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1.
Autops. Case Rep ; 9(4): e2019091, Oct.-Dec. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1024295

RESUMO

Desmoplastic fibroma (DF) is a rare bone tumor, which is known to involve mostly the gnathic bones. In this setting, the clinical presentation is usually represented by a bulging tumor of the face. Radiologically, the tumor is usually characterized by an expansile lytic bone lesion. The histopathology of the tumor shows a poorly circumscribed hypocellular lesion rich in collagen fibers with interspersed spindle cells having bland nuclear chromatin. Despite the lack of mitoses and nuclear pleomorphism, DF has an aggressive nature, presenting as a destructive growth causing entrapment of neuro-vascular bundles, sinusitis, or trismus. Some cases of DF show mutations in the adenomatous polyposis coli pathway shown by nuclear localization of the ß-catenin protein. Few reports showed an association with tuberous sclerosis, though most of these cases were sporadic. We discuss a rare case of desmoplastic fibroma involving the mandible, and a review of the literature of the DF cases involving the gnathic bones.


Assuntos
Humanos , Feminino , Pré-Escolar , Neoplasias Ósseas/patologia , Fibroma Desmoplásico/patologia , Mandíbula
2.
Anticancer Res ; 39(11): 6057-6062, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704832

RESUMO

BACKGROUND/AIM: The prognosis of patients with osteosarcoma is poor; therefore, new treatment strategies are urgently needed. Phosphodiesterase 2 (PDE2) is one of the 11 families (PDE1-PDE11) of the phosphodiesterase superfamily that regulates the intracellular concentrations and effects of cAMP and cGMP. This in vitro study was performed to investigate the role of PDE2 in human oral osteosarcoma HOSM-1 cells. MATERIALS AND METHODS: PDE2 expression was measured by a cAMP-PDE assay and real-time-PCR. The effects of the PDE2-specific inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), 8-bromo-cAMP, and 8-bromo-cGMP on cell proliferation and migration were assessed. RESULTS: PDE2 activity and PDE2A mRNA expression were detected in HOSM-1 cells. Cell proliferation was inhibited by EHNA and 8-bromo-cAMP but not by 8-bromo-cGMP. Cell migration was stimulated by EHNA and 8-bromo-cGMP, but it was inhibited by 8-bromo-cAMP. CONCLUSION: Cell proliferation is regulated by PDE2-cAMP signaling and cell migration is regulated by PDE2-cGMP signaling in HOSM-1 cells.


Assuntos
Neoplasias Ósseas/patologia , Movimento Celular , Proliferação de Células , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo , Neoplasias Bucais/patologia , Osteossarcoma/patologia , Adenina/análogos & derivados , Adenina/farmacologia , Apoptose , Compostos de Benzil/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/enzimologia , Ciclo Celular , AMP Cíclico/farmacologia , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/enzimologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/enzimologia , Transdução de Sinais , Células Tumorais Cultivadas
3.
Anticancer Res ; 39(11): 6145-6153, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704842

RESUMO

AIM: This study aimed to evaluate the antitumor effects of cyclolinopeptide (CL), which suppresses receptor activator of nuclear factor-κB ligand (RANKL) signalling on giant-cell tumours of the bone (GCTB) cells. MATERIALS AND METHODS: GCTB cell lines were established, and the inhibition of cell growth by CL was evaluated using the water-soluble tetrazolium salt-8 cell proliferation assay, cell cycle assay, and 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay. RANKL and runt-related transcription factor 2 (RUNX2) expression levels were evaluated using real-time polymerase chain reaction before and after CL administration. RESULTS: The dose-dependent inhibition of GCTB cells was significantly pronounced in the CL-administered group compared to the non-CL-administered group (p<0.05). In the CL-administered group, the ratio of cells in the G0/G1 phase was increased, but the ratio of EdU-positive cells was decreased (p<0.05). RANKL and RUNX2 levels were decreased in the CL-administered group (p<0.05). CONCLUSION: CL has antitumor effects on GCTB in vitro.


