Therapeutic interference

The term therapeutic interference has been confined to cases where there is chemical similarity between the two substances and hence no likelihood of their reacting chemically with one another. The phenomenon brings to mind the often-met situation in pharmacodynamics where an agonist can be converted, by an increase in molecular weight, to an antagonist of low or zero efficacy, but with a greater affinity for the receptor (see Section 7.5.2, p. 294). 

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Inhibitors of the Angiopoietin/Tie-2 and Ephrin/Eph systems are in preclinical development which parallels the biological target validation of these molecules. As vascular assembly, maturation, and homeostasis regulating molecules, therapeutic interference with these molecular systems may hold promise for a number of vascular indications. 

Interference with specific cell-cell and cell-matrix adhesion mechanisms is another rapidly advancing approach to therapeutically interfere with angiogenesis. Antagonistic antibodies (Vitaxin) to the integrin heterodimer av 33 have been shown to act on the blood vessels of tumors but not on the resting organ vasculature. Vitaxin demonstrated some promise in Phase II clinical trials. 

These examples clearly prove the viability of a structure-based peptidomimetic design approach for developing non-peptide peptidomimetics for therapeutic interference into protein-protein interaction events. 

Serotonin (5-hydroxytryptamine 5-HT) acts as transmitter and mediator on several locations in the body with quite different effects. There are multiple sub-types of the serotonin receptor. This offers the possibility of a selective therapeutic interference using subtype specific agonists or antagonists. 

It should be realized, however, that therapeutic interference with only one cell type may not be enough to treat liver cirrhosis, because all hepatic cell types contribute to some extent to the development of the disease. Therefore, a combination of drug-targeting preparations to stellate cells, KC, endothelial cells, and/ or hepatocytes might improve the pharmacological therapies and compete with the liver transplantation technique. In addition to therapeutic applications, modified albumins may also be used for diagnostic purposes (an issue that will be addressed in section VI.C.4). 

Wrapping Patterns as Universal Markers for Specificity in the Therapeutic Interference with Signaling Pathways... 

By definition, patches that significantly contribute to protein-water interfacial tension must translate into hot spots for protein-protein associations. Hence the laborious alanine scanning may be effectively replaced by a direct computational identification of patches of interfacial tension in the free subunits. This computational advance will no doubt simplify the engineering of therapeutic interference with protein-protein associations. 

Table 6.2 Therapeutic interference Injections into trypanosome-infected mice...

A large data set indicates that the polyamine pathway can be a molecular target for therapeutic interference in several types of cancers [57]. There are numerous studies that have correlated elevated polyamine levels not only with diseases such as cystic fibrosis, muscular dystrophy, psoriasis, and diabetes [102-105] but also with abnormal or rapid cell growth as shown for malignant tumors (for review see [2,22]). Over the last few years, research on the importance of polyamines in cancer progression has revealed many conflicting results. While increased polyamine levels are associated with increased cell proliferation, decreased apoptosis and increased expression of... 

THERAPEUTIC INTERFERENCE INJECTIONS INTO TRYPANOSOME-INFECTED MICE... 

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