Prognostic role of the recepteur d'origine nantais (RON) expression in primary high-grade osteosarcoma.

BACKGROUND: Osteosarcoma is a common primary malignant bone tumor susceptible to distant metastasis. The clinical outcome for patients remains poor due to the resistance to chemotherapy and lacking effective therapeutic targets. Recepteur d'origine nantais (RON), a transmembrane protein of the c-MET proto-oncogene family, has been reported to contribute to the malignant progression and bone metastasis in several tumors. The present study aimed to explore the prognostic significance of RON in primary high-grade osteosarcoma. METHODS: Immunohistochemistry (IHC) and western blotting (WB) were used to investigate the protein expression of RON in 80 surgically resected specimens (50 high-grade osteosarcoma specimens and 30 non-neoplastic bone tissues) and 6 cell lines. The χ2 test or independent-sample Student's t-test was used to assess the significance of RON difference between osteosarcoma and non-neoplastic bone tissues. The χ2 test and Fisher's exact test were used to analyze the association of RON with the clinicopathological features of osteosarcoma patients. Kaplan-Meier method and Cox proportional hazards model were used to assess the significance of RON for the survival of osteosarcoma patients. RESULTS: The results of IHC and WB observed significant overexpression of RON in osteosarcoma specimens (P < 0.001) and osteosarcoma cell lines. Moreover, immunohistochemical high expression of RON was associated with a poor response to chemotherapy (P = 0.032) as well as worse progression-free (P = 0.003) and overall (P < 0.001) survival of osteosarcoma patients. Multivariate analysis revealed that high expression of RON was independently associated with reduced progression-free (P = 0.027, HR = 2.31) and overall survival (P = 0.004, HR = 5.06) time of osteosarcoma patients. CONCLUSIONS: The present study demonstrated that high expression of RON held independent value for unfavorable survival in primary high-grade osteosarcoma. Its potential role as a therapeutic target for osteosarcoma treatment deserves further research.

Clinicopathological and prognostic values of ErbB receptor family amplification in primary osteosarcoma.

Osteosarcoma is a malignant bone tumor with extremely high invasion, metastasis and mortality. The prognosis of patients with osteosarcoma remains poor. The ErbB receptor family was found to be overexpressed in human cancers and associated with poor prognosis. However, the role of ErbB receptor family in osteosarcoma has not been fully understood. The present study aimed to investigate the clinicopathological and prognostic significances of ErbB receptors in primary osteosarcoma. Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to detect the protein and gene expression of ErbB receptors in 60 primary osteosarcoma specimens and 30 non-neoplastic bone tissues. WB and RT-qPCR analyses showed that the protein and mRNA expression levels of EGFR, ErbB3 and ErbB4 in osteosarcoma specimens were significantly higher than those in non-neoplastic bone tissues. Seventeen (28.33%), 15 (25.00%) and 15 (25.00%) osteosarcoma specimens presented with amplification of EGFR, ErbB3 and ErbB4 gene, respectively, which were significantly higher compared with non-neoplastic bone tissues. The amplification of ErbB3 and ErbB4 in osteosarcoma was associated with advanced surgical stage. The amplification of EGFR, ErbB3, ErbB4 and the co-amplification of EGFR-ErbB3, EGFR-ErbB4, ErbB3-ErbB4 was linked with poor response to chemotherapy and distant metastasis. The amplification of EGFR, ErbB3 and ErbB4, as well as their co-amplification demonstrated independent prognostic values for reduced survival time of osteosarcoma patients and may serve as potential therapeutic targets for osteosarcoma patients in the future.

Clinicopathological and prognostic values of fibronectin and integrin αvß3 expression in primary osteosarcoma.

