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Mechanisms of Resistance to Antineoplastic Drugs
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Philip J. Vickers, Alan J. Townsend, Kenneth H. Cowan
In some cases, cells can circumvent the metabolic block effected by a drug and thereby develop resistance to that agent by utilizing alternate biochemical pathways. For example, cells may overcome the inhibition of de novo nucleotide synthesis effected by MTX and 5-FU by increasing the activity of nucleotide salvage pathways.100-102
Instability of Human Mitochondrial DNA, Nuclear Genes and Diseases
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
The classical autosomal recessive MNGIE with mitochondrial DNA depletion is caused by mutations in TYMP, a gene encoding thymidine phosphorylase (22q13.33). It phosphorylates thymine to thymidine what makes it the basic enzyme necessary for nucleotide salvage biosynthesis pathway. Patients with TYMP mutations present with gastrointestinal symptoms, mainly dysmotility, polyneuropathy, PEO with ptosis. They also show the eating disorders, anorexia. The disease leads to cachexia and death. The onset and survival are variable, but the disease does not start in infancy42.
Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis
Published in Gut Microbes, 2022
Dušan Radojević, Marina Bekić, Alisa Gruden-Movsesijan, Nataša Ilić, Miroslav Dinić, Aleksandar Bisenić, Nataša Golić, Dragana Vučević, Jelena Đokić, Sergej Tomić
Gut microbiota produce soluble metabolites that reach the bloodstream by passing through the intestinal barrier.37 To investigate potential microbial functional composition, we performed phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt)2 analysis followed by LEfSe analysis to determine the differences in predicted microbial metabolic functions between the groups, showing only pathways meeting an LDA significance threshold of >2 (Figure 6B). These analyses showed several pathways involved in the biosynthesis of purine (PWY-6125) and pyrimidine (PWY-7199) nucleotides, amino acids (ASPASN-PWY), S-adenosyl-L-methionine cycle (PWY-6151), and polyprenyls (POLYISOPRENSYN-PWY), and one pathway in charge of purine nucleotide salvage (PWY-6609), as potential markers of the control group at the EAE peak.