Assuntos
Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Tumor de Células Gigantes do Osso/patologia , Peptídeos Cíclicos/farmacologia , Células Estromais/patologia , Biomarcadores Tumorais/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Tumor de Células Gigantes do Osso/tratamento farmacológico , Tumor de Células Gigantes do Osso/genética , Tumor de Células Gigantes do Osso/metabolismo , Humanos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Tumorais Cultivadas
4.
Anticancer Res ; 39(10): 5605-5610, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570456

RESUMO

BACKGROUND/AIM: We analyzed the process of healing at osteotomy sites and timing of achievement of full weight-bearing in sarcoma patients who underwent hemicortical or intercalary reconstruction using the extracorporeal irradiated autologous bone graft technique. PATIENTS AND METHODS: We studied 10 patients who had undergone tumor resection and reconstruction with hemicortical extracorporeal irradiated autologous bone graft at mid-shaft femur or tibia. The control group consisted of 30 patients who received the reconstruction using intercalary bone graft. RESULTS: Full weight-bearing was achieved in all 10 patients at a median time of 4.8 months. Function was excellent in all patients. When comparing the clinical outcome among the patients who received intercalary and hemicortical grafts, the duration to full weight-bearing achievement in patients who received hemicortical graft was shorter than that in those with intercalary graft. CONCLUSION: Early full weight-bearing may be achieved in patients undergoing hemicortical resection and reconstruction using extracorporeal irradiated autologous bone graft.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transplante Ósseo/métodos , Osso e Ossos/patologia , Osso e Ossos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia , Transplante Autólogo/métodos , Resultado do Tratamento
5.
Bull Cancer ; 106(11): 983-999, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31587802

RESUMO

INTRODUCTION: Osteosarcoma is the most common malignant bone tumor before 25 years of age. Response to neoadjuvant chemotherapy determines continuation of treatment and is also a powerful prognostic factor. There are currently no reliable ways to evaluate it early. The aim is to develop a method to predict the chemotherapy response using radiomics from pre-treatment MRI. METHODS: Clinical characteristics and MRI of patients treated for local or metastatic osteosarcoma were collected retrospectively in the Rhône-Alpes region, from 2007 to 2016. On initial MRI exams, each tumor was segmented by expert radiologist and 87 radiomic features were extracted automatically. Univariate analysis was performed to assess each feature's association with histological response following neoadjuvante chemotherapy. To distinguish good histological responder from poor, we built predictive models based on support vector machines. Their classification performance was assessed with the area under operating characteristic curve receiver (AUROC) from test data. RESULTS: The analysis focused on the MRIs of 69 patients, 55.1% (38/69) of whom were good histological responders. The model obtained by support vector machines from initial MRI radiomic data had an AUROC of 0.98, a sensitivity of 100% (IC 95% [100%-100%]) and specificity of 86% (IC 95% [59.7%-111%]). DISCUSSION: Radiomic based on MRI data would predict the chemotherapy response before treatment initiation, in patients treated for osteosarcoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Aprendizado de Máquina , Imagem por Ressonância Magnética , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Adolescente , Análise de Variância , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Feminino , França , Humanos , Lactente , Recém-Nascido , Masculino , Terapia Neoadjuvante , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
6.
Bone Joint J ; 101-B(10): 1313-1320, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564158

RESUMO

AIMS: The aim of this study was to report the outcomes of patients who underwent definitive surgery for secondary chondrosarcomas arising from osteochondromas. PATIENTS AND METHODS: A total of 51 patients with secondary chondrosarcomas occurring from osteochondromas were reviewed. Median age was 36 years (interquartile range (IQR) 15 to 82). Median follow-up was 6.9 years (IQR 2.8 to 10.6). The pelvis was the most commonly affected site (59%). Histological grades were grade I in 35 (69%), grade II in 13 (25%), and grade III in three patients (6%). RESULTS: Preoperative biopsy histology correctly predicted the final histological grade in 27% of patients. The ten-year disease-specific survival (DSS) for all patients was 89.4%. Local recurrence occurred in 15 patients (29%), more commonly in pelvic tumours (37%) compared with limb tumours (19%). Four patients with pelvic tumours died from progression of local recurrence. No patient with limb tumours died of disease. Wide/radical margin was associated with improved local recurrence-free survival (p = 0.032) and local recurrence was associated with worse DSS (p = 0.005). CONCLUSION: We recommend that a secondary chondrosarcoma arising from osteochondroma of the pelvis is resected with wide/radical resection margins. The balance between the morbidity of surgery and risk of local recurrence needs to be considered in patients with limb secondary chondrosarcomas. Cite this article: Bone Joint J 2019;101-B:1313-1320.


