Publications by authors named "Jinpeng Jia"

17 Publications

  • Page 1 of 1

LncRNA BCRT1 facilitates osteosarcoma progression via regulating miR-1303/FGF7 axis.

Aging (Albany NY) 2021 06 8;13(11):15501-15510. Epub 2021 Jun 8.

Department of Orthopedics, The First Medical Center of General Hospital of PLA, Beijing 100853, China.

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.
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http://dx.doi.org/10.18632/aging.203106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221344PMC
June 2021

A Highly Sensitive Electrochemiluminescence Biosensor for Pyrophosphatase Detection Based on Click Chemistry-Triggered Hybridization Chain Reaction in Homogeneous Solution.

ACS Appl Mater Interfaces 2020 Aug 22;12(31):34716-34722. Epub 2020 Jul 22.

Department of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350000, China.

The abnormal expression of pyrophosphatase (PPase) is closely related to many diseases and malignant tumors, so the detection for PPase is of great significance in clinical diagnosis, disease monitoring, and other biomedical aspects. In this study, a sensitive and specific electrochemiluminescence (ECL) biosensor combined highly specific Cu-catalyzed azide-alkyne cycloaddition (CuAAC) with high efficiency of hybridization chain reaction (HCR) for the purpose of detecting pyrophosphatase has been designed. Highly efficient hybridization chain reaction amplification processed in homogeneous solution and the amplification products were connected to the electrode surface in one step, which solved the problem of low DNA amplification efficiency on the electrode surface because of the steric hindrance. Ru(phen) was embedded into the dsDNA and functioned as ECL probes; the enhanced ECL intensity of the system had a linear relationship with the logarithm of PPase concentration in the range of 0.025-50 mU with a detection limit of 8 μU. The method was proved to be of good specificity, repeatability, and stability that could be used for screening and quantitatively determining pyrophosphatase inhibitor sodium fluoride. The practicability of this method in clinical application has been proved through the detection of serum from the clinical arthritis patients. Moreover, the method can be used to monitor PPase activity of arthritis patients before and after administration to provide reference for the effect of drug treatment.
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http://dx.doi.org/10.1021/acsami.0c10542DOI Listing
August 2020

Correlation of p16 and nm23-H1 expression levels with incidence and prognosis of soft tissue sarcoma.

Oncol Lett 2019 Jun 13;17(6):4865-4870. Epub 2019 Mar 13.

Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.

The expression levels of p16 and nm23-H1 genes in soft tissue sarcoma (STS) were evaluated to investigate correlation of the expression levels with the incidence and prognosis of STS. Tumor tissues and para-carcinoma normal tissues were collected from 64 STS patients. The messenger ribonucleic acid (mRNA) expression levels of p16 and nm23-H1 in the tissues were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the protein expression levels of p16 and nm23-H1 in tissues were detected using immunohistochemistry. Spearman's correlation analysis was used for the correlation between expression levels of p16 and nm23-H1 in STS tissues and the correlation between p16 and nm23-H1 mRNA and protein expression. Moreover, the correlation of p16 and nm23-H1 expression levels in tumor tissues with pathological parameters and prognosis of STS patients were analyzed combined with clinical data. Results of RT-qPCR showed that mRNA expression levels of p16 and nm23-H1 in tumor tissues of STS patients were significantly lower than those in para-carcinoma normal tissues (P<0.01). Results of immunohistochemistry showed that the positive expression rates of p16 and nm23-H1 in tumor tissues of STS patients (43.75 and 39.06% respectively) were significantly lower than those in para-carcinoma normal tissues (85.93 and 89.06% respectively). The expression of p16 and nm23-H1 mRNA was positively correlated with protein expression levels. There was a positive correlation between the expression levels of p16 and nm23-H1 in tumor tissues of STS patients. The negative expression of p16 in tumor tissues of STS patients correlated with tumor size, tumor metastasis and clinical staging, and the negative expression of nm23-H1 correlated with tumor metastasis and clinical staging. The overall 5-year survival rate of patients was 54.68%, and the prognosis of patients with positive expression levels of p16 and nm23-H1 was better. Univariate survival analyses revealed that p16 and nm23-H1 were influencing factors of the overall survival rate of STS patients. p16 and nm23-H1 expression in STS is low, and their expression levels are closely related to the pathological parameters and prognosis of STS patients, so they can serve as reference indexes for prognosis estimation of STS.
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http://dx.doi.org/10.3892/ol.2019.10145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507347PMC
June 2019

Ratiometric Immunosensor for GP73 Detection Based on the Ratios of Electrochemiluminescence and Electrochemical Signal Using DNA Tetrahedral Nanostructure as the Carrier of Stable Reference Signal.

