Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs) have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies.</p> <p>Methods</p> <p>CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis.</p> <p>Results</p> <p>The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs.</p> <p>Conclusions</p> <p>MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma.</p

Innovation capability and its role in enhancing the relationship between TQM practices and innovation performance

Innovation plays a critical role in predicting the long-term survival of organizations, determining an organization’s success and sustaining its global competitiveness, especially in an environment where technologies, competitive position and customer demands can change almost overnight, and where the life-cycle of products and services are becoming shorter.Therefore, the main purpose of this paper is to extend the existing knowledge as to the relationship between TQM practices and innovation performance by exploring the expected role of innovation capability as mediator to enhance this relationship.At the same time, this study attempted to shed a light on how to improve innovation performance of manufacturing companies in Malaysia.The gained results indicated that innovation capability mediates the relationship between TQM practices and innovation performance. More importantly, this study supports the findings of the past studies that questioned the role of TQM practices in improving innovation performance. Finally, in light of the obtained results, several recommendations were introduced to assist decision makers in manufacturing companies