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1.
Exp Mol Pathol ; 118: 104603, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33422488

RESUMO

The aim of this study was to assess the association between NF1 and PTEN gene polymorphisms and the risk of soft tissue sarcomas (STSs). This case-control study collected peripheral blood from 136 patients with STSs and 124 healthy controls. Six single nucleotide polymorphisms (SNPs) of the NF1 gene and five SNPs of the PTEN gene were investigated and genotyped using the SNaPshot assay. The association between the polymorphisms and the risk of STSs was estimated using unconditional logistic regression analysis. The results showed that individuals with the TC/CC genotype for NF1 rs2905789 displayed a significantly increased risk of STSs compared with individuals with wild-type TT (OR = 1.702, 95% CI = 1.002-2.890, P = 0.049). There were no significant differences in the distribution of the genotype or the allele frequencies of the polymorphisms of the NF1 and PTEN genes between the STSs patients and the controls in a Chinese population. Therefore, this study's results suggest that individuals carrying the TC/CC genotype for NF1 rs2905789 may be susceptible to STSs.

2.
BMC Cancer ; 20(1): 1139, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228579

RESUMO

BACKGROUND: The recommended cumulative doxorubicin dose in soft tissue sarcoma (STS) treatment was based on cardiotoxicity data from retrospective studies of breast cancer patients. However, the treatment and prognosis of STS and breast cancer are quite different, and reference to breast cancer data alone may not reflect the efficacy of doxorubicin treatment in STS. This study, thus, aimed to review and analyze clinical data of STS patients treated with a high cumulative doxorubicin dose, to provide a reference for treatment selection and clinical trial design. METHODS: We retrospectively collected and analyzed clinical data of patients with advanced STS who received doxorubicin-based chemotherapy from January 2016 to January 2020. The patients were divided into a standard-dose group (who received ≤6 cycles of doxorubicin after the initial diagnosis) and an over-dose group (who were re-administered doxorubicin [doxorubicin-rechallenge] after receiving 6 cycles of doxorubicin therapy discontinuously). Patient characteristics, cumulative doxorubicin dose, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), cardiotoxicity incidence, and treatment effectiveness were evaluated in both groups. RESULTS: A total of 170 patients with advanced STS were recruited (146 in the standard-dose group and 24 in the over-dose group). The average cumulative doxorubicin dose was 364.04 ± 63.81 mg/m2 in the standard-dose group and 714.38 ± 210.09 mg/m2 in the over-dose group. The ORR, DCR, and median PFS were 15.07, 58.9%, and 6 (95% confidence interval [CI]: 5.8-6.5) months in the standard-dose group and 16.67, 66.67%, and 4 (95%CI: 2.0-5.8) months in the over-dose group, respectively. Symptomatic heart failure occurred in five patients (3.42%) of the standard-dose group and in one patient (4.17%) of the over-dose group. In these patients with cardiotoxicity, doxorubicin was discontinued, and all of them died of uncontrolled tumor growth. No drug-related deaths occurred. CONCLUSIONS: The continuation of or rechallenge with doxorubicin beyond the recommended cumulative dose could be a promising therapeutic option in the treatment of chemotherapy-sensitive advanced sarcomas. Further evaluation is necessary in prospective trials.

3.
Cancer Sci ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164271

RESUMO

Mounting research papers have suggested that long non-coding RNAs (lncRNAs) elicit important functions in the progression of osteosarcoma (OS). This study focused on the role of TNK2-AS1 in OS. TNK2-AS1 was powerfully expressed in OS tissues and cell lines. In addition, TNK2-AS1 downregulation inhibited proliferative, migratory, and invasive capacities while promoting apoptosis in OS cells. miR-4319 was removed by TNK2-AS1 and therefore TNK2-AS1 elevated WDR1 expression in OS cells. miR-4319 had an inhibitory influence on OS progression, while WDR1 was a contributor to OS progression. Rescue assays certified that TNK2-AS1 promoted malignant phenotypes in vitro and the growth in vivo of OS cells by upregulating WDR1. In depth, we found that YY1 accelerated the transcription of TNK2-AS1 in OS cells, and that its role in OS also depended on TNK2-AS1-regulated WDR1. In conclusion, TNK2-AS1 was positively modulated by YY1 and aggravated the development of OS by 'sponging' miR-4319 to elevate WDR1. The findings highlighted that TNK2-AS1 might be a promising target for the treatment of OS.

