Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E and Z-2-haloethyldiazotates, which have been postulated as the ultimate electrophiles responsible for the biological activity of 2-haloethylnitrosoureas (HENUs), have been synthesized and characterized by 15N-nmr. Their stability and solubility in organic solvents are increased by forming crown ether complexes. While E and Z forms are configurationally stable in solution the Z form cyclizes at greater than or equal to -20 degrees C to a 1,2,3-oxadiazoline. The E isomers cross-link DNA, in contrast to the Z isomers. However, both E and Z (2'chloroethyl)thioethyldiazotates (neither of which may cyclize) cross-link DNA extremely efficiently. The cross-linking by these agents is a two-step process and increases with the (G + C) content of the DNA. E-2-chloroethyldiazotate exhibits activity against P388 leukaemia in vivo, lending credence to the suggestion that it is the ultimate electrophile from HENUs. Ab initio calculations predicted the optimized geometry, LUMO energies and atom contributions and the net atomic charges for the diazohydroxides and the HOMO energies and atom contributions for the alternative DNA base sites. An analysis based on Frontier Orbital methods invoking the Hard and Soft Acids and Bases theory permitted an interpretation of the formation of a cross-link site and several modified bases isolated from the reaction of HENUs with DNA.
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PMID:Mechanism of interstrand cross-linking of DNA by anticancer 2-haloethylnitrosoureas. 374 68

To quantify the effects of ageing and non-ageing factors, a characterization of the effects of ageing, genetic, and exogenous variables on 12 major non-communicable diseases was evaluated using a model assessing cumulative frequency of death and survival by age group from dead and surviving populations based on mortality statistics. Indices (0-1) of the roles of ageing (ARD), genetics (GRD) and exogenous (ERD) variables in deaths due to disease were established, and the sum of ARD, GRD and ERD was 1 (value of each indices was <1). Results showed that ageing plays an important role in death from chronic disease; exogenous factors may contribute more to the pattern of chronic disease than genetic factors (ARD, GRC and ERD were 0.818, 0.058 and 0.124 respectively for all non-communicable diseases). In descending order, ERD for non-communicable diseases were breast cancer, leukaemia, cancer of the cervix uteri and uterus, liver cancer, nephritis and nephropathy, stomach cancer, lung cancer, diabetes, cerebrovascular disease, coronary heart disease, COPD, and Alzheimer's disease, while a smaller ERD indicated a tendency of natural death. An understanding of the aforementioned complex relationships of specific non-communicable diseases will be beneficial in designing primary prevention measures for non-communicable diseases in China.
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PMID:Assessment of the role of ageing and non-ageing factors in death from non-communicable diseases based on a cumulative frequency model. 2881 18