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1.
Zhonghua Zhong Liu Za Zhi ; 42(8): 692-696, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867464

RESUMO

Objective: To evaluate the efficacy and safety of polyethylene glycol liposome doxorubicin (PLD) in the treatment of osteosarcoma. Methods: This study was a single-center retrospective clinical study. Two hundreds and seventy-six classical osteosarcoma treated in Beijing Jishuitan Hospital from 2015 to 2016 were enrolled. There were 213 patients who received combined chemotherapy of high dose methotrexate, ifosfamide, cisplatin and doxorubicin (ADM) were classified in ADM group. Other 63 patients received the same types, doses and cycles of chemotherapy drugs except ADM replaced by PLD were identified as PLD group. Clinical and imaging evaluation and surgical treatment were performed after neoadjuvant chemotherapy. Tumor necrosis rate was examined according to Huvos method. The efficacy of neoadjuvant chemotherapy was evaluated based on 90% necrosis rate. The recurrence, metastasis and survival were followed up regularly after operation. The adverse reactions of hematology, hepatorenal toxicity, gastrointestinal reaction and cardiotoxicity were evaluated. Results: There were no significant differences between PLD group and ADM group in age, sex, location, stage and surgical margin (all P>0.05). There were no significant differences in clinical symptoms and imaging evaluation between PLD group and ADM group after preoperative chemotherapy (all P>0.05). The tumor necrosis rate was detected in 134 cases. Among 27 cases of PLD group, tumor necrosis rates more than 90% were 11 cases, while among 107 cases of ADM group, tumor necrosis rates more than 90% were 45 cases. No significant difference of tumor necrosis rate between this two group was observed (P=0.901). The recurrence rates of PLD group and ADM group were 7.8% (4/51) and 7.3% (12/164), the metastasis rates were 19.6% (10/51) and 16.5% (27/164), the median progression free survival (PFS) were 42 and 37 months, respectively, without significant differences (all P>0.05). The incidence of granulocytopenia and decrease degree of granulocytes in PLD group were significantly lower than those in ADM group (P<0.001). There were no significant differences in the incidences of thrombocytopenia, anemia, gastrointestinal reaction, liver function damage and stomatitis between two groups (all P>0.05). Conclusions: PLD and ADM have similar chemotherapeutic effects in osteosarcoma. The incidences of adverse reactions of PLD are lower, especially the hematological toxicity represented by granulocytopenia is significantly reduced. PLD has a better application prospect.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/terapia , Lipossomos/uso terapêutico , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/patologia , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Extremidades , Humanos , Ifosfamida/administração & dosagem , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteossarcoma/patologia , Polietilenoglicóis , Prognóstico , Estudos Retrospectivos
2.
Anticancer Res ; 40(10): 5735-5738, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988899

RESUMO

BACKGROUND/AIM: Surgical staging is paramount to treatment of primary bone sarcomas. Often, bone scintigraphy and/or positron emission tomography-computed tomography (PET-CT) are used to exclude skeletal metastases; however, skeletal metastases in chondrosarcoma are rare. The purpose of this study was to assess the utility of these staging methods in patients with chondrosarcoma. PATIENTS AND METHODS: We reviewed 138 (87 males, 51 female) patients, mean age 54±20 years, with a chondrosarcoma, who had completed a bone scintigraphy or PET/CT as part of surgical staging. Sensitivity, specificity, and positive/negative predictive value of the scans was calculated. RESULTS: Seventeen (12%) patients had a positive bone scintigraphy or PET-CT for skeletal metastases. In cases of bone scintigraphy (n=11), 6 were benign and 5 were skeletal metastases. In cases of PET-CT, 6 were skeletal metastases, 3 were positive and 3 benign. All positive cases regarded dedifferentiated chondrosarcoma. The overall sensitivity and specificity of a bone scan or PET-CT was 100% and 93.1%; with a positive and negative predictive value of 47.1% and 100%, respectively. CONCLUSION: Skeletal metastases at presentation of chondrosarcoma are rare and associated with dedifferentiated chondrosarcoma. Bone scintigraphy or PET-CT should only be performed in cases of high grade and dedifferentiated histology.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Condrossarcoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Cintilografia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Condrossarcoma/patologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia Computadorizada por Raios X
3.
Gene ; 763: 145068, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-32827680

