Chemoprevention of cancer is a means of cancer control in which the occurrence of this disease is prevented by administra tion of one or several chemical compounds. This Perspective deals with the areas in cancer control that this field addresses, the promise that it holds, and the problems that must be solved in order to realize its goals. The most desirable way of eliminating the impact of cancer in humans is by prevention. The first set of strategies for achieving this objective is to remove the causative agents. In some instances, as with cigarette smoking, it is possible to eliminate the etiological agent. However, in others it is not. The causes of most cancers in the human are not known. Under some circumstances, even when causative factors are known, neoplasia may have been initiated, and prevention now falls into the realm of suppressing the evolution of the neoplastic process. Individuals already exposed to carcinogens fall into this category as do individuals at high risk to cancer because of genetic factors. Finally, there are a considerable number of suspect carcinogens in the environment that have been identified by virtue of mutagenicity testing. Many of these mutagenic substances occur in food. The carcinogenic potential of these compounds for the human is not clear. If they do in fact play a role in the occurrence of cancer, it would be exceedingly difficult to remove them from the environment. Flavones in food are an example of a class of compounds that are mutagenic and that would be virtually impossible to remove because of their ubiqui tous distribution. Likewise, if exposure to oxygen radicals and epoxides poses a hazard, as has been suggested by some investigators, such exposures would be difficult to prevent. While removal of causative agents is the primary goal of cancer pre vention, for the foreseeable future it is likely to be incomplete. Accordingly, the development of a second line of prevention based on Chemoprevention assumes considerable importance. The human constituencies that would be the target for Chemoprevention vary. Two extremes are apparent, but in all likelihood a continuum exists between them. At one extreme are individuals at very high risk of developing cancer because of genetic predisposition or exposure to carcinogens. At the other end of the risk spectrum are individuals lacking any evidence of an increase in risk factors. The strategies for dealing with groups at varying risks differ. As the risk for developing cancer increases, the compounds likely to be most effective are those that sup press evolution of the neoplastic process. The permissible risk of toxicity from the chemopreventive agent also will increase. In contrast, when one considers chemopreventive agents to be directed at populations with no enhanced risk from cancer, protection against attack from compounds that are involved in the causation of cancer assumes a greater importance. For this

https://cancerres.aacrjournals.org/content/canres/45/1/1.full.pdf

Chemoprevention of Cancer

Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increased plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.

Efficacy and Safety of Plant Stanols and Sterols in the Management of Blood Cholesterol Levels

Traditionally, access to structurally defined complex carbohydrates has been very laborious Although recent advancements in solid-phase synthesis have made the construction of complex oligosaccharides less tedious, a high level of technical expertise is still necessary to obtain the desired structures We describe the automated chemical synthesis of several oligosaccharides on a solid-phase synthesizer A branched dodecasaccharide was synthesized through the use of glycosyl phosphate building blocks and an octenediol functionalized resin The target oligosaccharide was readily obtained after cleavage from the solid support Access to certain complex oligosaccharides now has become feasible in a fashion much like the construction of oligopeptides and oligonucleotides

http://science.sciencemag.org/content/sci/291/5508/1523.full.pdf

Automated Solid-Phase Synthesis of Oligosaccharides

Applications of ionic liquids in carbohydrate chemistry: a window of opportunities.

Organic Synthesis on Soluble Polymer Supports: Liquid-Phase Methodologies.

Polymer-supported solution synthesis of oligosaccharides

Polymer-Supported Solution Synthesis of Oligosaccharides Using a Novel Versatile Linker for the Synthesis of D-Mannopentaose, a Structural Unit of D-Mannans of Pathogenic Yeasts

Silver Trifluoromethanesulfonate(Triflate) Activation of Trichloroacetimidates in Glycosylation Reactions

Syntheses of model oligosaccharides of biological significance. 2. Synthesis of a tetramannoside and of two lyxose-containing trisaccharides

Synthesis of methoxycarbonyloctyl 2-acetamido-4-O-[(2′-acetamido-2′-deoxy-β-D-glucopyranosyl)-6-O-α-L-fucopyranosyl]-2-deoxy-(β-D-glucopyranoside as shown in Scheme 1 is described together with cou...

Syntheses of model oligosaccharides of biological significance. VII: Synthesis of a fucosylated N,N'-diacetylchitobioside linked to bovine serum albumin and immunochemical characterization of rabbit antisera to this structure

Jiri J. Krepinsky

Papers

Polymer-supported solution synthesis of oligosaccharides

Polymer-Supported Solution Synthesis of Oligosaccharides Using a Novel Versatile Linker for the Synthesis of D-Mannopentaose, a Structural Unit of D-Mannans of Pathogenic Yeasts

Silver Trifluoromethanesulfonate(Triflate) Activation of Trichloroacetimidates in Glycosylation Reactions

Syntheses of model oligosaccharides of biological significance. 2. Synthesis of a tetramannoside and of two lyxose-containing trisaccharides

Syntheses of model oligosaccharides of biological significance. VII: Synthesis of a fucosylated N,N'-diacetylchitobioside linked to bovine serum albumin and immunochemical characterization of rabbit antisera to this structure