Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 18.354
Filtrar
1.
Medicine (Baltimore) ; 100(34): e26681, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449453

RESUMO

RATIONALE: Recently, the number of osteosarcomas has been increasing in elderly patients due to human longevity. Lung metastases are the primary cause of death from osteosarcomas. Complete resection of lung metastases can prolong the survival. However, complete resection in elderly patients is often difficult due to high risk of operative complications. Computed tomography (CT) guided radiofrequency ablation (RFA) is a minimally invasive technique to destroy tumor nodules using heat. In this report, we present the first case older than 65 years applying RFA for lung metastases due to osteosarcoma. PATIENT CONCERNS: A 74-year-old male presented with 1-year history of heel pain. A conventional high-grade osteosarcoma in his calcaneus was diagnosed. Below-knee amputation was performed. However, lung metastases were found in both lungs 1 year after amputation. CT-guided lung RFA was chosen since surgical intervention for lung metastases was abandoned because of tumor multiplicity and medical comorbidities. A total of 18 lung metastases were treated by CT-guided RFA. The most frequent complication was pneumothoraxes in 4 of 8 (50%) procedures and chest tube drainage was required in 2 of these (2 of 8 (25%) procedures). DIAGNOSES: Six lung metastases of osteosaroma were found in both lungs at 1 year after surgery. INTERVENTIONS: CT-guided lung RFA was performed. A total of 18 lung metastases were treated in 8 lung RF procedures. OUTCOMES: The patient has been alive with disease for 5.5 years after the initial surgery. LESSONS: CT-guided lung RFA is effective for elderly patients with osteosarcoma lung metastases in spite of discouragement of lung metastasectomy due to multiplicity of metastases and medical-comorbidities.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Osteossarcoma/patologia , Ablação por Radiofrequência/métodos , Idoso , Calcâneo/patologia , Humanos , Masculino , Radiografia Intervencionista , Tomografia Computadorizada por Raios X
2.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445574

RESUMO

Osteosarcoma is a frequent and extremely aggressive type of pediatric cancer. New therapeutic approaches are needed to improve the overall survival of osteosarcoma patients. Our previous results suggest that NMNAT1, a key enzyme in nuclear NAD+ synthesis, facilitates the survival of cisplatin-treated osteosarcoma cells. A high-throughput cytotoxicity screening was performed to identify novel pathways or compounds linked to the cancer-promoting role of NMNAT1. Nine compounds caused higher toxicity in the NMNAT1 KO U2OS cells compared to their wild type counterparts, and actinomycin D (ActD) was the most potent. ActD-treatment of NMNAT1 KO cells increased caspase activity and secondary necrosis. The reduced NAD+ content in NMNAT1 KO cells was further decreased by ActD, which partially inhibited NAD+-dependent enzymes, including the DNA nick sensor enzyme PARP1 and the NAD+-dependent deacetylase SIRT1. Impaired PARP1 activity increased DNA damage in ActD-treated NMNAT1 knockout cells, while SIRT1 impairment increased acetylation of the p53 protein, causing the upregulation of pro-apoptotic proteins (NOXA, BAX). Proliferation was decreased through both PARP- and SIRT-dependent pathways. On the one hand, PARP inhibitors sensitized wild type but not NMNAT1 KO cells to ActD-induced anti-clonogenic effects; on the other hand, over-acetylated p53 induced the expression of the anti-proliferative p21 protein leading to cell cycle arrest. Based on our results, NMNAT1 acts as a survival factor in ActD-treated osteosarcoma cells. By inhibiting both PARP1- and SIRT1-dependent cellular pathways, NMNAT1 inhibition can be a promising new tool in osteosarcoma chemotherapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/prevenção & controle , Dactinomicina/farmacologia , Regulação Neoplásica da Expressão Gênica , Nicotinamida-Nucleotídeo Adenililtransferase/metabolismo , Osteossarcoma/prevenção & controle , Antibióticos Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proliferação de Células , Humanos , Nicotinamida-Nucleotídeo Adenililtransferase/antagonistas & inibidores , Nicotinamida-Nucleotídeo Adenililtransferase/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Células Tumorais Cultivadas
3.
Br J Radiol ; 94(1125): 20201341, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34319796

