Purpose:The circulating soluble form of intercellular adhesion molecule-1 (sICAM-1) and vascular endothelial growth factor (VEGF) are elevated in women with breast cancer and associated with tumor progression and poor prognosis. This study examined the effects of anthracycline-based chemotherapy on plasma sICAM-1 and VEGF, as well as soluble P-selectin, von Willebrand factor, and interleukin-6 levels.Experimental Design: Twenty-six women diagnosed with stage I-IIIA breast cancer (mean age, 48.4 ؎ 10.4 years; range, 34 -79 years) were studied before (week 1) and at weeks 2 and 3 of cycles 1 and 4 of chemotherapy.Results: The initial effect of chemotherapy was to reduce sICAM-1 levels; compared with pretreatment, sICAM-1 levels were decreased at week 2 of both cycles (P values < 0.01). sICAM-1 levels were elevated, however, at the start of cycle 4 as compared with pretreatment (P < 0.01). Chemotherapy led to an increase in sICAM-1 levels in node-positive but not node-negative patients (P < 0.01). VEGF levels were decreased at week 2 of cycle 4 (P ‫؍‬ 0.001) and remained so at week 3. Similar to sICAM-1, VEGF levels were elevated at the start of cycle 4 as compared with pretreatment (P < 0.006). Soluble P-selectin levels decreased during week 2 of cycle 4 (P ‫؍‬ 0.026). Neither interleukin-6 or von Willebrand factor were significantly changed in response to chemotherapy.Conclusions: The findings support prior studies suggesting that sICAM-1 levels derive from sources other than endothelial cells. In addition, whereas the more immediate effect of chemotherapy is to reduce sICAM-1 and VEGF, continued treatment may lead to significant elevations.

Nocturnal BP non-dipping is associated with elevated levels of molecules related to endothelial dysfunction and atherosclerosis. The finding provides one possible mechanism linking non-dipping with cardiovascular disease.

In adults, exercise is a powerful and natural stimulator of immune cells and adhesion molecules. Far less is known about these exercise responses during childhood and whether or not exercise in real-life activities of healthy children might in¯uence immune responses. We compared laboratory exercise (10´2 min periods of heavy, constant intensity, cycle ergometer exercise with 1 min rests between exercise in nine subjects, aged 9±15 years) with ®eld exercise (90 min soccer practice in nine di erent subjects, aged 9±11 years). Blood was sampled before both protocols, 5 min after the 30 min laboratory protocol, and 10±15 min after the 90 min ®eld protocol. Both ®eld and laboratory exercise protocols led to signi®cant (P<0.05) increases in granulocytes, monocytes, and all lymphocyte subpopulations. The mean (SEM) increases were similar for the two protocols except for the signi®cantly greater increase in laboratory compared with ®eld protocols for natural killer cells [142 (39)% vs 12 (16) (25)%] protocol. Finally, the density of CD62L on lymphocytes signi®cantly decreased with laboratory exercise but showed no change in the ®eld protocol [±20 (3)% vs ±3 (3)%, P<0.001]. The rapid and substantial immune response in both laboratory and ®eld protocols suggests that exercise stimulation of the immune system occurs commonly in the real lives of children and may play a role in their overall immune status.

A hypercoagulable state might contribute to increased atherothrombotic risk in hypertension. The sympathetic nervous system is hyperactive in hypertension, and it regulates hemostatic function. We investigated the effect of nonspecific beta-adrenergic stimulation (isoproterenol) and blockade (propranolol) on clotting diathesis in hypertension. Fifteen hypertensive and 21 normotensive subjects underwent isoproterenol infusion in two sequential, fixed-order doses of 20 and then 40 ng. kg(-1). min(-1) for 15 min/dose. Thirteen subjects were double-blind studied after receiving placebo or propranolol (100 mg/day) for 5 days each. In hypertensive subjects, isoproterenol elicited a dose-dependent increase in plasma von Willebrand factor (vWF) antigen [F(2,34) = 5.02; P = 0.032] and a decrease in D-dimer [F(2,34) = 4.57; P = 0.040], whereas soluble tissue factor remained unchanged. Propranolol completely abolished the increase in vWF elicited by isoproterenol [F(1,12) = 10.25; P = 0.008] but had no significant effect on tissue factor and D-dimer. In hypertension, vWF is readily released from endothelial cells by beta-adrenergic stimulation, which might contribute to increased cardiovascular risk. However, beta-adrenergic stimulation alone may not be sufficient to trigger fibrin formation in vivo.