Tumors, blood vessels

We have previously developed an in vivo selection method in which peptides that home to specific vascular beds are selected after intravenous administration of a phage display random peptide library [5]. This strategy revealed a vascular address system that allows tissue-specific targeting of normal blood vessels [6-8] and angiogenesis-related targeting of tumor blood vessels [3, 6, 9-12]. While the biologi-... 

Targeting Tumor Blood Vessels With a Toxin Conjugate... 

Hallahan D, Chen A, Teng M, et al. Drug-radiation interactions in tumor blood vessels. Oncology 1999 13 71-77. 

Response of Tumor Blood Vessels to Ionizing Radiation Tumor Vascular Window Model Growth Factors Contribute... 

RESPONSE OF TUMOR BLOOD VESSELS TO IONIZING RADIATION... 

Previous studies of tumor blood vessel response to radiation have relied upon the clearance of Xe and the quantity of RBCs (Cr-59) within tumors following treatment with radiation (3,6,8). Currently available methods allow direct, longitudinal observation of tumor blood volume and blood flow (10,11). More recent models include the tumor vascular window (11), power Doppler sonography (10), and histologic evaluation of tumor blood vessels (12,13). These models permit characterization of the dose-dependent response in tumor blood vessels. 

Power Doppler sonography displays the amplitude of the Doppler signal but lacks the velocity and directional information present in frequency-based color Doppler sonography (10). However, power Doppler is more sensitive in the depiction of tumor vascularity (14-16), specifically within small tumor vessels (10,17). The hind limb tumor model and power Doppler can be utilized to measure the response of tumor blood vessels to radiation, providing longitudinal assessment of microvascular response within the same tumor without the need to section tumors for histology at various time intervals. 

The dorsal skin fold window model allows direct observation of tumor microvasculature (11). This model also permits longitudinal assessment of the tumor vascular response to therapy. An accurate systematic measurement of tumor blood vessels in the window model is the linear summation of blood vessels using Optimas software. This approach corrects for vascular dilation and hemorrhage. Quantification of red... 

VEGF Antagonist Gene Therapy Enhances the Radiation Effect in Tumor Blood Vessels... 

Hallahan DE, Staba-Hogan MJ, Virudachalam S, et al. X-ray-induced P-selectin localization to the lumen of tumor blood vessels. Cancer Res 1998 58(22) 5216-5220. 

Donnelly EF, Geng L, Wojcicki WE, et al. Quantified power Doppler US of tumor blood flow correlates with microscopic quantification of tumor blood vessels. Radiology 2001 219 166-170. 

A large number of tumor blood vessels increases the opportunity of the tumor cells to enter the circulation. In fact, the newly formed capillaries usually have a fragmented basement membrane, facilitating easier invasion. In the prevascular phase, with little or no angiogenic activity, the tumor is unable to expand beyond a few cubic millimeters, but once angiogenic factors are released in sufficient number, the onset of angiogenic activity stimulates rapid expansion of the tumor. 

Compound efficacy has been correlated with the inhibition of angiogenesis in a variety of assays (endothelial capillary tube formation, aortic ring assay, chorioallantoic membrane assay, real-time tumor blood flow and PO2 measurements, tumor blood vessel density, and tumor hypoxic and apoptotic fractions) [35]. 

Fabbrini M, Trachsel E, Soldani P, Bindi S, Alessi P, Bracci L, et al. Selective occlusion of tumor blood vessels by targeted delivery of an antibody-photosensitizer conjugate. Int J Cancer 2006 118 1805-1813. 

Maeda, H. The tumor blood vessel as an ideal target for macromolecular anticancer agents. J. Control. Release 1992, 19, 315-324. 

Although the architecture of tumor blood vessels has been studied using a number of techniques, one of the most fascinating involves the use of acrylic resin casts. This is exemplified by the work of Skinner et al (1), who studied a series of chemically induced tumors in rats. A resin solution was injected intraarterially into the anesthetized rat, the animal was killed, and the blood vessels to the tissue, were clamped while the resin set. Tissue was digested with alkali and the cast coated with gold and examined by electron microscopy. Whereas normal colon mucosa showed a consistent regular pattern, tissue from tumors showed considerable disorganization with marked dilation and tortuosity of capillaries. For small tumors it was possible to discern areas in the tumor that... 

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