The intervention within the tumor microenvironment by physical, chemical or biological means is relatively easy when the tumor is exposed at the outside of the body, for instance in the skin or subcutaneously. It is more difficult to reach within the body in the case of metastases. In such cases the application of ports, either intravenously or intra-arterially, may be appropriate for systemic or loco-regional delivery of chemical or biological substances. This is exemplified in the case of brain tumors where a cytokine immuno-gene therapy has been applied by means of intra-cranial cannula through which tumor cells were inoculated which were modified with either the gene coding for IL-2, IL-4 or TGF-0 2 antisense .
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