Anal Chem 2019 03 20;91(5):3717-3724. Epub 2019 Feb 20.

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Department of Chemistry , Fuzhou University , Fuzhou , Fujian 350116 , China.

DNA tetrahedron nanostructure (DTNs) has the merits of simple synthesis, high yield, structural stability, and mechanical rigidity, and its three-dimensional structure provides a satisfactory biosensing interface to the improvement of the binding efficiency of antigenic proteins and antibodies. Electrochemiluminescence (ECL) reagent, tris(4,4'-dicarboxylicacid-2,2'-bipyridyl)ruthenium(II) dichloride (Ru(dcbpy)Cl), was modified on the electrode through the formation of classical sandwich complex of antibody-antigen-antibody. ECL response of the system increased with the increment of the target (golgi protein 73 (GP73) in this study) with high selectivity. Besides, the composed double-stranded DNA (dsDNA) in each side of DTNs could act as an excellent carrier of methylene blue (MB), thus producing a stable electrochemical internal reference signal on the electrode surface to correct the potential interferences. Therefore, a highly selective and reproductive ratiometric immunosensor was developed on the basis of the ratio of ECL of Ru(dcbpy)Cl and electrochemistry of MB. The ratio value of the ECL/electrochemistry had a linear relationship with GP73 concentration in the range of 15 pg/mL-0.7 ng/mL, and the limit of detection was 15 pg/mL. The proposed ratiometric ECL immunoassay has been applied to detect GP73 in real serum samples with satisfactory results.
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http://dx.doi.org/10.1021/acs.analchem.9b00013DOI Listing
March 2019

The multidisciplinary treatment of osteosarcoma of the proximal tibia: a retrospective study.

BMC Musculoskelet Disord 2018 Sep 5;19(1):315. Epub 2018 Sep 5.

Department of Orthopaedics, PLA General Hospital, Beijing, 100853, China.

Background: Survival and reconstruction constitute important challenges in multimodal treatment of osteosarcoma of the proximal tibia. The purpose of this study was to assess the efficacy and prognosis of neoadjuvant chemotherapy and custom-designed endoprosthetic arthroplasty.

Methods: A total of 69 patients with osteosarcoma of the proximal tibia were evaluated, including 43 males and 26 females, treated with multidisciplinary limb-salvage remedy from October 2003 to December 2013. They were at least 12 years old (mean, 20 years; range, 12-57 years). The gap between tumor and main artery/nerve was showed in MRI. Mean follow up was 69.5 months (range, 9-144 months). Kaplan-Meier survival curves were generated to assess prognosis and relapse rate. The initial symptoms and disease duration for each patient were recorded. Correlation analyses were performed for the association of various parameters with prognosis. Functional outcomes were evaluated using the Musculoskeletal Tumor Society (MSTS) guidelines after 6 months postoperatively, to analyze the relation between bone excision size and function recovery.

Results: The resection lengths measured intraoperatively ranged from 80 to 230 mm, and contained 3 cm of normal bone around the tumor. A total of 3 courses of preoperative chemotherapy were administered to all cases. At final follow-up, 1 case showed recurrence. Meanwhile, 8 patients (11.6%) died from lung metastasis. Post-operative infection occurred in 3 patients; 1 case was maintained with revision surgery. Two cases underwent amputation. The mean MSTS system score was 21.6.

Conclusions: The multidisciplinary treatment result in an overall positive outcome, with improved function.
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http://dx.doi.org/10.1186/s12891-018-2245-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123999PMC
September 2018

[Effectiveness of unicompartment allografts replacement for bone tumor around the knee].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2017 08;31(8):908-912

Department of Orthopaedics, General Hospital of Chinese PLA, Beijing, 100853, P.R.China.