4.
Anticancer Drugs ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33105152

RESUMO

This study was performed to investigate pneumothorax characteristics and association with clinical outcomes in patients with osteosarcoma treated with apatinib. We retrospectively reviewed the medical records of osteosarcoma patients treated with apatinib between January 2016 and April 2020 at three institutions. We evaluated the prevalence, healing time, recurrence, severity, clinical management, and prognosis of pneumothorax in these patients. A total of 54 osteosarcoma patients who received apatinib treatment were enrolled in this study. Among them, 14 patients had pneumothorax. There were significant differences between the patients with and without pneumothorax with regard to the cavitating rate of lung metastases (92.86 vs. 32.50%, respectively, P < 0.001), objective response rate (42.86 vs. 10.00%, P = 0.013), disease control rate (85.71 vs. 42.50%, P = 0.006), 4-month progression-free survival (PFS) rate (57.10 vs. 20.00%, P < 0.001), and median PFS (5.65 vs. 2.90 months, P = 0.011). Compared with pneumothorax patients treated with chest tube drainage only [non-staphylococcal enterotoxin C (SEC) group], those treated with chest tube drainage and SEC thoracic perfusion in parallel (SEC group) had a shorter pneumothorax healing time (12.00 ± 4.50 days vs. 24.00 ± 14.63 days for SEC group and non-SEC group, respectively, P = 0.103), a lower recurrence rate of pneumothorax (25.00% vs. 66.67%, P = 0.277), and a longer median PFS (5.9 months vs. 4.75 months, P = 0.964). however, these numerical differences for the SEC/non-SEC data did not reach statistical significance. Pneumothorax and cavitation in lung metastases may be effective prognostic markers for patients with osteosarcoma treated with apatinib. SEC may be effective for treatment of such pneumothorax patients, warranting further study.

5.
Front Oncol ; 10: 564852, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072594

RESUMO

Soft tissue sarcomas are a set of malignancies of mesenchymal origin. Due to the rarity and similarity in clinical presentation, they are grouped together and treated similarly in clinic. The response rates for current chemotherapy are around 20% and the median overall survival for advanced soft tissue sarcoma are less than 2 years. Thus, the current strategy with identical treatment for all soft tissue sarcomas is far from satisfactory. In this study, we first reviewed the current clinical and genomic findings of soft tissue sarcoma, paying special attention to the heterogeneities among different tumors. Then we reviewed the state-of-art understanding of targeted therapy in soft tissue sarcoma. We observed tremendous heterogeneity both in clinical and genomic settings between different tumors. Individualized treatment plans demonstrated better response and disease control and should be advocated. In summary, heterogeneity of soft tissue sarcomas requires the development of individualized treatment plans such as targeted therapy.

6.
Life Sci ; 262: 118544, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035586

RESUMO

AIMS: Our previous study has demonstrated that high expression of ALDH1B1 promoted osteosarcoma tumor progression and was correlated with unfavorable prognosis in osteosarcoma patients. In the current study, we investigated the underlying mechanism and regulation of ALDH1B1 in osteosarcoma. MATERIALS AND METHODS: qRT-PCR assay was applied to detect miR-761 expression. CCK-8, colony formation and EdU assays were conducted to explore the functional role of miR-761/ALDH1B1 axis in osteosarcoma. Bioinformatics analysis and luciferase reporter assay was utilized to assess the regulation between miR-761 and ALDH1B1. Mechanism experiments were implemented to investigate the underlying molecular mechanism of miR-761/ALDH1B1 axis. KEY FINDINGS: ALDH1B1 was negatively regulated by microRNA-761 (miR-761). Functionally, miR-761 suppressed cell growth, migration, and invasion in osteosarcoma via targeting ALDH1B1 in vitro. Xenograft tumor model demonstrated that miR-761 inhibited osteosarcoma tumor development in vivo through regulating ALDH1B1. Consistently, we showed that miR-761 expression was decreased in osteosarcoma patients and low expression of miR-761 was correlated with worse prognosis in osteosarcoma patients. Mechanistically, we revealed that high expression of ALDH1B1 was significantly associated with enhanced TGF-ß signaling, epithelial-mesenchymal transition (EMT), and cell adhesion. Furthermore, miR-761 regulated TGF-ß and EMT/cell adhesion in osteosarcoma via targeting ALDH1B1. SIGNIFICANCE: Taken together, our findings suggest that the oncogenic ALDH1B1 is regulated by miR-761 during osteosarcoma development and progression, which might provide a novel prognostic biomarker and therapeutic strategy for osteosarcoma treatment.

