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Colon cancer is a common malignancy in the westernized world and is incurable in its advanced stages. This article summarizes the currently available information on colorectal cancer chemoprevention. A brief outline of the incidence and etiologic factors is followed by a discussion of the evidence on which chemopreventive strategies for colon cancer are modeled. This includes a description of the development of surrogate endpoint biomarkers and experimental models to study colorectal cancer chemopreventives, a review of the promising colorectal cancer chemopreventives, and a discussion of the issues to be addressed in the design of future chemoprevention trials. The article concludes with an emphasis on the development and validation of biomarkers and selection of high-risk cohorts using genetic and epidemiologic tools as the main goals of future colon cancer chemoprevention trials before large-scale, risk-reduction trials are conducted.

Lysophosphatidic acid (LPA) is a platelet-derived phospholipid which has been shown to cause immediate hypertension in rats. The following experiments were designed to assess the involvement of endothelin-1 (ET-1) in LPA-induced hypertension. LPA was found to upregulate preproET-1 transcripts in endothelial cells which were derived from rat hearts and aortae in a dose and time-dependent manner. PreproET-1 mRNA level was elevated within 15 min and maximal induction was achieved by 30 min after the addition of 0.5 μM LPA. Cycloheximide superinduced the preproET-1 mRNA level and actinomycin D abolished the induction. In addition, the induction could be blocked by H7, an inhibitor of protein kinase C. These findings indicate that the induction of preproET-1 transcripts by LPA involves the activation of protein kinase C and de novo RNA synthesis. Since ET-1 is a very potent vasoconstrictor with long lasting effect, the increase in ET-1 production may serve to amplify and augment the effect of LPA on hypertension.

Angiotensin II (All) was found to upregulate vascular endothelial growth factor (VEGF) gene expression in rat heart and mesenteric artery-derived endothelial cells in a dose and time-dependent manner. Maximal induction was achieved by 2 h after the addition of All, Addition of cyctoheximide superinduced and actinomycin D abolished the induction. In addition, the induction could be blocked by tosartan, an AT1 receptor antagonist and protein kinase C inhibitors, H7 and GF109203X. These results suggest that induction of VEGF transcripts by All is dependent on protein kinase C dependent pathway and de novo RNA synthesis. Immunoblot analysis revealed that VEGF was detectable in the conditioned medium 8 h after All stimulation. Our data suggest that All-induced VEGF plays a role in the change of endothelial cell permeability and angiogenesis in renovascular hypertension (Supported by Cécile Cox Quillen Chair of Geriatrics).

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The authors present four cases of physically aggressive behavior in geriatric patients with dementia managed with the use of valproic acid. There was improvement in the behavior in most patients; however it was frequently necessary to add a second medication for adequate behavior control, and the side effects were significant.