In solid cancers, invasion and metastasis account for more than 90% of mortality. However, in the current armory of anticancer therapies, a specific category of anti-invasion and antimetastatic drugs is missing. Here, we coin the term ‘migrastatics’ for drugs interfering with all modes of cancer cell invasion and metastasis, to distinguish this class from conventional cytostatic drugs, which are mainly directed against cell proliferation. We define actin polymerization and contractility as target mechanisms for migrastatics, and review candidate migrastatic drugs. Critical assessment of these antimetastatic agents is warranted, because they may define new options for the treatment of solid cancers.

SUMMARYThe bemodynamic response to mental stress (mental arithmetic) was studied in adolescents with varying risk factors for essential hypertension (EH). One group (genetic) consisted of nonnotensive well adolescents who had at least one parent with EH. Another group (labile) consisted of adolescents with labile hypertension each of whom also had at least one parent with EH. The control population consisted of normotensive adolescents with a negative family history of EH. Subjects with labile hypertension demonstrated a sustained increase in systolic and diastolic pressure and heart rate during stress. This response was significantly different than the control population (p < 0.001). The stress response of the nonnotensive genetic population was qualitatively similar to the group with labile hypertension and significantly different than the controls in diastolic pressure and heart rate (p < 0.001, < 0.02). Post-stress plasma catecholamines were higher in the labile hypertensive and genetic groups than in the control group. These findings demonstrate increased central nervous system mediated adrenergic activity and cardiovascular response in labile hypertension and also in some normotensive subjects with a genetic risk for hypertension. 1 Experimental and epidemiological studies have demonstrated that hypertension is also related to environmental conditions that require continuous behavioral and physiological adjustments. The mechanism through which the interaction of genetic and environmental factors operate, thus directing the development of increased arterial From the

The hemodynamic pattern of response to bilateral nephrectomy was studied in 29 patients with end-stage renal disease on maintenance hemodialysis. Four patterns of hemodynamic response were seen. In 12 patients with nonmalignant hypertension, bilateral nephrectomy reduced blood pressure and total peripheral resistance with no effects on cardiac output. In 5 patients with malignant hypertension, bilateral nephrectomy reduced blood pressure, increased cardiac index, and reduced total peripheral resistance more markedly. In these two groups, at equivalent levels of total exchangeable sodium, before and after bilateral nephrectomy, mean arterial pressure and total peripheral resistance were invaribly lower in the absence of renal tissue. In 3 additional patients with nonmalignant hypertension, the decrease in blood pressure after bilateral nephrectomy was delayed from 3 to 12 weeks. When this occurred spontaneously, it was accompanied by a decrease in total peripheral resistance. The fourth hemodynamic pattern was seen in 6 normotensive patients with end-stage renal disease. After bilateral nephrectomy, there were no significant changes in mean arterial pressure, total peripheral resistance, or cardiac output. Salt and water loading failed to elevate blood pressure significantly. Renal transplantation was performed in 3 hypertensive patients before removal of the end-stage kidney. The functioning renal homograft did not result in normal blood pressure as long as the end-stage kidneys remained in place. Removal of the end-stage kidneys significantly decreased mean arterial pressure and total peripheral resistance. In the anephric state, a sharp difference was seen in blood pressure response to salt and water loading between previously normotensive and previously hypertensive patients. Previously hypertensive patients responded with a progressive increase in blood pressure that reached hypertensive levels. Previously normotensive patients failed to elevate their blood pressure significantly. It is concluded that the vasopressor function of the kidney is the most important factor in the pathophysiology of hypertension of end-state renal disease. Expansion of body fluid plays a role, but elevates the blood pressure only in patients who were previously hypertensive. The antihypertensive function of the kidney does not appear to be a major factor in the regulation of blood pressure in end-stage renal disease.

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SUMMARYThe sequence of hemodynamic events during periods of salt-and water-loading was studied in anephric patients and those with end-stage kidney disease. The 10 patients studied showed four different sequential hemodynamic patterns: 1) no significant increase in blood pressure (BP) in two patients; 2) increase lit BP associated with an increase in cardiac output and without change in total peripheral resistance in two patients; 3) increase in BP associated with an increase in total peripheral resistance from the beginning without an increase in cardiac output in fire patients; and 4) increase in BP associated with an initial increase in cardiac output followed by an increase in total peripheral resistance in one patient. There was a significant positive correlation between BP and blood volume and between BP and total exchangeable sodium in the patients in whom salt-and water-loading increased the BP. It is concluded that during salt-and water-loading an initial rise in cardiac output is not necessary to increase BP and that a sustained rise in cardiac output does not always increase the total peripheral resistance. Mechanisms other than whole-body autoregulation play a role in increasing BP during salt-and water-loading in patients deprived of renal excretory function. In patients with end-stage kidney disease, the most important factor responsible for this increase in total peripheral resistance are the vasopressor function of the kidneys 1 ' f and the increase in body salt and water.2 " 1 In anephric patients, salt and water balance plays a major role in the regulation of BP.2 -*~8 The final effect of salt-and water-loading in anephric patients has been found to be an increase in total peripheral resistance.2 '" The precise mechanism by which expansion of body fluid increases BP remains uncertain, however. Received January 9, 1979; revision accepted September 24, 1979.In our previous experience with weekly hemodynamic studies, the BP increase induced by salt-and water-loading was associated with an increase in total peripheral resistance.2 Under similar experimental conditions, Coleman and co-workers 8 reported that the initial hemodynamic change observed during saltand water-loading was an increase in cardiac output; an increase in total peripheral resistance followed.' These findings were interpreted as demonstrating that during the development of this hypertension the initial increase in cardiac output results in perfusion of tissues above their metabolic needs, which in turn elicits myogenic constriction of peripheral vessels, thereby producing an increase in total peripheral resistance. 810 According to this theory, the initial increase in cardiac output is the cause of hypertension, and the subsequent rise in total peripheral resistance is the result.8 -10