RESUMO

CircRNAs are reported to exert a significant role in modulating genes in cancers, including osteosarcoma progression. Up to now, the function of circ_0010220 in osteosarcoma is still poorly known. The aim of our work was to figure out the potential mechanism of circ_0010220/miR-503-5p/CDCA4 axis in osteosarcoma progression. Firstly, quantitative RT-qPCR was utilized to measure the expression of circ_0010220 in osteosarcoma cells. Then, osteosarcoma cell proliferation, apoptosis, cell cycle, migration and invasion after loss of circ_0010220 were evaluated using CCK-8, flow cytometry, transwell migration, invasion and tumorigenesis experiments respectively. Circ_0010220 expression was markedly increased in osteosarcoma cells. Additionally, knockdown of circ_0010220 significantly depressed tumor growth. CCK-8 analysis indicated that down-regulation of circ_0010220 inhibited osteosarcoma cells proliferation. Flow cytometry assay showed that knockdown of circ_0010220 induced cell apoptosis and blocked cell cycle in the G1 phase. Meanwhile, cell migration an invasion was reduced by circ_0010220. Furthermore, miR-503-5p was predicted as the target for circ_0010220 and miR-503-5p inhibitors reversed cell growth suppressed through silencing circ_0010220. Then, our study demonstrated that Cell Division Cycle-Associated protein 4 (CDCA4) could be a downstream target of miR-503-5p. Additionally, circ_0010220 down-regulation reduced CDCA4 expression level and the inhibitors of miR-503-5p reversed that. In conclusion, we indicated circ_0010220 can be an important biomarker for osteosarcoma via regulating miR-503-5p and CDCA4.


Assuntos
Neoplasias Ósseas/genética , Proteínas de Ciclo Celular/genética , MicroRNAs/genética , Osteossarcoma/genética , RNA Circular/genética , Animais , Apoptose , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Carcinogênese/genética , Carcinogênese/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , RNA Circular/metabolismo
4.
Int J Nanomedicine ; 15: 5131-5146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764941

RESUMO

Background: Gene therapy is considered a novel way to treat osteosarcoma, and microRNAs are potential therapeutic targets for osteosarcoma. miR-214 has been found to promote osteosarcoma aggression and metastasis. Graphene oxide (GO) is widely used for gene delivery for the distinct physiochemical properties and minimal cytotoxicity. Methods: Polyethyleneimine (PEI)-functionalized GO complex was well-prepared and loaded with miR-214 inhibitor at different concentrations. The load efficacy was tested by gel retardation assay and the cy3-labeled fluorescence of cellular uptake. The experiments of wound healing, immunofluorescence staining, Western blot, qRT-PCR and immunohistochemical staining were performed to measure the inhibitory effect of the miR-214 inhibitor systematically released from the complexes against MG63, U2OS cells and xenograft tumors. Results: The systematic mechanistic elucidation of the efficient delivery of the miR-214 inhibitor by GO-PEI indicated that the inhibition of cellular miR-214 caused a decrease in osteosarcoma cell invasion and migration and an increase in apoptosis by targeting phosphatase and tensin homolog (PTEN). The synergistic combination of the GO-PEI-miR-214 inhibitor and CDDP chemotherapy showed significant cell death. In a xenograft mouse model, the GO-PEI-miR-214 inhibitor significantly inhibited tumor volume growth. Conclusion: This study indicates the potential of functionalized GO-PEI as a vehicle for miRNA inhibitor delivery to treat osteosarcoma with low toxicity and miR-214 can be a good target for osteosarcoma therapy.


Assuntos
Grafite/química , MicroRNAs/antagonistas & inibidores , Terapia de Alvo Molecular , Osteossarcoma/tratamento farmacológico , PTEN Fosfo-Hidrolase/metabolismo , Polietilenoimina/química , Polietilenoimina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Ósseas/patologia , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/genética , Terapia Combinada , Humanos , Camundongos , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia
5.
J Cancer Res Clin Oncol ; 146(11): 2871-2883, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32770382