RESUMO

OBJECTIVE: To determine the incidence and causes of pathological fractures in paediatric bone tumours and tumour-like lesions, and to determine if they are predictive of benign lesions. METHODS AND MATERIALS: Retrospective review of children with suspected bone tumours referred to a specialist musculoskeletal oncology service between September 2019 and August 2020. Data recorded included patient age and gender, lesion location, the presence of a pathological fracture on the initial plain radiograph, and the final diagnosis made either by image-guided biopsy/curettage or based on typical imaging features. RESULTS: 231 patients were included with 233 lesions (138 males and 93 females with mean age 10.5 years, range 3 months-18 years). Final diagnosis was based on histology in 85 (36.5%) cases and imaging in 148 (63.5%) cases, 52 (22.3%) lesions classed as non-neoplastic, 139 (59.7%) as benign and 42 (18%) as malignant. Pathological fractures were seen in 41 cases (17.6%) at presentation, involving the humerus in 19 (46.3%), the femur in 14 (34.1%), the tibia in 3 (7.3%), the fibula and radius in two each (4.9%) and the second toe proximal phalanx in 1 (2.4%) (p < 0.001). The commonest underlying lesions included simple bone cyst (n = 17; 41.5%) and non-ossifying fibroma (n = 10; 24.4%). Only 4 cases (9.75%) were malignant, one case each of osteosarcoma, Ewing sarcoma, leukaemia and BCOR undifferentiated round cell sarcoma. Pathological fracture occurred in 27.7% of non-malignant lesions and 9.5% of malignant lesions, this difference being statistically significant (p < 0.001). CONCLUSION: Pathological fractures were seen in 17.6% of paediatric bone tumours, tumour-like lesions, being significantly associated with humeral location and non-malignant diagnosis. ADVANCES IN KNOWLEDGE: Demonstrates the frequency, location and underlying diagnosis of pathological fractures in paediatric bone tumour and tumour-like lesions.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/patologia , Radiografia/métodos , Adolescente , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Biópsia Guiada por Imagem , Lactente , Masculino , Estudos Retrospectivos
4.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206757

RESUMO

Metastatic bone cancer occurs in every type of cancer but is prevalent in lung, breast, and prostate cancers. These metastases can cause extensive morbidity, including a range of skeletal-related events, often painful and linked with substantial hospital resource usage. The treatment used is a combination of chemotherapy and surgery. However, anticancer drugs are still limited due to severe side effects, drug resistance, poor blood supply, and non-specific drug uptake, necessitating high toxic doses. Bisphosphonates are the main class of drugs utilized to inhibit metastatic bone cancer. It is also used for the treatment of osteoporosis and other bone diseases. However, bisphosphonate also suffers from serious side effects. Thus, there is a serious need to develop bisphosphonate conjugates with promising therapeutic outcomes for treating metastatic bone cancer and osteoporosis. This review article focuses on the biological outcomes of designed bisphosphonate-based conjugates for the treatment of metastatic bone cancer and osteoporosis.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Animais , Conservadores da Densidade Óssea/química , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Difosfonatos/química , Humanos
5.
J Cardiothorac Surg ; 16(1): 192, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233697

RESUMO

INTRODUCTION: Chondroblastoma is a rare, benign locally but aggressive bone tumor. It accounts for < 1% of primary bony tumors, and mostly arises from long bones; the rib chondroblastoma is especial rare. Due to its rarity, there are no definitive or standard treatment guidelines. CASE PRESENTATION: A case of a 24-year-old male with a chondroblastoma located on the 6th posterior left rib. Computed tomography (CT) demonstrated a rib tumor that was a well-defined oval lesion of 20 mm × 18 mm, with lytic bone destruction. The imaging first diagnosis was Langerhans cell histiocytosis (LCH), a giant cell tumor, or other type of neoplasm. The whole tumor and a part of partial rib were resected by video-assisted thoracoscopy surgery (VATS). Pathological and immunohistochemical (IHC) examination made a diagnosis of chondroblastoma. Compared with traditional open thoracic surgery, VATS can achieve the same effects and cause less injury to patient. No postoperative adjuvant therapy was given, and had followed up 23 months after surgery, there was no recurrence or metastasis. CONCLUSION: Chondroblastoma has a risk of recurrence and metastasis, surgery plays an important role in the treatment of chondroblastoma, VATS can achieve the same outcome as traditional open thoracic surgery with less pain and lung function. Close follow-up is needed postoperative.


