total spondylectomy and instrumentation reconstruction in the treatment of cervical spinal tumor. METHODS: From October 1998 to October 2003, 39 patients with lower cervical bone tumors, including 34 cases with primary tumor and 5 cases with metastatic tumor, were admitted and operated on with total spondylectomy. The patients underwent anteroposterior total spondylectomy including anterior cervical plating, titanium mesh reconstruction and posterior instrumentation based on the location of tumor lesions in the lower cervical spine. One vertebral level total spondylectomy was performed in 29 cases, two level in 7 cases and three level in 3 cases. RESULTS: The postoperative follow-up ranged from 6 months to 4 years. A majority of patients achieved good results postoperatively. Nineteen cases had complete relief of neurological status. One patient died of multiple metastases and systemic failure 24 months later. One case with malignant neurilemmoma developed local recurrence one year postoperatively. CONCLUSION: Anteroposterior total spondylectomy and reconstruction can reduce local recurrence, improve neurological function and increase operation therapeutic effect. Meanwhile, the technique of cervical total spondylectomy carries relatively greater risks and should be more attention to the operation indication.
Assuntos
Vértebras Cervicais , Fusão Vertebral/métodos , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Vértebras Cervicais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Coluna Vertebral/patologia , Resultado do TratamentoRESUMO
IRF-1, a kind of transcription factor, is expressed in many cell types, except in early embryonal cells. IRF-1 has played an essential role in various physiological and pathological processes, including tumor immune surveillance, viral infection, development of immunity system and pro-inflammatory injury. However, the expression and function of IRF-1 in spinal cord injury (SCI) are still unknown. In this study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of IRF-1 expression in the spinal cord. Western blot have shown that IRF-1 protein levels gradually increased, reaching a peak at day 3 and then gradually declined to a normal level at day 14 after SCI. Double immunofluorescence staining showed that IRF-1 immunoreactivity was found in neurons, but not in astrocytes and microglia. Additionally, colocalization of IRF-1/active caspase-3 was detected in neurons. In vitro, IRF-1 depletion, by short interfering RNA, obviously decreases neuronal apoptosis. In conclusion, this is the first description of IRF-1 expression in spinal cord injury. Our results suggested that IRF-1 might play crucial roles in CNS pathophysiology after SCI.