RESUMO

PURPOSE: Polo-like kinase 4 (PLK4) inhibitors, such as CFI-400945 and centrinone, are emerging as promising antineoplastic agents. However, their effectiveness against Ewing's sarcoma, a highly aggressive childhood cancer, remains to be established. METHODS: CFI-400945 and centrinone were tested in three Ewing's sarcoma cell lines with different TP53 status. Effects were assessed by flow-cytometric analyses of cell death, dissipation of the mitochondrial transmembrane potential and cell cycle distribution, by cell viability assay as well as by caspase 3/7 activity measurement, by immunoblotting and by immunofluorescence microscopy. RESULTS: CFI-400945 and centrinone elicited cell death in p53 wild-type and mutant Ewing's sarcoma cells. Both agents induced mitochondrial membrane depolarisation, caspase 3/7 activation, PARP1 cleavage and DNA fragmentation, indicating an apoptotic form of cell death. In addition, the PLK4 inhibitors induced a G2/M cell cycle arrest, particularly when cell killing was attenuated by the pan-caspase inhibitor z-VAD-fmk. Moreover, CFI-400945 treatment produced polyploidy. CONCLUSION: Our findings show that PLK4 inhibitors were effective against Ewing's sarcoma cells in vitro and thus provide a rationale for their evaluation in vivo.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Ósseas/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Sarcoma de Ewing/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Indazóis/farmacologia , Indóis/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Pirimidinas/farmacologia , Sulfonas/farmacologia
6.
BMJ Case Rep ; 13(7)2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641312

RESUMO

A 17-year-old man with osteosarcoma of the proximal humerus was planned for possible limb salvage surgery after standard neoadjuvant chemotherapy. However, during the surgical phase of treatment, the COVID-19 or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) outbreak occurred changing the healthcare landscape due to uncertainty regarding the virus, risk of COVID-19 infection and complications, and implementation of an enhanced community quarantine restricting movement of people within cities. Instead of limb salvage surgery, the patient underwent a forequarter amputation. Exposure to the virus in a high-risk hospital setting was minimised with patient discharge after a short hospital stay and home convalescence monitored by video conferencing. Multidisciplinary sarcoma team meetings with family members and a sarcoma navigator nurse were crucial in managing expectations and deciding on appropriate treatment in the setting of a novel infectious disease causing a pandemic.


Assuntos
Amputação/métodos , Neoplasias Ósseas , Cisplatino/administração & dosagem , Infecções por Coronavirus , Doxorrubicina/administração & dosagem , Úmero , Salvamento de Membro/métodos , Osteossarcoma , Pandemias , Pneumonia Viral , Adolescente , Antineoplásicos , Betacoronavirus , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Humanos , Úmero/diagnóstico por imagem , Úmero/cirurgia , Imagem por Ressonância Magnética/métodos , Masculino , Estadiamento de Neoplasias , Osteossarcoma/patologia , Osteossarcoma/terapia , Pandemias/prevenção & controle , Seleção de Pacientes , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle
8.
Bone Joint J ; 102-B(6): 795-803, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32475245

RESUMO

AIMS: To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. METHODS: Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson's correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. RESULTS: OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. CONCLUSION: Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795-803.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Metotrexato/administração & dosagem , Osteossarcoma/tratamento farmacológico , Osteossarcoma/cirurgia , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Correlação de Dados , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Necrose/induzido quimicamente , Terapia Neoadjuvante , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Período Pré-Operatório , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
9.
Zhonghua Zhong Liu Za Zhi ; 42(6): 433-437, 2020 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-32575936

RESUMO

With the extension of survival period and the improvement of imaging technology, the incidence of bone metastasis from colorectal cancer gradually increases. Therefore, the early diagnosis and treatment of bone metastasis should not be neglected while the primary lesion was controlled.Currently, the available evidence for bone metastasis from colorectal cancer is very limited. In this article, the Chinese Society of Colorectal Cancer organized multi-disciplinary experts to integrate the relevant studies worldwide and combine with clinical practice, focused on the issues and controversies about clinical characteristics, diagnosis and treatment, and follow-up of bone metastatic patients with colorectal cancer.After discussion and voting, Chinese expert consensus on multidisciplinary treatment of bone metastasis from colorectal cancer (2020 version) was formed. This consensus could provide clinicians with more detailed multidisciplinary treatment strategies for bone metastasis from colorectal cancer.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Neoplasias do Colo/terapia , Neoplasias Colorretais/terapia , Guias de Prática Clínica como Assunto , Grupo com Ancestrais do Continente Asiático , Neoplasias Ósseas/patologia , China , Neoplasias do Colo/diagnóstico , Neoplasias Colorretais/diagnóstico , Consenso , Humanos , Comunicação Interdisciplinar , Equipe de Assistência ao Paciente , Resultado do Tratamento
10.
PLoS One ; 15(6): e0232466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492019