Assuntos
Neoplasias Ósseas/cirurgia , Condroblastoma/cirurgia , Cirurgia Torácica Vídeoassistida , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Condroblastoma/diagnóstico por imagem , Condroblastoma/patologia , Humanos , Masculino , Recidiva Local de Neoplasia , Radiografia Torácica , Costelas , Tomografia Computadorizada por Raios X , Adulto Jovem
6.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200964

RESUMO

For osteosarcoma (OS), the most common primary malignant bone tumor, overall survival has hardly improved over the last four decades. Especially for metastatic OS, novel therapeutic targets are urgently needed. A hallmark of cancer is aberrant metabolism, which justifies targeting metabolic pathways as a promising therapeutic strategy. One of these metabolic pathways, the NAD+ synthesis pathway, can be considered as a potential target for OS treatment. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the classical salvage pathway for NAD+ synthesis, and NAMPT is overexpressed in OS. In this study, five OS cell lines were treated with the NAMPT inhibitor FK866, which was shown to decrease nuclei count in a 2D in vitro model without inducing caspase-driven apoptosis. The reduction in cell viability by FK866 was confirmed in a 3D model of OS cell lines (n = 3). Interestingly, only OS cells with low nicotinic acid phosphoribosyltransferase domain containing 1 (NAPRT1) RNA expression were sensitive to NAMPT inhibition. Using a publicly available (Therapeutically Applicable Research to Generate Effective Treatments (TARGET)) and a previously published dataset, it was shown that in OS cell lines and primary tumors, low NAPRT1 RNA expression correlated with NAPRT1 methylation around the transcription start site. These results suggest that targeting NAMPT in osteosarcoma could be considered as a novel therapeutic strategy, where low NAPRT expression can serve as a biomarker for the selection of eligible patients.


Assuntos
Acrilamidas/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glioma/tratamento farmacológico , NAD/metabolismo , Osteossarcoma/tratamento farmacológico , Pentosiltransferases/antagonistas & inibidores , Piperidinas/farmacologia , Apoptose , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proliferação de Células , Glioma/metabolismo , Glioma/patologia , Humanos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Células Tumorais Cultivadas
7.
Aging (Albany NY) ; 13(13): 17442-17461, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229299

RESUMO

Metastatic cancer especially bone metastasis (BM) is the lethal end-stage of castration-resistant prostate cancer (CRPC). To understand the possible molecular mechanisms underlying the development of the distant metastasis is of potential clinical value. We sought to identify differentially expressed genes between patient-matched primary and bone metastatic CRPC tumors. Functional enrichment, protein-protein interaction networks, and survival analysis of DEGs were performed. DEGs with a prognostic value considered as candidate genes were evaluated, followed by genetic analysis of tumor infiltrating immune cells based on Wilcoxon test and immunofluorescence identification. Expression profiles analysis showed that 381 overlapping genes were screened as differentially expressed genes (DEGs), of which 16 DEGs were randomly selected to be validated and revealed that most of these genes showed a transcriptional profile similar to that seen in the datasets (Pearson's r = 0.76). Six core genes were found to be involved in regulation of extracellular matrix receptor interaction and chemotactic activity, and four of them were significantly correlated with the survival of PCa patients with bone metastases. Immune infiltration analysis showed that the expressions levels of COL3A1, RAC1, FN1, and SDC2 in CD4+T cells were significantly higher than those in tumor cells, especially regulatory T cell infiltration was significantly increased in BM tumors. We analyzed gene expression signatures specifically associated with the development of bone metastases of CRPC patients. Characterization of genes associated with BM of mCRPC is critical for identification of predictive biomarkers and potential therapeutic targets.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Neoplasias da Próstata/patologia , Linfócitos T Reguladores/patologia , Idoso , Neoplasias Ósseas/genética , Linfócitos T CD4-Positivos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/genética , Mapas de Interação de Proteínas , Transdução de Sinais/genética , Análise de Sobrevida
8.
Aging (Albany NY) ; 13(13): 17316-17327, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34238763

