Characterization of Heterogeneous Distribution of Tumor Blood Flow in the Rat

Abstract

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.

A Novel Combretastatin A‐4 Derivative, AC‐7700, Shows Marked Antitumor Activity against Advanced Solid Tumors and Orthotopically Transplanted Tumors

“…1,2) This observation was consistent with our results described above. However, why did AC-7700 exhibit antitumor activity in the advanced tumor model despite poor drug delivery?…”

“…It has been reported that, as tumors grow, low-or no-flow areas are generated in malignant tissue and interstitial fluid pressure also increases. [1][2][3] Clinical tumors at advanced stage often grow slowly, and their tumor cell population in the growth phase decreases compared with that in subcutaneous (s.c.) rodent tumors. These factors markedly reduce drug accessibility to malignant tissue and tumor cell sensitivity to chemotherapeutic agents whose effectiveness depends on the cell cycle.…”

Pixel-to-pixel correlation between images of absolute ATP concentrations and blood flow in tumours

“…Tumour blood flow, tissue oxygenation, and energetic status may vary over a wide range in different tumour entities and may show pronounced heterogeneities within one tumour (Jain, 1988;Vaupel et al, 1989b;Hori et al, 1991). These intratumoural variabilities make it difficult to establish correlations between these parameters, if data were averaged over the entire tumour.…”

Tumour targeting: biological factors and formulation advances in injectable lipid nanoparticles

“…Also unlike normal tissues, tumour tissues have similar arterial pressure and a lower venous pressure (Peters et al 1980). Most blood vessels in the internal regions of a tumour are veins or venules, whereas the peripheral regions of a tumour have few arteries or arterioles (Hori et al 1990(Hori et al , 1991. Therefore, the arteriole-venule pressure difference as a driving force for blood flow is negligible in the central region of a tumour, but is greater in the periphery.…”