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Ovarian Cancer

 

                              

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6/23/2008

 

 

 Exp Physiol. 2007 Oct 2; [Epub ahead of print]Click here to read Links

Effects of hydralazine on the pulmonary vasculature and respiratory control in humans.

Liu C, Balanos GM, Fatemian M, Smith TG, Dorrington KL, Robbins PA.

University of Oxford.

This study sought: 1) to clarify the effects of hydralazine on both the pulmonary vasculature and respiratory control in euoxia and hypoxia in healthy humans; and 2) to determine whether hydralazine alters the expression of genes regulated by hypoxia-inducible factor 1 (HIF-1). Ten volunteers participated in two 2-day protocols. Hydralazine (25 mg) or placebo was administered at 1 pm and 11 pm on the first day, and at 1 pm on the second day. In the mornings and afternoons of both days we measured plasma vascular endothelial growth factor (VEGF) and erythropoietin (EPO) concentrations (both HIF-regulated gene products), systemic arterial blood pressure, and changes in heart rate, cardiac output, maximum systolic pressure difference across the tricuspid valve (DeltaPmax) and ventilation in response to 20 min of isocapnic hypoxia. Recent hydralazine: 1) decreased diastolic blood pressure; 2) increased heart rate and cardiac output in euoxia and hypoxia whilst having no effect on DeltaPmax; 3) increased the ventilatory sensitivity to hypoxia. Hydralazine had no effect on plasma EPO and VEGF concentration. We conclude that hydralazine increases the sensitivity of the ventilatory response to hypoxia, but lacks any effect at the dose studied on the pulmonary vasculature. It did not affect the expression of HIF-regulated genes.

PMID: 17911356 [PubMed - as supplied by publisher]

Int J Cancer. 2007 Sep 24; [Epub ahead of print]Click here to read Links

Characterization of erythropoietin receptor and erythropoietin expression and function in human ovarian cancer cells.

Jeong JY, Feldman L, Solar P, Szenajch J, Sytkowski AJ.

Department of Medicine, Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology,Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

The identification of erythropoietin receptors (EpoR) on cancer cells has caused concern, since it implies the possibility that treatment of cancer patients with erythropoietin (Epo) and related agents with demonstrable antiapoptotic activity could enhance cancer growth and progression. However, the function and even the validity of the identification of these receptors have been called into question. We now report the characterization of EpoR and Epo expression by 4 human ovarian cancer cell lines: A2780, CaOV, SKOV and OVCAR-3. Using semiquantitative RT-PCR, restriction digestion of the PCR products and DNA sequence analysis, we determined that each of the lines expresses the EpoR and Epo at the mRNA level. A2780 cells were the highest expressers of both genes. We demonstrated EpoR protein both by western blotting and by immunofluorescence and biologically active Epo protein by quantitative in vitro bioassay. The EpoR on A2780 cells was shown to be functional, since Epo stimulation resulted in phosphorylation of Erk1/2, an important EpoR mitogenic signaling intermediate. None of the cell lines exhibited a growth response in culture to exogenous Epo. However, addition of a neutralizing anti-Epo antibody to A2780 cells resulted in partial growth inhibition that was reversed by the addition of excess Epo, providing evidence for an autocrine/paracrine mechanism of growth enhancement in these cells. (c) 2007 Wiley-Liss, Inc.

PMID: 17893874 [PubMed - as supplied by publisher]