ABSTRACT
Naringin, a citrus bioflavonoid, has anti-inflammatory actions and cardio- and neuroprotective effects. In addition, naringin exhibits multiple antitumor actions in several cancer types, including osteosarcoma, the most common type of bone cancer. Here, we show that naringin inhibits proliferation and invasion and induces apoptosis in human osteosarcoma cells by inhibiting zinc finger E-box binding homeobox 1 (Zeb1), a transcriptional repressor of epithelial differentiation involved in tumor metastasis. Our expression analyses confirm that Zeb1 is highly expressed in osteosarcoma specimens and cell lines. The effects of naringin, which included downregulation of Cyclin D1, MMP2, and bcl-2, where reproduced by siRNA-mediated Zeb1 silencing, whereas Zeb1 overexpression increased proliferation, migration, and Cyclin D1, MMP2, and bcl-2 levels. In addition, naringin administration reduced tumor nodule formation and attenuated the expression of the above proteins in the livers of mice injected with MG63 osteosarcoma cells. Our study provides preclinical evidence for the potential therapeutic application of naringin in the treatment of osteosarcoma.
Subject(s)
Bone Neoplasms/metabolism , Flavanones/pharmacology , Osteosarcoma/drug therapy , Zinc Finger E-box-Binding Homeobox 1/metabolism , Animals , Apoptosis , Cell Cycle , Cell Movement , Cell Survival , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice , Mice, Nude , Neoplasm Invasiveness , Neoplasms, Experimental , Osteosarcoma/metabolism , Young AdultABSTRACT
Osteosarcoma is an aggressive bone tumor primarily affecting children and adolescents. Its cause is not yet fully understood, and there is an urgent need for more effective treatment. In the present study we identified several miRNAs whose expression is altered in osteosarcoma compared to adjacent normal tissue. Moreover, expression levels of one of those miRNAs, miR-506-3p, correlated negatively with expression of RAB3D (a Ras-related protein). Suppression of miR-506-3p in osteosarcoma led to increased expression of RAB3D, which in turn led to increased CDK4 (cyclin-dependent kinase 4) and MMP9 (matrix metalloprotein 9) activities. Our results suggest that miR-506-3p acts as a tumor suppressor in osteosarcoma and that its downregulation leads to tumor cell proliferation and metastasis due to upregulation of RAB3D- and CDK4-mediated signaling. miR-506-3p thus appears be a potentially useful target for adjuvant therapy in osteosarcoma patients.
Subject(s)
Bone Neoplasms/metabolism , MicroRNAs/metabolism , Osteosarcoma/metabolism , rab3 GTP-Binding Proteins/metabolism , Adolescent , Adult , Animals , Bone Neoplasms/pathology , Cell Line , Cell Line, Tumor , Cell Proliferation , Child , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Male , Mice , Mice, Nude , MicroRNAs/genetics , Neoplasms, Experimental , Osteosarcoma/pathology , Young AdultABSTRACT
ObjectiveTo evaluate the value of the measurement with a scale in arthroscopic anatomic anterior cruciate ligament (ACL) reconstruction.Methods Thirty-six patients with unilateral ACL-deficient knees were divided into single bundle group and double bundle group based on the length of the major axis of the native ACL footprint measured with a scale.Consistent with the International Knee Documentation Committee (IKDC) scoring systems,Lysholm knee scoring scale and Tegner activity rating were used to evaluate the clinical results,and data from 23 to 26 months follow-up were gathered and analyzed statistically.ResultsIn terms of IKDC evaluation,19 patients( 90.4％ ) in the double band group and 13 patients( 86.7％ )in the single band group were graded as normal or nearly normal ( Z =7.82,6.33 ; P ＜ 0.05 ).The mean Lysholm scores were 93.8 ± 9.9 and 94.2 ± 9.6 and the mean Tegner scores were 6.6 ± 1.9 and 6.5 ± 1.7 for the double and single band groups,respectively( t =2.31,5.60,3.55,7.09 ;P ＜0.05 ).ConclusionArthroscopic measurement with a scale combined with other traditional methods to determine the tunnel location is easy to conduct and intuitional to understand.It could be useful in anatomic ACL reconstruction.
ABSTRACT
OBJECTIVE: To explore the diagnosis and treatment of ganglion cysts of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) of the knees. METHODS: Retrospective analysis of clinical data of patients with ganglion cysts of ACL and PCL as confirmed by arthroscopy and pathology. RESULTS: All patients were followed up at the clinic in a mean period of 2 years, and their symptoms including arthralgia, swelling and interlocking of the affected knees disappeared. Normal ranges of joint motion were restored successfully. CONCLUSION: Ganglion cysts of the cruciate ligaments can easily be detected by MRI and should be arthroscopically resected, not only treated by ultrasound but also by CT-guided paracentesis. Complete resection of the cyst and cyst walls is recommended to avoid recurrence. Positive diagnosis of this disease can be improved by clinical manifestations and specific MRI findings. Trauma and chronic strain were the primary etiological factors responsible for ganglion cysts that were more common in ACL than PCL.