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1.
Connect Tissue Res ; 64(6): 519-531, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37310074

RESUMO

BACKGROUND: DICER1-AS1 is reported to promote the progression and disturb the cell cycle in osteosarcoma; however, its mechanism has rarely been studied. MATERIALS AND METHODS: DICER1-AS1 expression levels were evaluated by qPCR and fluorescence in situ hybridization (FISH). The total, nuclear, and cytosolic levels of CDC5L were measured by western blotting and immunofluorescence (IF). Cell proliferation, apoptosis, and cell cycle analyses were conducted using the colony formation, CCK-8 assay, terminal transferase-mediated UTP nick end-labeling kit (TUNEL) assay, and flow cytometry. Levels of cell proliferation-, cell cycle-, and cell apoptosis-related proteins were determined by western blotting. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to evaluate the relationship between DICER1-AS1 and CDC5L. RESULTS: LncRNA DICER1-AS1 was highly expressed in samples of osteosarcoma tissue and in osteosarcoma cell lines. DICER1-AS1 knockdown inhibited cell proliferation, promoted cell apoptosis, and disturbed the cell cycle. Moreover, DICER1-AS1 was found to bind with CDC5L, and knockdown of DICER-AS1 inhibited the nuclear transfer of CDC5L. DICER1-AS1 knockdown also reversed the effects of CDC5L overexpression on cell proliferation, apoptosis, and the cell cycle. Moreover, CDC5L inhibition suppressed cell proliferation, promoted cell apoptosis, and disturbed the cell cycle, and those effects were further enhanced by DICER1-AS1 knockdown. Finally, DICER1-AS knockdown inhibited tumor growth and proliferation, and promoted cell apoptosis in vivo. CONCLUSION: LncRNA DICER1-AS1 knockdown inhibits the nuclear transfer of CDC5L protein, arrests the cell cycle, and induces apoptosis to suppress the development of osteosarcoma. Our results suggest a novel target (DICER1-AS1) for treatment of osteosarcoma.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Hibridização in Situ Fluorescente , Proliferação de Células/genética , Ciclo Celular/genética , Osteossarcoma/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica , Ribonuclease III/genética , Ribonuclease III/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo
2.
J Nanobiotechnology ; 13: 22, 2015 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-25880868

RESUMO

BACKGROUND: The combination of chemotherapeutic drugs with different pharmacological action has emerged as a promising therapeutic strategy in the treatment of cancers. Present study examines the antitumor potential of paclitaxel (PTX) and etoposide (ETP)-loaded PLGA nanoparticles for the treatment of osteosarcoma. RESULTS: The resulting drug-loaded PLGA NP exhibited a nanosize dimension with uniform spherical morphology. The NP exhibited a sustained release profile for both PTX and ETP throughout the study period without any sign of initial burst release. The combinational drug-loaded PLGA NP enhanced the cytotoxic effect in MG63 and Saos-2 osteosarcoma cell lines, in comparison to either native drug alone or in cocktail combinations. Additionally, NPs showed an appreciable uptake in MG63 cells in a time-based manner. Co-delivery of anticancer drugs resulted in enhanced cell cycle arrest and cell apoptosis. The results clearly showed that combinational drugs remarkably improved the therapeutic index of chemotherapeutic drugs. The greater inhibitory effect of nanoparticle combination would be of great advantage during systemic cancer therapy. CONCLUSION: Taken together, our study demonstrated that PTX-ETP/PLGA NP based combination therapy holds significant potential towards the treatment of osteosarcoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Nanopartículas/administração & dosagem , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Etoposídeo/administração & dosagem , Etoposídeo/química , Humanos , Ácido Láctico/química , Osteossarcoma/patologia , Paclitaxel/administração & dosagem , Paclitaxel/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
3.
Tumour Biol ; 35(7): 6809-14, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24729087