7.
Front Oncol ; 10: 1642, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984034

RESUMO

Recent clinical trials have shown several multi-target tyrosine kinase inhibitors (TKIs) to be effective in the treatment of osteosarcoma. However, these TKIs have a number of targets, and it is yet unclear which of these targets has a key role in osteosarcoma treatment. In this review, we first summarize the TKIs that were studied in clinical trials registered on ClinicalTrials.gov. Further, we compare and discuss the targets of these TKIs. We found that TKIs with promising therapeutic effect for osteosarcoma include apatinib, cabozantinib, lenvatinib, regorafenib, and sorafenib. The key targets for osteosarcoma treatment may include VEGFRs and RET. The receptor tyrosine kinases (RTKs) MET, IGF-1R, AXL, PDGFRs, KIT, and FGFRs might be relevant but unimportant targets for osteosarcoma treatment. Inhibition of one type of RTK for the treatment of osteosarcoma is not effective. It is necessary to inhibit several relevant RTKs simultaneously to achieve a breakthrough in osteosarcoma treatment. This review provides comprehensive information on TKI targets relevant in osteosarcoma treatment, and it will be useful for further research in this field.

8.
Front Oncol ; 10: 1209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850355

RESUMO

Surgeries of pelvic bone tumors are very challenging due to the complexity of anatomical structures and the irregular bone shape. CT and MRI are used in clinic for tumor evaluation, each with its own advantages and shortcomings. Combining the data of both CT and MRI images would take advantage of the merits of both images and provide better model for preoperative evaluation. We utilized an artificial intelligence (AI)-assisted CT/MRI image fusion technique and built a personalized 3-D model for preoperative tumor margin assessment. A young female patient with pelvic osteosarcoma was evaluated with our novel image fusion 3-D model in comparison with the 3-D model based solely on CT images. The fusion image model showed more detailed anatomical information and discovered multiple emboli within veins which were previously neglected. The discovery of emboli implied abysmal prognosis and discouraged any attempts for complex reconstruction after tumor resection. Based on the experience with this pelvic osteosarcoma, we believe that our image fusion model can be very informative with bone tumors. Though further validation with a large number of clinical cases is required, we propose that our model has the potential to benefit the clinic in the preoperative evaluation of bone tumors.

9.
BMC Cancer ; 20(1): 698, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32723378

RESUMO

BACKGROUND: The evidence that albumin-bound paclitaxel (nab-paclitaxel) is safe and efficacious for the treatment of many types of malignant tumors is continuously increasing. However, the evidence and clinical data of nab-paclitaxel and gemcitabine in metastatic soft tissue sarcoma (STS) treatment are rare. METHODS: The clinical data of metastatic STS patients who received nab-paclitaxel/ gemcitabine chemotherapy between January 2019 and February 2020 were retrospectively analysed. All these patients were treated with nab-paclitaxel/ gemcitabine only after doxorubicin-based chemotherapy had failed. We evaluated the effectiveness and safety of nab-paclitaxel and gemcitabine in these patients. RESULTS: A total of 17 patients treated with nab-paclitaxel/ gemcitabine were enrolled in this study. One patient with angiosarcoma achieved complete response, 6 patients had partial response, 5 patients achieved stable disease, and 5 patients had progressive disease. The average diameter change in target lesion from baseline was - 19.06 ± 45.74%. And median progression free survival was 6 months (95% CI, 2-9 months). Grade 3 / 4 adverse events were not common, included neutropenia (17.6%), fatigue (11.8%), anemia (11.8%), leukopenia (11.8%), nausea (5.9%), peripheral neuropathy (5.9%), diarrhea (5.9%), and thrombocytopenia (5.9%). No treatment-related deaths occurred. CONCLUSION: Nab-paclitaxel/ gemcitabine combination chemotherapy is comparatively effective in the treatment of STS, demonstrates low toxicity, and is worthy of further study.

