[Show abstract][Hide abstract] ABSTRACT: 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.
Experimental and therapeutic medicine 03/2015; 9(3):679-684. · 0.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Giant cell tumors of bone (GCTBs) exhibit aggressive bone lytic behavior. Studies have shown that interleukin 17A (IL-17A) is involved pathological bone resorption in various skeletal disorders. Thus, we have investigated the role of IL-17A in GCTBs.
We evaluated the progression of GCTBs using Campanacci grading and Enneking staging systems in 74 GCTB patients. The expression of IL-17A and the IL-17A receptor A (IL-17RA) was assessed in GCTB tissues and in both multinucleated giant cells (MNGCs) and stromal cells (SCs) cultured in vitro using immunostaining and RT-PCR. The effects of IL-17A on the osteolytic activity of the MNGCs and the proliferation of the SCs were investigated using the "pit" formation and MTT assays, respectively. The effects of IL-17A on the expression of pro-osteolytic factors were examined in primary cultured MNGCs and SCs using RT-PCR, Western blotting, and gene expression microarrays.
In GCTBs, we detected abundant levels of IL-17A, which were associated with tumor extension and grade. IL-17A is predominantly produced by MNGCs, whereas IL-17RA is expressed by both MNGCs and SCs in GCTBs. In the MNGCs, the IL-17A increased the mRNA expression of IL-17A and pro-osteolytic enzymes, also enhanced osteolytic ability. In the SCs, the IL-17A stimulated cellular proliferation and the expression of pro-osteolytic factors, including RANKL through myc and STAT3, respectively. In addition, IL-17A stimulated in vivo tumor growth and the extent of angiogenesis in GCTBs.
IL-17A stimulates the progression of GCTBs and might represent a useful candidate marker for progression and as a therapeutic target for GCTBs.
Clinical Cancer Research 07/2013; · 8.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: : Pelvic reconstruction after tumor resection is challenging.
A retrospective study had been preformed to compare the outcomes among patients who received pelvic reconstructive surgery with allogeneic bone graft after en bloc resection of pelvic tumors and patients who received en bloc resection only.
Patients without reconstruction had significantly lower functional scores at 3 months (10 vs. 15, P = 0.001) and 6 months after surgery (18.5 vs. 22, P = 0.0024), a shorter duration of hospitalization (16 day vs. 40 days, P < 0.001), and lower hospitalization costs (97,500 vs. 193,000 RMB, P < 0.001) than those who received pelvic reconstruction. Functional scores were similar at 12 months after surgery (21.5 vs. 23, P = 0.365) with no difference in the rate of complications between the two groups (P > 0.05).
: Pelvic reconstruction with allogeneic bone graft after surgical management of pelvic tumors is associated with satisfactory surgical and functional outcomes. Further clinical studies are required to explore how to select the best reconstruction method. Level of Evidence IV, Case Series.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Osteosarcoma is a highly metastatic malignancy often with poor prognosis. c-Myc amplification is implicated in osteosarcoma pathogenesis. However, the role of c-myc overexpression in osteosarcoma cell invasion remains unexplored. This study showed that c-myc overexpression enhanced MG-63 and SAOS-2 osteosarcoma cell invasion. Treatment of MEK inhibitor PD98059 or PI3K inhibitor LY294002 decreased cell invasion along with downregulation of MMP-2 and MMP-9 expression. c-Myc overexpression stimulated MEK-ERK pathway whereas inhibited the activity of PI3K-AKT pathway. Specifically, inhibition of MEK-ERK pathway by PD98509 blocked the enhancement effect on cell invasion as well as MMP-2 and MMP-9 expression. The present study demonstrates that c-myc overexpression promotes osteosarcoma cell invasion, probably via activation of MEK-ERK pathway.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 04/2012; 20(4):149-56. · 0.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a study in China to assess the health-related quality of life (HRQoL) in patients treated on for malignant bone tumors after surgery, and investigate the possible determinants.
The subjects were 120 patients surgically treated by amputation and limb-salvage for bone tumors during the period of June 2008 to June 2010. The Medical Outcomes Study Short Form 36 (SF-36) was employed to measure the HRQoL of all the patients before and after surgery.
With regard to the results of the general quality of life tool (SF-36), we observed a significant improvement of all the indexes of HRQoL after 6 months (p<0.05). PF, RP and BP scores showed significant increase between surgery after 6 and 12 months (p<0.05). The means of the HRQoL of bone tumor patients in our study were still much lower than those of general population in every domain, even 12 months after surgery. Logistic regression showed that female patients were found to have lower scores in physical component summary (PCS) than males (OR=0.64, 95% CI=0.35-0.89). Patients older than 15 years had lower scores in mental component summary (MCS) (OR=0.60, 95% CI=0.32-0.86). Ablative surgery was related to both lower MCS and PCS scores (For MCS, OR=0.54, 95% CI=0.31-0.83; for PCS, OR=0.43, 95% CI=0.25-0.73).
Our study showed the treatment for bone tumor could greatly alter the HRQoL of patients. Age, sex and type of surgery were associated with physical or mental HRQoL after surgery.
Asian Pacific journal of cancer prevention: APJCP 01/2012; 13(1):127-30. · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are no standard criteria for determining a sufficient resection margin in the treatment of osteosarcoma. The purposes of this study are to evaluate clinical outcomes using T1-weighted magnetic resonance imaging (MRI) for determining the margin of resection and to compare that with the results of different imaging modalities. Seventeen patients diagnosed with osteosarcoma who underwent en bloc resection with a margin of 2-3 cm based on T1-weighted MRI following chemotherapy were studied. Imaging modalities including conventional radiography, MRI, computed tomography (CT), visual assessment, and histopathological examination were performed and compared. Survival rates were determined. After follow-up of 45.5 ± 13.8 months, no local tumor recurrence was observed in any patient. The 1-, 3-, and 5-year survival rates were 94.1, 82.3, and 76.5%, respectively. The differences in the measurement errors among the five methods were analyzed using pathology as the gold standard. Errors were smallest using T1-weighted and fat-suppressed MRI. There were no significant differences between the measurement results of postoperative histopathological examination and that of T1-weighted imaging or T2 fat-suppressed imaging. The measurement results of radiography and CT were significantly different from that of postoperative pathological findings (P < 0.05). Thus, MRI examination is superior to radiography and CT for determining tumor invasion in patients with osteosarcoma. A resection margin of 2-3 cm determined by MRI provides adequate treatment, while minimizing tissue removal.
Medical Oncology 02/2011; 29(2):1347-53. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ObjectiveThe aim of this study was to report the oncological result of the treatment of 12 patients with osteosarcoma sustaining pathologic
MethodsThere were 9 male and 3 female patients, the average age was 17.6 years (ranged, 11–34 years). All patients received neoadjuvant
chemotherapy, wide margin resection was achieved and skeletal reconstruction was done with locally designed and custom-manufactured
prosthesis. Follow-up examination was carried out at an average of 36 months (range from 12–94 months).
ResultsNine patients had survived and of these 8 patients were free from disease while one patient was alive with disease. The functional
result (using the 30-point rating system of the Musculoskeletal Tumor Society) was excellent in three (25%), good in six (50%),
fair in three (25%).
ConclusionThe performance of a limb-salvage procedure in a patient with pathologic fracture, particularly for one that unites following
chemotherapy, does not significantly increase the risk of local recurrence or survival.
The Chinese-German Journal of Clinical Oncology 11/2009; 8(11):628-630.