RESUMO

Osteosarcoma has become a health threat for adolescents and young adults. To identify the genetic risk factor for the malignancy is in urgent need. Several studies have investigated the role of CD 152 polymorphisms in osteosarcoma in a sample of Chinese population. However, the association is poorly defined due to lack of a sufficiently large sample. In this study, we performed a meta-analysis of all CD 152 polymorphisms that had been implicated in osteosarcoma to examine the association. We searched the electronic MEDLINE database until December 31, 2013, to identify the studies regarding the association between CD 152 polymorphisms and osteosarcoma. Inclusion criteria were followed in the selection of eligible study. The genotypic and allelic data were collected from all studies included to evaluate the risk of osteosarcoma (odds ratio, OR). We found statistically significant evidence of the studied CD 152 polymorphisms and increased risk of osteosarcoma in homozygous (OR = 1.79, 95 % CI = 1.40-2.29, P = 0.958), recessive (OR = 1.77, 95 % CI = 1.40-2.25, P = 0.899), and allele model (OR = 1.21, 95 % CI = 1.09-1.34, P = 1.000). This increased risk was also revealed in single nucleotide polymorphism (SNP) +49G>A and SNP 326G>A. Our meta-analysis indicates that there may be an association between CD 152 polymorphisms and risk of osteosarcoma in Chinese population. Further validation of the observation is necessary.


Assuntos
Neoplasias Ósseas/genética , Antígeno CTLA-4/genética , Osteossarcoma/genética , Alelos , Povo Asiático , Neoplasias Ósseas/patologia , Predisposição Genética para Doença , Genótipo , Humanos , Osteossarcoma/patologia , Polimorfismo de Nucleotídeo Único
4.
World J Surg Oncol ; 12: 341, 2014 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-25391880

RESUMO

BACKGROUND: We report the long-term outcomes of patients with osteosarcoma who underwent effective preoperative chemotherapy and subsequently underwent marginal resection. METHODS: We reviewed the records of 50 patients with osteosarcoma who underwent marginal resection following effective preoperative chemotherapy; 18 were treated with the MMIA (high-dose methotrexate (HD-MTX), adriamycin (ADR), ifosfamide (IFO)) and cisplatin (DDP), and 32 patients were treated with the DIA (DDP, ADR and IFO). protocol. The functions of the affected limb were evaluated using the revised MSTS93 system. The Kaplan-Meier method was used for survival analysis. RESULTS: After a median follow-up of 5.5 years, the rates were: overall 5-year cumulative survival 61.7%, event-free survival 57.7%, recurrence 8.5%, pulmonary metastases 42.6%, and excellent to good function of the affected limb 57.7%. CONCLUSIONS: Our results showed that marginal resection can be performed in patients with osteosarcoma who obtain clinically favorable responses to chemotherapy. Patients had a good clinical course and there was no negative effect on rates of survival or local recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/terapia , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/terapia , Osteossarcoma/terapia , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Metotrexato/administração & dosagem , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico , Taxa de Sobrevida , Fatores de Tempo
5.
BMC Musculoskelet Disord ; 15: 453, 2014 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-25539904

RESUMO

BACKGROUND: We tried to compare the functional and psychosocial outcomes after various reconstruction methods according to tumor location following resection of osteosarcoma in distal femur. METHODS: We retrospectively reviewed 51 patients who underwent limb-salvage surgery of osteosarcoma in distal femur in our institution, 30 males and 21 females with an average age of 21 years (range 13-51 years). We classified osteosarcoma in distal femur into 3 types, and organized affected limb reconstruction methods after wide resection. MSTS and QOL scores were used to analyze the functional and psychological outcomes. RESULTS: After a mean follow-up of 43 months (12-225 months), there is no difference on functional results and QOL scores among three reconstruction groups (p > 0.05) and among three types groups (p > 0.05). No difference could be noticed on tumor-free survival and total survival among three reconstruction groups (p > 0.05) and three type groups (p > 0.05). In ≤2-year, better functional scores could be found in prosthesis group, rather than the other two inactivated-bone groups (p < 0.05). CONCLUSIONS: Biological reconstruction with alcohol-inactivated autograft replantation could avoid prosthesis related complications and achieved comparable results with prosthesis following resection of osteosarcoma in distal femur. Different reconstruction options could be chosen according to tumor location, such as the distance to Insall line.


