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Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, has a long history of human exposure. We now show that cinnamic acid induces cytostasis and a reversal of malignant properties of human tumor cells in vitro. The concentration causing a 50% reduction of cell proliferation (IC50) ranged from 1 to 4.5 mM in glioblastoma, melanoma, prostate and lung carcinoma cells. Using melanoma cells as a model, we found that cinnamic acid induces cell differentiation as evidenced by morphological changes and increased melanin production. Moreover, treated cells had reduced invasive capacity associated with modulation of expression of genes implicated in tumor metastasis (collagenase type IV, and tissue inhibitor metalloproteinase 2) and immunogenicity (HLA-A3, class-I major histocompatibility antigen). Further molecular analysis indicated that the anti-tumor activity of cinnamic acid may be due in part to the inhibition of protein isoprenylation known to block mitogenic signal transduction. The results presented here identify cinnamic acid as a new member of the aromatic fatty acid class of differentiation-inducers with potential use in cancer intervention.

An appropriate surgical technique for the production of cerebral infarction must fulfill, among others, the following criteria in order to be suitable for electron microscopy (EM) studies: (1) the method of arterial occlusion should yield a high percentage of infarcts with predictable average size; (2) there must be avoidance of surgical manipulation (i.e., retraction) of the cerebral tissues or exposure of the same to the atmosphere; and (3) the method for occluding the artery must be one that permits fixation by perfusion of the ischemic and nonischemic brain. Modifications to a previously devised method for induction of cerebral infarct are herein described. This new surgical approach has made it possible to conduct detailed and sequential ultrastructural analysis of experimental cerebral infarctions.

The sites of benzylation of adenosine and guanosine by different benzylating agents in various solvent mixtures were investigated in order to determine those properties of chemical reactivity which lead to reaction on the exocyclic amino and oxo groups. Modification of these sites, as opposed to ring nitrogen sites, can be associated with carcinogenic potential, and was found to be favored by changes in reaction medium or leaving group which would advance carbon leaving group bond breakage. The extents of reaction on the exocyclic amino group of guanosine were greater than for the exocyclic O1 23456 site but the ratio of reaction at 06 8/N2 increased with increasing leaving group hardness, suggesting that the charge localization or hardness of the reaction center determines the distribution of products over these two sites.

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