Chemotherapeutic intervention

Enyzme catalysis is thus essential for all life. Hence the selective inhibition of critical enzymes of infectious organisms (e.g., viruses, bacteria, and multicellular parasites) is an attractive means of chemotherapeutic intervention for infectious diseases. This strategy is well represented in modem medicine, with a significant portion of antiviral, antibiotic, and antiparasitic drugs in clinical use today deriving their therapeutic efficacy through selective enzyme inhibition (see Table 1.1 for some examples). 

Clinical observations have suggested that the organ environment can influence the response of tumors to therapy. For example, in women with breast cancer, lymph node and skin metastases are more sensitive to chemotherapeutic intervention than metastases in either the lung or the bone (34). Similarly, orthotopic implantation of human tumor cells from surgical specimens into nude mice has shown that colon carcinomas injected into the wall of the colon, results in more clinically relevant outcomes then subcutaneously injected colon carcinomas. Orthotopic implanta-... 

The gut is vulnerable to infection by viruses, bacteria, parasites and occasionally fungi. Virus infections are the most prevalent but are not susceptible to chemotherapeutic intervention. Bacterial infections are more readily recognized and raise questions concerning the role of antibiotic management. Parasitic infections of the gut are beyond the scope of this chapter. 

Hellen. C.U. et al. (1992) Viral proteases as targets for chemotherapeutic intervention. Curr. Opin. Biotechnol., 3.643-649. 

The folate pathway is one in which selective chemotherapeutic intervention has been very successful, and a number of drugs acting through this pathway are in current use. This is because of the fact that mammals receive FA from their diet and convert it into dihydrofolic acid (DHFA) and tetrahydrofolic acid (THFA), which give rise to folate cofactors. The bacteria and protozoans, on the other hand can not effectively utilize FA to get their requirements of DHFA and THFA. Consequently, these organisms synthesize DHFA de novo (for details, see Chapter 13). Further the affinity of the enzymes involved from different sources (mammalian, bacterial and protozoan) for different classes of inhibitors is quite different, which has resulted in the development of drugs with selective action. 

Moore BH, Gagle PT, Allen TC, et al. Topoisomerasae Il-alpha, minichromosome maintenance protein 2 (MCM2), and X-linked mammalian inhibitor of apoptosis protein (XIAP) expression in pleural diffuse malignant mesothelioma (PDMM) Possible role for chemotherapeutic intervention. Mod Pathol. 2008 21 347A. 

The various aspects of chemotherapeutic intervention may be discussed in an elaborated manner under the following defined categories, such as ... 

In addition to oxystress/apoptosis hypothesis induced by PZP, Peter Valent et al. [105, 112, 113] showed remarkable downregulation of oncogene BCRj ABL in CML which led to apoptosis. PZP or SZP exhibits also growth suppressing effect on imanitib-resistant CML as well as acute lymphoblastic leukemia (ALL) [105, 112-114]. These findings suggest that HO-1 (Hsp-32) is an attractive target for chemotherapeutic intervention for combination therapy. 

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