Increased Intratumor Concentration of Fluorescein-isothiocyanate-labeled Neocarzino-statin in Rats under Angiotensin-induced Hypertension

On the basis of the observation that the tumor tissue blood flow selectively increases under angiotensin (AT)-induced hypertension, the change of the drug concentration in the tumor and normal tissues was examined in male Donryu rats. The intratumor concentration of fluorescein isothiocyanate-labeled neocarzinostatin was about 2-fold higher in the AT-induced hypertension group than in the control up to 20 min after the drug injection. In the normal organs or the uninvolved organs of the tumor-bearing rats, however, no clear increase was seen in the experimental group compared with the control, as anticipated from the observation of the tissue blood flow. The present study supports the hypothesis that the enhanced anticancer effect in chemotherapy under AT-induced hypertension formerly reported is due to the tumor-selective enhancement of the drug delivery.     

Correlation of platelet aggregation, plasma factor activity, and megathrombocytes in diabetic subjects with an without vascular disease.

Second-phase platelet aggregation induced by adenosine diphosphate (ADP) and epinephrine was measured in fasting platelet-rich plasma in normals, "prediabetics," and diabetics with or without vascular disease. "Plasma factor" potentiation of ADP-induced second-phase platelet aggregation was also estimated, as were megathrombocyte numbers in the same patient groups. There was an increased sensitivity of second-phase platelet aggregation noted with both aggregating agents in all diabetic groups except for the prediabetics. This activity was paralleled by an increase in plasma factor activity. In vivo evidence of an increased turnover of platelets in frank diabetics was suggested by increased numbers of megathrombocytes. These studies demonstrate that platelets from diabetics are sensitive to aggregating agents and that this sensitivity may be related to plasma factor(s) present in diabetics. In vivo platelet aggregation may be present in diabetics. Longitudinal studies will be necessary to establish the relationship of these findings to the genesis of diabetic vascular disease.