W. Huhnt et As. Lubbe, GROWTH, MICROVESSEL DENSITY AND TUMOR-CELL INVASION OF HUMAN COLON ADENOCARCINOMA UNDER REPEATED TREATMENT WITH HYPERTHERMIA AND SEROTONIN, Journal of cancer research and clinical oncology, 121(7), 1995, pp. 423-428
The intratumoral microvessel density of malignant breast cancer has be
en shown to be an important prognostic marker. In this study, we teste
d whether repeated treatment with hyperthermia and serotonin (5-hydrox
ytryptamine) reduces tumor growth and alters tumor histology of a colo
n adenocarcinoma, and whether capillary density in this tumor can also
be regarded as an important prognostic marker. Previously we have sho
wn that acute treatment of colon adenocarcinoma with hyperthermia, alo
ne or in combination with serotonin, selectively constricted tumor mic
rovessels, which could reduce blood flow and inhibit tumor growth. Fou
rteen days after human colon adenocarcinoma had been transplanted unde
r the dorsal epidermis of the ear of athymic nude mice, the surgically
unprepared tumor-bearing ear of the sodium-pentobarbital-anesthetized
animal was treated with hyperthermia alone (group 1, 43 degrees C for
45 min), or with hyperthermia plus topically applied serotonin (1 mM/
1, 43 degrees C for 45 min, group 2) twice per week for 5 weeks. Contr
ol animals were not treated (group 3). Histological slides (stained wi
th hematoxylin/eosin) were prepared 42 days after implantation, for an
alysis of tumor grading, tumor cell invasion into the surrounding tiss
ue and microvessels, and the number of intratumoral microvessels. Repe
ated hyperthermia inhibited tumor growth, reduced the number of intrat
umoral microvessels, did not change tumor cell invasion and increased
the necrotic area. Hyperthermia and serotonin did not influence tumor
growth, but strongly reduced cell invasion and the number of microvess
els. The area of necrosis was very large. Thus, analysis of microvesse
l density in colon adenocarcinoma seems not to be an important tool fo
r predicting therapeutic efficacy.