Objective: To analyze the effectiveness of unicompartment allografts replacement for reconstructing bone defect after bone tumor resection around knee.

Methods: Between January 2007 and January 2014, a total of 9 patients received unicompartment allografts replacement to treat bone tumor around the knee, including 6 males and 3 females, with an average age of 25.8 years (range, 17-38 years). There were 7 patients with bone giant cell tumor (postoperative recurrence of bone giant cell tumor in 1 case) and 2 patients with chondromyxoid fibroma. The tumors were located at the distal femur in 7 cases and proximal tibia in 2 cases, and the tumors were almost at the lateral limbs. The symptom duration was 2-5 months (mean, 3.2 months). The size of lesion ranged from 6 cm×2 cm to 9 cm×4 cm by X-ray film and MRI; and the metastasis was excluded by CT. The length of the allograft was 8.0-9.2 cm (mean, 8.6 cm).

Results: The intraoperative blood loss volume was 400-550 mL (mean, 480 mL); and 0-3 U of erythrocyte was transfused after operation. The continuous exudate of incision occurred in 1 patient, and cured after 3 months; the other incisions healed primarily at 2 weeks after operation. All patients were followed up 3-10 years (mean, 6 years). No operation area infection, allograft bone poor healing or rupture was found. At 1 year after operation, the knee range of motion was 90-110° (mean, 100°); the Musculoskeletal Tumor Society score was 24-29 (mean, 26). Low density area (osteolysis) was found in 6 allografts; no articular surface collapse, hairline fracture, or fracture was found in patients; callus formation was observed in the contact surface between the allograft and the host bone, and the cortical bone showed good continuity.

Conclusion: Unicompartment allografts replacement can provide good support and function in terms of bone tumor resection, and achieve good effectiveness by biological reconstruction.
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http://dx.doi.org/10.7507/1002-1892.201704044DOI Listing
August 2017

Construction of versatile multilayered composite nanoparticles from a customized nanogel template.

Bioact Mater 2018 Mar 1;3(1):87-96. Epub 2017 Jul 1.

Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.

We present a highly adaptable design platform for multi-responsive, multilayered composite nanoparticles (MC-NPs) with fine-tunable functional layers. A flexible disulfide-linked nanogel template is obtained by a controlled gelation method, enabling a high degree of control over each successive layer. From this template, we optimize "smart" biomaterials with biofunctional surfaces, tunable drug release kinetics, and magnetic or pH-responsive functionality, fabricated into MC-NPs for targeted drug release and periosteum-mimetic structures for controlled rhBMP-2 release towards bone tissue formation . Such a versatile platform for the design of MC-NPs is a powerful tool that shows considerable therapeutic potential in clinical fields such as oncology and orthopedics.
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http://dx.doi.org/10.1016/j.bioactmat.2017.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935661PMC
March 2018

MicroRNA-300 decreases cell viability, inhibits migration and promotes apoptosis of osteosarcoma cells via downregulation of Twist1.

Mol Med Rep 2017 Sep 17;16(3):3613-3618. Epub 2017 Jul 17.

Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.

Osteosarcoma (OS) is the most frequently occurring pediatric bone malignancy in the world. Numerous miRNAs have previously been demonstrated to participate in the initiation and development of OS. The present study aimed to reveal the role of microRNA‑300 (miR‑300) in OS cells and elucidate the underlying mechanism involved. The expression of miR‑300 in the MG63 human OS cell line was monitored via quantitative polymerase chain reaction (qPCR). Following transfection with miR‑300 mimic, miR‑300 inhibitor or scramble control, MG63 cell viability, migration and apoptosis were respectively measured by 3‑(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphenyltetrazolium bromide (MTT), modified two‑chamber migration assay and flow cytometry. Dual‑Luciferase reporter assays, qPCR and western blot analysis were subsequently performed to verify whether Twist1 was a direct target of miR‑300. Furthermore, the expression levels of nuclear factor (NF)‑κB pathway proteins were detected via western blot analysis. In MG63 cells, miR‑300 was effectively overexpressed or suppressed by transfection with miR‑300 mimic or inhibitor, respectively (P<0.001). Overexpression of miR‑300 significantly suppressed cell viability and migration, whereas it enhanced apoptotic rate (P<0.001). miR‑300 suppression exhibited contrary results (P<0.05, P<0.01 or P<0.001). Twist1 was demonstrated to act as a direct target of miR‑300, and was negatively regulated by miR‑300. In addition, miR‑300 overexpression downregulated the expression of the primary factors involved in the NF‑κB signaling pathway. These effects on OS cell proliferation and apoptosis may be due to the miR‑300 targeting of Twist1 and the suppressive effect on the NF‑κB signaling pathway.
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http://dx.doi.org/10.3892/mmr.2017.7023DOI Listing
September 2017