Assuntos
Neoplasias Femorais/diagnóstico , Neoplasias Femorais/cirurgia , Salvamento de Membro/métodos , Osteossarcoma/diagnóstico , Osteossarcoma/cirurgia , Qualidade de Vida , Adolescente , Adulto , Feminino , Neoplasias Femorais/psicologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/psicologia , Qualidade de Vida/psicologia , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Heliyon ; 10(7): e27742, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560262

RESUMO

Introduction: Few studies have focused on the risk factors for hidden blood loss (HBL) during cement augmentation surgery for pathologic vertebral compression fraction (PVCFs). Method: From January 2014 to December 2020, the clinical data of 169 PVCF patients (283 levels) who underwent cement augmentation were retrospectively analysed. HBL was calculated according to the linear Gross formula using the patient's average Hct during the perioperative course and PBV. Multivariate linear regression analysis was performed to evaluate the independent factors associated with HBL. Results: The mean HBL was 448.2 ± 267.2 ml, corresponding to 10.8% ± 6.2% of the patient blood volume (PBV). There were significant differences between pre- and postoperative haematocrit (Hct) (P < 0.001) and Hb (P < 0.001), and 132 patients developed anaemia postoperatively, while 79 patients had anaemia preoperatively (P < 0.001). Multivariate linear regression revealed that bone lesion quality (p = 0.028), number of PVCFs (p = 0.002), amount of bone cement (p = 0.027), bone cement leakage (p = 0.001), and percentage of vertebral height loss (VHL) (p = 0.011) were independent risk factors for HBL. Conclusion: In conclusion, patients with lytic vertebral destruction, larger amounts of bone cement, greater amounts of bone cement leakage, more PVCF(s), and greater percentages of VHL may be more prone to HBL.

7.
World J Surg Oncol ; 11: 72, 2013 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-23497322

RESUMO

BACKGROUND: Giant cell tumor of the sacrum, especially involving the sacroiliac joint, is rare, but is particularly challenging to treat. The long term outcome of a patient was studied with giant cell tumor involving the sacroiliac joint treated with selective arterial embolization and curretage. METHOD: One patient with giant cell tumor involving the sacroiliac joint was treated with selective arterial embolization and curettage in our hospital in October 2002. The curettage and bone grafting was done after two times of selective arterial embolization;1600 ml of blood were transfused and no complications developed during the operation. RESULTS: At the final follow-up of 9 years after the operation, no local recurrence and metastasis developed and she retained normal activity in daily life. CONCLUSION: We think it is an optimal treatment for giant cell tumor involving the sacroiliac joint, with repeated selective arterial embolization and curettage, which has the advantage of less injury, less blood loss and fewer complications.


Assuntos
Neoplasias Ósseas/terapia , Curetagem , Embolização Terapêutica , Tumor de Células Gigantes do Osso/terapia , Articulação Sacroilíaca/patologia , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Terapia Combinada , Feminino , Tumor de Células Gigantes do Osso/diagnóstico por imagem , Tumor de Células Gigantes do Osso/patologia , Humanos , Articulação Sacroilíaca/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
BMC Musculoskelet Disord ; 14: 319, 2013 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-24209887

RESUMO

BACKGROUND: Giant cell tumors (GCT) around the knee are common and pose a special problem of reconstruction after tumor excision, especially for grade III GCT. We questioned whether en bloc resection and reconstruction with alcohol inactivated autograft-prosthesis composite would provide (1) local control and long-term survival and (2) useful limb function in patients who had grade III GCT around the knee. METHODS: We retrospectively reviewed eight patients (5 males and 3 females) treated with this procedure with mean age of 31 years (range 20 to 43 years) from Jan 2007 to Oct 2008. 5 lesions were located in distal femur and 3 in proximal tibia. 4 patients were with primary tumor and the other 4 with recurrence. 2 patients showed pathological fracture. RESULTS: Mean Follow-up is 54 months ranging from 38 to 47 months. No recurrence, metastasis, prosthesis loosening were found. The mean healing time between autograft and host bone was 5.5 months. The mean MSTS score was 26.3 (88%) ranging from 25 to 29. The mean ISOLS composite graft score was 32.8 (88.5%) ranging from 28 to 35. Creeping substitution is possibly the main way in bony junction. The healing time in femoral lesion is faster than that in tibial lesion. CONCLUSIONS: The technique of alcohol inactivated autograft-prosthesis composite could be able to achieve satisfactory oncological and functional outcomes in Grade III GCT.


