Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapeutic drug resistance is a major clinical problem and cause for failure in the therapy of human cancer. One of the goals of molecular oncology is to identify the underlying mechanisms, with the hope that more effective therapies can be developed. Several mechanisms have been suggested to contribute to chemoresistance: 1) amplification or overexpression of the P-glycoprotein family of membrane transporters (eg, MDR1, MRP, LRP) which decrease the intracellular accumulation of chemotherapy; 2) changes in cellular proteins involved in detoxification (eg, glutathione S-transferase pi, metallothioneins, human MutT homologue, bleomycin hydrolase, dihydrofolate reductase) or activation of the chemotherapeutic drugs (DT-diaphorase, nicotinamide adenine dinucleotide phosphate:cytochrome P-450 reductase); 3) changes in molecules involved in DNA repair (eg, O6-methylguanine-DNA methyltransferase, DNA topoisomerase II, hMLH1, p21WAF1/CIP1; 4) activation of oncogenes such as Her-2/neu, bcl-2, bcl-XL, c-myc, ras, c-jun, c-fos, MDM2, p210 BCR-abl, or mutant p53. An overview of these resistance mechanisms is presented, with a particular focus on the role of oncogenes. Some current strategies attempting to reverse their effects are discussed.
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PMID:Role of oncogenes in resistance and killing by cancer therapeutic agents. 909 Apr 98

The demonstration tha RNA can be cleavaged by cis-ribozyme(catalytic RNAs, RNA enzyme) has potentially important therapeutic implications. Ribozymes are effective for modulation of gene expression because of their simple structure, site-specific cleavage activity and catalytic potential. The targets of ribozyme-mediated gene modulation have ranged from cancer cells to foreign genes that cause infectious diseases. Additional target sites for ribozymes are in initial phases of development and design. Ribozymes have been targeted against myriad genes, including oncogenes (ras, BCR-ABL) and drug resistance genes(MDR-1, c-fos, DHFR). These ribozymes have cleaved the target RNAs in culture system(in vitro) and developed in vivo system. We reported that anti-fos ribozyme has altered the expression of c-fos and DNA repair genes in cisplatin-resistance cancer cells, and reversed the sensitivity to ciaplatin. Furthermore, we have developed high efficiency by the transfer system using an electroporation in vivo.
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PMID:[Circumventing multidrug resistance in human cancer by anti-ribozyme]. 915 62