RESUMO

Malignant fibrous histiocytoma of the bone (MFH-B) is an extremely rare and aggressive malignancy. The clinicopathological characteristics and prognosis of patients with MFH-B have not been defined. We conducted a retrospective study using the data of all MFH-B patients from the Surveillance, Epidemiology and End Results (SEER) database between 1975 and 2016. Initially, the clinicopathological characteristics were described. The difference in prognosis between patients with MFH-B and those with osteosarcoma was compared using propensity score matching analysis. Then, the features affecting the prognosis of patients with MFH-B were further determined using Cox regression analysis. A total of 318 patients with MFH-B were identified. The median overall survival (mOS) of all 318 patients with MFH-B was 29.0 months. The 1-, 3-, 5-, and 10- year survival rates were 67.4%, 53.6%, 38.7%, and 28.7%, respectively. The multivariate Cox regression analysis showed that older age, distant metastases, and flat bone lesion were independent factors for worse prognosis, whereas surgery was an independent factor for favorable survival, and this intervention could decrease risk of death by 61% (HR = 0.39, 95% CI 0.28-0.54). Apart from this, the prognosis of patients with MFH-B was significantly worse than that of patients with osteosarcoma in both unmatched and matched cohorts. In conclusion, MFH-B is a rare malignant bone cancer, with relatively worse prognosis than osteosarcoma. Older age, distant metastases, flat bone lesion, and surgery were independently associated with prognosis. In order to understand this disease more thoroughly and accurately, more cases with adequate information are required in the future.


Assuntos
Neoplasias Ósseas/patologia , Histiocitoma Fibroso Maligno/patologia , Adulto , Fatores Etários , Idoso , Neoplasias Ósseas/mortalidade , Bases de Dados Factuais , Feminino , Histiocitoma Fibroso Maligno/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida
11.
FP Essent ; 493: 27-29, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32573184

RESUMO

Metastatic bone disease is common, and affects more than 5 million individuals in the United States. Patients may present with bone pain. If a patient is known to have a cancer that commonly spreads to bone (ie, kidney, lung, breast, prostate, thyroid), metastatic bone disease should be considered as a cause. Bone metastases also may be detected incidentally on x-rays. For patients not known to have a cancer, medical history, physical examination, and laboratory tests may indicate the primary malignancy site. X-ray is the primary imaging modality, but magnetic resonance imaging study, computed tomography scan, and nuclear medicine studies also may help identify the site of the primary tumor and extent of metastatic disease. The diagnosis is confirmed with surgical or percutaneous biopsy. Patients with bone metastases are at risk of pathologic fractures, and measures should be taken to prevent these, such as avoidance of weight-bearing on affected extremities or surgical fixation. Patients also should receive, as appropriate for the type of cancer, chemotherapy, radiation, and other treatments. Drugs to promote bone health (eg, bisphosphonates, denosumab) should be considered for all patients with metastatic disease. (This is an off-label use of some bisphosphonates.) When appropriate, palliative care is indicated.


Assuntos
Neoplasias Ósseas , Metástase Neoplásica , Neoplasias Ósseas/patologia , Difosfonatos , Humanos , Imagem por Ressonância Magnética , Cuidados Paliativos , Tomografia Computadorizada por Raios X
12.
APMIS ; 128(8): 487-496, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32562574

RESUMO

Metastatic thyroid cancers are more difficult to treat and have a significantly worse prognosis than localized thyroid cancers. Previous studies have shown that follicular helper T cells (Tfh) may participate in antitumor immune responses. Here, we investigated the characteristics of Tfh cells in patients with differentiated thyroid cancer (DTC) at various severities, including patients with localized disease, cervical metastasis, and distant metastasis. In circulating CD4 T cells, the proportion of CD4+ CXCR5+ Tfh-like cells was significantly higher in patients with distant metastasis than in healthy controls, patients with local disease, and patients with cervical metastasis. Also, the expression of Tfh cell-associated surface molecules, such as PD-1, ICOS, and BTLA, tended to be higher in patients with cervical and distant metastasis than in healthy controls. However, the expression of secreted molecules, such as IL-10, IL-21, and CXCL13, was significantly lower in patients with distant metastasis than in healthy controls and patients with local disease. Additionally, circulating Tfh-like cells from patients with distant metastasis were less capable of supporting B-cell growth and IgM secretion. We also examined the CD4+ CXCR5+ Tfh-like cells in tumor samples. Tumor-infiltrating Tfh-like cells were highly enriched in the pulmonary metastasis compared to the local tumor and the cervical metastasis. However, tumor-infiltrating Tfh-like cells from pulmonary metastasis displayed higher PD-1, TIM-3, and lower IL-21 expression than those from the local tumor. Together, this study identified that the metastasis of DTC patients was associated with an overabundance of defective Tfh cells.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Pulmonares/patologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Antígenos de Superfície/análise , Linfócitos B/imunologia , Neoplasias Ósseas/secundário , Proliferação de Células , Feminino , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Imunoglobulina M/metabolismo , Fatores Imunológicos/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade
13.
J Cancer Res Ther ; 16(2): 215-221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474504