Assuntos
Autoenxertos/transplante , Neoplasias Ósseas/diagnóstico por imagem , Tumor de Células Gigantes do Osso/diagnóstico por imagem , Prótese do Joelho/estatística & dados numéricos , Recidiva Local de Neoplasia/diagnóstico por imagem , Adulto , Neoplasias Ósseas/cirurgia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Seguimentos , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Masculino , Recidiva Local de Neoplasia/cirurgia , Radiografia , Estudos Retrospectivos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Adulto Jovem
9.
Cancers (Basel) ; 15(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37686615

RESUMO

The management of sarcomas, a diverse group of cancers arising from connective tissues, presents significant challenges due to their heterogeneity and limited treatment options. Patient-derived sarcoma organoids (PDSOs) have emerged as a promising tool in the multimodal management of sarcomas, offering unprecedented opportunities for personalized medicine and improved treatment strategies. This review aims to explore the potential of PDSOs as a promising tool for multimodal management of sarcomas. We discuss the establishment and characterization of PDSOs, which realistically recapitulate the complexity and heterogeneity of the original tumor, providing a platform for genetic and molecular fidelity, histological resemblance, and functional characterization. Additionally, we discuss the applications of PDSOs in pathological and genetic evaluation, treatment screening and development, and personalized multimodal management. One significant advancement of PDSOs lies in their ability to guide personalized treatment decisions, enabling clinicians to assess the response and efficacy of different therapies in a patient-specific manner. Through continued research and development, PDSOs hold the potential to revolutionize sarcoma management and drive advancements in personalized medicine, biomarker discovery, preclinical modeling, and therapy optimization. The integration of PDSOs into clinical practice can ultimately improve patient outcomes and significantly impact the field of sarcoma treatment.

10.
Proc Inst Mech Eng H ; 236(2): 286-294, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34479452

RESUMO

Beta-tricalcium phosphate (ß-TCP) refers to one ideal bone repair substance with good biocompatibility and osteogenicity. A digital light processing (DLP)-system used in this study creates bioceramic green part by stacking up layers of photocurable tricalcium phosphate-filled slurry with various ß-TCP weight fractions. Results show that the sintering shrinkage is anisotropic and the shrinkage vertically reaches over that horizontally. The obtained porous ß-TCP parts have both macroporous outer structure and microporous inner structure, the macropore size is 400-600 µm and the micropore size is 500-1500 nm. The mechanical tests show that the porous ß-TCP bioceramic's compressive strength reaches 16.53 MPa. The cell culture confirmed that the porous ß-TCP bioceramic is capable of achieving the effective attaching, growing, and proliferating pertained to mouse osteoblast cells. This study identified considerable blood vessels and significant ectopic bone forming obviously based on the histologically-related assessment when implanting to rabbit femoral condyle deficiency for 3 months. Thus, under high bioactive property and osteoinductivity, and large precision and mechanical strength that can be adjusted, the DLP printed porous ß-TCP ceramics is capable of being promising for special uses of bones repairing.