Influence of neoadjuvant chemotherapy on prognosis of patients with synovial sarcoma.

World J Surg Oncol 2017 May 11;15(1):101. Epub 2017 May 11.

Department of Bone Tumor, The General Hospital of the People's Liberation Army, Beijing, 100853, China.

Background: This study aimed to explore the clinical efficacy of neoadjuvant chemotherapy combined with surgery in primary synovial sarcoma of the limbs and trunk through retrospective analysis of patients with primary synovial sarcoma of the limbs and trunk treated by this treatment in our hospital.

Methods: A total of 89 patients diagnosed with synovial sarcoma were enrolled in this study between January 2005 and December 2011 in PLA General Hospital. Most of the patients received neoadjuvant chemotherapy combined with operative treatment (84.3%), 10.1% of them received adjuvant chemotherapy combined with operative treatment, and only 5.6% received merely operative treatment. The influence on the prognosis of patients with synovial sarcoma was analyzed by the statistics overall survival (OS), progression-free survival (PFS), local control (LC), and freedom from distant metastasis (FFDM).

Results: The median follow-up time was 68.6 months. The 5-year OS, 5-year PFS, 5-year LC, and 5-year FFDM of the patients were 80.2, 60.5, 78.8, and 80.8%, respectively. The OS of the patients with a tumor size >5 cm was lower (91.4 vs 73.1%, P < 0.05). Besides, the OS and FFDM of neoadjuvant chemotherapy were better than those of adjuvant chemotherapy (84.5 vs 55.6%, P = 0.015, and 83.8 vs 55.6%, P = 0.028, respectively). However, there was no significant difference in the LC and PFS.

Conclusions: Neoadjuvant chemotherapy was beneficial for patients with synovial sarcoma, and it could improve survival time and control distant metastasis. Tumor size was an important factor influencing patients' prognosis.
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http://dx.doi.org/10.1186/s12957-017-1165-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425994PMC
May 2017

Ionic Colloidal Molding as a Biomimetic Scaffolding Strategy for Uniform Bone Tissue Regeneration.

Adv Mater 2017 May 21;29(17). Epub 2017 Feb 21.

Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun North First Street 2, Beijing, 100190, China.

Inspired by the highly ordered nanostructure of bone, nanodopant composite biomaterials are gaining special attention for their ability to guide bone tissue regeneration through structural and biological cues. However, bone malformation in orthopedic surgery is a lingering issue, partly due to the high surface energy of traditional nanoparticles contributing to aggregation and inhomogeneity. Recently, carboxyl-functionalized synthetic polymers have been shown to mimic the carboxyl-rich surface motifs of non-collagenous proteins in stabilizing hydroxyapatite and directing intrafibrillar mineralization in-vitro. Based on this biomimetic approach, it is herein demonstrated that carboxyl functionalization of poly(lactic-co-glycolic acid) can achieve great material homogeneity in nanocomposites. This ionic colloidal molding method stabilizes hydroxyapatite precursors to confer even nanodopant packing, improving therapeutic outcomes in bone repair by remarkably improving mechanical properties of nanocomposites and optimizing controlled drug release, resulting in better cell in-growth and osteogenic differentiation. Lastly, better controlled biomaterial degradation significantly improved osteointegration, translating to highly regular bone formation with minimal fibrous tissue and increased bone density in rabbit radial defect models. Ionic colloidal molding is a simple yet effective approach of achieving materials homogeneity and modulating crystal nucleation, serving as an excellent biomimetic scaffolding strategy to rebuild natural bone integrity.
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http://dx.doi.org/10.1002/adma.201605546DOI Listing
May 2017

Survival and prognostic factors in Chinese patients with osteosarcoma: 13-year experience in 365 patients treated at a single institution.