Assuntos
Neoplasias Ósseas/patologia , Condrossarcoma/secundário , Recidiva Local de Neoplasia/mortalidade , Osteocondroma/patologia , Adulto , Biópsia por Agulha , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/mortalidade , Condrossarcoma/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Extremidades/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Osteocondroma/diagnóstico por imagem , Osteocondroma/mortalidade , Osteocondroma/cirurgia , Ossos Pélvicos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
7.
Medicine (Baltimore) ; 98(39): e17197, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574827

RESUMO

Controversies exist between the previous two prognostic nomograms for patients with bone metastatic prostate cancer (PCa), and a nomogram applied to western patients has yet to be established. Thus, we aimed to build a reliable and generic nomogram to individualize prognosis.The independent prognostic factors were identified in a retrospective study of 1556 patients with bone metastatic PCa registered in the Surveillance, Epidemiology and End Results (SEER) database. Besides, the prognostic nomogram was developed using R software according to the result of multivariable Cox regression analysis. Then, the discriminative ability of the nomogram was assessed by analyses of receiver operating characteristic curves (ROC curves). We also performed 1-, 2-, and 3-year calibrations of the nomogram by comparing the predicted survival to the observed survival. Furthermore, the model was externally validated using the data of 711 patients diagnosed at different times enrolled in the SEER database.Age ≥70 years, Gleason score ≥8, PSA value of 201 to 900 ng/ml, stage T4, stage N1, with liver metastases, and Asian/Pacific ethnicity were identified as independent prognostic factors. In the primary cohort, 1-, 2-, and 3-year area under the ROC curve (AUC) of the nomogram for predicting cancer-specific survival (CSS) were 0.71, 0.70, and 0.70, respectively. Besides 1-, 2-, and 3-year AUC were 0.70, 0.68, and 0.69, respectively, in the external validation cohort. Moreover, calibration curves presented perfect agreements between the nomogram-predicted and actual 1-, 2-, and 3-year CSS rate in both the primary and external validation cohorts. In other words, our nomogram has great predictive accuracy and reliability in predicting 1-, 2-, and 3-year CSS for patients with bone metastatic prostate cancer.This study established and validated a prognostic nomogram applied to not only Asian patients but western patients with bone metastatic PCa, which will be useful for patients' counseling and clinical trial designing.


Assuntos
Neoplasias Ósseas/mortalidade , Nomogramas , Neoplasias da Próstata/mortalidade , Medição de Risco/normas , Idoso , Neoplasias Ósseas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Próstata/patologia , Neoplasias da Próstata/secundário , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida
8.
Cell Physiol Biochem ; 53(4): 731-745, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31613064

RESUMO

BACKGROUND/AIMS: 3-Deazaneplanocin, DZNep, has been reported to inhibit the EZH2 histone methylase and to induce cell apoptosis in chondrosarcomas (CS). The present study aims to confirm the therapeutic potential of EZH2 inhibitors and investigate the molecular mechanisms of DZNep in chondrosarcomas. METHODS: CS cell lines and primary cultures were used. Apoptosis was investigated using PARP cleavage, caspase 3/7 activity, or Apo2.7 expression. S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) were quantified by UHPLC-MS/MS. Differentially expressed genes in treated-chondrosarcomas and chondrocytes were researched by microarray analysis. RESULTS: DZNep induced apoptosis in chondrosarcomas both in vivo and in vitro. However, this effect was not correlated to EZH2 expression nor activity, and EZH2 knock-down by siRNA did not reduce CS viability. Additionally, the reduction of H3K27me3 induced by GSK126 or tazemetostat (EPZ-6438) did not provoke chondrosarcoma death. However, as expected, DZNep induced SAH accumulation and reduced SAM:SAH ratio. Further, microarray analysis suggests a key role of EGFR in antitumoral effect of DZNep, and pharmacological inhibition of EGFR reduced chondrosarcoma survival. CONCLUSION: EZH2 is not an adequate target for chondrosarcoma treatment. However, DZNep induces apoptosis in chondrosarcomas in vitro and in vivo, by a mechanism likely mediated though EGFR expression. Consequently, it would be worth initiating clinical trials to evaluating efficiency to S-adenosylhomocysteine hydrolase or EGFR inhibitors in patients with chondrosarcomas.


