Decreased expression of long non-coding RNA MEG3 acts as a potential predictor biomarker in progression and poor prognosis of osteosarcoma

Introduction: Long non-coding RNA MEG3 (lncRNA MEG3) has been showed to involve in a variety of cancers. However, the association between lncRNA MEG3 expression level and the prognosis of osteosarcoma is still unclear. Methods: The expression levels of lncRNA MEG3 in osteosarcoma tissues and adjacent non-tumor tissues were detected using quantitative real-time PCR (qRT-PCR). Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. Results: Our findings showed that expression of lncRNA MEG3 was clearly lower in osteosarcoma tissues compared with adjacent non-tumor tissues. The expression of lncRNA MEG3 was associated with clinical stage and distant metastasis (P<0.05). Kaplan-Meier analysis showed that patients with low lncRNA MEG3 expression had a shorter overall survival (log-rank test, P<0.05). Furthermore, multivariate analysis revealed that decreased expression of lncRNA MEG3, advanced clinical stage and distant metastasis were all independent predictors to overall survival of osteosarcoma patients. Conclusions: Downregulation of lncRNA MEG3 was associated with poor overall survival of osteosarcoma. LncRNA MEG3 could be a useful biomarker for progression and prognosis of osteosarcoma.     

Low-grade extraskeletal osteosarcoma of the mediastinum: report of a case and review of literature

Extraskeletal osteosarcoma (ESOS) is a rare soft tissue sarcoma, typically characterized by a bone-producing neoplasm. Low-grade extraskeletal osteosarcoma (LGESOS) is an extremely rare soft tissue tumor, and patients with LGESOS tend to have a better prognosis. Here, we reported a case of LGESOS of the mediastinum with lung metastasis, and describe its clinical, pathological and radiological features, and compared them with those of the reported cases.     

Inhibitory effects of lysophosphatidic acid receptor-5 on cellular functions of sarcoma cells

Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid that interacts with G protein-coupled LPA receptors (LPA receptor-1 (LPA₁) to LPA₆). Here, we investigated the effects of LPA signaling via LPA₅ on cellular functions of sarcoma cells by generating Lpar5 overexpressing and Lpar5 knockdown cells from rat osteosarcoma and malignant fibrous histiocytoma cells, respectively. The cell motility activity of Lpar5 overexpressing cells was significantly lower, while Lpar5 knockdown cells showed high cell motility, compared with respective controls. Gelatin zymography showed that LPA₅ suppressed the activation of matrix metalloproteinase-2. LPA₅ also inhibited the cell motility activity of endothelial cells, correlating with the expression levels of vascular endothelial growth factor genes. These results suggest that LPA signaling via LPA₅ negatively regulates the cellular functions of rat sarcoma cells.     

Adjuvant Interferon Treatment and the Late Development of Cerebral Metastases in a Patient with Osteosarcoma

A consecutive series of patients with osteosarcoma have been receiving adjuvant interferon therapy at the Karolinska Hospital in Stockholm. We report here a case of tibial chondroblastic Grade III osteosarcoma, a boy aged 17 years, who received interferon therapy for 15 months and survived more than 5 years. the first sign of tumour spread was multiple cerebral metastases—an observation suggesting an antitumour effect of human leucocyte interferon on osteosarcoma.     

No bone ingrowth into the tibia tunnel in anterior cruciate ligament-reconstructed patients: A 1-year prospective quantified CT study of 10 patients reconstructed with an autologous bone-patellar tendon-bone graft

10 patients with major instability symptoms due to an acute anterior cruciate ligament injury were operated on with a bone-patellar tendon-bone reconstruction. Tibial condyle bone mineral density (BMD), bone ingrowth and changes in diameter in the tibia bone tunnel were studied with quantified computed tomography (QCT) postoperatively and after 1, 3, 6 and 12 months. We found no sign of bone ingrowth in the form of increased bone mineral density (BMD) in the bone tunnels in any of the patients. The tunnel diameter increased in all patients during the first postoperative months. After 1 year, 5 patients had a smaller diameter than at the first postoperative examination, 2 had the same diameter as immediately after surgery and 2 patients had a larger diameter. A sclerotic zone developed in all patients along the perimeter of the tunnel during the 3-6 months of follow-up. The BMD in the tibial condyle decreased at 3 months; it then increased, but between 6 and 12 months, it levelled out and was slightly lower than postoperatively. In conclusion, we found no growth of bone into the tunnel and tendinous part of the graft during the first postoperative year.     

Doxorubicin induces ZAKα overexpression with a subsequent enhancement of apoptosis and attenuation of survivability in human osteosarcoma cells

Human osteosarcoma (OS) is a malignant cancer of the bone. It exhibits a characteristic malignant osteoblastic transformation and produces a diseased osteoid. A previous study demonstrated that doxorubicin (DOX) chemotherapy decreases human OS cell proliferation and might enhance the relative RNA expression of ZAK. However, the impact of ZAKα overexpression on the OS cell proliferation that is inhibited by DOX and the molecular mechanism underlying this effect are not yet known. ZAK is a protein kinase of the MAPKKK family and functions to promote apoptosis. In our study, we found that ZAKα overexpression induced an apoptotic effect in human OS cells. Treatment of human OS cells with DOX enhanced ZAKα expression and decreased cancer cell viability while increasing apoptosis of human OS cells. In the meantime, suppression of ZAKα expression using shRNA and inhibitor D1771 both suppressed the DOX therapeutic effect. These findings reveal a novel molecular mechanism underlying the DOX effect on human OS cells. Taken together, our findings demonstrate that ZAKα enhances the apoptotic effect and decreases cell viability in DOX‐treated human OS cells.     

Clinicopathological analysis of osteosarcoma of jaw bones

OBJECTIVES: To identify clinicopathological characteristics and prognosis of osteosarcoma of the jaw bones (JOS) and to compare the data with results of similar studies. To study the effectiveness of different treatment modalities currently available for this malignancy. SUBJECTS AND METHODS: Nineteen cases of JOS diagnosed from 1993 to 2003 were retrieved from the departmental archives. These were categorized into histopathological subtypes and graded according to the severity of the malignancies and the data analyzed. Fourteen cases were followed up and the success rate with different treatment modalities assessed. RESULTS: The mean age for JOS was 34.1 years. There were 11 mandibular lesions and eight maxillary lesions. Osteoblastic variant (53%) was the commonest histopathological subtype. High grade (grades III and IV) was more prevalent. All 14 followed up patients underwent surgical excision--five with adjuvant radiotherapy and six with adjuvant chemotherapy. Local recurrence was the commonest complication. Nine of the 14 were surviving with a survival rate of 64.2% for a median follow-up period of 5.25 years. CONCLUSIONS: JOS is a distinct group of lesions with a better prognosis if diagnosed and treated early. It does not show any ethnic variability. Existing histopathological typing and grading may not indicate the prognosis of JOS. Adjuvant chemotherapy is a better treatment modality than adjuvant radiotherapy.