RESUMO

Objective: Osteosarcoma is a malignant bone tumor and is generally treated with radiotherapy combined with radiosensitizers. The aim of the present study was to investigate the radiosensitization effects of berberine on osteosarcoma cells and the role of Rad51 in radiosensitivity by berberine. Materials and Methods: Cells from the human osteosarcoma cell line MG-63 were exposed to γ-ray irradiation (0, 2, 4, 6, and 8 Gy) and berberine (20 µM). Radiosensitivity was evaluated by determining cell viability using an MTT assay. Flow cytometry was used to determine cell cycle and apoptosis. Real-time PCR and western blot were performed to analyze the mRNA and protein expressions of Rad51. The protein levels of E-cadherin and vimentin were also measured to evaluate the epithelial-mesenchymal transition (EMT) process. Tumor invasion was determined by the Boyden chamber assay. Results: Berberine exacerbated the decline in viability of MG-63 cells exposed to γ-rays irradiation at various concentrations (25, 50, 75, and 100 µmol/L) and induced cell cycle arrest in the G2/M phase as well as apoptosis. The mRNA and protein expressions of Rad51 were significantly decreased by berberine in MG-63 cells. Inhibition of Rad51 by B02 enhanced the radiosensitivity of MG-63 cells. Berberine inhibited their invasive capability as well as increased E-cadherin and decreased vimentin protein levels; this indicated that berberine suppressed the EMT process in MG-63 cells exposed to γ-rays irradiation. Conclusion: Berberine enhances the radiosensitivity of MG-63 osteosarcoma cells. Rad51 is a potential target of berberine in the radiosensitization of osteosarcoma.


Assuntos
Berberina/farmacologia , Pontos de Checagem do Ciclo Celular , Sobrevivência Celular , Transição Epitelial-Mesenquimal , Osteossarcoma/radioterapia , Rad51 Recombinase/antagonistas & inibidores , Radiossensibilizantes/farmacologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/radioterapia , Linhagem Celular Tumoral , Humanos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Rad51 Recombinase/metabolismo
14.
J Cancer Res Ther ; 16(2): 335-342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474521

RESUMO

Context: Osteosarcoma (OS) is a progressive primary bone tumor that originates from immature stromal spindle cells. After chemotherapy, the serum-related indexes which are related to the prognosis. Aims: The aim of this study is to investigate the correlation between changes in serum cyclooxygenase-2 (COX-2), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-ß), and tumor-specific growth factor (TSGF) levels and prognosis of patients with osteosarcoma (OS) before and after treatment. Settings and Design: Data of 75 patients with OS (observation group) and 55 healthy controls (control group) were retrospectively analyzed. Materials and Methods: Chemotherapy was administered to the observation group. Serum lactate dehydrogenase, alkaline phosphatase, and TSGF levels were measured before and after treatment. The observation group patients were classified as normal or abnormal according to the changes in serum COX-2, bFGF, VEGF, TGF-ß, and TSGF levels after chemotherapy. Patients were followed up for 7.5 years, and the survival rate was determined. Statistical Analysis Used: Single-factor influencing prognosis was included in the Cox model, and independent factors influencing prognosis were analyzed. Results: After chemotherapy, the mean serum COX-2, bFGF, VEGF, and TSGF levels decreased significantly in the observation group but were still higher than those in the control group. Furthermore, serum TGF-ß levels increased in the observation group but were still lower than those in the control group. The 5-year survival rate of patients with normal serum COX-2, bFGF, VEGF, and TSGF levels was significantly higher in the normal subgroup than in the abnormal subgroup. Cox analysis showed that the Enneking stage and COX-2 level after chemotherapy were independent prognostic factors. Conclusions: The serum COX-2, bFGF, VEGF, and TSGF levels of patients with OS significantly changed after chemotherapy, and the short-term survival rate of patients with normal levels of these biomarkers after chemotherapy was high.