10.
Medicine (Baltimore) ; 99(27): e20715, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629645

RESUMO

To understand the feasibility, clinical effect, and complications related to biological reconstruction techniques for long limb malignant bone tumors after excision.This retrospective study included eighty patients with malignant bone tumors treated at our hospital between January 2007 and January 2019. After tumor resection, 52 cases of intercalary and 28 cases of osteoarticular bone grafts were used. The implanted bone included devitalized recycling bone, fibular, and allograft.The average follow up period was 42.19 months for 80 patients, among whom 15 (18.75%) died. The 5-year EFS and OS were 58% and 69%, respectively. The average length of the replanted bone was 18.57 cm. The MSTS scores of intercalary and osteoarticular bone grafts were 87.24% and 64.00%, respectively. In 23 cases (44.23%) of metaphyseal and 26 cases (32.5%) of the diaphysis, bone graft union was obtained at the first stage. The factors affecting bone union were the patient's gender, age, devitalization bone methods and whether the implanted bone was completely fixed. Postoperative complications included delayed bone union in 15 patients, fractures in 25 cases, nonunion in 22 cases, bone resorption in 14 cases, and postoperative infection in 4 cases. Twenty-eight cases of bone grafting required revision surgery, including replacement of internal fixation, autologous bone graft, debridement, removal of internal fixation, and replacement with prosthetic replacement.Biological reconstructions with massive bone grafts are useful in the reconstruction of certain malignant extremity bone tumors after wide excision.


Assuntos
Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Neoplasias Femorais/cirurgia , Úmero/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Sarcoma/cirurgia , Tíbia/cirurgia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
11.
Pathol Res Pract ; 216(6): 152983, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32327283

RESUMO

Cancers are deadly diseases. The general mystery of carcinogenesis, primary and acquired drug resistance and distant organ metastasis are still puzzles to be solved. Long noncoding RNAs (lncRNAs) are receiving more and more attention in recent years since their roles in transcriptional regulation have been unveiled. Detailed functional annotations of lncRNAs have showed that their regulatory roles are largely determined by their binding partners. LncRNAs directly bind to DNA, RNA and proteins and regulate gene expression at transcriptional, post-transcriptional and post-translational levels. Here we review the current understanding of molecular functions of lncRNAs, will emphasize on their binding partners and summarize their biological roles in cancer.

12.
Med Sci Monit ; 26: e920826, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32193367

RESUMO

BACKGROUND This study aimed to investigate the role of gene mutation site distribution, biological function, pathway enrichment, and gene association analysis in the occurrence, development, and migration of osteosarcoma. MATERIAL AND METHODS Somatic mutation screening was performed using the whole-exome sequencing of osteosarcoma samples, and the distribution of mutations was demonstrated by Circos diagrams. Metascape was used to analyze the GO and KEGG signal pathway enrichment of the genes harboring protein coding alterations, and GeneMANIA was used to analyze the interaction of mutated genes. RESULTS The results showed that the protein coding alterations were found throughout the whole genome in 3 osteosarcoma samples. A large number of identical or related biological processes and pathways were found in osteosarcoma samples. The GeneMANIA analysis of the 10 mutations shared by 3 samples showed that the target gene minichromosome maintenance complex component 4 (MCM4) and 3 lateral genes were most functional, and were all related to DNA replication. The analysis of GO and KEGG signal pathway enrichment showed that the mutated genes were involved mainly in tumor-related metabolic pathways. Three mutated genes were involved in the cell process, and 2 mutated genes were involved in the metabolic process. Known driver gene mutations were also observed in the samples. CONCLUSIONS The gene analysis confirmed that patients with osteosarcoma had a wide range of common gene mutations related to each other, which are involved in tumor-related metabolic pathways. These findings provide a basis for further gene-targeted therapy and pathway research.


Assuntos
Neoplasias Ósseas/genética , Mutação , Osteossarcoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Transdução de Sinais , Sequenciamento Completo do Exoma
13.
World J Surg Oncol ; 18(1): 23, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996228

