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By using transparent chambers in rats, we have directly observed tumor‐induced neovascularization in the early stage and the formation of intricate networks in Yoshida rat ascites hepatoma AH109A and Sato lung carcinoma at high magnification. We counted branching point numbers per unit area in the microvascular network with and without tumors in order to clarify the sites from which new vascular sprouts originate. Branching point number per unit area in normal tissue was 13.6 ± 7.4/0.1 mm2 in the field near a terminal arteriole, and 12.9 ± 7.3/0.1 mm2 in the field distant from a terminal arteriole. There was no significant difference between these two fields in the normal vascular network. On the other hand, in the tumor vascular network, the branching point number in the field near a terminal arteriole was 50.4 ± 12.6/0.1 mm2, and 30.1 ± 11.5/0.1 mm2 in the field distant from a terminal arteriole. The difference is highly significant (P<0.001). The frequency with which new capillaries originated from veins and venules was very low. We concluded from these results that the position from which tumor vessels originated was usually the terminal portion of a terminal arteriole.

To elucidate the significance of angiotensin II (AID‐induced hypertension chemotherapy, changes of tissue blood flow both in normal subcutis and in tumors (AH109A, LY80) were measured with the hydrogen gas clearance method. A newly‐developed anesthetic machine was used to keep the animals' condition constant. Tissue blood flow in normal subcutis and tumors always fluctuated with time under normotension. The nature and the rate of fluctuation in tumor Wood flow were almost identical in two different types of tumors. However, the fluctuation of blood flow in tumor and that in normal subcutis were almost always inversely related when blood flows in these different tissues were measured simultaneously, i.e., when tissue blood flow in normal subcutis decreased, tumor blood flow increased, and vice versa. The findings supported the idea that the connection mode between the tumor vascular bed and normal vascular bed is a parallel circuit. Vascular resistance in the normal vascular bed under All‐induced hypertension seemed to be greater than that under normotension, because the All‐increased tumor blood flow always exceeded the maximum tumor blood flow under normotension. Due to the fluctuations of tumor blood flow, no‐flow or low‐flow areas, resistant to delivery of anti‐cancer drugs, moved sporadically within the tumor under the normotensive condition. However, good conditions for drug delivery to tumor tissue were induced by All‐induced hypertension.

This review describes some aspects of tumor vessels and the influence of vasoactive agents on tumor blood flow, particularly the characteristic microcirculation of tumors with regard to its selective increase in blood flow. Elevation of blood pressure by infusion of angiotensin II produced a severalfold increase in tumor blood flow. The increase was selective and specific to the tumor vessels as long as the mean arterial blood pressure was kept under 150 mm Hg. Pressure elevation by angiotensin II also selectively increased tumor oxygen tension and influx of lymph flow from the primary transplanted lesion to the lymph node metastatic lesion. Newly devised techniques for analyzing microhemodynamics of tumor vessels showed that the velocity of tumor blood flow, the vascular area in tumor tissue, and the hydrostatic pressure difference between the tumor vessel and extravascular tissue were markedly enhanced. Thus, the extravasation of material into tumor tissues can be increased by the enhancement of blood flow. This demonstration allowed the development of a new approach to cancer chemotherapy, in which the delivery to tumor tissue of systemically administered anticancer drugs can be selectively enhanced.

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Land plant genomes carry tens to hundreds of Resistance (R) genes to combat pathogens. The induction of antiviral R-gene-mediated resistance often results in a hypersensitive response (HR), which is characterized by virus containment in the initially infected tissues and programmed cell death (PCD) of the infected cells. Alternatively, systemic HR (SHR) is sometimes observed in certain R gene–virus combinations, such that the virus systemically infects the plant and PCD induction follows the spread of infection, resulting in systemic plant death. SHR has been suggested to be the result of inefficient resistance induction; however, no quantitative comparison has been performed to support this hypothesis. In this study, we report that the average number of viral genomes that establish cell infection decreased by 28.7% and 12.7% upon HR induction by wild-type cucumber mosaic virus and SHR induction by a single-amino acid variant, respectively. These results suggest that a small decrease in the level of resistance induction can change an HR to an SHR. Although SHR appears to be a failure of resistance at the individual level, our simulations imply that suicidal individual death in SHR may function as an antiviral mechanism at the population level, by protecting neighboring uninfected kin plants.

Angioarchitectures of ascites hepatoma AH109A and Sato lung carcinoma (SLC) were quantitatively compared by measuring the following morphometric parameters: vascular density, vascular length, distance hetween tissues and their nearest blood vessel, and total length of microvascular network per unit area. When the vascular networks in these two types of tumors were compared in the initial stage, the morphological parameters were almost identical. Correlations between tumor size and the number of starting vessels and between enlargement of the tumor and the ensuing increase in pressure of the starting vessel were also evaluated with a microcomputer and an apparatus for measuring micro–vascular pressure. The total length of tumor vascular network to which one starting vessel supplied blood increased exponentially as the tumor increased in size exponentially. There was a positive correlation between tumor size and the number of starting vessels. The range of the blood supply from one starting vessel was evidently limited. The pressure of the starting vessel increased with enlargement of the tumor size. As soon as the pressure of the starting vessel reached a plateau, however, there was a rapid increase in low–flow or no–flow areas in regions within the tumor. From the results obtained, we consider that low–flow or no–flow areas, resistant to delivery of anticancer drugs, inevitably appear with the progression of tumor growth.

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