Assuntos
Fosfatos de Cálcio , Alicerces Teciduais , Animais , Osso e Ossos , Cerâmica , Força Compressiva , Camundongos , Porosidade , Coelhos
11.
Transl Cancer Res ; 11(4): 678-688, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571669

RESUMO

Background: An imperative need for better management strategies to improve the survival in patients with undifferentiated pleomorphic sarcoma (UPS). Methods: The retrospective analysis of clinicopathological data of 166 UPS patients, who have undergone surgical treatment in our hospital, was carried out from January 2005 to January 2018. Cox regression model and Kaplan-Meier method were employed to identify the relevant factors affecting the rate of local recurrence (LR), distant metastasis (DM), and overall survival (OS) via univariate and multivariate analysis. The P<0.05 were found to be statistically considerable. Results: At the end of follow-up, the rate of LR, DM and OS in 166 UPS patients was 22.9% (38/166), 32.5% (54/166) and 75.3% (125/166) with a median follow-up time of 55 months. The existing study reveals that the UPS in trunk, tumor size ≥5 cm and R1/R2 resection margin are the prognostic markers of poor survival rate. Women are more susceptible to LR, and R1/R2 resection margin is significantly correlated with a high rate of LR. Old Patients (>60 years), the UPS in trunk and R1/R2 resection margin are susceptible to DM. Conclusions: R0 resection margin was an only independent favorable prognostic factor, which was correlated with LRFS, DMFS, and OS.

12.
Exp Ther Med ; 22(1): 727, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34007336

RESUMO

The aim of the present manuscript was to retrospectively evaluate the efficacy of fluoroscopy-guided percutaneous vertebroplasty (PVP) for the relief of osteoblastic spinal metastases pain. PVP was performed in 39 consecutive patients with 82 osteoblastic metastatic spinal vertebras. 19 vertebras had pathologic compressive fracture and the other 63 vertebras had no compressive fracture with obvious imaging abnormalities. The ages of the patients ranged from 40 to 77 years with a mean age of 58.5±9.0 years. Visual analog scale (VAS) and QLQ-BM22 score were used to evaluate pain and quality of life at 2 days pre-operation and at 1 week and 3 months post-operation. Among all 82 vertebras, 35 vertebras had been injected bilaterally and the other 47 vertebras unilaterally. The amount of cement injected per lesion ranged from 0.5 to 4.5 ml with a mean volume of 1.6±0.8 ml. Cement deposition in all lesions was uniform. The patients were followed up from 3 to 15.5 months with a mean follow up time of 5.6±3.4 months. Mean VAS score declined significantly from preoperative 4.3±2.4 to postoperative 3.0±1.7 at 1 week and 2.4±2.0 at 3 months after the procedure (P=0.001). Mean QLQ-BM22 score declined significantly from preoperative 49.1±12.3 to postoperative 42.4±9.5 at 1 week and 39.6±10.4 at 3 months after the procedure (P<0.001). Extraosseous cement leakage occurred in 21 vertebras of 13 cases and in 1 case into the thoracic vertebra canal without causing any clinical complications. No further procedures were performed after leakage. PVP is an effective treatment for painful osteoblastic spinal metastases. It can relieve pain, reduce disability and improve function. The main complications are bone cement leakage and incomplete pain relief.

13.
J Orthop Surg (Hong Kong) ; 29(3): 23094990211029349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34405755

RESUMO

BACKGROUND: Few studies have focused on the correlation between the clinical variables and the survival in Epithelioid Sarcoma (ES). The aim of this study was to investigate the relevant clinical variables influencing the survival of ES patients. METHODS: From March 2000 to April 2018, 36 patients (median age, 38 years, range 22-61 years) with ES were evaluated, treated, and followed up. RESULTS: All 36 patients underwent resection in our hospital. Among them, the 2 and 5 years local recurrence rates were 32.0% and 45.1%, respectively, with a better prognosis in patients with R0 resection margin. Distant metastasis rates for the 33 patients with M0 after 2 and 5 years were 51.5% and 70.8%, respectively. Overall survival rates at 2 and 5 years for 36 patients were 74.8% and 43.3%, respectively. Tumor size (>5 cm) and M1 were significantly associated with a poor overall survival. But the R0 resection margin was the only prognostic factor for influencing the LRFS and DMFS. CONCLUSIONS: The R0 resection margin and small tumor size were critical for a better prognosis.