Pathol Res Pract 2017 Feb 13;213(2):119-125. Epub 2016 Nov 13.

Department of Orthopaedics, The General Hospital of Chinese People's Liberation Army, NO28 Fuxing Road, Beijing 100853, China. Electronic address:

This study was designed to retrospectively analyze the survival and prognostic factors in Chinese osteosarcoma patients received neoadjuvant chemotherapy or/and surgery in a single institution. A total of 365 patients with pathological proved osteosarcoma undergoing neoadjuvant chemotherapy or/and surgery in a single institution between December 1999 and December 2012 were retrospectively analyzed for the demographic, tumor-related, and treatment-related variables, prognostic factors for survival rate and chemotherapy response. There were 231 males and 134 females (ratio, 1.72:1). The average age was 21±10years, with peak age between 10 and 20 years old (62%, 226/365). Of 365 patients, 319 (87.4%) suffered from primary tumor only, and 46 (12.6%) had metastases upon initial presentation. The overall 5-year survival rate was 65%. Upon univariate analysis, tumor site (femur 60.3%; other long bone 70.2%; trunk 33.6%; P=0.012), primary metastases (yes 36.7%; no 68.9%; P=0.000), tumor response to preoperative chemotherapy (good 89.8%; poor 47.5%; P=0.001) and recurrence/metastases after treatment (yes 36.2%; no 63.8%; P=0.000) were associated with higher 5-year survival rate. All factors except tumor site maintained their significance in multivariate testing. Male sex and nonconventional subtype of tumor were related to a higher likelihood of poor chemotherapy response.The absence of metastases at initial presentation, negative local recurrence or metastases after treatment, and tumor response to chemotherapy are of independent prognostic value in osteosarcoma. The overall prognostic factors and survival in Chinese patients are similar to those patients reported in western countries.
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http://dx.doi.org/10.1016/j.prp.2016.11.009DOI Listing
February 2017

ABT-737, a Bcl-2 Selective Inhibitor, and Chloroquine Synergistically Kill Renal Cancer Cells.

Oncol Res 2016 ;24(1):65-72

Department of Nephrology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.

Renal cell carcinoma (RCC) is the most common malignancy in the kidney in the world, and the 5-year overall survival for patients remains poor due to the lack of effective treatment strategies. Although ABT-737, as a Bcl-2/Bcl-xL inhibitor, has recently emerged as a novel cancer therapeutic reagent, apoptosis induced by ABT-737 is often blocked in several types of cancer cells. This study investigated whether the combination of the small-molecule BH3 mimetic ABT-737 and the lysosome inhibitor chloroquine was an effective strategy for treating renal cancer cells. We found that the combination of ABT-737 and chloroquine synergistically decreased cell viability when compared to treatment with either single reagent. Cell apoptosis induced by a combined treatment was markedly inhibited by the caspase inhibitors z-DEVD-FMK and z-VAD-FMK. It was also inhibited by cathepsin inhibitor E-64 and CTSI (cathepsin inhibitor), which suggested that apoptosis was dependent on the cascade of caspase activation and cathepsins released from lysosomes. Furthermore, we found that ABT-737 could increase the cell level of ROS, which triggers cathepsin-mediated cell death and augments the role of chloroquine in cell death. So the combination of ABT-737 and chloroquine was an effective strategy for the treatment of renal cancer cells, and this combined strategy may widen the therapeutic window of ABT-737 and chloroquine as well as enhance the clinical efficacy of synergistic drug combinations.
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http://dx.doi.org/10.3727/096504016X14587366983838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838628PMC
March 2017

Effects of vascular endothelial growth factor expression on pathological characteristics and prognosis of osteosarcoma.

Clin Exp Med 2016 Nov 29;16(4):577-584. Epub 2015 Aug 29.

Department of Orthopaedics, General Hospital of Chinese PLA, No. 28, Fuxing Road, Haidian District, Beijing, 100853, China.

