Blood supply in neoplasms

Abstract

The present study is based on the finding that treatment with the new anticancer drug, ICRF 159, completely inhibited the formation of metastases in mice implanted with the Lewis lung carcinoma (3LL), at doses which had little effect on the growth rate of the primary tumour. The mode of action of the drug appeared to be on the development of the blood vessels of the primary tumour.

Studies were carried out to demonstrate the nature of the changes occurring in the structure and function of tumour blood vessels brought about by treatment with ICRF 159. X-ray angiography, carbon black (Pelikan ink) labelling and intravital staining with lissamine green have demonstrated that many of the characteristics of tumour blood vessels were absent In tumours treated with ICRF 159. Further, the blood vessels of treated tumours were relatively normal in structure and arrangement.

Any alteration of the morphology of tumour blood vessels may affect the rate of blood flow through the tumour. As this could be critical for most therapeutic modalities, the rate of blood flow through 3LL tumours treated with ICRF 159 was measured but was found not to be significantly different from control values.

It has been reported that tumour blood vessels are abnormally sensitive to serotonin at doses which have little effect on the blood vessels of normal tissue. Although control 3LL tumours demonstrated a marked response to serotonin, no such effect was shown in tumours treated with ICRF 159. Finally, It was demonstrated that ICRF 159 did not alter the viability of 3LL cells found in areas of the tumour which were devoid of functional blood vessels. These cells were capable of propagating the growth of new tumours.

The profound modification of the morphology and functional character of tumour blood vessels brought about by treatment with ICRF 159, termed "angiometamorphic", could be of considerable importance in the treatment of primary and secondary tumours.