Assuntos
Adenosina/análogos & derivados , Regulação para Baixo/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Adenosina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Condrossarcoma/metabolismo , Condrossarcoma/patologia , Dano ao DNA/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Histonas/metabolismo , Humanos , Masculino , Camundongos , Camundongos Nus , Mapas de Interação de Proteínas/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , S-Adenosil-Homocisteína/metabolismo
9.
Anticancer Res ; 39(9): 5027-5031, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519610

RESUMO

AIM: The purpose of this study was to identify patient-, facility-, disease-, and treatment-specific characteristics that increase mortality in patients with upper limb osteosarcoma. PATIENTS AND METHODS: The National Cancer Data Base (NCDB) was queried for bone cancer. With Cox regression, the demographic, facility, tumor-specific and treatment characteristics were analyzed to identify factors that increased mortality. RESULTS: Cox regression model showed that patients older than 40 years had a significantly higher likelihood of dying from upper limb osteosarcoma than those aged 0-14 years [hazard ratio (HR)=4.12, 95% confidence interval (CI)=2.261-7.508]. Patients with an income of $38,000-47,999 (HR=3.335, 95%CI=1.694-657) or less than $38,000 (HR=2.41, 95%CI=1.098-5.288) were also at greater risk of dying from their tumor. Patients who received radiation therapy (HR=2.457, 95%CI=1.056-5.717) had a higher likelihood of dying than patients who did not undergo this therapy. CONCLUSION: Age, gender, income, education, stage at diagnosis, radiation therapy and type of surgery seem to increase mortality from upper limb osteosarcoma.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Extremidade Superior/patologia , Adolescente , Adulto , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estadiamento de Neoplasias , Osteossarcoma/epidemiologia , Osteossarcoma/terapia , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Socioeconômicos , Carga Tumoral , Estados Unidos/epidemiologia , Adulto Jovem
10.
Gene ; 721: 144093, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31473323

RESUMO

Previous studies have determined that long non-coding RNA (lncRNA) Fer-1-like protein 4 (FER1L4) is suppressed in osteosarcoma (OS) and inhibits the tumorigenesis in a variety of cancer. However, the precise biological of FER1L4 in OS has not been cleared. The aim of this study is to investigate the roles and potential mechanisms of FER1L4 in apoptosis and epithelial-mesenchymal transition (EMT) in OS. In the present study, the levels of FER1L4 were decreased significantly in OS tissues and cell lines compared with non-tumorous tissues or hFOB1.19. Knockdown of FER1L4 in OS cells decreased the apoptosis rate, but increased the OS cell proliferation, upregulated the expression levels of CD133 and Nanog, as well as promoted Twist1 expression, increased the N-cadherin and Vimentin expression. In turn, the opposite trends were observed upon overexpression of FER1L4. In addition, the expression of PI3K, p-AKT (Ser470) and p-AKT (Thr308) was upregulated by siFER1L4, while decreased upon overexpression of FER1L4. MicroRNA (miRNA) -18a-5p, an osteosarcoma-promoting miRNA which was suggested a target of FER1L4 in osteosarcoma, was identified to be a functional target of FER1L4 on the regulating of cell apoptosis and EMT, presently. The effects of FER1L4 overexpression on the markers of cell apoptosis, proliferation, EMT, and stemness and PI3K/AKT signaling were all reversed by miR-18a-5p upregulation. Furthermore, the suppressor of cytokine signaling 5 (SOCS5) was confirmed a target gene of miR-18a-5p by luciferase gene reporter assay and SOCS5 suppression by miR-18a-5p attenuated the effects of FER1L4 overexpression on the OS cells apoptosis and the expressed levels of PI3K, AKT, Twist1, N-cadherin and Vimentin. In conclusion, our data indicated thatthe overexpression of FER1L4 promoted apoptosis and inhibited the EMT markers expression and PI3K/AKT signaling pathway activation in OS cells via downregulating miR-18a-5p to promote SOCS5.