Vascular endothelial growth factor (VEGF) has been linked with tumor invasion and metastasis. However, the role of VEGF expression in osteosarcoma remains controversial. By searching the PubMed, Embase, and Google Scholar databases, we conducted a meta-analysis to evaluate the pathological and prognostic significance of VEGF in osteosarcoma. Studies were pooled, and the odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated. Nine relevant articles were included in this meta-analysis study. We performed pooled analysis with available data on the association between VEGF expression and age, gender, tumor stages IIB-III versus I-IIA, tumor recurrence, response to chemotherapy, and tumor metastasis. Our results revealed that VEGF expression might be closely associated with metastasis of osteosarcoma (OR 4.74, 95 % CI 2.53-8.87, P < 0.001). Furthermore, our findings also demonstrated that patients with grade IIB-III osteosarcoma showed a higher frequency of VEGF expression than those with grade I-IIA osteosarcoma (OR 5.33, 95 % CI 2.03-13.98, P = 0.001). We failed to find the association between VEGF expression and age (OR 0.82, 95 % CI 0.44-1.53, P = 0.539), gender (OR 1.33, 95 % CI 0.52-3.42, P = 0.553), tumor recurrence (OR 1.47, 95 % CI 0.56-3.86, P = 0.429), and response to chemotherapy (OR 1.26, 95 % CI 0.14-11.72, P = 0.839). In conclusion, VEGF is related to the grade and metastasis of osteosarcoma. It may play a significant role in clinical guidelines for the treatment and prognostic evaluation.
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http://dx.doi.org/10.1007/s10238-015-0382-1DOI Listing
November 2016

Reconstruction using massive allografts after resection of extremity osteosarcomas the study design: A retrospective cohort study.

Int J Surg 2015 Sep 29;21:108-11. Epub 2015 Jul 29.

Department of Orthopaedics, General Hospital of Chinese PLA, Beijing 100853, China.

Purpose: Allografts have been shown useful in the reconstruction of bone defects after tumor resection. This study aimed to investigate the feasibility of using massive allografts to reconstruct bone defects after resection of extremity osteosarcomas.

Methods: The clinical data of 15 patients treated with massive allograft reconstruction after resection of extremity osteosarcomas from January 2005 to January 2008 were retrospectively reviewed. Neoadjuvant and postoperative chemotherapy was used in all patients. The postoperative functions of the salvaged limbs were evaluated using the scoring system proposed by the Musculoskeletal Tumor Society (MSTS).

Results: All patients were followed up for a mean of 61 months (range, 14-99 months). No nonunion occurred during follow-up. The mean time to union was 9 months (range, 3-21 months). No immune rejection, allograft infection, allograft fracture, and limb length disparity occurred. However, 2 patients had broken implants. The mean MSTS score at the last follow-up was 26 points. Four patients died and 2 patients had tumor recurrence. The 5-year disease free survival rate was 73.3%.

Conclusion: Massive allograft reconstruction is safe and effective for bone defects caused by resection of extremity osteosarcomas.
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http://dx.doi.org/10.1016/j.ijsu.2015.07.686DOI Listing
September 2015

MicroRNA-124 functions as a tumor suppressor and indicates prognosis in human osteosarcoma.

Exp Ther Med 2015 Mar 30;9(3):679-684. Epub 2014 Dec 30.

Department of Orthopedics, General Hospital of PLA, Beijing 100853, P.R. China.

MicroRNA-124 (miR-124) has been demonstrated to be downregulated in numerous human malignancies and correlated with tumor progression. However, its expression and clinical significance in osteosarcoma remains unclear. Thus, the aim of the present study was to explore the effects of miR-124 in osteosarcoma tumorigenesis and development. Using reverse transcription-quantitative polymerase chain reaction, miR-124 expression was detected in primary osteosarcoma tissues and osteosarcoma cell lines. The correlation of miR-124 expression with clinicopathological factors and prognosis was statistically analyzed. MTT, flow cytometric, and Transwell invasion and migration assays were used to test the proliferation, apoptosis, invasion and migration of osteosarcoma cells transfected with miR-124 mimic. It was found that the expression levels of miR-124 in osteosarcoma tissues were significantly lower than those in corresponding noncancerous bone tissues (P<0.001). In addition, miR-124 downregulation more frequently occurred in osteosarcoma specimens with advanced clinical stage (P<0.001), positive distant metastasis (P=0.005) and poor response to neoadjuvant chemotherapy (P=0.013). Univariate and multivariate analysis identified low miR-124 expression as an unfavorable prognostic factor for overall survival. Furthermore, transfection of miR-124 mimic into MG63 cells was able to reduce cell proliferation, invasion and migration, and promote cell apoptosis. These findings indicate that miR-124 may act not only as a novel diagnostic and prognostic marker, but also as a potential target for the molecular therapy of osteosarcoma.
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http://dx.doi.org/10.3892/etm.2014.2161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316987PMC
March 2015

Osteosarcoma around the knee treated with neoadjuvant chemotherapy and a custom-designed prosthesis.