BACKGROUND: Osteosarcoma is a malignant bone tumor with a high potential for lung metastasis, and the prognosis for patients with metastatic disease is very poor. The interaction between fibronectin (FN) and integrin αvß3 in soft-tissue sarcoma promotes cell migration, invasion, and lung metastasis. This study aimed to investigate the prognostic significance of FN and αvß3 in osteosarcoma. METHODS: Immunohistochemistry and western blotting were used to detect the expression of FN and αvß3 in 60 osteosarcoma specimens and in 30 osteochondroma specimens. Furthermore, correlations of FN and αvß3 with the clinicopathological features of osteosarcoma patients were analyzed using the χ2 test and Fisher's exact test. Disease-free survival and overall survival of osteosarcoma patients were assessed using the Kaplan-Meier method and Cox proportional hazards model. The predictive accuracy of the model was determined by the Harrell concordance index. RESULTS: FN (P < 0.05) and αvß3 (P < 0.05) were overexpressed in osteosarcoma specimens compared with osteochondroma specimens. High FN expression was associated with a poor response to chemotherapy (P = 0.001) and poor disease-free (P < 0.001) and overall (P < 0.001) survival. High expression of αvß3 was linked to an advanced surgical stage (P = 0.028), a poor response to chemotherapy (P = 0.002), and both poor disease-free survival (P < 0.001) and overall survival (P < 0.001). FN and αvß3 co-expression were associated with sex (P = 0.011), an advanced surgical stage (P = 0.013), and a poor response to chemotherapy (P = 0.002). Moreover, high expression of both proteins can serve as an independent prognostic value for reduced survival time in osteosarcoma patients. CONCLUSIONS: The results of this study suggest that FN and αvß3 expression is associated with an unfavorable clinical outcome of osteosarcoma, and these molecules may constitute attractive therapeutic targets for osteosarcoma treatment. To improve the survival of osteosarcoma patients, further investigations are required to clarify their prognostic values in a larger population.

Framework-structured weak ferromagnets.

Framework-structured weak ferromagnets are new rising stars in molecule-based magnetic materials. The framework structures are powerful carriers for long-range ordering of spins. And weak ferromagnetism due to spin canting is an effective approach for magnets because of its frequent occurrence and desired spontaneous magnetization as long as the canting angle γ is large enough. In this critical review, we provide an overview of the various framework-structured weak ferromagnets based on different grades of ligands (from mono-atom to three-atom-like ligands). Particular emphasis is given to the relationships between structural features and the properties, rational employment of the ligands, and weak ferromagnetic strategies for molecule-based magnets with exciting properties and applications (273 references).

Prognostic significance of the expression of HER family members in primary osteosarcoma.

The prognosis of patients with metastatic osteosarcoma is poor and has shown no significant improvement in nearly 20 years. The human epidermal growth factor (EGF) receptor (HER) family is frequently overexpressed in the majority of human carcinomas, and is involved in promoting the proliferation and survival of cancer cells. However, the role of EGFR and HER-2 expression in osteosarcoma survival remains controversial and no previous study has simultaneously investigated the association of the expression of all the four HER family members with the prognostic significance of osteosarcoma. Therefore, the present study investigated the expression levels of the complete members of the HER family in osteosarcoma specimens, as well as their associations with the clinicopathological parameters, progression-free survival (PFS) and overall survival (OS) time of patients with osteosarcoma. The expression of HER family members was detected in osteosarcoma tumor specimens from 60 patients using immunohistochemistry. The association of the expression of HER receptors in osteosarcoma with clinicopathological parameters was analyzed using χ2 test and Fishers exact test. Survival analyses were evaluated by Kaplan-Meier method and Cox proportional hazards regression model. Overall, 18 (30%), 13 (22%), 23 (38%) and 19 (32%) patients presented with high expression of EGFR, HER-2, HER-3 and HER-4, respectively, and the co-expression of 2, 3 and all 4 members of the HER family was observed. High expression of EGFR and HER-4 was associated with distant metastasis. High HER-3 expression was significantly associated with an advanced Enneking stage and distant metastasis. Multivariate analysis demonstrated that the expression of EGFR, HER-3, HER-4, EGFR/HER-3, EGFR/HER-4 and HER-3/HER-4 was an independent predictor of poor PFS and OS time in osteosarcoma patients with stage I-IIB disease. In patients with stage IIB osteosarcoma, the expression of HER-4 and EGFR/HER-4 demonstrated a more significant effect on PFS and OS time. In conclusion, therapies targeting EGFR, HER-3 and HER-4 may provide promising strategies for primary osteosarcoma.