RESUMO

Anoctamin 5 (ANO5) is a member of the Anoctamin (ANO) family of calcium-activated chloride channels. Although ANO5 expression is upregulated in various cancers, its role in osteosarcoma remains largely unknown. In this study, bioinformatics analysis, western blot, and immunohistochemical staining revealed that ANO5 was upregulated in osteosarcoma cell lines and osteosarcoma tissues, and ANO5 expression was positively associated with tumor size, tumor grade, and metastasis. Functional experiments demonstrated that inhibition of ANO5 decreased, while ANO5 overexpression increased, osteosarcoma cell proliferation and mobility in vitro. Immunoprecipitation, western blot, and confocal microscopy experiments showed that ANO5 bound to and promoted the degradation of Nel-like proteins 1 (NELL1) and 2 (NELL2). Moreover, a subcutaneous tumor transplantation model revealed that ANO5 knockdown reduced osteosarcoma cell proliferation and increased NELL1 and NELL2 expression in vivo. Finally, rescue experiments showed that knockdown of NELL1 or NELL2 reversed the inhibitory effects of ANO5 knockdown on osteosarcoma cell proliferation and migration. These results demonstrated that upregulation of ANO5 promoted osteosarcoma development by decreasing the stability of the NELL1 and NELL2 proteins and that ANO5 may be an effective target for the treatment of osteosarcoma.


Assuntos
Anoctaminas/genética , Neoplasias Ósseas/genética , Proteínas de Ligação ao Cálcio/genética , Proteínas do Tecido Nervoso/genética , Osteossarcoma/genética , Adolescente , Adulto , Animais , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Biologia Computacional , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica/genética , Transplante de Neoplasias , Osteossarcoma/patologia , Regiões Promotoras Genéticas , Cicatrização , Adulto Jovem
9.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202300

RESUMO

Cancer-induced bone degradation is part of the pathological process associated with both primary bone cancers, such as osteosarcoma, and bone metastases originating from, e.g., breast, prostate, and colon carcinomas. Typically, this includes a cancer-dependent hijacking of processes also occurring during physiological bone remodeling, including osteoclast-mediated disruption of the inorganic bone component and collagenolysis. Extensive research has revealed the significance of osteoclast-mediated bone resorption throughout the course of disease for both primary and secondary bone cancer. Nevertheless, cancer cells representing both primary bone cancer and bone metastasis have also been implicated directly in bone degradation. We will present and discuss observations on the contribution of osteoclasts and cancer cells in cancer-associated bone degradation and reciprocal modulatory actions between these cells. The focus of this review is osteosarcoma, but we will also include relevant observations from studies of bone metastasis. Additionally, we propose a model for cancer-associated bone degradation that involves a collaboration between osteoclasts and cancer cells and in which both cell types may directly participate in the degradation process.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Reabsorção Óssea/etiologia , Reabsorção Óssea/metabolismo , Comunicação Celular , Osteoclastos/metabolismo , Osteossarcoma/complicações , Osteossarcoma/patologia , Animais , Neoplasias Ósseas/diagnóstico por imagem , Remodelação Óssea , Reabsorção Óssea/diagnóstico , Progressão da Doença , Suscetibilidade a Doenças , Humanos , Osteogênese
10.
J Photochem Photobiol B ; 221: 112235, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34126589

RESUMO

The investigation of in-vitro response of cell cultures derived from tumor material of individual patients with similar tumor localizations to photodynamic treatment is presented. Tumor types included in the research were renal cell carcinoma, melanoma and alveolar, synovial, lypo- and osteo- sarcomas. Long-term observations of treatment-induced morphological changes in cells were performed by means of digital holographic microscopy. A substantial variance in response of cells of individual patients with similar tumor types and localizations to photodynamic treatment with the same dose has been observed. These peculiarities are indicative of the demand to personalized protocols of photodynamic treatment. The elevated resistance of cells of some patients to treatment at high doses highlights potential limitations of photodynamic therapy for some patients. Digital holographic microscopy is shown to be an informative label-free noninvasive tool allowing for long-term monitoring of cell samples in vitro and providing quantitative information on necrosis rate and loss of cellular dry mass. The developed methodology can be generalized for analysis of cellular response to various therapies.