Assuntos
Apoptose , Neoplasias Ósseas/metabolismo , Transição Epitelial-Mesenquimal , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/biossíntese , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Proteínas Supressoras da Sinalização de Citocina/genética
13.
J Surg Oncol ; 120(7): 1252-1258, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31486107

RESUMO

BACKGROUND AND OBJECTIVES: With recent advances in chemotherapy and surgical techniques, the trend in the treatment of osteosarcoma continues to progress towards limb salvage. However, studies comparing limb salvage with amputation continue to be limited by selection bias and small sample sizes. This study utilized propensity-score matching to minimize potential confounders and selection bias to compare the survival rates in patients with osteosarcoma that were treated with amputation vs limb salvage surgery. METHODS: The Surveillance, Epidemiology, and End Results Program was utilized to identify all patients with a diagnosis of extremity osteosarcoma. Patients were matched with demographics, tumor characteristics, and treatment information. These variables were then fitted in a multivariate model and hazard ratios (HR) for overall- and disease-specific mortality was calculated. RESULTS: A total of 4107 patients were identified, of which, 1538 were left after propensity-score matching. Older age, Black race, upper extremity location, and higher American joint committee on cancer (AJCC) class were associated with worse overall- and disease-specific mortality rates (P ≤ .0389). Compared with their matched counterparts, patients treated with amputation had higher overall mortality (HR 1.677; P < .0001) and higher disease-specific mortality (HR 1.678; P < .0001). CONCLUSION: Patients whose tumor characteristics preclude limb salvage have significantly higher overall- and disease-specific mortality rates.


Assuntos
Amputação/mortalidade , Neoplasias Ósseas/cirurgia , Salvamento de Membro/mortalidade , Osteossarcoma/cirurgia , Terapia de Salvação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Osteossarcoma/patologia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Adulto Jovem
14.
Life Sci ; 234: 116771, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421084

RESUMO

AIMS: We aimed to elucidate the effects and mechanisms of MAT1 in the progression of osteosarcoma, especially for its lung metastasis. MAIN METHODS: CCK-8 and flow cytometry assays were carried out to detect the proliferation and apoptosis of osteosarcoma cells. Wound healing and transwell assays were used to determine cell migration and invasion abilities. Real time quantitative PCR (RT-PCR) and western blot technologies were applied to detect the expression levels of RNA and protein, respectively. KEY FINDS: The results showed that both the mRNA and protein expression levels of MAT1 were elevated in osteosarcoma tissues with lung metastasis and metastatic lung tissues, particularly in the metastatic lung tissues, as compared to the osteosarcoma tissues without lung metastasis. High expression level of MAT1 in osteosarcoma patients showed a negative association with the overall survival. In addition, upregulation of MAT1 induced significant increases in cell growth, migration and invasion and an obvious inhibition in cell apoptosis in osteosarcoma MG63 and 143B cells, as well as elevated AKT1 expression level. Moreover, knockdown of AKT1 obviously impaired MAT1-mediated promotions in cell migration and invasion in vitro, as well as repressed tumor growth and reduced the number of metastatic lung tumors in xenografted nude mice. SIGNIFICANCE: This study reveals that high expression of MAT1 closely related to the poor prognosis and malignant clinical process of osteosarcoma patients. MAT1 serves as a promoter in the lung metastasis of osteosarcoma through increasing AKT1 expression. Our study may provide a potent therapeutic target for the lung metastasis of osteosarcoma.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Neoplasias Ósseas/patologia , Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Adulto , Animais , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/genética , Regulação para Cima , Adulto Jovem
15.
Life Sci ; 233: 116757, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31419446

RESUMO

AIMS: Previous studies have demonstrated that long non-coding RNAs (lncRNAs) were involved in tumorigenesis in various human neoplasms, including osteosarcoma (OS). However, the expression and specific role of lncRNA linc00460 in OS remain unknown. MATERIALS AND METHODS: Bioinformatics analysis, Quantitative real-time polymerase chain reaction (qRT-PCR), CCK-8 assay, Colony formation assay, Wound healing assay, Transwell assay, Dual luciferase reporter assay, RNA immunoprecipitation and Western blot were utilized to analyze or detect survival, gene expression, cell proliferation, cell migration, cell invasion and interest protein levels, respectively. KEY FINDINGS: In this study, we found high linc00460 expression predicted poor prognosis of pan-cancer patients. Linc00460 was up-regulated in OS tissues and cells. High linc00460 expression was positively correlated with distant metastasis and poor overall survival of OS patients. Knockdown of linc00460 suppressed OS cells proliferation and metastasis in vitro. In addition, an inverse correlation between linc00460/miR-1224-5p and miR-1224-5p/FADS1 was observed in OS. Mechanistically, linc00460 functioned as a competitively endogenous RNA (ceRNA) to up-regulate FADS1 expression via sponging miR-1224-5p in OS, thereby promoting OS progression. SIGNIFICANCE: In conclusion, this study recognized linc00460 as a new oncogenic lncRNA in OS and suggests that the linc00460/miR-1224-5p/FADS1 axis might be a potential therapeutic target for OS.