RESUMO

BACKGROUND: The proximal humerus is one of the most common sites of primary or metastatic malignant tumors. Reconstruction of the shoulder after tumor resection is controversial and challenging. When intra-articular resection is performed, biological reconstruction (osteoarticular allograft and autologous bone implantation) may be the first choice rather than prosthetic reconstruction. OBJECTIVE: To observe the mid- to long-term effects of oncologic, reconstructive, and functional outcomes of two different biological reconstruction methods for resection of humerus osteosarcoma involving caput humeri. METHODS: This was a retrospective study of 13 consecutive patients who underwent humeral reconstruction of osteosarcoma including caput humeri using osteoarticular allograft (n = 7) and tumor bone inactivated and reimplantation (TBIR, n = 6) in our clinic between 2007 and 2017. Patients' general information, resection and reconstruction techniques, oncological and functional outcomes, and complications were collected and evaluated. Different complications of implantations were compared and analyzed for the different biological methods. RESULTS: The study included ten males and three females with an average age of 19.15 years. The operation time was about 3.65 h with an average blood loss of 631 ml. The resection tumor bones were 13-45 cm (23.54 cm on average). The mean follow-up period was 5.27 years. The shoulder movement was 10-70° (average, 44.00°) in abduction, 0-30° (average, 14.17°) in flexion, and 0-20° (average, 11.90°) in extention at the last follow-up. The complications included fracture in four TBIR patients and two allograft patients with an average of 2.67 years postoperation. Fracture rate was higher and appeared time was earlier in TBIR patients than in allograft patients (p = 0.04); caput humeri absorption occurred in all seven allograft patients and three TBIR patients at an average of 3.10 years after surgery; severe graft bone resorption appeared in five TBIR patients and two allograft patients at an average of 2.57 years of follow-up. CONCLUSIONS: Humerus biological reconstruction involving caput humeri was associated with a high complication rate and acceptable limb function in the mid to long term. New combined biological methods should be explored and adopted in the future.


Assuntos
Neoplasias Ósseas/cirurgia , Úmero/cirurgia , Osteossarcoma/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Ombro/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/patologia , Criança , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Úmero/patologia , Masculino , Osteossarcoma/patologia , Prognóstico , Estudos Retrospectivos , Ombro/patologia , Adulto Jovem
14.
Cancer Manag Res ; 11: 5293-5300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239779

RESUMO

Purpose: Apatinib has shown effectiveness in treating sarcoma. This study aimed to assess the safety and efficacy of apatinib and doxorubicin combination therapy in metastatic soft tissue sarcomas (STS) and to compare the therapeutic effects of two treatments (apatinib after doxorubicin vs apatinib plus doxorubicin) on STS. Patients and methods: A total of 76 patients with metastatic STS who received apatinib and doxorubicin between May 2016 and June 2017 were retrospectively reviewed. Patients were divided into either the apatinib after doxorubicin group (in which apatinib was used after six cycles of doxorubicin chemotherapy) or the apatinib plus doxorubicin group (in which apatinib was used in combination with doxorubicin chemotherapy). Results: There were 55 patients in the apatinib after doxorubicin group and 21 patients in the apatinib plus doxorubicin group. There were significant differences between the apatinib plus doxorubicin group and the apatinib after doxorubicin group in the objective response rate (57.14% vs 25.45%, respectively, p=0.016) and average change from baseline in the target lesion size (-41.71±43.75% vs -1.89±51.61%, respectively, p=0.03). There were no significant differences in disease control rate (85.71% vs 63.64%, p=0.093) and median progression-free survival (8.8 months vs 10.3 months, p=1). Grade 3-4 adverse events were more common with apatinib plus doxorubicin than with apatinib after doxorubicin, and these included leukopenia (5.45% vs 38.1%, respectively, p=0.001), anemia (7.27% vs 28.57%, respectively, p=0.023), oral mucositis (3.64% vs 19.05%, respectively, p=0.046), transaminase increases (0% vs 14.29%, respectively, p=0.011). Conclusion: Our results do not support the use of apatinib plus doxorubicin for metastatic STS unless the specific objective is tumor shrinkage.