Assuntos
Proliferação de Células/efeitos dos fármacos , Holografia/métodos , Fármacos Fotossensibilizantes/farmacologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Humanos , Melanoma/metabolismo , Melanoma/patologia , Microscopia de Fluorescência , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Fármacos Fotossensibilizantes/química , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas
11.
Aging (Albany NY) ; 13(11): 15501-15510, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102610

RESUMO

Growing studies noted that lncRNA was closely related with the initiation and progression of tumors. However, the role of BCRT1 in the progression of osteosarcoma remains unknown. We noted that BCRT1 is significantly upregulated in osteosarcoma specimens and cells. Elevated expression of BCRT1 promotes cell growth and cell cycle in osteosarcoma cell. Moreover, BCRT1 induces EMT and secretion of inflammatory mediators in osteosarcoma cell. We illustrated that elevated expression of BCRT1 decreases miR-1303 expression in MG-63 cell. The expression of miR-1303 is lower in osteosarcoma specimens than in non-tumor specimens. There is an inverse interrelation between miR-1303 levels and BCRT1 levels in osteosarcoma specimens. Furthermore, we identified FGF7 is one direct target gene of miR-1303 in osteosarcoma cell. Ectopic expression of miR-1303 suppresses FGF7 expression and elevated expression of BCRT1 enhanced FGF7 expression in MG-63 cell. Finally, we illustrated that BCRT1 induces osteosarcoma cell cycle and proliferation and promotes EMT progression and inflammatory mediators secretion via modulating FGF7 expression. Our study suggested that BCRT1 acts as one oncogene in osteosarcoma progression.


Assuntos
Neoplasias Ósseas/genética , Progressão da Doença , Fator 7 de Crescimento de Fibroblastos/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/patologia , RNA Longo não Codificante/metabolismo , Sequência de Bases , Neoplasias Ósseas/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Fator 7 de Crescimento de Fibroblastos/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais/genética , Regulação para Cima/genética
12.
Medicine (Baltimore) ; 100(23): e26322, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115046

RESUMO

RATIONALE: Severe tension pneumocephalus can lead to drowsiness, coma, and even brain hernia and death. The occurrence of delayed pneumocephalus after spinal surgery is rarely reported and often ignored. Herein, we report a case of delayed pneumocephalus after repeated percutaneous aspiration following spinal surgery. PATIENT CONCERNS: A 55-year-old man was admitted in October 2020 because of aggravation in bilateral lower limb weakness and dysuria for seven days. He was diagnosed with liver cancer a year ago, and he underwent several operations because of tumor recurrence. The patient underwent thoracic vertebrae tumor excision on this admission, and no cerebrospinal fluid leakage was discovered during surgery. After the third drainage by percutaneous aspiration, the patient complained of severe headache and vomiting on postoperative day 16. DIAGNOSIS: Emergency brain computed tomography revealed massive pneumocephalus. INTERVENTIONS: Thereafter, suction drainage was discontinued, and he was placed on bed rest and administered intravenous mannitol. OUTCOMES: Repeated computed tomography showed complete resolution of the pneumocephalus after five days. LESSONS: Wound exudates and cystic fluid after spinal surgery should be differentiated from cerebrospinal fluid leakage. Reckless percutaneous aspirations can form pneumocephalus in patients with an occult dural injury, and pneumocephalus can occur up to 16 days after surgery. Early diagnosis of pneumocephalus is crucial to avoid severe consequences.


Assuntos
Neoplasias Ósseas , Descompressão Cirúrgica/efeitos adversos , Drenagem/efeitos adversos , Procedimentos Ortopédicos , Complicações Pós-Operatórias , Vértebras Torácicas , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Neoplasias Ósseas/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Descompressão Cirúrgica/métodos , Diuréticos Osmóticos/administração & dosagem , Drenagem/métodos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Manitol/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neuroimagem/métodos , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Pneumocefalia/diagnóstico , Pneumocefalia/etiologia , Pneumocefalia/fisiopatologia , Pneumocefalia/terapia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Reoperação/efeitos adversos , Reoperação/métodos , Vértebras Torácicas/patologia , Vértebras Torácicas/cirurgia , Resultado do Tratamento
13.
ACS Appl Mater Interfaces ; 13(27): 31542-31553, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34191477

