OBJECTIVE To emphasize the importance of reconstruction and repair after resection of soft tissue sarcoma. METHODS From November 1990 to November 1996, in 107 cases of soft tissue sarcoma 32 cases had received various reconstructive or reparative operations. Among the 32 cases, 4 cases were primary sarcomas and 28 cases were recurrent sarcomas. In surgical grading, 3 cases were of I B, 3 cases of II A and 26 cases of II B. Radical resection was performed in 13 cases, widen local resection in 17 cases and local excision in 2 cases. After operation, 13 cases received chemotherapy and 7 cases received radiotherapy. Reconstruction of blood vessels was performed in 3 cases, reconstruction of kinetic function in 16 cases, and repair of defect was carried out in 23 cases. RESULTS Thirty patients were followed up for 4 months to 6 years and 6 months. The clinical results showed that the local control rate of sarcoma was 80%, limb-salvage rate after reconstruction of blood vessels was 100%, the excellent and good rate after reconstruction of kinetic function was 87.5%, and the survival rate of the tissue flap of transplantation and transposition was 96%. CONCLUSION It was concluded that the reconstruction and repair after resection of soft tissue sarcoma was the extension of operative treatment, and was very important in lowering the recurrence rate and improving the life quality of the sufferings.
Objective To investigate the effect of ursolic acid on the proliferation and apoptosis of human osteosarcoma cell line U2-OS and analyze its mechanism. Methods Human osteosarcoma cell line U2-OS was divided into 4 groups, which was cultured with ursolic acid of 0, 10, 20, and 40 μmol/L, respectively. At 0, 24, 48, and 72 hours after being cultured, the cell proliferation ability was detected by cell counting kit 8 (CCK-8). At 48 hours, the effects of ursolic acid on cell cycle and apoptosis of U2-OS cells were measured by flow cytometry. Besides, the expressions of cyclin D1 and Caspase-3 were detected by real-time fluorescent quantitative PCR and Western blot. Results CCK-8 tests showed that the absorbance (A) value of each group was not significant at 0 and 24 hours (P>0.05); but the differences between groups were significant at 48 and 72 hours (P<0.05). Flow cytometry results showed that, with the ursolic acid concentration increasing, the G1 phase of U2-OS cells increased, the S phase and G2/M phase decreased, and cell apoptosis rate increased gradually. There were significant differences between groups (P<0.05). Compared with the 0 μmol/L group, the relative expressions of cyclin D1 mRNA and protein in 10, 20, and 40 μmol/L groups significantly decreased (P<0.05); whereas, there was no significant difference in relative expression of Caspase-3 mRNA between groups (P>0.05). However, with the ursolic acid concentration increasing, the relative expressions of pro-Caspase-3 protein decreased and the relative expressions of activated Caspase-3 increased; there were significant differences between groups (P<0.05). Conclusion Ursolic acid can effectively inhibit the proliferation of osteosarcoma cell line U2-OS, induce the down-regulation of cyclin D1 expression leading to G0/G1 phase arrest, increase the activation of Caspase-3 and promote cell apoptosis.
目的 总结小细胞性骨肉瘤的临床特征及诊治情况。 方法 回顾性分析1995年12月－2012年6月收治的12例小细胞性骨肉瘤患者的临床资料。结合文献分析该病的诊治特点。 结果 全组患者手术11例，化学治疗（化疗）8例，术后辅助放射治疗（放疗）2例。随访截止时，全组患者总生存4～55个月。文献回顾方面，通过检索策略获得探讨相关治疗方案的文献8篇，涉及小细胞性骨肉瘤患者79例。治疗方式以手术+辅助化疗为主。 结论 小细胞性骨肉瘤发病率低，预后较普通骨肉瘤更差。手术为主要治疗方式，新辅助化疗及辅助化疗可能使患者进一步受益，放疗的治疗效果目前还不明确。
ObjectiveTo investigate the effects of cinobufagin on the apoptosis in U-2OS osteosarcomas cells (U-2OS cells) and explore its potential mechanism. MethodsThe cytostatic effects of cinobufagin (10, 20, 50, 100, 200, and 400 nmol/L) on U-2OS cells were evaluated by MTT assay at 24, 48, and 72 hours after culture; simple U-2OS cells served as control group. The impact of cinobufagin (100 nmol/L) on the apoptosis in U-2OS cells was determined by flow cytometry at 48 hours after culture, which were treated with cinobufagin (experimental group) or with cinobufagin plus Z-VAD-FMK (control group), and simple U-2OS cells served as blank control group. The Caspase-3 activity was measured by Caspase-3 activity assay kit at 48 hours after culture, which were treated with cinobufagin (20, 50, and 100 nmol/L), and simple U-2OS cells served as control group.The expression of apoptosis signal pathway related proteins in U-2OS cells treated with cinobufagin were detected by Western blot at 48 hours after culture, which were treated with cinobufagin (20, 50, and 100 nmol/L), and simple U-2OS cells served as control group. ResultsThe results of MTT assay showed that cinobufagin inhibited the proliferation of U-2OS cells in a dose- and time-dependent manners. At each time point, the growth rate of