Assuntos
Recidiva Local de Neoplasia , Sarcoma , Adulto , Humanos , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Sarcoma/epidemiologia , Sarcoma/cirurgia , Taxa de Sobrevida , Adulto Jovem
14.
Int J Biol Markers ; 35(3): 14-22, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32520634

RESUMO

BACKGROUND: The aim of this study was to evaluate the landscape of gene mutations and the clinical significance of tumor mutation burden (TMB) in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy. METHODS: A total of 68 patients with soft tissue sarcoma were included. Postoperative tumor tissue specimens from the patients were collected for DNA extraction. Targeted next-generation sequencing of cancer-relevant genes was performed for the detection of gene mutations and the analysis of TMB. Univariate analysis between TMB status and prognosis was carried out using the Kaplan-Meier survival analysis, and multivariate analysis was adjusted by the Cox regression model. RESULTS: No specific genetic mutations associated with soft tissue sarcoma were found. The mutation frequency of TP53, PIK3C2G, NCOR1, and KRAS of the 68 patients with soft tissue sarcoma were observed in 19 cases (27.94%), 15 cases (22.06%), 14 cases (20.59%), and 14 cases (20.59%), respectively. With regard to the analysis of TMB, the overall TMB of the 68 patients with soft tissue sarcoma was relatively low (median: 2.05 per Mb (range: 0∼15.5 per Mb)). Subsequently, TMB status was divided into TMB-Low and TMB-Middle according to the median TMB. Patients with TMB-Low and TMB-Middle were 37 cases (54.41%) and 31 cases (45.59%), respectively. Overall survival analysis indicated that the median overall survival of patients with TMB-Low and TMB-Middle was not reached, and 4.5 years, respectively (P=0.015). CONCLUSION: This study characterizes the genetic background of patients with STS soft tissue sarcoma. The TMB was of clinical significance for patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy.


Assuntos
Quimioterapia Adjuvante/métodos , Sarcoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Sarcoma/genética , Adulto Jovem
15.
Bone ; 130: 115139, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31706051

RESUMO

Bone metastasis is common in late-stage breast cancer patients and leads to skeletal-related events that affect the quality of life and decrease survival. Numerous miRNAs have been confirmed to be involved in metastatic breast cancer, such as the miR200 family. Our previous study identified microRNA-429 (miR-429) as a regulatory molecule in breast cancer bone metastasis. However, the effects of miR-429 and its regulatory axis in the metastatic breast cancer bone microenvironment have not been thoroughly investigated. We observed a positive correlation between miR-429 expression in clinical tissues and the bone metastasis-free interval and a negative correlation between miR-429 expression and the degree of bone metastasis. We cultured bone metastatic MDA-MB-231 cells and used conditioned medium (CM) to detect the effect of miR-429 on osteoblast and osteoclast cells in vitro. We constructed an orthotopic bone destruction model and a left ventricle implantation model to examine the effect of miR-429 on the metastatic bone environment in vivo. The transfection experiments showed that the expression levels of V-crk sarcoma virus CT10 oncogene homolog-like (CrkL) and MMP-9 were negatively regulated by miR-429. The in vitro coculture experiments showed that miR-429 promoted osteoblast differentiation and that CrkL promoted osteoclast differentiation. The two animal models showed that miR-429 diminished local bone destruction and distant bone metastasis but CrkL enhanced these effects. Furthermore, CrkL and MMP-9 expression decreased simultaneously in response to increased miR-429 expression. These findings further reveal the possible mechanism and effect of the miR-429/CrkL/MMP-9 regulatory axis in the bone microenvironment in breast cancer bone metastasis.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , MicroRNAs , Animais , Neoplasias Ósseas/genética , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloproteinase 9 da Matriz/genética , MicroRNAs/genética , Metástase Neoplásica , Qualidade de Vida , Microambiente Tumoral
16.
Biomaterials ; 29(17): 2588-96, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18378303