RESUMO

Conventional biomaterial-mediated osteosarcoma therapy mainly focuses on its antitumor effect yet often fails to overcome the problem of post-treatment bone tissue defect repair. Simultaneously, minimally invasive drug delivery methods are becoming spotlights for normal tissue preservation. Herein, an injectable curcumin-microsphere/IR820 coloaded hybrid methylcellulose hydrogel (Cur-MP/IR820 gel) platform was designed for osteosarcoma therapy and bone regeneration. In vitro, the K7M2wt osteosarcoma cells were eradicated by hyperthermia and curcumin. Later, the sustained release of curcumin promoted alkaline phosphatase expression and calcium deposition of bone mesenchymal stem cells. In vivo, this hybrid hydrogel could reach tumor site via injection and turned into hydrogel due to heat sensitivity. Under the irradiation of an 808 nm laser, localized hyperthermia (∼51 °C) generated in 5 min to ablate the tumor. Meanwhile, the thermal-accelerated curcumin release and thermal-increased cell membrane permeability led to tumor cell apoptosis. Tumors in photothermal-co-chemotherapy group were successfully restrained from day 2 after treatment. After that, bone reconstruction was promoted because of sustained released curcumin. The chemo-co-thermal efficacy and osteogenic capacity of Cur-MP/IR820 hydrogel suggest a promising approach to the treatment of osteosarcoma and provide provoking inspiration for treating bone tumors and repairing bone tissue.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Curcumina/química , Curcumina/farmacologia , Hidrogéis/química , Hipertermia Induzida , Verde de Indocianina/análogos & derivados , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/efeitos dos fármacos , Terapia Combinada , Curcumina/metabolismo , Curcumina/uso terapêutico , Humanos , Verde de Indocianina/química , Microesferas , Osteossarcoma/patologia
14.
Medicine (Baltimore) ; 100(26): e26568, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190199

RESUMO

ABSTRACT: Due to the rarity of solitary bone plasmacytoma (SBP), few studies reported the prognosis and survival predictors of SBP, especially for patients with extremity SBP.A total of 552 patients with extremity SBP were identified from the Surveillance Epidemiology and Ends Results (SEER) database between 1973 and 2016. In order to obtain independent predictors of survival, we performed both univariate and multivariate analysis via Cox proportional hazards model. Additionally, we used the Kaplan-Meier method to construct survival curves.The mean and median age at diagnosis of all patients were 64 and 65 years, respectively. The ratio of male versus women was 1.3:1. Overall survival for this special population was 51.2% and 34.9% at 5 and 10 years, respectively. Cancer-specific survival (CSS) for this special population was 63.5% and 47.5% at 5 and 10 years, respectively. Age at diagnosis and radiotherapy treatment were found to be significant independent predictors of both overall survival and CSS. Additionally, multivariate analysis showed that year of diagnosis and marital status were significantly correlated with CSS.This is the first study to identify prognostic factors of extremity SBP by using the SEER database. Our findings highlight that radiotherapy is the mainstream treatment for extremity SBP. Additionally, age, year of diagnosis, and marital status were significant independent predictors of survival. Knowledge of these survival predictors may help clinicians provide appropriate management for extremity SBP patients.


Assuntos
Neoplasias Ósseas , Extremidades/patologia , Estado Civil/estatística & dados numéricos , Plasmocitoma , Radioterapia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/radioterapia , China/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Plasmocitoma/diagnóstico , Plasmocitoma/mortalidade , Plasmocitoma/patologia , Prognóstico , Radioterapia/métodos , Radioterapia/estatística & dados numéricos , Programa de SEER/estatística & dados numéricos
15.
Aging (Albany NY) ; 13(13): 17901-17913, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34170850

RESUMO

BACKGROUND: Osteosarcoma (OS) is characterized by a high rate of metastasis. It has been found that tumor cells can bypass apoptosis which leads to an uncontrolled proliferation, but chloroquine (CQ) can have an effect on the tumors by inducing apoptosis. We aimed to explore the effects and the hypothetical mechanism of CQ effects on OS. METHODS: We first estimated the CQ effects on proliferation, apoptosis, migration, invasion, and lamellipodia formation of OS cells. Mice bearing xenograft model were used to test the anti-tumor growth and lung metastasis effects of CQ in OS. Western blot and immunohistochemistry were used to explore the mechanism of CQ effects and the association between p-STAT3 expression and lung metastasis of OS patients. RESULTS: CQ induces the apoptosis and suppressed the viability, proliferation, migration, invasion, and lamellipodia formation of OS cells in vitro. In vivo experiments demonstrated that CQ inhibited tumor growth and lung metastasis. CQ induced apoptosis was dependent on the lysosomal inhibition and inhibition of protein turnover. The lung metastasis was associated with the p-STAT3 expression in OS patients. CONCLUSION: CQ inhibited progression of OS cells in vitro, and suppressed tumor growth and lung metastasis in vivo. p-STAT3 can be a predictive biomarker for lung metastasis in osteosarcoma patients.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Proliferação de Células/efeitos dos fármacos , Cloroquina/farmacologia , Invasividade Neoplásica/patologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Fator de Transcrição STAT3/metabolismo , Adulto , Animais , Neoplasias Ósseas/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica/prevenção & controle , Osteossarcoma/metabolismo , Fosforilação , Pseudópodes/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
16.
Br J Radiol ; 94(1124): 20201391, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34111978