Assuntos
Biomarcadores Tumorais/sangue , Osteossarcoma/sangue , Osteossarcoma/patologia , Adolescente , Adulto , Antígenos de Neoplasias/sangue , Neoplasias Ósseas/sangue , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Estudos de Casos e Controles , Criança , Ciclo-Oxigenase 2/sangue , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/sangue , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Humanos , Masculino , Proteínas de Neoplasias/sangue , Osteossarcoma/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fator de Crescimento Transformador beta/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
15.
Arch Bronconeumol ; 56(10): 674-676, 2020 10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32586699

Assuntos
Adenocarcinoma/diagnóstico por imagem , Betacoronavirus , Neoplasias Ósseas/diagnóstico por imagem , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Biópsia Guiada por Imagem/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pandemias , Pneumonia Viral/diagnóstico , Sarcoma de Ewing/diagnóstico por imagem , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Idoso , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Neoplasias Ósseas/complicações , Neoplasias Ósseas/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Feminino , Humanos , Achados Incidentais , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Masculino , Invasividade Neoplásica , Equipamento de Proteção Individual , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/secundário , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Caixa Torácica/diagnóstico por imagem , Sarcoma de Ewing/complicações , Sarcoma de Ewing/patologia , Canal Vertebral/diagnóstico por imagem , Canal Vertebral/patologia , Telecomunicações , Adulto Jovem
16.
Nat Cell Biol ; 22(7): 868-881, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32483387

RESUMO

Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon-intron fusion genes in osteosarcoma cell lines and tissues. These fusion genes are derived from chromosomal translocations that juxtapose the coding region for amino acids 1-38 of Rab22a (Rab22a1-38) with multiple inverted introns and untranslated regions of chromosome 20. The resulting translation products, designated Rab22a-NeoFs, acquire the ability to drive lung metastasis of osteosarcoma. The Rab22a1-38 moiety governs the function of Rab22a-NeoFs by binding to SmgGDS-607, a GTP-GDP exchange factor of RhoA. This association facilitates the release of GTP-bound RhoA from SmgGDS-607, which induces increased activity of RhoA and promotes metastasis. Disrupting the interaction between Rab22a-NeoF1 and SmgGDS-607 with a synthetic peptide prevents lung metastasis in an orthotopic model of osteosarcoma. Our findings may provide a promising strategy for a subset of osteosarcoma patients with lung metastases.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Translocação Genética , Proteínas rab de Ligação ao GTP/metabolismo , Adulto , Animais , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Osteossarcoma/genética , Osteossarcoma/metabolismo , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem , Proteínas rab de Ligação ao GTP/genética
17.
Tech Vasc Interv Radiol ; 23(2): 100678, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32591190

RESUMO

Image-guided percutaneous thermal ablation plays an increasingly important role in the multidisciplinary management of musculoskeletal lesions. Established indications for ablation in this setting include the treatment of osteoid osteomas, palliation of painful skeletal metastases, local control of oligometastatic disease, and consolidation of bone tumors at risk for fracture. Emerging indications include the treatment of symptomatic soft tissue masses such as extra-abdominal desmoid tumors and abdominal wall endometriosis. This review will discuss considerations in patient selection and preprocedural workup, ablation technology and techniques, strategies to avoid complications, and expected outcomes of ablation in the musculoskeletal system.


Assuntos
Neoplasias Ósseas/cirurgia , Criocirurgia/tendências , Eletroporação/tendências , Micro-Ondas/uso terapêutico , Ablação por Radiofrequência/tendências , Neoplasias de Tecidos Moles/cirurgia , Cirurgia Assistida por Computador/tendências , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Tomada de Decisão Clínica , Criocirurgia/efeitos adversos , Humanos , Micro-Ondas/efeitos adversos , Seleção de Pacientes , Complicações Pós-Operatórias/etiologia , Ablação por Radiofrequência/efeitos adversos , Fatores de Risco , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , Cirurgia Assistida por Computador/efeitos adversos , Resultado do Tratamento
18.
Adv Exp Med Biol ; 1257: 193-207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483741

RESUMO

Exercise has the potential to positively affect patients with osteosarcoma by improvement of function, mitigation of disability, and maintenance of independence and quality of life. Exercise may also directly impact cancer treatment efficacy. This chapter examines the feasibility and use of exercise or physical activity as therapy in the treatment of osteosarcoma and its survivors. It additionally presents the benefits of physical activity as treatment and rehabilitation both preoperatively (prehabilitation) and postoperatively. This chapter will also discuss barriers to exercise and physical activity for patients with osteosarcoma and its survivors, emphasizing the need for a comprehensive and cohesive support system to promote its incorporation into patient treatment plans and ensure compliance.