Orthopedics 2013 Apr;36(4):e444-50

Department of Orthopaedics and Rehabilitation, PLA General Hospital, Beijing, China.

This article describes a novel approach using high-dose neoadjuvant chemotherapy with wide tissue resection and a specially designed artificial joint in 104 patients with stage IIB osteosarcoma near the knee. Sixty-four lesions were located at the distal femur, 39 at the proximal tibia, and 1 invaded the proximal tibia from the distal femur. Pathological fracture was present in 9 patients. Three courses of high-dose methotrexate, doxorubicin, and ifosfamide were administered preoperatively, and 6 courses were administered postoperatively. Preoperative radiographs and magnetic resonance images were obtained to determine the required tumor resection range and prosthesis size. Osteotomy of 3 cm of normal bone outside the tumor and wide resection of normal peripheral soft tissue were performed. Reconstruction with a rotary hinge or simple hinge prosthesis, as appropriate, was then performed. The Musculoskeletal Tumor Society 93 scoring system was used to evaluate limb function 6 months postoperatively. At final follow-up, recurrence, complication, survival, and amputation rates were 4%, 18%, 85%, and 4%, respectively. No recurrences were observed at the ends of amputated bones. Complications included infection (6%), nerve injury (3%), and prosthesis-related events (2% dislocation, 3% breakage, and 1% dislocation-related). Mean Musculoskeletal Tumor Society 93 score was 28 points, which indicated an excellent functional outcome. The low recurrence rate is attributed to the efficacy of the chemotherapy and the accuracy of the margin of resection.Effective chemotherapy reduces the risk of tumor metastasis and clarifies the tumor margin. Accurate identification of the resection margin reduces the risk of local recurrence.
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http://dx.doi.org/10.3928/01477447-20130327-20DOI Listing
April 2013

Cimetidine suppresses lung tumor growth in mice through proapoptosis of myeloid-derived suppressor cells.

Mol Immunol 2013 May 5;54(1):74-83. Epub 2012 Dec 5.

Department of Respiratory and Critical Care Medicine, Fuzong Clinical College of Fujian Medical University, Fuzhou General Hospital, Fuzhou, Fujian 350000, PR China.

Cimetidine, a histamine type-2 receptor antagonist, is known to inhibit the growth of several tumors in human and animals, however the mechanism of action underlying this effect remains largely unknown. Here, in the mice model of 3LL lung tumor, cimetidine showed significant inhibition of tumor growth. However, an in vitro study demonstrated that cimetidine showed no effect on proliferation, survival, migration and invasion of 3LL cells. We found that cimetidine reduced CD11b(+)Gr-1(+) myeloid derived-suppressive cell (MDSC) accumulation in spleen, blood and tumor tissue of tumor-bearing mice. In vitro coculture assay showed that cimetidine reversed MDSC-mediated T-cell suppression, and improved IFN-γ production. Further investigation demonstrated that the NO production and arginase I expression of MDSCs were reduced, and MDSCs prone to apoptosis by cimetidine treatment. However, MDSC differentiation was not affect by cimetidine. Importantly, although histamine H2 receptor was expressed in MDSC surface, histamine could not reverse the proapoptosis of cimetidine. Moreover, famotidine also did not have this capacity. We found that cimetidine could induce Fas and FasL expression in MDSC surface, and sequentially regulate caspase-dependent apoptosis pathway. Thus, these findings revealed a novel mechanism for cimetidine to inhibit tumor via modulation of MDSC apoptosis.
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http://dx.doi.org/10.1016/j.molimm.2012.10.035DOI Listing
May 2013
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