Assuntos
Neoplasias Ósseas/patologia , Ácidos Graxos Dessaturases/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/patologia , RNA Longo não Codificante/genética , Adulto , Apoptose , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/cirurgia , Movimento Celular , Proliferação de Células , Progressão da Doença , Ácidos Graxos Dessaturases/genética , Feminino , Humanos , Masculino , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/cirurgia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Adulto Jovem
16.
Rev Med Suisse ; 15(659): 1462-1465, 2019 Aug 21.
Artigo em Francês | MEDLINE | ID: mdl-31436063

RESUMO

Osteoid osteoma is frequent benign tumor, descripted initially by Bergstrand in 1930 followed by Jaffe in 1935. The painful feature of the osteoid osteoma explains the specific consideration by the medical community for this entity. The debate was focused on pathologic and imaging pattern as well as the treatment modalities. Currently, the treatment options are varied and percutaneous treatment is increasingly used. The radiofrequency is widely validated as efficient method without serious adverse and with low rate of recurrence. We hope through this this work to revue the current knowledge of the treatment of osteoid osteoma.


Assuntos
Neoplasias Ósseas , Osteoma Osteoide , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Ablação por Cateter , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Osteoma Osteoide/patologia , Osteoma Osteoide/terapia , Ablação por Radiofrequência/normas
17.
J Surg Oncol ; 120(6): 985-993, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31381161

RESUMO

PURPOSE: The purpose of this study was to clarify which local treatment is oncologically and functionally effective in pelvic Ewing sarcoma (ES). METHODS: A consecutive series of patients who underwent pelvic resections and acetabular reconstructions after chemotherapy between 1986 and 2016 at a supra-regional center were evaluated. RESULTS: The cohort consisted of 35 patients. The 5-year overall survival (OS) and local recurrence-free survival (LRFS) was 61% and 72%, respectively. Preoperative radiotherapy (RT) and surgery provided an excellent/good histological response in 92% and achieved significantly better OS (5 years, 64%) and LRFS (5 years, 100%) than surgery alone or surgery with postoperative RT. The Musculoskeletal Tumor Society functional scores were significantly better in patients with hip transposition than those with structural reconstructions (74% vs 57%; P = .031) using custom-made prostheses, irradiated autografts, and ice-cream cone prostheses. These scores were significantly lower if patients had deep infection (P = .035), which was the most common complication (28%) in structural reconstructions but did not occur in hip transposition even when performed after preoperative RT. CONCLUSION: Acetabular reconstruction with hip transposition resulted in no deep infection and superior function in patients with pelvic ES even when combined with preoperative RT, which improved tumor necrosis and rate of local control and survival.


Assuntos
Acetábulo/cirurgia , Neoplasias Ósseas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Ossos Pélvicos/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Terapia de Salvação , Sarcoma de Ewing/cirurgia , Acetábulo/patologia , Adolescente , Adulto , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Criança , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Ossos Pélvicos/patologia , Prognóstico , Estudos Retrospectivos , Sarcoma de Ewing/patologia , Sarcoma de Ewing/terapia , Taxa de Sobrevida , Adulto Jovem
18.
Yonsei Med J ; 60(9): 832-841, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31433581