U-2OS cells was significantly reduced with the increasing cinobufagin concentration, and as time prolonged, the growth rate of U-2OS cells behaved the same way in the same group. There were significant differences among different time points and groups (P<0.05). The apoptotic rate of experimental group (46.87%±11.23%) was significantly higher than that of the control group (2.34%±0.98%) and blank control group (1.04%±0.25%) (P<0.05). The Caspase-3 activity in 20, 50, and 100 nmol/L groups were 1.14±0.32, 1.31±0.41, and 1.92±0.54, respectively, which were significantly higher than that in control group (P<0.05). Compared with 20 and 50 nmol/L groups, 100 nmol/L group significantly increased the Caspase-3 activity in U-2OS cells (P<0.05). Compared with the control group, the expressions of cleaved Caspase-3, cleaved Caspase-9, and Bax were obviously up-regulated; the Bcl-2 expression was down-regulated; and the ratio of Bax/Bcl-2 was increased in different cinobufagin-treated groups (P<0.05). The same tendency was seen in different cinobufagin-treated goups, showing significant differences among groups (P<0.05). ConclusionCinobufagin can inhibite the proliferation of U-2OS cells, and induce cell apoptosis. The potential mechanism of cinobufagin-induced apoptosis may be related to the mitochondria-mediated pathway.
Objective To assess effectiveness of chemotherapy versus non-chemotherapy in the treatment of soft tissue sarcoma. Methods We searched MEDLINE (1966 to Dec. 2008), EMBASE (1984 to Dec. 2008), OVID (1980 to Dec. 2008), CBMdisc (1980 to Dec. 2008), and the Cochrane Central Register of Controlled Trials. We also handsearched Journal of Chinese Oncology, Journal of Chinese Clinical Oncology, and Tumor (from inception to Dec. 2008). The quality of the included studies was evaluated by two reviewers independently and meta-analysis was performed for results of the homogenous studies. Results Six studies involving 836 participants related to primary, high grade, nonmetastatic soft tissue sarcoma were included. All included studies were unclear in reporting randomization and blinding; all studies reported the number and the reason of withdraw; and baseline conditions of all studies were compared. The results of meta-analyses showed that there were no significant differences in 5-year overal survival (RR=0.90, 95%CI0.76 to 1.06), local recurrence (OR=0.69, 95%CI 0.36 to 1.32), distant recurrence (OR=0.83, 95%CI 0.62 to 1.11), and overall recurrence (RR=0.91, 95%CI 0.78 to 1.06) between the chemotherapy group and the control group. But as to 5-year disease-free survival, the chemotherapy group was better than the control group (RR=0.73, 95%CI 0.63 to 0.86). Conclusion There is no advantage for the chemotherapy group over the control group in 5-year overal survival, local recurrence, distant recurrence and overall recurrence. Due to the risk of selection bias, performance bias and published bias, the evidence is not b enough to judge whether chemotherapy is better than control in treating soft tissue sarcoma. Our conclusion suggests that larger-scale randomized trials should be performed in future.
Objective To investigate the clinical features, diagnosis, and treatment of patients with localized epithelioid sarcoma (ES).Methods From January 2000 to September 2006, 11 patients with ES weretreated. There were 7 males and 4 females aged 14-41 years. The patients’ agesat the initial onset were 9-41 years, averaged 27.7 years. The ES was located in the upper extremity in 7 patients，lower extremity in 3, and abdomen in 1. Among the patients, 10 had a recurrence. Tumor lt; 2cm was seen in 7 patients, 2-5cm in 1, and gt;5 cm in 3. One patient underwent an operation of local resection at another hospital. Seven patients underwent an expanding resection surgery, and the tumors with the surrounding normal tissues 3 cm above were removed. Three patients underwent a radical surgery, including extremity amputation or finger amputation. All the patients underwent routine radiotherapy and chemotherapy after operation. Results All the wounds had a healing at the firstintention without complications. All the flaps survived and the grafted bone had a fusion. Among the 11 patients followed up for 5-54 months averaged 23.2 months, 8 had a recurrence 2-20 months (average, 8.9 months) after operation, witha recurrence rate of 73%. And among the patients, 3 had a further radical surgery of extremity amputation. Four patients had a metastasis in the axillary lymphnodes 6-24 months after operation, and 1 patient had a lung metastasis 10 months after operation. They did not have a further surgical treatment. Four patients died of systemic failure 6-14 months after operation. Conclusion An early expanding resection surgery combined with postoperative chemotherapy and radiotherapy is the therapy of choice for treating ES.