15.
Medicine (Baltimore) ; 98(19): e15650, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083265

RESUMO

Recently, apatinib has been shown to be effective in treating sarcoma. This study aimed to assess the safety and efficacy of apatinib in the treatment of patients with osteosarcoma after failed of standard multimodal therapy and to compare the therapeutic effects of apatinib on osteosarcoma between high-dose group and low-dose group.A total of 27 patients with osteosarcoma who received apatinib between January 2016 and August 2017 were retrospectively reviewed. Among the 27 patients, the objective response rate (ORR) and the disease control rate (DCR) were 25.93% and 66.67%, respectively. The median of progression-free survival (m-PFS) was 3.5 months (95% confidence interval [CI], 2.5-4.8 months), and the median of overall survival (m-OS) was 9.5 months (95% CI, 7.8-10.5 months). There was no statistically significant difference in ORR (36.36% vs 18.75%), DCR (63.64% vs 68.75%), m-PFS (4.3 months [95% CI, 1.8-7 months) vs 3.35 months (95% CI, 1.8-4 months]), and m-OS (9.5 months [95% CI, 7.8-10.5 months] vs 9.4 months [95% CI, 7.8-10.8 months]) (P > .05) between the high-dose group (the average dose was 659 mg/qd) and the low-dose group (the average dose was 516 mg/qd). Most of the adverse events (AEs) were in grade 1 or grade 2. The main AEs in grade 3 were hypertension, rash, weight loss, hand-foot syndrome, and diarrhea.Apatinib is safe and effective in the treatment of advanced osteosarcoma. We recommend that the initial dose of apatinib should be 500 mg/qd in the treatment of osteosarcoma.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/terapia , Osteossarcoma/terapia , Piridinas/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/mortalidade , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Osteossarcoma/mortalidade , Piridinas/efeitos adversos , Retratamento , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
Oncotarget ; 9(2): 2502-2514, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29416787

RESUMO

Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood and adolescence with poor prognosis. The mechanism underlying tumorigenesis and development of OS is largely unknown. ALDH1B1 has been reported to involve in many kinds of human cancers and functions as an oncogene, but the role of ALDH1B1 in OS has not been investigated comprehensively. In the present study, we aimed to examine clinical value and biological function of ALDH1B1 in OS. Firstly, we investigated the roles of ALDH1B1 on an OS tissue microarray (TMA) as well as two OS cohorts from GEO database. We found that ALDH1B1 was significantly up-regulated in OS tissues and was independently associated with poor prognosis. Moreover, ALDH1B1 silencing could suppress the proliferation, migration, invasion in vitro and inhibit the growth of xenograft tumor and of OS cells in vivo. Additional, ALDH1B1 knockdown increased the apoptosis rate and lead to cell cycle arrest in G1 stage of OS cell in vitro. More importantly, the inhibition of ALDH1B1 expression could increase the sensitivity of OS cells to chemotherapy, which suggested that ALDH1B1 might be served as a therapeutic target to reverse drug resistance in chemotherapy in OS patients. Taken together, our founding suggested that ALDH1B1 contributes to OS tumor progression and drug resistance, which may represent a novel prognostic marker and potential therapeutic target for OS patients.

17.
Oncol Lett ; 14(5): 5241-5248, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29113159

RESUMO

Limb sparing surgery in growing young patients with malignant tumors is difficult as invasion of the physis by the tumor or surgical resection through the metaphysis may cause significant limb discrepancy following surgery. At present, hinged tumor prosthesis or biological reconstructions are the main methods following tumor resection in these patients. The aim of the present study was to assess different procedures for the treatment of osteosarcoma around knee joints in immature patients. A retrospective study of 56 patients (<15 years old, open physis) who had been treated for osteosarcoma around the knee joint between January 2007 and December 2015 was performed. Clinical data collected included patient demographics (age at diagnosis, sex and date of diagnosis), tumor characteristics [location, Enneking stage and subtype on magnetic resonance imaging (MRI)], treatment (response to neoadjuvant chemotherapy and type of primary surgery) and clinical outcomes (limb function, discrepancy and overall survival). The median age at the time of diagnosis was 12.14 years (range, 3-15 years). There were 32 male patients (57.1%). A total of 41 (82%) tumors were located at the distal femur, and 15 (18%) at the proximal tibia. A total of 49 (87.5%) patients were diagnosed with stage IIB tumors, and 7 (12.5%) had stage III, according to the Enneking stage classification. Different surgical methods, including amputation, rotation-plasty, endoprosthesis and biological instructions (e.g., allograft) were performed according to MRI type classification. During follow-up, 21 patients (37.5%) succumbed to disease. The Musculoskeletal Tumor Society score ranged from excellent to fair functional result. Recurrence (2 cases, 16.67%) and infection (2, cases, 16.67%) were the main complications following endoprosthesis replacement, while delayed union (12 cases, 57.14%) and fracture (3 cases, 14.29%) were the main causes for biological reconstructions. Limb-length discrepancy ranged from 0-10 cm in limb-saving surgery. The overall survival rate was 57.66% with different cohorts in Enneking stages IIB and III, with or without involvement of the physis and different cycles of chemotherapy. Results of the present study indicated that different limb saving surgeries, including epiphysis/physis preservation with biological construction in patients with MRI types I to III and endoprosthetic/osteoarticular reconstruction in patients with MRI types IV and V, are useful in the management of osteosarcoma in growing young patients with proper surgery indications, and knee joint function was maintained with acceptable complications including limb discrepancy, delayed union, infection, recurrence and fracture.

