Adenosine is released in increased amounts during hypoxic conditions and is a potential mediator of angiogenesis. The aims of this study were to determine the effect of adenosine on the release of angiogenic factors from the glioblastoma cell line U87MG and the subtypes of adenosine receptors that mediate this effect of adenosine. The adenosine analog NECA increased the release of IL-8 to 160713% of control at 24 h. As a positive control, cobalt (100 mM), a metal ion capable of inducing hypoxia-like effects, increased the release of IL-8 to 362799% of control at 24 h. Using real-time RT-PCR, it was found that U87MG cells expressed mRNA transcripts of the A 1 , A 2A , and A 2B adenosine receptors. The functional presence of A 2B adenosine receptors in this cell line was confirmed using pharmacological approaches. NECA stimulated cAMP accumulations with an EC 50 value of 2.9370.91 mM and this effect of NECA was inhibited by the selective A 2B antagonist IPDX. In addition, NECA also caused an increase in the intracellular calcium concentration. Furthermore, cobalt increased the level of A 2B mRNA to 187716% and 259737% of the vehicle control at 5 h and 24 h, respectively. In conclusion, these results suggest that A 2B adenosine receptors are upregulated during hypoxia and may play an important role in mediating the effect of adenosine to increase the release of angiogenic factor IL-8 by tumor cells. Drug Dev. Res. 58: 405-411, 2003.
Patients who are considered low risk for HBV recurrence at the time of liver transplant may safely be able to utilize a short-term duration of HBIG with indefinite antiviral maintenance therapy afterwards, whereas high-risk patients will likely need long-term HBIG in combination with antiviral therapy.
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