RESUMO

In this study, the in vivo bone-regenerative capacity and resorption of the porous beta-calcium silicate (beta-CaSiO(3), beta-CS) bioactive ceramics were investigated in a rabbit calvarial defect model, and the results were compared with porous beta-tricalcium phosphate (beta-Ca(3)(PO(4))(2), beta-TCP) bioceramics. The porous beta-CS and beta-TCP ceramics were implanted in rabbit calvarial defects and the specimens were harvested after 4, 8 and 16 weeks, and evaluated by Micro-CT and histomorphometric analysis. The Micro-CT and histomorphometric analysis showed that the resorption of beta-CS was much higher than that of beta-TCP. The TRAP-positive multinucleated cells were observed on the surface of beta-CS, suggesting a cell-mediated process involved in the degradation of beta-CS in vivo. The amount of newly formed bone was also measured and more bone formation was observed with beta-CS as compared with beta-TCP (p<0.05). Histological observation demonstrated that newly formed bone tissue grew into the porous beta-CS, and a bone-like apatite layer was identified between the bone tissue and beta-CS materials. The present studies showed that the porous beta-CS ceramics could stimulate bone regeneration and may be used as bioactive and biodegradable materials for hard tissue repair and tissue engineering applications.


Assuntos
Materiais Biocompatíveis/química , Regeneração Óssea , Compostos de Cálcio/química , Cerâmica , Silicatos/química , Crânio/cirurgia , Animais , Reabsorção Óssea , Substitutos Ósseos/normas , Fosfatos de Cálcio/química , Força Compressiva , Microanálise por Sonda Eletrônica , Implantes Experimentais , Teste de Materiais , Microscopia Eletrônica de Varredura , Porosidade , Coelhos , Crânio/patologia , Tomografia Computadorizada por Raios X
17.
Cell Cycle ; 17(18): 2296-2308, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30257602

RESUMO

Melanoma was the most malignant skin neoplasm with an increasing morbidity around the world. Although new immunotherapies and targeted therapies have emerged recently, the long-term survival of melanoma patients still remains low. To reveal effective diagnostic methods and therapeutic strategies, the potential mechanism of melanoma is urgently needed to be studied. Long non-coding RNAs (lncRNAs) have become an important regulatory factor in the occurrence and development of cancer, and it can be used as a new prognostic and diagnostic marker. In this study, we aimed to inspect the effects of lncRNA colorectal neoplasia differentially expressed (CRNDE) on the melanoma cell viability, invasion and migration. After microarray analysis, 106 dysregulated lncRNAs and 1187 abnormally expressed mRNAs were screened out. Further, the lncRNA CRNDE and CCL18 expression in melanoma tissues and cell lines were examined. It was determined that they were both overexpressed in melanoma tissues and cell lines. The down-regulation of lncRNA CRNDE and CCL18 induced melanoma cell apoptosis and inhibited cell viability. Then, miR-205 which had binding site with lncRNA CRNDE and CCL18 was involved in the next experiment, and it was down-regulated in melanoma that negatively correlated with lncRNA CRNDE expression. In addition, overexpression of miR-205 results in the restore of cell viability and aggressiveness. In conclusion, LncRNA CRNDE promotes the migration and invasion of melanoma by sponging miR-205 and releasing CCL18.


Assuntos
Quimiocinas CC/metabolismo , Melanoma/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Antagomirs/metabolismo , Apoptose , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocinas CC/química , Quimiocinas CC/genética , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Melanoma/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência
18.
Zhonghua Yi Xue Za Zhi ; 87(3): 200-3, 2007 Jan 16.
Artigo em Zh | MEDLINE | ID: mdl-17425853