RESUMO

OBJECTIVE: This study aims to build machine learning-based CT radiomic features to predict patients developing metastasis after osteosarcoma diagnosis. METHODS AND MATERIALS: This retrospective study has included 81 patients with a histopathological diagnosis of osteosarcoma. The entire dataset was divided randomly into training (60%) and test sets (40%). A data augmentation technique for the minority class was performed in the training set, along with feature's selection and model's training. The radiomic features were extracted from CT's image of the local osteosarcoma. Three frequently used machine learning models tried to predict patients with lung metastases (MT) and those without lung metastases (non-MT). According to the higher area under the curve (AUC), the best classifier was chosen and applied in the testing set with unseen data to provide an unbiased evaluation of the final model. RESULTS: The best classifier for predicting MT and non-MT groups used a Random Forest algorithm. The AUC and accuracy results of the test set were bulky (accuracy of 73% [ 95% coefficient interval (CI): 54%; 87%] and AUC of 0.79 [95% CI: 0.62; 0.96]). Features that fitted the model (radiomics signature) derived from Laplacian of Gaussian and wavelet filters. CONCLUSIONS: Machine learning-based CT radiomics approach can provide a non-invasive method with a fair predictive accuracy of the risk of developing pulmonary metastasis in osteosarcoma patients. ADVANCES IN KNOWLEDGE: Models based on CT radiomic analysis help assess the risk of developing pulmonary metastases in patients with osteosarcoma, allowing further studies for those with a worse prognosis.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Aprendizado de Máquina , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/secundário , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto Jovem
17.
Cancer Sci ; 112(9): 3769-3783, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34181803

RESUMO

The large-conductance Ca2+ -activated K+ channel KCa 1.1 plays a pivotal role in tumor development and progression in several solid cancers. The three-dimensional (3D) in vitro cell culture system is a powerful tool for cancer spheroid formation, and mimics in vivo solid tumor resistance to chemotherapy in the tumor microenvironment (TME). KCa 1.1 is functionally expressed in osteosarcoma and chondrosarcoma cell lines. KCa 1.1 activator-induced hyperpolarizing responses were significantly larger in human osteosarcoma MG-63 cells isolated from 3D spheroid models compared with in those from adherent 2D monolayer cells. The present study investigated the mechanisms underlying the upregulation of KCa 1.1 and its role in chemoresistance using a 3D spheroid model. KCa 1.1 protein expression levels were significantly elevated in the lipid-raft-enriched compartments of MG-63 spheroids without changes in its transcriptional level. 3D spheroid formation downregulated the expression of the ubiquitin E3 ligase FBXW7, which is an essential contributor to KCa 1.1 protein degradation in breast cancer. The siRNA-mediated inhibition of FBXW7 in MG-63 cells from 2D monolayers upregulated KCa 1.1 protein expression. Furthermore, a treatment with a potent and selective KCa 1.1 inhibitor overcame the chemoresistance of the MG-63 and human chondrosarcoma SW-1353 spheroid models to paclitaxel, doxorubicin, and cisplatin. Among several multidrug resistance ATP-binding cassette transporters, the expression of the multidrug resistance-associated protein MRP1 was upregulated in both spheroids and restored by the inhibition of KCa 1.1. Therefore, the pharmacological inhibition of KCa 1.1 may be an attractive new strategy for acquiring resistance to chemotherapeutic drugs in the TME of KCa 1.1-positive sarcomas.


