No abstract

BackgroundOsteosarcoma 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.MethodsCSCs 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.ResultsThe 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.ConclusionsMNNG/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.

This work describes the production of two clinically relevant metal radioisotopes [Formula: see text] and [Formula: see text] with a medical cyclotron by the irradiation of liquid targets. New results are presented for the implementation of this methodology in a fully automated system, using commercially available equipment. Liquid target solutions containing enriched [Formula: see text] and [Formula: see text] were loaded, bombarded and transferred to synthesis modules where a purified solution containing the desired radiometal is obtained and can then be used to further radiolabeling within only one hour after End-Of-Bombardment (EOB). Typical production runs using enriched material lead to the production of 5 GBq and 6 GBq (0.14 MBq/([Formula: see text]Ah ⋅ mg) and 1.5 MBq/([Formula: see text]Ah ⋅ mg)) of [Formula: see text] and [Formula: see text]; although the technique can be used to obtain up to 25 GBq and 40 GBq, respectively, by simply scaling up the amount of the enriched material. Purified solutions containing [Formula: see text] and [Formula: see text] were obtained within 30 min after EOB and used to produce [Formula: see text]-ATSM and [Formula: see text]–DOTA–NOC, respectively, with quality parameters suitable for human use.

The TBR but not CUL is higher in men than women while the CUL but not TBR is related to the number of CV risk factors. These results are hypothesis-generating and require validation in larger studies.

No abstract