RESUMO

OBJECTIVE: To explore the feasibility, effectiveness, and mechanism of culturing osteoblasts on calcium phosphate cement (CPC) scaffolds with controlled internal channel architectures in a rotating bioreactor, and to develop a novel method for construction of segmental tissue engineered bone in vitro. METHODS: Self-hardening CPC scaffolds with controlled internal channel architectures were designed and fabricated using computer aided design (CAD) and indirect rapid prototyping (RP) techniques. A rotating bioreactor was developed. Osteoblasts were isolated from the skull of rabbit and seeded onto the CPC scaffolds, cultured for up to 21 days in static or rotating three-dimensional (3D) dynamic conditions. 7, 14, and 21 days after the incubation the proliferation, metabolic activity, and differentiation of the osteoblasts were determined by MTT, glucose consumption, and alkaline phosphate activity (ALP) assays respectively. The distribution of cells throughout the scaffolds was observed by scanning electron microscopy (SEM) and the sphere like structures which the SEM images showed within the extracellular matrix were assessed by energy dispersive X-ray (EDX) analysis. RESULTS: At all culture time points, the rotatingly cultured constructs demonstrated greater proliferation, metabolic activity, and osteoblastic differentiation than those of the statically cultured constructs as evidenced by MTT, glucose consumption and ALP assays. SEM indicated that 21 days after the distribution of cells in the scaffolds in the rotating culture was much more uniform than in the static culture. The sphere like structures was identified as calcium phosphate nodules by EDX analysis. CONCLUSION: As a novel method for construction of segmental tissue engineered bone in vitro, the rotating 3D dynamic culture of osteoblasts on CPC scaffolds with controlled internal channel architectures improves the properties such as proliferation, metabolic activity, osteoblastic differentiation, and uniform distribution of the seeded cells over those that maintain in static culture.


Assuntos
Osteoblastos/citologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Animais Recém-Nascidos , Reatores Biológicos , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Coelhos , Crânio/citologia
19.
Oncol Lett ; 13(3): 1343-1347, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28454259

RESUMO

A wide resection of the tumor with or without chemotherapy is the treatment of choice for periosteal osteosarcoma (PO) of the extremities, however, post-operative limb function and quality of life could be compromised. The present study reports two cases of 14-year-old boys who presented with progressively enlarging masses in their right knee regions. Computed tomography and magnetic resonance imaging scans indicated a fusiform space-occupying mass encircling the bone cortex, with stippled calcification. A diagnosis of PO was suspected. The histological findings confirmed the diagnosis of intermediate PO. Pre-operative chemotherapies were started, and good responses were detected by clinical evaluation and histological findings. Surgeries preserving the functional structures, including neurovascular bundles, tendons, muscles and epiphyses, were performed, followed by routine chemotherapy. The two patients experienced disease-free survival with follow-up times of 37 and 108 months, respectively. The patients were satisfied with the results of the treatment and they returned to normal life activities. These two cases indicated that a marginal resection of the tumor in conjunction with effective neoadjuvant chemotherapy may be an ideal alternative treatment for intermediate PO, since survival along with well-preserved limb function could be guaranteed. By contrast, a wide excision could result in the loss of limb function.

20.
Oncotarget ; 8(62): 104785-104795, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29285213

RESUMO

OBJECTIVE: To investigate the clinicopathological features and prognosis of malignant peripheral nerve sheath tumors (MPNST). RESULTS: A total of 159 patients with MPNST were enrolled in the study. The ratio of male to female was 1.04 to 1. The median age was 40 (range: 5-76) years at the time of diagnosis. The 3- and 5-year overall survival rates were 50.0% and 43.0%, respectively. The median follow-up period was 31.0 (range: 2.0-199.0) months. Multivariate analysis showed that AJCC stage and S-100 were independent factors affecting overall survival (p < 0.05 for both). 3- and 5-year tumor-free survival rates for 140 completely resected patients were 40.0% and 34.0%, respectively. Multivariate analysis showed that AJCC stage, S-100 and Ki67 staining were independent factors of tumor-free survival (p < 0.05 for all). MATERIALS AND METHODS: The clinical data of MPNST patients who were treated at Cancer Institute and Hospital, Chinese Academy of Medical Science from January 1999 to January 2016 was retrospectively reviewed. CONCLUSIONS: MPSNT is a highly aggressive tumor with poor prognosis and this study may be useful for prognostic assessment and management decisions. This had been largest documented retrospective study of MPSNT among Chinese populations. Some characteristics were different from those of foreign populations which may suggest the specificity of Chinese patients.

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