As the most common primary malignant bone tumor in children and adolescents, osteosarcoma has the characteristics of high malignancy, easy metastasis and poor prognosis. The recurrence, metastasis and multi-drug resistance of osteosarcoma are the main problems that limit the therapeutic effect and survival rate of osteosarcoma. Among them, lung metastasis is often the main target organ for distant metastasis of osteosarcoma. In recent years, people have paid attention to the signaling pathway of the occurrence and development of osteosarcoma and made in-depth studies on its mechanism. A variety of relevant signaling pathways have been constantly clarified. At present, there is still a lack of systematic and multi-directional exploration and summary on the signaling pathway related to the pulmonary metastasis of osteosarcoma. This paper explores the new direction of targeted therapy for osteosarcoma by elucidating the relationship between the signaling pathway associated with osteosarcoma and the pulmonary metastasis of osteosarcoma.
ObjectiveTo investigate the value of integrin αvβ3 targeted microPET/CT imaging with 68Ga-NODAGA-RGD2 as radiotracer for the detection of osteosarcoma and theranostics of osteosarcoma lung metastasis.MethodsThe 68Ga-NODAGA-RGD2 and 177Lu-NODAGA-RGD2 were prepared via one-step method and their stability and integrin αvβ3 binding specificity were investigated in vitro. Forty-one nude mice were injected with human MG63 osteosarcoma to established the animal model bearing subcutaneous osteosarcoma (n=21), osteosarcoma in tibia (n=5), and osteosarcoma pulmonary metastatic (n=15). The microPET-CT imaging was carried out in 3 animal models at 1 hour after tail vein injection of 68Ga-NODAGA-RGD2. Biodistribution study of 68Ga-NODAGA-RGD2 was performed in animal model bearing subcutaneous osteosarcoma at 10, 60, and 120 minutes. The animal model bearing pulmonary metastatic osteosarcoma was injected with 177Lu-NODAGA-RGD2 at 7 weeks after model establishment to observe the therapeutic effect of pulmonary metastatic osteosarcoma. Histological and immunohistochemistry examinations were also done to confirm the establishment of animal model and integrin β3 expression in animal models bearing subcutaneous osteosarcoma and bearing pulmonary metastatic osteosarcoma.Results68Ga-NODAGA-RGD2 and 177Lu-NODAGA-RGD2 had good stability in vitro with the 50% inhibitory concentration value of (5.0±1.1) and (6.5±0.8) nmol/L, respectively. The radiochemical purity of 68Ga-NODAGA-RGD2 at 1, 4, and 8 hours was 98.5%±0.3%, 98.3%±0.5%, and 97.9%±0.4%; while the radiochemical purity of 177Lu-NODAGA-RGD2 at 1, 7, and 14 days was 99.3%±0.7%, 98.7%±1.2%, and 96.0%±2.8%. 68Ga-NODAGA-RGD2 microPET-CT showed that the accumulation of 68Ga-NODAGA-RGD2 in animal models bearing subcutaneous osteosarcoma and osteosarcoma in tibia and in lung metastasis as small as 1-2 mm in diameter of animal model bearing pulmonary metastatic osteosarcoma. Biodistribution study of 68Ga-NODAGA-RGD2 in animal model bearing subcutaneous osteosarcoma revealed rapid clearance from blood with tumor peak uptake of (3.85±0.84) %ID/g at 120 minutes. The distribution of 177Lu-NODAGA-RGD2 in lung metastasis was similar with 68Ga-NODAGA-RGD2. The number and size of osteosarcoma metastasis decreased at 2 weeks after 177Lu-NODAGA-RGD2 administration and integrin targeting specificity was confirmed by pathology examination.Conclusion68Ga-NODAGA-RGD2 was potential for positive imaging and early detection of osteosarcoma and metastasis. Targeted radiotherapy with 177Lu-NODAGA-RGD2 was one potential alternative for osteosarcoma lung metastasis.