Vascular structure of the C3H mammary carcinoma, the B16 melanoma and the Lewis lung carcinoma in syngeneic, conventional mice and congenitally athymic mice.

The vascular system of three commonly used murine experimental tumours, the C3H mammary carcinoma, the B16 melanoma and the Lewis lung carcinoma, in syngeneic (C3D2F1/Bom or C57BL/6J/Bom) and athymic (BALB/c/nu/nu/Bom) mice was studied. The main vascular characteristics of each tumour, i.e. the mean vessel diameter, the total vessel volume and the distribution of the total vessel volume among vessels with different diameters, did not change upon transplantation from conventional to athymic mice. However, the length of vessels with diameters in the range 5-15 micron was for all tumours shorter in athymic than in conventional mice. The vascular volume of the B16 melanoma per unit histologically intact tumour volume in athymic mice (0.040 +/- 0.004) was considerably larger than that of five human melanoma xenografts previously studied (0.009 +/- 0.001 to 0.022 +/- 0.002). This difference was mainly due to occurrence of vessels with diameters in the range 55-145 micron in the B16 melanoma; vessels which were generally not observed in the human melanoma xenografts.

Tumour growth delay, cell inactivation and vascular damage following hyperthermic treatment of a human melanoma xenograft.

The effect of hyperthermia at 42.5 degrees C on a human melanoma xenograft in athymic mice was studied. The tumours were heated in vivo in a water-bath. Tumour growth delay and single-cell survival in vitro were used as endpoints. Qualitative information regarding heat-induced vascular damage was obtained from microangiographic analysis. Tumour growth delay after a given treatment was considerably longer than that expected from the cell survival measured in vitro immediately after treatment. Experiments in which removal of the tumours was delayed revealed that tumour cells were continuously dying for at least 24 hr after heat treatment. The volume of the tumour vasculature was considerably reduced after treatment, suggesting that the delayed cell death was attributed to vascular occlusion which resulted in an insufficient supply of oxygen and nutrients and an increased tumour acidity. The present work indicates that at least two mechanisms may be involved in heat-induced cell inactivation in our xenograft: firstly, direct cytotoxic effect of heat; secondly, indirect effect following heat-induced vascular damage.

Vascular changes in a human malignant melanoma xenograft following single-dose irradiation.

The effects of single-dose irradiation (5.0-25.0 Gy) on the vascular structure, i.e., the vascular network architecture, of a human melanoma grown in athymic nude mice were studied. The vessels were filled with a radio-opaque medium administered via the abdominal aorta of the mice. X-ray images obtained from 720-micron thick tumor sections provided qualitative information on the vascular structure. Vessel length, surface, and volume per unit tumor volume for vessels with diameters in the ranges 5-15, 15-25, 25-35, 35-45, and greater than 45 micron were obtained by stereological analysis on 2-micron thick tumor sections. A considerable fraction of the vessels was severely damaged after irradiation. Manifestation of the damage as a reduction in the number of functional vessels appeared mainly 0.5-1.5 weeks after irradiation. About 35-45% of the original vessels with diameters in the range 5-15 micron was found to be nonfunctional 1 week after doses of 10.0-15.0 Gy while vessels with larger diameters required doses above 15.0 Gy to become nonfunctional 1 week after exposure. Loss of 50% of the functional vessels with diameters in the ranges 5-15, 15-25, and 25-35 micron was found to require doses of about 16, 21, and 20 Gy, respectively. In spite of a considerable early loss of functional vessels, tumors exposed to 20.0 and 25.0 Gy eventually became supervascularized after irradiation due to extensive radiation-induced tumor shrinkage. Regrowth of irradiated tumors appeared to be preceded by neovascularization, and regrowing tumors could even be better vascularized than unirradiated ones, probably as a result of efficient neovascularization.

Vascular structure of five human malignant melanomas grown in athymic nude mice.

The vascular structure of 5 human malignant melanomas grown in athymic nude mice was characterized. The vessels were filled with a radio-opaque medium administered via the abdominal aorta of the mice. X-ray images, obtained from 720 micrometers-thick tumour sections, provided qualitative information on the vascular structure of the tumours. Histograms for vessel length, surface, and volume as a function of vessel diameter were obtained by stereological analysis of 2 micrometers-thick sections. The volume fraction of necrotic tissue in the tumours was also determined by stereological analysis. The 5 melanomas exhibited individual, characteristic vascular structures as well as individual, characteristic necrotic fractions. The total vessel length ranged from 32 +/- 2 to 80 +/- 4 mm, the total vessel surface from 1.6 +/- 0.1 to 3.8 +/- 0.2 mm2, and the total vessel volume from 0.009 +/- 0.001 to 0.022 +/- 0.002 mm3--all values per mm3 histologically intact tumour tissue. The necrotic fractions ranged from 30 +/- 1 to 49 +/- 4%, and tended to be higher in the poorly than in the well-vascularized melanomas. The volume doubling times ranged from 4.2 to 21.6 days. Melanomas with short volume-doubling times had lower necrotic fractions and tended to be better vascularized than those with long volume-doubling times.