[A new drug delivery system in metastatic foci of cancer].
To improve the cancer chemotherapeutic effects on metastatic foci, we have developed a new drug delivery system based on two functional characteristics of the tumor vessels. Two functional characteristics of tumor vessel are summarized as follows: 1) A several-fold increase in tumor blood flow was brought about by angiotensin II-induced hypertension. The increase was selective and universal to the tumor vessels as long as the mean arterial blood pressure was kept under 150 mmHg. Such characterization was observed in micrometastatic foci. The concentration of anticancer drugs in tumor tissue could be increased by this function. Angiotensin-induced hypertension chemotherapy has been developed based on this characterization of tumor vessels. 2) Tumor blood flow almost decreased to zero when the mean arterial blood pressure was decreased to 60-65 mmHg by infusion of sodium nitroprusside. The stasis of tumor blood flow was also selective for the tumor tissues. The stasis suppressed a drug efflux from tumor tissues. By utilizing combination of these functional characteristics, we were able to enhance drug concentration X retention time in tumors remarkably. We named this drug delivery system "Flooding-the-castle chemotherapy". In these experiments, optimum blood pressures were kept under control by a computer system.
Suzuki
M
M
Department of Experimental Oncology, Tohoku University, Sendai.
Hori
K
K
Saito
S
S
Tanda
S
S
Li
Y L
YL
Zhang
Q H
QH
Abe
I
I
D000804:Angiotensin II / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000556:secondary*; D009599:Nitroprusside / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000804:Angiotensin II; D009599:Nitroprusside