RESUMO

PURPOSE: Epirubicin is one of the most effective drugs against osteosarcoma. miR-1301 is involved in the occurrence and development of osteosarcoma. Whether miR-1301 is responsible for the chemosensitivity of osteosarcoma cells to epirubicin remains largely unknown. MATERIALS AND METHODS: U2OS and SAOS-2 cells were treated with various concentrations of epirubicin. Flow cytometry was employed to evaluate cell apoptotic rate. Cell proliferation was measured by Cell Counting Kit-8 assay. Western blot and quantitative real-time polymerase chain reaction were utilized to detect the expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 assaciated X protein (Bax), cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerases (PARP1), TP53-regulated inhibitor of apoptosis 1 (TRIAP1), and microRNA-1301 (miR-1301). The relationship between miR-1301 and TRIAP1 was determined by luciferase reporter assay. RESULTS: Epirubicin inhibited proliferation in a dose-dependent manner, induced apoptosis, decreased the expression of Bcl-2, and increased the expressions of Bax, cleaved-caspase-3, and cleaved-PARP1 in osteosarcoma cells. miR-1301 was downregulated in U2OS and SAOS-2 cells. Importantly, epirubicin significantly increased the levels of miR-1301. Overexpression of miR-1301 suppressed proliferation and promoted apoptosis. Interestingly, those effects were enhanced by epirubicin. In contrast, miR-1301 depletion attenuated the epirubicin-mediated anti-osteosarcoma effect. miR-1301 negatively regulated the expression of TRIAP1 in U2OS and SAOS-2 cells. Furthermore, epirubicin inhibited the mRNA and protein levels of TRIAP1 by upregulating miR-1301 levels. Epirubicin suppressed cell proliferation by downregulating TRIAP1. CONCLUSION: miR-1301 was implicated in the chemosensitivity of osteosarcoma to epirubicin by modulating TRIAP1.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Epirubicina/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/genética , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Caspase 3/biossíntese , Linhagem Celular Tumoral , Regulação para Baixo , Epirubicina/farmacologia , Citometria de Fluxo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Osteossarcoma/genética , Osteossarcoma/patologia , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
19.
Yonsei Med J ; 60(9): 882-886, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31433587

RESUMO

Ameloblastoma in the tibia is rare. Limb reconstruction after tumor resection is challenging in terms of selection of the operative method. Here, we report a case of radical resection of an ameloblastoma in the mid-distal tibia combined with limb salvage using a three-dimensional (3D)-printed prosthesis replacement, with 1-year follow-up results. After receiving local institutional review board approval, a titanium alloy prosthesis was designed using a computer and manufactured with 3D-printing technology. During the operation, the stem of the prosthesis was inserted closely into the proximal tibial medullary cavity. Then, the metal ankle mortise and the talus were compacted closely. Radiographic results at 1-year follow up showed that the prosthesis was well placed, and no loosening was observed. The Musculoskeletal Tumor Society (MSTS) 93 functional score was 26 points, and the functional recovery percentage was 86.7%. Computer-assisted 3D-printing technology allowed for more volume and structural compatibility of the prosthesis, thereby ensuring a smooth operation and initial prosthetic stabilization. During the follow up, the presence of bone ingrowths on the porous surface of some segments of the prosthesis suggested good outcomes for long-term biological integration between the prosthesis and host bone.


Assuntos
Ameloblastoma/cirurgia , Neoplasias Ósseas/cirurgia , Salvamento de Membro/métodos , Impressão Tridimensional , Desenho de Prótese/métodos , Implantação de Prótese , Tíbia/patologia , Tíbia/cirurgia , Adulto , Ameloblastoma/patologia , Neoplasias Ósseas/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Próteses e Implantes , Resultado do Tratamento
20.
Cancer Sci ; 110(10): 3157-3172, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432600

RESUMO

The underlying mechanisms of breast cancer cells metastasizing to distant sites are complex and multifactorial. Bone sialoprotein (BSP) and αvß3 integrin were reported to promote the metastatic progress of breast cancer cells, particularly metastasis to bone. Most theories presume that BSP promotes breast cancer metastasis by binding to αvß3 integrin. Interestingly, we found the αvß3 integrin decreased in BSP silenced cells (BSPi), which have weak ability to form bone metastases. However, the relevance of their expression in primary tumor and the way they participate in metastasis are not clear. In this study, we evaluated the relationship between BSP, αvß3 integrin levels, and the bone metastatic ability of breast cancer cells in patient tissues, and the data indicated that the αvß3 integrin level is closely correlated to BSP level and metastatic potential. Overexpression of αvß3 integrin in cancer cells could reverse the effect of BSPi in vitro and promote bone metastasis in a mouse model, whereas knockdown of αvß3 integrin have effects just like BSPi. Moreover, The Cancer Genome Atlas data and RT-PCR analysis have also shown that SPP1, KCNK2, and PTK2B might be involved in this process. Thus, we propose that αvß3 integrin is one of the downstream factors regulated by BSP in the breast cancer-bone metastatic cascade.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Integrina alfaVbeta3/metabolismo , Sialoproteína de Ligação à Integrina/metabolismo , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Quinase 2 de Adesão Focal/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Inativação Gênica , Humanos , Sialoproteína de Ligação à Integrina/genética , Células MCF-7 , Camundongos , Transplante de Neoplasias , Osteopontina/genética , Canais de Potássio de Domínios Poros em Tandem/genética
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