Assuntos
Neoplasias Ósseas , Exercício Físico , Osteossarcoma , Qualidade de Vida , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Terapia por Exercício/normas , Humanos , Osteossarcoma/patologia , Osteossarcoma/terapia , Sobreviventes/estatística & dados numéricos
19.
Anticancer Res ; 40(5): 2813-2819, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366428

RESUMO

BACKGROUND/AIM: Methionine addiction is a general and fundamental hallmark of cancer. Methionine addiction can be targeted by methionine restriction (MR). Our laboratory has studied methionine addiction in cancer and MR for almost 50 years. The present study describes oral recombinant methioninase (o-rMETase), as a supplement, to induce MR in cancer patients. PATIENTS AND METHODS: One patient, a 67-year-old female with high-stage ovarian cancer took o-rMETase twice a day at 250 units per dose for approximately one month. A second patient, a 76-year-old male with bone-metastatic prostate cancer, took o-rMETase twice a day at 250 units per dose during three months. RESULTS: The first patient's circulating methionine levels decreased 50% within 4 hours of taking 250 units of o-rMETase. The second patient's PSA dropped approximately 70% over 3 months. During this time the patient's hemoglobin increased. CONCLUSION: o-rMETase has no side effects and is potentially efficacious. Future studies involving larger cohorts of patients with high-stage cancer are required to determine if o-rMETase, as a supplement, can increase survival and improve the quality of life.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Ósseas/secundário , Liases de Carbono-Enxofre/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Antígeno Prostático Específico/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Administração Oral , Idoso , Animais , Antimetabólitos Antineoplásicos/farmacologia , Neoplasias Ósseas/patologia , Liases de Carbono-Enxofre/farmacologia , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias da Próstata/patologia , Qualidade de Vida
20.
Yonsei Med J ; 61(5): 359-370, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32390359

RESUMO

PURPOSE: Osteosarcoma (OS) is the most common primary bone tumor, with high morbidity in infants and adolescents. Long noncoding RNA LINC00313 has been found to modulate papillary thyroid cancer tumorigenesis and to be dysregulate in lung cancer. However, the role of LINC00313 in OS has not yet been addressed. MATERIALS AND METHODS: We evaluated mRNA and protein expression using real-time quantitative PCR and Western blotting. Cell proliferation was evaluated using MTT; apoptosis and autophagy were assessed with flow cytometry, Western blotting, and/or GFP-LC3 assay. Transwell assay was conducted to measure cell migration and invasion. Potential target sites for LINC00313 and miR-342-3p were predicted with starBase v.2.0 and TargetScan Human, and verified using luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay. In vivo, xenogeneic tumors were induced with U2OS and MG-63 cells, separately. RESULTS: LINC00313 was upregulated and miR-342-3p was downregulated in OS tissues and cells. High expression of LINC00313 was associated with shorter overall survival. FOSL2 downregulation and miR-342-3p overexpression suppressed cell proliferation and migratory and invasive abilities while promoting apoptosis and autophagy, all of which were consistent with the effects of LINC00313 knockdown. miR-342-3p, sponged by LINC00313, inversely modulated FOSL2 by targeting MG-63 cells, and FOSL2 expression was positively controlled by LINC00313. LINC00313 knockdown suppressed tumor growth in vivo. CONCLUSION: LINC00313 is upregulated in OS, and LINC00313 knockdown plays a vital anti-tumor role in OS cell progression through a miR-342-3p/FOSL2 axis. Our study suggests that LINC00313 may be a novel, promising biomarker for diagnosis and prognosis of OS.


Assuntos
Carcinogênese/patologia , Antígeno 2 Relacionado a Fos/genética , Técnicas de Silenciamento de Genes , MicroRNAs/metabolismo , Osteossarcoma/genética , Osteossarcoma/patologia , RNA Longo não Codificante/genética , Regulação para Cima/genética , Adulto , Sequência de Bases , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Antígeno 2 Relacionado a Fos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Metástase Neoplásica , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto Jovem
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