ABSTRACT. The pretreatment of samples for radiocarbon measurements, transforming a variety of materials into graphite solid targets, represents a critical point in the accelerator mass spectrometry (AMS) procedure. We describe the new, state-ofthe-art CIRCE AMS preparation laboratory, particularly the setup and optimization of an alternative method, the zinc reduc tion method, for graphite target production, compared to the more common hydrogen reduction method. Measured ,4 C values on standard and blank samples reduced via zinc reaction revealed mean background levels, accuracy, and sensitivity compa rable to those obtained by our conventional hydrogen reaction lines. Zinc line reduction at the CIRCE laboratory represents an effective and powerful alternative to the conventional hydrogen reduction, ensuring higher sample throughput with lower costs at a comparable performance level.
Constitutive bcl-2 overexpression increases the tumorigenic and metastatic potential of doxorubicin-resistant, estrogen-independent, MCF-7 ADR human breast cancer cells. We evaluated the sensitivity to taxanes (paclitaxel, docetaxel and IDN 5109) of 2 bcl-2-overexpressing MCF-7 ADR clones and control neomycin-transfected MCF-7 ADR neo cells. The 2 bcl-2-overexpressing MCF-7 ADR clones were relatively resistant to all 3 taxanes, whereas the MCF-7 ADR neo cells were relatively resistant to paclitaxel and docetaxel, but sensitive to IDN 5109. We found that both MCF-7 ADR neo and bcl-2-overexpressing MCF-7 ADR clones express high levels of the epidermal growth factor receptor (EGFR) and its ligand, transforming growth factor-␣ (TGF-␣). Therefore, we tested the growth inhibitory effect of ZD1839 (Iressa™, AstraZeneca, Macclesfield, UK), an orally active, selective EGFR tyrosine kinase inhibitor (EGFR-TKI) that is in clinical development. ZD1839 inhibited the growth in soft agar of all 3 clones in a dose-dependent manner (IC 50 of approximately 0.1 M). This effect was accompanied by a dose-dependent inhibition of EGFR tyrosine autophosphorylation and of the production of TGF-␣, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). To determine whether the blockade of EGFR signaling might affect the sensitivity of bcl-2-overexpressing MCF-7 ADR cells to taxanes, cells were treated with ZD1839 in combination with paclitaxel, docetaxel or IDN 5109, and dose-dependent cooperative growth inhibition as well as apoptosis potentiation were observed. Combined treatment with IDN 5109 and ZD1839 also resulted in a significant inhibition of bcl-2 expression in bcl-2-overexpressing MCF-7 ADR cells. These results demonstrate the ability of ZD1839 to overcome taxane resistance in a model of hormone-independent, multidrug-resistant, human breast cancer.
A system with several lines for the preparation of graphite targets for radiocarbon analysis has been built at the new accelerator mass spectrometry (AMS) facility in Caserta, Italy. Special attention has been paid in the design to the reduction of background contamination during sample preparation. Here, we describe the main characteristics of these preparation lines. Results of tests performed to measure 14C background levels and isotope fractionation in several blank samples with the Caserta AMS system are presented and discussed.
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