Nucleoside analogues: mechanisms of drug resistance and reversal strategies

Resistance Mechanisms for Nucleoside Analogues

The aim of the thesis was to elucidate the mechanisms underlying resistance to nucleoside analogues used in the treatment of leukemias, with focus on cellular metabolism and induction of apoptosis. Cladribine (CdA), Clofarabine (CAFdA), Fludarabine (Fara-A) and Nelarabine (Ara-G) are nucleoside analogues with activity against various types of leukemias. CAFdA is a relatively new nucleoside anal...

5-Fluorouracil: mechanisms of resistance and reversal strategies.

The purpose of this work is to review the published studies on the mechanisms of action and resistance of 5-fluorouracil. The review is divided into three main sections: mechanisms of anti-tumor action, studies of the resistance to the drug, and procedures for the identification of new genes involved in resistance with microarray techniques. The details of the induction and reversal of the drug...

Chemical Synthesis of Nucleoside Analogues Chemical Synthesis of Nucleoside Analogues

Mechanisms of Drug Resistance

Progress of research into the problem of resistance to antibiotics is held back by lack of knowledge of the biochemical mechanisms by which these drugs act. Fortunately, it is possible to study some of the mechanisms of drug resistance, even at a biophysical or biochemical level, without necessarily knowing very much about how the drug works—just as it is possible to study (at least at a biolog...

Nucleoside analogues and mitochondrial toxicity.

An evaluation of the US Food and Drug Administration's Adverse Event Reporting System identified that patients coinfected with human immunodeficiency virus and chronic hepatitis C virus who were treated with a regimen of ribavirin and didanosine, with or without stavudine, were at increased risk for events associated with mitochondrial toxicity, including fatal hepatic failure, peripheral neuro...