A sufficient decrease in tumor vascular parameters was observed at a dose chosen for additional phase II testing by conventional toxicity criteria. In addition, the day 2 vascular response measured using DCE-MRI seems to be a useful indicator of drug pharmacology, and additional research is needed to determine if it is a suitable marker for predicting clinical activity.

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Chronic food restriction decreases secretion of LH as a result of inhibitory influences on secretion of LHRH. We have previously reported that neuropeptide-Y (NPY) may directly or indirectly mediate this inhibitory effect on LHRH secretion. In the study reported here, we tested the hypothesis that long-term food restriction suppresses tonic release of LH as a result of 1) an increase in biosynthetic activity of NPY neurons in the arcuate nucleus of the hypothalamus, 2) an increase in activity of neurons that secrete beta-endorphin, and 3) a decrease in biosynthesis of LHRH. To test predictions of the hypothesis, we compared levels of mRNA encoding NPY, proopiomelanocortin (POMC; the precursor peptide of beta-endorphin), and LHRH, as well as tonic secretion of LH in food-restricted and well-nourished ewe lambs. Ten ewe lambs were ovariectomized at 18 wk of age and randomly assigned to receive either 100% nutritional requirements (FED; n = 5), or 30% requirements (R; n = 5) between 18 and 25 wk of age. At 25 wk of age, blood samples were taken every 10 min for 6 h and assayed for LH. The tonic release of LH in R lambs was less than that of FED lambs. Hypothalami were collected 4 days after blood sampling and sectioned at 12 microns for use in in situ hybridization. Radiolabeled molecular probes specific for mRNAs encoding NPY, POMC, or LHRH were hybridized to hypothalamic tissue sections. Levels of NPY mRNA were 88% greater in R vs. FED lambs (p < 0.01), whereas levels of POMC mRNA were 52% lower in R vs. FED lambs (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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