18.
Med Sci Monit ; 23: 665-672, 2017 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-28163298

RESUMO

BACKGROUND The aim of this study was to investigate the correlation between Hector Battifora mesothelial-1 (HBME-1) expression and the clinical pathological characteristics and prognosis of osteosarcoma (OS). MATERIAL AND METHODS HBME-1 expression was assessed using immunohistochemistry in OS tissues (n=152), osteochondroma tissues (n=91), and normal bone tissues (n=74). We carried out a follow-up lasting 8-60 months to investigate HBME-1 expression and its correlations with the clinical pathological characteristics and prognosis of OS. RESULTS HBME-1 was highly expressed in OS tissues compared with osteochondroma tissues and normal bone tissues, and was highly expressed in osteochondroma tissues compared with normal bone tissues (all P<0.05). HBME-1 expression was correlated with clinical stages, postoperative recurrence, metastasis, and 5-year survival (all P<0.05). The area under the receiver operating characteristics curve of HBME-1 expression was 0.864, with sensitivity of 80.92%, specificity of 91.89%, and accuracy of 84.51%. The survival rate was lower in the HBME-1 positive expression group than the HBME-1 negative expression group (P<0.05). Clinical stages, metastasis, and HBME-1 expression were independent risk factors for the survival of patients with OS (all P<0.05). CONCLUSIONS HBME-1 expression was correlated with the occurrence and development of OS. HBME-1 positive expression was a risk factor for the prognosis of OS.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Adolescente , Adulto , Criança , Transição Epitelial-Mesenquimal , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Osteocondroma/metabolismo , Osteocondroma/patologia , Prognóstico , Curva ROC , Fatores de Risco
19.
Arch Med Sci ; 11(4): 886-92, 2015 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-26322102

RESUMO

INTRODUCTION: The aim of the study was to explore an effective method to induce adipose-derived stem cells (ADSCs) to differentiate into Schwann-like cells in vitro. MATERIAL AND METHODS: Reagents were applied in two different ways (Dezawa inducing method and modified inducing method) in which inducers including ß-mercaptoethanol (ß-ME), all-trans-retinoic acid (ATRA), type I collagenase, forskolin, heregulin, basic fibroblast growth factor (BFGF) and brain-derived neurotrophic factor (BDNF) were used in different ways to induce ADSCs of rats to differentiate into Schwann-like cells. After induction, the cell morphologic characteristics and the cellular immunohistochemical staining positive rate of anti-S100 and anti-GFAP (glial fibrillary acidic protein) antibodies and the gray value of immunocytochemical dye with anti-S100 and anti-GFAP antibodies and cell activity measured by the MTT method were compared with each other to evaluate the induction effects. RESULTS: Both methods can induce differentiation of ADSCs of rats into Schwann-like cells, but the cellular morphology of the modified method was more similar to Schwann cells than that of the Dezawa inducing method, there was a higher cellular immunohistochemical staining positive rate and staining grey value in immunocytochemical dye with anti-S100 and anti-GFAP antibodies, and less damage in the cell activity of the modified inducing method than that of the Dezawa inducing method. CONCLUSIONS: The effect of the modified method to induce ADSCs to differentiate into Schwann-like cells in vitro is superior to that of the Dezawa inducing method.

20.
Int J Clin Exp Med ; 8(7): 11818-23, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26380023

RESUMO

Increasing studies have demonstrated that altered expression of histone deacetylases (HDACs) plays a critical role in the tumorigenesis through up-regulation or down-regulation of key genes involved in cell proliferation, cell-cycle regulation and apoptosis. In the present study, the expression and function of HDAC9 were investigated in osteosarcoma. Quantitative real-time PCR and Western blot analysis found that HDAC9 was up-regulated in osteosarcoma tissues, when compared with that in adjacent normal tissues. In vitro studies further demonstrated that overexpression of HDAC9 in U2OS and MG63 cells promoted cell proliferation and invasion. Using chromatin immunoprecipitation (ChIP) assay, we found that HDAC9 epigenetically repressed p53 transcription through binding to its proximal promoter region. Therefore, our data suggest an important role for HDAC9/p53 regulatory pathway in the osteosarcoma progression.

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