Service Communautaire d'Information sur la Recherche et le Développement - CORDIS

Neoglycoconjugates as prognostic tumour markers

Molecular determinants govern the intracellular and intercellular communication of cells. The precise definition of distinct epitopes will thus provide suitable information on the status of cells that may explain their apparent functional activities, thereby opening up the possibility to turn the results of basic research into clinical benefit. Evidently, such knowledge would advance the panel of markers for tumour diagnosis and therapy.

Polymerization of activated esters of acrylic acid and incorporation of suitably spaced carbohydrate ligands and biotin derivatives into the polymeric backbone yielded substituted poly(2-hydroxymethyl acrylamide) derivatives, which are potentially valuable tools for medical applications. Initial histopathological monitoring has fully proven this assumption. Presence of specific binding sites is not restricted to any unique type of human cancer, which would restrict the application of this class of marker. Indeed, common human tumours such as breast, colon, bladder and lung carcinomas or melanomas display respective receptor sites. In addition to unequivocally establishing the concept correlation of the histochemical results (obtained semiquantitatively and quantitatively by a tailor-made computer program structure), clinical data yielded the first evidence for prognostic significance. This applies to the survival of patients with T3/T4 non-small cell lung carcinomas and with carcinoids. Moreover, detection of preneoplastic lesions in the lung was reliably assessable. To go beyond the histochemical monitoring by assaying the responses of defined cell populations in vitro, the elicitation of hydrogen peroxide- production by protein-carbohydrate interaction was proven. The inherent developments in the degree of complexity of chemical synthesis and of optimization of the histochemical as well as cell biological/immunological procedures are a firm foundation to proceed to further elaboration of the concept that neoglycoconjugates are valuable markers for tumour diagnosis with relevance to trigger distinct parameters of the host defence system.