Assuntos
Neoplasias Ósseas/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Osteossarcoma/metabolismo , Esferoides Celulares/metabolismo , Regulação para Cima/genética , Antineoplásicos/farmacologia , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Proteína 7 com Repetições F-Box-WD/genética , Proteína 7 com Repetições F-Box-WD/metabolismo , Humanos , Indóis/farmacologia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/antagonistas & inibidores , Osteossarcoma/patologia , Paclitaxel/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , RNA Interferente Pequeno/genética , Transfecção , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética
18.
Int J Mol Sci ; 22(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070338

RESUMO

The high mortality rate together with an ever-growing number of annual cases have defined neoplastic disorders as "the real 21st-century disease". Its dubious distinction also results from conventional therapy failure, which has made cancer an orphan disease. Therefore, innovative and alternative therapeutic strategies are mandatory. The ability to leverage human naturally occurring anti-tumor defenses has always represented a fascinating perspective, and the immuno blockage approval in cancer treatment represents in timeline the latest success. As a multifunctional organ, adipose tissue releases a large amount of adipokines having both carcinogenic and antitumor properties. The negative correlation between serum levels and risk for developing malignancies, as well as the huge number of existing preclinical studies, have identified adiponectin as a potential anticancer adipokine. Nevertheless, its usage in clinical has constantly clashed with the inability to reproduce a mimic synthetic compound. Between 2011 and 2013, two distinct adiponectin receptor agonists were recognized, opening new scenarios even in cancer. Here, we review the first orally active adiponectin receptor agonists AdipoRon, from the discovery to the anticancer evidence. Including our latest findings in osteosarcoma models, we summarize AdipoRon and other existing agonists state-of-art, questioning about the feasibility assessment of this strategy in cancer treatment.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Proteínas de Neoplasias/agonistas , Osteossarcoma/tratamento farmacológico , Piperidinas/uso terapêutico , Receptores de Adiponectina/agonistas , Animais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Humanos , Proteínas de Neoplasias/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Receptores de Adiponectina/metabolismo
19.
Anticancer Res ; 41(6): 2993-2999, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083290

RESUMO

BACKGROUND/AIM: The delayed initiation of treatment is not associated with good clinical outcomes in patients with malignancies. However, few previous studies have examined prognostic factors, including the delayed initiation of treatment, in malignant bone tumors. PATIENTS AND METHODS: One hundred and one patients with malignant bone tumors were enrolled. Univariate and multivariate analyses were performed to identify factors predicting metastasis, including factors that delay the initiation of treatment. RESULTS: The multivariate analysis revealed that high-grade bone malignancy (p<0.01), a >30-day delay in referral to a specialized hospital by a general practitioner (p=0.03), and large tumor size (>77 mm) (p=0.04), were independently associated with metastasis of malignant bone tumors. CONCLUSION: When general practitioners notice a patient with a >77 mm bone tumor, early referral to a specialized hospital within one month might be essential for preventing metastasis.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Metástase Neoplásica , Osteossarcoma/patologia , Osteossarcoma/terapia , Tempo para o Tratamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Encaminhamento e Consulta , Análise de Sobrevida , Adulto Jovem
20.
Front Immunol ; 12: 623762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959121

RESUMO

Osteosarcoma (OSA) is the most common bone malignancy and displays high heterogeneity of molecular phenotypes. This study aimed to characterize the molecular features of OSA by developing a classification system based on the gene expression profile of the tumor microenvironment. Integrative analysis was performed using specimens and clinical information for OSA patients from the TARGET program. Using a matrix factorization method, we identified two molecular subtypes significantly associated with prognosis, S1 (infiltration type) and S2 (escape type). Both subtypes displayed unique features of functional significance features and cellular infiltration characteristics. We determined that immune and stromal infiltrates were abundant in subtype S1 compare to that in subtype S2. Furthermore, higher expression of immune checkpoint PDCD1LG2 and HAVCR2 was associated with improved prognosis, while a preferable chemotherapeutic response was associated with FAP-positive fibroblasts in subtype S1. Alternatively, subtype S2 is characterized by a lack of effective cytotoxic responses and loss of major histocompatibility complex class I molecule expression. A gene classifier was ultimately generated to enable OSA classification and the results were confirmed using the GSE21257 validation set. Correlations between the percentage of fibroblasts and/or fibrosis and CD8+ cells, and their clinical responses to chemotherapy were assessed and verified based on 47 OSA primary tumors. This study established a new OSA classification system for stratifying OSA patient risk, thereby further defining the genetic diversity of OSA and allowing for improved efficiency of personalized therapy.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Linfócitos T CD8-Positivos/imunologia , Fibroblastos Associados a Câncer/patologia , Perfilação da Expressão Gênica , Linfócitos do Interstício Tumoral/imunologia , Osteossarcoma/genética , Transcriptoma , Microambiente Tumoral , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linfócitos T CD8-Positivos/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Criança , Bases de Dados Genéticas , Feminino , Fibrose , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Osteossarcoma/imunologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...